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Vet Microbiol. 2014 Jul 16;171(3-4):480-6. doi: 10.1016/j.vetmic.2013.12.021. Epub 2014 Jan 9.

Pharmacokinetic-pharmacodynamic (PK-PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs.

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North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, NC 27607, USA. Electronic address:


One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic-pharmacodynamic (PK-PD) principles to dosing regimens. If antimicrobials are used appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK-PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK-PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration.


Antibiotic; Antimicrobial; Monte Carlo simulation; Pharmacodynamic; Pharmacokinetic; Resistance.

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