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Keywords:

  • pharmacokinetics;
  • pharmacodynamics;
  • Monte Carlo simulation;
  • antibiotics;
  • β-lactams

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.