Biphasic kinetics of bacterial killing by quinolones.

The early phases of the bactericidal dynamics of three quinolones against two Escherichia coli strains were studied. Four concentrations of nalidixic acid, pefloxacin and ofloxacin were tested against each strain. In each case biphasic killing of bacteria was observed after a lag phase, and a biexponential model of microbial death could be fitted to the data. A direct relationship existed between the length of the lag phase and the drug concentration. The other parameters of the model appeared to be either strain-dependent, drug-dependent or both, and were characterised by narrow fluctuations. The degree of killing was always higher for ofloxacin. A paradoxical effect seemed to exist for nalidixic acid and pefloxacin in that survival was greater in the presence of 5 x MIC than in the presence of 3 x MIC. It was clear that ofloxacin did not act in the same way as nalidixic acid and pefloxacin. The study illustrated the relevance of mathematical modelling to investigations of the bactericidal effects of antibiotics.