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Rapid Response Report: Peer-Reviewed Summary with Critical Appraisal CADTH Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
October 2010
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Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
Sarah Ndegwa, BScPharm1 Karen Cimon1 Melissa Severn, MISt1
October 2010
1 Canadian Agency for Drugs and Technologies in Health, Ottawa, ON
Health technology assessment (HTA) agencies face the challenge of providing quality assessments of medical technologies in a timely manner to support decision-making. Ideally, all important deliberations would be supported by comprehensive health technology assessment reports, but the urgency of some decisions often requires a more immediate response.
The Health Technology Inquiry Service (HTIS) provides Canadian health care decision-makers with health technology assessment information, based on the best available evidence, in a quick and efficient manner. Inquiries related to the assessment of health care technologies (drugs, devices, diagnostic tests, and surgical procedures) are accepted by the service. Information provided by the HTIS is tailored to meet the needs of decision-makers, taking into account the urgency, importance, and potential impact of the request.
Consultations with the requestor of this HTIS assessment indicated that a review of the literature would be beneficial. The research question and selection criteria were developed in consultation with the requestor. The literature search was carried out by an information specialist using a standardized search strategy. The review of evidence was conducted by one internal HTIS reviewer. The draft report was internally reviewed and externally peer-reviewed by two or more peer reviewers. All comments were reviewed internally to ensure that they were addressed appropriately.
Reviewers These individuals kindly provided comments on this report:
Ken Bassett, MD, PhD Dena S. Hammoudi, MD Professor Resident, Postgraduate Year 5 University of British Columbia University of Toronto Vancouver, BC Toronto, ON
W.E.S Connolly, MD, FRCSC Associate Professor McGill University Montreal, QC
Industry: The following manufacturers were provided with an opportunity to comment on an earlier version of this report: Sandoz Canada Inc., Allergan Inc., and Alcon Canada Inc. All comments that were received were considered when preparing the final report.
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Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: i Review of Clinical and Cost-Effectiveness and Guidelines
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ii Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
ACRONYMS AND ABBREVIATIONS
CI confidence interval ESCRS European Society of Cataract and Refractive Surgeons MRSA methicillin-resistant Staphylococcus aureus OR odds ratio RCT randomized controlled trial RR relative risk
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: iii Review of Clinical and Cost-Effectiveness and Guidelines
TABLE OF CONTENTS
ACRONYMS AND ABBREVIATIONS ...... iii
EXECUTIVE SUMMARY ...... 1
1 CONTEXT AND POLICY ISSUES...... 3
2 RESEARCH QUESTIONS...... 3
3 METHODS ...... 3 3.1 Literature search ...... 3 3.2 Article selection ...... 4
4 SUMMARY OF FINDINGS ...... 4 4.1 Randomized controlled trials...... 4 4.1.1 Intracameral cefuroxime...... 4 4.1.2 Intracameral moxifloxacin...... 6 4.1.3 Intracameral vancomycin and gentamicin ...... 6 4.2 Observational studies...... 7 4.2.1 Intracameral cefuroxime...... 7 4.2.2 Intracameral vancomycin...... 8 4.2.3 Intracameral cefazolin...... 8 4.2.4 Intracameral moxifloxacin...... 9 4.3 Economic evaluations...... 9 4.4 Guidelines and recommendations...... 10 4.5 Limitations ...... 12
5 CONCLUSIONS AND IMPLICATIONS FOR DECISION- OR POLICY-MAKING ...... 12
6 REFERENCES...... 13
APPENDIX 1: LITERATURE SEARCH STRATEGY...... 17 APPENDIX 2: SELECTION OF PUBLICATIONS...... 21
iv Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
TITLE: Intracameral Antibiotics for the Ovid MEDLINE, Ovid MEDLINE(R) In- Prevention of Endophthalmitis Post- Process & Other Non-Indexed Citations, Cataract Surgery: Review of Clinical PubMed, Embase, The Cochrane Library (Issue and Cost-Effectiveness and Guidelines 5, 2010), the University of York Centre for Reviews and Dissemination (CRD) databases, DATE: October 2010 EuroScan, international health technology agencies, and a focused Internet search. The search was limited to English language articles EXECUTIVE SUMMARY that were published between January 1, 2005 and May 17, 2010. Regular alerts are current to Context and Policy Issues July 22, 2010. No filters were applied to limit Endophthalmitis is a rare complication that can the retrieval by study type for research questions occur after routine cataract surgery. It is often 1 and 2. A filter was applied to research question associated with a poor prognosis and may result 3 to limit the retrieval to guidelines. Two in severe, permanent vision loss. Despite independent reviewers screened articles using advances in medical technologies and pre-defined criteria. treatments, there is evidence that the incidence of post-operative endophthalmitis is increasing. Summary of Findings There is significant variation among surgeons Intracameral cefuroxime with respect to antibiotic prophylaxis for post- In a randomized controlled trial (RCT), the operative endophthalmitis. The intracameral European Society of Cataract and Refractive injection of antibiotics has been investigated for Surgeons (ESCRS) assessed the clinical the benefit of delivering an instantaneous, high effectiveness of using intracameral cefuroxime concentration of antibiotic to the anterior with or without perioperative topical chamber of the eye at the end of surgery. The levofloxacin for the prevention of exposure of intraocular tissues to high antibiotic endophthalmitis after routine concentrations may increase the risk of toxic phacoemulsification cataract surgery. The study effects, including macular edema and toxic was halted early when a preliminary analysis of anterior segment syndrome. This report reviews 16,211 patients showed that the absence of the evidence on the clinical effectiveness, safety, prophylactic intracameral cefuroxime was and cost-effectiveness of using intracameral associated with a statistically significant increase antibiotics for the prevention of endophthalmitis in the risk of presumed infectious post-operative after cataract surgery. Current evidence-based endophthalmitis. The absence of perioperative guidelines for the use of intracameral antibiotics topical levofloxacin did not significantly are also presented. increase the risk of post-operative endophthalmitis. The results of six observational Research Questions studies support the superiority of using 1. What is the clinical effectiveness of intracameral cefuroxime over alternatives, intracameral antibiotics for the prevention of including topical antibiotics and subconjunctival endophthalmitis post-cataract surgery? cefuroxime, for the prophylaxis of post- 2. What is the cost-effectiveness of operative endophthalmitis. No anaphylactic intracameral antibiotics for the prevention of reactions or signs of toxicity were reported in endophthalmitis post-cataract surgery? two RCTs and one observational study. 3. What are the guidelines for the use and preparation of intracameral antibiotics? Intracameral moxifloxacin One RCT and one observational study evaluated Methods the safety of using intracameral moxifloxacin compared with intracameral balanced salt A literature search was conducted on health solution. No drug-related adverse events technology assessment resources, including occurred, and there were no statistically
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 1 Review of Clinical and Cost-Effectiveness and Guidelines
significant differences in safety parameters Conclusions and Implications for between the two groups. A second observational Decision- or Policy-Making study evaluating the safety of using intracameral moxifloxacin showed no statistically significant There is consistent evidence that the use of differences between pre- and post-surgical intracameral cefuroxime reduces the risk of measurements of safety parameters. post-operative endophthalmitis without significant safety issues. An economic analysis Intracameral vancomycin determined that the use of intracameral One RCT found no statistically significant cefuroxime was more cost-effective than differences in macular edema or visual acuity intracameral moxifloxacin or topical antibiotics when intracameral vancomycin plus gentamicin in the prevention of post-operative was compared with no antibiotics. One endophthalmitis. Based on the identified observational study showed a statistically literature, there is insufficient evidence to significant reduction in the incidence of post- support the use of the other intracameral operative endophthalmitis when intracameral antibiotics that were evaluated in the included vancomycin plus topical fusidic acid was studies. The included studies did not support the compared with topical fusidic acid alone. routine use of topical fluoroquinolones over intracameral cefuroxime. Despite these findings, Intracameral cefazolin most guidelines leave the choice of prophylactic Two observational studies showed a statistically antibiotic and mode of administration to the significant reduction in the rate of post-operative individual surgeon’s discretion, and many endophthalmitis with the use of intracameral surgeons favor the use of topical moxifloxacin cefazolin plus topical antibiotics compared with or gatifloxacin. Until more information is topical antibiotics alone. No toxic effects or available, the strengths and limitations of the anaphylactic reactions were reported in either available evidence, clinical experience, changes study. in microbial resistance, emergence of new pathogens, and institution-specific budgets may Economic evaluations be considerations regarding the choice of antibiotic and mode of administration for the One US cost-effectiveness analysis conducted prophylaxis of post-operative endophthalmitis. from a societal perspective determined that intracameral cefuroxime was more cost-effective than intracameral moxifloxacin or topical antibiotics for the prevention of endophthalmitis after cataract surgery.
