The pharmacodynamic effects of subinhibitory concentrations of different ,B-lactam antibiotics were investigated. A postantibiotic effect (PAE) was induced for different bacterial species by exRosure to lOx MIC of several ,B-lactam antibiotics for 2 h in vitro. The antibiotic-bacterial combinations used in this study were imipenemPseudomonas aeruginosa, benzylpenicillin-Streptococcus pneumonae and -Streptococcus pyogenes, cgefcanel-S. pyogenes, ampicillin-Escherichia coli, and piperacillin-E. coli. After the induction of the PAE, the exposed cultures as well as the unexposed controls were washed and diluted. Thereafter, the cultures in the postantibiotic phase (PA phase) and the cultures not previously treated with antibiotics were exposed to 0.1, 0.2, and 0.3x MIC of the relevant drug and the growth curves were compared. When bacteria in the PA phase were exposed to sub-MICs, a substantial prolongation of the time before regrowth was demonstrated, especially in antibioticbacterial combinations for which a PAE wqs found. In contrast, sub-MICs on cultures not previously exposed to suprainhibitory antibiotic concentrations yielded oidy a slight reduction in growth rate compared with the controls. Thus, it seems important to distinguish the direct effects of sub-MICs on bacteria not previously exposed to suprainhibitory concentrations from the effects of sub-MICs on bacteria in the PA phase.The effects on bacteria of subinhibitory antibiotic concentrations (sub-MICs) were noted early in the antibiotic era. In 1944, Eagle and Musselman reported a temporary inhibition of the growth of spirochetes after exposure to sub-MICs of penicillin in vitro (10). Clinical experience at that time also revealed satisfactory results when patients with pneumococcal pneumonia were treated with low doses of penicillin which could hardly have yielded concentrations in serum above the MIC (38). Furthermore, Eagle and coworkers showed, both in vitro and in a rabbit model, that grampositive bacteria exposed to a suprainhibitory concentration of penicillin did not return to a growth phase immediately after the concentration in serum had fallen under the MIC (9, 11). This effect was later named the postantibiotic effect (PAE) and is one of many explanations for the success of intermittent dosage with antibiotics (7). Another factor of importance for the success of discontinuous antibiotic dosing is the function of a normal host defense system. For example, it does not seem to be necessary to keep the level of P-lactam antibiotics in serum above the MIC to clear an infection in immunocompetent animals, whereas several studies using neutropenic animals have shown the importance of maintaining levels of P-lactam antibiotics in serum above the MIC in order to avoid regrowth of gram-negative bacteria (3,14,33). One reason for the difference between immunocompetent and neutropenic animals is that bacteri,a exposed to sub-MICs in immunocompetent animals are more susceptible to phagocytic cell functions (13,19,24,26,41). Sub-MICs can also exert a d...