Antibiotic dosing in critical illness.

Early and effective antibiotic therapy is essential in the management of infection in critical illness. The loading dose is probably the most important dose and is a function of the volume of distribution of the drug and the desired plasma concentration but independent of renal function. Antibiotics are classified in a number of ways that have implications for dosing. Doses of hydrophilic agents such as β-lactams should be increased in the early stages of sepsis as the extravascular space increases. For lipophilic agents such as macrolides, the inflammatory process is less important, although factors such as obesity will affect dosing. Classification can also be based on pharmacodynamic properties. Concentration-dependent antibiotics such as aminoglycosides should be administered by extended interval regimens, which maximize bactericidal effect, minimize nephrotoxicity and allow time between doses for the post-antibiotic effect. The critical factor for time-dependent agents, such as β-lactams, is time above the MIC. Ideally administration of these agents should be continuous, although vascular access availability can restrict infusion time to between 4 and 6 h, which is probably adequate. As well as antibiotic factors, patient factors such as hepatic and renal failure will affect dosing. Hepatic failure will affect antibiotic metabolism, although it is most important in end-stage failure. Renal failure and support will affect drug elimination. Knowledge of these factors is essential. Patient safety and prevention of unnecessary harm is a weighty consideration in critical illness. To ensure effective treatment and minimize adverse effects, therapy should be reviewed daily and adjusted in the light of changes in patient organ function and underlying pathology.