Pharmacokinetic contributions to postantibiotic effects. Focus on aminoglycosides.

The postantibiotic effect (PAE) refers to a period of time after complete removal of an antimicrobial 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. Various factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, antimicrobial combinations, and inoculum and medium used. beta-Lactams demonstrate a PAE against Gram-positive cocci, but produce only a short PAE with Gram-negative bacilli. Antimicrobial agents that inhibit RNA or protein synthesis have a PAE against Gram-positive cocci and Gram-negative bacilli. In vivo studies of aminoglycosides suggest that area under the plasma concentration-time curve is the pharmacokinetic parameter that best correlates with clinical efficacy. This is thought to be due to the concentration-dependent killing and PAE possessed by these antimicrobials. Animal and human studies have reported that once-daily administration of aminoglycoside is as effective as, or more effective than, and possibly less toxic than traditional multiple daily administration.