Antibiotic Prophylaxis

PHARMACOLOGY OF BONE AND JOINT SURGERY

JASSIN M. JOURIA, MD

Dr. Jassin M. Jouria is a practicing Emergency Medicine physician, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serve as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e- module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology.

ABSTRACT

Pharmacological strategies should be tailored to specific treatment needs of the patient before, during, and after orthopedic surgery. Medical clinicians need to consider their entire strategy, beginning with the prophylactic approach of antibiotic use and thromboprophylaxis to prevent surgical site infection and blood clot formation. However, it is equally important to consider the patient’s comfort following orthopedic surgery. Ensuring that the patient has appropriate access to analgesics and anxiolytics is standard care for the orthopedic patient.

1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Policy Statement

This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 2.5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 2.5 hours.

Statement of Learning Need

Infection, blood clot and pain prevention are common medical considerations for patients undergoing bone and joint surgery. Multiple research studies have been conducted to determine the best course of pharmacological treatment. Additional studies are needed, however the general guidelines for medical care during the pre-, intra- and post-operative phases of bone and joint surgery include drug selection, dosing, and safe use that are required clinician competencies to ensure best patient outcomes.

Course Purpose

To provide health clinicians with knowledge of pharmacology recommendations for bone and joint surgery.

2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Target Audience

Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

3 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. The most prevalent species of orthopedic and trauma device- related infection (ODRI) is/are caused by

a. anaerobic infections. b. bacterial meningitis. c. Staphylococci. d. Lyme disease.

2. With biofilm infections, curative therapy

a. requires removal of the prosthesis. b. is limited to antibiotic treatment. c. is limited to antibiotics placed on the site directly. d. includes surgical debridement.

3. When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that

a. this does not reflect the ability of that antibiotic to kill the bacteria when growing in a biofilm. b. the prosthesis must still be removed. c. surgical debridement is then avoided. d. All of the above

4. There is more clinical evidence to support the selection of prophylactic antibiotic treatment for ______than for other bacteria.

a. enterococci b. staphylococci c. streptococci d. Gram-negatives

5. Rifampicin is important in treating

a. Gram-negatives. b. infections by itself. c. staphylococci as an anti-staphylococcal biofilm antibiotic. d. staphylococci so long as it is not growing in a biofilm.

4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

Introduction

Orthopedic surgery involving hip or joint replacement is increasing as clinicians and patients turn to these procedures to treat degenerative bone conditions. One of the risks of these procedures is the presence of an infection associated with the implanted device. Infection can negatively impact clinical outcomes in orthopedic surgery. Antibiotic treatments are used with bone and joint surgery to address these infections. While there is a place for surgical prophylactic antibiotics in treatment of patients in orthopedic surgery, there is no consensus among clinicians on the timing of prophylactic antibiotics, the choice of antibiotics, and the duration of prophylactic antibiotics.

Antibiotic Prophylaxis And Infection Prevention

Antibiotic prophylaxis is the use of antibiotics before surgery to prevent a bacterial infection because infection can negatively impact clinical outcomes.10 This practice was more prevalent in the past and its use has declined because the use of antibiotics has led to an increase of antibiotic- resistant bacteria, among other things. In orthopedic surgery, however, antibiotic prophylaxis is more widely used. Antibiotic treatments are used as prophylaxis when pathogens are identified. Even when using the best practices in surgical management, neither treatment nor prophylaxis can prevent infection in all cases; instead, as noted by Moriarty, et al., orthopedic and trauma device-related infection (ODRI) remains a major complication in orthopedic surgery.10

Current issues of infection with surgery result from antibiotic resistance and weaknesses of antibiotic delivery practices. The most prevalent species of ODRI are Staphylococci. They account for 20 to 30 percent of infection after

5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com a fracture fixation or prosthetic joint infection. Moriarty, et al., address the issue of infection caused by an antibiotic resistant pathogen as a major public health concern where treatment can become a challenge.10

Bio-films and MRSA

Among the most difficult pathogens to treat with respect to ODRI is bacteria that is resistant to the anti-biofilm activity. Biofilms are microorganisms capable of attaching to just about any surface; they have a gelatinous form. Another significant concern is methicillin-resistant Staphylococcus aureus (MRSA). Between 25% and 32% of infections after fracture fixation in the United States are caused by MRSA. There is a rise in antimicrobial resistance in the treatment of ODRI and dealing with this issue is a major challenge.10

Methicillin-resistant Staphylococcus aureus infections are associated with higher mortality. Medical treatment decisions should focus on the identified pathogen and not simply on its methicillin resistance characteristic. When treating ODRI, the goal should be long-term elimination of pain, restoration of joint function, and consolidation of any fracture while preventing osteomyelitis (inflammation of the bone). Typically, therapy seeks to eradicate micro-organisms that cause infection. In some cases, this can mean long-term, suppressive antibiotic therapy. Each treatment should meet the needs and conditions of the individual patient.10

With biofilm infections, curative therapy includes surgery as antibiotics are not able to eradicate these infections. The approach for surgery can be debridement with retention of the prosthesis. It can also be a one-stage or two-stage exchange procedure. The approach should include a team of orthopedic surgeons and infectious disease specialists and/or microbiologists. Decisions about therapy tend to be based on retrospective

6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com data, results from animal models, and on pharmacokinetic or pharmacodynamic principles.10

Optimally, an antibiotic reaches high bactericidal concentrations in the organic and inorganic bone tissue, on the surface of the device, and in intracellular compartments. The antibiotic should be active against slow- growing biofilms and also against metabolically quiescent small colony variants. It should also have low propensity to induce bacterial resistance plus low toxicity towards the patient. It is essential to know what bacteria is responsible for an infection. A clinician should withhold antibiotics until appropriate diagnostics are performed.

