The importance of antibiotic pharmacokinetics in critical illness

Antibiotics are the most commonly used drugs in the surgical patient. Pharmacokinetics is the study of processes that result in the delivery of drugs to effector sites. Drug absorption, distribution, biotransformation, and excretion are the critical elements of drug delivery to effector sites. The biologic elimination half-life (t1/2) and the volume of distribution (Vd) are terms used to describe the active processes of pharmacokinetics; t1/2 and Vd are determined for antibiotics by employing healthy volunteers or minimally ill patients. From these data, dosing schedules for each antibiotic are determined. This article reviews the literature on the impact of critical illness and sepsis on antibiotic pharmacokinetics. The data identify that t1/2 may be reduced in the hyperdynamic states of stress and sepsis and that the Vd is expanded. These changes mean that currently accepted dosing regimens of antibiotics in critically ill patients are inadequate. Subtherapeutic antibiotic concentrations in these patients may account for treatment failures and may be of significance in the emergence of bacterial resistance.