Emerging 8-methoxyfluoroquinolone resistance among methicillin-susceptible Staphylococcus epidermidis isolates recovered from patients with endophthalmitis

Fluoroquinolones remain the most commonly used antimicrobials for the prevention and management of bacterial endophthalmitis. Coagulase-negative staphylococci are the most frequently recovered pathogens. Increasing resistance among this group has paralleled the presence of methicillin resistance. From 2005 to 2010, we recovered 38 methicillin-susceptible Staphylococcus epidermidis (MSSE) isolates from endophthalmitis patients at our institute, including 15 (39.5%) isolates resistant to gatifloxacin and moxifloxacin, members of the C-8-methoxyfluoroquinolones family. Mutations in the quinolone resistance-determining regions (QRDR) of gyrA and parC were determined and correlated with fluoroquinolone MICs based on Etests of these 15 MSSE isolates. High-level resistance (MIC,>32 μg/ml) to gatifloxacin and moxifloxacin was documented for 46.7% of the MSSE isolates, and low-level resistance (MIC, 2 to 4 μg/ml) was determined for 53.3%. The MICs for ciprofloxacin, levofloxacin, and ofloxacin were>32 μg/ml for all isolates. The amino acid substitution Ser84Phe in gyrA was found among all isolates. A second mutation in gyrA (Glu88Lys) resulted in high-level resistance to moxifloxacin and gatifloxacin. Almost all (92.8%) isolates presented double point mutations in the parC gene at codons 80 and 84 with different combinations. Eighty-seven percent of the patients had prior exposure to topical 8-methoxyfluoroquinolones. Prior exposure to the 8-methoxyfluoroquinolones may contribute to the selection of MSSE strains containing multiple mutations in the QRDRs of gyrA and parC that results in low- and high-level resistance to these agents.