Target site modifications and efflux phenotype in clinical isolates of Streptococcus pneumoniae from Hong Kong with reduced susceptibility to fluoroquinolones

Abstract

Ciprofloxacin-susceptible (n = 7) and -resistant (MIC >or=4 mg/L) (n = 15) clinical isolates of Streptococcus pneumoniae from diverse sources in Hong Kong were studied for target site modifications and efflux phenotype. Reserpine-inhibited efflux of ciprofloxacin and/or levofloxacin was common in both susceptible and non-susceptible isolates. The ParC substitutions K137N and/or S79F or Y were associated with increased ciprofloxacin MICS. The GyrA substitution S81F was only found in isolates with full resistance to ciprofloxacin (MIC >or=16 mg/L) and levofloxacin (MIC >or=8 mg/L). Among clinical isolates of S. pneumoniae, accumulation of target site mutations in strains with an efflux mechanism was associated with increasing MICs of fluoroquinolones.

Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001

“…Eight of the 11 strains were from Hong Kong. All were of the same serotype (14) and had similar mutations as those described by Ho et al (14), suggesting the presence of a specific clone in that area. The Australian isolates also were clonal in nature; they all came from the one center, were of the same serotype (14), and exhibited similar QRDR mutations.…”

“…All were of the same serotype (14) and had similar mutations as those described by Ho et al (14), suggesting the presence of a specific clone in that area. The Australian isolates also were clonal in nature; they all came from the one center, were of the same serotype (14), and exhibited similar QRDR mutations. Similar shifts in MICs of clinafloxacin, gatifloxacin, trovafloxacin, and gemifloxacin have been demonstrated with levofloxacin-resistant isolates of S. pneumoniae (19).…”

Molecular Characterization of Clinical Streptococcus pneumoniae Isolates with Reduced Susceptibility to Fluoroquinolones Emerging in Italy

“…A triple mutant, containing the unusual change Tyr96 Ǟ Cys in GyrA and the substitutions Asp83 Ǟ Tyr in ParC and Ile460 Ǟ Val in ParE, was low-level resistant to ciprofloxacin but was resistant to ulifloxacin and levofloxacin. Amino acid changes in ParE have usually been regarded as being of minor or unclear significance 3,6,19,43,44 ; however, while this is certainly true of the common Ile460 Ǟ Val substitution (observed in 12 of our 15 isolates), the unusual Thr478 Ǟ Ser substitution (not previously reported as far as we know) was identified in the only isolate resistant to moxifloxacin. Two parC-parE double mutants with identical amino acid changes (Asp83 Ǟ Gly in ParC and Ile460 Ǟ Val in ParE) were, respectively, lowlevel and high-level resistant to ciprofloxacin; the latter, however, was the only high-level ciprofloxacin-resistant isolate demonstrating no cross-resistance to the newer fluoroquinolones (sparfloxacin, trovafloxacin, and moxifloxacin MICs, all 0.25 g/ml).…”

“…It was aimed at making data from our country available and comparable with those resulting from similar molecular studies carried out in the United States, 3,11,43 Canada, 44 Hong Kong, 19 Spain, 29 or in the context of international surveys. 6,10,21 It is well established that the persistence, spread, and increasing prevalence of fluoroquinolone resistance is associated with a small number of successful clones.…”

Molecular Characterization and Antimicrobial Susceptibility of Fluoroquinolone-Resistant or -Susceptible Streptococcus pneumoniae from Hong Kong

“…However, "hot spots" with considerably higher fluoroquinolone resistance rates do occur. Ho and colleagues have previously described high levels of fluoroquinolone resistance in pneumococci from Hong Kong due to well-established mutations in topoisomerase IV and DNA gyrase (6,7). The same research group, using isolates from a different period, found fluoroquinolone resistance in Hong Kong to be due to a single strain, the Spain 23F -1 clone, but the mechanism of fluoroquinolone resistance was not determined (8).…”