Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 1 G Evidence-Based Clinical Guidelines for Multidisciplinary Ethodolo

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Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 1 g Evidence-Based Clinical Guidelines for Multidisciplinary ethodolo

Spine Care M ne i del i u /G on Antibiotic Prophylaxis in i ntroduct

Spine Surgery I

NASS Evidence-Based Clinical Guidelines Committee

William O. Shaffer, MD Committee Chair

Jamie Baisden, MD Robert Fernand, MD Paul Matz, MD

on Financial Statement This clinical guideline was developed and funded in its entirety by the North American Spine Society (NASS). All participating /G authors have disclosed potential conflicts of interest consistent with NASS’ disclosure policy. Disclosures are listed below: u i del Range Key: i ne William O. Shaffer, MD Nothing to disclose. Level A. $100 to $1,000

M Level B. $1,001 to $10,000 ethodolo Paul G. Matz, MD Nothing to disclose. Level C. $10,001 to $25,000 Level D. $25,001 to $50,000 Level E. $50,001 to $100,000 Jamie Baisden, MD Nothing to disclose. Level F. $100,001 to $500,000 g Level G. $500,001 to $1M y Level H. $1,000,001 to $2.5M Robert Fernand, MD Nothing to disclose. Level I. Greater than $2.5M

Comments Comments regarding the guideline may be submitted to the North American Spine Society and will be considered in development of future revisions of the work.

Special Thanks The North American Spine Society would like to express its thanks to Dr. Nikolai Bogduk for generating the calculations in Ap- pendix E to explain the prohibitive nature of the sample sizes required to yield Level I data for the efficacy of antibiotic prophylaxis.

North American Spine Society Clinical Guidelines for Multidisciplinary Spine Care Antibiotic Prophylaxis in Spine Surgery

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Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 3 g Table of Contents ethodolo M ne i del i

I. Introduction ...... 4 u /G on II. Guideline Development Methodology ...... 5 i

III. Recommendations Regarding Antibiotic Prophylaxis in Spine Surgery ...... 8 A. Efficacy ...... 8 ntroduct B. Protocol ...... 20 I . C Redosing ...... 37 . D Discontinuation ...... 40 E. Wound Drains ...... 44 . F Body Habitus ...... 46 G. Comorbidities ...... 48 H. Complications ...... 52

IV. Appendices ...... 55 A. Levels of Evidence for Primary Research Questions ...... 55 B. Grades of Recommendations for Summaries or Reviews of Studies ...... 56 . C Linking Levels of Evidence to Grades of Recommendation ...... 57 D. NASS Literature Search Protocol ...... 58 E. Comparing the Prevalence of Rare Events ...... 59 F. Comparing 2007 Recommendations to Current Recommendations ...... 60

V. References ...... 66

A technical report, including the literature search parameters and evidentiary tables developed by the authors, can be accessed at http://www.spine.org/Documents/Antibiotic_Prophylaxis_TechRept.pdf

M idence-Based Clinical Guideline on Antibiotic Prophylaxis in related to efficacy and protocol for the use of antibiotic prophy-

ethodolo g y Spine Surgery is to provide evidence-based recommendations to laxis in percutaneous procedures. address key clinical questions surrounding the use of prophylactic antibiotics in spine surgery. The guideline is intended to THIS GUIDELINE DOES NOT REPRESENT A “STAN- address these questions based on the highest quality clinical lit- DARD OF CARE,” nor is it intended as a fixed treatment pro- erature available on this subject as of June 2011. The goals of the tocol. It is anticipated that there will be patients who will require guideline recommendations are to assist in delivering optimum, less or more treatment than the average. It is also acknowledged efficacious treatment with the goal of preventing surgical infec- that in atypical cases, treatment falling outside this guideline tion. will sometimes be necessary. This guideline should not be seen as prescribing the type, frequency or duration of intervention. Scope, Purpose and Intended User Treatment should be based on the individual patient’s need and doctor’s professional judgment. This document is designed to This document was developed by the North American Spine function as a guideline and should not be used as the sole reason Society Evidence-based Guideline Development Committee as for denial of treatment and services. This guideline is not intend- an educational tool to assist spine surgeons in preventing surgi- ed to expand or restrict a health care provider’s scope of practice cal site infections. This guideline is an update to the 2007 ver- or to supersede applicable ethical standards or provisions of law. sion. The NASS Clinical Guideline on Antibiotic Prophylaxis in Spine Surgery addresses the efficacy and appropriate protocol for antibiotic prophylaxis and discusses redosing, discontinuation, Patient Population wound drains, as well as special considerations related to the po- The patient population for this guideline encompasses adults (18 tential impact of comorbidities on antibiotic prophylaxis proto- years or older) undergoing spine surgery.

Through objective evaluation of the evidence and transparency cate the strength of the recommendations made in the guideline in the process of making recommendations, it is NASS’ goal to based on the quality of the literature. develop evidence-based clinical practice guidelines for the diag- u i del ne nosis and treatment of adult patients with various spinal condi- Grades of Recommendation: /G tions. These guidelines are developed for educational purposes A: Good evidence (Level I studies with consistent findings) to assist practitioners in their clinical decision-making process- for or against recommending intervention. es. It is anticipated that where evidence is very strong in support of recommendations, these recommendations will be operation- B: Fair evidence (Level II or III studies with consistent find- ntroduct i on alized into performance measures. ings) for or against recommending intervention. I

Multidisciplinary Collaboration C: Poor quality evidence (Level IV or V studies) for or With the goal of ensuring the best possible care for adult patients against recommending intervention. suffering with spinal disorders, NASS is committed to multidisciplinary involvement in the process of guideline and perfor- I: Insufficient or conflicting evidence not allowing a recom- mance measure development. To this end, NASS has ensured mendation for or against intervention. that representatives from medical, interventional and surgical spine specialties have participated in the development and re- Levels of evidence have very specific criteria and are assigned to view of all NASS guidelines. To ensure broad-based representa- studies prior to developing rec-ommendations. Recommenda- tion, NASS has invited and welcomes input from other societies tions are then graded based upon the level of evidence. To better and specialties un-derstand how levels of evidence inform the grades of recommendation and the standard nomencla-ture used within the rec- Evidence Analysis Training of All NASS ommendations see Appendix C. Guideline Developers Guideline recommendations are written utilizing a standard NASS has initiated, in conjunction with the University of Al- language that indicates the strength of the recommendation. berta’s Centre for Health Evidence, an online training program “A” recommendations indicate a test or intervention is “recom- geared toward educating guideline developers about evidence mended”; “B” recommendations “suggest” a test or intervention analysis and guideline development. All participants in guide- and “C” recommendations indicate a test or in-tervention “may line development for NASS have completed the training prior be considered” or “is an option.” “I” or “Insufficient Evidence” to participating in the guideline development program at NASS. statements clearly indicate that “there is insufficient evidence to This training includes a series of readings and exercises, or in- make a recommendation for or against” a test or in-tervention. teractivities, to prepare guideline developers for systematically Work group consensus statements clearly state that “in the ab- evaluating literature and developing evidence-based guidelines. sence of reliable evidence, it is the work group’s opinion that” a The online course takes approximately 15-30 hours to complete test or intervention may be appropriate. and participants have been awarded CME credit upon comple- The levels of evidence and grades of recommendation imple- tion of the course. mented in this guideline have also been adopted by the Journal of Bone and Joint Surgery, the American Academy of Orthopae- Disclosure of Potential Conflicts of Interest dic Surgeons, Clinical Orthopaedics and Related Research, the All participants involved in guideline development have dis- journal Spine and the Pediatric Orthopaedic Society of North closed potential conflicts of interest to their colleagues and their America. potential conflicts have been documented in this guideline. Par- In evaluating studies as to levels of evidence for this guide- ticipants have been asked to update their disclosures regularly line, the study design was interpreted as establishing only a po- throughout the guideline development process. tential level of evidence. As an example, a therapeutic study designed as a randomized controlled trial would be considered a Levels of Evidence and Grades of Recom- potential Level I study. The study would then be further analyzed mendation as to how well the study design was implemented and significant short comings in the execution of the study would be used to NASS has adopted standardized levels of evidence (Appendix A) downgrade the levels of evidence for the study’s con-clusions. In and grades of recommendation (Appendix B) to assist practitio- the example cited previously, reasons to downgrade the results of ners in easily understanding the strength of the evidence and a potential Level I randomized controlled trial to a Level II study recommendations within the guidelines. The levels of evidence would include, among other possibilities: an under-powered range from Level I (high quality randomized controlled trial) to study (patient sample too small, variance too high), inadequate Level V (expert consensus). Grades of recommendation indi- randomization or masking of the group assignments and lack of validated outcome measures.

In addition, a number of studies were reviewed several times and (3) represent the current best research evidence available. in answering different questions within this guideline. How NASS maintains a search history in Endnote, for future use or

/G a given question was asked might influence how a study was reference.

u i del ne evaluated and interpreted as to its level of evidence in answering that particular question. For example, a randomized control Step 5: Review of Search Results/Identification of trial reviewed to evaluate the differences between the outcomes Literature to Review of surgically treated versus untreated patients with lumbar spinal Work group members reviewed all abstracts yielded from the M stenosis might be a well designed and implemented Level I ther- literature search and identified the literature they will review ethodolo g y apeutic study. This same study, however, might be classified as in order to address the clinical questions, in accordance with giving Level II prognostic evidence if the data for the untreated the Literature Search Protocol. Members have identified the controls were extracted and evaluated prognostically. best research evidence available to answer the targeted clinical questions. That is, if Level I, II and or III literature is available to Guideline Development Process answer specific questions, the work group was not required to Step 1: Identification of Clinical Questions review Level IV or V studies. Trained guideline participants were asked to submit a list of clin- Step 6: Evidence Analysis ical questions that the guideline should address. The lists were compiled into a master list, which was then circulated to each Members have independently developed evidentiary tables sum- member with a request that they independently rank the ques- marizing study conclusions, identifying strengths and weakness- tions in order of importance for consideration in the guideline. es and assigning levels of evidence. In order to systematically The most highly ranked questions, as determined by the partici- control for potential biases, at least two work group members pants, served to focus the guideline. have reviewed each article selected and independently assigned levels of evidence to the literature using the NASS levels of evi- Step 2: Identification of Work Groups dence. Any discrepancies in scoring have been addressed by two Multidisciplinary teams were assigned to work groups and as- or more reviewers. The consensus level (the level upon which signed specific clinical questions to address. Because NASS is two-thirds of reviewers were in agreement) was then assigned comprised of surgical, medical and interventional specialists, it to the article. is imperative to the guideline development process that a cross- As a final step in the evidence analysis process, members section of NASS membership is represented on each group. This have identified and documented gaps in the evidence to educate also helps to ensure that the potential for inadvertent biases in guideline readers about where evidence is lacking and help guide evaluating the literature and formulating recommendations is further needed research by NASS and other societies. minimized. Step 7: Formulation of Evidence-Based Step 3: Identification of Search Terms and Parameters Recommendations and Incorporation of Expert Consensus One of the most crucial elements of evidence analysis to support development of recommendations for appropriate clinical care Work groups held face-to-face meetings to discuss the evidence- is the comprehensive literature search. Thorough assessment of based answers to the clinical questions, the grades of recommen- the literature is the basis for the review of existing evidence and dations and the incorporation of expert consensus. Expert con- the formulation of evidence-based recommendations. In order sensus has been incorporated only where Level I-IV evidence is to ensure a thorough literature search, NASS has instituted a Lit- insufficient and the work group has deemed that a recommenda- erature Search Protocol (Appendix D) which has been followed tion is warranted. Transparency in the incorporation of consen- to identify literature for evaluation in guideline development. In sus is crucial, and all consensus-based recommendations made keeping with the Literature Search Protocol, work group mem- in this guideline very clearly indicate that Level I-IV evi-dence bers have identified appropriate search terms and parameters to is insufficient to support a recommendation and that the recom- direct the literature search. mendation is based only on expert consensus. Specific search strategies, including search terms, parameters Consensus Development Process and databases searched, are documented in the technical report that accompanies this guideline. Voting on guideline recommendations was conducted using a modification of the nominal group technique in which each Step 4: Completion of the Literature Search work group member independently and anonymously ranked Once each work group identified search terms/parameters, the a recommendation on a scale ranging from 1 (“extremely inap- literature search was implemented by a medical/research librar- propriate”) to 9 (“extremely appropriate”). Consensus was ob- ian, consistent with the Literature Search Protocol. tained when at least 80% of work group members ranked the Following these protocols ensures that NASS recommenda- recommendation as 7, 8 or 9. When the 80% threshold was not tions (1) are based on a thorough review of relevant literature; attained, up to three rounds of discussion and voting were held (2) are truly based on a uniform, comprehensive search strategy; to resolve disagreements. If disagreements were not resolved after these rounds, no recommendation was adopted.

After the recommendations were established, work group mem- Step 10: Submission for Publication and National bers developed the guideline content, addressing the literature Guideline Clearinghouse (NGC) Inclusion which supports the recommendations. Following NASS Board approval, the guidelines have been slat- ethodolo g y ed for publication and submitted for inclusion in the National M Step 8: Submission of the Draft Guidelines for Review/ Guidelines Clearinghouse (NGC). No revisions were made at Comment this point in the process, but comments have been and will be

Guidelines were submitted to the full Evidence-Based Guideline saved for the next iteration. u i del ne

Development Committee and the Research Council Director for /G review and comment. Revisions to recommendations were con- Step 11: Review and Revision Process sidered for incorporation only when substantiated by a prepon- The guideline recommendations will be reviewed every three derance of appropriate level evidence. years by an EBM-trained multidisciplinary team and revised as appropriate based on a thorough review and assessment of rel- Step 9: Submission for Board Approval evant literature published since the development of this version ntroduct i on Once any evidence-based revisions were incorporated, the drafts of the guideline. I were prepared for NASS Board review and approval. Edits and revisions to recommendations and any other content were con- Nomenclature for Medical/Interventional Treatment sidered for incorporation only when substantiated by a prepon- Throughout the guideline, readers will see that what has tra- derance of appropriate level evidence. ditionally been referred to as “nonoperative,” “nonsurgical” or “conservative” care is now referred to as “medical/interventional care.” The term medical/interventional is meant to encompass pharmacological treatment, physical therapy, exercise therapy, manipulative therapy, modalities, various types of external stim- ulators and injections.

For patients undergoing open spine surgery, does antibiotic prophylaxis result in decreased infection rates compared to patients who do not receive prophylaxis? R ecommendations P r o p hylaxis Preoperative prophylactic antibiotics are suggested to decrease infection rates in patients undergoing spine surgery.

Grade of Recommendation: B in R S ega r ding p ine S

u r ge y 1

A Barker et al described a meta-analysis based on a systematic hours prior to surgery) and 71 received placebo. Presence of

ntibiotic review of the literature concerning the efficacy of prophylactic infection was assessed at 30 days, with surgical site infection antibiotics on the incidence of postoperative spinal infection. defined as drainage of purulent material from the operative By pooling data from six randomized controlled trials, they site and a positive bacteriological culture, or inflammation of

found a 2.2% (10 of 451) infection rate if antibiotics were given an area more than 20 mm in diameter; for urinary tract infec- and a 5.9% (23 of 392) infection rate if antibiotics were not tion, more than 100,000 colony forming units/mL on culture; administered. Whereas each of the individual studies did not and for pneumonia, the clinical diagnosis was made by the treat- find a statistical difference, the pooled data did (p<0.01). In ing physician. There were 21 wound or urinary infections in critique of this analysis, the individual studies included in the the 71 patients who received placebo and nine in the 70 who meta-analysis did not show a statistically significant difference received cephazolin (p < 0.05). Nine patients (12.7%) who re- in infection rate with antibiotic use. However, the pooled results ceived placebo and three (4.3%) who received cephazolin devel- did show a significantly lower rate of infection with prophylactic oped wound infections (p = 0.07). All but three of the infections antibiotic use. These data offer Level II therapeutic evidence that in the placebo group were confirmed by bacterial culture. All antibiotics can lead to lower rates of infection for general spine the organisms isolated from the patients who received placebo surgical procedures. (except the group-D streptococci which are inherently resistant) Pavel et al2 reported a prospective, randomized controlled were sensitive to cephazolin whereas in the cephazolin prophy- trial comparing the use of antibiotic prophylaxis with cepha- lactic group 43% of the organisms isolated were resistant or had loridine with a placebo on the rate of postoperative infection in reduced sensitivity to the drug. The authors concluded that the orthopedic surgical procedures. When separately analyzed, the administration of a single dose of cephazolin preoperatively is infection rate after spinal procedures was 9.2% in the placebo recommended for patients undergoing lumbar spinal surgery. group, compared to 3% in the group who received cephalori- In critique, the sample size was small and the study’s follow-up dine. In critique of this study, the numbers were too small in the period was short. In addition, the authors expanded the defini- spine subgroup to detect a statistically significant difference. tion of infection to include wound, urinary tract infection and While this is a Level I study relative to orthopedic procedures, it pneumonia in order to achieve statistical significance. Due to provides Level II therapeutic evidence that the use of periopera- these limitations, this potential Level I study provides Level II tive cephalosporin antibiotic can significantly reduce the rate of therapeutic evidence that for uncomplicated spine surgery, a perioperative infection in the subgroup of patients undergoing single preoperative dose of cephazolin decreases infection rate; orthopedic spinal procedures. however, it does not significantly decrease the rate of wound in- Rubinstein et al3 performed a prospective, randomized fection. The use of cephazolin appears to be associated with an controlled trial to investigate the efficacy of a single dose of 1 increase in development of resistant organisms. g of cephazolin in reducing postoperative infections in patients undergoing ‘clean’ operations on the lumbar spine. Of the 141 patients included in the study, 70 received 1 g intravenous cephazolin upon arrival to the operative room (approximately two

For a typical, uncomplicated lumbar laminotomy and discectomy, a single preoperative dose of antibiotics is suggested to decrease the risk of infection and/or discitis.

Grade of Recommendation: B

Petignat et al4 conducted a prospective, randomized controlled sensitive to cephazolin whereas in the cephazolin prophylactic trial assessing the efficacy of one preoperative 1.5 g dose of ce- group 43% of the organisms isolated were resistant or had re- furoxime in preventing surgical site infection after lumbar lami- duced sensitivity to the drug. The authors concluded that the notomy and discectomy for herniated disc. Of the 1237 patients administration of a single dose of cephazolin preoperatively is included in the study, 613 received 1.5 g intravenous cefuroxime recommended for patients undergoing lumbar spinal surgery. on induction and 624 received placebo. Presence of infection, In critique, the sample size was small and the study’s follow-up as defined by the Centers for Disease Control (CDC) guide- period was short. In addition, the authors expanded the defini-

lines, was assessed at six weeks, three months and six months. tion of infection to include wound, urinary tract infection and Baseline characteristics were similar in patients allocated to ce- pneumonia in order to achieve statistical significance. Due to furoxime (n = 613) or placebo (n=624). Eight (1.3%) patients these limitations, this potential Level I study provides Level II ntibiotic A in the cefuroxime group and 18 patients (2.8%) in the placebo therapeutic evidence that for uncomplicated spine surgery, a u r ge y group developed a surgical site infection (p =0.073). A diagno- single preoperative dose of cephazolin decreases infection rate; S sis of spondylodiscitis or epidural abscess was made in nine pa- however, it does not significantly decrease the rate of wound in- p ine ega r ding

tients in the placebo group, but none in the cefuroxime group fection. The use of cephazolin appears to be associated with an S R in

(p < 0.01), which corresponded to a number necessary to treat increase in the development of resistant organisms. of 69 patients to prevent one of these infections. There were no Rohde et al5 described a retrospective comparative study de- significant adverse events attributed to either cefuroxime or signed to report the incidence of post-operative spondylodiscitis placebo. Overall, the surgical site infection rate was 1.3% with in 1642 consecutive cases in which no antibiotic prophylaxis was

antibiotics versus 2.8% with placebo (p=0.073), and the discitis used and to define the value of a collagenous sponge containing r o p hylaxis rate was 0/613 versus 9/624 (p<0.01), respectively. The authors gentamicin in preventing disc space infections. No topical or P concluded that a single, preoperative dose of cefuroxime signifi- systemic antibiotics were administered in the first 508 patients. ecommendations cantly reduces the risk of organ-space infection, most notably A 4 cm × 4 cm collagenous sponge containing 8 mg of genta- R spondylodiscitis, after surgery for herniated disc. Cefuroxime is micin was placed in the cleared disc space in the sub-sequent protective against spondylodiscitis. This study provides Level I 1134 patients. Surgery was performed for 1584 primary lumbar therapeutic evidence that for uncomplicated lumbar microdis- disc herniations (two-level discectomy in 39 cases, three-level cectomy, a single dose of cefuroxime versus placebo tends to de- discectomy in one case) and 169 operations for recurrent herni- crease rate of post operative infection and significantly reduces ations. In all patients, the erythrocyte sedimentation rate (ESR) the rate of spondylodiscitis specifically. was obtained before surgery and on the first day after surgery. Beginning in January 1992, C-reactive protein (CRP) also was Rubinstein et al3 performed a prospective, randomized con- analyzed before surgery, one day after surgery, and six days after trolled trial to investigate the efficacy of a single dose of 1 g of surgery. All patients were clinically reexamined on days 10-14 cephazolin in reducing postoperative infections in patients un- after surgery (day of discharge). Final follow-up was at 60 days. dergoing ”clean” operations on the lumbar spine. Of the 141 In 19 of these 508 patients, a postoperative spondylodiscitis patients included in the study, 70 received 1 g intravenous cep- developed, accounting for an incidence rate of 3.7%. None of hazolin upon arrival to the operative room (approximately two the 1134 patients receiving antibiotic prophylaxis developed a hours prior to surgery) and 71 received placebo. Presence of postoperative spondylodiscitis during the follow-up period of infection was assessed at 30 days, with surgical site infection de- 60 days. Therefore, the incidence of postoperative spondylodis- fined as drainage of purulent material from the operative site citis was 0%. Using the Fisher exact test, the difference in the and a positive bacteriological culture or inflammation of an area incidence rates between the patient groups with and without more than 20 mm in diameter; for urinary tract infection, more antibiotic prophylaxis during lumbar discectomy was highly sig- than 100,000 colony forming units/mL on culture; and for pneu- nificant (p < 0.00001). The authors observed no complications monia, the clinical diagnosis was made by the treating physician. related to the use of a collagenous sponge containing gentamicin There were 21 wound or urinary infections in the 71 patients for antibiotic prophylaxis. The authors concluded that a 3.7% who received placebo and nine in the 70 who received cephazo- incidence of postoperative spondylodiscitis was found in the ab- lin (p < 0.05). Nine patients (12.7%) who received placebo and sence of prophylactic antibiotics. Gentamicin-containing collag- three (4.3%) who received cephazolin developed wound infec- enous sponges placed in the cleared disc space were effective in tions (p = 0.07). All but three of the infections in the placebo preventing postoperative spondylodiscitis. This study provides group were confirmed by bacterial culture. All of the organ- Level III therapeutic evidence that for uncomplicated lumbar isms isolated from the patients who received placebo (except microdiscectomy, topical administration of a gentamicin soaked the group-D streptococci which are inherently resistant) were collagen sponge is more effective than placebo in preventing clinically significant discitis.

Future Directions for Research 2002;51(2):391-400; discussion 400-391. For practical purposes, the North American Spine Society is sat- 2. Pavel A, Smith RL, Ballard A, Larson IJ. Prophylactic antibiot- isfied to base its recommendations for the use of prophylactic ics in elective orthopedic surgery: a prospective study of 1591 antibiotics on the results of existing data and does not call for a cases. South Med J. 1977;Suppl 1:50-55. 3. Rubinstein E, Findler G, Amit P, Shaked I. Perioperative prophy- definitive study to be conducted. lactic cephazolin in spinal surgery. A double-blind placebo- If further evidence is sought to strengthen the recommenda- controlled trial. J Bone Joint Surg Br. Jan 1994;76B(1):99-102. tions above, randomized controlled trials should be conducted 4. Petignat C, Francioli P, Harbarth S, et al. Cefuroxime prophy- that stratify results on specific patient populations, specific co- laxis is effective in noninstru-mented spine surgery: a double- morbidities, clinical conditions (eg, paraplegia), dosing and blind, placebo-controlled study. Spine (Phila Pa 1976). Aug 15 route of administration. 2008;33(18):1919-1924. 5. Rohde V, Meyer B, Schaller C, Hassler WE. Spondylodiscitis Efficacy (Mixed Groups) References after lumbar discectomy. Incidence and a proposal for prophy- 1. Barker FG 2nd. Efficacy of prophylactic antibiotic therapy laxis. Spine (Phila Pa 1976). Mar 1 1998;23(5):615-620. in spinal surgery: a meta-analysis. Neurosurgery. Aug R ecommendations P r o p

hylaxis For patients undergoing open spine surgery without spinal implants, does antibiotic prophylaxis result in

in decreased infection rates compared to patients who do R

S ega

p not receive prophylaxis? ine r ding

u Prophylactic antibiotics are suggested to decrease the rate of spinal infec- r

A ge tions following uninstrumented lumbar spinal surgery. ntibiotic r y Grade of Recommendation: B

Petignat et al1 conducted a prospective, randomized controlled Luer et al2 described a retrospective case control study compar- trial assessing the efficacy of one preoperative 1.5 g dose of ce- ing postoperative infections after laminectomy/discectomy to furoxime in preventing surgical site infection after lumbar lami- examine variables that may be associated with infection. The notomy and discectomy for herniated disc. Of the 1237 patients antibiotic protocol included a single intravenous dose of 1 g ce- included in the study, 613 received 1.5 g intravenous cefuroxime fazolin with varied timing (within one hour preoperatively, to on induction and 624 received placebo. Presence of infection, within two hours, to greater than two hours, to post incision). as defined by the Centers for Disease Control (CDC) guidelines, Infection was confirmed via bacterial cultures. The clinical eval- was assessed at six weeks, three months and six months. Base- uation for infection was not described. Of the 22 patients with line characteristics were similar in patients allocated to cefurox- documented wound infection, 12 had received prophylactic an- ime (n = 613) or placebo (n=624). Eight (1.3%) patients in the tibiotics with 33% (4/12) having received cefazolin within two cefuroxime group and 18 patients (2.8%) in the placebo group hours of incision versus 57% (8/14) of the uninfected matched developed a surgical site infection (P =0.073). A diagnosis of controls, p=0.001. The surgical incision was closed less than two spondylodiscitis or epidural abscess was made in nine patients hours after incision in 43% (6/14) of uninfected patients and in the placebo group, but none in the cefuroxime group (p < 17% (2/12) with infection (p<0.001). The authors reported that 0.01), which corresponded to a number necessary to treat of 69 wound culture data did not indicate infection by organisims re- patients to prevent one of these infections. There were no signifi- sistant to cefazolin. They concluded that the choice of cefazolin cant adverse events attributed to either cefuroxime or placebo. appears adequate but administration needs to occur in the ap- Overall surgical site infection rate was 1.3% with antibiotics propriate time frame. This small study provides Level III thera- versus 2.8% with placebo (p=0.073), and discitis rate was 0/613 peutic evidence that antibiotic prophylaxis with cephalosporin versus 9/624 (p<0.01), respectively. The authors concluded that more than two hours prior to incision appears to yield a higher a single, preoperative dose of cefuroxime significantly reduces infection rate, and dosing within two hours of incision may im- the risk of organ-space infection, most notably spondylodiscitis, prove infection rate. after surgery for herniated disc. Cefuroxime is protective against Piotrowski et al3 performed a retrospective comparative spondylodiscitis. This study provides Level I therapeutic evi- study of 5041 patients, evaluating the rate of postoperative dis- dence that for uncomplicated lumbar microdiscectomy, a single citis during two time periods: one in which perioperative anti- preoperative 1.5 g dose of cefuroxime is more effective in pre- biotics were given, and one in which they were not. During the venting infection than placebo. former, the rate of discitis was 0.6%; during the latter, it was 2.3% (p<0.001). This was statistically significant. There were no other

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 11 reported differences during these two time periods. In critique for antibiotic prophylaxis. The authors concluded that a 3.7% of this large study, while it was stated that first or second-gen- incidence of postoperative spondylodiscitis was found in the ab- eration cephalosporin were given, the dosing protocol was not sence of prophylactic antibiotics. Gentamicin-containing collag- detailed. This study offers Level III therapeutic evidence that enous sponges placed in the cleared disc space were effective in perioperative antibiotics lower the infection rate at the level of preventing postoperative spondylodiscitis. This study provides the disc after lumbar disc surgery. Level III therapeutic evidence that for uncomplicated lumbar Rohde et al4 described a retrospective comparative study de- microdiscectomy, topical administration of a gentamicin soaked signed to report the incidence of post-operative spondylodiscitis collagen sponge is more effective than placebo in preventing in 1642 consecutive cases in which no antibiotic prophylaxis was clinically significant discitis. used and to define the value of a collagenous sponge containing gentamicin in preventing disc space infections. No topical or Future Directions for Research systemic antibiotics were administered in the first 508 patients. For practical purposes, the North American Spine Society is sat- A 4 cm × 4 cm collagenous sponge containing 8 mg of genta- isfied to base its recommendations for the use of prophylactic micin was placed in the cleared disc space in the subsequent antibiotics on the results of existing data and does not call for a 1134 patients. Surgery was performed for 1584 primary lumbar definitive study to be conducted. disc herniations (two-level discectomy in 39 cases, three-level If further evidence is sought to strengthen the recommenda- discectomy in one case) and 169 operations for recurrent herni- tions above, randomized controlled trials should be conducted ations. In all patients, the erythrocyte sedimentation rate (ESR) that stratify results on specific patient populations, specific co- ntibiotic A was obtained before surgery and on the first day after surgery. morbidities, clinical conditions (eg, paraplegia), dosing and u r ge y

Beginning in January 1992, C-reactive protein (CRP) also was route of administration. S analyzed before surgery, one day after surgery, and six days after p ine surgery. All patients were clinically reexamined on days 10-14 Efficacy (Noninstrumented) References ega r ding S R 1. Petignat C, Francioli P, Harbarth S, et al. Cefuroxime prophy- in after surgery (day of discharge). Final follow-up was at 60 days. In 19 of these 508 patients, a postoperative spondylodiscitis laxis is effective in noninstrumented spine surgery: a double- developed, accounting for an incidence rate of 3.7%. None of blind, placebo-controlled study. Spine (Phila Pa 1976). Aug 15 the 1134 patients receiving antibiotic prophylaxis developed a 2008;33(18):1919-1924. 2. Luer MS, Hatton J. Appropriateness of antibiotic selection and postoperative spondylodiscitis during the follow-up period of use in laminectomy and microdiskectomy. Am J Hosp Pharm. r o p hylaxis 60 days. Therefore, the incidence of postoperative spondylo- Apr 1993;50(4):667-670. P discitis was 0%. Using the Fisher exact test, the difference in the 3. Piotrowski WP, Krombholz MA, Muhl B. Spondylodiscitis after ecommendations incidence rates between the patient groups with and without lumbar disk surgery. Neurosurg Rev. 1994;17(3):189-193. R antibiotic prophylaxis during lumbar discectomy was highly sig- 4. Rohde V, Meyer B, Schaller C, Hassler WE. Spondylodiscitis nificant (p < 0.00001). The authors observed no complications after lumbar discectomy. Incidence and a proposal for prophy- related to the use of a collagenous sponge containing gentamicin laxis. Spine. Mar 1 1998;23(5):615-620.

