Economic benefit of a meropenem dosage strategy based on pharmacodynamic concepts

Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

“…A computer program then randomly selects parameters from each of the distributions and computes the probability distribution of achieving the preset pharmacodynamic targets, outlined in the next section. [3][4][5][6] Pharmacodynamic parameters predictive of outcome An optimal bacterial and clinical outcome may be predicted by various pharmacokinetic and pharmacodynamic parameters that determine in vivo potency. Pharmacokinetic parameters of importance are the drug's peak concentration (C max ), AUC, and half-life for the determination of the duration the serum concentration remains above MIC.…”

“…Classification of oral cephalosporins according to their capacity to maintain plasma concentrations above minimum inhibitory concentrations (MICs) for important pathogens during at least 50% of the dosing interval carbapenems, 20%-40%) when the MIC is 4 µg/ml. 6 Thus, there is a very high probability of achieving adequate exposure with meropenem, particularly when many of the MICs for carbapenems are less than 1 µg/ml.…”

The new treatment paradigm and the role of carbapenems

“…Pharmacokinetic and pharmacodynamic research has investigated new dosing regimens such as altered frequency of administration and extended infusion [74]. Although new dosing regimens are not currently licensed for carbapenems, these new strategies are promising [75][76][77]; however, their potential needs to be confirmed by randomised controlled clinical trials. These studies are now starting to be published, with a recent evaluation of a 4-h infusion of 500 mg doripenem (1.5 g daily in three doses) being compared with imipenem/cilastatin (2 g daily in four doses or 3 g daily in three doses) in the management of VAP.…”

“…The pharmacokinetic properties and pharmacodynamic characteristics of meropenem may allow it to be administered as a smaller dose more frequently [76,77]. Kuti et al [76] used Monte Carlo simulation to compare different doses of meropenem over different infusion periods.…”

“…Kuti et al [76] used Monte Carlo simulation to compare different doses of meropenem over different infusion periods. Their computer modelling suggested that if lower doses were administered more frequently, a similar percentage of the dosing interval with drug concentrations remaining above the MIC (%T > MIC) was observed compared with standard doses.…”