In vitro activity of sparfloxacin and clinafloxacin against multidrug-resistant enterococci

Abstract

We evaluated the in vitro susceptibility of 140 clinical enterococcal isolates to the quinolones sparfloxacin and clinafloxacin. Isolates included Enterococcus faecalis (107), Enterococcus faecium (29), Enterococcus raffinosus (3), and one Enterococcus gallinarum. There were 111 isolates that showed high-level [minimum inhibitory concentrations ( MICs) ≥ 2000 μg/ ml) resistance to gentamicin and were resistant to high levels of all other aminoglycosides; five isolates produced β-lactamase; 21 isolates were resistant ( MIC ≥ 16 μg/ ml) to ampicillin and were not β-lactamase producers; and 13 strains were resistant ( MIC ≥ 32 μg/ ml) to vancomycin. Most strains were susceptible to low concentrations of sparfloxacin and clinafloxacin, with MIC 90s of 0.6 μg/ml and 0.5 μg/ml, respectively. There were no inoculum effects. Time-kill experiments were performed with 22 strains; using 2 × MIC at 24 h, a ≥2 log 10 reduction in growth was observed with sparfloxacin and clinafloxacin for 14 and 17 strains, respectively. Time-kill synergism experiments were performed with 15 strains lacking high-level aminoglycoside resistance. In vitro bacterial synergism with the combination of sparfloxacin or clinafloxacin with streptomycin or gentamicin was observed for five and 12 isolates, respectively. The bactericidal activity of sparfloxacin and clinafloxacin suggest that these antibiotics may prove useful for therapy of multidrug resistant enterococci.