Abstract
Objectives: To investigate the molecular events involved in the development of quinolone resistance in enterococci. Methods: Clinical isolates of Enterococcus faecium and Enterococcus faecalis were exposed to inhibitory and subinhibitory concentrations of DX-619, ciprofloxacin, levofloxacin, gatifloxacin and moxifloxacin. Mutational frequencies were calculated and susceptibility changes were determined. The quinolone resistance determining regions (QRDRs) of gyrA and parC in less-susceptible mutants were amplified by PCR and sequenced. Results: Single-step mutants of E. faecalis and E. faecium were selected with all drugs. There were no differences in the frequencies of mutant selection among drugs, with frequencies ranging from 101-5 to 10-8. All single-step mutants were inhibited by 0.03-1 mg/L DX-619, 0.25-8 mg/L moxifloxacin, 0.5-8 mg/L gatifloxacin, 1-16 mg/L levofloxacin and 1-32 mg/L ciprofloxacin. No QRDR changes were observed in single-step mutants. Less-susceptible mutants selected after five passages on agar containing subinhibitory quinolone concentrations were inhibited by 0.12-8 mg/L DX-619, 1-64 mg/L moxifloxacin, 2-64 mg/L gatifloxacin and 2-128 mg/L levofloxacin and ciprofloxacin. QRDR changes were detected in only 9 of the 20 fifth-passage mutants, suggesting that mutations outside the purported QRDRs and/or other resistance mechanisms were also involved. Conclusions: The relatively high frequencies at which single-step mutants were selected with all drugs indicate that caution is necessary if quinolones are to be considered for monotherapy of serious enterococcal infections. DX-619, the most potent quinolone, may have potential as an anti-enterococcal agent if sufficient concentrations can be safely attained in vivo.
Original language | English (US) |
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Pages (from-to) | 1268-1273 |
Number of pages | 6 |
Journal | Journal of Antimicrobial Chemotherapy |
Volume | 58 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2006 |
All Science Journal Classification (ASJC) codes
- Pharmacology
- Microbiology (medical)
- Infectious Diseases
- Pharmacology (medical)