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

从眼内炎患者体内分离出的甲氧西林敏感表皮葡萄球菌菌株中出现了对8-甲氧基氟喹诺酮类药物的耐药性

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Abstract

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.

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