For patients undergoing open spine surgery with spinal implants, does antibiotic prophylaxis result in decreased infection rates as compared to patients who do not receive prophylaxis?

Prophylactic antibiotics may be considered to decrease the rate of infections following instrumented spine fusion.

R Grade of Recommendation: C ecommendations P r o p hylaxis

Rechtine et al1 described a retrospective case series study of 235 lexin every six hours for seven days. Because of untoward drug consecutive fracture patients. Of the 235 patients, 117 under- reaction or deviation from the antibiotic protocol, 36 of the 269 in R went surgical stabilization. Of the 117 patients, 12 suffered a patients were eliminated from the study. Therefore, 233 patients S ega r ding perioperative infection, two had a staphylococcal infection and completed the entire study; 117 received preoperative antibiot- p ine 10 had a polymicrobial infection with gram-negative and gram- ics only, and 116 received pre- and postoperative antibiotics. At

S positive organisms. There was a statistically higher infection rate 21 days follow-up, there was no significant difference in infec- u r ge y in completely neurologically injured patients compared to those tion rates between the two antibiotic protocols. The postopera- A

ntibiotic with no deficit or incomplete injuries. The authors concluded tive infection rates were 4.3% for the preoperative only protocol that aggressive and earlier intervention is required in this pa- and 1.7% for the preoperative with extended antibiotic protocol. tient population. In critique, the study was designed to assess The overall postoperative infection rate was 3%. However, the the incidence of spinal infection in a spine trauma population study did identify five variables that appeared to demonstrate a

and does not state the duration of follow-up. This study provides trend toward increase in infection rate: blood transfusion, elec- Level IV therapeutic evidence that the infection rate in instru- trophysiological monitoring, increased height, increased weight, mented spinal surgery for trauma in patients receiving antibiotic and increased body mass index. Increased tobacco use trended prophylaxis is 10%. With neurologic injury, the infection rate is toward a lower infection rate. Statistical significance was not higher and the infections are polymicrobial. It supports the ef- achieved. The authors concluded that a larger study of 1400 pa- ficacy of prophylactic antibiotics in instrumented spinal surgery tients would possibly provide more statistically significant infor- in patients with incomplete cord injury or in spinal fractures mation. Although a prospective comparative study by design, without cord injury. However, in the subgroup with spinal cord for the purpose of this question, this study provides Level IV injury, infections were more likely a result of multiple organisms (case series) evidence that a single dose of cephazolin is as effec- including gram-negative species. This study raises compelling tive as a multiple dosage protocol in lumbar patients undergoing questions about antibiotic choice for prophylaxis in spinal cord instrumented lumbar procedures when compared to previously injury patients. This does not answer the question directly but reported historical infection rates. gives epidemiological evidence that instrumented spinal proce- Wimmer et al3 performed a prospective series detailing an- dures have a higher than expected infection rate and when spinal tibiotic prophylaxis in an instrumented spinal fusion popula- cord injury occurs the rate is much higher and frequently com- tion. There were 110 patients with Cotrel – Doubassait (CD) plicated. This suggests that more varied and comprehensive pro- or Moss Miami instrumentation. Of the 110 patients, 56 were phylaxis needs to be undertaken in the specific subsets of spinal instrumented for painful spondylolisthesis and 54 for scoliosis. trauma and cord injury. Two grams of cefamandole were given preoperatively followed Hellbusch et al2 conducted a prospective, randomized con- by three postoperative doses of 2 g per day for three days. One trolled trial examining the effects of multiple dosing regiments infection was reported early in the spondylolisthesis group and on the postoperative infection rate in instrumented lumbar spi- one late infection was reported in the scoliosis group. The au- nal fusion. Two hundred sixty-nine patients were randomized thors concluded that this prophylactic regimen was effective into either a preoperative only protocol or preoperative with an in decreasing the expected infection rate in this instrumented extended postoperative antibiotic protocol. Patients in the preop- group. This study offers Level IV therapeutic evidence that peri- erative only protocol group received a single dose of intravenous operative prophylactic antibiotics lowered the infection rates in cefazolin 1 g or 2 g based on weight 30 minutes before incision. instrumented spinal surgery when compared to previously re- The extended postoperative antibiotic protocol group received ported historical infection rates. the same preoperative dose plus postoperative intravenous cefazolin every eight hours for three days followed by oral cepha-

Future Directions for Research Efficacy (Instrumented) References For practical purposes, the North American Spine Society is sat- 1. Rechtine GR, Bono PL, Cahill D, Bolesta MJ, Chrin AM. Post- isfied to base its recommendations for the use of prophylactic operative wound infection after instrumentation of thoracic and antibiotics on the results of existing data and does not call for a lumbar fractures. J Orthop Trauma. Nov 2001;15(8):566-569. definitive study to be conducted. 2. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. multiple-dose antibiotic prophylaxis in instrumented lumbar If further evidence is sought to strengthen the recommenda- fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- tions above, randomized controlled trials should be conducted 627; discussion 627. that stratify results on specific patient populations, specific co- 3. Wimmer C, Nogler M, Frischut B. Influence of antibiotics on morbidities, clinical conditions (eg, paraplegia), dosing and infection in spinal surgery: A prospective study of 110 patients. route of administration. J Spinal Disord. 1998;11:498-500.

What rate of surgical site infections can be

expected with the use of antibiotic prophylaxis,

considering both patients with and patients ntibiotic A u r ge y

without medical comorbidities? S p ine ega r ding S R in

CONSENSUS STATEMENT: Despite appropriate prophylaxis, the rate of surgical site infections in spine surgery is 0.7% - 10%. The expected rate for patients without comorbidities ranges from 0.7 – 4.3% and for patients with comorbidities ranges from 2.0 - 10%. Current best practice r o p hylaxis with antibiotic protocols has failed to eliminate (reach an infection rate of P

0.0%) surgical site infections. ecommendations R

Chen et al1 performed a retrospective case control study to de- operative only protocol group received a single dose of intra- termine the role diabetes plays in spinal infection risk. Of the venous cefazolin 1 g or 2 g based on weight 30 minutes before 195 spinal infection patients included in the study, 30 had dia- incision. The extended postoperative antibiotic protocol group betes and 165 did not. Prophylactic protocols varied and the received the same preoperative dose plus postoperative intra- spinal surgeries were heterogeneous with instrumented and un- venous cefazolin every eight hours for three days followed by instrumented procedures at all levels. Outcomes were reviewed oral cephalexin every six hours for seven days. Because of un- at 30 days for all patients and at one year for patients with fixa- toward drug reaction or deviation from the antibiotic protocol, tion. Known risk factors for surgical site infection in spinal sur- 36 of the 269 patients were eliminated from the study. Therefore, gery were examined: age, gender, tobacco use, body mass index, 233 patients completed the entire study; 117 receiving preopera- American Society of Anesthesiologists (ASA) class, intraoperative antibiotics only, and 116 receiving pre- and postoperative tive antibiotic redosing, surgical time, bone allograft use, esti- antibiotics. At 21 days follow-up, there was no significant dif- mated blood loss (EBL) and drain use. The adjusted relative risk ference in infection rates between the two antibiotic protocols. of having diabetes for developing surgical site infection was 4.10 The postoperative infection rates were 4.3% for the preopera- (95% C.I. = 1.37–12.32). Other factors did not appear as risk tive only protocol and 1.7% for the preoperative with extended factors for surgical site infections. The data confirm that diabetes antibiotic protocol. The overall postoperative infection rate was is a risk factor for surgical site infections in spinal arthrodesis 3%. However, the study did identify five variables that appeared surgery. This study provides Level II prognostic evidence that to demonstrate a trend toward increase in infection rate: blood diabetes alone, and not body habitus or other risk factors, in- transfusion, electrophysiological monitoring, increased height, creases the risk of infection after spinal surgery. increased weight and increased body mass index. Increased to- Hellbusch et al2 conducted a prospective, randomized con- bacco use trended toward a lower infection rate. Statistical sig- trolled trial examining the effects of multiple dosing regiments nificance was not achieved. The authors concluded that a larger on the postoperative infection rate in instrumented lumbar spi- study of 1400 patients would possibly provide more statistically nal fusion. Two hundred sixty-nine patients were randomized significant information. The overall infection rate even with a into either a preoperative only protocol or preoperative with an prophylaxis was 1.7% - 4.3% with an overall infection rate of 3%. extended postoperative antibiotic protocol. Patients in the pre- Because the follow-up was not standardized, this potential Level

I study provides Level II prognostic evidence that a 3% infection cocci which are inherently resistant) were sensitive to cephazolin rate (range: 1.7% - 4.3%) occurs in the face of antibiotic prophy- whereas in the cephazolin prophylactic group 43% of the organ- laxis. isms isolated were resistant or had reduced sensitivity to the Sweet et al3 performed a retrospective comparative study to drug. The authors concluded that the administration of a single evaluate the safety and efficacy of adjunctive local application dose of cephazolin preoperatively is recommended for patients of vancomycin for infection prophylaxis in posterior instru- undergoing lumbar spinal surgery. In critique, the sample size mented thoracic and lumbar spine wounds compared to intra- was small and the study’s follow-up period was short. In ad- venous cephalexin alone. Since 2000, 1732 consecutive thoracic dition, the authors expanded the definition of infection to in- and lumbar posterior instrumented spinal fusions have been clude wound, urinary tract infection and pneumonia in order performed with routine 24 hours of perioperative intravenous to achieve statistical significance. Due to these limitations, this antibiotic prophylaxis with cephalexin. Since 2006, 911 of these potential Level I study provides Level II prognostic evidence that instrumented thoracic and lumbar cases had 2 g of vancomycin the rate of infection with appropriate prophylaxis is 4.3%. For powder applied to the wound prior to closure in addition to in- uncomplicated lumbar microdiscectomy, a single preoperative travenous antibiotics. A retrospective review for infection rates dose (1 g) of cephazolin is more effective than placebo in mini- R

ecommendations and complications was performed with an average follow-up of mizing infection. 2.5 years (range: 1-7 years). If wound infection was suspected Kanayama et al5 performed a retrospective comparative P r o p hylaxis based on clinical and constitutional symptoms, aspiration was study reviewing the rate of surgical site infections in lumbar completed. If aspiration demonstrated purulent material or spine surgeries for two different antibiotic prophylaxis protocols. the wound was clinically suspicious for subfascial infection, One group received a preoperative dose and redosing at three the wound was explored and aerobic, anaerobic and fungal cul- hours, and the second group received a prolonged postoperative

tures were obtained. Posterior instrumented thoracic and lum- dosing regimen. A first-generation cephalosporin was admin- in R

S bar fusions were performed in 821 patients using intravenous istered unless the patient had a history of a significant allergy ega r ding p ine cephalexin prophylaxis with a total of 21 resulting deep wound such as anaphylactic shock, systemic skin eruption, or toxic liver infections (2.6%). Coag negative staph was the most commonly dysfunction. Postoperative-dose group patients received antibi- S

u r ge y isolated organism. Posterior instrumented thoracic and lumbar otics for five to seven days after surgery. No postoperative-dose A fusions were performed in 911 patients with intravenous cepha- group patients received antibiotics only on the day of surgery; ntibiotic lexin plus adjunctive local vancomycin powder with two ensu- antibiotics were given 30 minutes before skin incision. An ad- ing deep wound infections (0.2%). The reduction in wound in- ditional dose was administered every three hours to maintain fections was statistically significant (p < 0.0001). There were no therapeutic levels throughout surgery. The rate of surgical site adverse clinical outcomes or wound complications related to the infection was compared between the two prophylaxis groups. At local application of vancomycin. The authors concluded that ad- a maximum of six months, a positive wound culture and/or typi- junctive local application of vancomycin powder decreases the cal infectious signs including a purulent exudate, surrounding post surgical wound infection rate with statistical significance erythema, and wound fluctuance detected infections. Labora- in posterior instrumented thoracolumbar spine fusions. This tory studies were also referenced, such as prolonged elevation study provides Level II prognostic evidence that adjunctive local in the C-reactive protein value. There were 1133 patients in the application of vancomycin powder decreases the post surgical postoperative-dose group and 464 patients in the no postopera- wound infection rate compared with intravenous cephalexin in tive-dose group. The rate of instrumentation surgery was not sta- posterior instrumented thoracolumbar fusion. tistically different between the postoperative-dose group (43%) Rubinstein et al4 performed a prospective, randomized and the no postoperative-dose group (39%). The overall rate of controlled trial to investigate the efficacy of a single dose of 1 surgical site infection was 0.7%. The infection rate was 0.8% in g of cephazolin in reducing postoperative infections in patients the postoperative-dose group and 0.4% in the no postoperative- undergoing ‘clean’ operations on the lumbar spine. Of the 141 dose group; the difference between the two was not significant. It patients included in the study, 70 received 1 g intravenous cep- is important to note that the rate of SSI was determined accord- hazolin upon arrival to the operative room (approximately two ing to the number of wound infections requiring additional sur- hours prior to surgery) and 71 received placebo. Presence of gical interventions; thus, the rate of surgical site infection neces- infection was assessed at 30 days, with surgical site infection sarily was underestimated in this study. Regarding the organisms defined as drainage of purulent material from the operative site of surgical site infection, resistant strains of bacteria were cul- and a positive bacteriological culture, or inflammation of an area tured in five (83.3%) of six patients in the postoperative-dose more than 20 mm in diameter; for urinary tract infection, more group, whereas none was cultured in the no postoperative-dose than 100,000 colony forming units/mL on culture; and for pneu- group. This study provides Level II prognostic evidence that de- monia, the clinical diagnosis was made by the treating physician. spite many different regimens of prophylaxis, the best achieved There were 21 wound or urinary infections in the 71 patients who infection rate was 0.7%. received placebo and nine in the 70 who received cephazolin (p Olsen (2003) et al6 performed a retrospective case control < 0.05). Nine patients (12.7%) who received placebo and three study to identify the specific independent risk factors for surgi- (4.3%) who received cephazolin developed wound infections (p cal site infections occurring after laminectomy or spinal fusion. = 0.07). All but three of the infections in the placebo group were All patient received standard prophylaxis with cephalosporin or confirmed by bacterial culture. All the organisms isolated from vancomycin in penicillin sensitive patients. Infection was de- the patients who received placebo (except the group-D strepto- fined using the CDC guideline definition, with infections identi-

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 15 fied between two and 83 days (median time from surgery to in- in completely neurologically injured patients compared to those fection was 14 days). Of the 53 of 1918 patients who experienced with no deficit or incomplete injuries. The authors concluded surgical site infections, 12 were excluded due to missing data. that aggressive and earlier intervention is required in this patient These patients were compared with 179 noninfected matched population. In critique, the study was designed to assess the inci- controls. Infection rate even with prophylaxis was 2.76% with dence of spinal infection in a spine trauma population and does no significant variation in the infection rate during the four-year not state the duration of follow-up. It offers Level III prognostic period. The authors identified postoperative incontinence, obe- evidence the infection rate in spinal surgery for trauma in pa- sity, tumor resection and posterior approach as risk factors. This tients receiving antibiotic prophylaxis is 10%. With neurologic study provides Level III prognostic evidence that incontinence injury, the infection rate is higher and the infections are poly- (resulting from neurologic injury), obesity, tumor resection (re- microbial. The critical evidence is the epidemiologic fact that lated to neurologic deficits) and posterior approach increase risk polymicrobial infections are most common in the neurologically of infection. In the face of antibiotic prophylaxis with all com- injured as opposed to non-injured patients and antibiotic selec- ers and comorbidities represented, a 2.76% infection rate can be tion to include gram-negative coverage in this subset should be expected. considered. Olsen (2008) et al7 described a retrospective case control Fang et al9 reported a retrospective case control study analyz- study designed to determine independent risk factors for sur- ing preoperative and intraoperative risk factors for spinal infec- gical site infection following orthopedic spinal operations. All tion after surgery, with characterization of the nature and timing patient received standard prophylaxis with cephalosporin or of the infections. A first generation cephalosporin was given ntibiotic A vancomycin in penicillin sensitive patients. Of 2316 patients, unless the patient had a history of a significant allergy, in which u r ge y

46 patients with superficial, deep or organ-space surgical site case vancomycin was given. Antibiotics were redosed during S infections were identified and compared with 227 uninfected prolonged cases (greater than six hours) or after significant p ine control patients. The overall rate of spinal surgical site infec- blood loss. Antibiotics were continued for 48 hours after the pro- ega r ding S R in

tion during the five years of the study was 2.0% (46/2316). Uni- cedure, except for simple decompressions, which only received variate analyses showed serum glucose levels, preoperatively and antibiotics until discharge. A review of three month follow-up within five days after the operation, to be significantly higher in data on 1629 procedures performed on 1095 patients revealed patients in whom surgical site infection developed than in un- that a postoperative infection developed in 48 patients (4.4%). infected control patients. Independent risk factors for surgical Data regarding preoperative and intraoperative risk factors were r o p hylaxis site infection that were identified by multivariate analysis were gathered from patient charts for these and a randomly selected P

diabetes (odds ratio = 3.5, 95% confidence interval = 1.2, 10.0), control group of 95 uninfected patients. For analysis, these pa- ecommendations suboptimal timing of prophylactic antibiotic therapy (odds ratio tient groups were further divided into adult and pediatric sub- R = 3.4, 95% confidence interval = 1.5, 7.9), a preoperative serum groups, with an age cutoff of 18 years. Preoperative risk factors glucose level of >125 mg/dL (>6.9 mmol/L) or a postoperative reviewed included smoking, diabetes, previous surgery, previ- serum glucose level of >200 mg/dL (>11.1 mmol/L) (odds ratio ous infection, steroid use, body mass index and alcohol abuse. = 3.3, 95% confidence interval = 1.4, 7.5), obesity (odds ratio = Intraoperative factors reviewed included staging of procedures, 2.2, 95% confidence interval = 1.1, 4.7), and two or more surgical estimated blood loss, operating time and use of allograft or in- residents participating in the operative procedure (odds ratio = strumentation. The majority of infections occurred during the 2.2, 95% confidence interval = 1.0, 4.7). A decreased risk of sur- early postoperative period (less than three months). Age greater gical site infection was associated with operations involving the than 60 years, smoking, diabetes, previous surgical infection, in- cervical spine (odds ratio = 0.3, 95% confidence interval = 0.1, creased body mass index and alcohol abuse were statistically sig- 0.6). The authors concluded that diabetes was associated with nificant preoperative risk factors. The most likely procedure to the highest independent risk of spinal surgical site infection, be complicated by an infection was a combined anterior/poste- and an elevated preoperative or postoperative serum glucose rior spinal fusion performed in a staged manner under separate level was also independently associated with an increased risk of anesthesia. Infections were primarily monomicrobial, although surgical site infection. The role of hyperglycemia as a risk factor five patients had more than four organisms identified. The most for surgical site infection in patients not previously diagnosed common organism cultured from the wounds was Staphylococ- with diabetes should be investigated further. Administration of cus aureus. All patients were treated with surgical irrigation and prophylactic antibiotics within one hour before the operation debridement and appropriate antibiotics to treat the cultured or- and increasing the antibiotic dosage to adjust for obesity are also ganism. The authors concluded that the 4.4% infection risk in important strategies to decrease the risk of surgical site infection patients with diabetes requires aggressive treatment of patients after spinal operations. This study provides Level III prognostic undergoing complex or prolonged spinal procedures to prevent evidence that infection occurred at a 2% overall rate in all pa- and treat infections. Understanding a patient’s preoperative risk tients in the face of prophylactic antibiotics. factors may help the physician to optimize a patient’s preopera- Rechtine et al8 described a retrospective case control study of tive condition. Additionally, awareness of critical intraoperative 235 consecutive fracture patients. Of the 235 patients, 117 un- parameters will help to optimize surgical treatment. It may be derwent surgical stabilization. Of the 117 patients, 12 suffered a appropriate to increase the duration of prophylactic antibiotics perioperative infection; two had a staphylococcal infection, and or implement other measures to decrease the incidence of in- 10 had a polymicrobial infection with gram- negative and gram- fection for high risk patients. Because of lack of standardized positive organisms. There was a statistically higher infection rate follow-up, this potential Level III study provides Level IV evi-

dence that diabetes is a specific risk factor for infection in instru- antibiotic protocol for a variety of spinal surgeries. Over a three mented lumbar fusion patients. year period 973 patients received 1.5 g intravenous ampicillin/ Liao et al10 described a retrospective case control study exam- sulbactam on induction or intravenous 400 mg Teicoplanin on ining infection risk in patients with diabetes undergoing instru- induction (if surgery longer than two hours) with redosing of mented lumbar fusion. Intravenous cefamezine (500 mg) was teicoplanin at four hours or 1500 mL blood loss. Data was gath- administered 30 minutes before surgery and the antibiotics were ered at six weeks to one year regarding drainage from the wound, continued for three days (intravenous cefamezine 500 mg every wound abscess or positive culture. Wound infection occurred in six hours). Spinal procedures that became infected after surgery nine cases (1%) and discitis in four of 657 (0.06%) patients. This were analyzed to identify the significance of preoperative and in- study provides Level IV prognostic evidence that a 1% infection traoperative risk factors. Characterization of the nature and tim- rate with 0.6% rate of discitis can be expected despite the use of ing of the infections was also performed. Of 337 patients who prophylaxis. underwent posterior spinal instrumented fusion between 1995 and 1997, 39 were diabetic. Plasma glucose concentration, body mass index, type of instrument, operation time, blood loss, hos- Despite appropriate prophylaxis, diabetes R

ecommendations pital stay and complications were recorded. The pathogenic or- carries an increased infection rate compared ganism and treatments for infection were also described. Wound P with non-diabetic patients. r o p hylaxis infection characterized by wound erythematous changes, partial wound dehiscence with purulent discharge and wound culture data was obtained from the charts at one year minimum follow- Level of Evidence: III up (average 2.75 years). The rate of wound infection in diabetic 1 patients was 10.3% compared with 0.7% in non-diabetic patients Chen et al performed a retrospective case control study to de- in R

S (p = 0.003). Body mass index and preoperative blood sugar were termine the role diabetes plays in spinal infection risk. Of the ega r ding p ine also significantly different between the two groups (p = 0.02, p < 195 spinal infection patients included in the study, 30 had dia- 0.001). The authors concluded that patients with a diabetic his- betes and 165 did not. Prophylactic protocols varied and the S

u r ge y tory or preoperative hyperglycemia had a higher infection rate spinal surgeries were heterogeneous with instrumented and un- A after posterior spinal instrumented fusion when compared with instrumented procedures at all levels. Outcomes were reviewed ntibiotic non-diabetic patients. Due to the small sample size of patients at 30 days for all patients and at one year for patients with fixa- not enrolled at the same point in their disease, this potential tion. Known risk factors for surgical site infection in spinal sur- Level III study provides Level IV prognostic evidence that dia- gery were examined: age, gender, tobacco use, body mass index, betic history or hyperglycemia preoperatively increases the risk American Society of Anesthesiologists (ASA) class, intraopera- of infection in complex spinal surgery. tive antibiotic redosing, surgical time, bone allograft use, esti- Mastronardi (2005) et al11 reported a retrospective compara- mated blood loss (EBL) and drain use. The adjusted relative risk tive study evaluating the efficacy of two intraoperative antibiotic of having diabetes for developing surgical site infection was 4.10 prophylaxis protocols in a large series of lumbar microdiscec- (95% C.I. = 1.37–12.32). Other factors did not appear as risk fac- tomies performed in two different neurosurgical centers. Of tors for surgical site infections. The data confirm that diabetes the 1167 patients included in the study, 450 received a single is a risk factor for surgical site infections in spinal arthrodesis intravenous dose of cefazoline 1 g at induction of general anes- surgery. This study provides Level II prognostic evidence that thesia (Group A) and 717 received a single dose of intravenous diabetes alone, and not body habitus or other risk factors, in- ampicillin 1 g and sulbactam 500 mg at induction of anesthesia creases the risk of infection after spinal surgery. (Group P). At six months, a diagnosis of postoperative spon- Olsen (2008) et al7 described a retrospective case control dylodiscitis was made in three out of 450 patients in Group A study designed to determine independent risk factors for sur- (0.67%) and in five out of 717 patients in Group P (0.69%). In gical site infection following orthopedic spinal operations. All all cases, treatment consisted of rigid thoracolumbar orthesis patient received standard prophylaxis with cephalosporin or and four to six week administration of amoxicillin/clavulanate vancomycin in penicillin sensitive patients. Of 2316 patients, compound (500/125 mg). The authors concluded that the low 46 patients with superficial, deep or organ-space surgical site incidence of postoperative spondylodiscitis obtained with both infections were identified and compared with 227 uninfected protocols seems to confirm that intraoperative antibiotic pro- control patients. The overall rate of spinal surgical site infec- phylaxis is associated with the same rate of discitis seen with tion during the five years of the study was 2.0% (46/2316). Uni- prolonged prophylaxis still adopted in many centers, but is more variate analyses showed serum glucose levels, preoperatively and advantageous both in terms of welfare and comfort for patients within five days after the operation, to be significantly higher in and in economic terms. However, at the moment it is not possi- patients in whom surgical site infection developed than in un- ble identify the ideal antibiotic for this purpose. A 0.7% infection infected control patients. Independent risk factors for surgical risk can be expected despite prophylaxis. Although a compara- site infection that were identified by multivariate analysis were tive study by design, this study provides Level IV (case series) diabetes (odds ratio = 3.5, 95% confidence interval = 1.2, 10.0), prognostic evidence that a 0.7% infection rate can be expected suboptimal timing of prophylactic antibiotic therapy (odds ratio despite prophylactic antibiotic use. = 3.4, 95% confidence interval = 1.5, 7.9), a preoperative serum Mastronardi (2004) et al12 presented a retrospective case se- glucose level of >125 mg/dL (>6.9 mmol/L) or a postoperative ries evaluating the safety and efficacy of a specific intraoperative serum glucose level of >200 mg/dL (>11.1 mmol/L) (odds ratio

= 3.3, 95% confidence interval = 1.4, 7.5), obesity (odds ratio = tive condition. Additionally, awareness of critical intraoperative 2.2, 95% confidence interval = 1.1, 4.7), and two or more surgical parameters will help to optimize surgical treatment. It may be residents participating in the operative procedure (odds ratio = appropriate to increase the duration of prophylactic antibiotics 2.2, 95% confidence interval = 1.0, 4.7). A decreased risk of sur- or implement other measures to decrease the incidence of in- gical site infection was associated with operations involving the fection for high risk patients. Because of lack of standardized cervical spine (odds ratio = 0.3, 95% confidence interval = 0.1, follow-up, this potential Level III study provides Level IV evi- 0.6). The authors concluded that diabetes was associated with dence that diabetes is a specific risk factor for infection in instru- the highest independent risk of spinal surgical site infection, mented lumbar fusion patients. and an elevated preoperative or postoperative serum glucose Liao et al10 described a retrospective case control study ex- level was also independently associated with an increased risk of amining infection risk in patients with diabetes undergoing in- surgical site infection. The role of hyperglycemia as a risk factor strumented lumbar fusion. Intravenous cefamezine (500 mg) for surgical site infection in patients not previously diagnosed was administered 30 minutes before surgery and the antibiot- with diabetes should be investigated further. Administration of ics were continued for three days (intravenous cefamezine 500 prophylactic antibiotics within one hour before the operation mg every six hours). Spinal procedures that became infected and increasing the antibiotic dosage to adjust for obesity are also after surgery were analyzed to identify the significance of pre- important strategies to decrease the risk of surgical site infection operative and intraoperative risk factors. Characterization of after spinal operations. This study provides Level III prognostic the nature and timing of the infections was also performed. Of evidence that diabetes is the highest independent risk factor, and 337 patients who underwent posterior spinal instrumented fu- ntibiotic A infection occurred at a 2% overall rate in all patients in the face sion between 1995 and 1997, 39 were diabetic. Plasma glucose u r ge y of prophylactic antibiotics. concentration, body mass index, type of instrument, operation S Fang et al9 reported a retrospective case control study analyz- time, blood loss, hospital stay and complications were recorded. p ine ing preoperative and intraoperative risk factors for spinal infec- The pathogenic organism and treatments for infection were also ega r ding S R in

tion after surgery, with characterization of the nature and timing described. Wound infection characterized by wound erythema- of the infections. A first generation cephalosporin was given tous changes, partial wound dehiscence with purulent discharge unless the patient had a history of a significant allergy, in which and wound culture data was obtained from the charts at one year case vancomycin was given. Antibiotics were redosed during minimum follow-up (average 2.75 years). The rate of wound in- prolonged cases (greater than six hours) or after significant fection in diabetic patients was 10.3% compared with 0.7% in r o p hylaxis blood loss. Antibiotics were continued for 48 hours after the pro- non-diabetic patients (p = 0.003). Body mass index and preop- P

cedure, except for simple decompressions, which only received erative blood sugar were also significantly different between the ecommendations antibiotics until discharge. A review of three month follow-up two groups (p = 0.02, p < 0.001). The authors concluded that pa- R data on 1629 procedures performed on 1095 patients revealed tients with a diabetic history or preoperative hyperglycemia had that a postoperative infection developed in 48 patients (4.4%). a higher infection rate after posterior spinal instrumented fusion Data regarding preoperative and intraoperative risk factors were when compared with non-diabetic patients. Due to the small gathered from patient charts for these and a randomly selected sample size of patients not enrolled at the same point in their control group of 95 uninfected patients. For analysis, these pa- disease, this potential Level III study provides Level IV prog- tient groups were further divided into adult and pediatric sub- nostic evidence that diabetic history or hyperglycemia preopera- groups, with an age cutoff of 18 years. Preoperative risk factors tively increases the risk of infection in complex spinal surgery. reviewed included smoking, diabetes, previous surgery, previous infection, steroid use, body mass index and alcohol abuse. Intraoperative factors reviewed included staging of procedures, There is insufficient evidence to make a estimated blood loss, operating time and use of allograft or in- statement regarding the impact of obesity strumentation. The majority of infections occurred during the on the rate of surgical site infection in pro- early postoperative period (less than three months). Age greater than 60 years, smoking, diabetes, previous surgical infection, in- phylaxed patients. creased body mass index and alcohol abuse were statistically significant preoperative risk factors. The most likely procedure to Level of Evidence: I (Insufficient) be complicated by an infection was a combined anterior/posterior spinal fusion performed in a staged manner under separate Chen et al1 performed a retrospective case control study to de- anesthesia. Infections were primarily monomicrobial, although termine the role that diabetes and other risk factors play in the five patients had more than four organisms identified. The most development of surgical site infection in spinal surgery patients. common organism cultured from the wounds was Staphylococ- Of the 195 spinal infection patients included in the study, 30 had cus aureus. All patients were treated with surgical irrigation and diabetes and 165 did not. Prophylactic protocols varied and the debridement and appropriate antibiotics to treat the cultured or- spinal surgeries were heterogeneous with instrumented and un- ganism. The authors concluded that the 4.4% infection risk in instrumented procedures at all levels. Outcomes were reviewed patients with diabetes requires aggressive treatment of patients at 30 days for all patients and at one year for patients with fixa- undergoing complex or prolonged spinal procedures to prevent tion. In addition to diabetes, known risk factors for surgical site and treat infections. Understanding a patient’s preoperative risk infection in spinal surgery were examinedincluding: age, gender, factors may help the physician to optimize a patient’s preopera- tobacco use, body mass index >35 (morbid obesity), American