Guidelines and recommendations
Two international guidelines recommend the use of intracameral antibiotics for the prophylaxis of post-operative endophthalmitis. One guideline does not specify the choice of antibiotic, and the other guideline recommends the use of intracameral cefuroxime, but not intracameral vancomycin. Two North American guidelines leave the choice of prophylactic antibiotic and mode of administration to the individual surgeon’s discretion.
2 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
In light of the significant morbidity that is 1 CONTEXT AND associated with endophthalmitis, an assessment POLICY ISSUES of different prophylactic options is needed. This report reviews evidence on the clinical Endophthalmitis is a rare complication that can effectiveness, safety, and cost-effectiveness of occur after routine cataract surgery.1 It is often using intracameral antibiotics for the prevention associated with a poor prognosis and may result of endophthalmitis after cataract surgery. in severe, permanent vision loss.1 Gram-positive Current evidence-based guidelines for the use of bacteria, including Staphylococcus epidermidis intracameral antibiotics are also presented. (S. epidermis) and Staphylococcus aureus, account for more than 90% of post-operative 2 RESEARCH endophthalmitis infections.1,2 Infections due to other gram-positive bacteria (including various QUESTIONS Streptococci and Enterococci species) and gram- negative bacteria have also been reported.1,2 1. What is the clinical effectiveness of Several studies have estimated the incidence of intracameral antibiotics for the prevention of post-operative endophthalmitis to be between endophthalmitis post-cataract surgery? 0.043% and 0.15% in Canada.3-6 Despite 2. What is the cost-effectiveness of advances in medical technologies and intracameral antibiotics for the prevention of treatments, there is evidence that the incidence endophthalmitis post-cataract surgery? of post-operative endophthalmitis is increasing.7 3. What are the guidelines for the use and Changes in surgical techniques, incision type, preparation of intracameral antibiotics? and an aging population may be some of the factors that are driving this trend.5,7,8 Furthermore, recent data show that the number 3 METHODS of cataract procedures performed in Canada continues to increase.9 A total of 255,800 3.1 Literature search cataract surgeries were performed nationally between 2007 and 2008, representing a 15% Peer-reviewed literature searches were increase from the number of surgeries that were conducted to obtain published literature for this performed between 2004 and 2005.9 review. All search strategies were developed by the information specialist with input from the Because of the health and economic burden project team. associated with endophthalmitis, prophylaxis with antibiotics has been introduced to prevent The following bibliographic databases were infection.10 There is significant variation among searched through the Ovid interface: MEDLINE, surgeons with respect to choice of the antibiotic MEDLINE In-Process & Other Non-Indexed and the administration route.3,4,11-14 Intracameral Citations, and EMBASE. Parallel searches were injection has been investigated for the benefit of run in PubMed and The Cochrane Library (Issue delivering an instantaneous, high concentration 5, 2010). The search strategy comprised of antibiotic to the anterior chamber of the eye at controlled vocabulary, such as the National the end of surgery.15 However, the exposure of Library of Medicine’s MeSH (Medical Subject intraocular tissues to high antibiotic Headings) and keywords. No filters were applied concentrations may increase the risk of toxic to limit the retrieval by study type for research effects, including macular edema (swelling of questions 1 and 2. A filter was applied to the central portion of the retina resulting in research question 3 to limit the retrieval to visual distortion) and toxic anterior segment guidelines. The detailed search strategies appear syndrome (a noninfectious inflammatory in Appendix 1. reaction with signs and symptoms that mimic endophthalmitis infection).15,16 The search was restricted to English language articles that were published between January 1,
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 3 Review of Clinical and Cost-Effectiveness and Guidelines
2005 and May 17, 2010. Regular alerts were established on Embase and MEDLINE, and 4 SUMMARY OF information that was retrieved through alerts FINDINGS was current to July 22, 2010. Of the 334 citations that were identified in the Grey literature (literature that is not literature search, 283 were excluded after commercially published) was identified by screening of titles and abstracts, and 51 were searching the websites of health technology retrieved for full-text screening. Four relevant assessment and related agencies, professional publications were identified in the grey literature associations, and other specialized databases. search. Twenty publications were included in Google and other Internet search engines were this review, and the remaining 35 articles were used to search for additional information. These excluded (Appendix 2). Four RCTs,17-20 11 searches were supplemented by handsearching observational studies,8,21-30 one economic the bibliographies and abstracts of key papers, evaluation,31 and four evidence-based and through contacts with appropriate experts guidelines32-35 were identified. The literature and agencies. search did not identify any health technology assessments, systematic reviews, meta-analyses, 3.2 Article selection or controlled clinical trials.
Two independent reviewers (SN, KC) screened 4.1 Randomized controlled the titles and abstracts of the retrieved trials publications. The same two reviewers independently evaluated the full-text 4.1.1 Intracameral cefuroxime publications for final article selection.
