Use of pharmacokinetics and pharmacodynamics to optimize antimicrobial treatment of Pseudomonas aeruginosa infections

Abstract

The study of pharmacodynamics has greatly enhanced our understanding of antimicrobials and has enabled us to optimize dosing regimens. Applying this knowledge to the clinical setting can be critical for the treatment of Pseudomonas aeruginosa infections. Because of its selectively permeable outer membrane and multiple efflux pump mechanisms, P. aeruginosa has high intrinsic resistance to many available antimicrobials. Numerous studies have established pharmacodynamic values for concentration-dependent agents (maximum serum concentration:minimum inhibitory concentration [MIC] and area under the serum concentration-time curve: MIC) and concentration-independent agents (i.e., percentage of time that the drug concentration remains greater than the MIC) that help predict the probability of a successful outcome. Current therapies attempt to meet these target values. However, to reduce the risk of clinical failures, combination therapy (typically, a β-lactam with an aminoglycoside or fluoroquinolone) is commonly used to enhance eradication rates and decrease the risk of developing resistance. Although combination therapy ensures a greater chance of selection of appropriate treatment, timely initial administration of antimicrobial therapy remains a key factor for reducing the likelihood of death for these patients.