Loss of bactericidal activities of quinolones during the post-antibiotic effect induced by rifampicin

The post-antibiotic effect (PAE) is the phenomenon of persisting suppression of bacterial growth as a result of prior antimicrobial exposure. In antimicrobial therapy, multiple doses of either a single drug or a combination of drugs are common. Accordingly, the following question may arise: what impact might the PAE induced by the previous dose impose on the subsequent bactericidal action of a cycle-specific antibiotic. To answer the question, a study was conducted using pefloxacin, norfloxacin, ciprofloxacin and ofloxacin as test drugs, rifampicin as the PAE inducer and Escherichia coli ATCC 25922 as the test organism. Bacterial kill kinetics were determined for each quinolone at 4 x MIC before rifampicin treatment and during the PAE period following rifampicin challenge. The relative bactericidal activity of the quinolones during the PAE period was calculated. During the PAE period, pefloxacin, norfloxacin, ciprofloxacin and ofloxacin displayed only 6%, 8%, 7% and 33% of their normal activities, respectively. The results were compared to those obtained at low temperature (4 degrees C) and when the cells were challenged simultaneously with a quinolone and with rifampicin. The findings of this study suggest that prolonging the dosing interval by taking the PAE into account may not only lower the cost of antimicrobial therapy and the risk of toxicity, but also ensure the efficacy of subsequent doses.