The European Society of Cataract and The criteria for inclusion were: Refractive Surgeons (ESCRS) study was a Population Patients undergoing cataract multicentre, double-blind, placebo-controlled, surgery. partially masked RCT.17 Twenty-four European ophthalmology units and eye clinics assessed the Intervention Intracameral antibiotics for the clinical effectiveness of using intracameral prevention of endophthalmitis. cefuroxime with or without perioperative topical Comparator Other prophylactic therapies or levofloxacin for the prevention of no prophylaxis. endophthalmitis after routine phacoemulsification cataract surgery. Patients Outcomes Clinical effectiveness, safety, who were allergic to penicillins or costs, cost-effectiveness, cephalosporins; those in long-term nursing guidelines. homes, those who were pregnant, those who had Study design Systematic reviews, systematic- severe thyroid disease, or those who were review-based meta-analyses, younger than 18 years old; and all groups who randomized controlled trials were severely “at risk” for infection, including (RCTs), controlled clinical those with severe atopic keratoconjunctivitis or trials, observational studies, active blepharitis, were excluded from the study. economic studies, evidence- The majority (58%) of participants were women based guidelines. with a median age of 73 years to 75 years. Approximately 14% of the study population had
diabetes. The random allocation divided patients The criteria for exclusion were: into four treatment groups based on a 2 x 2 factorial design. Two of the four groups were in vitro studies treated with intracameral cefuroxime (1 mg in experimental animal model studies. 0.1 mL normal saline solution) at the end of
4 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
surgery. Two groups (one treated with 0.074%). The statistical significance was not intracameral cefuroxime, one untreated) calculated. A logistic regression analysis showed received perioperative topical levofloxacin 0.5% that the absence of prophylactic intracameral in a standard regimen. The study was masked for cefuroxime was associated with a statistically levofloxacin but not for intracameral significant increase in the risk of presumed cefuroxime. All groups also received povidone- infectious post-operative endophthalmitis (odds iodine 5% preoperatively and topical ratio [OR] 4.92; 95% confidence interval [CI] levofloxacin 0.5% four times daily post- 1.87 to 12.9; P = 0.001). The absence of topical operatively for six days. The primary study end levofloxacin was not associated with a points were the overall number of patients with statistically significant increase in risk of presumed infectious post-operative presumed infectious post-operative endophthalmitis and the number of patients with endophthalmitis (OR 1.41; 95% CI 0.67 to 2.95, infectious post-operative endophthalmitis proven P = 0.368). No cases of anaphylaxis were using culture, Gram stain, or polymerase chain observed in the patients receiving intracameral reaction. cefuroxime. No other safety outcomes were reported. Based on these findings, the authors The outcomes of the four groups appear in concluded that an intracameral injection of Table 1. The researchers planned to randomize cefuroxime reduces the risk of infectious post- 32,000 patients but the study was stopped early, operative endophthalmitis after after analysis of the available data from 16,211 phacoemulsification cataract surgery. patients showed that the incidence of endophthalmitis in the groups not receiving In a single-centre, double-masked RCT, Gupta intracameral cefuroxime was statistically et al. investigated whether intracameral significantly higher than that in the groups cefuroxime increases the risk of macular receiving intracameral cefuroxime. A total of 29 edema.18 Patients were randomized to receive cases of post-operative endophthalmitis were intracameral cefuroxime (1 mg of cefuroxime in reported, 20 of which had a proven infectious 0.1 mL normal saline solution) (34 patients) or cause. Five of the 29 reported cases occurred in an equal volume of intracameral balanced salt groups receiving intracameral cefuroxime. Of solution (28 patients) after phacoemulsification these five cases, three had a proven infectious cataract surgery. Macular edema was measured cause (two cases of S. epidermis in the group using ocular coherence tomography. There were receiving intracameral cefuroxime and one case no significant differences between groups in of Staphylococcus warneri in the group demographic or surgical characteristics. The receiving intracameral cefuroxime and topical results showed there were no statistically levofloxacin). Toxic anterior segment syndrome significant differences between groups in was not believed to be the cause of the macular edema four to six weeks after surgery. presenting signs and symptoms in the two The use of intracameral cefuroxime did not remaining unproven cases. The incidence of affect post-operative visual acuity. The authors post-operative endophthalmitis was lower in concluded that these results support the safety of patients receiving intracameral cefuroxime and using intracameral cefuroxime in routine perioperative topical levofloxacin than cataract surgery. intracameral cefuroxime alone (0.049% versus
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 5 Review of Clinical and Cost-Effectiveness and Guidelines
Table 1: Results of ESCRS Study17 Group A Group B Intervention Intervention Placebo vehicle drops 5* Placebo vehicle drops 5* No intracameral injection Intracameral cefuroxime 1 mg
Endophthalmitis incidence rates Endophthalmitis incidence rates Intent-to-treat (n = 4,054) Intent-to-treat (n = 4,056) Total: 14 (0.345%; 95% CI 0.119% to 0.579%) Total: 3 (0.074%; 95% CI 0.015% to 0.216%) Proven: 10 (0.247%; 95% CI 0.118% to 0.453%) Proven: 2 (0.049%; 95% CI 0.006% to 0.178%)
Per-Protocol (n = 3,990) Per-Protocol (n = 3,997) Total: 13 (0.326%; 95% CI 0.174% to 0.557%) Total: 3 (0.075%; 95% CI 0.016% to 0.219%) Proven: 9 (0.226%; 95% CI 0.103% to 0.428%) Proven: 2 (0.050%; 95% CI 0.006% to 0.181%) Group C Group D Intervention Intervention Levofloxacin drops 0.5% 5* Levofloxacin drops 0.5% 5* No intracameral injection Intracameral cefuroxime 1 mg
Endophthalmitis incidence rates Endophthalmitis incidence rates Intent-to-treat (n = 4,049) Intent-to-treat (n = 4,052) Total: 10 (0.247%; 95% CI 0.119% to 0.454%) Total: 2 (0.049%; 95% CI 0.006% to 0.178%) Proven: 7 (0.173%; 95% CI 0.070% to 0.356%) Proven: 1 (0.025%; 95% CI 0.001% to 0.137%)
Per-Protocol (n = 3,984) Per-Protocol (n = 4,000) Total: 10 (0.251%; 95% CI 0.120% to 0.461%) Total: 2 (0.050%; 95% CI 0.006% to 0.181%) Proven: 7 (0.176%; 95% CI 0.071% to 0.362%) Proven: 1 (0.025%; 95% CI 0.001% to 0.139%)
CI=confidence interval; ESCRS = European Society of Cataract and Refractive Surgeons. *Two drops given preoperatively and three drops given post-operatively. All groups also received povidone-iodine 5% preoperatively and topical levofloxacin 0.5% four times daily post-operatively for six days.
4.1.2 Intracameral moxifloxacin edema), inflammation in the anterior chamber (aqueous cell count), and effects on the blood- In a multicentre, open-label RCT, Lane et al. aqueous barrier (aqueous flare). The results evaluated the safety of intracameral showed that there were no statistically moxifloxacin.19 Participants were randomized to significant differences between the two groups receive an intracameral injection of a 250 in safety parameters preoperatively or at follow- g/0.050 mL dose of undiluted moxifloxacin up visits at one day, two to four weeks, or three 0.5% ophthalmic solution (26 eyes) or an equal months post-operatively. No study-related volume of balanced salt solution (31 eyes) at the adverse events occurred. The authors concluded end of routine phacoemulsification cataract that an intracameral injection of a commercially surgery. The two study groups were comparable available moxifloxacin ophthalmic solution at baseline for demographic and clinical appears to be safe for the prophylaxis of characteristics. The mean age of participants was endophthalmitis after cataract surgery. 74 years 9.3 years (range 51 years to 88 years), and most (59.6%) were women. The 4.1.3 Intracameral vancomycin and safety parameters that were assessed included gentamicin macular edema, visual acuity, intraocular pressure, effects on the cornea (endothelial cell In a single-centre, evaluator-blinded RCT, Ball density and thickness, corneal clarity, and et al. investigated whether the use of
