Influence of Pharmacokinetic and Pharmacodynamic Principles on Antibiotic Selection.
When evaluating the efficacy of antibiotics for the treatment of respiratory tract infections, such as community acquired pneumonia and acute exacerbations of chronic bronchitis, assessment of clinical cure may not be the most relevant parameter, as it may not be related to microbiological eradication or to the minimum inhibitory concentration (MIC) of the infecting pathogen. It is more relevant to study the efficacy of the antibiotic in eradicating the bacterial pathogen, because this is frequently related to both the MIC of the pathogen and the antibiotic dosage regimen. Pharmacodynamics correlates the concentration of antibiotic in the blood or at the infection site with its biological effect against the organism (bacteriological eradication). For beta-lactams, the pharmacodynamic parameter that best correlates with eradication is time (T) above MIC (T > MIC); for aminoglycosides and fluoroquinolones, it is the area under the curve at 24 hours (AUC(24))-to-MIC ratio (AUC(24)/MIC). Knowledge of pharmacodynamics allows optimum use of antibiotics; in vitro models, animal models, and retrospective and prospective clinical trials have shown that the use of such knowledge optimizes bacteriological eradication and enhances patient outcome. In the future, pharmacodynamic studies will be used not only to assess optimal ways for antibiotics to eradicate resistant pathogens, but also to investigate the ability of antibiotics to prevent the development of resistance on therapy and to eradicate pathogens from colonizing sites.
Zhanel
George G.
GG
Faculties of Medicine and Pharmacy, University of Manitoba; Departments of Medicine and Microbiology, Health Sciences Centre, 820 Sherbrook Street, Room MS673, Winnipeg, Manitoba R3A 1R9 Canada. ggzhanel@pcs.mb.ca.