Killing and regrowth of bacteria in vitro: a review

Minimum inhibitory and bactericidal concentrations do not describe the time course of a drug's antimicrobial activity against bacteria. Some antimicrobials exhibit concentration dependent killing over a wide range of concentrations (e.g. aminoglycosides and quinolones), while others show maximal killing at concentrations near the MIC (e.g. beta-lactams and glycopeptides). The aminoglycosides and quinolones can require high drug concentrations (about 10-fold higher than the MIC) to prevent the selection of resistant subpopulations of bacteria. Persistent suppression of bacterial growth after antimicrobial exposure is called the 'postantibiotic effect' (PAE) and varies in duration depending on the drug-organism combination, as well as the concentration and duration of drug exposure. Antimicrobials which are inhibitors of protein and nucleic acid synthesis exhibit prolonged PAEs with a large variety of bacteria. While beta-lactam antibiotics demonstrate PAEs with Gram-positive cocci, very short or no PAEs are observed with these drugs with Gram-negative bacilli. The only exception is that penem antibiotics can induce PAEs with some strains of Gram-negative bacilli, primarily Pseudomonas aeruginosa. Thus, the pharmacodynamic activity of an antimicrobial can vary markedly depending on the microorganism and the class of drug and its concentration.