Duration of antibiotic treatment in surgical infections of the abdomen. Pharmacokinetic basis for short courses of antimicrobial therapy.

Pharmacokinetics relate to distribution of drugs between various body compartments; pharmacodynamics pertain to antimicrobial action at the site of infection. In this review the pharmacokinetic/pharmacodynamic justification for short courses of antibiotics is presented. A simplified pharmacokinetic model for most antimicrobials divides the body into a central compartment, the bloodstream, and a peripheral compartment consisting of extravascular fluid. The latter is the site of most infections. Adequate drug concentrations have to be achieved and sustained within the peripheral compartment to kill bacteria, or at least to inhibit bacterial growth and enhance killing by host defence mechanisms. Laboratory data with standardised bacterial inocula suggest that bacteria need to be exposed to either the minimal inhibitory concentration (MIC) or the minimal bactericidal concentration (MBC) for 16-24 hours to inhibit growth or to kill 99.9% of bacteria, respectively. Antimicrobials that yield tissue compartment concentrations in excess of the MIC or MBC, therefore, may be equally effective, and eliminate bacteria within 16-24 hours, once operation has reduced the bacterial inoculum. From this standpoint pharmacokinetics variables such as the time above MIC, which express the antibiotic-microbial-time relationship, become more important. The duration of administration, therefore, must be tailored by clinical judgement to the magnitude of the remaining bacterial inoculum, and the condition of the patient. Pharmacokinetics indicate that courses of treatment can be shortened.