Pharmacodynamic effects of subinhibitory concentrations of beta-lactam antibiotics in vitro

The pharmacodynamic effects of subinhibitory concentrations of different beta-lactam antibiotics were investigated. A postantibiotic effect (PAE) was induced for different bacterial species by exposure to 10x MIC of several beta-lactam antibiotics for 2 h in vitro. The antibiotic-bacterial combinations used in this study were imipenem-Pseudomonas aeruginosa, benzylpenicillin-Streptococcus pneumoniae and -Streptococcus pyogenes, cefcanel-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 antibiotic-bacterial combinations for which a PAE was found. In contrast, sub-MICs on cultures not previously exposed to suprainhibitory antibiotic concentrations yielded only 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.