Society of Anesthesiologists (ASA) class >3, intraoperative an- tion after surgery, with characterization of the nature and timing tibiotic redosing, surgical time, bone allograft use, estimated of the infections. A first generation cephalosporin was given blood loss (EBL) and drain use. The adjusted relative risk of hav- unless the patient had a history of a significant allergy, in which ing diabetes for developing surgical site infection was significant case vancomycin was given. Antibiotics were redosed during (RR 4.10, 95% C.I. = 1.37–12.32); however, the other factors did prolonged cases (greater than six hours) or after significant not appear as significant risk factors in univariate or multivariate blood loss. Antibiotics were continued for 48 hours after the pro- analysis. This study provides Level II prognostic evidence that cedure, except for simple decompressions, which only received diabetes alone, and not body habitus or other risk factors, in- antibiotics until discharge. A review of three month follow-up creases the risk of infection after spinal surgery. data on 1629 procedures performed on 1095 patients revealed Olsen (2003) et al6 performed a retrospective case control that a postoperative infection developed in 48 patients (4.4%). study to identify the specific independent risk factors for surgi- Data regarding preoperative and intraoperative risk factors were cal site infections occurring after laminectomy or spinal fusion. gathered from patient charts for these and a randomly selected All patients received standard prophylaxis with cephalosporin control group of 95 uninfected patients. For analysis, these pa- or vancomycin in penicillin sensitive patients. Infection was de- tient groups were further divided into adult and pediatric sub- R

ecommendations fined using the CDC guideline definition, with infections identi- groups, with an age cutoff of 18 years. Preoperative risk factors fied between two and 83 days (median time from surgery to in- reviewed included smoking, diabetes, previous surgery, previ- P r o p hylaxis fection was 14 days). Of the 53/1918 patients who experienced ous infection, steroid use, body mass index and alcohol abuse. surgical site infections, 12 were excluded due to missing data. Intraoperative factors reviewed included staging of procedures, These patients were compared with 179 noninfected matched estimated blood loss, operating time and use of allograft or in- controls. Infection rate even with prophylaxis was 2.76% with strumentation. The majority of infections occurred during the

no significant variation in the infection rate during the four-year early postoperative period (less than three months). Age greater in R

S period. Through multivariate anlaysis, the authors identified than 60 years, smoking, diabetes, previous surgical infection and ega r ding p ine postoperative incontinence, morbid obesity, tumor resection alcohol abuse were statistically significant preoperative risk fac- and posterior approach as independent risk factors for the de- tors. Infected patients also had increased BMI in comparison to S

u r ge y velopment of surgical site infection. This study provides Level control patients; however, this factor was not statistically signifi- A III prognostic evidence that morbid obesity is associated with a cant when pediatric patients were excluded from the analysis. ntibiotic fivefold increased risk of surgical site infection after spinal sur- The most likely procedure to be complicated by an infection gery (OR 5.2, 95% C.I.=1.9-14.2). was a combined anterior/posterior spinal fusion performed in Olsen (2008) et al7 described a retrospective case control a staged manner under separate anesthesia. Infections were pri- study designed to determine independent risk factors for sur- marily monomicrobial, although five patients had more than gical site infection following orthopedic spinal operations. All four organisms identified. The most common organism cultured patients received standard prophylaxis with cephalosporin or from the wounds was Staphylococcus aureus. All patients were vancomycin in penicillin sensitive patients. Of 2316 patients, 46 treated with surgical irrigation and debridement and appropri- patients with superficial, deep or organ-space surgical site infec- ate antibiotics to treat the cultured organism. Understanding a tions were identified and compared with 227 uninfected control patient’s preoperative risk factors may help the physician to opti- patients. The overall rate of spinal surgical site infection during mize a patient’s preoperative condition. Additionally, awareness the five years of the study was 2.0% (46/2316). Independent risk of critical intraoperative parameters will help to optimize sur- factors for surgical site infection that were identified by multi- gical treatment. It may be appropriate to increase the duration variate analysis were diabetes (odds ratio = 3.5, 95% confidence of prophylactic antibiotics or implement other measures to de- interval = 1.2, 10.0), suboptimal timing of prophylactic antibiot- crease the incidence of infection for high risk patients. Because ic therapy (odds ratio = 3.4, 95% confidence interval = 1.5, 7.9), a of lack of standardized follow-up, this potential Level III study preoperative serum glucose level of >125 mg/dL (>6.9 mmol/L) provides Level IV evidence that age greater than 60 years, smok- or a postoperative serum glucose level of >200 mg/dL (>11.1 ing, diabetes, previous surgical infection and alcohol abuse are mmol/L) (odds ratio = 3.3, 95% confidence interval = 1.4, 7.5), statistically significant preoperative risk factors for infection in obesity (odds ratio = 2.2, 95% confidence interval = 1.1, 4.7), instrumented lumbar fusion patients; however, increased BMI and two or more surgical residents participating in the operative did not prove to be a significant risk factor when analyzing adult procedure (odds ratio = 2.2, 95% confidence interval = 1.0, 4.7). patients only. A decreased risk of surgical site infection was associated with Liao et al10 described a retrospective case control study exam- operations involving the cervical spine (odds ratio = 0.3, 95% ining infection risk in patients with diabetes undergoing instru- confidence interval = 0.1, 0.6). The authors suggest that increas- mented lumbar fusion. Intravenous cefamezine (500 mg) was ing the antibiotic dosage to adjust for obesity is an important administered 30 minutes before surgery and the antibiotics were strategy to decrease the risk of surgical site infection after spinal continued for three days (intravenous cefamezine 500 mg every operations. This study provides Level III prognostic evidence six hours). Spinal procedures that became infected after surgery that obesity is an independent risk factor for surgical site infec- were analyzed to identify the significance of preoperative and in- tion in spinal surgery patients, and infection occurred at a 2% traoperative risk factors. Of 337 patients who underwent poste- overall rate in all patients in the face of prophylactic antibiotics. rior spinal instrumented fusion between 1995 and 1997, 39 were Fang et al9 reported a retrospective case control study analyz- diabetic. Plasma glucose concentration, body mass index, type ing preoperative and intraoperative risk factors for spinal infec- of instrument, operation time, blood loss, hospital stay and com-

cal site infection in spinal surgery. J Neurosurg. Mar 2003;98(2 tients not enrolled at the same point in their disease, this poten- Suppl):149-155. tial Level III study provides Level IV prognostic evidence that 7. Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical diabetic history or hyperglycemia preoperatively increases the site infection following orthopaedic spinal operations. J Bone risk of infection in complex spinal surgery. Joint Surg Am. Jan 2008;90(1):62-69. ntibiotic A

8. Rechtine GR, Bono PL, Cahill D, Bolesta MJ, Chrin AM. Post- u r ge y

Future Directions for Research operative wound infection after instrumentation of thoracic and S For purposes of comparative effectiveness, well-designed prog- lumbar fractures. J Orthop Trauma. Nov 2001;15(8):566-569. 9. Fang A, Hu SS, Endres N, Bradford DS. Risk factors for infec- p ine nostic studies defining the rate of surgical site infections in pa- ega r ding tion after spinal surgery. Spine. 1460;30(12):1460-1465. S R in

tients with and without comorbidities need to be performed. 10. Liao JC, Chen WJ, Chen LH, Niu CC. Postoperative wound To optimize outcomes for patients with comorbidities, evi- infection rates after posterior instrumented spinal surgery in dence is needed regarding specific antibiotic regimens, dosing diabetic patients. Chang Gung Med J. 2006;29(5):480-485. and route of administration for patients with comorbidities. 11. Mastronardi L, Rychlicki F, Tatta C, Morabito L, Agrillo U, Ducati A. Spondylodiscitis after lumbar microdiscectomy: effec- r o p hylaxis

Rate of Surgical Site Infections References tiveness of two protocols of intraoperative antibiotic prophylaxis P

1. Chen S, Anderson MV, Cheng WK, Wongworawat MD. Diabe- in 1167 cases. Neurosurg Rev. Oct 2005;28(4):303-307. ecommendations

tes Associated with Increased Surgical Site Infections in Spinal 12. Mastronardi L, Tatta C. Intraoperative antibiotic prophylaxis in R Arthrodesis. Clin Orthop Relat Res. Jul 2009;467(7):1670-1673. clean spinal surgery: a retrospective analysis in a consecutive 2. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. series of 973 cases. Surg Neurol. Feb 2004;61(2):129-135; discus- multiple-dose antibiotic prophylaxis in instrumented lumbar sion 135.

B. Protocol

For patients receiving antibiotic prophylaxis prior to open spine surgery, what are the recommended drugs, their dosages, administration routes and timing resulting in decreased postoperative infection rates? R ecommendations P r o p hylaxis Preoperative antibiotic prophylaxis is suggested to decrease infection rates in patients undergoing spine surgery. In typical, uncomplicated spinal procedures, the superiority of one agent, dose or route of

administration over any other has not been clearly demonstrated. When in R S

ega r ding determining the appropriate drug choice, the patient’s risk factors, p ine allergies, length and complexity of the procedure and issues of antibiotic

S resistance should be considered. u r ge y A

ntibiotic Grade of Recommendation: B

Petignat et al1 conducted a prospective, randomized controlled with a documented trend for reduced post op infection and sig- trial assessing the efficacy of one preoperative 1.5 g dose of ce- nificantly reduces the incidence of spondylodiscitis specifically. furoxime in preventing surgical site infection after lumbar lami- Barker et al2 performed a retrospective meta-analysis of 451 notomy and discectomy for herniated disc. Of the 1237 patients prophylaxed patients compared with 392 controls to examine included in the study, 613 received 1.5 g intravenous cefuroxime the efficacy of antibiotic prophylaxis in spinal surgery combin- on induction and 624 received placebo. Presence of infection, ing orthopaedic and neurosurgery trials (one spinal trial, four as defined by the Centers for Disease Control (CDC) guidelines, neurosurgical trials, one orthopedic trial). Types of prophylaxis was assessed at six weeks, three months and six months. Base- and protocols varied across the 451 patients receiving prophy- line characteristics were similar in patients allocated to cefurox- laxis. Duration of follow-up varied with infection confirmed ime (n = 613) or placebo (n=624). Eight (1.3%) patients in the by masked observer assessment of bacteriological cultures and cefuroxime group and 18 patients (2.8%) in the placebo group presence of purulent draining. All six trials reported lower in- developed a surgical site infection (p =0.073). A diagnosis of fection rates but significance was not achieved for any one trial spondylodiscitis or epidural abscess was made in nine patients (odds ration=0-0.74), p values ranged from 0.07 to 1.0. On me- in the placebo group, but none in the cefuroxime group (p < ta-analysis, the random effects model demonstrated significant 0.01), which corresponded to a number necessary to treat of 69 effects for efficacy, with an odds ratio of 0.37 (0.17-0.78, p<0.01). patients to prevent one of these infections. There were no sig- The fixed effects model yielded similar results (odds ratio=0.35, nificant adverse events attributed to either cefuroxime or place- p<0.006). Three trials used antibiotics with both gram-positive bo. Overall surgical site infection rate was 1.3% with antibiotics and gram-negative coverage and three trials used gram-positive versus 2.8% with placebo (p=0.073), and discitis rate was 0/613 coverage alone. There was no evidence of different treatment -ef versus 9/624 (p<0.01), respectively. The authors concluded that fects with the inclusion of gram-negative coverage. Investigation a single, preoperative dose of cefuroxime significantly reduces of the optimal timing of administration was not possible. The the risk of organ-space infection, most notably spondylodis- authors concluded that prophylactic antibiotic therapy for spinal citis, after surgery for herniated disc. Cefuroxime is protective operations is effective under a wide range of clinical conditions. against spondylodiscitis. This study provides Level I therapeu- No difference in the efficacies of differing antibiotic regimens tic evidence that for uncomplicated lumbar microdiscectomy, a was observed, provided at least one preoperative dose of gram- single preoperative 1.5 g dose of cefuroxime relative to placebo, positive coverage was administered. Investigation of optimal

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 21 timing of administration was not possible. This study provides period was short. In addition, the authors expanded the defini- Level II therapeutic evidence that prophylactic antibiotic thera- tion of infection to include wound, urinary tract infection and py with gram-positive coverage is effective in reducing the risk pneumonia in order to achieve statistical significance. Due to of infection after spinal surgery. The superiority of one agent or these limitations, this potential Level I study provides Level II regimen was not demonstrated. therapeutic evidence that for uncomplicated spine surgery, a Pons et al3 described a prospective, randomized trial com- single preoperative dose of cephazolin decreases infection rate; paring perioperative antibiotic protocols that included either 2 however, it does not significantly decrease the rate of wound in- g ceftizoxime or 1 g vancomycin plus 80 mg gentamicin in 291 fection. The use of cephazolin appears to be associated with an patients who underwent various clean spine surgeries. Of the increase in development of resistant organisms. 291 patients, 142 received ceftizoxime and 149 vancomycin/gen- Dobzyniak et al5 described a retrospective comparative study tamicin one hour prior to incision. Infections were confirmed examining the efficacy of single versus multiple dosing for lum- using bacterial cultures for deep infections, urinary tract infec- bar disc surgery. The antibiotics used for prophylaxis consisted tion, or catheter infections; pneumonia diagnosed by purulent of cephazolin 1 g, 525 patients; clindamycin 600 mg, 15 patients; sputum and/or new infiltrate on CXR; and cellulitis was diag- vancomycin 1 g plus clindamycin 600 mg, 46 patients; and van- nosed by presence of spreading induration or erythema. Pri- comycin 1 g alone, 24 patients. The choice of an antibiotic other mary infections were reported in 2.8% (4/142) of the ceftizox- than cephazolin was based on a patient allergy to penicillin or ime patients and 2.7% (4/149) of the vancomycin-gentamicin cephalosporin and surgeons preference when these allergies patients. Secondary infections were reported in 4.2% (6/142) were encountered. Of the 635 consecutive patients included in ntibiotic A and 4.0% (6/149) patients, respectively. The authors concluded the study, 418 received the multidose regimen, 192 received the u r ge y that the design of the trial does not allow for statistical analysis single dose and 25 patients were eliminated from the study as no S of subgroups, however, an overview of the data does not sug- preoperative dose was documented. Infection was confirmed at p ine gest a relationship between postoperative infection and any of six weeks via cultures and attending physician’s assessment. The ega r ding S R in

the technical or clinical variables. Ceftizoxime is less toxic than infection rate was 1.56% (3/192) with single dosing versus 1.20% vancomycin/gentamicin and equally as effective in preventing (5/418) with multiple dosing, p=0.711, Fisher exact test. The au- infections after clean neurosurgical procedures. Because the thors concluded that a single preoperative dose of prophylactic study design does not permit subgroup analysis, this potential antibiotics is as effective as preoperative plus postoperative anti- Level I study provides Level II evidence that ceftizoxime and biotics in the prevention of wound infections in lumbar disc sur- r o p hylaxis vancomycin-gentamicin are equally effective in reducing infec- gery. They recommend preoperative antibiotics alone, citing no P

tions with ceftizoxime being less toxic. However, the study was advantage in prolonging a patient’s discharge following lumbar ecommendations not designed for subgroup analysis. The superiority of one agent disc excision to administer postoperative antibiotics. This study R or regimen was not demonstrated. provides Level III therapeutic evidence that single dosing is as Rubinstein et al4 performed a prospective, randomized con- effective as multiple dosing; however, different antibiotics do not trolled trial to investigate the efficacy of a single dose of 1 g of appear to affect the rate of wound infection. The superiority of cephazolin in reducing postoperative infections in patients un- one agent or regimen was not demonstrated. dergoing ‘clean’ operations on the lumbar spine. Of the 141 Hellbusch et al6 conducted a prospective, randomized con- patients included in the study, 70 received 1 g intravenous cep- trolled trial examining the effects of multiple dosing regiments hazolin upon arrival to the operative room (approximately two on the postoperative infection rate in instrumented lumbar spi- hours prior to surgery) and 71 received placebo. Presence of nal fusion. Two hundred sixty-nine patients were randomized infection was assessed at 30 days, with surgical site infection de- into either a preoperative only protocol or preoperative with an fined as drainage of purulent material from the operative site extended postoperative antibiotic protocol. Patients in the pre- and a positive bacteriological culture, or inflammation of an operative only protocol group received a single dose of intra- area more than 20 mm in diameter; for urinary tract infection, venous cefazolin 1 g or 2 g based on weight 30 minutes before more than 100,000 colony forming units/mL on culture; and incision. The extended postoperative antibiotic protocol group for pneumonia, the clinical diagnosis was made by the treat- received the same preoperative dose plus postoperative intrave- ing physician. There were 21 wound or urinary infections in nous cefazolin every eight hours for three days followed by oral the 71 patients who received placebo and nine in the 70 who cephalexin every six hours for seven days. Because of untoward received cephazolin (p < 0.05). Nine patients (12.7%) who re- drug reaction or deviation from the antibiotic protocol, 36 of ceived placebo and three (4.3%) who received cephazolin devel- the 269 patients were eliminated from the study. Therefore, 233 oped wound infections (p = 0.07). All but three of the infections patients completed the entire study; 117 received preoperative in the placebo group were confirmed by bacterial culture. All antibiotics only and 116 received pre- and postoperative anti- the organisms isolated from the patients who received placebo biotics. At 21 days follow-up, there was no significant differ- (except the group-D streptococci which are inherently resistant) ence in infection rates between the two antibiotic protocols. were sensitive to cephazolin whereas in the cephazolin prophy- The postoperative infection rates were 4.3% for the preopera- lactic group 43% of the organisms isolated were resistant or had tive only protocol and 1.7% for the preoperative with extended reduced sensitivity to the drug. The authors concluded that the antibiotic protocol. The overall postoperative infection rate was administration of a single dose of cephazolin preoperatively is 3%. However, the study did identify five variables that appeared recommended for patients undergoing lumbar spinal surgery. to demonstrate a trend toward increase in infection rate: blood In critique, the sample size was small and the study’s follow-up transfusion, electrophysiological monitoring, increased height,

increased weight and increased body mass index. Increased wound culture and/or typical infectious signs including a pu- tobacco use trended toward a lower infection rate. Statistical rulent exudate, surrounding erythema, and wound fluctuance significance was not achieved, and the authors suggested that a detected infections. Laboratory studies were also referenced, larger sample size of 700 patients per group was needed to prove such as prolonged elevation in the C-reactive protein value. statisical superiority or equivalency between treatment groups. There were 1133 patients in the postoperative-dose group and The authors concluded that preoperative prophylactic antibiotic 464 patients in the no postoperative-dose group. The rate of in- use in instrumented lumbar spinal fusion is generally accepted strumentation surgery was not statistically different between the and has been shown consistently to decrease postoperative in- postoperative-dose group (43%) and the no postoperative-dose fection rates. Prolonged postoperative antibiotic dosing carries group (39%). The overall rate of surgical site infection was 0.7%. with it an increased cost and potential complications. Due to The infection rate was 0.8% (9/1133) in the postoperative-dose questions about the method of randomization and lack of vali- group and 0.4% (2/464) in the no postoperative- dose group; the dated outcome measures, this potential Level II study provides difference between the two was not significant. Regarding the Level III therapeutic evidence that preoperative prophylactic an- organisms of surgical site infection, resistant strains of bacteria tibiotic use in instrumented lumbar spinal fusion is effective in were cultured in five (83.3%) of six patients in the multiple-dose R

ecommendations reducing the risk of infection. The superiority of one agent or group, whereas none was cultured in the single-dose group. The regimen was not demonstrated. authors concluded there was no statistical difference was ob- P 7 r o p hylaxis Kakimaru et al reported results from a retrospective com- served between protocols. The CDC protocol of preoperative parative study comparing the infection rates following spinal dosing prevents development of resistant strains while reduc- surgery with and without postoperative antimicrobial prophy- ing the risk of surgical site infections. This study provides Level laxis. Of the 284 patients included in the study, 141 received pre- III therapeutic evidence that postoperative dosing is unneces-

operative and postoperative dosing while 143 received preop- sary and that preoperative plus intraoperative dosing only is ef- in R

S erative and intraoperative dosing. The antibiotics used included ficacious in preventing surgical site infection. Also, extended ega r ding p ine cefazolin 1 g in 108 patients, flomoxef 1 g in 26 patients, and dosing may induce resistant strains. Suction drains were left in piperacillin 1 g in 7 patients for the postoperative group. For place in fusions for two to three days. Accordingly, multidos- S

u r ge y the no postoperative dosing group, cefazolin 1 g was given to ing of antibiotics until drains are removed may not be beneficial. A 142 patients and minocycline 100 mg was given to 1 patient. The superiority of one agent or regimen was not demonstrated. ntibiotic Patients in the postoperative dosing group had an intravenous Luer et al9 described a retrospective case control study com- dose within 30 minutes of skin incision, a dose postoperatively paring postoperative infections after laminectomy/discectomy intravenously, and oral antibiotics for an average of 2.7 days, or to examine variables that may be associated with infection. The the preoperative dose with intraoperative redosing at three hour antibiotic protocol included a single intravenous dose of 1 g ce- intervals and a single postoperative dose. Patients in the no fazolin with varied timing (within one hour preoperatively, to postoperative doing group receieved a preoperative dose within within two hours, to greater than two hours, to postincision). 30 minutes of skin incision followed by intraoperative dosing at Infection was confirmed via bacterial cultures. The clinical eval- three hour intervals until skin closure. Infection was confirmed uation for infection was not described. Of the 22 patients with via bacterial cultures and inspection of wound for redness, heat, documented wound infection, 12 had received prophylactic an- swelling and pain. In the postoperative dosing group, 2.8% tibiotics with 33% (4/12) having received cefazolin within two (4/141) developed infections (three superficial and one deep); in hours of incision versus 57% (8/14) of the uninfected matched the no postoperative dosing group, 1.4% (2/143) developed in- controls, p=0.001. The surgical incision was closed less than two fections (p=0.335). The authors concluded that the duration of hours after incision in 43% (6/14) of uninfected patients and antimicrobial prophylaxis does not influence the rate of surgical 17% (2/12) with infection (p<0.001). The authors reported that site infections. Postoperative administration of antimicrobials wound culture data did not indicate infection by organisims re- appears unnecessary. This study provides Level III evidence that sistant to cefazolin. They concluded that the choice of cefazolin the duration of antimicrobial prophylaxis does not influence the appears adequate but administration needs to occur in the ap- incidence of surgical site infections. The superiority of one agent propriate time frame. This small study provides Level III thera- or regimen was not demonstrated. peutic evidence that antibiotic prophylaxis with cephalosporin Kanayama et al8 performed a retrospective comparative more than two hours prior to incision appears to yield a higher study to compare the rate of surgical site infections in lumbar infection rate, and dosing within two hours of incision may im- spine surgeries for two different antibiotic prophylaxis protocols. prove infection rate. A first-generation cephalosporin was administered unless the Mastronardi (2005) et al10 reported a retrospective compara- patient had a history of a significant allergy such as anaphylac- tive study evaluating the efficacy of two intraoperative antibiotic tic shock, systemic skin eruption, or toxic liver dysfunction. The prophylaxis protocols in a large series of lumbar microdiscec- postoperative group received antibiotics for five to seven days tomies performed in two different neurosurgical centers. Of after surgery. The no postoperative dose group received antibiot- the 1167 patients included in the study, 450 received a single ics only on the day of surgery; antibiotics were given 30 minutes intravenous dose of cefazoline 1 g at induction of general anes- before skin incision. An additional dose was administered every thesia (Group A) and 717 received a single dose of intravenous three hours to maintain therapeutic levels throughout surgery. ampicillin 1 g and sulbactam 500 mg at induction of anesthesia The rate of surgical site infection was compared between the two (Group P). At six months, a diagnosis of postoperative spon- prophylaxis groups. At a maximum of six months, a positive dylodiscitis was confirmed via lumbar MRI and sedimentation

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 23 rate in three out of 450 patients in Group A (0.67%) and in five travenous antibiotics. A retrospective review for infection rates out of 717 patients in Group P (0.69%). In all cases, treatment and complications was performed with an average follow-up of consisted of rigid thoracolumbar orthesis and four to six week 2.5 years (range: 1-7 years). If wound infection was suspected administration of amoxicillin/clavulanate compound (500/125 based on clinical and constitutional symptoms, aspiration was mg). The authors concluded that administration of a single completed. If aspiration demonstrated purulent material or dose of antibiotic at time of induction appears safe and effective. the wound was clinically suspicious for subfascial infection, the Multicenter trials would be needed to assess superiority of an wound was explored and aerobic, anaerobic and fungal cultures agent. This study provides Level III therapeutic evidence both were obtained. Posterior instrumented thoracic and lumbar fu- cefazolin and ampicillin/sulbactam are effective agents when sions were performed in 821 patients using intravenous cepha- given at the time of induction for prevention of discitis follow- lexin prophylaxis with a total of 21 resulting deep wound ining lumbar discectomy. The superiority of one agent or regimen fections (2.6%). Coag negative staph was the most commonly was not demonstrated. isolated organism. Posterior instrumented thoracic and lumbar Rohde et al11 described a retrospective comparative study de- fusions were performed in 911 patients with intravenous cepha- signed to report the incidence of postoperative spondylodiscitis lexin plus adjunctive local vancomycin powder with two ensu- in 1642 consecutive cases in which no antibiotic prophylaxis was ing deep wound infections (0.2%). The reduction in wound in- used and to define the value of a collagenous sponge containing fections was statistically significant (p < 0.0001). There were no gentamicin in preventing disc space infections. No topical or adverse clinical outcomes or wound complications related to the systemic antibiotics were administered in the first 508 patients. local application of vancomycin. The authors concluded that ad- ntibiotic A

