Post-antibiotic effects in experimental infection models: relationship to in-vitro phenomena and to treatment of infections in man

Persistent suppression of bacterial growth, called the post-antibiotic effect (PAE), has been studied in six different animal infection models. Prolonged in-vivo PAEs are observed for all antimicrobials with staphylococci and for imipenem and inhibitors of protein and nucleic acid synthesis with streptococci and Gram-negative bacilli. Penicillins and cephalosporins produce short or no in-vivo PAEs with these latter organisms. The presence of neutrophils prolongs the in-vivo PAEs found with aminoglycosides and quinolones. Simulation of human pharmacokinetics also enhances the duration of in-vivo PAE for aminoglycosides. In-vivo PAEs tend to be longer than those observed in vitro. The in-vitro PAE for penicillin with streptococci has been observed in vivo in only one of four experimental infection models. The presence of a prolonged in-vivo PAE can allow wider dosing intervals. The primary clinical application of the in-vivo PAE has been with once-daily dosing of aminoglycosides.