6 Intracameral Antibiotics for Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
vancomycin and gentamicin increases the risk of In a single-centre, retrospective (October 2001 macular edema after phacoemulsification to April 2007) chart review of patients cataract surgery.20 Forty-one patients (25 eyes in undergoing phacoemulsification cataract each group) were randomized to receive no surgery, Sobaci et al. evaluated the effectiveness antibiotics or vancomycin (20 g/mL) and of using intracameral cefuroxime.22 Before the gentamicin (8 g/mL) in the infusion fluid at the introduction of intracameral cefuroxime, 3,075 time of cataract surgery. There were no patients received topical ofloxacin 0.3% four significant differences between groups in times daily for one week after surgery, which preoperative or surgical factors. The mean age was then tapered and stopped after two weeks. was 70.2 years in the control group and 68.5 In 2004, the intracameral injection of years in the antibiotic group, and most (56%) of cefuroxime (1.0 mg in 0.1 mL normal saline) the participants were male. The results showed was added to the prophylactic regimen in 3,024 no statistically significant differences in macular surgeries. The incidence of post-operative edema or visual acuity between groups five endophthalmitis was statistically significantly weeks post-operatively. Based on these findings, higher in patients who received topical ofloxacin the authors concluded that the use of alone compared with patients who also received intracameral vancomycin and gentamicin in the intracameral cefuroxime (0.42% versus 0.13% infusion fluid at the time of cataract surgery respectively; OR 3.20; 95% CI 1.04 to 9.84; does not increase the risk of macular edema or P = 0.031). Three of the four cases of negatively affect visual function post- endophthalmitis occurring in the group receiving operatively. intracameral cefuroxime had a proven infectious cause (one case each of Aspergillus fumigatus, 4.2 Observational studies Pseudomonas aeruginosa, and Streptococcus pneumonia). No signs of toxicity, including 4.2.1 Intracameral cefuroxime toxic anterior segment syndrome or anaphylactic reactions, were documented in the intracameral In a single-centre, 10-year (January 1999 to cefuroxime group. December 2008) study, Garcia-Sáenz et al. prospectively evaluated the effectiveness of In a single-centre retrospective (January 2000 to using intracameral cefuroxime for the prevention December 2006) database analysis, Yu-Wai- of endophthalmitis in patients who underwent Man et al. evaluated the clinical effectiveness of cataract surgery.21 Before the introduction of using intracameral cefuroxime (1 mg in 0.1 mL intracameral cefuroxime, 6,595 patients received normal saline) in 17,318 procedures compared topical ofloxacin 0.3% four times daily for a with the use of subconjunctival cefuroxime (50 week after surgery. In 2005, antibiotic mg in 0.5 mL normal saline) in 19,425 prophylaxis in 7,057 patients was switched to procedures, for the prevention of endophthalmitis after phacoemulsification intracameral injection cefuroxime (1.0 mg in 23 0.1 mL normal saline) at the end of cataract cataract surgery. The incidence of presumed surgery. The incidence in post-operative infectious endophthalmitis was statistically endophthalmitis was statistically significantly significantly higher in the subconjunctival higher in the group who received topical cefuroxime group than in the intracameral ofloxacin compared with those who received cefuroxime group (0.139% versus 0.046% intracameral cefuroxime (0.590% versus 0.043% respectively; OR 3.01; 95% CI 1.37 to 6.63; P = respectively; relative risk [RR] 0.072; 95% CI 0.0068). No safety outcomes were reported. 0.022 to 0.231; P < 0.05). The causative organisms in the cases of endophthalmitis Two multicentre studies used prospective data occurring after the introduction of intracameral from the Swedish National Cataract Register to assess the risk factors for the development of cefuroxime could not be identified using culture. 8,24 No safety outcomes were reported. endophthalmitis after cataract surgery. The first study collected data between 1999 and 2001.24 Surgeries using intracameral antibiotics
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 7 Review of Clinical and Cost-Effectiveness and Guidelines
for prophylaxis were compared with surgeries after the introduction of intracameral not using intracameral antibiotics (151,874 vancomycin.26 Before the introduction of versus 6,805 surgeries respectively). intracameral vancomycin, patients received Intracameral cefuroxime was used in 98.5% of topical fusidic acid for 10 days post-operatively patients. Intracameral infusion of gentamicin (3,904 surgeries). In 2001, vancomycin (1 mg in and vancomycin was used in the remaining 1.5% 0.1 mL normal saline) injected intracamerally of patients. The frequency of post-operative into the capsular bag after surgery was added to endophthalmitis was statistically significantly the antibiotic prophylaxis protocol (12,702 higher in patients who had not received surgeries). The results showed a statistically intracameral antibiotics (OR 3.649; 95% CI significant reduction in the incidence of post- 2.291 to 5.812; P < 0.001). The second study8 operative endophthalmitis after the introduction collected data between January 2002 and of intracameral vancomycin compared with December 2004 and compared 223,156 surgeries topical fusidic acid alone (0.008% versus 0.3% using intracameral cefuroxime with 2,315 respectively; P < 0.0001; RR 38; 95% CI 7 to surgeries not using intracameral cefuroxime for 252). The absolute risk reduction with the use of prophylaxis. The frequency of post-operative intracameral vancomycin was calculated to be endophthalmitis was statistically significantly 292 cases per 100,000 cataract surgeries. The higher in patients who had not received one case of endophthalmitis occurring after the intracameral cefuroxime (OR 7.236; 95% CI introduction of intracameral vancomycin was 3.71 to 14.11; P < 0.001). Using multiple negative on Gram stain or culture. No safety regression analyses, both studies showed that not outcomes were reported. receiving intracameral cefuroxime was an independent predictor for the development of 4.2.3 Intracameral cefazolin post-operative endophthalmitis (P < 0.001). In a single-centre retrospective (January 2002 to In a single-centre, retrospective, case-control December 2007) study, Garat et al. assessed the study, Wejde et al. assessed risk factors for the clinical effectiveness of using intracameral development of endophthalmitis among 46,292 cefazolin for the prevention of post-operative cataract surgeries that were performed between endophthalmitis after phacoemulsification January 1994 and December 2000.25 Fifty-nine cataract surgery.27 The cumulative incidence of cases of endophthalmitis in the study group were post-operative endophthalmitis occurring before compared with 235 control cases that were (5,930 surgeries) and after (12,649 surgeries) the selected at random. A statistically significantly addition of intracameral cefazolin (2.5 mg in 0.1 lower risk of post-operative endophthalmitis was mL normal saline) was compared. All patients found when prophylaxis with intracameral also received post-operative topical ofloxacin cefuroxime (1.0 mg in 0.1 mL normal saline) 0.3% drops and tobramycin-dexamethasone was used in addition to preoperative topical drops four times daily for a week post- gentamicin 0.3% drops (OR 4.6; 95% CI 2.5 to operatively. The results showed a statistically 8.5; P < 0.001) compared with topical significant reduction in the rate of gentamicin alone. Multiple logistic regression endophthalmitis with the use of intracameral analyses showed that prophylaxis using topical cefazolin compared with topical prophylaxis gentamicin alone was an independent risk factor alone (0.047% versus 0.422% respectively; for the development of post-operative P < 0.0001), corresponding to an RR reduction endophthalmitis (OR 5.7; 95% CI 2.8 to 11.9; of 88.7% (95% CI 72.6% to 95.4%). Four of the P < 0.001). six cases of endophthalmitis occurring with the use of intracameral cefazolin were proven on 4.2.2 Intracameral vancomycin Gram stain or culture (two cases of Streptococcus oralis and one case each of S. In a single-centre retrospective (January 1998 to epidermis and Proteus mirabilis). No adverse December 2008) study, Anijeet et al. compared events including post-operative inflammation or the incidence of endophthalmitis before and negative changes in visual acuity were observed.
