Optimizing antimicrobial pharmacodynamics: dosage strategies for meropenem.
BACKGROUND
Carbapenems are broad-spectrum antibiotics that are often employed as the last line of therapy for patients with nonresponsive nosocomial infections. Consideration of pharmacodynamic principles in dosage regimens for these agents can maximize their antibacterial effectiveness and reduce the number of bacterial strains that survive to mutate or continue infection.


OBJECTIVE
The objectives of this review were to highlight examples of the application of pharmacodynamics to the carbapenems (particularly meropenem) and to comment on clinical utility of these dosage regimens.


METHODS
Relevant information was identified through a MEDLINE search of the literature (1980-present) using the terms carbapenem, pharmacodynamic, pharmacokinetic, pharmacoeconomic, meropenem, imipenem, ertapenem, biapenem, and panipenem. Additionally, meeting posters were identified from the International Conference of Antimicrobial Agents and Chemotherapy (years 2001-2003) and the International Conference of the American Thoracic Society (years 2002-2003). All studies demonstrating the pharmacodynamics of the carbapenems by incorporating changes in dosage strategies were included.


RESULTS
Only relevant data for meropenem were identified in our literature search. The dosage scheme for meropenem may be modified to maximize the percentage of the dosage interval that drug concentrations remain above the minimum inhibitory concentration, an important parameter related to the bacterial kill rate. Only relevant data for meropenem were identified in our literature search. Human volunteer and Monte Carlo simulation studies suggested that in the treatment of susceptible pathogens, higher meropenem doses, increased frequency of administration, or prolonged duration of infusion resulted in improved pharmacodynamics.


CONCLUSIONS
When proper pharmacodynamic principles are applied to dosage strategies for meropenem, clinical and microbiological outcomes can be optimized.
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
Holly M
HM
Mattoes
Joseph L
JL
Kuti
George L
GL
Drusano
David P
DP
Nicolau
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D000077731:Meropenem; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D000077731:Meropenem