Objectives: To explore the urine bactericidal activity of co-amoxiclav and norfloxacin against Escherichia coli in an in vitro pharmacodynamic model simulating the human urinary concentrations observed after administration of a single oral dose of 2000/125 mg sustained-release co-amoxiclav and 400 mg norfloxacin.
Methods: Six E. coli isolates exhibiting amoxicillin/clavulanic acid MICs of 4/2 (two strains), 8/4, 16/8, 32/16 and 64/32 mg/L and norfloxacin MICs of < or =0.25 mg/L (three strains), 32, 64 and 256 mg/L were used. Colony counts were determined over 12 h and differences between the bacterial counts of initial inocula and the bacterial counts at each sampling time-point were calculated.
Results: With co-amoxiclav, bactericidal activity (>3 log(10) reduction) was obtained against the susceptible (MIC < or = 8/4 mg/L) and intermediate (MIC = 16/8 mg/L) strains from 3 to 12 h, and from 3 to 10 h against the resistant strains (MIC > or = 32/16 mg/L), which exhibited a 2 log(10) reduction at 12 h. With norfloxacin, bactericidal activity was obtained against the susceptible strains from 4 to 12 h and from 8 to 12 h against the resistant strain with an MIC of 32 mg/L. Regrowth, with respect to initial inocula, occurred from 8 h onwards with the strain with MIC = 64 mg/L and from 3 h onwards with the strain with MIC = 256 mg/L.
Conclusions: While regrowth occurs after exposure of high norfloxacin-resistant E. coli to urine physiological concentrations of norfloxacin, this study suggests that clavulanic acid can be given twice daily (to protect amoxicillin activity) with respect to uncomplicated cystitis due to E. coli exhibiting amoxicillin/clavulanic acid MICs up to 64/32 mg/L.