8 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
In a single-centre retrospective (January 2001 to measurements. No drug-related adverse effects December 2004) study, Romero et al. evaluated were observed. the use of prophylactic intracameral cefazolin for the prevention of endophthalmitis after In a single-centre, prospective study, Espiritu et cataract surgery.28 The cumulative incidence of al. investigated the safety of using intracameral post-operative endophthalmitis occurring before moxifloxacin in 65 patients undergoing (3,650 surgeries) and after (3,618 surgeries) the phacoemulsification cataract surgery.30 addition of intracameral cefazolin (1 mg in 0.1 Undiluted moxifloxacin 0.5% drops at a dose of mL of normal saline) was compared. All patients 500 g/0.1 mL was used. The safety parameters also received post-operative tobramycin- that were assessed were inflammation in the dexamethasone drops every four hours. The anterior chamber (aqueous cells), effects on the results showed a statistically significant cornea (endothelial cell density and thickness), reduction in the rate of endophthalmitis with the and effects on the blood-aqueous barrier use of intracameral cefazolin compared with (aqueous flare). The results at one month post- topical prophylaxis alone (0.055% versus operatively did not show any statistically 0.63%; P < 0.0001). The bacteria that were significant changes in endothelial cells or cultured for the two cases of endophthalmitis corneal thickness compared with preoperative occurring with the use of intracameral cefazolin measurements. No eye showed signs of were Klebsiella and Corynebacterium. No significant anterior chamber inflammation one patients in the intracameral cefazolin group week post-operatively or lost a line of visual showed signs of toxic effects to the cornea or acuity. retina, and no anaphylactic reactions were reported. 4.3 Economic evaluations
4.2.4 Intracameral moxifloxacin Sharifi et al. determined the cost-effectiveness from a societal perspective in the US of different In a single-centre retrospective chart review, antibiotic regimens for the prevention of Arbisser assessed the safety of an intracameral endophthalmitis after cataract surgery.31 The injection of moxifloxacin after cataract modes of administration for the antibiotics were 29 surgery. The safety outcomes among 141 intracameral (cefuroxime or moxifloxacin), patients receiving moxifloxacin 0.5% drops topical (sulfacetamide, polymyxin/trimethoprim, diluted with balanced salt solution to a 100 ciprofloxacin, ofloxacin, moxifloxacin, or g/0.1 mL dose were compared with those of 50 gatifloxacin), and subconjunctival (gentamicin randomly selected patients who had cataract or cefazolin). A combination regimen of surgery before the implementation of intracameral cefuroxime, subconjunctival intracameral moxifloxacin. All patients also gentamicin, subconjunctival cefazolin, and received topical moxifloxacin 0.5% drops four topical sulfacetamide was also assessed. The times daily for two days preoperatively and then different prophylactic therapies were compared four times daily for a week post-operatively. No with no intervention. A decision-analytic model statistically significant differences were noted for a hypothetical cohort of 100,000 patients between groups in anterior chamber aged 70 years and older undergoing cataract inflammation (aqueous cell counts) at one week surgery was used. The analysis used a six week post-operatively. No post-operative epithelial time horizon. Clinical effectiveness estimates defects or stromal edema was observed in the were derived from the ESCRS study17 and the intracameral moxifloxacin group. A prospective authors’ assumptions. The risk of analysis of 18 patients was done to measure endophthalmitis in the absence of any macular edema. Ocular coherence tomography intervention was estimated to be 0.247% (95% measurements at six weeks post-operatively did CI 0.208% to 0.288%). The risk of not show any statistically significant differences endophthalmitis when intracameral cefuroxime in macular edema compared with preoperative or the four antibiotic combination regimen was
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 9 Review of Clinical and Cost-Effectiveness and Guidelines
used was estimated to be 0.045% (95% CI topical fluoroquinolone, ciprofloxacin, was 0.036% to 0.054%). Because no clinical data needed over intracameral cefuroxime to achieve were available, the economic model assumed the same cost-effectiveness ratio. The most 100% prevention of endophthalmitis with all expensive topical fluoroquinolones, gatifloxacin other options. The economic analysis included and moxifloxacin, needed to be at least 19 times the costs of each antibiotic and the treatment of more effective than intracameral cefuroxime to endophthalmitis or toxic anterior segment achieve cost-effective equivalence. For all syndrome. The cost per case of endophthalmitis regimens, except topical sulfacetamide and was estimated to be US$3,793. The productivity subconjunctival gentamicin, the number of cases losses due to endophthalmitis were excluded in that would need to be prevented exceeded the the cost analysis. Intracameral cefuroxime was number of cases expected without treatment used as a reference standard in the analysis (247 per 100,000 patients). Sensitivity analyses because it was the only method that had been varying the cost of antibiotics, cost of studied. endophthalmitis treatment, risk of infection, and degree of complications from intracameral A threshold effectiveness (the number of injections (anaphylaxis or toxic anterior segment endophthalmitis cases prevented) at which point syndrome) confirmed the robustness of these a given antibiotic would achieve the same cost- findings. The authors concluded that the use of effectiveness ratio as intracameral cefuroxime intracameral cefuroxime was more cost-effective was calculated. The results appear in Table 2. than that of commonly used topical antibiotics Four options (intracameral cefuroxime, for the prevention of endophthalmitis after subconjunctival gentamicin, subconjunctival cataract surgery. cefazolin, and topical sulfacetamide) were associated with savings in net costs. 4.4 Guidelines and Intracameral cefuroxime yielded a net cost recommendations savings of approximately US$480,000 in the cohort because of the endophthalmitis cases that The Canadian Ophthalmological Society were averted. When the treatment costs saved published practice guidelines for cataract from prevented cases of endophthalmitis were surgery in 2008.32 The recommendations are excluded, the cost-effectiveness ratio of based on a non-systematic literature review. In intracameral cefuroxime over no intervention the absence of direct evidence, the was US$1,403 per case of post-operative recommendations reflect a unanimous consensus endophthalmitis prevented. None of the of the Expert Committee. The guidelines state fluoroquinolones (ciprofloxacin, ofloxacin, that surgeons should be aware of their personal moxifloxacin, or gatifloxacin) were cost saving, and institutional risk of endophthalmitis, and if even after assuming that all potential cases of the rate of endophthalmitis is higher than endophthalmitis were averted after their use. A published norms or the risk is higher because of near five-fold increase in clinical effectiveness intraoperative complications, intracameral of intracameral moxifloxacin over intracameral antibiotics may be considered (based on cefuroxime was needed to achieve the same consensus). No details regarding the choice of cost-effectiveness ratio. An eight-fold increase antibiotic are provided. in clinical effectiveness of the least expensive
10 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
Table 2: Results of Cost-Effectiveness Analysis of Antibiotic Prophylaxis31 Antibiotic Cost per Cohort Cost- Threshold Effectiveness Prophylaxis Person Net Cost* Effectiveness Ratio Compared with (US$) (US$ Ratio† Intracameral Cefuroxime millions) (number of prevented cases) Intracameral Cefuroxime 2.83 −0.48 Cost saving NA Moxifloxacin 13.81 0.44 1,800 4.87 (984) Subconjunctival Gentamicin 2.95 −0.64 Cost saving 1.04 (210) Cefazolin 3.57 −0.58 Cost saving 1.26 (254) Topical Sulfacetamide 2.30 −0.71 Cost saving 0.81 (164) Polymyxin/ 12.36 0.30 1,211 4.36 (881) trimethoprim Ciprofloxacin 24.90 1.55 6,288 8.79 (1,775) Ofloxacin 33.74 2.44 9,867 11.90 (2,405) Moxifloxacin 55.00 4.56 18,474 19.40 (3,920) Gatifloxacin 57.60 4.82 19,527 20.32 (4,105) Four antibiotic 11.65 0.40 1,976 4.11 (831) combination‡
NA = not applicable *Net cost in a cohort of 100,000 eyes includes cost savings of prevented infections. †Includes cost saving from averted endophthalmitis. ‡Intracameral cefuroxime, subconjunctival gentamicin, subconjunctival cefazolin, and topical sulfacetamide.
