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The Role of Topical Antibiotic Prophylaxis to Prevent Endophthalmitis After Intravitreal Injection

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The Role of Topical Antibiotic Prophylaxis to Prevent Endophthalmitis After Intravitreal Injection The Role of Topical Antibiotic Prophylaxis to Prevent Endophthalmitis after Intravitreal Injection Philip Storey, MD, MPH,1 Michael Dollin, MD,1 John Pitcher, MD,1 Sahitya Reddy, BA,2 Joseph Vojtko, BA,2 James Vander, MD,1 Jason Hsu, MD,1 Sunir J. Garg, MD,1for the Post-Injection Endophthalmitis Study Team* Objective: To compare the incidence of endophthalmitis after intravitreal injection with and without topical postinjection antibiotic prophylaxis. Design: Retrospective case-control study. Participants: All patients treated with intravitreal injection of ranibizumab, bevacizumab, or aflibercept for a variety of retinal vascular diseases at a single, large retina practice between January 1, 2009, and October 1, 2012, were included. Methods: The total numbers of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and from an infection log. All cases of endophthalmitis were confirmed with chart review. A 28-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 9-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded to allow for the conversion of antibiotic prescription practices. Main Outcome Measures: Incidence of endophthalmitis, visual acuity outcomes, and microbial spectrum. Results: During the study period, a total of 117 171 intravitreal injections were performed (57 654 injections during the topical antibiotic period, 24 617 during the transition period, and 34 900 during the no-antibiotic period), with a total of 44 cases of suspected endophthalmitis (0.038%; 1 in 2663 injections), 17 of which showed culture-positive results (0.015%; 1 in 6892 injections). During the 28-month topical antibiotic period, there were 28 cases of suspected endophthalmitis (0.049%; 1 in 2059 injections), 10 of which showed culture- positive results (0.017%; 1 in 5765 injections). During the 9-month no-antibiotic period, there were 11 cases of suspected endophthalmitis (0.032%; 1 in 3173 injections), 4 of which showed culture-positive results (0.011%; 1 in 8725 injections). Topical antibiotic use was associated with a trend toward increased risk of suspected endophthalmitis (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.77e3.10) and culture-positive endoph- thalmitis (OR, 1.51; 95% CI, 0.47e4.83). Conclusions: The incidence of endophthalmitis after intravitreal injection is low. Using postinjection topical antibiotic drops does not reduce the risk of endophthalmitis developing and is associated with a trend toward higher incidence of endophthalmitis. Ophthalmology 2014;121:283-289 ª 2014 by the American Academy of Ophthalmology. *Group members listed online in Appendix 1 (available at http://aaojournal.org). The use of intravitreal injections for eye disease has increased demonstrated a reduction in postprocedure or postinjection dramatically because of the efficacy of several medications, endophthalmitis through use of prophylactic antibiotic including steroids and antievascular endothelial growth drops.4e6 Recent evidence suggests that topical antibiotics factor (VEGF) agents. Although uncommon, postinjection may even be harmful by increasing antibiotic-resistant endophthalmitis can cause significant ocular morbidity.1 bacterial strains7,8 and may increase the risk of endoph- Prophylactic measures, including the use of various topical thalmitis.9 The previous studies were relatively small and may antibiotics, have been used to reduce the incidence of not have been powered adequately to detect a difference in endophthalmitis. Topical antibiotics long have been endophthalmitis incidence. Many physicians continue to the standard of care after ocular surgery, and this prescribe antibiotics after intravitreal injection.10 This study practice was carried over to ocular injections. Although evaluates the role of topical antibiotic prophylaxis after topical antibiotics reduce conjunctival bacterial growth2 intravitreal injection of anti-VEGF agents as well as the and may have a possible synergistic effect when combined microbial spectrum after injection in the largest series of with povidoneeiodine,3 no randomized trials have intravitreal injections to date. Ó 2014 by the American Academy of Ophthalmology ISSN 0161-6420/14/$ - see front matter 283 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2013.08.037 Ophthalmology Volume 121, Number 1, January 2014 Methods Transition Period Overview Before May 2011, all patients were prescribed postinjection topical antibiotics to use 4 times daily for 4 days. As early as June 2011, This single-center retrospective, comparative, case-control study