Association Between Repeated Prophylactic Antimicrobial Eye Drop Use and Reduced Antimicrobial Susceptibility in Conjunctival and Nasal Commensal Bacteria.

Background/Objectives: The objective of this study was to clarify changes in the antimicrobial susceptibility of commensal bacteria in the conjunctival sac and nasal cavity associated with repeated use of prophylactic antimicrobial eye drops during intravitreal anti-vascular endothelial growth factor injections. Methods: Patients were divided into Group A, comprising 21 patients before the first use of prophylactic antimicrobial eye drops, and Group B, comprising 26 patients after receiving 20 or more injections. Minimum inhibitory concentration and susceptibility testing were performed on bacteria isolated from the conjunctival sac and nasal cavity using cefmenoxime, ceftazidime, levofloxacin, gatifloxacin, and moxifloxacin. Genetic mutations in the quinolone resistance-determining region of Staphylococcus epidermidis, phylogenetic relationships, and the nasal microbiome were also analyzed. Results:Corynebacterium, S. epidermidis, and Cutibacterium acnes were detected in both sites. In Group B, S. epidermidis and Corynebacterium showed reduced susceptibility to quinolones, whereas C. acnes did not. GyrA_S84 and ParC_S80 mutation rates in S. epidermidis were higher in Group B than in Group A. Among the patients with quinolone-resistant S. epidermidis isolated from both sites, 4 out of 10 patients had paired conjunctival and nasal isolates with the same ST type, suggesting that isolates from the two anatomical sites may be genetically related. The nasal microbiome α- and β-diversity did not differ significantly between groups, although exploratory LEfSe analysis suggested candidate taxon-level differences. Conclusions: Repeated prophylactic use of antibiotic eye drops was associated with reduced susceptibility in both the conjunctival sac and nasal cavity.