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Pharmacodynamics of Meropenem and Imipenem Against Enterobacteriaceae, Acinetobacter baumannii , and Pseudomonas aeruginosa
Author(s) -
Kuti Joseph L.,
Florea Naomi R.,
Nightingale Charles H.,
Nicolau David P.
Publication year - 2004
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.24.1.8.34804
Subject(s) - meropenem , acinetobacter baumannii , imipenem , microbiology and biotechnology , pseudomonas aeruginosa , klebsiella pneumoniae , enterobacteriaceae , enterobacter cloacae , carbapenem , acinetobacter , biology , antibiotics , bacteria , antibiotic resistance , escherichia coli , biochemistry , genetics , gene
Study Objective. To compare the pharmacodynamics of meropenem and imipenem, both administered as 500 mg every 6 hours, against populations of Enterobacteriaceae, Acinetobacter baumannii , and Pseudomonas aeruginosa . Design. Ten thousand–subject Monte Carlo simulation. Intervention. Variability in total body clearance (Cl T ), volume of distribution as calculated by the terminal elimination rate (Vd β ), and minimum inhibitory concentration (MIC) distributions ( Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, A. baumannii, P. aeruginosa ) were derived from the literature for both meropenem and imipenem. For the free drug concentrations, the percentage of the dosing interval that the drug concentrations remain above the MIC (%T>MIC) for each carbapenem‐bacteria combination was calculated for 10,000 iterations, substituting a different Cl T , Vd β , fraction of unbound drug, and MIC into the equation each time based on the probability distribution for each parameter. Probabilities of attaining targets of 30%, 50%, and 100% T>MIC were calculated. Measurements and Main Results. Meropenem free drug %T>MIC exposure was significantly greater than that of imipenem against Enterobacteriaceae and P. aeruginosa , whereas imipenem exposure was greater for A. baumannii . For both agents, free drug %T>MIC exposure was greatest against Enterobacteriaceae and less for A. baumannii and P. aeruginosa . Probabilities of target attainment for 30% and 50% T>MIC were similar between drugs for most bacteria. At 100% T>MIC, meropenem target attainments were greater than those of imipenem against Enterobacteriaceae and P. aeruginosa , and imipenem attainment was higher for A. baumannii . Conclusion. The probability of attaining lower pharmacodynamic targets for most gram‐negative bacteria is similar for these carbapenems; however, differences become apparent as the pharmacodynamic requirement increases. Further study of the benefits of achieving this pharmacodynamic breakpoint with a higher probability of attaining targets is necessary.