A 4 cm × 4 cm collagenous sponge containing 8 mg of gentami- junctive local application of vancomycin powder decreases the u r ge y cin was placed in the cleared disc space in the subsequent 1134 post surgical wound infection rate with statistical significance S patients. Surgery was performed for 1584 primary lumbar disc in posterior instrumented thoracolumbar spine fusions. This p ine herniations (two-level discectomy in 39 cases, three-level dis- study provides Level III therapeutic evidence that adjunctive lo- ega r ding S R in

cectomy in one case) and 169 operations for recurrent hernia- cal application of vancomycin powder decreases the post surgi- tions. In all patients, the erythrocyte sedimentation rate (ESR) cal wound infection rate compared with intravenous cephalexin was obtained before surgery and on the first day after surgery. in posterior instrumented thoracolumbar fusion. Beginning in January 1992, C-reactive protein (CRP) also was Takahashi et al13 performed a retrospective comparative analyzed before surgery, one day after surgery and six days after study to compare the effectiveness of preoperative cephalospo- r o p hylaxis surgery. All patients were clinically re-examined on days 10-14 rin with various postoperative dosing schedules in reducing P

after surgery (day of discharge). Final follow-up was at 60 days. infection rates following a variety of spinal surgeries including ecommendations In 19 of these 508 patients, a postoperative spondylodiscitis decompression with or without fusion, with or without fixation. R developed, accounting for an incidence rate of 3.7%. None of Group 1 received first- or second-generation cephalosporin or the 1134 patients receiving antibiotic prophylaxis developed a penicillin administered by intravenous drip infusion for seven postoperative spondylodiscitis during the follow-up period of days (4 g/day) after the operation. After the drip infusion, ceph- 60 days. Therefore, the incidence of postoperative spondylo- alosporin was administered orally for one week. Group 2 re- discitis was 0%. Using the Fisher exact test, the difference in the ceived first- or second- generation cephalosporin administered incidence rates between the patient groups with and without by intravenous drip infusion. The initial dose was given at the antibiotic prophylaxis during lumbar discectomy was highly sig- time of anesthesia induction. When the operating time exceeded nificant (p < 0.00001). The authors observed no complications five hours, an additional dose was given intraoperatively. The -ad related to the use of a collagenous sponge containing gentamicin ministration was continued for five days (2 g/day) after the oper- for antibiotic prophylaxis. The authors concluded that a 3.7% ation, including the day of the operation. After the drip infusion, incidence of postoperative spondylodiscitis was found in the ab- a cephalosporin was given orally for one week. Group 3 received sence of prophylactic antibiotics. Gentamicin-containing collag- first- or second-generation cephalosporin administered by in- enous sponges placed in the cleared disc space were effective in travenous drip infusion, with the initial dose given at the time of preventing postoperative spondylodiscitis. This study provides anesthesia induction. Additional doses were administered every Level III therapeutic evidence that for uncomplicated lumbar three hours during the operation. The administration was then microdiscectomy, topical administration of a gentamicin soaked continued for three days (2 g/day) after the operation, including collagen sponge is more effective than placebo in preventing the day of the operation. After the drip infusion, a cephalosporin clinically significant discitis. was given orally for one week. Group 4 received first generation Sweet et al12 performed a retrospective comparative study to cephalosporin administered by intravenous drip infusion with evaluate the safety and efficacy of adjunctive local application the initial dose given at the time of anesthesia induction. Addi- of vancomycin for infection prophylaxis in posterior instru- tional doses were given every three hours during the operation. mented thoracic and lumbar spine wounds compared to intra- The administration was then continued for two days (2 g/day) venous cephalexin alone. Since 2000, 1732 consecutive thoracic after the operation, including the day of the operation. Of the and lumbar posterior instrumented spinal fusions have been 1415 patients included in the study, 539 were included in Group performed with routine 24 hours of perioperative intravenous 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- antibiotic prophylaxis with cephalexin. Since 2006, 911 of these ing the CDC guideline criteria, surgical site infections involving instrumented thoracic and lumbar cases had 2 g of vancomycin only the skin and/or subcutaneous tissues at the site of the inci- powder applied to the wound prior to closure in addition to in- sion were designated superficial infections, and those involving

deeper soft tissues (e.g., fascial and muscle layers) at the site of nal fusion. Two hundred sixty-nine patients were randomized the incision were designated deep infections. The overall fre- into either a preoperative only protocol or preoperative with an quency of surgical site infections for the different groups were: extended postoperative antibiotic protocol. Patients in the preop- Group 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, erative only protocol group received a single dose of intravenous 0/257 and 0/83, respectively. Comparision using Tukey’s mul- cefazolin 1 g or 2 g based on weight 30 minutes before incision. tiple comparison test showed p<0.05 for comparing infections The extended postoperative antibiotic protocol group received rates between Groups 1, 2 and 3. The authors concluded that the same preoperative dose plus postoperative intravenous ce- when thorough prophylactic countermeasures are undertaken fazolin every eight hours for three days followed by oral cepha- against perioperative surgical site infections, the frequency of lexin every six hours for seven days. Because of untoward drug these infections can be decreased, with a decrease in the duration reaction or deviation from the antibiotic protocol, 36 of the 269 of antimicrobial prophylaxis administration from seven days to patients were eliminated from the study. Therefore, 233 patients two days. This study provides Level III therapeutic evidence that completed the entire study; 117 received preoperative antibiot- shorter duration of antimicrobial prophylaxis is more effective, ics only and 116 received pre- and postoperative antibiotics. At and two days of antibiotic administration is recommended com- 21 day follow-up there was no significant difference in infection R

ecommendations pared to longer durations. rates between the two antibiotic protocols, and the superiority of one agent or regimen was not demonstrated. The postopera- P r o p hylaxis tive infection rates were 4.3% for the preoperative only protocol In typical, uncomplicated spinal procedures, and 1.7% for the preoperative with extended antibiotic protocol. a single dose of preoperative prophylactic The overall postoperative infection rate was 3%. However, the antibiotics with intraoperative redosing as study did identify five variables that appeared to demonstrate a trend toward increase in infection rate: blood transfusion, in R

S needed is suggested. electrophysiological monitoring, increased height, increased ega r ding p ine weight and increased body mass index. Increased tobacco use trended toward a lower infection rate. The authors concluded S Grade of Recommendation: B

u r ge y that preoperative prophylactic antibiotic use in instrumented A A single preoperative dose of prophylaxis with intraoperative re- lumbar spinal fusion is generally accepted and has been shown ntibiotic dosing as needed was demonstrated to be equivalent to extended consistently to decrease postoperative infection rates. Prolonged protocols for typical, uncomplicated spinal procedures. Extend- postoperative antibiotics increase cost and potential complica- ed protocols of more than three days have been shown to result tions. Due to questions about the method of randomization and in increased risk of antibiotic resistance. lack of validated outcome measures, this potential Level II study Dobzyniak et al5 described a retrospective comparative study provides Level III therapeutic evidence that preoperative pro- examining the efficacy of single versus multiple dosing for lum- phylactic antibiotic use in instrumented lumbar spinal fusion is bar disc surgery. The antibiotics used for prophylaxis consisted effective at reducing the risk of infection. 7 of cephazolin 1 g, 525 patients; clindamycin 600 mg, 15 patients; Kakimaru et al reported results from a retrospective com- vancomycin 1 g plus clindamycin 600 mg, 46 patients; and van- parative study comparing the infection rates following spinal comycin 1 g alone, 24 patients. The choice of an antibiotic other surgery with and without postoperative antimicrobial prophy- than cephazolin was based on a patient allergy to penicillin or laxis. Of the 284 patients included in the study, 141 received pre- cephalosporin and surgeons preference when these allergies operative and postoperative dosing while 143 received preop- were encountered. Of the 635 consecutive patients included in erative and intraoperative dosing. The antibiotics used included the study, 418 received the multidose regimen, 192 received the cefazolin 1 g in 108 patients, flomoxef 1 g in 26 patients, and single dose, and 25 patients were eliminated from the study since piperacillin 1 g in 7 patients for the postoperative group. For no preoperative dose was documented. Infection was confirmed the no postoperative dosing group, cefazolin 1 g was given to at six weeks via cultures and attending physician’s assessment. 142 patients and minocycline 100 mg was given to 1 patient. Pa- The infection rate was 1.56% (3/192) with single dosing versus tients in the postoperative dosing group had an intravenous dose 1.20% (5/418) with multiple dosing, p=0.711, Fisher exact test. within 30 minutes of skin incision, a dose postoperatively intra- The authors concluded that a single preoperative dose of prophy- venously, and oral antibiotics for an average of 2.7 days, or the lactic antibiotics is as effective as preoperative plus postoperative preoperative dose with intraoperative redosing at three hour in- antibiotics in the prevention of wound infections in lumbar disc tervals and a single postoperative dose. For the no postoperative surgery. They recommend preoperative antibiotics alone, citing dosing group, patients received a preoperative dose within 30 no advantage in prolonging a patient’s discharge following lum- minutes of skin incision with intraoperative dosing at three hour bar disc excision to administer postoperative antibiotics. This intervals until skin closure. Infection was confirmed via bacte- study provides Level III therapeutic evidence that single dosing rial cultures and inspection of wound for redness, heat, swell- is as effective as multiple dosing; however, different antibiotics ing and pain. In the postoperative dosing group, 2.8% (4/141) do not appear to affect the rate of wound infection. The superi- developed infections (three superficial and one deep); in the no ority of one agent or regimen was not demonstrated. postoperative dosing group, 1.4% (2/143) developed infections Hellbusch et al6 conducted a prospective, randomized con- (p=0.335). The authors concluded that the duration of antimi- trolled trial examining the effects of multiple dosing regiments crobial prophylaxis does not influence the rate of surgical site on the postoperative infection rate in instrumented lumbar spi- infections, and the superiority of one agent or regimen was not

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 25 demonstrated. This study provides Level III evidence that the first- or second-generation cephalosporin administered by induration of antimicrobial prophylaxis does not influence the intravenous drip infusion, with the initial dose given at the time of cidence of surgical site infections, and postoperative administra- anesthesia induction. Additional doses were administered every tion of antimicrobials appears unnecessary. three hours during the operation. The administration was then Kanayama et al8 performed a retrospective comparative continued for three days (2 g/day) after the operation, including study to compare the rate of surgical site infections in lumbar the day of the operation. After the drip infusion, a cephalosporin spine surgeries for two different antibiotic prophylaxis proto- was given orally for one week. Group 4 received first-generation cols. A first-generation cephalosporin was administered unless cephalosporin administered by intravenous drip infusion with the patient had a history of a significant allergy such as anaphy- the initial dose given at the time of anesthesia induction. Addi- lactic shock, systemic skin eruption or toxic liver dysfunction. tional doses were given every three hours during the operation. The postoperative dose group received antibiotics for five to The administration was then continued for two days (2 g/day) seven days after surgery. The no postoperative dose group re- after the operation, including the day of the operation. Of the ceived antibiotics only on the day of surgery; antibiotics were 1415 patients included in the study, 539 were included in Group given 30 minutes before skin incision and an additional dose 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- was administered every three hours to maintain therapeutic ing the CDC guideline criteria, surgical site infections involving levels throughout surgery. The rate of surgical site infection was only the skin and/or subcutaneous tissues at the site of the inci- compared between the two prophylaxis groups. At a maximum sion were designated superficial infections, and those involving of six months, a positive wound culture and/or typical infectious deeper soft tissues (eg, fascial and muscle layers) at the site of the ntibiotic A signs including a purulent exudate, surrounding erythema and incision were designated deep infections. The overall frequency u r ge y wound fluctuance detected infections. Laboratory studies were of surgical site infections for the different groups were: Group S also referenced, such as prolonged elevation in the C-reactive 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 p ine protein value. There were 1133 patients in the postoperative and 0/83, respectively. Comparision using Tukey’s multiple ega r ding S R in

dose group and 464 patients in the no postoperative dose group. comparison test showed p<0.05 for comparing infections rates The rate of instrumentation surgery was not statistically dif- between Groups 1, 2 and 3. The authors concluded that when ferent between the postoperative dose group (43%) and the no thorough prophylactic countermeasures are undertaken against postoperative dose group (39%). The overall rate of surgical site perioperative surgical site infections, the frequency of these in- infection was 0.7%. The infection rate was 0.8% (9/1133) in the fections can be decreased, with a decrease in the duration of an- r o p hylaxis postoperative dose group and 0.4% (2/464) in the no postopera- timicrobial prophylaxis administration from seven days to two P

tive dose group; the difference between the two was not signifi- days. This study provides Level III therapeutic evidence that a ecommendations cant. Regarding the organisms of surgical site infection, resistant shorter duration of antimicrobial prophylaxis is more effective R strains of bacteria were cultured in five (83.3%) of six patients in compared to longer durations. the postoperative dose group, whereas none were cultured in the no postoperative dose group. The authors concluded there was CONSENSUS STATEMENT: In patients no statistical difference was observed between protocols, and with comorbidities or for those undergo- the superiority of one agent or regimen was not demonstrated. The CDC protocol of preoperative dosing prevents developing complicated spine surgery, alternative ment of resistant strains while reducing the risk of surgical site prophylactic regimens including redosing, infections. This study provides Level III therapeutic evidence gram-negative coverage or the addition of that preoperative plus intraoperative redosing is efficacious in intrawound application of vancomycin or preventing surgical site infection. Also, extended dosing may in- gentamicin, are suggested to decrease the duce resistant strains. Suction drains were left in place in fusions for two to three days. Accordingly, extended dosing of antibiot- incidence of surgical site infections when ics until drains are removed may not be beneficial. compared to standard prophylaxis regimens. Takahashi et al13 performed a retrospective comparative study to compare the effectiveness of preoperative cephalospo- CONSENSUS STATEMENT: Comorbidities rin with various postoperative dosing schedules in reducing and risk factors reviewed in the literature infection rates following a variety of spinal surgeries including decompression with or without fusion, with or without fixation. include obesity, diabetes, neurologic defi- Group 1 received first- or second-generation cephalosporin or cits, incontinence, preoperative serum glu- penicillin administered by intravenous drip infusion for seven cose level of >125 mg/dL or a postoperative days (4 g/day) after the operation. After the drip infusion, ceph- serum glucose level of >200 mg/dL, trauma alosporin was administered orally for one week. Group 2 re- and prolonged multilevel instrumented sur- ceived first- or second-generation cephalosporin administered by intravenous drip infusion. The initial dose was given at the gery. Olsen (2003) et al14 and Olsen (2008) time of anesthesia induction. When the operating time exceeded et al15 are provided as support studies five hours, an additional dose was given intraoperatively. The -ad below to further define the risk factors as- ministration continued for five days (2 g/day) after the opera- sociated with surgical site infection in spine tion, including the day of the operation. After the drip infusion, surgery patients. a cephalosporin was given orally for one week. Group 3 received

Olsen (2003) et al14 performed a retrospective case control study betes was associated with the highest independent risk of spinal to identify the specific independent risk factors for surgical site surgical site infection, and an elevated preoperative or postop- infections occurring after laminectomy or spinal fusion. All pa- erative serum glucose level was also independently associated tients received standard prophylaxis with cephalosporin or van- with an increased risk of surgical site infection. The role of hy- comycin in penicillin sensitive patients. Infection was defined perglycemia as a risk factor for surgical site infection in patients using the CDC guideline definition, with infections identified not previously diagnosed with diabetes should be investigated between two and 83 days (median time from surgery to infection further. Administration of prophylactic antibiotics within one was 14 days). Of the 53 of 1918 patients who experienced surgi- hour before the operation and increasing the antibiotic dosage cal site infections, 12 were excluded due to missing data. These to adjust for obesity are also important strategies to decrease the patients were compared with 179 noninfected matched controls. risk of surgical site infection after spinal operations. This study The infection rate, even with prophylaxis, was 2.76% with no provides Level III prognostic evidence that diabetes, suboptimal significant variation in the infection rate during the four-year timing of antibiotic prophylaxis, preoperative gluclose level of period. Cultures were obtained from infected patients and >125 mg/dL, postoperative gluclose level of >200mg/dL and gram-negative rods and/or anaerobes were present in 17 of 39 obesity are indepdent risk factors for surgical site infection fol- R

ecommendations (44%) cultures. Additionally, gram-negative rods and/or anaer- lowing orthopaedic spinal operations. Alternative prophylactic obes were isolated significantly more often in patients who -un regimens, including higher dosages for obese patients, may be P r o p hylaxis derwent lumbar or lumbosacral procedures (15/24) compared to necessary to further reduce the risk of infection in patients with patients who underwent thoracic or cervical procedures (2/15, risk factors for surgical site infection. p<0.001). The authors identified postoperative incontinence, Kakimaru et al7 reported results from a retrospective com- obesity, tumor resection and posterior approach as significant parative study comparing the infection rates following spinal

risk factors. The length of stay was significantly longer in -pa surgery without instrumentation. Of the 284 patients included in R

S tients with a surgical site infection compared to those without in the study, 141 received preoperative and postoperative dosing ega r ding p ine infection. This study provides Level III prognostic evidence that and 143 received preoperative and intraoperative dosing. The incontinence (resulting from neurologic injury), obesity, tumor antibiotics used included cefazolin 1 g in 108 patients, flomoxef S

u r ge y resection (related to neurologic deficits) and posterior approach 1 g in 26 patients and piperacillin 1 g in 7 patients for the post- A increase risk of infection and gram-negative bacteria and/or operative group. For the no postoperative group, cefazolin 1 g ntibiotic anaerobes are likely to be isolated from a portion of infected was given to 142 patients and minocycline 100 mg was given to patients. In the face of antibiotic prophylaxis with all comers one patient. Patients in the postoperative dosing group had an and comorbidities represented, a 2.76% infection rate can be ex- intravenous dose within 30 minutes of skin incision, a dose post- pected. Alternative prophylactic regimens may be necessary to operatively intravenously and oral antibiotics for an average of further reduce the infection rate in patients with risk factors for 2.7 days, or the preoperative dose with intraoperative redosing surgical site infection. at three hour intervals and a single postoperative dose. For the Olsen (2008) et al15 described a retrospective case control no postoperative dosing group, patients had a preoperative dose study designed to determine independent risk factors for sur- within 30 minutes of skin incision with intraoperative dosing at gical site infection following orthopedic spinal operations. All three hour intervals until skin closure. Infection was confirmed patients received standard prophylaxis with cephalosporins or via bacterial cultures and inspection of wound for redness, heat, vancomycin in penicillin sensitive patients. Of 2316 patients, 46 swelling and pain. The authors found no statisically signficant patients with superficial, deep or organ-space surgical site infec- difference in infection rates between the protocols, and the su- tions were identified and compared with 227 uninfected control periority of one agent or regimen was not demonstrated. In the patients. In the face of prophylactic antibiotics, the overall rate postoperative dosing group, 2.8% (4/141) developed infections of spinal surgical site infection during the five years of the study (three superficial and one deep); in the no postoperative dosing was 2.0% (46/2316). Univariate analyses showed serum glucose group, 1.4% (2/143) developed infections (p=0.335). Altogether, levels, preoperatively and within five days after the operation, to 28 patients had diabetes including 10.6% (15/141) of patients be significantly higher in patients in whom surgical site infection the postoperative group and 9% (13/143) of patients in the no developed than in uninfected control patients. Independent risk postoperative group. None of the diabetic patients developed factors for surgical site infection that were identified by multi- surgical site infections. The authors concluded that the duration variate analysis were diabetes (odds ratio = 3.5, 95% confidence of antimicrobial prophylaxis does not influence the incidence of interval = 1.2, 10.0), suboptimal timing of prophylactic antibi- surgical site infections and postoperative administration of an- otic therapy (odds ratio = 3.4, 95% confidence interval = 1.5, timicrobials appears unnecessary. This study provides Level III 7.9), a preoperative serum glucose level of >125 mg/dL (>6.9 evidence that preoperative administration of antimicrobial pro- mmol/L) or a postoperative serum glucose level of >200 mg/dL phylaxis plus intraoperative redosing at three hour intervals is (>11.1 mmol/L) (odds ratio = 3.3, 95% confidence interval = 1.4, effective at preventing surgical site infection. 7.5), obesity (odds ratio = 2.2, 95% confidence interval = 1.1, 4.7) Kanayama et al8 performed a retrospective comparative and two or more surgical residents participating in the operative study to compare the rate of surgical site infections in lumbar procedure (odds ratio = 2.2, 95% confidence interval = 1.0, 4.7). spine surgeries for two different antibiotic prophylaxis proto- A decreased risk of surgical site infection was associated with cols. A first-generation cephalosporin was administered unless operations involving the cervical spine (odds ratio = 0.3, 95% the patient had a history of a significant allergy such as anaphy- confidence interval = 0.1, 0.6). The authors concluded that dia- lactic shock, systemic skin eruption or toxic liver dysfunction.

The postoperative dose group patients received antibiotics for Fisher exact test, the difference in the incidence rates between five to seven days after surgery. The no postoperative dose group the patient groups with and without antibiotic prophylaxis dur- patients received antibiotics only on the day of surgery; antibiot- ing lumbar discectomy was highly significant (p < 0.00001). The ics were given 30 minutes before skin incision. An additional authors observed no complications related to the use of a collag- dose was administered every three hours to maintain therapeu- enous sponge containing gentamicin for antibiotic prophylaxis. tic levels throughout surgery. Infection was defined as a posi- The authors concluded that a 3.7% incidence of postoperative tive wound culture and/or typical infectious signs including a spondylodiscitis was found in the absence of prophylactic an- purulent exudate, surrounding erythema and wound fluctuance tibiotics. Gentamicin-containing collagenous sponges placed in detected at a maximum of six months. Laboratory studies were the cleared disc space were effective in preventing postoperative also referenced, such as prolonged elevation in the C-reactive spondylodiscitis. This study provides Level III therapeutic evi- protein value. For the purposes of this study, the surgical site dence that for uncomplicated lumbar microdiscectomy, topical infection incidence rate was determined according to the num- administration of gentamicin soaked collagen sponge is more ef- ber of wound infection requiring additional surgical infections. fective than placebo in preventing clinically significant discitis. There were 1133 patients in the postoperative-dose group and Sweet et al12 performed a retrospective comparative study to 464 patients in the no postoperative group. The rate of instru- evaluate the safety and efficacy of adjunctive local application mentation surgery was not statistically different between the of vancomycin for infection prophylaxis in posterior instru- postoperative-dose group (43%) and the no postoperative-dose mented thoracic and lumbar spine wounds compared to intra- group (39%). The overall rate of surgical site infection was 0.7%. venous cephalexin alone. Since 2000, 1732 consecutive thoracic ntibiotic A

The infection rate was 0.8% (9/1133) in the postoperative-dose and lumbar posterior instrumented spinal fusions have been u r ge y group and 0.4% (2/464) in the no postoperative-dose group; the performed with routine 24 hours of perioperative intravenous S difference between the two was not significant. Regarding the antibiotic prophylaxis with cephalexin. Since 2006, 911 of these p ine organisms of surgical site infection, resistant strains of bacteria instrumented thoracic and lumbar cases had 2 g of vancomycin ega r ding S R in

were cultured in five (83.3%) of six patients in the postoperative- powder applied to the wound prior to closure in addition to in- dose group, whereas none was cultured in the no postoperative- travenous antibiotics. A retrospective review for infection rates dose group. The authors concluded there was no statistical dif- and complications was performed with an average follow-up of ference was observed between protocols and the superiority of 2.5 years (range: 1-7 years). If wound infection was suspected one agent or regimen was not demonstrated. The CDC protocol based on clinical and constitutional symptoms, aspiration was r o p hylaxis of preoperative dosing prevents development of resistant strains completed. If aspiration demonstrated purulent material or P

while reducing the risk of surgical site infections. This study pro- the wound was clinically suspicious for subfascial infection, the ecommendations vides Level III therapeutic evidence that preoperative plus intrawound was explored and aerobic, anaerobic and fungal cultures R operative dosing at three hour intervals throughout surgery is were obtained. Posterior instrumented thoracic and lumbar fu- efficacious in preventing surgical site infection. Also, extended sions were performed in 821 patients using intravenous cepha- dosing may induce resistant strains. Suction drains were left in lexin prophylaxis with a total of 21 resulting deep wound in- place in fusions for two to three days. Accordingly, multidosing fections (2.6%). Coag negative staph was the most commonly of antibiotics until drains are removed may not be beneficial. isolated organism. Posterior instrumented thoracic and lumbar Rohde et al11 described a retrospective comparative study de- fusions were performed in 911 patients with intravenous cepha- signed to report the incidence of postoperative spondylodisci- lexin plus adjunctive local vancomycin powder with two ensu- tis in 1642 consecutive cases in which no antibiotic prophylaxis ing deep wound infections (0.2%). The reduction in wound in- was used and to define the value of single dose administration fections was statistically significant (p< 0.0001). There were no of a collagenous sponge containing gentamicin as an antibiotic adverse clinical outcomes or wound complications related to the prophylaxis alternative for preventing disc space infections. No local application of vancomycin. The authors concluded that ad- topical or systemic antibiotics were administered in the first 508 junctive local application of vancomycin powder decreases the patients. A 4 cm × 4 cm collagenous sponge containing 8 mg post surgical wound infection rate with statistical significance of gentamicin was placed in the cleared disc space in the subse- in posterior instrumented thoracolumbar spine fusions. This quent 1134 patients. Surgery was performed for 1584 primary study provides Level III therapeutic evidence that adjunctive lo- lumbar disc herniations (two-level discectomy in 39 cases, three- cal application of vancomycin powder decreases the post surgi- level discectomy in one case) and 169 operations for recurrent cal wound infection rate compared with intravenous cephalexin herniations. In all patients, the erythrocyte sedimentation rate in posterior instrumented thoracolumbar fusion. (ESR) was obtained before surgery and on the first day after sur- Takahashi et al13 performed a retrospective comparative study gery. Beginning in January 1992, C-reactive protein (CRP) also to compare the effectiveness of preoperative cephalosporin with was analyzed before surgery, one day after surgery and six days various postoperative dosing schedules in reducing infection after surgery. All patients were clinically re-examined on days rates following a variety of spinal surgeries including decom- 10-14 after surgery (day of discharge). Final follow-up was at pression with or without fusion, with or without fixation. Group 60 days. In 19 of these 508 patients, a postoperative spondy- 1 (n=539) received first- or second-generation cephalosporin or lodiscitis developed, accounting for an incidence rate of 3.7%. penicillin administered by intravenous drip infusion for seven None of the 1134 patients receiving antibiotic prophylaxis de- days (4 g/day) after the operation followed by oral cephalosporin veloped a postoperative spondylodiscitis during the follow-up for one week. Group 2 (n=536) received first- or second- genera- period of 60 days resulting in an incidence of 0%. Using the tion cephalosporin administered by intravenous drip infusion at

the time of anesthesia induction. When the operating time ex- Protocol (Mixed Groups) References ceeded five hours, an additional dose was given intraoperatively. 1. Petignat C, Francioli P, Harbarth S, et al. Cefuroxime prophy- The administration was continued for five days (2 g/day) after laxis is effective in noninstrumented spine surgery: a double- the operation, including the day of the operation. After the drip blind, placebo-controlled study. Spine (Phila Pa 1976). Aug 15 infusion, a cephalosporin was given orally for one week. Group 2008;33(18):1919-1924. 2. Barker FG, 2nd. Efficacy of prophylactic antibiotic therapy 3 (n=257) received first- or second-generation cephalosporin in spinal surgery: a meta-analysis. Neurosurgery. Aug administered by intravenous drip infusion, with the initial dose 2002;51(2):391-400; discussion 400-391. given at the time of anesthesia induction. Additional doses were 3. Pons VG, Denlinger SL, Guglielmo BJ, et al. Ceftizoxime versus administered every three hours during the operation. The ad- vancomycin and gentamicin in neurosurgical prophylaxis: a ministration was then continued for three days (2 g/day) after randomized, prospective, blinded clinical study. Neurosurgery. the operation, including the day of the operation. After the drip Sep 1993;33(3):416-422; discussion 422-413. infusion, a cephalosporin was given orally for one week. Group 4. Rubinstein E, Findler G, Amit P, Shaked I. Perioperative prophy- 4 (n=83) received first generation cephalosporin administered lactic cephazolin in spinal surgery. A double-blind placebo- by intravenous drip infusion with the initial dose given at the controlled trial. J Bone Joint Surg Br. Jan 1994;76(1):99-102. R 5. Dobzyniak MA, Fischgrund JS, Hankins S, Herkowitz HN.

ecommendations time of anesthesia induction. Additional doses were given every Single versus multiple dose antibiotic prophylaxis in lumbar disc three hours during the operation. The administration was then P surgery. Spine. Nov 1 2003;28(21):E453-455. r o p hylaxis continued for two days (2 g/day) after the operation, including 6. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. the day of the operation. Patients with diabetes mellitus, meta- multiple-dose antibiotic prophylaxis in instrumented lumbar static spinal tumors, on dialysis, or receiving daily steroid ad- fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- ministration of 5 mg or more for at least 90 days were defined 627; discussion 627.

as compromised hosts and included 19.1%, 16.0%, 19.1%, and 7. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- in R

S 28.9% of patients in groups 1-4. Adopting the CDC guideline erative antimicrobial prophylaxis following spinal decompres- ega r ding p ine criteria, surgical site infections involving only the skin and/or sion surgery: is it necessary? J Orthop Sci. May;15(3):305-309. 8. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. subcutaneous tissues at the site of the incision were designated S Effective prevention of surgical site infection using a Centers for u r ge y superficial infections, and those involving deeper soft tissues (eg, Disease Control and Prevention guideline-based antimicrobial A fascial and muscle layers) at the site of the incision were des- prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr ntibiotic ignated deep infections. The overall frequency of surgical site 2007;6(4):327-329. infections for the different groups were: Group 1, 2.6% (14/539); 9. Luer MS, Hatton J. Appropriateness of antibiotic selection and Group 2, 0.9% (5/536); Group 3 and 4, 0/257 and 0/83, respec- use in laminectomy and microdiskectomy. Am J Hosp Pharm. tively. Comparision using Tukey’s multiple comparison test Apr 1993;50(4):667-670. showed p<0.05 for comparing infections rates between Groups 10. Mastronardi L, Rychlicki F, Tatta C, Morabito L, Agrillo U, 1, 2 and 3. In addition, there was no significant difference in the Ducati A. Spondylodiscitis after lumbar microdiscectomy: effectiveness of two protocols of intraoperative antibiotic prophylaxis frequency of surgical site infection between the compromised in 1167 cases. Neurosurg Rev. Oct 2005;28(4):303-307. hosts and rest of the patients. The authors concluded that when 11. Rohde V, Meyer B, Schaller C, Hassler WE. Spondylodiscitis thorough prophylactic countermeasures are undertaken against after lumbar discectomy. Incidence and a proposal for prophy- surgical site infections, the frequency of these infections can be laxis. Spine. Mar 1 1998;23(5):615-620. decreased, with a decrease in the duration of antimicrobial pro- 12. Sweet FA, Roh M, Sliva C. Intra-wound application of vancomy- phylaxis administration from seven days to two days. This study cin for prophylaxis In instrumented thoracolumbar fusions: ef- provides Level III therapeutic evidence that shorter duration of ficacy, drug levels, and patient outcomes.Spine (Phila Pa 1976). antimicrobial prophylaxis is more effective at preventing infec- 2011 Nov 15;36(24):2084-8. tion in patients undergoing spinal surgery with and without in- 13. Takahashi H, Wada A, Lida Y, et al. Antimicrobial prophylaxis for spinal surgery. J Orthop Sci. Jan 2009;14(1):40-44. strumentation compared to longer durations. 14. Olsen MA, Mayfield J, Lauryssen C, et al. Risk factors for surgical site infection in spinal surgery. J Neurosurg. Mar 2003;98(2 Future Directions for Research Suppl):149-155. Large multicenter randomized controlled trials assessing the ef- 15. Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical ficacy of various protocols should be tailored to specific patient site infection following orthopaedic spinal operations. J Bone populations (eg, obesity, diabetes, trauma, neuromuscular in- Joint Surg Am. Jan 2008;90(1):62-69. jury or disease, prolonged multilevel instrumented surgery) at increased risk for surgical site infections.

For patients receiving antibiotic prophylaxis prior to open spine surgery without spinal implants, what are the recommended drugs, their dosages, administration routes and timing resulting in decreased postoperative infections rates?

