Emerging 8-Methoxyfluoroquinolone Resistance among Methicillin-Susceptible Staphylococcus epidermidis Isolates Recovered from Patients with Endophthalmitis

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 g/ml) to gatifloxacin and moxifloxacin was documented for 46.7% of the MSSE isolates, and low-level resistance (MIC, 2 to 4 g/ml) was determined for 53.3%. The MICs for ciprofloxacin, levofloxacin, and ofloxacin were >32 g/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.

Correlation between clinical data and antibiotic resistance in coagulase-negative Staphylococcus species isolated from 68 patients with acute post-cataract endophthalmitis

“…All previously published studies were conducted in the USA [4,6,7,14,15] or India [16]. Our case series was highly homogeneous for the microorganisms involved (CNS strains, including 82.4% S. epidermidis), the type of surgery (cataract), and the absence of cefuroxime prophylaxis.…”

Identification of Major Sequence Types among Multidrug-Resistant Staphylococcus epidermidis Strains Isolated from Infected Eyes and Healthy Conjunctiva

“…We like other workers also found a mutation in gyrA (Ser84 → F/Y) in S . epidermidis strains that showed a significant association with high level of resistance to fluoroquinolones (Yamada et al, 2008 ; Betanzos-Cabrera et al, 2009 ; Bispo et al, 2013 ). In addition to the reported mutation in parC (Ser80 → F/Y and D → A), we found two novel mutations (D84 → C and V82 → L).…”

Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris

“…Substitution(s) in the QRDR of DNA gyrase (gyrA) and DNA topoisomerase IV (parC) is the predominant resistance determinant for S. epidermidis. 16 Hence, the QRDR sequences of S. epidermidis strains were determined, and quinolone-resistant strains were classified into four groups ( Table 2). The strains that were susceptible to all tested quinolones and lacked amino acid mutation in the QRDR were classified into group Sus.…”