Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic principles: a qualitative systematic review.

Objective: To systematically review evidence comparing traditional and alternative dosing strategies for meropenem, based on clinical and pharmacoeconomic outcomes.

Data Sources: MEDLINE (1950-September 2009), EMBASE (1980-September 2009), and International Pharmaceutical Abstracts (1970-September 2009) were searched, using the terms meropenem, carbapenems, pharmacodynamics, and pharmacokinetics. Reference citations from publications identified were reviewed.

Study Selection And Data Extraction: Articles discussing administration of meropenem to adults with normal renal function and comparing at least 2 regimens, 1 of which included the manufacturer-recommended regimen of 0.5 g or 1 g every 8 hours infused over 30 minutes, with clinical, pharmacodynamic, or pharmacoeconomic endpoints, were included. The pharmacodynamic endpoint of interest was percent time that the unbound drug concentration exceeded the minimal inhibitory concentration for a bacterial pathogen.

Data Synthesis: Sixteen studies were reviewed, which included 13 pharmacokinetic and dynamic assessments using Monte Carlo simulations, 5 clinical evaluations, and 3 pharmacoeconomic appraisals. Data on clinical and economic outcomes are largely nonrandomized retrospective analyses and case reports. Meropenem via intermittent prolonged infusion potentially increases the likelihood of achieving pharmacodynamic targets. However, a strong link with improved clinical outcomes is lacking. Smaller doses with shorter intervals appear to provide pharmacodynamic target attainment rates and clinical outcomes similar to those with traditional dosing, with potential pharmacoeconomic benefits. Meropenem via continuous infusion appears to increase the likelihood of achieving pharmacodynamic targets, compared with intermittent infusions. The sparsity of clinical evidence supporting this practice limits its broad application to practice. No studies have formally examined adverse effects with alternative dosing regimens.

Conclusions: Meropenem alternative dosing strategies provide similar pharmacodynamic target attainment rates compared with traditional dosing strategies. Small doses with shorter interval dosing provide additional pharmacoeconomic benefits and similar clinical outcomes. Alternative dosing strategies for meropenem were largely studied in healthy subjects; individuals with pharmacokinetic parameters that differ significantly may be ideal subjects for empiric dose modification.