Preoperative antibiotic prophylaxis is suggested to decrease infection rates in patients undergoing spine surgery without spinal implants. In these typical, uncomplicated spinal procedures, the superiority of one agent, dose or route of administration over any other has not been clearly ntibiotic A demonstrated. When determining the appropriate drug choice, the pa- u r ge y tient’s risk factors, allergies, length and complexity of the procedure and S p ine

issues of antibiotic resistance should be considered. ega r ding S R in

Grade of Recommendation: B r o p hylaxis P

1 ecommendations

Petignat et al conducted a prospective, randomized controlled patients who underwent various clean spine surgeries. Of the R trial assessing the efficacy of one preoperative 1.5 g dose of ce- 291 patients, 142 received ceftizoxime and 149 vancomycin/gen- furoxime in preventing surgical site infection after lumbar lami- tamicin one hour prior to incision. Infections were confirmed notomy and discectomy for herniated disc. Of the 1237 patients using bacterial cultures for deep infections, urinary tract infec- included in the study, 613 received 1.5 g intravenous cefuroxime tion, or catheter infections; pneumonia diagnosed by purulent on induction and 624 received placebo. Presence of infection, sputum and/or new infiltrate on CXR; and cellulitis was diag- as defined by the Centers for Disease Control (CDC) guidelines, nosed by presence of spreading induration or erythema. Pri- was assessed at six weeks, three months and six months. Base- mary infections were reported in 2.8% (4/142) of the ceftizox- line characteristics were similar in patients allocated to cefuroxime patients and 2.7% (4/149) of the vancomycin-gentamicin ime (n = 613) or placebo (n=624). Eight (1.3%) patients in the patients. Secondary infections were reported in 4.2% (6/142) cefuroxime group and 18 patients (2.8%) in the placebo group and 4.0% (6/149) patients, respectively. The authors concluded developed a surgical site infection (p =0.073). A diagnosis of that the design of the trial does not allow for statistical analysis spondylodiscitis or epidural abscess was made in nine patients of subgroups, however, an overview of the data does not sug- in the placebo group, but none in the cefuroxime group (p < gest a relationship between postoperative infection and any of 0.01), which corresponded to a number necessary to treat of 69 the technical or clinical variables. Ceftizoxime is less toxic than patients to prevent one of these infections. There were no signifi- vancomycin/gentamicin and equally as effective in preventing cant adverse events attributed to either cefuroxime or placebo. infections after clean neurosurgical procedures. Because the Overall surgical site infection rate was 1.3% with antibiotics study design does not permit subgroup analysis, this potential versus 2.8% with placebo (p=0.073), and discitis rate was 0/613 Level I study provides Level II evidence that ceftizoxime and versus 9/624 (p<0.01), respectively. The authors concluded that vancomycin-gentamicin are equally effective in reducing infec- a single, preoperative dose of cefuroxime significantly reduces tions with ceftizoxime being less toxic. However, the study was the risk of organ-space infection, most notably spondylodiscitis, not designed for subgroup analysis. The superiority of one agent after surgery for herniated disc. Cefuroxime is protective against or regimen was not demonstrated. spondylodiscitis. This study provides Level I therapeutic evi- Rubinstein et al3 performed a prospective, randomized con- dence that for uncomplicated lumbar microdiscectomy, a single trolled trial to investigate the efficacy of a single dose of 1 g of preoperative 1.5 g dose of cefuroxime is more effective in pre- cephazolin in reducing postoperative infections in patients un- venting infection than placebo. dergoing ‘clean’ operations on the lumbar spine. Of the 141 Pons et al2 described a prospective, randomized trial com- patients included in the study, 70 received 1 g intravenous cep- paring perioperative antibiotic protocols that included either 2 hazolin upon arrival to the operative room (approximately two g ceftizoxime or 1 g vancomycin plus 80 mg gentamicin in 291 hours prior to surgery) and 71 received placebos. Presence of

infection was assessed at 30 days, with surgical site infection 141 received preoperativeand postoperative dosing while 143 defined as drainage of purulent material from the operative received preoperative and intraoperative dosing. The antibiotics site and a positive bacteriological culture, or inflammation of used included cefazolin 1 g in 108 patients, flomoxef 1 g in 26 an area more than 20 mm in diameter; for urinary tract infec- patients, and piperacillin 1 g in seven patients for the postopera- tion, more than 100,000 colony forming units/mL on culture; tive group. For the no postoperative dosing group, cefazolin 1 and for pneumonia, the clinical diagnosis was made by the treat- g was given to 142 patients and minocycline 100 mg was given ing physician. There were 21 wound or urinary infections in to one patient. Patients in the postoperative dosing group had the 71 patients who received placebo and nine in the 70 who an intravenous dose within 30 minutes of skin incision, a dose received cephazolin (p < 0.05). Nine patients (12.7%) who re- postoperatively intravenously and oral antibiotics for 2.7 days ceived placebo and three (4.3%) who received cephazolin devel- average, or the preoperative dose with intraoperative redosing oped wound infections (p = 0.07). All but three of the infections at three hour intervals and a single postoperative dose. For the in the placebo group were confirmed by bacterial culture. All no postoperative group, patients received a preoperative dose the organisms isolated from the patients who received placebo within 30 minutes of skin incision with intraoperative dosing at (except the group-D streptococci which are inherently resistant) three hour intervals until skin closure. Infection was confirmed R

ecommendations were sensitive to cephazolin whereas in the cephazolin prophy- via bacterial cultures and inspection of wound for redness, heat, lactic group 43% of the organisms isolated were resistant or had swelling and pain. In the postoperative dosing group, 2.8% P r o p hylaxis reduced sensitivity to the drug. The authors concluded that the (4/141) developed infections (three superficial and one deep); administration of a single dose of cephazolin preoperatively is in the no postoperative dosing group, 1.4% (2/143) developed recommended for patients undergoing lumbar spinal surgery. infections (p=0.335). The authors concluded that the duration In critique, the sample size was small and the study’s follow-up of antimicrobial prophylaxis does not influence the rate of surgi-

period was short. In addition, the authors expanded the defini- cal site infections. This study provides Level III evidence that in R

S tion of infection to include wound, urinary tract infection and the duration of antimicrobial prophylaxis does not influence the ega r ding p ine pneumonia in order to achieve statistical significance. Due to incidence of surgical site infections and postoperative adminis- these limitations, this potential Level I study provides Level II tration of antimicrobials appears unnecessary. The superiority S

u r ge y therapeutic evidence that for uncomplicated spine surgery, a of one agent or regimen was not demonstrated. A single preoperative dose of cephazolin decreases infection rate; Luer et al6 described a retrospective case control study com- ntibiotic however, it does not significantly decrease the rate of wound in- paring postoperative infections after laminectomy/discectomy fection. The use of cephazolin appears to be associated with an to examine variables that may be associated with infection. The increase in development of resistant organisms. antibiotic protocol included a single intravenous dose of 1 g ce- Dobzyniak et al4 described a retrospective comparative study fazolin with varied timing (within one hour preoperatively, to examining the efficacy of single versus multiple dosing for lum- within two hours, to greater than two hours, to postincision). bar disc surgery. The antibiotics used for prophylaxis consisted Infection was confirmed via bacterial cultures. The clinical eval- of cephazolin 1 g, 525 patients; clindamycin 600 mg, 15 patients; uation for infection was not described. Of the 22 patients with vancomycin 1 g plus clindamycin 600 mg, 46 patients; and van- documented wound infection, 12 had received prophylactic an- comycin 1 g alone, 24 patients. The choice of an antibiotic other tibiotics with 33% (4/12) having received cefazolin within two than cephazolin was based on a patient allergy to penicillin or hours of incision versus 57% (8/14) of the uninfected matched cephalosporins and surgeons preference when these allergies controls, p=0.001. The surgical incision was closed less than two were encountered. Of the 635 consecutive patients included in hours after incision in 43% (6/14) of uninfected patients and the study, 418 received the multidose regimen, 192 received the 17% (2/12) with infection (p<0.001). The authors reported that single dose, and 25 patients were eliminated from the study as no wound culture data did not indicate infection by organisims re- preoperative dose was documented. Infection was confirmed at sistant to cefazolin. They concluded that the choice of cefazolin six weeks via cultures and attending physician’s assessment. The appears adequate but administration needs to occur in the ap- infection rate was 1.56% (3/192) with single dosing versus 1.20% propriate time frame. This small study provides Level III thera- (5/418) with multiple dosing, p=0.711, Fisher exact test. The au- peutic evidence that antibiotic prophylaxis with cephalosporin thors concluded that a single preoperative dose of prophylactic more than two hours prior to incision appears to yield a higher antibiotics is as effective as preoperative plus postoperative anti- infection rate, and dosing within two hours of incision may im- biotics in the prevention of wound infections in lumbar disc sur- prove infection rate. gery. They recommend preoperative antibiotics alone, citing no Mastronardi (2005) et al7 reported a retrospective compara- advantage in prolonging a patient’s discharge following uncom- tive study evaluating the efficacy of two intraoperative antibiotic plicated lumbar disc excision to administer postoperative anti- prophylaxis protocols in a large series of lumbar microdiscec- biotics. This study provides Level III therapeutic evidence that tomies performed in two different neurosurgical centers. Of single dosing is as effective as multiple dosing; however, different the 1167 patients included in the study, 450 received a single antibiotics do not appear to affect the rate of wound infection. intravenous dose of cefazoline 1 g at induction of general anes- The superiority of one agent or regimen was not demonstrated. thesia (Group A) and 717 received a single dose of intravenous Kakimaru et al5 reported results from a retrospective com- ampicillin 1 g and sulbactam 500 mg at induction of anesthesia parative study comparing the infection rates following uninstru- (Group P). At six months, a diagnosis of postoperative spon- mented spinal surgery with and without postoperative antimi- dylodiscitis was confirmed via lumbar MRI and sedimentation crobial prophylaxis. Of the 284 patients included in the study, rate in three out of 450 patients in Group A (0.67%) and in five

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 31 out of 717 patients in Group P (0.69%). In all cases, treatment rin was given orally for one week. Group 3 received first- or consisted of rigid thoracolumbar orthesis and four to six week second-generation cephalosporin administered by intravenous administration of amoxicillin/clavulanate compound (500/125 drip infusion, with the initial dose given at the time of anesthe- mg). The authors concluded that administration of a single sia induction. Additional doses were administered every three dose of antibiotic at time of induction appears safe and effective. hours during the operation. The administration was then con- Multicenter trials would be needed to assess superiority of an tinued for three days (2 g/day) after the operation, including the agent. This study provides Level III therapeutic evidence both day of the operation. After the drip infusion, a cephalosporin cefazolin and ampicillin/sulbactam are effective agents when was given orally for one week. Group 4 received first generation given at the time of induction for prevention of discitis follow- cephalosporin administered by intravenous drip infusion with ing lumbar discectomy. The superiority of one agent or regimen the initial dose given at the time of anesthesia induction. Addi- was not demonstrated. tional doses were given every three hours during the operation. Rohde et al8 described a retrospective comparative study de- The administration was then continued for two days (2 g/day) signed to report the incidence of postoperative spondylodiscitis after the operation, including the day of the operation. Of the in 1642 consecutive cases in which no antibiotic prophylaxis was 1415 patients included in the study, 539 were included in Group used and to define the value of a collagenous sponge containing 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- gentamicin in preventing disc space infections. No topical or ing the CDC guideline criteria, surgical site infections involving systemic antibiotics were administered in the first 508 patients. only the skin and/or subcutaneous tissues at the site of the inci- A 4 cm × 4 cm collagenous sponge containing 8 mg of gentami- sion were designated superficial infections, and those involving ntibiotic A cin was placed in the cleared disc space in the subsequent 1134 deeper soft tissues (eg, fascial and muscle layers) at the site of the u r ge y patients. Surgery was performed for 1584 primary lumbar disc incision were designated deep infections. The overall frequency S herniations (two-level discectomy in 39 cases, three-level dis- of surgical site infections for the different groups were: Group p ine cectomy in one case) and 169 operations for recurrent hernia- 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 ega r ding S R in

tions. In all patients, the erythrocyte sedimentation rate (ESR) and 0/83, respectively. Comparision using Tukey’s multiple was obtained before surgery and on the first day after surgery. comparison test showed p<0.05 for comparing infections rates Beginning in January 1992, C-reactive protein (CRP) also was between Groups 1, 2 and 3. The authors concluded that when analyzed before surgery, one day after surgery and six days af- thorough prophylactic countermeasures are undertaken against ter surgery. All patients were clinically re-examined on days perioperative surgical site infections, the frequency of these in- r o p hylaxis

10-14 after surgery (day of discharge). Final follow-up was at fections can be decreased, with a decrease in the duration of an- P

60 days. In 19 of these 508 patients, a postoperative spondy- timicrobial prophylaxis administration from seven days to two ecommendations lodiscitis developed, accounting for an incidence rate of 3.7%. days. This study provides Level III therapeutic evidence that R None of the 1134 patients receiving antibiotic prophylaxis de- shorter duration of antimicrobial prophylaxis is more effective veloped a postoperative spondylodiscitis during the follow-up compared to longer durations. period of 60 days. Therefore, the incidence of postoperative spondylodiscitis was 0%. Using the Fisher exact test, the differ- In typical, uncomplicated open spine surgery ence in the incidence rates between the patient groups with and without spinal implants, a single dose of without antibiotic prophylaxis during lumbar discectomy was preoperative prophylactic antibiotics with highly significant (p < 0.00001). The authors observed no complications related to the use of a collagenous sponge containing intraoperative redosing as needed is sug- gentamicin for antibiotic prophylaxis. This study provides Level gested. III therapeutic evidence that for uncomplicated lumbar microdiscectomy, topical administration of a gentamicin soaked col- Grade of Recommendation: B lagen sponge is more effective than placebo in preventing clinically significant discitis. 4 Takahashi et al9 performed a retrospective comparative Dobzyniak et al described a retrospective comparative study ex- study to compare the effectiveness of preoperative cephalospo- amining the efficacy of single versus multiple dosing for lumbar rin with various postoperative dosing schedules in reducing disc surgery. The antibiotics used for prophylaxis consisted of infection rates following a variety of spinal surgeries including cephazolin 1 g, 525 patients; clindamycin 600 mg, 15 patients; decompression with or without fusion, with or without fixa- vancomycin 1 g plus clindamycin 600 mg, 46 patients; and van- tion. Group 1 received first- or second-generation or penicillin comycin 1 g alone, 24 patients. The choice of an antibiotic other administered by intravenous drip infusion for seven days (4 g/ than cephazolin was based on a patient allergy to penicillin or day) after the operation. After the drip infusion, cephalosporin cephalosporins and surgeons preference when these allergies was administered orally for one week. Group 2 received first- or were encountered. Of the 635 consecutive patients included in second- generation cephalosporin administered by intravenous the study, 418 received the multidose regimen, 192 received the drip infusion. The initial dose was given at the time of anesthesia single dose, and 25 patients were eliminated from the study since induction. When the operating time exceeded five hours, an ad- no preoperative dose was documented. Infection was confirmed ditional dose was given intraoperatively. The administration was at six weeks via cultures and attending physician’s assessment. continued for five days (2 g/day) after the operation, including The infection rate was 1.56% (3/192) with single dosing versus the day of the operation. After the drip infusion, a cephalospo- 1.20% (5/418) with multiple dosing, p=0.711, Fisher exact test. The authors concluded that a single preoperative dose of prophy-

lactic antibiotics is as effective as preoperative plus postoperative sia induction. Additional doses were administered every three antibiotics in the prevention of wound infections in lumbar disc hours during the operation. The administration was then con- surgery. They recommend preoperative antibiotics alone, citing tinued for three days (2 g/day) after the operation, including the no advantage in prolonging a patient’s discharge following lum- day of the operation. After the drip infusion, a cephalosporin bar disc excision to administer postoperative antibiotics. This was given orally for one week. Group 4 received first-generation study provides Level III therapeutic evidence that single dosing cephalosporin administered by intravenous drip infusion with is as effective as multiple dosing; however, different antibiotics the initial dose given at the time of anesthesia induction. Addi- do not appear to affect the rate of wound infection. The superi- tional doses were given every three hours during the operation. ority of one agent or regimen was not demonstrated. The administration was then continued for two days (2 g/day) Kakimaru et al5 reported results from a retrospective com- after the operation, including the day of the operation. Of the parative study comparing the infection rates following uninstru- 1415 patients included in the study, 539 were included in Group mented spinal surgery with and without postoperative antimi- 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- crobial prophylaxis. Of the 284 patients included in the study, ing the CDC guideline criteria, surgical site infections involving 141 received preoperative and postoperative dosing and 143 only the skin and/or subcutaneous tissues at the site of the inci- R

ecommendations received preoperative and intraoperative dosing. The antibiot- sion were designated superficial infections, and those involving ics used included cefazolin 1 g in 108 patients, flomoxef 1 g in deeper soft tissues (eg, fascial and muscle layers) at the site of the P r o p hylaxis 26 patients, and iperacillin 1 g in 7 patients for the postopera- incision were designated deep infections. The overall frequency tive group. For the no postoperative group, cefazolin 1 g was of surgical site infections for the different groups were: Group given to 142 patients and minocycline 100 mg was given to 1 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 patient. Patients in the postoperative dosing group had an intra- and 0/83, respectively. Comparision using Tukey’s multiple

venous dose within 30 minutes of skin incision, a dose postop- comparison test showed p<0.05 for comparing infections rates in R

S eratively intravenously, and oral antibiotics for 2.7days average, between Groups 1, 2 and 3. The authors concluded that when ega r ding p ine or the preoperative dose with intraoperative redosing at three thorough prophylactic countermeasures are undertaken against hour intervals and a single postoperative dose. No posotopera- perioperative surgical site infections, the frequency of these in- S

u r ge y tive dosing group patients received a preoperative dose within 30 fections can be decreased, with a decrease in the duration of an- A minutes of skin incision with intraoperative dosing at three hour timicrobial prophylaxis administration from seven days to two ntibiotic intervals until skin closure. Infection was confirmed via bacte- days. This study provides Level III therapeutic evidence that rial cultures and inspection of wound for redness, heat, swell- shorter duration of antimicrobial prophylaxis is more effective at ing and pain. In the postoperative dosing group, 2.8% (4/141) preventing surgical site infection in spinal surgery patients com- developed infections (three superficial and one deep); in the no pared to longer durations. postoperative dosing group, 1.4% (2/143) developed infections (p=0.335). The authors concluded that the duration of antimi- Future Directions for Research crobial prophylaxis does not influence the rate of surgical site Large multicenter randomized controlled trials assessing the ef- infections andpostoperative administration of antimicrobials ficacy of various protocols should be tailored to specific patient appears unnecessary. This study provides Level III therapeutic populations (eg, obesity, diabetes, trauma, neuromuscular in- evidence that preoperative administration of antimicrobial pro- jury or disease, prolonged multilevel instrumented surgery) at phylaxis plus intraoperative redosing at three hour intervals is increased risk for surgical site infections. effective at preventing surgical site infection in patients undergoing spinal surgery without instrumentation. The superiority Protocol (Noninstrumented) References of one agent or regimen was not demonstrated. 1. Petignat C, Francioli P, Harbarth S, et al. Cefuroxime prophy- Takahashi et al9 performed a retrospective comparative study laxis is effective in noninstrumented spine surgery: a double- to compare the effectiveness of preoperative cephalosporin with blind, placebo-controlled study. Spine (Phila Pa 1976). Aug 15 various postoperative dosing schedules in reducing infection 2008;33(18):1919-1924. 2. Pons VG, Denlinger SL, Guglielmo BJ, et al. Ceftizoxime versus rates following a variety of spinal surgeries including decom- vancomycin and gentamicin in neurosurgical prophylaxis: a pression with or without fusion, with or without fixation. Group randomized, prospective, blinded clinical study. Neurosurgery. 1 received first- or second-generation cephalosporin or penicil- Sep 1993;33(3):416-422; discussion 422-413. lin administered by intravenous drip infusion for seven days (4 3. Rubinstein E, Findler G, Amit P, Shaked I. Perioperative prophy- g/day) after the operation. After the drip infusion, cephalosporin lactic cephazolin in spinal surgery. A double-blind placebo- was administered orally for one week. Group 2 received first- or controlled trial. J Bone Joint Surg Br. Jan 1994;76(1):99-102. second- generation cephalosporin administered by intravenous 4. Dobzyniak MA, Fischgrund JS, Hankins S, Herkowitz HN. drip infusion. The initial dose was given at the time of anesthesia Single versus multiple dose antibiotic prophylaxis in lumbar disc induction. When the operating time exceeded five hours, an ad- surgery. Spine. Nov 1 2003;28(21):E453-455. 5. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- ditional dose was given intraoperatively. The administration was erative antimicrobial prophylaxis following spinal decompres- continued for five days (2 g/day) after the operation, including sion surgery: is it necessary? J Orthop Sci. May 2010;15(3):305- the day of the operation. After the drip infusion, a cephalospo- 309. rin was given orally for one week. Group 3 received first- or 6. Luer MS, Hatton J. Appropriateness of antibiotic selection and second-generation cephalosporin administered by intravenous use in laminectomy and microdiskectomy. Am J Hosp Pharm. drip infusion, with the initial dose given at the time of anesthe- Apr 1993;50(4):667-670. 7. Mastronardi L, Rychlicki F, Tatta C, Morabito L, Agrillo U,

Ducati A. Spondylodiscitis after lumbar microdiscectomy: effec- 8. Rohde V, Meyer B, Schaller C, Hassler WE. Spondylodiscitis tiveness of two protocols of intraoperative antibiotic prophylaxis after lumbar discectomy. Incidence and a proposal for prophy- in 1167 cases. Neurosurgical Review. Oct 2005;28(4):303-307. laxis. Spine. Mar 1 1998;23(5):615-620. 9. Takahashi H, Wada A, Iida Y, et al. Antimicrobial prophylaxis for spinal surgery. J Orthop Sci. Jan 2009;14(1):40-44.

For patients receiving antibiotic prophylaxis prior to open spine surgery with spinal implants, what are the recommended drugs, their dosages, administration routes and timing resulting in decreased postoperative infections ntibiotic A

rates? u r ge y S p ine ega r ding Preoperative antibiotic prophylaxis is suggested to decrease infection S R in rates in patients undergoing spine surgery with spinal implants. In these complex spinal procedures, the superiority of one agent, dose or route of administration over any other has not been clearly demonstrated. When determining the appropriate drug choice, the patient’s risk factors, al- r o p hylaxis lergies, length and complexity of the procedure and issues of antibiotic P ecommendations resistance should be considered. R

Grade of Recommendation: B

Hellbusch et al1 conducted a prospective, randomized controlled trophysiological monitoring, increased height, increased weight, trial examining the effects of multiple dosing regiments on the and increased body mass index. Increased tobacco use trended postoperative infection rate in instrumented lumbar spinal fu- toward a lower infection rate. Statistical significance was not sion. Two hundred sixty-nine patients were randomized into achieved. The authors concluded that preoperative prophylactic either a preoperative only protocol or preoperative with an ex- antibiotic use in instrumented lumbar spinal fusion is generally tended postoperative antibiotic protocol. Patients in the preop- accepted and has been shown consistently to decrease postoperative only protocol group received a single dose of intravenous erative infection rates. Prolonged postoperative antibiotic dos- cefazolin 1 g or 2 g based on weight 30 minutes before incision. ing increases cost and potential complications. Due to questions The extended postoperative antibiotic protocol group received about the method of randomization and lack of validated out- the same preoperative dose plus postoperative intravenous ce- come measures, this potential Level II study provides Level III fazolin every eight hours for three days followed by oral cepha- therapeutic evidence that preoperative prophylactic antibiotic lexin every six hours for seven days. Because of untoward drug use in instrumented lumbar spinal fusion is effective at reducing reaction or deviation from the antibiotic protocol, 36 of the 269 the risk of infection. The superiority of one agent or regimen patients were eliminated from the study. Therefore, 233 patients was not demonstrated. completed the entire study; 117 receiving preoperative antibiot- Sweet et al2 performed a retrospective comparative study to ics only, and 116 receiving pre- and postoperative antibiotics. At evaluate the safety and efficacy of adjunctive local application 21 days follow-up, there was no significant difference in infec- of vancomycin for infection prophylaxis in posterior instru- tion rates between the two antibiotic protocols. The postopera- mented thoracic and lumbar spine wounds compared to intra- tive infection rates were 4.3% for the preoperative only protocol venous cephalexin alone. Since 2000, 1732 consecutive thoracic and 1.7% for the preoperative with extended antibiotic protocol. and lumbar posterior instrumented spinal fusions have been The overall postoperative infection rate was 3%. However, the performed with routine 24 hours of perioperative intravenous study did identify five variables that appeared to demonstrate a antibiotic prophylaxis with cephalexin. Since 2006, 911 of these trend toward increase in infection rate: blood transfusion, elec- instrumented thoracic and lumbar cases had 2 g of vancomycin

powder applied to the wound prior to closure in addition to in- or anaerobes were isolated significantly more often in patients travenous antibiotics. A retrospective review for infection rates who underwent lumbar or lumbosacral procedures (15/24) and complications was performed with an average follow-up of compared to patients who underwent thoracic or cervical pro- 2.5 years (range: 1-7 years). If wound infection was suspected cedures (2/15, p<0.001). The authors identified postoperative based on clinical and constitutional symptoms, aspiration was incontinence, obesity, tumor resection and posterior approach completed. If aspiration demonstrated purulent material or as risk factors. This study provides Level III prognostic evidence the wound was clinically suspicious for subfascial infection, that incontinence (resulting from neurologic injury), obesity, tu- the wound was explored and aerobic, anaerobic and fungal cul- mor resection (related to neurologic deficits) and posterior ap- tures were obtained. Posterior instrumented thoracic and lum- proach increase risk of infection. Alternative prophylactic regi- bar fusions were performed in 821 patients using intravenous mens, such as broad-spectrum antibiotics, may be necessary to cephalexin prophylaxis with a total of 21 resulting deep wound further reduce this infection rate. infections (2.6%). Coag negative staph was the most commonly Olsen (2008) et al5 described a retrospective case control isolated organism. Posterior instrumented thoracic and lumbar study designed to determine independent risk factors for surgi- fusions were performed in 911 patients with intravenous cepha- cal site infection following orthopaedic spinal operations. All R

ecommendations lexin plus adjunctive local vancomycin powder with two ensuing patients received standard prophylaxis with cephalosporins or deep wound infections (0.2%). The reduction in wound infec- vancomycin in penicillin sensitive patients. Of 2316 patients, P r o p hylaxis tions was statistically significant (p< 0.0001). There were no ad- 46 patients with superficial, deep or organ-space surgical site verse clinical outcomes or wound complications related to the infections were identified and compared with 227 uninfected local application of vancomycin. The authors concluded that ad- control patients. The overall rate of spinal surgical site infec- junctive local application of vancomycin powder decreases the tion during the five years of the study was 2.0% (46/2316). Uni-

post surgical wound infection rate with statistical significance variate analyses showed serum glucose levels, preoperatively and in R

S in posterior instrumented thoracolumbar spine fusions. This within five days after the operation, to be significantly higher in ega r ding p ine study provides Level III therapeutic evidence that adjunctive lo- patients in whom surgical site infection developed than in un- cal application of vancomycin powder decreases the post surgi- infected control patients. Independent risk factors for surgical S

u r ge y cal wound infection rate compared with intravenous cephalexin site infection that were identified by multivariate analysis were A in posterior instrumented thoracolumbar fusion. diabetes (odds ratio = 3.5, 95% confidence interval = 1.2, 10.0), ntibiotic suboptimal timing of prophylactic antibiotic therapy (odds ratio CONSENSUS STATEMENT. In patients with = 3.4, 95% confidence interval = 1.5, 7.9), a preoperative serum risk factors for polymicrobial infection, ap- glucose level of >125 mg/dL (>6.9 mmol/L) or a postoperative

propriate broad-spectrum antibiotics are serum glucose level of >200 mg/dL (>11.1 mmol/L) (odds ratio = 3.3, 95% confidence interval = 1.4, 7.5), obesity (odds ratio = suggested to decrease the risk of infection 2.2, 95% confidence interval = 1.1, 4.7) and two or more surgical when instrumented fusion is performed. residents participating in the operative procedure (odds ratio = 2.2, 95% confidence interval = 1.0, 4.7). A decreased risk of sur- Kanafani et al3 described a case control study comparing risk gical site infection was associated with operations involving the factors in patients who did or did not develop infections. All cervical spine (odds ratio = 0.3, 95% confidence interval = 0.1, patients received antibiotics, although patients with infections 0.6). The authors concluded that diabetes was associated with more frequently received first-generation as opposed to second- the highest independent risk of spinal surgical site infection, and generation cephalosporins. Also, there was a higher percentage an elevated preoperative or postoperative serum glucose level of patients with instrumentation in the infection group. This was also independently associated with an increased risk of sur- paper offers Level III evidence that patients who require instru- gical site infection. The role of hyperglycemia as a risk factor for mented fusions have a higher rate of infection than patients who surgical site infection in patients not previously diagnosed with do not require such extensive procedures. diabetes should be investigated further. Administration of pro- Olsen (2003) et al4 performed a retrospective case control phylactic antibiotics within one hour before the operation and study to identify the specific independent risk factors for surgi- increasing the antibiotic dosage to adjust for obesity are also im- cal site infections occurring after laminectomy or spinal fusion. portant strategies to decrease the risk of surgical site infection All patients received standard prophylaxis with cephalosporins after spinal operations. This study provides Level III prognostic or vancomycin in penicillin sensitive patients. Infection was de- evidence that diabetes, preoperative gluclose level of >125 mg/ fined using the CDC guideline definition, with infections iden- dL, postoperative gluclose level of >200mg/dL, and obesity are tified between two and 83 days (median time from surgery to indepdent risk factors for surgical site infection following or- infection was 14 days). Of the 53 of 1918 patients who expe- thopaedic spinal operations. Alternative prophylactic regimens, rienced surgical site infections, 12 were excluded due to miss- such as broad-spectrum antibiotics, may be necessary to further ing data. These patients were compared with 179 noninfected reduce this infection rate. matched controls. Infection rate even with prophylaxis was Rechtine et al6 described a retrospective case control study of 2.76% with no significant variation in the infection rate during 235 consecutive fracture patients. Of the 235 patients, 117 un- the four-year period. Cultures were obtained from infected pa- derwent surgical stabilization. Of the 117 patients, 12 suffered a tients and gram-negative rods and/or anaerobes were present in perioperative infection, two had a staphylococcal infection and 17 of 39 (44%) cultures. Additionally, gram-negative rods and/ 10 had a polymicrobial infection with gram-negative and gram-

2 Sweet et al performed a retrospective comparative study to ficacy of various protocols should be tailored to specific patient evaluate the safety and efficacy of adjunctive local application populations (eg, obesity, diabetes, trauma, neuromuscular in- of vancomycin for infection prophylaxis in posterior instru- jury or disease, prolonged multilevel instrumented surgery) at mented thoracic and lumbar spine wounds compared to intra- increased risk for surgical site infections. ntibiotic venous cephalexin alone. Since 2000, 1732 consecutive thoracic A u r ge y

and lumbar posterior instrumented spinal fusions have been Protocol (Instrumented) References S performed with routine 24 hours of perioperative intravenous 1. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. p ine

antibiotic prophylaxis with cephalexin. Since 2006, 911 of these multiple-dose antibiotic prophylaxis in instrumented lumbar ega r ding S R instrumented thoracic and lumbar cases had 2 g of vancomycin fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- in powder applied to the wound prior to closure in addition to in- 627; discussion 627. travenous antibiotics. A retrospective review for infection rates 2. Sweet FA, Roh M, Sliva C. Intra-wound application of vancomy- and complications was performed with an average follow-up of cin for prophylaxis in instrumented thoracolumbar fusions: efficacy, drug levels, and patient outcomes.Spine (Phila Pa 1976). 2.5 years (range: 1-7 years). If wound infection was suspected

2011 Nov 15;36(24):2084-8. r o p hylaxis based on clinical and constitutional symptoms, aspiration was 3. Kanafani ZA, Dakdouki GK, El-Dbouni O, Bawwab T, Kanj SS. P completed. If aspiration demonstrated purulent material or Surgical site infections following spinal surgery at a tertiary care ecommendations the wound was clinically suspicious for subfascial infection, the center in Lebanon: incidence, microbiology, and risk factors. R wound was explored and aerobic, anaerobic and fungal cultures Scand J Infect Dis. 2006;38(8):589-592. were obtained. Posterior instrumented thoracic and lumbar fu- 4. Olsen MA, Mayfield J, Lauryssen C, et al. Risk factors for surgi- sions were performed in 821 patients using intravenous cepha- cal site infection in spinal surgery. J Neurosurg. Mar 2003;98(2 lexin prophylaxis with a total of 21 resulting deep wound in- Suppl):149-155. fections (2.6%). Coag negative staph was the most commonly 5. Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical site infection following orthopaedic spinal operations. J Bone isolated organism. Posterior instrumented thoracic and lumbar Joint Surg Am. Jan 2008;90(1):62-69. fusions were performed in 911 patients with intravenous cepha- 6. Rechtine GR, Bono PL, Cahill D, Bolesta MJ, Chrin AM. Post- lexin plus adjunctive local vancomycin powder with two ensu- operative wound infection after instrumentation of thoracic and ing deep wound infections (0.2%). The reduction in wound in- lumbar fractures. J Orthop Trauma. Nov 2001;15(8):566-569.