The Scottish Intercollegiate Guidelines Network systematic review, or RCT and directly released a guideline for antibiotic prophylaxis in applicable to the target population). The surgery in 2008.33 The guideline is based on a guidelines note that careful dilution must be systematic literature review. The guideline undertaken to prevent potential toxicity and recommends intracameral antibiotic prophylaxis provide steps to ensure the accurate preparation to reduce the risk of developing endophthalmitis of cefuroxime for intracameral injection. The after cataract surgery (level of evidence A; based guidelines do not recommend the use of on at least one high quality meta-analysis, intracameral vancomycin in the irrigating systematic review, or RCT with a very low risk solution, because of insufficient evidence for of bias and directly applicable to the target clinical effectiveness and the potential for retinal population). No other details regarding the toxicity and antibiotic resistance (level of choice of antibiotic are provided in the evidence C; based on expert committees reports, guideline. or opinions and/or clinical experiences of respected authorities). Clinical practice guidelines for the management of post-operative infectious endophthalmitis The American Academy of Ophthalmology were developed by the Ministry of Health released guidelines for the management of Malaysia in 2006.34 The recommendations are cataracts in 2006.35 The recommendations are based on a non-systematic literature review. The based on a systematic literature review. The guidelines recommend intracameral cefuroxime guidelines state that, given the absence of clear (1 mg cefuroxime in 0.1 mL normal saline) at evidence for the benefit of prophylactic the end of surgery to prevent post-operative measures other than 5% povidone iodine, the endophthalmitis (level of evidence A; based on individual ophthalmologist should decide on the at least one good quality meta-analysis, use of a particular strategy, including
Intracameral Antibiotics for Prevention of Endophthalmitis Post-Cataract Surgery: 11 Review of Clinical and Cost-Effectiveness and Guidelines
intracameral antibiotics, for the prevention of endophthalmitis during the perioperative period 5 CONCLUSIONS AND (not graded for strength of evidence). IMPLICATIONS FOR
4.5 Limitations DECISION- OR POLICY-MAKING A limited literature search was conducted for this report. Potentially relevant evidence The ESCRS study17 was the only identified RCT published before 2005 or of a non-English that evaluated the clinical effectiveness of using language may have been excluded. intracameral antibiotics for the prevention of The ESCRS study reported a higher endophthalmitis after cataract surgery. The incidence of post-operative endophthalmitis results showed a near five-fold decrease in the in groups not receiving intracameral risk of presumed infectious post-operative cefuroxime than that generally reported in 36 endophthalmitis after the use of intracameral the literature. Hence, it is debatable cefuroxime. The ESCRS study also showed that whether findings from the ESCRS study can intracameral cefuroxime was clinically superior be generalized to Canadian settings with to perioperative topical levofloxacin for the lower incidences of post-operative prevention of post-operative endophthalmitis. endophthalmitis. Furthermore, the estimate These findings are supported in several for the reduction of endophthalmitis with observational studies.8,21,22,24,25 In addition, an intracameral cefuroxime had a wide CI and observational study23 indicated that the use of should not be viewed as a precise estimate intracameral cefuroxime was superior for the of the treatment effect. prevention of post-operative endophthalmitis Early termination of the ESCRS study based compared with subconjunctival cefuroxime. on a beneficial outcome may have led to an overestimation of the treatment effect of 37 Despite evidence that the use of intracameral intracameral cefuroxime. cefuroxime reduces the risk of post-operative Findings on the clinical effectiveness of endophthalmitis, many ophthalmologists favour intracameral antibiotics from observational topical fourth generation fluoroquinolones studies may be subject to selection bias in (moxifloxacin or gatifloxacin) over intracameral the treatment groups. cefuroxime for prophylaxis.3,11 A barrier to the Studies assessing safety outcomes may have uptake of intracameral cefuroxime in clinical lacked a sufficient sample size to detect practice appears to be the lack of a commercially infrequent adverse events and excluded available pre-formulated preparation for patients with significant comorbidities intracameral use.11,12,36 Currently, intracameral including diabetes and ocular pathologies, cefuroxime is extemporaneously prepared using and those with intraoperative complications. a product that is intended for intravenous It is unclear whether the findings of the US administration.38 The extemporaneous cost-effectiveness analysis can be preparation of cefuroxime solution carries a risk generalized to the institution-specific costs of dilution errors that may result in toxic anterior and public health care funding of a Canadian segment syndrome.15,38 Other limitations of setting. using cefuroxime include restricted coverage against gram-negative bacteria, Enterococci, and methicillin-resistant Staphylococcus aureus (MRSA), and the potential for hypersensitivity reactions.2,39
The results of observational studies indicate that intracameral cefazolin may be an effective alternative to intracameral cefuroxime for the
12 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
prevention of post-operative of post-operative endophthalmitis without endophthalmitis.27,28 Cefazolin offers a broader significant safety issues. Based on the identified spectrum of activity against gram-positive literature, there is insufficient evidence to bacteria and lower cost compared with support the use of the other intracameral cefuroxime.27,28 Similar to cefuroxime, cefazolin antibiotics that were evaluated in the included has limitations including the need for studies. The included studies did not support the extemporaneous intracameral preparation; routine use of topical fluoroquinolones over limited coverage against gram-negative bacteria, intracameral cefuroxime. Despite these findings, Enterococci, and MRSA; and the potential for most guidelines leave the choice of prophylactic hypersensitivity reactions.27,28,40 Although there antibiotic and mode of administration to the is some evidence to support the use of individual surgeon’s discretion. The clinical intracameral vancomycin with or without effectiveness and safety of the intracameral gentamicin for the prophylaxis of post-operative administration of antibiotics compared with endophthalmitis,20,26 some believe that it should other modes of administration requires further be reserved for the treatment of infections investigation. It is unclear whether the addition caused by multi-resistant gram-positive bacteria of intracameral antibiotics to perioperative to reduce the risk of resistance.34,41 The clinical topical antibiotics, particularly fourth generation effectiveness of intracameral moxifloxacin has fluoroquinolones, produces a clinically not been evaluated. Moxifloxacin is significant decrease in the incidence of post- commercially available as a preservative-free operative endophthalmitis. Until more ophthalmic formulation and may be a viable information is available, the strengths and option for the treatment of a minority of limitations of the available evidence, clinical infections caused by gram-negative bacteria, experience, changes in microbial resistance, atypical microorganisms, and anaerobes.40,42 The emergence of new pathogens, and institution- safety results of one RCT19 and one specific budgets may be considerations observational study30 did not indicate any toxic regarding the choice of antibiotic and mode of effects when the commercial product was administration for the prophylaxis of post- directly administered into the eye with no further operative endophthalmitis. preparation. However, one economic evaluation31 indicated that because of its cost, intracameral moxifloxacin is not cost-effective 6 REFERENCES compared with intracameral cefuroxime even 1. Kernt M, Kampik A. Endophthalmitis: under best-case assumptions of clinical pathogenesis, clinical presentation, effectiveness. management, and perspectives. clin ophthalmol [Internet]. 2010 [cited 2010 Jun All intracameral antibiotics that were evaluated 2];4:121-35. Available from: in the included studies appeared to be well http://www.ncbi.nlm.nih.gov/pmc/articles/PM tolerated with no signs of toxicity or negative C2850824/pdf/opth-4-121.pdf 17-20,22,27-30 effects on visual acuity. No studies 2. Costagliola C, dell'Omo R, Parmeggiani F, directly linked toxic anterior segment syndrome Romano MR, Semeraro F, Sebastiani A. with intracameral administration. These studies Endophthalmitis. Anti-Infective Agents in may have lacked sufficient sample size to detect Medicinal Chemistry. 2009;8(2):151-68. infrequent adverse effects, and larger studies are 3. Lloyd JC, Braga-Mele R. Incidence of needed to confirm the safety of intracameral postoperative endophthalmitis in a high- administration, particularly when used in volume cataract surgicentre in Canada. Can J patients with comorbidities including diabetes Ophthalmol [Internet]. 2009 Jun [cited 2010 and ocular pathologies, and those with Jun 2];44(3):288-92. Available from: intraoperative complications. http://article.pubs.nrc- cnrc.gc.ca/RPAS/rpv?hm=HInit&calyLang=en In summary, there is consistent evidence that the g&journal=cjo&volume=44&afpf=i09-052.pdf use of intracameral cefuroxime reduces the risk