When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that this does not reflect the ability of that antibiotic to kill the bacteria when growing in a biofilm. Most clear is the evidence for antibiotic selection for staphylococci. Less clear is antibiotic selection for other bacteria such as streptococci, enterococci, Gram-negatives.

Rifampicin

Rifampicin is critically important in treating staphylococci as an anti- staphylococcal biofilm antibiotic. It has been associated with higher rates for success in treatment. Rifampicin should not be administered by itself because of the propensity for bacteria to develop resistance to the drug. Researchers have reported that the “initial partner antibiotic most often consists of a beta-lactam,” followed by quinolone (historically ciprofloxacin, nowadays often levofloxacin).

“In case of quinolone resistance, various other antibiotic partners have been used such as fusidic acid, cotrimoxazole, linezolid, clindamycin or

7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com minocycline. In the case of rifampicin resistance, alternative antibiotics are chosen, with one study showing good results with moxifloxacin monotherapy. Alternatives to beta-lactams, for example in the case of methicillin-resistant staphylococci, are vancomycin or daptomycin, both of which are generally well-tolerated.”10

Local Antibiotic Delivery

Local antibiotic delivery at the site of the infection is now a regular part of treatment of ODRIs.11,12 Local delivery has theoretical advantages when compared to systemic delivery. With antibiotics placed on the site directly, an intact vascular system is not required for reaching the surgical site. This can be important especially for a trauma patient.11 Local delivery can also provide a local concentration that exceeds what can be done systemically, and can require a smaller total drug amount. This can reduce the risk of systemic toxicity.

Studies have shown that the local application of antibiotics can offer protection against bacteria resistant to an applied antibiotic. This can indicate that local delivery could provide an improvement in antibiotic therapy with bacteria that is resistant to conventional and systemic dosing.12 Since the 1970s, local application of an antibiotic in orthopedic medicine used with gentamicin loaded bone cement testing in humans has been done. Routinely used in cemented arthroplasty, bone cement was a convenient method of antibiotic delivery.10

Because it can withstand the elevated temperatures of curing bone cement, gentamicin is a suitable antibiotic. It also offers an acceptable profile against the most common pathogens found with ODRI. There has been improved ODRI outcomes with antibiotic loaded bone cements. Bone cement was not

8 nursece4less.com nursece4less.com nursece4less.com nursece4less.com designed at first as a means of delivering antibiotic. With over four decades of using antibiotic loaded bone cements, Moriarty, et al., concluded that “pharmacodynamics principles are still not established specifically for use in this way. Therefore, it is perhaps not surprising that resistance against gentamicin has emerged secondary to gentamicin use in local delivery vehicles. The reason for the development of resistance is probably the prolonged release of antibiotics at sub-therapeutic levels from local delivery vehicles, which is in direct opposition to ideal release kinetics for a concentration dependent antibiotic such as gentamicin.”10 Moriarty, el al., further stated that as antimicrobial loaded device surfaces and coatings have passed through the regulatory approval process and are described in clinical studies, a greater number can be expected to emerge in the future; however, a number of important issues must be resolved before the maximum benefit of local antibiotic delivery is achieved.10,16

Active and Passive Vaccines

Active and passive vaccines are an approach to prevent, treat, and possibly eradicate ODRIs. This is unparalleled when compared to other medical interventions and based on its cost effectiveness. Efforts to develop a vaccine against Staphylococcus aureus (or S. aureus) have failed, which is the primary pathogen involved in ODRI.10-12, The reason for this is that S. aureus has co-evolved with mammalian hosts to become human commensal, in contrast to successful bacterial vaccines, which exclusively are against transient flora. All patients have some level of acquired immunity against S. aureus prior to surgery.16-20

Keeping in mind vaccine development, there are descriptions of anti-S. aureus immune responses in physiological and pathological situations to elucidate the immune proteome of S. aureus.10,21 A multiplex immunoassay

9 nursece4less.com nursece4less.com nursece4less.com nursece4less.com for characterizing a patient’s immune response was developed against fourteen known S. aureus antigens. This was used to determine if certain antigens dominate humoral immunity, and was done in a pilot study of patients with osteomyelitis versus uninfected controls.21 Follow up research is ongoing. In an era of personalized medicine, measurement of immune response against S. aureus could help guide future prophylaxis and therapy. As S. aureus is primarily an extracellular pathogen, its clearance from within mammalian hosts is dependent primarily on neutrophils.

