The Postantibiotic Effect: A Review of in Vitro and in Vivo Data

Abstract

The term postantibiotic effect (PAE) refers to a period of time after complete removal of an antibiotic during which there is no growth of the target organism. The PAE appears to be a feature of most antimicrobial agents and has been documented with a variety of common bacterial pathogens. Several factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, and antimicrobial combinations. In vitro, beta-lactam antimicrobials demonstrate a PAE against gram-positive cocci but fail to produce a PAE with gram-negative bacilli. Antimicrobials that inhibit RNA or protein synthesis produce an in vitro PAE against gram positive cocci and also produce a PAE against gram-negative bacilli. In vitro methods used to determine the PAE include colony counts, optical density, and measurement of adenosine triphosphate in bacteria. The exact mechanisms by which antimicrobials induce the PAE have not been clearly delineated. Animal studies reveal in vivo PAEs in accordance with PAEs obtained in vitro for most organism/ antimicrobial combinations. The clinical relevance of the PAE is probably most important when designing dosage regimens. The presence of a long PAE allows aminoglycosides to be dosed infrequently; the lack of an in vivo PAE suggests that beta-lactam antimicrobials require frequent or continuous dosing. Important questions remain to be answered concerning the PAE.