What is a reasonable algorithmic approach for antibiotic selection for a given patient?

CONSENSUS STATEMENT: Simple uncomplicated spine surgery (without instrumentation or comorbidities) => one single preoperative dose of antibiotic of choice with intraoperative redosing as needed

CONSENSUS STATEMENT: Instrumented spine surgery, prolonged procedures, comorbidities (eg, diabetes, neuromuscular disease, cord injury

R or general spine trauma) => one single preoperative dose of antibiotic of ecommendations choice + consideration of additional gram-negative coverage and/or the P r o p hylaxis application of intrawound vancomycin or gentamicin

in Future Directions for Research R S

ega r ding Large multicenter randomized controlled trials assessing the ef- p ine ficacy of various protocols should be tailored to specific patient

S populations (eg, obesity, diabetes, trauma, neuromuscular in- u r ge y jury or disease, prolonged multilevel instrumented surgery) at A increased risk for surgical site infections. ntibiotic

C. Redosing

For patients receiving antibiotic prophylaxis prior to open spine surgery, what are the intraoperative redosing recommendations for the recommended drugs (including dosages and time of administration) resulting in decreased postoperative infection rates?

ntibiotic A

CONSENSUS STATEMENT: Intraoperative redosing within 3-4 hours may u r ge y be considered to maintain therapeutic antibiotic levels throughout the S

procedure. The superiority of one drug has not been demonstrated in the p ine ega r ding literature. When determining the appropriate drug choice, the patient’s S R in risk factors, allergies, length and complexity of the procedure and issues of antibiotic resistance should be considered. r o p hylaxis P ecommendations R There is no study directly comparing redosing to not redosing. comparative study by design, this study provides Level IV thera- However, several studies did use redosing in their cohorts, and peutic evidence that patients with prolonged procedures that are are consistent with the consensus statement. redosed have a similar infection rate to simpler procedures with- Hellbusch et al1 conducted a prospective, randomized con- out a redosing regimen. trolled trial examining the effects of multiple dosing regiments Kakimaru et al2 reported results from a retrospective com- on the postoperative infection rate in instrumented lumbar spi- parative study comparing the infection rates following spinal nal fusion. Two hundred sixty-nine patients were randomized surgery with and without postoperative antimicrobial prophy- into either a preoperative only protocol or preoperative with an laxis. Of the 284 patients included in the study, 141 received extended postoperative antibiotic protocol. Patients in the pre- preoperatieve and postoperative dosing and 143 received preop- operative only protocol group received a single dose of intra- erative and intraoperative dosing. The antibiotics used included venous cefazolin 1 g or 2 g based on weight 30 minutes before cefazolin 1 g in 108 patients, flomoxef 1 g in 26 patients, and incision. The extended postoperative antibiotic protocol group piperacillin 1 g in seven patients for the postoperative group. received the same preoperative dose plus postoperative intrave- For the preoperative plus intraoperative dosing group, cefazolin nous cefazolin every eight hours for three days followed by oral 1 g was given to 142 patients and minocycline 100 mg was given cephalexin every six hours for seven days. Because of untow- to one patient. Patients in the postoperative dosing group had ard drug reaction or deviation from the antibiotic protocol, 36 an intravenous dose within 30 minutes of skin incision, a dose of the 269 patients were eliminated from the study. Therefore, postoperatively intravenously, and oral antibiotics for 2.7 days 233 patients completed the entire study; 117 receiving preopera- average, or the preoperative dose with intraoperative redosing at tive antibiotics only, and 116 receiving pre- and postoperative three hour intervals and a single postoperative dose. Preopera- antibiotics. At 21 days follow-up, there was no significant dif- tive plus intraoperative dosing patients had a preoperative dose ference in infection rates between the two antibiotic protocols. within 30 minutes of skin incision with intraoperative dosing at The postoperative infection rates were 4.3% for the preopera- three hour intervals until skin closure. Infection was confirmed tive only protocol and 1.7% for the preoperative with extended via bacterial cultures and inspection of wound for redness, heat, antibiotic protocol. The overall postoperative infection rate was swelling and pain. In the postoperative dosing group, 2.8% 3%. However, the study did identify five variables that appeared (4/141) developed infections (three superficial and one deep); in to demonstrate a trend toward increase in infection rate: blood the preoperative plus intraoperative dosing group, 1.4% (2/143) transfusion, electrophysiological monitoring, increased height, developed infections (p=0.335). The authors concluded that the increased weight and increased body mass index. Increased to- duration of antimicrobial prophylaxis does not influence the bacco use trended toward a lower infection rate. Although a rate of surgical site infections and postoperative administration

of antimicrobials appears unnecessary. Although a comparative science behind the use of cefuroxime and gentamicin as read- study by design, this study provides Level IV therapeutic evi- ily disc eluting antibiotics as compared with cephazolin as a less dence that intraoperative redosing resulted in similar infection disc-eluting antibiotic. In critique of this study, it was a retro- rates as single dosing in shorter cases. spective chart review evaluating postoperative infection in an Kanayama et al3 performed a retrospective case control study extremely small cohort of patients. With such a small sample to compare the rate of surgical site infections in lumbar spine sur- size, no conclusions regarding efficacy of a specific regimen can geries for two different antibiotic prophylaxis protocols. A first- be drawn. This is an extension of a basic science study looking at generation cephalosporin was administered unless the patient the penetration of cephazolin, gentamicin and cefuroxime into had a history of a significant allergy such as anaphylactic shock, disc tissue. It provides Level IV therapeutic evidence that redos- systemic skin eruption or toxic liver dysfunction. Postoperative ing resulted in similar infection rates as single dosing in shorter group patients received antibiotics for five to seven days after cases. surgery. No postoperative dose group patients received antibiot- Takahashi et al6 performed a retrospective comparative study ics only on the day of surgery; antibiotics were given 30 minutes to compare the effectiveness of preoperative cephalosporin with before skin incision. An additional dose was administered every various postoperative dosing schedules in reducing infection R

ecommendations three hours to maintain therapeutic levels throughout surgery. rates following a variety of spinal surgeries including decom- The rate of surgical site infection was compared between the two pression with or without fusion, with or without fixation. Group P r o p hylaxis prophylaxis groups. At a maximum of six months, a positive 1 received first- or second-generation cephalosporin or penicil- wound culture and/or typical infectious signs including a puru- lin administered by intravenous drip infusion for seven days (4 lent exudate, surrounding erythema, and wound fluctuance de- g/day) after the operation. After the drip infusion, cephalosporin fined infections. Laboratory studies were also referenced, such as was administered orally for one week. Group 2 received first- or

prolonged elevation in the C-reactive protein value. There were second- generation cephalosporin administered by intravenous in R

S 1133 patients in the postoperative-dose group and 464 patients drip infusion. The initial dose was given at the time of anesthesia ega r ding p ine in the no postoperative-dose group. The rate of instrumentation induction. When the operating time exceeded five hours, an ad- surgery was not statistically different between the postoperative- ditional dose was given intraoperatively. The administration was S

u r ge y dose group (43%) and the no postoperative-dose group (39%). continued for five days (2 g/day) after the operation, including A The overall rate of surgical site infection was 0.7%. The infec- the day of the operation. After the drip infusion, a cephalospo- ntibiotic tion rate was 0.8% (9/1133) in the postoperative-dose group and rin was given orally for one week. Group 3 received first- or 0.4% (2/464) in the no postoperative-dose group; the difference second-generation cephalosporin administered by intravenous between the two was not significant. Regarding the organisms drip infusion, with the initial dose given at the time of anesthe- of surgical site infection, resistant strains of bacteria were cul- sia induction. Additional doses were administered every three tured in five (83.3%) of six patients in the postoperative-dose hours during the operation. The administration was then con- group, whereas none was cultured in the no postoperative-dose tinued for three days (2 g/day) after the operation, including the group. The authors concluded there was no statistical difference day of the operation. After the drip infusion, a cephalosporin was observed between protocols. Although a comparative study was given orally for one week. Group 4 received first-generation by design, this study provides Level IV therapeutic evidence that cephalosporin administered by intravenous drip infusion with intraoperative redosing resulted in similar infection rates as sin- the initial dose given at the time of anesthesia induction. Addi- gle dosing in shorter cases. tional doses were given every three hours during the operation. Mastronardi (2004) et al4 presented a retrospective case se- The administration was then continued for two days (2 g/day) ries evaluating the safety and efficacy of a specific intraopera- after the operation, including the day of the operation. Of the tive antibiotic protocol for a variety of spinal surgeries. Over 1415 patients included in the study, 539 were included in Group a three-year period, 973 patients received ampicillin/sulbactam 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- 1.5 g intravenous on induction or Teicoplanin 400 mg intrave- ing the CDC guideline criteria, surgical site infections involving nous on induction (if surgery longer than two hours) with re- only the skin and/or subcutaneous tissues at the site of the inci- dosing of teicoplanin at four hours or 1500 mL blood loss. Data sion were designated superficial infections, and those involving was gathered at six weeks to one year regarding drainage from deeper soft tissues (eg, fascial and muscle layers) at the site of the the wound, wound abscess or positive culture. Wound infection incision were designated deep infections. The overall frequency occurred in nine cases (1%) and discitis in four of 657 (0.06%) of surgical site infections for the different groups were: Group 1, patients. This study provides Level IV therapeutic evidence that 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 and intraoperative redosing resulted in similar infection rates as sin- 0/83, respectively. Comparision using Tukey’s multiple compar- gle dosing in shorter cases. ison test showed p<0.05 for comparing infections rates between Riley et al5 described a retrospective study of one year’s pa- Groups 1, 2 and 3. The authors concluded that when thorough tients (40) who had either simple discectomy or instrumented prophylactic countermeasures are undertaken against periop- procedures. Patients received 1.5 g cefuroxime preoperatively erative surgical site infections, the frequency of these infections and every four hours for a 48-hour duration. Intravenous gen- can be decreased, with a decrease in the duration of antimicrobi- tamicin (80 mg) was administered preoperatively, with redosing al prophylaxis administration from seven days to two days. Al- every six hours intraoperatively and every eight hours postop- though a comparative study by design, this study provides Level eratively for a 48-hour duration. No infections occurred in the IV therapeutic evidence that intraoperative redosing resulted in 40 patients. The study provides a good discussion of the basic similar infection rates as single dosing in shorter cases.

Future Directions for Research 2. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- Recommendation #1: erative antimicrobial prophylaxis following spinal decompres- A case controlled study is suggested utilizing available national sion surgery: is it necessary? J Orthop Sci. May;15(3):305-309. databases to determine the relative efficacy of redosing antibiot- 3. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. Effective prevention of surgical site infection using a Centers for ic prophylaxis in specific patient populations undergoing spine Disease Control and Prevention guideline-based antimicrobial surgery. prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr 2007;6(4):327-329. Recommendation #2: 4. Mastronardi L, Tatta C. Intraoperative antibiotic prophylaxis in A series of randomized controlled studies evaluating dosing reg- clean spinal surgery: a retrospective analysis in a consecutive imens is recommended; each study could address a specific sub- series of 973 cases. Surg Neurol. Feb 2004;61(2):129-135; discus- population defined by diagnosis, procedure and comorbidity. sion 135. 5. Riley LH, 3rd. Prophylactic antibiotics for spine surgery: de- Redosing References scription of a regimen and its rationale. J South Orthop Assoc. Fall 1998;7(3):212-217. 1. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs.

6. Takahashi H, Wada A, Iida Y, et al. Antimicrobial prophylaxis multiple-dose antibiotic prophylaxis in instrumented lumbar for spinal surgery. J Orthop Sci. Jan 2009;14(1):40-44. fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- 627; discussion 627. ntibiotic A u r ge y S p ine ega r ding S R in

r o p hylaxis P ecommendations R

D. Discontinuation

For patients receiving antibiotic prophylaxis prior to open spine surgery, does discontinuation of prophylaxis at 24 hours result in decreased or increased postoperative

R infection rates as compared to longer periods of ecommendations

P administration? r o p hylaxis

For typical, uncomplicated cases, a single dose of preoperative

prophylactic antibiotics with intraoperative redosing as needed is in R S

ega r ding suggested to decrease the risk of surgical site infection. p ine

S Grade of Recommendation: B u r ge y A ntibiotic

Dobzyniak et al1 described a retrospective comparative study ex- extended postoperative antibiotic protocol. Patients in the pre- amining the efficacy of single versus multiple dosing for lumbar operative only protocol group received a single dose of intra- disc surgery. The antibiotics used for prophylaxis consisted of venous cefazolin 1 g or 2 g based on weight 30 minutes before cephazolin 1 g, 525 patients; clindamycin 600 mg, 15 patients; incision. The extended postoperative antibiotic protocol group vancomycin 1 g plus clindamycin 600 mg, 46 patients; and van- received the same preoperative dose plus postoperative intrave- comycin 1 g alone, 24 patients. The choice of an antibiotic other nous cefazolin every eight hours for three days followed by oral than cephazolin was based on a patient allergy to penicillin or cephalexin every six hours for seven days. Because of untoward cephalosporins and surgeons preference when these allergies drug reaction or deviation from the antibiotic protocol, 36 of were encountered. Of the 635 consecutive patients included in the 269 patients were eliminated from the study. Therefore, 233 the study, 418 received the multidose regimen, 192 received the patients completed the entire study; 117 receiving preoperative single dose and 25 patients were eliminated from the study since antibiotics only and 116 receiving pre- and postoperative antibi- no preoperative dose was documented. Infection was confirmed otics. At 21 days follow-up, there was no significant difference at six weeks via cultures and attending physician’s assessment. in infection rates between the two antibiotic protocols. The post- The infection rate was 1.56% (3/192) with single dosing versus operative infection rates were 3% overall, 4.3% for the preopera- 1.20% (5/418) with multiple dosing, p=0.711, Fisher exact test. tive only protocol and 1.7% for the preoperative with extended The authors concluded that a single preoperative dose of prophy- antibiotic protocol. Statistical significance was not achieved, and lactic antibiotics is as effective as preoperative plus postoperative the authors suggested that a larger sample size of 700 patients per antibiotics in the prevention of wound infections in lumbar disc group was needed to prove statisical superiority or equivalency surgery. They recommend preoperative antibiotics alone, citing between treatment groups. The authors concluded that preoper- no advantage in prolonging a patient’s discharge following lum- ative prophylactic antibiotic use in instrumented lumbar spinal bar disc excision to administer postoperative antibiotics. This fusion is generally accepted and has been shown consistently to study provides Level III therapeutic evidence that single dosing decrease postoperative infection rates. Prolonged postoperative is as effective as multiple dosing; however, different antibiotics antibiotic dosing carries with it an increased cost and potential do not appear to affect the rate of wound infection. The superi- complications. Due to questions about the method of random- ority of one agent or regimen was not demonstrated. ization and lack of validated outcome measures, this potential Hellbusch et al2 conducted a prospective, randomized con- Level II study provides Level III therapeutic evidence that pre- trolled trial examining the effects of multiple dosing regiments operative prophylactic antibiotic use in instrumented lumbar on the postoperative infection rate in instrumented lumbar spi- spinal fusion is effective at reducing the risk of infection. Anti- nal fusion. Two hundred sixty-nine patients were randomized biotic prophylaxis can be discontinued within 24 hours with no into either a preoperative only protocol or preoperative with an significant change in infection rate.

Kakimaru et al3 reported results from a retrospective com- statistical difference was observed between protocols. The CDC parative study comparing the infection rates following spinal protocol of preoperative dosing prevents development of resis- surgery with and without postoperative antimicrobial prophy- tant strains while reducing the risk of surgical site infections. laxis. Of the 284 patients included in the study, 141 received pre- This study provides Level III therapeutic evidence that preopera- operative and postoperative dosing and 143 received a preop- tive and intraoperative redosing is efficacious in preventing sur- erative and intraoperative dosing. The antibiotics used included gical site infection. Also, extended dosing may induce resistant cefazolin 1 g in 108 patients, flomoxef 1 g in 26 patients and strains. Suction drains were left in place in fusions for two to piperacillin 1 g in seven patients for the postoperative group. three days. Accordingly, multidosing of antibiotics until drains For the no postoperative dosing group, cefazolin 1 g for was are removed may not be beneficial. The superiority of one agent given to 142 patients and minocycline 100 mg for was given or regimen was not demonstrated. to one patient. Patients in the postoperative dosing group had Takahashi et al5 performed a retrospective comparative study an intravenous dose within 30 minutes of skin incision, a dose to compare the effectiveness of preoperative cephalosporin with postoperatively intravenously, and oral antibiotics for 2.7 days various postoperative dosing schedules in reducing infection average, or the preoperative dose with intraoperative redosing at rates following a variety of spinal surgeries including decompres- three hour intervals and a single postoperative dose. No postop- sion with or without fusion, with or without fixation. Group 1 erative dosing patients had a preoperative dose within 30 min- received first- or second-generation cephalosporin or penicillin utes of skin incision with intraoperative dosing at three hour in- administered by intravenous drip infusion for seven days (4 g/ tervals until skin closure. Infection was confirmed via bacterial day) after the operation. After the drip infusion, cephalosporin ntibiotic A cultures and inspection of wound for redness, heat, swelling and was administered orally for one week. Group 2 received first- or u r ge y pain. In the postoperative dosing group, 2.8% (4/141) developed second- generation cephalosporin administered by intravenous S infections (three superficial and one deep); in the no postopera- drip infusion. The initial dose was given at the time of anesthesia p ine tive dosing group, 1.4% (2/143) developed infections (p=0.335). induction. When the operating time exceeded five hours, an ad- ega r ding S R in

The authors concluded that the duration of antimicrobial pro- ditional dose was given intraoperatively. The administration was phylaxis does not influence the rate of surgical site infections continued for five days (2 g/day) after the operation, including andpostoperative administration of antimicrobials appears un- the day of the operation. After the drip infusion, a cephalospo- necessary. This study provides Level III evidence that preopera- rin was given orally for one week. Group 3 received first- or tive plus intraoperative redosing of antimicrobial prophylaxis as second-generation cephalosporin administered by intravenous r o p hylaxis needed is effective at preventing surgical site infection in spinal drip infusion, with the initial dose given at the time of anesthe- P

surgery patients. The superiority of one agent or regimen was sia induction. Additional doses were administered every three ecommendations not demonstrated. hours during the operation. The administration was then con- R Kanayama et al4 performed a retrospective comparative tinued for three days (2 g/day) after the operation, including the study to compare the rate of surgical site infections in lumbar day of the operation. After the drip infusion, a cephalosporin spine surgeries for two different antibiotic prophylaxis proto- was given orally for one week. Group 4 received first-generation cols. A first-generation cephalosporin was administered unless cephalosporin administered by intravenous drip infusion with the patient had a history of a significant allergy such as anaphy- the initial dose given at the time of anesthesia induction. Addi- lactic shock, systemic skin eruption or toxic liver dysfunction. tional doses were given every three hours during the operation. Postoperative-dose group patients received antibiotics for five to The administration was then continued for two days (2 g/day) seven days after surgery. No postoperative-dose group patients after the operation, including the day of the operation. Of the received antibiotics only on the day of surgery; antibiotics were 1415 patients included in the study, 539 were included in Group given 30 minutes before skin incision. An additional dose was 1, 536 in Group 2, 257 in Group 3 and 83 in Group 4. Adopt- administered every three hours to maintain therapeutic levels ing the CDC guideline criteria, surgical site infections involving throughout surgery. Infection was defined as a positive wound only the skin and/or subcutaneous tissues at the site of the inci- culture and/or typical infectious signs including a purulent exu- sion were designated superficial infections, and those involving date, surrounding erythema and wound fluctuance detected deeper soft tissues (eg, fascial and muscle layers) at the site of the within six months of surgery. Laboratory studies were also refer- incision were designated deep infections. The overall frequency enced, such as prolonged elevation in the C-reactive protein val- of surgical site infections for the different groups were: Group ue. There were 1133 patients in the postoperative-dose group, 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 and 464 patients in the no postoperative-dose group. The rate of and 0/83, respectively. Comparision using Tukey’s multiple instrumentation surgery was not statistically different between comparison test showed p<0.05 for comparing infections rates the postoperative-dose group (43%) and the no postoperative- between Groups 1, 2 and 3. The authors concluded that when dose group (39%). The overall rate of surgical site infection was thorough prophylactic countermeasures are undertaken against 0.7%. The infection rate was 0.8% (9/1133) in the postopera- perioperative surgical site infections, the frequency of these in- tive-dose group and 0.4% (2/464) in the no postoperative- dose fections can be decreased, with a decrease in the duration of an- group; the difference between the two was not significant. Re- timicrobial prophylaxis administration from seven days to two garding the organisms of surgical site infection, resistant strains days. This study provides Level III therapeutic evidence that of bacteria were cultured in five (83.3%) of six patients in the shorter duration of antimicrobial prophylaxis is more effective postoperative-dose group, whereas none was cultured in the no compared to longer durations. postoperative-dose group. The authors concluded there was no

diabetes (odds ratio = 3.5, 95% confidence interval = 1.2, 10.0), Prolonged postoperative regimens may be suboptimal timing of prophylactic antibiotic therapy (odds ratio considered in complex situations (ie, trauma, = 3.4, 95% confidence interval = 1.5, 7.9), a preoperative serum cord injury, neuromuscular disease, diabetes glucose level of >125 mg/dL (>6.9 mmol/L) or a postoperative serum glucose level of >200 mg/dL (>11.1 mmol/L) (odds ratio or other comorbidities). Comorbidities and = 3.3, 95% confidence interval = 1.4, 7.5), obesity (odds ratio = complex situations reviewed in the literature 2.2, 95% confidence interval = 1.1, 4.7) and two or more surgical include obesity, diabetes, neurologic defi- residents participating in the operative procedure (odds ratio = cits, incontinence, preoperative serum glu- 2.2, 95% confidence interval = 1.0, 4.7). A decreased risk of sur- cose level of >125 mg/dL or a postoperative gical site infection was associated with operations involving the cervical spine (odds ratio = 0.3, 95% confidence interval = 0.1, serum glucose level of >200 mg/dL, trauma, 0.6). The authors concluded that diabetes was associated with prolonged multilevel instrumented surgery the highest independent risk of spinal surgical site infection and and other comorbidities. an elevated preoperative or postoperative serum glucose level R

ecommendations was also independently associated with an increased risk of surgical site infection. The role of hyperglycemia as a risk factor for P Grade of Recommendation: C r o p hylaxis surgical site infection in patients not previously diagnosed with diabetes should be investigated further. Administration of pro- While there appear to be clinical scenarios where prolonged an- phylactic antibiotics within one hour before the operation and tibiotics may be helpful, at this time the evidence is weak, and increasing the antibiotic dosage to adjust for obesity are also im- the specific indications are not completely clear. Until better portant strategies to decrease the risk of surgical site infection in R data is available, the surgeon should make this decision based S after spinal operations. This study provides Level III prognostic ega r ding p ine on their experience, the regional historical profile of infections evidence that diabetes, suboptimal timing of antibiotic prophy- in their centers, the complexity of the surgery and the specific laxis, preoperative gluclose level of >125 mg/dL, postoperative S comorbidities of the patient. u r ge y 6 gluclose level of >200mg/dL and obesity are independent risk A Olsen (2003) et al performed a retrospective case control factors for surgical site infection following orthopedic spinal op- ntibiotic study to identify the specific independent risk factors for surgi- erations. Prolonged prophylactic regimens may be necessary to cal site infections occurring after laminectomy or spinal fusion. further reduce the infection rate in patients with risk factors for All patients received standard prophylaxis with cephalosporins surgical site infection. or vancomycin in penicillin sensitive patients. Infection was de- Hellbusch et al2 conducted a prospective, randomized con- fined using the CDC guideline definition, with infections identi- trolled trial examining the effects of multiple dosing regiments fied between two and 83 days (median time from surgery to in- on the postoperative infection rate in instrumented lumbar spi- fection was 14 days). Of the 53 of 1918 patients who experienced nal fusion. Two hundred sixty-nine patients were randomized surgical site infections, 12 were excluded due to missing data. into either a preoperative only protocol or preoperative with an These patients were compared with 179 noninfected matched extended postoperative antibiotic protocol. Patients in the preop- controls. Infection rate, even with prophylaxis, was 2.76% with erative only protocol group received a single dose of intravenous no significant variation in the infection rate during the four-year cefazolin 1 g or 2 g based on weight 30 minutes before incision. period. The authors identified postoperative incontinence, obe- The extended postoperative antibiotic protocol group received sity, tumor resection and posterior approach as risk factors. This the same preoperative dose plus postoperative intravenous ce- study provides Level III prognostic evidence that incontinence fazolin every eight hours for three days followed by oral cepha- (resulting from neurologic injury), obesity, tumor resection (re- lexin every six hours for seven days. Because of untoward drug lated to neurologic deficits) and posterior approach increase risk reaction or deviation from the antibiotic protocol, 36 patients of infection. Prolonged prophylactic regimens may be necessary were eliminated from the study. Therefore, 233 patients complet- to further reduce the infection rate in patients with risk factors ed the entire study; 117 receiving preoperative antibiotics only for surgical site infection. 7 and 116 receiving pre- and postoperative antibiotics. At 21 days Olsen (2008) et al described a retrospective case control follow-up, there was no significant difference in infection rates study designed to determine independent risk factors for sur- between the two antibiotic protocols. The postoperative infec- gical site infection following orthopedic spinal operations. All tion rates were 4.3% for the preoperative only protocol and 1.7% patients received standard prophylaxis with cephalosporins or for the preoperative with extended antibiotic protocol. The over- vancomycin in penicillin sensitive patients. Of 2316 patients, all postoperative infection rate was 3%. Although not statisti- 46 patients with superficial, deep or organ-space surgical site cally significant, the study identified five variables that appeared infections were identified and compared with 227 uninfected to demonstrate a trend toward increased infection rate: blood control patients. The overall rate of spinal surgical site infec- transfusion, electrophysiological monitoring, increased height, tion during the five years of the study was 2.0% (46/2316). Uni- increased weight and increased body mass index. The authors variate analyses showed serum glucose levels, preoperatively and concluded that there were no significant differences in infection within five days after the operation, to be significantly higher in rates between the antibiotic protocols. Preoperative prophylactic patients in whom surgical site infection developed than in un- antibiotic use in instrumented lumbar spinal fusion is generally infected control patients. Independent risk factors for surgical accepted and has been shown consistently to decrease postop- site infection that were identified by multivariate analysis were

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 43 erative infection rates, but the ideal duration could be variable in multiple-dose antibiotic prophylaxis in instrumented lumbar patients at high risk for infection. Although a comparative study fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- by design, this study provides Level IV therapeutic evidence that 627; discussion 627. prolonged postoperative regimens decrease the infection rate. 3. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- erative antimicrobial prophylaxis following spinal decompression surgery: is it necessary? J Orthop Sci. May 2010;15(3):305- Future Directions for Research 309. Controlled studies are suggested comparing infection rates in 4. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. spinal surgical patients with trauma, neuromuscular disease, di- Effective prevention of surgical site infection using a Centers for abetes, or other comorbiditties who received antibiotics, which Disease Control and Prevention guideline-based antimicrobial were discontinued within 24 hours, as compared with groups prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr who received antibiotics for a longer period of time. 2007;6(4):327-329. 5. Takahashi H, Wada A, Iida Y, et al. Antimicrobial prophylaxis Discontinuation References for spinal surgery. J Orthop Sci. Jan 2009;14(1):40-44. 1. Dobzyniak MA, Fischgrund JS, Hankins S, Herkowitz HN. 6. Olsen MA, Mayfield J, Lauryssen C, et al. Risk factors for surgi- Single versus multiple dose antibiotic prophylaxis in lumbar disc cal site infection in spinal surgery. J Neurosurg. Mar 2003;98(2 surgery. Spine. Nov 1 2003;28(21):E453-455. Suppl):149-155. 2. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. 7. Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical site infection following orthopaedic spinal operations. J Bone Joint Surg Am. Jan 2008;90(1):62-69. ntibiotic A u r ge y S p ine ega r ding S R in

r o p hylaxis P ecommendations R

E. Wound Drains

For patients receiving antibiotic prophylaxis prior to open spine surgery and who receive placement of wound drains at wound closure, does discontinuation of prophylaxis at 24 hours result in decreased or increased postoperative R

ecommendations infection rates as compared to discontinuation P r o p hylaxis of antibiotics at time of drain removal?