For vaccine development, an innate immune mechanism was modeled in an assay used to quantify S. aureus killing in vitro. T helper cells are involved in antibody response. Also, it is known that Th27 cells enhance neutrophil function and bacterial clearance.10,24,25 With common vaccines, there is active immunization of a host with a purified molecular constituent of a pathogen. It requires the host evolve protective immunity for the non- virulent challenge. An advantage of an active vaccine is robust immunity. This includes both cellular and humoral immunity. It also includes the life- long immunity from the generation of protective memory T cells and B cells.25 A limitation is the unpredictability of vaccination in individuals with compromised immunity and established comorbidity, i.e., autoimmunity, aging, diabetes, and obesity.27

Complications of Vaccination

Researchers have indicated that it was not surprising that two recent large clinical trials with active S aureus vaccines did not meet their endpoints. It is surprising that vaccination was reportedly associated with increased multi- organ failure, sepsis, and death for patients having heart valve replacement and developing S. aureus infection. Moriarty and colleagues reported that this “observation raises a new concern that some anti-S. aureus immune

10 nursece4less.com nursece4less.com nursece4less.com nursece4less.com responses exacerbate infection and/or its sequelae, and that additional preclinical testing is needed to confirm a vaccine’s mechanism of action. It also supports transfusion of purified functional anti-S. aureus antibodies as a passive immunization, which is a safer and more predictable vaccine approach. However, it should be noted that passive S. aureus vaccines such as Altastaph, Veronate, Aurexis, Aurograb, and Pagibaximab have also failed in clinical trials.”10

A challenging complication in orthopedics is still ODRI. A range of options is available. Improvement in strategies for prevention and therapy are needed, and is critical for the challenge of antibiotic resistant bacteria. Because of emerging technologies, clinicians can expect to improve treatment success.

Research has focused on antibiotic resistance and biofilm formation. These are the targets for future interventional strategies. The interventions could reduce infection rate and improve outcomes. Currently, there are few regulatory bodies that have approved antibiotic functionalized devices for orthopedic and trauma applications. This could improve and grow in the future and would improve outcomes in the prevention and treatment of ODRIs.

Post-Operative Infection

A dreaded complication of orthopedic surgery is infection. Associated with this are increased mortality, disability, and prolonged morbidity. In the United States, over two percent of nearly 30 million operations are complicated with a surgical site infection.1 An increase in the mortality rate of two to three times after infection has been reported. Rafati, et al., reviewed the incidences of surgical site infection and suggested that they vary from fourteen to sixteen percent. They also reported that about 1%–

11 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5% of wounds develop a superficial or deep infection in clean orthopedic operations such as total hip replacement (THR) and total knee replacement.1

The World Health Organization (WHO) recommended before any surgical procedure to use a safety check list to reduce complication and also include prophylactic antibiotics. For the last three decades, systemic antibiotic prophylaxis is standard practice in orthopedic implant surgeries.31 Dhammi, et al., suggested that many studies show that prophylactic antibiotics reduce risks for infection when an implant is used even in an ultra-clean environment though this is not entirely undisputed.1 The authors further indicated that there is enough evidence to conclude that prophylactic antibiotics should be used to reduce surgical site infection in orthopedics. Other researchers had systematically reviewed antibiotic prophylaxis and also found that it reduced the absolute risks of wound infection by 81 percent compared with no prophylaxis for a patient undergoing total hip and knee replacement. Controversial issues include the timing of administration, duration, and which prophylactic antibiotics to use.30,31

Timing of Antibiotic Use

The actual timing for antibiotic administration is controversial. It can vary depending on the research study from 15 minutes to 120 minutes before incision of the skin.32-34 Dhammi, et al., reported that some researchers advocated for antibiotic use thirty to sixty minutes before surgery.1 It can also be at the time of induction of anesthesia or at least 10 minutes before tourniquet inflation. Others reported that initiating prophylaxis after incision of the skin is ineffective. In a 2010 study, Niimi, et al., reported on a case control study of 223 patients with intravenous infusions of antibiotics thirty minutes before surgery. None of the arthroplasty patients developed a wound infection immediately after or at least twelve months after surgery.33

12 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Prior research had shown that most antibiotics should be administered thirty minutes before incision of the skin. If administration is greater than sixty minutes before surgery/incision, this is associated with a higher risk of surgical infection. This is due to a short half-life of commonly used antibiotics. This included cloxacillin and cephalosporin; for cloxacillin, the half-life is 30 minutes. Most studies had raised that prophylactic antibiotics should be administered thirty to sixty minutes before incision of the skin.34

Dhammi, et al., also reported that antibiotic concentration in blood and bone typically appeared within 20 and 60 minutes, respectively.1 This must be maintained above the minimum inhibitory concentration of the infecting organism until there is closure of the skin. The least effect for prophylaxis is when the antibiotic is administered after application of a tourniquet. The extremity remains unprotected from antibiotic prophylaxis for a long time.36

