Pharmacokinetics and pharmacodynamics of antimicrobials.

Antibiotics are some of our most commonly used drugs. Until recently, little has been known about how to optimize administration of these agents. Unfortunately, the rate of discovery of new antibiotics has been declining, coincident with the explosion in the number of multidrug-resistant organisms in both the community and hospital environments. This development makes the identification of optimal regimens that will result in good clinical and microbiological outcomes important, but it also makes clear the necessity of identifying regimens that will suppress the emergence of resistant organisms. Given that new agents for multidrug-resistant pathogens will take nearly a decade to become available to physicians, keeping organisms susceptible to drugs that are already available is even more critical. Pharmacodynamics allows identification of the drug exposure measure that is closely associated with the ability to kill organisms and, also, to suppress the emergence of resistant subpopulations of organisms. Use of Monte Carlo simulation allows identification of drug doses in the clinical arena to accomplish these ends. Such approaches should be applied to all old and new antibacterial agents.