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 13 Review of Clinical and Cost-Effectiveness and Guidelines
4. Hammoudi DS, Abdolell M, Wong DT. 12. Gore DM, Angunawela RI, Little BC. United Patterns of perioperative prophylaxis for Kingdom survey of antibiotic prophylaxis cataract surgery in Canada. Can J Ophthalmol practice after publication of the ESCRS [Internet]. 2007 Oct [cited 2010 Jun Endophthalmitis Study. J Cataract Refract 2];42(5):681-8. Available from: Surg. 2009 Apr;35(4):770-3. http://article.pubs.nrc- 13. Gordon-Bennett P, Karas A, Flanagan D, cnrc.gc.ca/RPAS/rpv?hm=HInit&calyLang=en Stephenson C, Hingorani M. A survey of g&journal=cjo&volume=42&afpf=i07-122.pdf measures used for the prevention of 5. Hatch WV, Cernat G, Wong D, Devenyi R, postoperative endophthalmitis after cataract Bell CM. Risk factors for acute surgery in the United Kingdom. Eye. 2008 endophthalmitis after cataract surgery: a May;22(5):620-7. population-based study. Ophthalmology. 2009 14. Ang GS, Barras CW. Prophylaxis against Mar;116(3):425-30. infection in cataract surgery: a survey of 6. Freeman EE, Roy-Gagnon MH, Fortin E, routine practice. Eur J Ophthalmol. 2006 Gauthier D, Popescu M, Boisjoly H. Rate of May;16(3):394-400. endophthalmitis after cataract surgery in 15. Mamalis N. Intracameral medication: is it Quebec, Canada, 1996-2005. Arch worth the risk? J Cataract Refract Surg. 2008 Ophthalmol. 2010 Feb;128(2):230-4. Mar;34(3):339-40. 7. Taban M, Behrens A, Newcomb RL, Nobe 16. Mamalis N, Edelhauser HF, Dawson DG, MY, Saedi G, Sweet PM, et al. Acute Chew J, LeBoyer RM, Werner L. Toxic endophthalmitis following cataract surgery: a anterior segment syndrome. J Cataract Refract systematic review of the literature. Arch Surg. 2006 Feb;32(2):324-33. Ophthalmol [Internet]. 2005 May [cited 2010 Jun 29];123(5):613-20. Available from: 17. ESCRS Endophthalmitis Study Group. http://assets0.pubget.com/pdf/15883279.pdf Prophylaxis of postoperative endophthalmitis following cataract surgery: Results of the 8. Lundström M, Wejde G, Stenevi U, Thorburn ESCRS multicenter study and identification of W, Montan P. Endophthalmitis after cataract risk factors. J Cataract Refract Surg. surgery: a nationwide prospective study 2007;33(6):978-88. evaluating incidence in relation to incision type and location. Ophthalmology. 2007 18. Gupta MS, McKee HDR, Saldana M, Stewart May;114(5):866-70. OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract 9. Canadian Institute for Health Information Refract Surg. 2005;31(6):1163-6. (CIHI). Surgical volume trends, 2009: within and beyond wait time priority areas [Internet]. 19. Lane SS, Osher RH, Masket S, Belani S. Ottawa: CIHI; 2009. [cited 2010 Jun 30]. Evaluation of the safety of prophylactic Available from: intracameral moxifloxacin in cataract surgery. http://secure.cihi.ca/cihiweb/products/surgical J Cataract Refract Surg. 2008 Sep;34(9):1451- _volumes_2009_e.pdf 9. 10. Schmier JK, Halpern MT, Covert DW, Lau 20. Ball JL, Barrett GD. Prospective randomized EC, Robin AL. Evaluation of Medicare costs controlled trial of the effect of intracameral of endophthalmitis among patients after vancomycin and gentamicin on macular retinal cataract surgery. Ophthalmology. 2007 thickness and visual function following Jun;114(6):1094-9. cataract surgery. J Cataract Refract Surg. 2006 May;32(5):789-94. 11. Chang DF, Braga-Mele R, Mamalis N, Masket S, Miller KM, Nichamin LD, et al. 21. García-Sáenz MC, Arias-Puente A, Rodríguez- Prophylaxis of postoperative endophthalmitis Caravaca G, Bañuelos JB. Effectiveness of after cataract surgery: results of the 2007 intracameral cefuroxime in preventing ASCRS member survey. J Cataract Refract endophthalmitis after cataract surgery ten-year Surg [Internet]. 2007 Oct [cited 2010 Jun comparative study. J Cataract Refract Surg. 30];33(10):1801-5. Available from: 2010 Feb;36(2):203-7. http://bms.brown.edu/surgery/ophthalmology/r esident/documents/Intracameral_Abx2.pdf
14 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
22. Sobaci G, Uysal Y, Mutlu FM, Bayer A, 31. Sharifi E, Porco TC, Naseri A. Cost- Gungor R, Karagul S. Prophylactic usage of effectiveness analysis of intracameral intracameral cefuroxime in the prevention of cefuroxime use for prophylaxis of postoperative endophthalmitis. International endophthalmitis after cataract surgery. Journal of Ophthalmology. 2009;9(8):1439-43. Ophthalmology. 2009 Oct;116(10):1887-96. 23. Yu-Wai-Man P, Morgan SJ, Hildreth AJ, Steel 32. Canadian Ophthalmological Society Cataract DH, Allen D. Efficacy of intracameral and Surgery Clinical Practice Guideline Expert subconjunctival cefuroxime in preventing Committee. Canadian Ophthalmological endophthalmitis after cataract surgery. J Society evidence-based clinical practice Cataract Refract Surg. 2008 Mar;34(3):447-51. guidelines for cataract surgery in the adult eye. Can J Ophthalmol [Internet]. 2008 Oct [cited 24. Wejde G, Montan P, Lundström M, Stenevi U, 2010 Jun 29];43 Suppl 1:S7-57. Available Thorburn W. Endophthalmitis following from: http://article.pubs.nrc- cataract surgery in Sweden: national cnrc.gc.ca/RPAS/rpv?hm=HInit&calyLang=en prospective survey 1999-2001. Acta g&journal=cjo&volume=43&afpf=i08-133.pdf Ophthalmol Scand. 2005 Feb;83(1):7-10. 33. Scottish Intercollegiate Guidelines Network. 25. Wejde G, Samolov B, Seregard S, Koranyi G, Antibiotic prophylaxis in surgery:a national Montan PG. Risk factors for endophthalmitis clinical guideline [Internet]. Edinburgh: SIGN; following cataract surgery: a retrospective 2008. #104. [cited 2010 Jun 29]. Available case-control study. Journal of Hospital from: http://www.sign.ac.uk/pdf/sign104.pdf Infection. 2005 Nov;61(3):251-6. 34. Ministry of Health Malaysia. Management of 26. Anijeet DR, Palimar P, Peckar CO. post-operative infectious endophthalmitis Intracameral vancomycin following cataract [Internet]. MOH/P/PAK/116.06 (GU). surgery: an eleven-year study. Clin Putrajaya (MY): The Ministry; 2006. 41 p. Ophthalmol [Internet]. 2010 [cited 2010 Jun [cited 2010 Jun 29]. Available from: 2];4:321-6. Available from: http://www.acadmed.org.my/view_file.cfm?fil http://www.ncbi.nlm.nih.gov/pmc/articles/PM eid=258 C2861939/pdf/opth-4-321.pdf 35. American Academy of Ophthalmology 27. Garat M, Moser CL, Martin-Baranera M, (AAO). Cataract in the adult eye: preferred Alonso-Tarrés C, Alvarez-Rubio L. practice pattern [Internet]. San Francisco: Prophylactic intracameral cefazolin after AAO; 2006. [cited 2010 Jun 29]. Available cataract surgery: endophthalmitis risk from: reduction and safety results in a 6-year study. J http://one.aao.org/CE/PracticeGuidelines/PPP_ Cataract Refract Surg. 2009 Apr;35(4):637-42. Content.aspx?cid=a80a87ce-9042-4677-85d7- 28. Romero P, Méndez I, Salvat M, Fernández J, 4b876deed276 Almena M. Intracameral cefazolin as 36. Liesegang TJ. Intracameral antibiotics: prophylaxis against endophthalmitis in cataract questions for the United States based on surgery. J Cataract Refract Surg. 2006 prospective studies. J Cataract Refract Surg. Mar;32(3):438-41. 2008 Mar;34(3):505-9. 29. Arbisser LB. Safety of intracameral 37. Bassler D, Briel M, Montori VM, Lane M, moxifloxacin for prophylaxis of Glasziou P, Zhou Q, et al. Stopping endophthalmitis after cataract surgery. J randomized trials early for benefit and Cataract Refract Surg. 2008 Jul;34(7):1114-20. estimation of treatment effects: systematic 30. Espiritu CR, Caparas VL, Bolinao JG. Safety review and meta-regression analysis. JAMA. of prophylactic intracameral moxifloxacin 2010 Mar 24;303(12):1180-7. 0.5% ophthalmic solution in cataract surgery 38. Lockington D, Flowers H, Young D, Yorston patients. J Cataract Refract Surg. 2007 D. Assessing the accuracy of intracameral Jan;33(1):63-8. antibiotic preparation for use in cataract surgery. J Cataract Refract Surg. 2010 Feb;36(2):286-9.