Types of Antibiotic Use

Musmar, et al., suggested that the selected antibiotic should be, in general, nontoxic, inexpensive, and of limited spectrum.37 For prosthetic-related infections the most prevalent organisms are gram-positive Staphylococcus aureus and epidermidis. These can adhere to an implant and multiply and are normally present in skin flora.1 According the American Society of Health System Pharmacists (ASHP) “cefazolin was the most used antibiotic in preoperative prophylaxis, combination of cefazolin with gentamicin was the second common regimen while 3rd generation cephalosporin were 3rd widely used antibiotics. National clinical practice guidelines on rationale use of antibiotics in orthopedic surgery in Malaysia recommends cloxacillin in combination with gentamicin as first choice, 2nd generation cephalosporin as second choice antibiotics in arthroplasty and open reduction and internal

13 nursece4less.com nursece4less.com nursece4less.com nursece4less.com fixation of fractures.”1 Yeap, et al., compared 2nd generation cephalosporin and 3rd generation cephalosporin antibiotics prophylaxis:1

• Cefuroxime (2nd generation cephalosporin) was used in 52.7% cases and 3rd generation (cefoperazone or ceftriaxone) was used in 47.3% cases of internal fixation in this series. • In patients undergoing arthroplasty 2nd generation (cefuroxime) was used in 11.8% cases, in rest of cases 3rd generation cephlosprin (cephotriaxone and cefoperazone) was used in same series. • Cephalosporins are by far the most popular choice of antibiotics for prophylaxis. • In this study, 3rd generation cephalosporins were used for arthroplasty and 2nd generation cepholospirins were used for fracture fixation. This is although the spectrum of infecting organisms in surgery for closed fractures is similar to that following prosthetic joint surgery.

Dhammi, et al., noted that S. aureus is probably the most common organism causing infection.1 In theory, third generation cephalosporins are less active against Gram positive bacteria compared to second generations. They are more active against Gram negative bacteria. What is yet to be proven is what antibiotic is statistically superior. The first line antibiotic recommended as prophylaxis is second generation cephalosporin. This is followed by third generation cephalosporin. The trend is to use third generation cephalosporins for a patient undergoing arthroplasty. Cloxacillin as a first line treatment or prophylaxis has been recommended by some medical researchers.36

Many studies recommend second generation cephalosporins (cefuroxime). Dhammi, et al., concluded that “there is insufficient evidence to suggest that a particular generation of cephalosporin is more effective and superior to

14 nursece4less.com nursece4less.com nursece4less.com nursece4less.com cloxacillin. In a systematic analysis cephalosporin versus teicoplanin; cephalosporin versus penicillin derivatives (cloxacillin) and comparisons between 2nd generation and 1st generation cephalosporins, there was no significant difference in clinical effect.”1

Duration of Antibiotic Use

Dhammi, et al., noted that controversy persists concerning antibiotic administration.1 This can vary from a single dose to three doses to five days or fourteen days of antibiotic administration. To prevent the emergence of resistance, Musmar, et al., suggested discontinuing the antibiotic within twenty-four hours after surgery ends.51 Dhammi, et al., noted guidelines for antibiotic prophylaxis recommended: 1) a prophylactic antibiotic regimen at time of induction of anesthesia and two subsequent doses at 8 and 16 hours postoperatively, 2) the same recommendation with three doses within 24 hours, and 3) two doses at the time of induction and another 6 hours after surgery.37 They also noted that with a tropical country such as India the climate is hot and humid, and such an environment is conducive for Gram positive and Gram negative bacterial colonization of skin, linen, and wards in general.1 Studies should be tailored to this environment. Further, “antibiotics should not stop at skin closure but should continue till epithelization of wound occurs.”1

Niimi, et al., looked at a retrospective study and compared arthroplasty case outcomes of a one-day intravenous administration with long-term intravenous administration. They used an antibiotic for one day and for at least three days. Surgery involved an environment with vertical laminar flow and a body exhaust system. No patient developed a wound infection during follow up of at least twelve months. The conclusion was that one-day antibiotic infusion was effective.33

15 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Long-term antibiotic infusion prevents infection after arthroplasty; and researchers have associated drug-resistant bacteria, drug-induced hepato/nephropathy, and high costs with long-term use. The ideal duration of postoperative antibiotic administration is not clearly defined yet. Most reports state no additional benefit with prophylactic antibiotic administration for more than 24 hours after surgery. Rafati, et al., noted that according to pharmacy guidelines, the minimal duration of antimicrobial coverage includes the time from incision to closure of incision, and that usually a single antibiotic dose suffices.30

There is high variability in the duration of postoperative antibiotic administration. A single dose prophylaxis is rare in practice and the duration of prophylactic antibiotics continues to be discussed in medical circles. No consensus on this issue has occured.1 Surgical prophylactic antibiotic usage is the current standard recommendation. Controversy relates to a lack of evidence concerning timing, duration, and choice of antibiotics for prophylactic antibiotics for orthopedic surgery. Some of the medical literature suggests the use of second generation cephalosporins (cefuroxime) prophylactic antibiotics for thirty minutes to one hour before skin incision and preferably for 24 hours to three days in intravenous infusion post-operatively.1

Summary

Orthopedic surgery involving hip or joint replacement is increasing as health clinicians rely on these procedures to treat bone conditions. One of the risks of these procedures is the presence of an infection associated with the implanted device. Infection can negatively impact clinical outcomes in orthopedic surgery.

