ABSTRACT
Bacterial resistance to antibiotics is a serious consequence of the use and overuse of antibacterial agents in the environment, and the impact of antibacterial resistance on patients and society is staggering. Compared to infections caused by susceptible pathogens, infections caused by resistant pathogens are associated with higher rates of morbidity and mortality (1,2). Furthermore, microbial drug resistance has been projected to add between $100 million and $30 billion annually to health-care costs (3). Considering the distressing decrease in the number of novel agents entering the clinical arena, the judicious utilization of currently available antibiotics becomes essential for preservation of their clinical efficacy. Unfortunately, preventing antibacterial resistance problems is not as simple as reducing the use of antibiotics, but must also involve a more scientific approach to dosing strategies. This is especially true since inadequate exposure of bacteria to drugs during therapy is likely a key factor in selection of resistant mutants. The field of antimicrobial pharmacodynamics strives to establish relationships between the pharmacokinetics of a drug and the effective treatment of infections. However, just as important is the relationship between pharmacokinetics, pharmacodynamics, and the emergence of resistance during therapy. This chapter will review some of the most critical resistance problems facing clinicians today and the role of pharmacodynamic strategies in slowing the emergence of resistance during therapy, including the development of effective antibacterial combinations.