some physicians stopped using antibiotic prophylaxis, and on was approved by the Wills Eye Institute Institutional Review September 1, 2011, retinal physicians practicing at Wills Eye Board. As part of an ongoing infection surveillance program, the Institute adopted a practice-wide policy stopping use of post- authors prospectively recorded endophthalmitis cases occurring injection topical antibiotics. We considered May 1, 2011, through after intravitreal injection secondary to intravitreal injection of December 31, 2011, to be a transition period during which bevacizumab (Genentech, South San Francisco, CA), ranibizumab physicians and patients changed prophylaxis strategies. A review (Genentech), triamcinolone, or aflibercept (Regeneron, Tarrytown, of all endophthalmitis cases confirmed that all patients from NY). The endophthalmitis log and billing records were used to January 1, 2009, through April 30, 2011, received postinjection identify retrospectively all cases of endophthalmitis treated with antibiotics, whereas all patients from January 1, 2012, through vitreous tap and injection between January 1, 2009, and October 1, October 1, 2012, did not receive postinjection antibiotics. We did 2012, at a single retina practice. The total number of intravitreal not include injections or endophthalmitis cases during the transi- injections performed during the period was determined from billing tion period in our analysis of endophthalmitis incidence. We did, data. Charts of all patients who were treated for endophthalmitis however, include transition period cases in our analysis of visual were reviewed. Recorded data included date of causative injection; outcomes and bacterial spectrum. date of tap and injection; visual acuity before causative injection, at time of tap and injection, at 3 months after the procedure, and at 6 Outcomes months after the procedure; type of injection; lot number; under- lying diagnosis; culture results; and antibiotic resistance. The primary outcome was occurrence of endophthalmitis after intravitreal injection. Secondary outcomes were microbial spec- Inclusion and Exclusion Criteria trum and clinical outcomes including return to baseline visual acuity (plus or minus 2 lines of Snellen acuity), final visual acuity All eyes with presumed infectious endophthalmitis following of counting fingers or worse, and the presence of pain, vitreitis, or intravitreal injection of an anti-VEGF medication were included. fi hypopyon on initial presentation. Endophthalmitis results were Endophthalmitis was de ned as any case in which clinical suspi- considered culture positive if there were positive gram stain or cion was high enough to warrant tap and inject (typically decreased positive growth results on culture plates. Clinical variables were visual acuity, pain, 2þ anterior chamber cell, and vitreitis). Eyes fl analyzed using Excel (Microsoft, Redmond, WA), and statistical with presumed in ammatory endophthalmitis treated primarily analysis was performed using GraphPad Software (GraphPad, La with topical steroids without tap-and-inject treatment were Jolla, CA). excluded from analysis. Injection Technique Results All injections were performed in office-based settings. Eyes were prepped in a standardized method with a topical nonviscous Effect of Antibiotics anesthetic, one topical antibiotic drop during the initial 28 months of the study period, topical 5% povidoneeiodine (Betadine 5%; Between January 1, 2009, and October 1, 2012, a total of 117 171 Alcon Labs, Fort Worth, TX), followed by another drop of topical intravitreal injections (71 791 ranibizumab, 44 007 bevacizumab, fl anesthetic and another drop of 5% povidoneeiodine before injec- and 1373 a ibercept) were performed, and a total of 44 patients tion. Rarely, a subconjunctival 2% lidocaine injection was with suspected endophthalmitis after intravitreal injection under- administered before the second administration of topical anesthetic went vitreous tap with antibiotic injection (0.038%; 1 in 2663 and 5% povidoneeiodine. A sterile drape and eyelash preparation injections). Seventeen cases showed culture-positive results were not used. Injection with a 30- or 31-gauge needle was per- (0.015%; 1 in 6892 injections). Overall rates of suspected formed 3.5 to 4.0 mm from the limbus. Physicians individually endophthalmitis were 24 in 71 791 injections for ranibizumab determined use of a bladed lid speculum, conjunctival displace- (0.033%; 1 in 2991 injections); 20 in 44 007 injections for bev- ment before injection, and superior versus inferior injection site. acizumab (0.045%; 1 in 2200 injections); and 0 in 1373 injections for aflibercept. Overall rates of culture-positive endophthalmitis Endophthalmitis Treatment Protocol were 12 in 71 791 for ranibizumab
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