Application of antimicrobial pharmacodynamic concepts into clinical practice:: Focus on β-lactam antibiotics -: Insights from the society of infectious diseases pharmacists

In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of beta-lactams and microbiologic response. For beta-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 pharmacokineti cs, a pharmacodynamic target, and microbiologic surveillance data to generate empiric beta-lactain 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 schemesopti mized 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.