Ophthalmic Antibiotics and Antimicrobial Resistance: A Randomized, Controlled Study of Patients Undergoing Intravitreal Injections

Abstract

Purpose: : To determine whether repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics promotes antimicrobial resistance in patients undergoing intravitreal injections for choroidal neovascularization (CNV).

Methods: : This was a prospective, randomized, controlled, clinical trial involving 48 eyes of 24 patients undergoing unilateral intravitreal injections for CNV. Subjects were randomly assigned to 1 of 4 ophthalmic antibiotics (azithromycin 1%, ofloxacin 0.3%, gatifloxacin 0.3%, moxifloxacin 0.5%) to be used after each injection in the treatment eye only. Bilateral conjunctival and unilateral nasopharyngeal cultures on the treatment side were taken at baseline and repeated at each subsequent visit for 1 year. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Genomic analysis of bacteria strains was performed using pulse-field gel electrophoresis. Main outcome measures were changes in antibiotic susceptibility patterns of conjunctival and nasopharyngeal flora over time and emergence of resistant strains.

Results: : Eight subjects (33%) grew Staphylococcus aureus from the nasopharynx and one subject (13%) showed emergence of a resistant strain. Coagulase-negative staphylococci(CNS) cultured from eyes repeatedly exposed to fluoroquinolone antibiotics demonstrated significantly increased rates of resistance to 3^rd and 4^th generation fluoroquinolones compared to untreated eyes. Resistance to ofloxacin and levofloxacin was roughly 85% (P = 0.003) and resistance to gatifloxacin and moxifloxacin approached 67% (P = 0.009) and 77% (P < 0.001) respectively. In contrast, CNS isolated from eyes repeatedly exposed to azithromycin demonstrated significantly increased resistance (94%) to erythromycin and azithromycin when compared to control eyes (P = 0.009) and decreased resistance to 3^rd (P < 0.03) and 4^th (P < 0.001) generation fluoroquinolones when compared to eyes exposed to fluoroquinolones.

Conclusions: : Repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics selects for resistant strains.

Clinical Trial: : http://www.clinicaltrials.gov NCT00831961

Keywords: endophthalmitis • age-related macular degeneration • antibiotics/antifungals/antiparasitics