16 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Antibiotic treatments are used with bone and joint surgery to address these infections. While there is a place for surgical prophylactic antibiotics in the treatment of orthopedic patients, there is no consensus among clinicians on the timing of prophylactic antibiotics, the choice of antibiotics, and the duration of prophylactic antibiotics.

The pharmacological strategy for treating frequently used parts of the body should be tailored to the specific location. Important topics related to the special care required with surgery on bones and joints should consider strategies that include a medical approach before, during, and after surgery. Medical clinicians should consider the entire treatment strategy and approach, including the use of prophylactic antibiotics.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation.

Completing the study questions is optional and is NOT a course requirement.

17 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. The most prevalent species of orthopedic and trauma device- related infection (ODRI) is/are caused by

a. anaerobic infections. b. bacterial meningitis. c. Staphylococci. d. Lyme disease.

2. With biofilm infections, curative therapy

a. requires removal of the prosthesis. b. is limited to antibiotic treatment. c. is limited to antibiotics placed on the site directly. d. includes surgical debridement.

3. When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that

4. There is more clinical evidence to support the selection of prophylactic antibiotic treatment for ______than for other bacteria.

a. enterococci b. staphylococci c. streptococci d. Gram-negatives

5. Rifampicin is important in treating

a. Gram-negatives. b. infections by itself. c. staphylococci as an anti-staphylococcal biofilm antibiotic. d. staphylococci so long as it is not growing in a biofilm.

18 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6. Antibiotic treatments are used as prophylaxis

a. only when biofilm infections are identified. b. when pathogens are identified. c. only when a patient is significantly symptomatic. d. before a specific pathogen is identified.

7. True or False: A clinician should administer a panoply of antibiotics immediately with an orthopedic and trauma device- related infection (ODRI) because there is no time to wait and identify the bacteria responsible for an infection.

a. True b. False

8. To ensure enough antibiotic concentration, preoperative antibiotic prophylaxis should be administered ______incision of the skin.

a. from 15 minutes to 120 minutes before b. immediately before c. contemporaneously with the d. ten minutes before

9. The duration of postoperative antibiotic administration

a. follows an accepted pre-set duration based on the type of infection. b. should not be more than 7 to 10 days. c. generally requires a single prophylactic dose. d. is highly variable.

10. Optimally, an antibiotic reaches high bactericidal concentrations

a. in the organic and inorganic bone tissue. b. on the surface of the device. c. in intracellular compartments. d. All of the above

19 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11. When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that in those cases

a. antibiotic resistance is no longer a factor. b. the antibiotic will not be toxic for the patient. c. the antibiotic may not be able to kill the bacteria if it is growing in a biofilm. d. a single prophylactic dose is all that will be needed.

12. Staphylococci account for ______of infection after a fracture fixation or prosthetic joint infection.

a. half b. 30 to 40 percent c. 20 to 30 percent d. 10 percent

13. True or False: Rifampicin should not be administered by itself because of the propensity for bacteria to develop resistance to the drug.

a. True b. False

14. ______is a suitable antibiotic to add to bone cement because it can withstand the elevated temperatures associated with the process of curing bone cement.

a. Rifampicin b. Ciprofloxacin c. Cefuroxime d. Gentamicin

15. With an orthopedic and trauma device-related infection (ODRI), local antibiotic delivery at the site of the infection

a. is not as effective as systemic delivery of antibiotics. b. is now a regular part of treatment. c. requires an intact vascular system to be effective. d. increases the risk of systemic toxicity.

20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com CORRECT ANSWERS:

1. The most prevalent species of orthopedic and trauma device- related infection (ODRI) is/are caused by

c. Staphylococci.

“The most prevalent species of ODRI are Staphylococci.”

2. With biofilm infections, curative therapy

d. includes surgical debridement.

“With biofilm infections, curative therapy includes surgery as antibiotics are not able to eradicate these infections. The approach for surgery can be debridement with retention of the prosthesis.”

3. When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that

a. this does not reflect the ability of that antibiotic to kill the bacteria when growing in a biofilm.

“When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that this does not reflect the ability of that antibiotic to kill the bacteria when growing in a biofilm.”

4. There is more clinical evidence to support the selection of prophylactic antibiotic treatment for ______than for other bacteria.

b. staphylococci

“Most clear is the evidence for antibiotic selection for staphylococci. Less clear is antibiotic selection for other bacteria such as streptococci, enterococci, Gram-negatives.”

5. Rifampicin is important in treating

c. staphylococci as an anti-staphylococcal biofilm antibiotic.

“Rifampicin is critically important in treating staphylococci as an anti-staphylococcal biofilm antibiotic. It has been associated with higher rates for success in treatment.”

21 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6. Antibiotic treatments are used as prophylaxis

b. when pathogens are identified.

