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

doi:10.1016/j.ophtha.2013.08.037

Ophthalmology

Volume 121, Issue 1, January 2014, Pages 283-289

Presented at: Wills Eye Hospital Annual Conference, 2013; Retina Society Annual Meeting, 2013; and as a poster at: Association for Research in Vision and Ophthalmology Annual Meeting, 2013; and American Academy of Ophthalmology Annual Meeting, November 2013, New Orleans, LA.

https://doi.org/10.1016/j.ophtha.2013.08.037 Get rights and content

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], 0.77–3.10) and culture-positive endophthalmitis (OR, 1.51; 95% CI, 0.47–4.83).

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.

Section snippets

Overview

This single-center retrospective, comparative, case-control study was approved by the Wills Eye Institute Institutional Review Board. As part of an ongoing infection surveillance program, the authors prospectively recorded endophthalmitis cases occurring after intravitreal injection secondary to intravitreal injection of bevacizumab (Genentech, South San Francisco, CA), ranibizumab (Genentech), triamcinolone, or aflibercept (Regeneron, Tarrytown, NY). The endophthalmitis log and billing records

Effect of Antibiotics

Between January 1, 2009, and October 1, 2012, a total of 117 171 intravitreal injections (71 791 ranibizumab, 44 007 bevacizumab, and 1373 aflibercept) were performed, and a total of 44 patients with suspected endophthalmitis after intravitreal injection underwent vitreous tap with antibiotic injection (0.038%; 1 in 2663 injections). Seventeen cases showed culture-positive results (0.015%; 1 in 6892 injections). Overall rates of suspected endophthalmitis were 24 in 71 791 injections for

Discussion

In this single-center, retrospective, case-control study, we compared endophthalmitis incidence during a 28-month period when topical antibiotics were prescribed with that during a 9-month period when no antibiotics were prescribed, separated by an 8-month transition period as providers and patients altered prophylaxis practices. We found that postinjection topical antibiotics did not decrease endophthalmitis incidence and that the clinical presentation and visual outcomes of patients with

