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2024 OMIG Abstract

Clinical and Genomic Profile of Antimicrobial Resistance Among Bacterial Keratitis Isolates at Johns Hopkins

Nakul S. Shekhawat¹, Kamini Reddy¹, Patricia J. Simner<sup>2

1</sup>Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland;
²Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Purpose: To characterize clinical and genomic profiles of antimicrobial resistance (AMR) among bacterial keratitis isolates at Johns Hopkins Medicine.

Methods: Bacterial isolates were obtained from eyes with culture-confirmed bacterial keratitis. Isolates were evaluated for clinical AMR to commonly used ophthalmic antibiotics using minimum inhibitory concentration (MIC) testing. For each isolate and antibiotic combination tested, MIC testing results were categorized as susceptible, intermediate, or resistant. All isolates were also submitted for whole genome sequencing (WGS) to characterize presence or absence of AMR genes. We examined the most common bacterial species in the overall study population, prevalence of clinical AMR within each bacterial species, and the most commonly present AMR genes within each species.

Results: Out of 92 bacterial keratitis isolates obtained from April 13, 2023 to April 4, 2024, the majority were Gram positive bacteria (N=64, 69.6%) while a smaller proportion were Gram negative (N=28, 30.4%). The most common organisms were coagulase-negative staphylococci (N=37, 40.2%), Staphylococcus aureus (N=17, 18.5%), Pseudomonas aeruginosa (N=11, 12.0%), Corynebacterium spp. (N=5, 5.4%), and Escherichia coli (N=4, 4.4%). On MIC testing, Gram positive isolates were most commonly resistant to erythromycin (N=29, 45.3%), oxacillin (N=19, 29.7%), levofloxacin (N=10, 15.6%), and moxifloxacin (N=6, 9.4%) but all tested Gram positive isolates were susceptible to vancomycin (N=58 of 58, 100%). Gram negative isolates tested for AMR were most commonly resistant to fluoroquinolones including ciprofloxacin (N=4, 14.3%), levofloxacin (N=3, 10.7%), and moxifloxacin (N=2, 7.1%) with only a single tested isolate resistant to tobramycin (N=1, 3.6%). WGS of Coagulase-negative staphylococci isolates showed that the most common AMR genes were sdrM (N=25, 67.6%), norC (N=24, 64.9%), ermC (N=23, 62.2%), mgrA (N=23, 62.2%), fosB (N=21, 56.8%), dfrC (N=21, 56.8%), blaZ (N=20, 54.0%), norA (N=20, 54.0%), blaI (N=20, 54.0%), and mphC (N=15, 40.5%). Among Pseudomonas aeruginosa isolates, WGS showed the most common AMR genes were for efflux pump systems such as MexA, MexB, MexC, MexD, MexE, OpmB, OprJ, OprM, OpmH, and OpmD (all N=7, 73%).

Conclusions: Gram positive organisms caused a majority of bacterial keratitis and nearly 50% of Gram positive isolates showed macrolide resistance, raising concern that the widespread use of erythromycin ointment for infection prophylaxis and treatment should be reconsidered. Coagulase-negative staphylococci were by far the most commonly implicated species, with a high proportion of isolates containing genes such as ermC and mph(A-C) that have been associated with macrolide resistance.


Disclosure:

N (KR); C (NS, KeraLink International, Recordati Rare Diseases; Simner, OpGen Inc., bioMérieux Inc., Qiagen, BD Diagnostics, Shionogi Inc., GeneCapture, Inoviva Specialty Therapeutics Inc., Day Zero Diagnostics, Next Gen Diagnostics); S (NS, NIH K23EY032988, Wilmer Eye Institute Pooled Professor Fund, Research to Prevent Blindness, Stephen F Raab and Mariellen Brickley-Raab Family Rising Professorship; Simner, Affinity Biosensors,T2 Diagnostics).