A comprehensive review of the literature did not yield evidence to address the question related to the effect in R on postoperative infection rates of the duration of prophylaxis in the presence of a wound drain. S ega r ding p ine There is insufficient evidence to make a recommendation for or against S the early discontinuation of antibiotic prophylaxis in patients with wound u r ge y A drains. ntibiotic

Grade of Recommendation: I (Insufficient Evidence)

Kanayama et al1 performed a retrospective comparative study dose group, whereas none was cultured in the no postoperative- to compare the rate of surgical site infections in lumbar spine dose group. This study provides Level III therapeutic evidence surgeries for two different antibiotic prophylaxis protocols. Al- that the protocol of preoperative antibiotic prophylaxis plus in- though the purpose of this study was not to evaluate the optimal traoperative redosing every three hours is as effective as preop- duration of antibiotic prophylaxis in the presence of drains, this erative plus postoperative dosing of antibiotics. Also, extended was the only study identified in the literature review to address dosing may induce resistant strains. Suction drains were left in a drain removal protocol. A first-generation cephalosporin was place in fusions for two to three days. Accordingly, multidosing administered unless the patient had a history of a significant al- of antibiotics until drains are removed may not be beneficial. lergy such as anaphylactic shock, systemic skin eruption or toxic liver dysfunction. Postoperative-dose group patients (n=1133) received antibiotics for five to seven days after surgery. No post- The use of drains is not recommended as a operative dose group patients (n=464) received antibiotics only means to reduce infection rates following on the day of surgery; antibiotics were given 30 minutes before single level surgical procedures. skin incision. An additional dose was administered every three hours to maintain therapeutic levels throughout surgery. Infec- tion was defined as a positive wound culture and/or typical infec- Grade of Recommendation: I (Insufficient tious signs including a purulent exudate, surrounding erythema, Evidence) and wound fluctuance detected within six months after surgery. The rate of instrumentation surgery was not statistically differ- Payne et al2 described a randomized controlled trial of drain use ent between the multiple-dose group (43%) and the single-dose in 205 patients undergoing a single level laminectomy without group (39%). The overall rate of surgical site infection was 0.7%. fusion. The patients were randomized to determine whether they The infection rate was 0.8% (9/1133) in the postoperative-dose would receive a wound drain. There was no difference between group and 0.4% (2/464) in the no postoperative-dose group; the the groups in terms of infection rates. In critique, this study ap- difference between the two was not significant. Regarding the pears on the surface to provide Level I evidence. However, it was organisms of surgical site infection, resistant strains of bacteria downgraded to Level II because it was substantially underpow- were cultured in five (83.3%) of six patients in the postoperative- ered. It provides Level II therapeutic evidence that drains have

Future Directions for Research Wound Drains References Recommendation #1: 1. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. Controlled studies are suggested comparing infection rates Effective prevention of surgical site infection using a Centers for in nonfusion and nonimplanted spinal surgical patients with Disease Control and Prevention guideline-based antimicrobial drains and discontinuation at 24 hours as compared with longer prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr 2007;6(4):327-329. duration prophylaxis. 2. Pavel A, Smith RL, al e. Prophylactic antibiotics in elective orthopedic surgery: A prospective study of 1591 cases. South Med Recommendation #2: J. 1977;Suppl 1:50-55. Controlled studies are suggested comparing infection rates in

ntibiotic A u r ge y S p ine ega r ding S R in

r o p hylaxis P ecommendations R

F. Body Habitus

For patients receiving antibiotic prophylaxis prior to spine surgery, should the recommended protocol differ based upon body habitus (eg, body mass index)?

R Obese patients are at higher risk for postoperative infection, when given ecommendations a standardized dose of antibiotic prophylaxis. In spite of this conclusion, P r o p hylaxis there is insufficient evidence to make a recommendation for or against recommending a different protocol for patients based upon body habitus.

Grade of Recommendation: I (Insufficient Evidence) in R S ega r ding p ine

S Chen et al1 performed a retrospective case control study to de- Level IV prognostic evidence that morbid obesity is associated u r ge y

A termine the role that diabetes and other known risk factors play with a five-fold increased risk of surgical site infection after spi-

ntibiotic in the development of surgical site infection in spinal surgery pa- nal surgery (OR 5.2, 95% C.I.=1.9-14.2). tients. Of the 195 spinal infection patients included in the study, Olsen (2008) et al3 described a retrospective case control 30 had diabetes and 165 did not. Prophylactic protocols varied study designed to determine independent risk factors for sur-

and the spinal surgeries were heterogeneous with instrumented gical site infection following orthopedic spinal operations. All and uninstrumented procedures at all levels. Outcomes were re- patients received standard prophylaxis with cephalosporins or viewed at 30 days for all patients and at one year for patients with vancomycin in penicillin sensitive patients. Of 2316 patients, fixation. In addition to diabetes, known risk factors for surgi- 46 patients with superficial, deep, or organ-space surgical site cal site infection in spinal surgery were examined: age, gender, infections were identified and compared with 227 uninfected tobacco use, body mass index > 35 (morbid obesity), American control patients. Univariate analyses showed serum glucose lev- Society of Anesthesiologists (ASA) class, intraoperative antibi- els, preoperatively and within five days after the operation, to be otic redosing, surgical time, bone allograft use, estimated blood significantly higher in patients in whom surgical site infection loss (EBL) and drain use. The adjusted relative risk of having developed than in uninfected control patients. Independent risk diabetes for developing surgical site infection was significant factors for surgical site infection that were identified by multi- (RR 4.10, 95% C.I. = 1.37–12.32); however, the other factors did variate analysis were diabetes (odds ratio = 3.5, 95% confidence not appear as significant risk factors.This study provides Level interval = 1.2, 10.0), suboptimal timing of prophylactic antibi- IV prognostic evidence that body mass index was not found to otic therapy (odds ratio = 3.4, 95% confidence interval = 1.5, be a risk for developing an infection after spinal surgery. 7.9), a preoperative serum glucose level of >125 mg/dL (>6.9 Olsen (2003) et al2 performed a retrospective case control mmol/L) or a postoperative serum glucose level of >200 mg/dL study to identify the specific independent risk factors for surgi- (>11.1 mmol/L) (odds ratio = 3.3, 95% confidence interval = 1.4, cal site infections occurring after laminectomy or spinal fusion. 7.5), obesity (odds ratio = 2.2, 95% confidence interval = 1.1, 4.7) All patients received standard prophylaxis with cephalosporins and two or more surgical residents participating in the operative or vancomycin in penicillin sensitive patients. Infection was de- procedure (odds ratio = 2.2, 95% confidence interval = 1.0, 4.7). fined using the CDC guideline definition, with infections iden- A decreased risk of surgical site infection was associated with tified between two and 83 days (median time from surgery to operations involving the cervical spine (odds ratio = 0.3, 95% infection was 14 days). Of the 53 of 1918 patients who expe- confidence interval = 0.1, 0.6). The authors suggest that increas- rienced surgical site infections, 12 were excluded due to missing the antibiotic dosage to adjust for obesity is an important ing data. These patients were compared with 179 noninfected strategy to decrease the risk of surgical site infection after spinal matched controls. Infection rate even with prophylaxis was operations. This study provides Level IV prognostic evidence 2.76% with no significant variation in the infection rate during that obesity is an independent risk factor for surgical site infec- the four-year period. Through multivariate anlaysis, the authors tion in spinal surgery patients, and infection occurred at a 2% identified postoperative incontinence, morbid obesity, tumor re- overall rate in all patients in the face of prophylactic antibiotics. section and posterior approach as independent risk factors for Wimmer et al4 performed a retrospective study of 850 spinal the development of surgical site infection. This study provides procedures, in which all patients received 2 gm of cefazolin in-

4. Wimmer C, Nogler M, Frischut B. Influence of antibiotics on infection in spinal surgery: A prospective study of 110 patients. J Spinal Disord. 1998;11:498-500. ntibiotic A u r ge y S p ine ega r ding S R in

r o p hylaxis P ecommendations R

G. Comorbidities

For patients receiving antibiotic prophylaxis prior to open spine surgery, do comorbidities (other than obesity) such as diabetes, smoking, nutritional depletion, immunodeficiencies and concurrent use of antithrombotic therapies alter R ecommendations the recommendations for antibiotic prophylaxis? P r o p hylaxis

CONSENSUS STATEMENT: In patients with comorbidities or for those in R

S undergoing complicated spine surgery, alternative prophylactic regimens ega r ding p ine are suggested to decrease the incidence of surgical site infections when

S compared to standard prophylaxis regimens. u r ge y A

ntibiotic There is insufficient evidence to make a recommendation for or against the specific alternative regimens that are efficacious. However, promising alternative regimens that have been studied include redosing, gram-negative coverage and the addition of intrawound application of vancomycin or gentamicin.

Grade of Recommendation: I (Insufficient Evidence)

Kanafani et al1 described a case control study comparing risk Olsen (2003) et al2 performed a retrospective case control factors in patients who did or did not develop infections. This study to identify the specific independent risk factors for surgi- study reported the incidence of postoperative infection after spi- cal site infections occurring after laminectomy or spinal fusion. nal surgeries at a single institution. They also compared infected All patients received standard prophylaxis with cephalosporins cases with control samples from the same population in order to or vancomycin in penicillin sensitive patients. Infection was de- identify risk factors. The presence of diabetes, older age and im- fined using the CDC guideline definition, with infections identi- plants (spinal hardware) were the only three variables that were fied between two and 83 days (median time from surgery to in- significantly higher in the infected group. Both cases and con- fection was 14 days). Of the 53 of 1918 patients who experienced trols received preoperative antibiotic prophylaxis, but infected surgical site infections, 12 were excluded due to missing data. cases received a first generation cephalosporin more often. The These patients were compared with 179 noninfected matched authors documented infection rates for patients who received controls. Infection rate even with prophylaxis was 2.76% with first-generation cephalosporin, second-generation, third-gen- no significant variation in the infection rate during the four-year eration or a glycopeptide. The average duration of antibiotic period. Cultures were obtained from infected patients and gram- administration was 2.2 days in infected cases and 1.5 hours in negative rods and/or anaerobes were present in 17/39 (44%) of controls. In critique of this study, the efficacy of antibiotic pro- the cultures. Additionally, gram-negative rods and/or anaerobes phylaxis could not be analyzed for instrumented versus nonin- were isolated significantly more often in patients who underwent strumented cases. The study offers Level III prognostic evidence lumbar or lumbosacral procedures (15/24) compared to patients that diabetes, older age and the use of instrumentation are risk who underwent thoracic or cervical procedures (2/15, p<0.001). factors for postoperative wound infection despite the use of peri- The authors identified postoperative incontinence, obesity, tu- operative antibiotic prophylaxis. This study does not offer any mor resection and posterior approach as risk factors. This study evidence suggesting alterations in antibiotic prophylaxis in the provides Level III prognostic evidence that incontinence, tumor presence of specific co-morbidities. resection and posterior approach increase risk of infection and

This clinical guideline should not be construed as including all proper methods of care or excluding or other acceptable methods of care reason- ably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution Antibiotic Prophylaxis in Spine Surgery | NASS Clinical Guidelines 49 gram-negative bacteria and/or anaerobes are likely to be isolated continued for five days (2 g/day) after the operation, including from a portion of infected patients. Alternative prophylactic reg- the day of the operation. After the drip infusion, a cephalospo- imens may be necessary to further reduce the infection rate in rin was given orally for one week. Group 3 received first- or patients with risk factors for surgical site infection. second-generation cephalosporin administered by intravenous Olsen (2008) et al3 described a retrospective case control drip infusion, with the initial dose given at the time of anesthe- study designed to determine independent risk factors for sur- sia induction. Additional doses were administered every three gical site infection following orthopedic spinal operations. All hours during the operation. The administration was then con- patients received standard prophylaxis with cephalosporins or tinued for three days (2 g/day) after the operation, including the vancomycin in penicillin sensitive patients. Of 2316 patients, day of the operation. After the drip infusion, a cephalosporin 46 patients with superficial, deep or organ-space surgical site was given orally for one week. Group 4 received first generation infections were identified and compared with 227 uninfected cephalosporin administered by intravenous drip infusion with control patients. The overall rate of spinal surgical site infec- the initial dose given at the time of anesthesia induction. Addi- tion during the five years of the study was 2.0% (46/2316). Uni- tional doses were given every three hours during the operation. variate analyses showed serum glucose levels, preoperatively and The administration was then continued for two days (2 g/day) within five days after the operation, to be significantly higher in after the operation, including the day of the operation. Patients patients in whom surgical site infection developed than in un- with diabetes mellitus, metastatic spinal tumors, on dialysis or infected control patients. Independent risk factors for surgical receiving daily steroid administration of 5 mg or more for at site infection that were identified by multivariate analysis were least 90 days were defined as compromised hosts and included ntibiotic A diabetes (odds ratio = 3.5, 95% confidence interval = 1.2, 10.0), 19.1%, 16.0%, 19.1% and 28.9% of patients in groups 1-4. Adopt- u r ge y suboptimal timing of prophylactic antibiotic therapy (odds ratio ing the CDC guideline criteria, surgical site infections involving S = 3.4, 95% confidence interval = 1.5, 7.9), a preoperative serum only the skin and/or subcutaneous tissues at the site of the inci- p ine glucose level of >125 mg/dL (>6.9 mmol/L) or a postoperative sion were designated superficial infections and those involving ega r ding S R in

serum glucose level of >200 mg/dL (>11.1 mmol/L) (odds ratio deeper soft tissues (eg, fascial and muscle layers) at the site of the = 3.3, 95% confidence interval = 1.4, 7.5), obesity (odds ratio = incision were designated deep infections. The overall frequency 2.2, 95% confidence interval = 1.1, 4.7) and two or more surgical of surgical site infections for the different groups were: Group residents participating in the operative procedure (odds ratio = 1, 2.6% (14/539); Group 2, 0.9% (5/536); Group 3 and 4, 0/257 2.2, 95% confidence interval = 1.0, 4.7). A decreased risk of sur- and 0/83, respectively. Comparision using Tukey’s multiple r o p hylaxis gical site infection was associated with operations involving the comparison test showed p<0.05 for comparing infections rates P

cervical spine (odds ratio = 0.3, 95% confidence interval = 0.1, between Groups 1, 2 and 3. In addition, there was no significant ecommendations 0.6). The authors concluded that diabetes was associated with difference in the frequency of surgical site infection between the R the highest independent risk of spinal surgical site infection and compromised hosts and rest of the patients. The authors con- an elevated preoperative or postoperative serum glucose level cluded that when thorough prophylactic countermeasures are was also independently associated with an increased risk of sur- undertaken against perioperative surgical site infections, the fre- gical site infection. The role of hyperglycemia as a risk factor for quency of these infections can be decreased, with a decrease in surgical site infection in patients not previously diagnosed with the duration of antimicrobial prophylaxis administration from diabetes should be investigated further. Administration of pro- seven days to two days. This study provides Level III therapeu- phylactic antibiotics within one hour before the operation and tic evidence that shorter duration of antimicrobial prophylaxis increasing the antibiotic dosage to adjust for obesity are also im- is more effective, and two days of antibiotic administration is portant strategies to decrease the risk of surgical site infection recommended compared to longer durations. after spinal operations. This study provides Level III prognostic Hellbusch et al5 conducted a prospective, randomized con- evidence that diabetes is the highest independent risk factor, and trolled trial examining the effects of multiple dosing regiments infection occurred at a 2% overall rate in all patients in the face on the postoperative infection rate in instrumented lumbar spi- of prophylactic antibiotics. Alternative prophylactic regimens nal fusion. Two hundred sixty-nine patients were randomized may be necessary to further reduce the infection rate in patients into either a preoperative only protocol or preoperative with an with diabetes and other risk factors for surgical site infection. extended postoperative antibiotic protocol. Patients in the pre- Takahashi et al4 performed a retrospective comparative study operative only protocol group received a single dose of intra- to compare the effectiveness of preoperative cephalosporin with venous cefazolin 1 g or 2 g based on weight 30 minutes before various postoperative dosing schedules in reducing infection incision. The extended postoperative antibiotic protocol group rates following a variety of spinal surgeries including decompres- received the same preoperative dose plus postoperative intrave- sion with or without fusion, with or without fixation. Group 1 nous cefazolin every eight hours for three days followed by oral received first- or second-generation cephalosporin or penicillin cephalexin every six hours for seven days. Because of untoward administered by intravenous drip infusion for seven days (4 g/ drug reaction or deviation from the antibiotic protocol, 36 pa- day) after the operation. After the drip infusion, cephalosporin tients were eliminated from the study. Therefore, 233 patients was administered orally for one week. Group 2 received first- or completed the entire study; 117 receiving preoperative antibiot- second-generation cephalosporin administered by intravenous ics only, and 116 receiving pre- and postoperative antibiotics. At drip infusion. The initial dose was given at the time of anesthesia 21 days follow-up, there was no significant difference in infec- induction. When the operating time exceeded five hours, an ad- tion rates between the two antibiotic protocols. The postopera- ditional dose was given intraoperatively. The administration was tive infection rates were 4.3% for the preoperative only protocol

and 1.7% for the preoperative with extended antibiotic protocol. antibiotic prophylaxis with cephalexin. Since 2006, 911 of these The overall postoperative infection rate was 3%. Although not instrumented thoracic and lumbar cases had 2 g of vancomycin statistically significant, the study identified five variables that ap- powder applied to the wound prior to closure in addition to in- peared to demonstrate a trend toward increased infection rate: travenous antibiotics. A retrospective review for infection rates blood transfusion, electrophysiological monitoring, increased and complications was performed with an average follow-up of height, increased weight and increased body mass index. In- 2.5 years (range: 1-7 years). If wound infection was suspected creased tobacco use trended toward a lower infection rate. The based on clinical and constitutional symptoms, aspiration was authors concluded that preoperative prophylactic antibiotic use completed. If aspiration demonstrated purulent material or in instrumented lumbar spinal fusion is generally accepted and the wound was clinically suspicious for subfascial infection, has been shown consistently to decrease postoperative infection the wound was explored and aerobic, anaerobic and fungal cul- rates, but the ideal duration could be variable in patients at high tures were obtained. Posterior instrumented thoracic and lum- risk for infection. Although a comparative study by design, this bar fusions were performed in 821 patients using intravenous study provides Level IV therapeutic evidence that prolonged cephalexin prophylaxis with a total of 21 resulting deep wound postoperative regimens decrease the infection rate. infections (2.6%). Coag negative staph was the most commonly R 6

ecommendations Rohde et al described a retrospective comparative study de- isolated organism. Posterior instrumented thoracic and lumbar signed to report the incidence of postoperative spondylodiscitis fusions were performed in 911 patients with intravenous cepha- P r o p hylaxis in 1642 consecutive cases in which no antibiotic prophylaxis was lexin plus adjunctive local vancomycin powder with two ensuing used and to define the value of a collagenous sponge containing deep wound infections (0.2%). The reduction in wound infec- gentamicin in preventing disc space infections. No topical or tions was statistically significant (p< 0.0001). There were no ad- systemic antibiotics were administered in the first 508 patients. verse clinical outcomes or wound complications related to the

A 4 cm × 4 cm collagenous sponge containing 8 mg of gentami- local application of vancomycin. The authors concluded that in R

S cin was placed in the cleared disc space in the subsequent 1134 adjunctive local application of vancomycin powder, used as an ega r ding p ine patients. Surgery was performed for 1584 primary lumbar disc alternative to traditional antibiotic prophylaxis, decreases the herniations (two-level discectomy in 39 cases, three-level dis- post surgical wound infection rate with statistical significance S

u r ge y cectomy in one case) and 169 operations for recurrent hernia- in posterior instrumented thoracolumbar spine fusions. This A tions. In all patients, the erythrocyte sedimentation rate (ESR) study provides Level III therapeutic evidence that adjunctive lo- ntibiotic was obtained before surgery and on the first day after surgery. cal application of vancomycin powder decreases the post surgi- Beginning in January 1992, C-reactive protein (CRP) was also cal wound infection rate compared with intravenous cephalexin analyzed before surgery, one day after surgery and six days af- in posterior instrumented thoracolumbar fusion. ter surgery. All patients were clinically re-examined on days 10- 14 after surgery (day of discharge). Final follow-up was at 60 Future Directions for Research days. In 19 of these 508 patients, a postoperative spondylodis- Large multicenter randomized controlled trials assessing the ef- citis developed, accounting for an incidence rate of 3.7%. None ficacy of various protocols should be tailored to specific patient of the 1134 patients receiving antibiotic prophylaxis developed populations (eg, diabetes, trauma, neuromuscular injury or dis- a postoperative spondylodiscitis during the follow-up period ease, prolonged multilevel instrumented surgery) at increased of 60 days. Therefore, the incidence of postoperative spondy- risk for surgical site infections. lodiscitis was 0%. Using the Fisher exact test, the difference in the incidence rates between the patient groups with and without Comorbidities References antibiotic prophylaxis during lumbar discectomy was highly sig- 1. Kanafani ZA, Dakdouki GK, El-Dbouni O, Bawwab T, Kanj SS. nificant (p < 0.00001). The authors observed no complications Surgical site infections following spinal surgery at a tertiary care related to the use of a collagenous sponge containing gentamicin center in Lebanon: incidence, microbiology, and risk factors. for antibiotic prophylaxis. The authors concluded that a 3.7% Scand J Infect Dis. 2006;38(8):589-592. 2. Olsen MA, Mayfield J, Lauryssen C, et al. Risk factors for surgi- incidence of postoperative spondylodiscitis was found in the cal site infection in spinal surgery. J Neurosurg. Mar 2003;98(2 absence of prophylactic antibiotics. Gentamicin-containing col- Suppl):149-155. lagenous sponges placed in the cleared disc space, used as an 3. Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical alternative to traditional antitiobic prophylaxis, were effective in site infection following orthopaedic spinal operations. J Bone preventing postoperative spondylodiscitis. This study provides Joint Surg Am. Jan 2008;90(1):62-69. Level III therapeutic evidence that for uncomplicated lumbar 4. Takahashi H, Wada A, Iida Y, et al. Antimicrobial prophylaxis microdiscectomy, topical administration of a gentamicin soaked for spinal surgery. J Orthop Sci. Jan 2009;14(1):40-44. collagen sponge is more effective than placebo in preventing 5. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs. clinically significant discitis. multiple-dose antibiotic prophylaxis in instrumented lumbar 7 fusion--a prospective study. Surg Neurol. Dec 2008;70(6):622- Sweet et al performed a retrospective comparative study to 627; discussion 627. evaluate the safety and efficacy of adjunctive local application 6. Rohde V, Meyer B, Schaller C, Hassler WE. Spondylodiscitis of vancomycin for infection prophylaxis in posterior instru- after lumbar discectomy. Incidence and a proposal for prophy- mented thoracic and lumbar spine wounds compared to intra- laxis. Spine. Mar 1 1998;23(5):615-620. venous cephalexin alone. Since 2000, 1732 consecutive thoracic 7. Sweet FA, Roh M, Sliva C. Intra-wound application of vancomy- and lumbar posterior instrumented spinal fusions have been cin for prophylaxis in instrumented thoracolumbar fusions: ef- performed with routine 24 hours of perioperative intravenous ficacy, drug levels, and patient outcomes.Spine (Phila Pa 1976). 2011 Nov 15;36(24):2084-8.

For patients with a history of MRSA infection, does prophylaxis with vancomycin reduce infections with MRSA compared to other antimicrobial agents?

Although no literature was available to address this specific question about patients with a history of MRSA, the search did identify studies that addressed prophylaxis to reduce infections with MRSA.

There is insufficient evidence to make a recommendation for or against the prophylactic use of vancomycin compared with other antimicrobial agents to reduce infections with MRSA.

ntibiotic

Grade of Recommendation: I (Insufficient Evidence) A u r ge y S

Klekamp et al1 performed a retrospective review to determine the suspicious for subfascial infection, the wound was explored and p ine ega r ding risk factors associated with methicillin resistant staphyloccocus aerobic, anaerobic and fungal cultures were obtained. Poste- S R in aureua (MRSA) wound infection after spinal surgery. The study rior instrumented thoracic and lumbar fusions were performed compared 35 patients with postoperative methicillin-resistant in 821 patients using intravenous cephalexin prophylaxis with a Staphylococcus aureas (MRSA) infection to 35 uninfected control total of 21 resulting deep wound infections (2.6%). Coag nega- patients in order to determine risk factors. Regarding antibiotic tive staph was the most commonly isolated organism. Posterior prophylaxis, 19% of patients in the MRSA group received vanco- instrumented thoracic and lumbar fusions were performed in 911 r o p hylaxis P mycin at the time of index surgery, while 46% of the control group patients with intravenous cephalexin plus adjunctive local vanco- ecommendations

patients did not. The authors found that lymphopenia, history of mycin powder with two ensuing deep wound infections (0.2%). R chronic infections, alcohol abuse, recent hospitalization and pro- The reduction in wound infections was statistically significant longed postoperative wound drainage were significant risk factors (p< 0.0001). There were no adverse clinical outcomes or wound for MRSA infection. In critique of this study, the authors did not complications related to the local application of vancomycin. The state which prophylaxis regimen was used if vancomycin was not authors concluded that adjunctive local application of vancomy- administered; the reader is left to assume that it is cephazolin or a cin powder decreases the post surgical wound infection rate with similar agent. There was an equivalent rate of instrumented cases statistical significance in posterior instrumented thoracolumbar in the infected and noninfected groups; however, conclusions re- spine fusions. This study provides Level III therapeutic evidence garding the efficacy of vancomycin prophylaxis based only on the that adjunctive local application of vancomycin powder decreases presence of instrumented fusion are difficult to draw. The authors the post surgical wound infection rate compared with intravenous concluded that the there is potential for resistance to develop with cephalexin in posterior instrumented thoracolumbar fusion. increased use of vancomycin. This study offers Level III prognostic evidence that if intravenous vancomycin prophylaxis is to be Future Directions for Research considered, it should be utilized in patients at risk for MRSA and Recommendation #1: not the general population. Large multicenter randomized controlled trials assessing the Sweet et al2 performed a retrospective comparative study to efficacy of various protocols should be tailored to present sub- evaluate the safety and efficacy of adjunctive local application of group analyses on patients with a history of MRSA. vancomycin for infection prophylaxis in posterior instrumented thoracic and lumbar spine wounds compared to intravenous Recommendation #2: cephalexin alone. Since 2000, 1732 consecutive thoracic and lum- Additional studies should be performed to assess the efficacy of bar posterior instrumented spinal fusions have been performed intravenous versus intrawound vancomycin and other antimi- with routine 24 hours of perioperative intravenous antibiotic pro- crobial agents in reducing the rate of MRSA infections. phylaxis with cephalexin. Since 2006, 911 of these instrumented thoracic and lumbar cases had 2 g of vancomycin powder applied MRSA References to the wound prior to closure in addition to intravenous antibiot- 1. Klekamp J, Spengler DM, McNamara MJ, Haas DW. Risk factors ics. A retrospective review for infection rates and complications associated with methicillin-resistant staphylococcal wound infec- was performed with an average follow-up of 2.5 years (range: 1-7 tion after spinal surgery. J Spinal Disord. Jun 1999;12(3):187-191. years). If wound infection was suspected based on clinical and 2. Sweet FA, Roh M, Sliva C. Intra-wound application of vancomycin for prophylaxis in instrumented thoracolumbar fusions: ef- constitutional symptoms, aspiration was completed. If aspira- ficacy, drug levels, and patient outcomes.Spine (Phila Pa 1976). tion demonstrated purulent material or the wound was clinically 2011 Nov 15;36(24):2084-8.

