ABSTRACT
This chapter provides examples of improving antimicrobial dosing by employing pharmacodynamic principles and demonstrates methods to develop clinical programs based on these concepts. The application of antimicrobial pharmacodynamics to daily clinical practice is derived from early implementation of clinical pharmacy services, specifically pharmacokinetic consulting. Antimicrobials exhibit two primary patterns of bacterial killing: concentration-dependent and concentration-independent, or time-dependent, killing. Aminoglycoside-associated nephrotoxicity is caused by accumulation of the drug molecule in the proximal renal tubular epithelial cells, inducing cellular toxicity and necrosis. Like the aminoglycosides, metronidazole displays concentration-dependant bactericidal activity. Accordingly, at Hartford Hospital, twice-daily dosing of metronidazole combined with a third-generation cephalosporin such as ceftizoxime or ceftriaxone has replaced the use of the cephamycins in intra-abdominal procedures. Piperacillin/tazobactam has become a popular antimicrobial in the treatment of nosocomial infectious processes and is used frequently in the institutional setting. As a result, this agent is often responsible for a large percentage of antimicrobial expenditures.
