Postantibiotic effects of imipenem, norfloxacin, and amikacin in vitro and in vivo.

The postantibiotic effects (PAEs) of imipenem and norfloxacin were tested against Staphylococcus aureus, Streptococcus (Enterococcus) faecalis, Escherichia coli, and Pseudomonas aeruginosa. Amikacin was tested against the same bacteria except Streptococcus faecalis. For in vitro tests, a viable count-washing method was used, and for in vivo tests, the thread technique in normal mice was used. All three drugs produced PAEs of 1.1 to 3.8 h in vitro and 1.4 to 4.3 h in vivo against the pathogens tested. In vitro and in vivo results correlated well. The PAE had a significantly (P less than 0.01 to 0.001) longer duration in vivo than in vitro, but the PAE of imipenem on Staphylococcus aureus was longer in vitro. The PAE was not due to residual antibiotics at the site of infection, and no PAE was obtained if at any time the antibiotic concentration at the infection site reached the MIC for the pathogen tested. The results indicate that the presence of a PAE may enable antibiotics to be given more intermittently without a loss of efficacy and that the PAE can only be induced if the level of the antibiotic exceeds the MIC for the pathogen in question for at least several minutes.