“Antibiotic treatments are used as prophylaxis when pathogens are identified.”

b. False

“It is essential to know what bacteria is responsible for an infection. A clinician should withhold antibiotics until appropriate diagnostics are performed.”

8. To ensure enough antibiotic concentration, preoperative antibiotic prophylaxis should be administered ______incision of the skin.

a. from 15 minutes to 120 minutes before

“The actual timing for administration is controversial. It can vary depending on the study from 15 minutes to 120 minutes before incision of the skin.”

9. The duration of postoperative antibiotic administration

d. is highly variable.

“... there is high variability in the duration of postoperative antibiotic administration.”

22 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10. Optimally, an antibiotic reaches high bactericidal concentrations

a. in the organic and inorganic bone tissue. b. on the surface of the device. c. in intracellular compartments. d. All of the above [correct answer]

“Optimally, an antibiotic reaches high bactericidal concentrations in the organic and inorganic bone tissue, on the surface of the device, and in intracellular compartments.”

11. When bacteria are reported to be sensitive to an antibiotic, the clinician should understand that in those cases

c. the antibiotic may not be able to kill the bacteria if it is growing in a biofilm.

12. Staphylococci account for ______of infection after a fracture fixation or prosthetic joint infection.

c. 20 to 30 percent

“The most prevalent species of ODRI are Staphylococci. They account for 20 to 30 percent of infection after a fracture fixation or prosthetic joint infection.”

13. True or False: Rifampicin should not be administered by itself because of the propensity for bacteria to develop resistance to the drug.

a. True

“Rifampicin should not be administered by itself because of the propensity for bacteria to develop resistance to the drug.”

23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14. ______is a suitable antibiotic to add to bone cement because it can withstand the elevated temperatures associated with the process of curing bone cement.

d. Gentamicin

“Because it can withstand the elevated temperatures of curing bone cement, gentamicin is a suitable antibiotic. It also offers an acceptable profile against the most common pathogens found with ODRI.”

15. With an orthopedic and trauma device-related infection (ODRI), local antibiotic delivery at the site of the infection

b. is now a regular part of treatment.

“Local antibiotic delivery at the site of the infection is now a regular part of treatment of ODRIs. Local delivery has theoretical advantages when compared to systemic delivery. With antibiotics placed on the site directly, an intact vascular system is not required for reaching the surgical site.... Local delivery can also provide a local concentration that exceeds what can be done systemically, and can require a smaller total drug amount. This can reduce the risk of systemic toxicity.”

24 nursece4less.com nursece4less.com nursece4less.com nursece4less.com References

The reference section of in-text citations includes published works intended as helpful material for further reading. [References are for a multi-part series on [PHARMACOLOGY OF BONE AND JOINT SURGERY].

1. Dhammi, I. and Haq, R., Kumar, S. (2015). Prophylactic antibiotics in orthopedic surgery: Controversial issues in its use. Indian J Orthop. 49(4): 373–376. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510788/ 2. Pountos, I., et al. (2012). Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis. Scientific World Journal. 606404. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259713/ 3. Bollinger, A., et al. (2015). Is Scheduled Intravenous Acetaminophen Effective in the Pain Management Protocol of Geriatric Hip Fractures? Geriatr Orthop Surg Rehabil. 6(3):202-8. Retrieved online at https://www.ncbi.nlm.nih.gov/pubmed/26328237. 4. Sakallaris, B., et al. (2015). Optimal Healing Environments. Glob Adv Health Med. 4(3): 40–45. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424933/ 5. Cleveland Clinic. (2017). Pain control after surgery. Retrieved online at https://my.clevelandclinic.org/health/articles/11307-pain-control- after-surgery 6. Soffin, E. and YaDeau, J. (2016). Enhanced recovery after surgery for primary hip and knee arthroplasty: a review of the evidence. British Journal of Anaesthesia; Volume 117, Issue suppl 3. Retrieved online at https://academic.oup.com/bja/article/117/suppl_3/iii62/2664402 7. Duivenvoorden, T., et al. (2013). Anxiety and depressive symptoms before and after total hip and knee arthroplasty: a prospective multicentre study. Osteoarthritis and Cartilage. Volume 21, Issue 12; 1834-1840. Retrieved online at https://www.sciencedirect.com/science/article/pii/S106345841300940 0 8. Kinman, T. (2016). Anticoagulant and Antiplatelet Drugs. Retrieved online at https://www.healthline.com/health/anticoagulant-and- antiplatelet-drugs#modal-close 9. Solayar, G. and Shannon, F. (2014). Thromboprophylaxis and Orthopaedic Surgery: Options and Current Guidelines. Malays J Med Sci. 2014 May; 21(3): 71–77. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163561/

