In vitro activity of delafloxacin against enterococcal isolates from male urinary tract infections and genetic determinants of resistance
Abstract
ABSTRACT Delafloxacin (DLX) is a novel fluoroquinolone (FQ) with enhanced activity against gram-positive bacteria and under acidic conditions. Since the pH of urine is usually acidic, DLX could be an alternative to current drugs for urinary tract infections (UTIs), especially in male patients, for whom good prostatic tissue penetration is required. The aim of this study was to evaluate in vitro the activity of DLX and FQ comparators against Enterococcus faecalis and Enterococcus faecium, to characterize the resistance pattern of E. faecalis against FQs, and to decipher the genetic basis of resistance among in vitro-selected mutants. DLX showed higher in vitro activity than both levofloxacin and moxifloxacin against E. faecalis, with an MIC50 of 0.06 mg/L, which was 16- and 4-fold lower than those of these two FQs, respectively. None of the three antibiotics was effective against E. faecium (MICs mostly >8 mg/L). DLX exhibited increased activity under acidic conditions, as the MIC50 for 12 E. faecalis isolates decreased by a 3-log2 dilution between pH 7.2 and pH 5, whereas comparator activities were impaired. A total of 19 mutants with significant increases in DLX MICs were selected in vitro, including 12/19 (63%) with at least one mutation in the quinolone resistance-determining region (QRDR) of GyrA (mainly at the position S84). Interestingly, four mutants lacked QRDR mutations but carried mutations in eno or infB genes, which have not previously been reported in FQ…
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