The sub-MIC effects (SMEs) and the postantibiotic sub-MIC effects (PA SMEs) of vancomycin, roxithromycin, and sparfloxacin for Streptococcus pyogenes and Streptococcus pneumoniae and of amikacin for Escherichia coli and Pseudomonas aeruginosa were investigated. A postantibiotic effect was induced by exposing strains to 10x the MIC of the antibiotic for 2 h in vitro. After the induction, the exposed cultures were washed to eliminate the antibiotics. Unexposed controls were treated similarly. Thereafter, the exposed cultures (PA SME) and the controls (SME) were exposed to different subinhibitory concentrations (0.1, 0.2, and 0.3 x the MIC) of the same drug and growth curves for a period of 24 h were compared. In general, the PA SMEs were much more pronounced than the SMEs. However, for amikacin and E. coli the SME of 0.2 and 0.3 x the MIC also had an initial bactericidal effect. The longest PA SMEs were demonstrated for the combinations with the most pronounced killing during the induction and for the combinations which exhibited the longest PAEs.In the early 1940s, the dosage schedules devised for penicillin therapy were based on the assumption that drug concentrations must be maintained above the MIC. This assumption was based on previous experiments with the sulfonamides (1, 26). However, a few years after the introduction of penicillin, it was shown both in animal experiments and in clinical studies that a discontinuous penicillin therapy was as effective as a continuous one, even if the concentrations in serum had fallen under the MIC (4, 26, 28). At that time, Eagle et al. showed, both in vitro and in a thigh infection model in mice, that there was a lag phase before regrowth of bacteria after a first challenge of penicillin (5, 6). This concept aroused new interest in the 1970s and was named the postantibiotic effect (PAE) (3,14,33). The PAE has been extensively studied both in vitro and in vivo and has been cited as one explanation for the success of intermittent dosing regimens (3, 32). However, in most antibioticbacterium combinations the sum of the time that the drug concentration is above the MIC and the PAE does not cover the whole dosing interval. Also, in the in vivo situation, a suprainhibitory concentration of a drug will always be followed by subinhibitory concentrations (sub-MICs).We have shown earlier that subinhibitory antibiotic concentrations may have different effects on bacteria exposed previously to suprainhibitory antibiotic concentrations (postantibiotic sub-MIC effect [PA SME]), compared with the effects on bacteria not previously exposed to antibiotics (sub-MIC effect [SME]) (18,20). In most of the investigated combinations with P-lactam antibiotics, we found a pronounced difference in time between the PA SME and the SME, with two exceptions. In the combinations with no PAE, neither a PA SME nor an SME was found, and in the combination of imipenem with Pseudomonas aeruginosa, both a long PA SME and an SME were seen (20).The aim of this study was to investigate the occurrence of PA SME...