25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10. Moriarty, T., et al. (2016). Orthopaedic device related infection: current and future interventions for improved prevention and treatment. EFORT Open; 1:89-99. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367564/ 11. Hake, M., et al. (2015). Local antibiotic therapy strategies in orthopaedic trauma: Practical tips and tricks and review of the literature. Injury; 46:1447-56. 12. Boo, G., et al. (2015). Antimicrobial delivery systems for local infection prophylaxis in orthopedic and trauma surgery. Biomaterials; 52:113- 25. 13. Bauer, K. and Lip, G. (2018). Overview of the causes of venous thrombosis. UpToDate. Retrieved online at https://www.uptodate.com/contents/overview-of-the-causes-of- venous- thrombosis?search=venous%20thromboembolism&source=search_res ult&selectedTitle=1~150&usage_type=default&display_rank=1. 14. Harter, K., Levine, M., and Henderson, S. (2015). Anticoagulation Drug Therapy: A Review. West J Emerg Med. 2015 Jan; 16(1): 11–17. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307693/. 15. Stewart, D. and Freshour, J. (2013). Aspirin for the prophylaxis of venous thromboembolic events in orthopedic surgery patients: a comparison of the AAOS and ACCP guidelines with review of the evidence. Ann Pharmacother; 47(1):63–74. 16. Metsemakers, W., et al. (2015). A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus. J Control Release; 209:47-56 17. Brooks, B., Brooks, A., and Grainger, D. (2013). Antimicrobial medical devices in preclinical development and clinical use. In: Moriarty TF, Zaat SAJ, Busscher HJ, editors., eds. Biomaterials Associated Infection. New York: Springer:307-54. 18. Proctor, R. (2012) Is there a future for a Staphylococcus aureus vaccine? Vaccine; 30:2921-7 19. Proctor, R. (2012). Challenges for a universal Staphylococcus aureus vaccine. Clin Infect Dis; 54:1179-86 20. Jansen, K., Girgenti, D., et al. (2013). Vaccine review: Staphyloccocus aureus vaccines: problems and prospects. Vaccine; 31:2723-30 21. den Reijer, P., et al. (2013). Characterization of the humoral immune response during Staphylococcus aureus bacteremia and global gene expression by Staphylococcus aureus in human blood. PLoS One. 8:e53391

26 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22. Gedbjerg, N., et al. (2013). Anti-glucosaminidase IgG in sera as a biomarker of host immunity against Staphylococcus aureus in orthopaedic surgery patients. J Bone Joint Surg [Am];95:e171 23. Nishitani, K., et al. (2015). A diagnostic serum antibody test for patients with Staphylococcus aureus osteomyelitis. Clin Orthop Relat; 473:2735-49 24. Nanra, J., et al. (2013). Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus. Hum Vaccin Immunother; 9:480-7 25. Joshi, A., et al. (2012). Immunization with Staphylococcus aureus iron regulated surface determinant B (IsdB) confers protection via Th17/IL17 pathway in a murine sepsis model. Hum Vaccin Immunother; 8:336-46 26. Varrone, J., et al. (2014). Passive immunization with anti- glucosaminidase monoclonal antibodies protects mice from implant- associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters. J Orthop Res; 32:1389-96 27. Aggarwal, V., et al. (2014). Mitigation and education. J Orthop Res 2014; 32Suppl 1:S16-25 28. Fowler, V., et al. (2013). Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA; 309:1368-78 29. Musmar, S., Ba’ba, H., and Owais, A. (2014). Adherence to guidelines of antibiotic prophylactic use in surgery: A prospective cohort study in North West Bank, Palestine. BMC Surg. 14:69. Retrieved online at https://bmcsurg.biomedcentral.com/articles/10.1186/1471-2482-14- 69 30. Rafati, M., et al (2014). Adherence to American society of health- system pharmacists surgical antibiotic prophylaxis guidelines in a teaching hospital. J Res Pharm Pract;3:62–6 31. Mathur, P., et al. (2013). Implementation of a short course of prophylactic antibiotic treatment for prevention of postoperative infections in clean orthopaedic surgeries. Indian J Med Res;137:111–6 32. W-Dahl, A., et al (2011). Timing of preoperative antibiotics for knee arthroplasties: Improving the routines in Sweden. Patient Saf Surg; 5:22. 33. Niimi, R., et al. (2011). One-day antibiotic infusion for the prevention of postoperative infection following arthroplasty: A case control study. ISRN Orthop; 839641 34. Andersson, A., et al. (2012). The application of evidence-based measures to reduce surgical site infections during orthopedic surgery – Report of a single-center experience in Sweden. Patient Saf Surg; 6:11.

