Mutant prevention concentration of nalidixic acid, ciprofloxacin, clinafloxacin, levofloxacin, norfloxacin, ofloxacin, sparfloxacin or trovafloxacin for Escherichia coli under different growth conditions.

Abstract

We used two different strains of Escherichia coli, E.coli ATCC 25922 and a recent urinary isolate from a clinical sample, to investigate in vitro how the MIC and mutant prevention concentration (MPC) are affected by different temperatures (37 or 20 degrees C) or oxygen tension (aerobic or anaerobic atmosphere; MIC, MIC(an); MPC, MPC(an)). MIC and MPC for E.coli ATCC 25922 and the clinical isolate were determined on agar containing ciprofloxacin or levofloxacin, and for the ATCC strain on agar supplemented with nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin or clinafloxacin. Results for the ATCC strain and the clinical strain for ciprofloxacin or levofloxacin were similar. The MPC values for E.coli ATCC 25922 were 2 x MIC (trovafloxacin), 4 x MIC (ciprofloxacin, norfloxacin, ofloxacin), 8 x MIC (clinafloxacin, levofloxacin), 16 x MIC (sparfloxacin) and 32 x MIC (nalidixic acid) at 37 degrees C and under aerobic conditions. Generally, a 37 degrees C aerobic atmosphere was associated with the highest MPC values. As an exception, both the MIC and the MPC of ciprofloxacin were higher under anaerobic versus aerobic conditions (MIC(an) approximately 8 x MIC; MPC(an) = 4 x MPC) for both E.coli isolates. Irrespective of the quinolone or growth conditions, the MIC for mutants was 1-256 x wild-type MIC. Calculated from published serum half-lives and the MPC values from this study, a putative selection period, in which resistant mutants might be selected, was calculated to be 14 h for nalidixic acid, 16 h for norfloxacin and ciprofloxacin, 28 h for ofloxacin, 30 h for trovafloxacin, 35 h for levofloxacin, 40 h for clinafloxacin, and 120 h for sparfloxacin. As calculated from our model in respect to the length of the selection period, long serum half-lives of recently developed compounds could not be compensated for by a more favourable activity in terms of MPC. Higher concentrations of ciprofloxacin may be required under an anaerobic atmosphere to prevent the emergence of resistant mutants among 10(10) cfu.