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To determine the risk of endophthalmitis in eyes undergoing intravitreal injections (IVIs) of anti-VEGF based on cumulative number of injections per eye.
Retrospective cohort study.
Patients from a single center undergoing IVIs of ranibizumab, aflibercept, or bevacizumab.
Eyes were divided into quartiles based on injection number causative of endophthalmitis between January 1, 2011, and June 1, 2022.
Interquartile clinical outcomes and cumulative risk of endophthalmitis per injection and per eye.
A total of 43 393 eyes received 652 421 anti-VEGF injections resulting in 231 endophthalmitis cases (0.035% per injection, 1 in 2857), of which 215 were included. The cumulative endophthalmitis risk increased from 0.0018% (1 in 55 556) after 1 injection to 0.013% (1 in 7692) after 11 injections (0.0012 percentage point change), versus 0.014% (1 in 7143) after 12 injections to 0.025% (1 in 4000) after 35 injections (0.00049 percentage point change), versus 0.025% (1 in 4000) after 36 injections to 0.031% (1 in 3226) after 66 injections (0.00017 percentage point change), versus 0.031% (1 in 3226) after 63 injections to 0.033% (1 in 3030) after 126 injections (0.000042 percentage point change) (P < 0.001). Likewise, the cumulative endophthalmitis risk per eye increased from 0.028% (1 in 3571) to 0.20% (1 in 500) between injections 1 and 11 (0.018 percentage point change), versus 0.21% (1 in 476) to 0.38% (1 in 263) between injections 12 and 35 (0.0075 percentage point change), versus 0.38% (1 in 263) to 0.46% (1 in 217) between injections 36 and 66 (0.0026 percentage point change), versus 0.46% (1 in 217) to 0.50% (1 in 200) between injections 67 and 126 (0.00063 percentage point change) (P < 0.001).
The cumulative endophthalmitis risk per injection and per eye increased with greater number of injections received but appeared to do so at a higher rate during earlier injections and at a lower rate further into the treatment course.
Proprietary or commercial disclosure may be found after the references.
The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti–Vascular Endothelial Growth Factor Injections
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Routine use of face masks for patients and physicians during intravitreal anti–vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE).
Retrospective, multicenter, comparative cohort study.
Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers.
Cases were divided into a “no face mask” group if no face masks were worn by the physician or patient during intravitreal injections or a “universal face mask” group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections.
Rate of endophthalmitis, microbial spectrum, and visual acuity (VA).
Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the “no face mask” group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the “universal face mask” group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51–1.18; P = 0.097). In the “no face mask” group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the “universal face mask” group (OR, 0.46; 95% CI, 0.22–0.99; P = 0.041). Three cases of oral flora–associated endophthalmitis occurred in the “no face mask” group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the “universal face mask” group (P = 0.645). Patients presented a mean (range) 4.9 (1–30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for “no face mask” group compared with 1.65 (~20/900) for the “universal face mask” group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764).
In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.
A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis
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Endophthalmitis is an infectious disease that affects the entire eye spreading to the internal retinal layers and the vitreous and causes severe sight-threatening conditions. Current treatment strategies rely on intraocular injections of antibiotics that are invasive, may lead to procedural complications and, ultimately, blindness. In this study, we developed a non-invasive strategy as an eyedrop containing nanoparticle-based dual-drug delivery system in which the hydrophobic poly-L-lactide core was loaded with azithromycin or triamcinolone acetonide, and the hydrophilic shell was made of chitosan. The developed nanoparticles were ~200–250 nm in size, spherical in shape, moderately hydrophilic, lysozyme tolerant, cytocompatible, and hemocompatible. Application of these chitosan-coated nanoparticles as eye drops to C57BL/6 mice showed higher bioavailability in choroid and retina when compared to the uncoated nanoparticles. The delivery system showed sustained release of drug for 300 h and exhibited antimicrobial effects against Gram-positive and Gram-negative bacteria and anti-inflammatory effects on activated microglial cells. Interestingly, the combination of the nanoparticles loaded with azithromycin and the nanoparticles loaded with triamcinolone acetonide acted synergistically as compared to either of the nanoparticles/drugs alone. Overall, the developed dual-drug delivery system is non-invasive, has antimicrobial and anti-inflammatory effects, and shows potential as an eye drop formulation against endophthalmitis.
Outcomes of Infectious Endophthalmitis in Patients with Systemic Antibiotic Allergies to Penicillins, Cephalosporins, or Vancomycin
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The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration.
Single-center, retrospective cohort study.
All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes.
Retrospective chart review.
Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit.
Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection.
There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use.
Aqueous Chlorhexidine Compared with Povidone-Iodine as Ocular Antisepsis before Intravitreal Injection: A Randomized Clinical Trial
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Citation Excerpt :
Iodine is the active antimicrobial ingredient in PI; acts by denaturing key proteins, fatty acids, and nucleic acids; and has a broad spectrum of activity.12 Rates of endophthalmitis after IVI with anti-VEGF agents are low when using PI, with a range of 0.01% to 0.26%.13–16 However, physicians may avoid PI use in patients with self-reported “allergies” to iodinated intravenous contrast or seafood due to concerns about cross-reactivity.
Topical povidone-iodine (PI) is widely used as an ocular surface antiseptic for intravitreal injections (IVIs). Although PI is generally well tolerated, it can be associated with significant ocular irritation. Aqueous chlorhexidine (AqCHX) has been described as a possibly better tolerated antimicrobial for ophthalmic procedures. We compared patient pain scores, ocular surface characteristics, and antimicrobial efficacy between PI 5% and AqCHX 0.1% during IVIs.
Prospective single-center, randomized clinical trial.
Patients receiving same-day bilateral intravitreal anti–vascular endothelial growth factor (VEGF) injections.
Each patient had 1 eye randomized to PI or AqCHX, and the second eye received the other agent. Both eyes received topical proparacaine 0.5%.
After IVIs, participants rated their pain (Wong-Baker, scale 0–10) for each eye 1 minute after PI or AqCHX instillation and 1 day after the procedure. Each eye was assessed using a standardized quantitative grading system of corneal epitheliopathy (ocular staining score). Microbial swab cultures of the conjunctiva both before instillation of topical antisepsis and 10 minutes after IVIs were given.
A total of 100 eyes of 50 patients were included. The mean patient age was 68 years (range, 39–92), and 30 of 50 (60%) were male. Compared with AqCHX, eyes receiving PI had a greater mean pain score immediately after injection (1.44 vs. 0.44, P < 0.001) but not on postprocedure day 1 (1.04 vs. 0.48, P = 0.06). Eyes that received PI had a higher ocular staining score indicating worse corneal epitheliopathy (4.22 vs. 3.10, P < 0.001). There was no difference in rates of positive microbial cultures between groups. There was no difference in rates of adverse events between groups (P = 0.99), and no cases of endophthalmitis occurred.
Povidone-iodine demonstrated greater ocular surface discomfort and corneal epitheliopathy compared with AqCHX during same-day bilateral IVIs. The 2 agents otherwise demonstrated no difference in positive microbial cultures or adverse events. Aqueous chlorhexidine may be a better tolerated alternative to PI for antimicrobial prophylaxis during IVIs for some patients.
Disease quiescence in endophthalmitis patients treated with anti-VEGF injections for retinal pathologies
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: *Group members listed online in Appendix 1 (available at http://aaojournal.org).

: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

^∗: A full listing of The Post-Injection Endophthalmitis (PIE) Study Team is available online in appendix 1 (http://aaojournal.org). All members of the PIE Study Team are from The Retina Service of Wills Eye Hospital, MidAtlantic Retina, Thomas Jefferson University, Philadelphia, PA.

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Original articleThe Role of Topical Antibiotic Prophylaxis to Prevent Endophthalmitis after Intravitreal Injection

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Overview

Effect of Antibiotics

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Lancet Infect Dis

Original article
The Role of Topical Antibiotic Prophylaxis to Prevent Endophthalmitis after Intravitreal Injection