27 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35. Beswick, A., et al. (2012). What is the evidence base to guide surgical treatment of infected hip prostheses? Systematic review of longitudinal studies in unselected patients. BMC Med; 10:18. 36. Kapadia, B., et al. (2016). Periprosthetic joint infection. Lancet; 387:386-94. 37. Musmar, S., Ba’ba, H., and Owais, A. (2014). Adherence to guidelines of antibiotic prophylactic use in surgery: A prospective cohort study in North West Bank, Palestine. BMC Surg. 14:69. Retrieved online at https://bmcsurg.biomedcentral.com/articles/10.1186/1471-2482-14- 69 38. Solomon, D. (2018). Nonselective NSAIDs: Overview of adverse effects. UpToDate. Retrieved online at https://www.uptodate.com/contents/nonselective-nsaids-overview-of- adverse- effects?search=ibuprofen%20and%20GI&source=search_result&select edTitle=6~150&usage_type=default&display_rank=6. 39. Poonai, N., et al. (2017). Oral morphine versus ibuprofen administered at home for postoperative orthopedic pain in children: a randomized controlled trial. CMAJ. 2017 Oct 10; 189(40): E1252–E1258. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636628/ 40. Stapleton, F. (2017). Ibuprofen Is Effective for Postoperative Orthopedic Pain. CMAJ. Retrieved online at https://www.jwatch.org/na45296/2017/10/18/ibuprofen-effective- postoperative-orthopedic-pain 41. Halford, G., Lordkipanidzé, M., and Watson, S. (2012). 50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams. Platelets. 23(6):415-22. Retrieved online at https://www.ncbi.nlm.nih.gov/pubmed/22098129 42. Kaplan, V. and Eroglu, C. (2016). Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study. J Oral Maxillofac Surg. 2016 Oct; 74(10):1946.e1-6. Retrieved online at https://www.ncbi.nlm.nih.gov/pubmed/27311846 43. O'Neill, D. and Webb, T. (2014). Less is more: limiting narcotic prescription quantities for common orthopedic procedures. Phys Sportsmed. 2014 Nov;42(4):100-5. 44. Bollinger, A., et al. (2015). Is Scheduled Intravenous Acetaminophen Effective in the Pain Management Protocol of Geriatric Hip Fractures? Geriatr Orthop Surg Rehabil. 6(3): 202–208. Retrieved online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536513/ 45. Orthoinfo.aaos.org. (n.d.) Managing Pain With Medications After Orthopaedic Surgery. AAOS. Retrieved online at https://orthoinfo.aaos.org/en/recovery/managing-pain-with- medications/

28 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46. Pandharipande, P. and McGrane, S. (2018). Pain control in the critically ill adult patient. UpToDate. Retrieved online https://www.uptodate.com/contents/pain-control-in-the-critically-ill- adult- patient?search=ketorolac&source=search_result&selectedTitle=4~85& usage_type=default&display_rank=7. 47. Lieberman, J. and Pensak, M. (2013). Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am;95(19):1801–1811. 48. Nutescu, E. (2013). Pharmacoeconomic implications of thromboprophylaxis with new oral anticoagulants after total hip or knee replacement in the USA. Expert Opin Pharmacother; 14(4):525– 34. 49. Revankar, N., et al. (2013). A Canadian study of the cost-effectiveness of apixaban compared with enoxaparin for postsurgical venous thromboembolism prevention. Postgrad Med. 2013; 125(4):141–53. 50. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. (2012). Chest. 141(2 Suppl): e89S–e119S. Retrieved online at https://www.ncbi.nlm.nih.gov/pubmed/22315278 51. Roe, M., et al. (2012). Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization. N Engl J Med 2012; 367:1297- 1309. Retrieved online at http://www.nejm.org/doi/full/10.1056/NEJMoa1205512. 52. Tietze, K. and Fuchs, B. (2018). Sedative-analgesic medications in critically ill adults: Properties, dosage regimens, and adverse effects. UpToDate. Retrieved online at https://www.uptodate.com/contents/sedative-analgesic-medications- in-critically-ill-adults-properties-dosage-regimens-and-adverse- effects?search=benzodiazepines&source=search_result&selectedTitle= 5~150&usage_type=default&display_rank=5. 53. Filho, J.O. and Mullen, M. (2018). Antithrombotic treatment of acute ischemic stroke and transient ischemic attack. UpToDate. Retrieved online at https://www.uptodate.com/contents/antithrombotic- treatment-of-acute-ischemic-stroke-and-transient-ischemic- attack?search=NICE%20guidelines%20for%20thromboprophylaxis&so urce=search_result&selectedTitle=1~150&usage_type=default&displa y_rank=1. 54. Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism. UpToDate. 2018. Retrieved online at https://www.uptodate.com/contents/society-guideline-links- superficial-vein-thrombosis-deep-vein-thrombosis-and-pulmonary- embolism?search=NICE%20guidelines%20for%20thromboprophylaxis

29 nursece4less.com nursece4less.com nursece4less.com nursece4less.com &source=search_result&selectedTitle=2~150&usage_type=default&dis play_rank=2 55. Choy, Yujuan, Treatment of acute procedural anxiety in adults. UpToDate. Retrieved online at https://www.uptodate.com/contents/treatment-of-acute-procedural- anxiety-in- adults?search=lorazepam%20and%20surgery&source=search_result& selectedTitle=4~150&usage_type=default&display_rank=4.

The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare.

The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals.

Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication.

Hospitals and facilities that use this publication agree to defend and indemnify, and shall hold NurseCe4Less.com, including its parent(s), subsidiaries, affiliates, officers/directors, and employees from liability resulting from the use of this publication.

The contents of this publication may not be reproduced without written permission from NurseCe4Less.com.

30 nursece4less.com nursece4less.com nursece4less.com nursece4less.com