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39. Villada JR, Vicente U, Javaloy J, Alio JL. 41. Hospital Infection Control Practices Advisory Severe anaphylactic reaction after intracameral Committee (HICPAC). Recommendations for antibiotic administration during cataract preventing the spread of vancomycin surgery. J Cataract Refract Surg. 2005 resistance. Infect Control Hosp Epidemiol. Mar;31(3):620-1. 1995 Feb;16(2):105-13. 40. O'Brien TP, Arshinoff SA, Mah FS. 42. Alcon Canada. Product monograph: Perspectives on antibiotics for postoperative Vigamox® [Internet]. Mississauga: Alcon; endophthalmitis prophylaxis: potential role of 2004. [cited 2010 Jun 30]. Available from: moxifloxacin. J Cataract Refract Surg. 2007 http://www.alcon.ca/pdf/Product_pharma/Prod Oct;33(10):1790-800. uct_pharma_vigamox_eng.pdf
16 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
APPENDIX 1: LITERATURE SEARCH STRATEGY
OVERVIEW Interface: Ovid Databases: EMBASE <1996 to 2010 Week 20> Ovid Medline <1950 to May Week 3> Ovid Medline In-Process & Other Non-Indexed Citations
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 17 Review of Clinical and Cost-Effectiveness and Guidelines
Multi-database Strategy # Searches 1 Vancomycin/ 2 (vancomycin or diatracin or lyphocin or vancamycin or vancocin or vancocine or vancoled or vanococin or einecs 215-772-6 or hsdb 3262 or vancomicina or vancomycine or vancomycinum).ti,ab. 3 Cefazolin/ 4 (cefazolin or brn 4169371 or brn4169371 or cefazolina or cefazolinum or cephazolidin or cephazoline or elzogram or ancef or ansef or cefacidal or cefamezin or cefamezine or cefazoline or celmetin or cephamezin or cephazolin or kefazolin or kefzol or kezolin or kurgan or reflin or totacef or vulmizolin or zolicef).ti,ab. 5 Cefuroxime/ 6 (cefuroxime or brn 5783190 or brn5783190 or biofuroksym or cefuril or cefuroxim or cefuroxime or cefuroximo or cefuroximum or sharox or altacef or anaptivan or biocefal or cefoxurime or cefumax or ceplus or ceroxime or curocef or curoxim or curoxima or curoxime or kefazol or kefurox or kesint or ketocef or polixima or sn 107 or ultroxim or zinacef or zinocef).ti,ab. 7 Moxifloxacin/ use emef 8 Quinolines/ use prmz 9 Fluoroquinolones/ use prmz 10 (moxifloxacin or actira or avalox or avelox or bay 12 8039 or bay 128039 or bay128039 or octegra or proflox or vigamox or ccris 8690 or ccris8690).ti,ab. 11 Gatifloxacin/ use emef 12 (Gatifloxacin or am 1155 or am1155 or bms 206584 or bms206584 or bonoq or cg 5501 or cg5501 or gatiflo or tequin or zymar or pd 135432 or gatispan or gatiquin or gatilox or gatiflo or gaity).ti,ab. 13 (1404-90-6 or 151096-09-2 or 112811-59-3 or 180200-66-2 or 25953-19-9 or 55268-75-2 or 27164-46-1 or 56238-63-2 or 1404-93-9).rn. 14 or/1-13 15 Anti-Bacterial Agents/ use prmz 16 Antibiotic Prophylaxis/ 17 antibiotic agent/ use emef 18 ((Anti Bacterial or Antibacterial or antibiotic or Bacteriocidal or Bacteriocides or Anti Mycobacterial or Antimycobacterial) adj3 (Agents or agent or Premedication or premedications or prophylaxis or medication or medications or drug or drugs or injection or bolus or injections or therapy or therapies or treatment or treatments or pharmaceutical or pharmaceuticals)).ti,ab. 19 antibiotics.ti,ab. 20 or/15-19 21 Endophthalmitis/ 22 (endophthalmitis or endophthalmitides or ophthalmia or ophthalmias or Panophthalmitis).ti,ab. 23 ((eye or intraocular or internal coats or internal coat or aqueous humor or aqueous humour or vitreous humor or vitreous humour) adj3 (swelling or swell or swelled or inflammation or inflammatory or inflamed or irritation or irritated)).ti,ab. 24 or/21-23 25 Intraocular injections/ use prmz 26 Anterior Chamber/de use prmz 27 intracameral drug administration/ use emef
18 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
Multi-database Strategy # Searches 28 (intracameral* or intra cameral or intravitreal or intra viteral or intravitreous).ti,ab. 29 ((inject* or bolus or administered or administering or administer or administration) adj3 (chamber or chambers or eye or eyes or vitreous or periocular or intra ocular or intraocular)).ti,ab. 30 or/25-29 31 14 and 24 and 30 32 20 and 24 and 30 33 (14 or 20) and 30 34 remove duplicates from 33 35 limit 34 to english language 36 limit 35 to yr="2005 -Current" 37 31 or 32 38 remove duplicates from 37 39 limit 38 to english language 40 limit 39 to yr="2005 -Current" 41 exp clinical pathway/ 42 exp clinical protocol/ 43 exp consensus/ 44 exp consensus development conference/ 45 exp consensus development conferences as topic/ 46 critical pathways/ 47 exp guideline/ 48 guidelines as topic/ 49 exp practice guideline/ 50 practice guidelines as topic/ 51 health planning guidelines/ 52 exp treatment guidelines/ 53 (guideline or practice guideline or consensus development conference or consensus development conference, NIH).pt. 54 (position statement* or policy statement* or practice parameter* or best practice*).ti,ab. 55 (standards or guideline or guidelines).ti,ab. 56 ((practice or treatment) adj guideline*).ab. 57 (CPG or CPGs).ti. 58 (CPG or CPGs).ab. /freq=2 59 consensus*.ti. 60 consensus*.ab. /freq=2 61 ((critical or clinical or practice) adj2 (path or paths or pathway or pathways or protocol*)).ti,ab. 62 recommendat*.ti. 63 (care adj2 (standard or path or paths or pathway or pathways or map or maps or plan or plans)).ti,ab. 64 (algorithm* adj2 (screening or examination or test or tested or testing or assessment* or diagnosis or diagnoses or diagnosed or diagnosing)).ti,ab. 65 (algorithm* adj2 (pharmacotherap* or chemotherap* or chemotreatment* or therap* or treatment*
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 19 Review of Clinical and Cost-Effectiveness and Guidelines
Multi-database Strategy # Searches or intervention*)).ti,ab. 66 or/41-65 67 36 and 66 OTHER DATABASES PubMed Same MeSH, keywords, limits, and study types used as per MEDLINE search, with appropriate syntax used. The Cochrane Same MeSH, keywords, and date limits used as per MEDLINE search, excluding Library study types and human restrictions. Syntax adjusted for The Cochrane Library Issue 5, 2010 databases.
Grey Literature
Dates for search: May 2010 Keywords: Included terms for intracameral, endophthalmitis, vancomycin, cefazolin, cefuroxime, Moxifloxacin, gatifloxacin Limits: Publication years 2005-present
The following sections of the CADTH grey literature checklist, Grey matters: a practical tool for evidence-based searching (http://www.cadth.ca/index.php/en/cadth/products/grey-matters) were searched: Health Technology Assessment Agencies Health Economic Clinical Practice Guidelines Databases (free) Internet Search Advisories and Warnings Clinical Trial Listings Statistics/Prevalence.
20 Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: Review of Clinical and Cost-Effectiveness and Guidelines
APPENDIX 2: SELECTION OF PUBLICATIONS
334 citations identified from electronic literature search and screened
283 citations excluded
51 potentially relevant articles retrieved for scrutiny (full text, if available)
4 potentially relevant reports retrieved from other sources (grey literature, handsearch)
55 potentially relevant reports
35 reports excluded: inappropriate study design (10) inappropriate intervention (6) inappropriate population (1) inappropriate outcomes (8) other (editorial, preliminary results) (10).
20 reports included in review
Intracameral Antibiotics for the Prevention of Endophthalmitis Post-Cataract Surgery: 21 Review of Clinical and Cost-Effectiveness and Guidelines