Correlation between Growth Curves and Killing Curves of <i>Escherichia coli </i>in the Presence of Fleroxacin and Ampicillin

Abstract

Fleroxacin, a new long-acting quinolone, induces rapid killing and bacterial filamentation as do other quinolones. Ten strains of Escherichia coli were exposed comparatively to fleroxacin and ampicillin in order to determine the effect of sub- and supra-inhibitory concentrations of each of these two compounds on turbidimetric growth curves and viable counts. By comparing the maximal early increase in optical density (OD, PIOD) as colony-forming units per milliliter (CFU/ml) after 2 and 6 h of exposure to antibiotics, we observed a reduced number of CFU/ml in comparison with the control after the 2-hour exposure at 1/4 the minimum inhibition concentration (MIC) and after 6 h at 1/8 MIC, but a high OD value was also seen among the fleroxacin exposed bacteria. For ampicillin, PIOD rates and killing rates were slower and dose dependent. This discrepancy was due to filament formation, which increased the PIOD value to the same extent as the control curve. After exposure to fleroxacin at 1/2 MIC the PIOD decreased significantly and after 2 and 6 h E. coli killing rates of 99 and 99.9%, respectively, were observed. With exposure to 2 and 4 x MIC, both PIOD values and CFU/ml decreased substantially. Combined analysis of continuous turbidimetric monitoring and viable counts showed that subinhibitory concentrations of fleroxacin and beta-lactam had different effects on E. coli. Fleroxacin's rapid killing rate, despite filament formation, contrasted with the result obtained with ampicillin. The minimum antibiotic concentration of fleroxacin against E. coli was around 1/8 MIC.