H. Complications

What are the incidence and severity of complications/adverse events resulting from the use of prophylactic antibiotics? R ecommendations

P CONSENSUS STATEMENT: Reported isolated complications related to r o prophylactic antibiotics include flushing, hypotension, rashes, intramem- p hylaxis branous colitis and, most seriously, Stevens-Johnson syndrome. in R

S ega 1 p Petignat et al conducted a prospective, randomized controlled travenous antibiotics. A retrospective review for infection rates ine r

ding trial to compare infection rates and adverse events in those pa- and complications was performed with an average follow-up of

S tients who received 1.5 g cefuroxime versus placebo for lumbar 2.5 years (range: 1-7 years). There were no adverse clinical out- u r

ge discectomy. Of the 1237 patients included in the study, 613 re- comes or wound complications related to the local application ntibiotic

r ceived 1.5 g intravenous cefuroxime on induction and 624 re- of vancomycin. This study provides Level II prognostic evidence y ceived placebo. Presence of infection, as defined by the Centers that there are no adverse clinical outcomes or wound complica- for Disease Control (CDC) guidelines, was assessed at six weeks, tions related to the intrawound application of vancomycin. 4 three months and six months. There were no significant adverse Kakimaru et al reported results from a retrospective compar- events attributed to either cefuroxime or placebo. This study ative study comparing the infection rates following spinal sur- provides Level I prognostic evidence that there are no significant gery with and without postoperative antimicrobial prophylaxis. side effects attributable to cefuroxime or placebo. Of the 284 patients included in the study, 141 received preopera- Pons et al2 described a prospective, randomized trial com- tive and postoperative dosing and 143 received preoperative and paring perioperative antibiotic protocols that included either intraoperative dosing. The antibiotics used included cefazolin 1 2 g Ceftizoxime or 1 g vancomycin plus 80 mg gentamicin in g in 108 patients, flomoxef 1 g in 26 patients, and piperacillin 291 patients who underwent various clean spine surgeries. Of 1 g in seven patients for the postoperative group. Two cases of the 291 patients, 142 received Ceftizoxime and 149 vancomycin/ pseudomembranous colitis were seen in the postoperative dos- gentamicin one hour prior to incision. No patients in the cefti- ing group. Although a comparative study by design, this study zoxime group experienced drug reactions, however six of the provides Level IV prognostic evidence that pseudomembranous 404 patients who received the vancomycin / gentamicin proto- colitis is a potential complication resulting from the use of pro- col had clinically significant hypotension and/or flushing (‘red- phylactic antibiotics. man syndrome’) even though the antibiotics were infused over Kanayama et al5 performed a retrospective comparative 45 minutes to minimize this effect. The authors concluded that study to compare the rate of surgical site infections in lumbar flushing/hypotension is a reported adverse reaction which re- spine surgeries for two different antibiotic prophylaxis proto- solved by slowing or stopping the antibiotics until the symptoms cols. A first-generation cephalosporin was administered unless resolved. This study provides Level II prognostic evidence that the patient had a history of a significant allergy such as anaphy- flushing/hypotension have been reported upon infusion with lactic shock, systemic skin eruption or toxic liver dysfunction. vancomycin/gentamicin. Postoperative-dose group patients received antibiotics for five to Sweet et al3 performed a retrospective comparative study to seven days after surgery. No postoperative-dose group patients evaluate the safety and efficacy of adjunctive local application received antibiotics only on the day of surgery; antibiotics were of vancomycin for infection prophylaxis in posterior instru- given 30 minutes before skin incision. An additional dose was mented thoracic and lumbar spine wounds compared to intra- administered every three hours to maintain therapeutic levels venous cephalexin alone. Since 2000, 1732 consecutive thoracic throughout surgery. Resistant strains of bacteria were cultured and lumbar posterior instrumented spinal fusions have been in five (83.3%) of six patients in the multiple-dose group, where- performed with routine 24 hours of perioperative intravenous as none was cultured in the no postoperative-dose group. Al- antibiotic prophylaxis with cephalexin. Since 2006, 911 of these though a comparative study by design, this study provides Level instrumented thoracic and lumbar cases had 2 g of vancomycin IV prognostic evidence that extended antibiotic prophylaxis powder applied to the wound prior to closure in addition to in- protocols may lead to antibiotic resistance.

Laurencin et al6 described a single case of Stevens-Johnson Incidence of Complications References syndrome caused by vancomycin. The complication presented 1. Petignat C, Francioli P, Harbarth S, et al. Cefuroxime prophy- on day 29 following instrumented occipitocervical fusion. The laxis is effective in noninstrumented spine surgery: a double- study provides Level IV prognostic evidence that vancomycin blind, placebo-controlled study. Spine (Phila Pa 1976). Aug 15 treatment may result in Stevens-Johnson syndrome. 2008;33(18):1919-1924. 2. Pons VG, Denlinger SL, Guglielmo BJ, et al. Ceftizoxime versus Mastronardi (2005) et al7 reported a retrospective compara- vancomycin and gentamicin in neurosurgical prophylaxis: a tive study evaluating the efficacy of two intraoperative antibiotic randomized, prospective, blinded clinical study. Neurosurgery. prophylaxis protocols in a large series of lumbar microdiscec- Sep 1993;33(3):416-422; discussion 422-413. tomies performed in two different neurosurgical centers. Of 3. Sweet FA, Roh M, Sliva C. Intra-wound application of vancomy- the 1167 patients included in the study, 450 received a single cin for prophylaxis in instrumented thoracolumbar fusions: ef- intravenous dose of cefazoline 1 g at induction of general anes- ficacy, drug levels, and patient outcomes. Spine (Phila Pa 1976). thesia (Group A) and 717 received a single dose of intravenous 2011 Nov 15;36(24):2084-8. ampicillin 1 g and sulbactam 500 mg at induction of anesthesia 4. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- (Group P). Rash was seen in 0.89% of the cefazolin group and erative antimicrobial prophylaxis following spinal decompression surgery: is it necessary? J Orthop Sci. May 2010;15(3):305- 0.84% in the ampicillin and sublactam group. Although a com- 309. parative study by design, this study provides Level IV prognostic 5. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. evidence that skin rash is a minor adverse reaction that may re- Effective prevention of surgical site infection using a Centers for sult from antibiotic prophylaxis. Disease Control and Prevention guideline-based antimicrobial ntibiotic 8 A Mastronardi (2004) et al presented a retrospective case se- prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr u r ge y ries evaluating the safety and efficacy of a specific intraopera- 2007;6(4):327-329. S tive antibiotic protocol for a variety of spinal surgeries. Over a 6. Laurencin CT, Horan RF, Senatus PB, Wheeler CB, Lipson SJ. p ine three-year period 973 patients received ampicillin/sulbactam 1.5 Stevens-Johnson-type reaction with vancomycin treatment. Ann ega r ding Pharmacother. Dec 1992;26(12):1520-1521. S R in

g intravenous on induction or Teicoplanin 400 mg intravenous 7. Mastronardi L, Rychlicki F, Tatta C, Morabito L, Agrillo U, on induction (if surgery longer than two hours) with redosing Ducati A. Spondylodiscitis after lumbar microdiscectomy: effec- of teicoplanin at four hours or 1500 mL blood loss. Rash was tiveness of two protocols of intraoperative antibiotic prophylaxis seen in 0.7% of patients. This study provides Level IV prognos- in 1167 cases. Neurosurgical Review. Oct 2005;28(4):303-307. tic evidence that skin rash is a minor transient side effect that 8. Mastronardi L, Tatta C. Intraoperative antibiotic prophylaxis in r o p hylaxis may result from antibiotic prophylaxis. clean spinal surgery: a retrospective analysis in a consecutive P

series of 973 cases. Surg Neurol. Feb 2004;61(2):129-135; discus- ecommendations

Future Directions for Research sion 135. R As new antibiotic prophylaxis protocols are investigated, complications should be accurately reported.

What strategies can be implemented to minimize complications/adverse events resulting from the use of prophylactic antibiotics in spine surgery?

CONSENSUS STATEMENT: In typical, uncomplicated spinal procedures, a single dose of preoperative prophylactic antibiotics with intraoperative redosing as needed is suggested to reduce the risk of complications/adverse events.

Reported isolated complications/adverse events related to prophylactic antibiotics are discussed in the previous section and include: flushing, hypotension, rashes, intramembranous colitis and, most seriously, Stevens- Johnson Syndrome.

Kakimaru et al1 reported results from a retrospective compara- strains while reducing the risk of surgical site infections. This tive study comparing the infection rates following spinal surgery study provides Level III therapeutic evidence that there was no with and without postoperative antimicrobial prophylaxis. Of significant difference between the postoperative and no postop- the 284 patients included in the study, 141 received preopera- erative dosing group protocols, ie this study suggests no advan- tive and postoperative dosing and 143 received preoperative and tage to giving extra antibiotic doses. intraoperative dosing. The antibiotics used included cefazolin 1 Klekamp et al3 performed a retrospective review to determine g in 108 patients, flomoxef 1 g in 26 patients, and piperacillin 1 the risk factors associated with methicillin resistant staphylocco- g in 7 patients for the postoperative group. For the preoperative cus aureua (MRSA) wound infection after spinal surgery. The only group, cefazolin 1 g for 142 patients and minocycline 100 study compared 35 patients with postoperative methicillin-resis- mg for one patient. Patients in the postoperative dosing group tant Staphylococcus aureas (MRSA) infection to 35 uninfected had an intravenous dose within 30 minutes of skin incision, a control patients in order to determine risk factors. Regarding dose postoperatively intravenously and oral antibiotics for 2.7 antibiotic prophylaxis, 19% of patients in the MRSA group re- days average, or the preoperative dose with intraoperative redos- ceived vancomycin at the time of index surgery, while 46% of ing at three hour intervals and a single postoperative dose. No the control group patients did not. The authors found that lym- postoperative dose patients had a preoperative dose within 30 phopenia, history of chronic infections; alcohol abuse, recent minutes of skin incision with intraoperative dosing at three hour hospitalization and prolonged postoperative wound drainage intervals. Infection was confirmed via bacterial cultures and in- were significant risk factors for MRSA infection. In critique of spection of wound for redness, heat, swelling and pain. In the this study, the authors did not state which prophylaxis regimen postoperative dosing group, 2.8% (4/141) developed infections was used if vancomycin was not administered; the reader is left (three superficial and one deep); in the no postoperative dosing to assume that it is cefazolin or a similar agent. There was an group, 1.4% (2/143) developed infections (p=0.335). The au- equivalent rate of instrumented cases in the infected and non- thors concluded that the duration of antimicrobial prophylaxis infected groups; however, conclusions regarding the efficacy of does not influence the rate of surgical site infections. This study vancomycin prophylaxis based only on the presence of instru- provides Level III evidence that postoperative administration of mented fusion are difficult to draw. The authors concluded that antimicrobials appears unnecessary and preoperative plus intra- the there is potential for resistance to develop with increased use operative redosing of antibiotic prophylaxis reduces complica- of vancomycin. This study offers Level III prognostic evidence tions. that if intravenous vancomycin prophylaxis is to be considered, Kanayama et al2 performed a retrospective comparative it should be utilized in patients at risk for MRSA and not the study to compare the rate of surgical site infections in lumbar general population. spine surgeries for two different antibiotic prophylaxis protocols. A first-generation cephalosporin was administered unless the Future Directions for Research patient had a history of a significant allergy such as anaphylac- Large multicenter randomized controlled trials should be con- tic shock, systemic skin eruption or toxic liver dysfunction. The ducted to assess the efficacy of various protocols designed to postoperative group patients received antibiotics for five to sev- decrease the complications resulting from antibiotic adminis- en days after surgery. The no postoperative dose group patients tration and emergence of antibiotic resistance bacterial strains. received antibiotics only on the day of surgery; antibiotics were These should be tailored to specific patient populations (eg, given 30 minutes before skin incision. An additional dose was obesity, diabetes, trauma, neuromuscular injury or disease, pro- administered every three hours to maintain therapeutic levels longed multilevel instrumented surgery) at increased risk for throughout surgery. The rate of surgical site infection was com- surgical site infections. pared between the two prophylaxis groups. At a maximum of six months, a positive wound culture and/or typical infectious Minimizing Complications References signs including a purulent exudate, surrounding erythema and 1. Kakimaru H, Kono M, Matsusaki M, Iwata A, Uchio Y. Postop- wound fluctuance detected infections. Laboratory studies were erative antimicrobial prophylaxis following spinal decompres- also referenced, such as prolonged elevation in the C-reactive sion surgery: is it necessary? J Orthop Sci. May 2010; 15(3): protein value. There were 1133 patients in the postoperative 305-309. 2. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Togawa D. dose group and 464 patients in the no postoperative-dose group. Effective prevention of surgical site infection using a Centers for The rate of instrumentation surgery was not statistically differ- Disease Control and Prevention guideline-based antimicrobial ent between the postoperative-dose group (43%) and the no prophylaxis in lumbar spine surgery. J Neurosurg Spine. Apr postoperative-dose group (39%). The overall rate of surgical site 2007; 6(4): 327-329. infection was 0.7%. The infection rate was 0.8% (9/1133) in the 3. Klekamp J, Spengler DM, McNamara MJ, Haas DW. Risk factors postoperative-dose group and 0.4% (2/464) in the no postopera- associated with methicillin-resistant staphylococcal wound tive- dose group; the difference between the two was not signifi- infection after spinal surgery. J Spinal Disord. Jun 1999; 12(3): cant. Regarding the organisms of surgical site infection, resistant 187-191. strains of bacteria were cultured in five (83.3%) of six patients in the postoperative-dose group, whereas none was cultured in the single-dose group. The authors concluded there was no statistical difference was observed between protocols. The CDC protocol of preoperative dosing prevents development of resistant

Types of Studies Therapeutic Studies – Prognostic Studies – Diagnostic Studies – Economic and Decision Investigating the results of Investigating the effect of Investigating a diagnostic Analyses – treatment a patient characteristic on test Developing an economic or the outcome of disease decision model Level I • High quality • High quality • Testing of previously • Sensible costs and randomized trial with prospective study4 (all developed diagnostic alternatives; values statistically significant patients were enrolled criteria on consecutive obtained from many difference or no at the same point in patients (with studies; with multiway statistically significant their disease with universally applied sensitivity analyses difference but narrow ≥ 80% follow-up of reference “gold” • Systematic review2 of confidence intervals enrolled patients) standard) Level I studies • Systematic review2 • Systematic review2 of • Systematic review2 of of Level I RCTs (and Level I studies Level I studies study results were homogenous3)

Level II • Lesser quality RCT • Retrospective6 study • Development of • Sensible costs and (eg, < 80% follow- • Untreated controls diagnostic criteria on alternatives; values up, no blinding, from an RCT consecutive patients obtained from limited or improper • Lesser quality (with universally studies; with multiway randomization) prospective study applied reference sensitivity analyses • Prospective4 (eg, patients enrolled “gold” standard) • Systematic review2 of comparative study5 at different points in • Systematic review2 of Level II studies • Systematic review2 their disease or <80% Level II studies of Level II studies or follow-up) Level 1 studies with • Systematic review2 of inconsistent results Level II studies Level III • Case control study7 Case control study7 • Study of non- • Analyses based on • Retrospective6 consecutive patients; limited alternatives comparative study5 without consistently and costs; and poor • Systematic review2 of applied reference estimates Level III studies “gold” standard • Systematic review2 of • Systematic review2 of Level III studies

Level III studies ppendices A

Level IV Case series8 Case series • Case-control study Analyses with no sensitivity • Poor reference analyses standard Level V Expert Opinion Expert Opinion Expert Opinion Expert Opinion

1. A complete assessment of quality of individual studies requires critical appraisal of all aspects of the study design. 2. A combination of results from two or more prior studies. 3. Studies provided consistent results. 4. Study was started before the first patient enrolled. 5. Patients treated one way (eg, cemented hip arthroplasty) compared with a group of patients treated in another way (eg, unce- mented hip arthroplasty) at the same institution. 6. The study was started after the first patient enrolled. 7. Patients identified for the study based on their outcome, called “cases” (eg, failed total arthroplasty) are compared to those who did not have outcome, called “controls” (eg, successful total hip arthroplasty). 8. Patients treated one way with no comparison group of patients treated in another way.

B. Grades of Recommendation for Summaries or Reviews of Studies

A: Good evidence (Level I Studies with consistent finding) for or against recommending intervention.

B: Fair evidence (Level II or III Studies with consistent findings) for or against recommending intervention.

C: Poor quality evidence (Level IV or V Studies) for or against recommending intervention.

I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention. A ppendices

C. Linking Levels of Evidence to Grades of Recommendation

Grade of Standard Language Levels of Evidence Recommendation A Recommended Two or more consistent Level I studies B Suggested One Level I study with additional Two or more consistent Level II supporting Level II or III studies or III studies C May be considered; is an option One Level I, II or III study with Two or more consistent Level IV supporting Level IV studies studies I (Insufficient Insufficient evidence to make A single Level I, II, III or IV More than one study with or Conflicting recommendation for or against study without other supporting inconsistent findings* Evidence) evidence *Note that in the presence of multiple consistent studies, and a single outlying, inconsistent study, the Grade of Recommendation will be based on the level of consistent studies. ppendices A

D. Protocol for NASS Literature Searches

One of the most crucial elements of evidence analysis to sup- This search will encompass, at minimum, a search of PubMed, port development of recommendations for appropriate clinical EMBASE, Cochrane and Web of Science. Additional data- care or use of new technologies is the comprehensive literature bases may be searched depending upon the topic. search. Thorough assessment of the literature is the basis for the review of existing evidence, which will be instrumental to these 2. Search results with abstracts will be compiled by the medi- activities. It is important that all searches conducted at NASS cal librarian in Endnote software. The medical librarian typi- employ a solid search strategy, regardless of the source of the re- cally responds to requests and completes the searches within quest. To this end, this protocol has been developed and NASS- two to five business days. Results will be forwarded to the re- wide implementation is recommended. search staff, who will share it with the appropriate NASS staff member or requesting party(ies). (Research staff has access NASS research staff will work with the requesting parties and to EndNote software and will maintain a database of search the NASS-contracted medical librarian to run a comprehensive results for future use/documentation.) search employing at a minimum the following search techniques: 3. NASS staff shares the search results with an appropriate con- 1. A comprehensive search of the evidence will be conducted tent expert (NASS Committee member or other) to assess rel- using the following clearly defined search parameters (as de- evance of articles and identify appropriate articles to review. termined by the content experts). The following parameters are to be provided to research staff to facilitate this search. 4. NASS research staff will work with Galter library to obtain requested full-text articles for review. • Time frames for search • Foreign and/or English language 5. NASS members reviewing full-text articles should also review • Order of results (chronological, by journal, etc.) the references at the end of each article to identify additional • Key search terms and connectors, with or without articles which should be reviewed, but may have been missed MeSH terms to be employed in the search. • Age range • Answers to the following questions: Following this protocol will help ensure that NASS recom- o Should duplicates be eliminated between searches? mendations are (1) based on a thorough review of relevant o Should searches be separated by term or as one large literature; (2) are truly based on a uniform, comprehensive package? search strategy; and (3) represent the current best research o Should human studies, animal studies or cadaver evidence available. Research staff will maintain a search his- studies be included? tory in EndNote for future use or reference.

A ppendices

E. Comparing the Prevalence of Rare Events Nikolai Bogduk, MD

When events, such as infections, are uncommon or rare, comparing their prevalence in two separate populations requires large sample sizes in order to achieve statistical significance.

If the prevalence in one sample is p1, and the prevalence in a second sample is p2, and the sample size is n, the two prevalences are significantly different statistically if the 95% confidence intervals of the two prevalences do not overlap. Algebraically, this condition is determined by the equation:

For this condition to apply, when p1 and p2 are small, as applies in the case of postoperative infection rates, n needs to be large.

For example, if: p1 = 2% p2 = 6% n needs to be larger than 343, effectively 350 in round numbers.

ppendices A

n = 342.5

Such a number is prohibitively large for a study to undertake with the express purpose of showing a statistically significant difference in infection rates of this order of magnitude. It would require deliberately exposing 0.06 x 343 = 21 patients to infection and its risk of complications.

F. Comparison of 2007 Guideline Recommendations to Current Guideline Recommendations

Research Question 2007 Recommendations Current Recommendations A. EFFICACY For patients undergoing spine Patients undergoing spine surgery should Preoperative prophylactic antibiotics are surgery, does antibiotic receive preoperative prophylactic antibiotics. suggested to decrease infection rates in prophylaxis result in decreased patients undergoing spine surgery. infection rates compared to Grade of Recommendation: B patients who do not receive Grade of Recommendation: B prophylaxis? For a typical, uncomplicated lumbar laminotomy and discectomy, a single preoperative dose of antibiotics is suggested to decrease the risk of infection and/or discitis.

Grade of Recommendation: B For patients undergoing spine Prophylactic antibiotics are recommended to Prophylactic antibiotics are suggested to surgery without spinal implants, decrease the rate of spinal infections decrease the rate of spinal infections does antibiotic prophylaxis result following uninstrumented lumbar spinal following uninstrumented lumbar spinal in decreased infection rates as surgery. surgery. compared to patients who do not receive prophylaxis? Grade of Recommendation: B Grade of Recommendation: B For patients undergoing spine Prophylactic antibiotics are recommended to Prophylactic antibiotics may be considered to surgery with spinal implants, does decrease the rate of infections following decrease the rate of infections following antibiotic prophylaxis result in instrumented spine fusion. instrumented spine fusion. decreased infection rates as compared to patients who do not Grade of Recommendation: C Grade of Recommendation: C receive prophylaxis? What rate of surgical site Not Addressed CONSENSUS STATEMEMT: Despite A

ppendices infections can be expected with appropriate prophylaxis, the rate of surgical the use of antibiotic prophylaxis, site infections in spine surgery is 0.7% ‐ 10%. considering both patients with The expected rate for patients without and patients without medical comorbidities ranges from 0.7 – 4.3% and for comorbidities? patients with comorbidities ranges from 2.0 ‐ 10%. Current best practice with antibiotic protocols has failed to eliminate (reach an infection rate of 0.0%) surgical site infections.

Despite appropriate prophylaxis, diabetes carries an increased infection rate compared with non‐diabetic patients.

Level of Evidence: III

Research Question 2007 Recommendations Current Recommendations There is insufficient evidence to make a statement regarding the impact of obesity on the rate of surgical site infection in prophylaxed patients.

Level of Evidence: I (Insufficient) B. PROTOCOL For patients receiving antibiotic Patients undergoing spine surgery should Preoperative antibiotic prophylaxis is prophylaxis prior to spine surgery, receive preoperative prophylactic antibiotics suggested to decrease infection rates in what are the recommended drugs, to decrease infection rates. The superiority of patients undergoing spine surgery. their dosages and time of one agent or schedule over any other has not administration resulting in been clearly demonstrated. In typical, uncomplicated spinal procedures, decreased postoperative infection the superiority of one agent, dose or route of rates? Grade of Recommendation: B administration over any other has not been clearly demonstrated. When determining the appropriate drug choice, the patient’s risk factors, allergies, length and complexity of the procedure and issues of antibiotic resistance should be considered.

Grade of Recommendation: B

In typical, uncomplicated spinal procedures, a single dose of preoperative prophylactic antibiotics with intraoperative redosing as needed is suggested.

Grade of Recommendation: B

CONSENSUS STATEMENT: In patients with comorbidities or for those undergoing

complicated spine surgery, alternative ppendices prophylactic regimens including redosing, A gram‐negative coverage or the addition of intrawound application of vancomycin or gentamicin, are suggested to decrease the incidence of surgical site infections when compared to standard prophylaxis regimens. For patients receiving antibiotic Review of the current literature does not Preoperative antibiotic prophylaxis is prophylaxis prior to spine surgery allow recommendation of one specific suggested to decrease infection rates in without spinal implants, what are antibiotic protocol or dosing regimen over patients undergoing spine surgery without the recommended drugs, their another in the prevention of postoperative spinal implants. In these typical, dosages and time of infections following uninstrumented spinal uncomplicated spinal procedures, the administration resulting in surgery. superiority of one agent, dose or route of administration over any other has not been

Research Question 2007 Recommendations Current Recommendations decreased postoperative Level of Evidence: II clearly demonstrated. When determining the infections rates? appropriate drug choice, the patient’s risk factors, allergies, length and complexity of the procedure and issues of antibiotic resistance should be considered.

Grade of Recommendation: B

In typical, uncomplicated open spine surgery without spinal implants, a single dose of preoperative prophylactic antibiotics with intraoperative redosing as needed is suggested.

Grade of Recommendation: B For patients receiving antibiotic A systematic review of the literature did not Preoperative antibiotic prophylaxis is prophylaxis prior to spine surgery reveal any high quality comparative studies suggested to decrease infection rates in with spinal implants, what are the addressing this specific question. The patients undergoing spine surgery with spinal recommended drugs, their evidence reviewed does indicate that certain implants. In these complex spinal dosages and time of subpopulations are prone to polymicrobial procedures, the superiority of one agent, administration resulting in infections. These populations include, but dose or route of administration over any decreased postoperative may not be limited to, patients with other has not been clearly demonstrated. infections rates? neuromuscular scoliosis, myelodysplasia and When determining the appropriate drug traumatic complete spinal cord injury. Other choice, the patient’s risk factors, allergies, potential subgroups may exist, but have not length and complexity of the procedure and yet been identified in the literature. issues of antibiotic resistance should be considered. In patients with risk factors for polymicrobial infection, it is recommended that Grade of Recommendation: B appropriate broad spectrum antibiotics be considered when instrumented fusion is performed. CONSENSUS STATEMENT: In patients with risk factors for polymicrobial infection, A

ppendices Grade of Recommendation: C appropriate broad‐spectrum antibiotics are suggested to decrease the risk of infection when instrumented fusion is performed. What is a reasonable algorithmic Not Addressed CONSENSUS STATEMENT: Simple approach for antibiotic selection uncomplicated spine surgery (without for a given patient? instrumentation or comorbidities) => one single preoperative dose of antibiotic of choice with intraoperative redosing as needed

CONSENSUS STATEMENT: Instrumented spine surgery, prolonged procedures,

Research Question 2007 Recommendations Current Recommendations comorbidities (eg, diabetes, neuromuscular disease, cord injury or general spine trauma) => one single preoperative dose of antibiotic of choice + consideration of additional gram‐ negative coverage and/or the application of intrawound vancomycin or gentamicin

C. REDOSING For patients receiving antibiotic Dosing regimens do not appear to affect CONSENSUS STATEMENT: Intraoperative prophylaxis prior to spine surgery, infection rates. Although no study has shown redosing within 3‐4 hours may be considered what are the intraoperative any significant advantage to intraoperative to maintain therapeutic antibiotic levels redosing recommendations for redosing compared with a single dose, throughout the procedure. The superiority of the recommended drugs specific clinical situations may dictate one drug has not been demonstrated in the (including dosages and time of additional doses (eg, length of surgery, literature. When determining the appropriate administration) resulting in comorbidities). drug choice, the patient’s risk factors, decreased postoperative infection allergies, length and complexity of the rates? Level of Evidence: IV procedure and issues of antibiotic resistance should be considered. D. DISCONTINUATION For patients receiving antibiotic A comprehensive review of the spine For typical, uncomplicated cases, a single prophylaxis prior to spine surgery, literature did not yield evidence to address dose of preoperative prophylactic antibiotics does discontinuation of the question related to the effect on with intraoperative redosing as needed is prophylaxis at 24 hours result in postoperative infection rates of suggested to decrease the risk of surgical site decreased or increased discontinuation of prophylaxis at 24 hours infection. postoperative infection rates as compared with longer periods of compared to longer periods of administration. Grade of Recommendation: B administration? Prolonged postoperative regimens may be considered in complex situations (i.e., trauma, cord injury, neuromuscular disease, diabetes, or other comorbidities). Comorbidities and complex situations reviewed in the literature include obesity, diabetes, neurologic deficits, incontinence, preoperative serum glucose level of >125 mg/dL or a postoperative serum glucose level of >200 mg/dL, trauma,

prolonged multilevel instrumented surgery, ppendices and other comorbidities. A

Grade of Recommendation: C E. WOUND DRAINS For patients receiving antibiotic A comprehensive review of the literature did A comprehensive review of the literature did prophylaxis prior to spine surgery not yield evidence to address the question not yield evidence to address the question and who receive placement of related to the effect on postoperative related to the effect on postoperative

Research Question 2007 Recommendations Current Recommendations wound drains at wound closure, infection rates of the duration of prophylaxis infection rates of the duration of prophylaxis does discontinuation of in the presence of a wound drain. in the presence of a wound drain. prophylaxis at 24 hours result in decreased or increased The use of drains is not recommended as a There is insufficient evidence to make a postoperative infection rates as means to reduce infection rates following recommendation for or against the early compared to discontinuation of single level surgical procedures. discontinuation of antibiotic prophylaxis in antibiotics at time of drain patients with wound drains. removal? Grade of Recommendation: I (Insufficient Evidence) Grade of Recommendation: I (Insufficient Evidence)

The use of drains is not recommended as a means to reduce infection rates following single level surgical procedures.

Grade of Recommendation: I (Insufficient Evidence)

F. BODY HABITUS For patients receiving antibiotic Obese patients are at higher risk for Obese patients are at higher risk for prophylaxis prior to spine surgery, postoperative infection, when given a postoperative infection, when given a should the recommended standardized dose of antibiotic prophylaxis. standardized dose of antibiotic prophylaxis. In protocol differ based upon body In spite of this conclusion, the literature spite of this conclusion, there is insufficient habitus (eg, body mass index)? search did not yield sufficient evidence to evidence to make a recommendation for or recommend any specific modifications to against recommending a different protocol antibiotic protocols for this specific for patients based upon body habitus. population. Grade of Recommendation: I (Insufficient Level of Evidence: III Evidence) G. COMORBIDITIES For patients receiving antibiotic Based on the literature reviewed to address CONSENSUS STATEMENT: In patients with

A prophylaxis prior to spine surgery, this question, information was only available comorbidities or for those undergoing ppendices do comorbidities (other than on patients with diabetes, older age or complicated spine surgery, alternative obesity) such as diabetes, instrumentation. While this information prophylactic regimens are suggested to smoking, nutritional depletion suggests that these three groups are at decrease the incidence of surgical site and immunodeficiencies alter the higher risk for postoperative infection when infections when compared to standard recommendations for antibiotic given a standardized dose of antibiotic prophylaxis regimens. prophylaxis? prophylaxis, the literature search did not yield sufficient evidence to recommend any specific modifications to antibiotic protocols There is insufficient evidence to make a for this specific population. recommendation for or against the specific alternative regimens that are efficacious. Level of Evidence: III However, promising alternative regimens that have been studied include redosing, gram‐

Research Question 2007 Recommendations Current Recommendations negative coverage and the addition of intrawound application of vancomycin or gentamicin.

Grade of Recommendation: I (Insufficient Evidence) For patients with a history of Not Addressed Although no literature was available to MRSA infection, does prophylaxis address this specific question about patients with vancomycin reduce with a history of MRSA, the search did infections with MRSA compared identify studies that addressed prophylaxis to to other antimicrobial agents? reduce infections with MRSA.

There is insufficient evidence to make a recommendation for or against the prophylactic use of vancomycin compared with other antimicrobial agents to reduce infections with MRSA.

Grade of Recommendation: I (Insufficient Evidence) H. COMPLICATIONS What are the incidence and Not Addressed CONSENSUS STATEMENT: Reported isolated severity of complications/adverse complications related to prophylactic events resulting from the use of antibiotics include flushing, hypotension, prophylactic antibiotics? rashes, intramembranous colitis and, most seriously, Stevens‐Johnson Syndrome. What strategies can be Not Addressed CONSENSUS STATEMENT: In typical, implemented to minimize uncomplicated spinal procedures, a single complications/adverse events dose of preoperative prophylactic antibiotics resulting from the use of with intraoperative redosing as needed is prophylactic antibiotics in spine suggested to reduce the risk of surgery? complications/adverse events.

Reported isolated complications/adverse events related to prophylactic antibiotics are

discussed in the previous section and include: ppendices

flushing, hypotension, rashes, A intramembranous colitis and, most seriously, Stevens‐Johnson Syndrome.

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