Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on β-Lactam Antibiotics
Insights from the Society of Infectious Diseases Pharmacists
Article first published online: 6 JAN 2012
2006 Pharmacotherapy Publications Inc.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 26, Issue 9, pages 1320–1332, September 2006
How to Cite
Lodise, T. P., Lomaestro, B. M. and Drusano, G. L. (2006), Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on β-Lactam Antibiotics. Pharmacotherapy, 26: 1320–1332. doi: 10.1592/phco.26.9.1320
- Issue published online: 6 JAN 2012
- Article first published online: 6 JAN 2012
- Monte Carlo simulation;
In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of β-lactams and microbiologic response. For β-lactams, in vitro and animal studies suggest that the amount of time in which free or non–protein-bound antimicrobial concentration exceeds the minimum inhibitory concentration (MIC) of the organism (fT>MIC) is the best predictor of bacterial killing and microbiologic response. Using population pharmacokinetic modeling and Monte Carlo simulation, it is possible to integrate pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate empiric β-lactam dosing strategies that maximize the likelihood of achieving fT>MIC associated with near-maximal bactericidal effect against the range of pathogens encountered in clinical practice. At Albany Medical Center Hospital, these mathematical modeling techniques were used to devise alternative dosing schemes for piperacillin-tazobactam, meropenem, and cefepime. These alternative schemes optimized fT>MIC at a lower total daily dose than would be employed with traditional dosing methods. Moreover, they achieved the targeted fT>MIC with less administration time/day than would be needed for continuous infusion.