title: Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients.
abstract: The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis. Patients with creatinine clearance (CrCl) higher than 50 ml/min received 1 g meropenem three times daily (Group I) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group II). Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection. The pharmacokinetic parameters differed between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1 microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5 +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6 microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7 +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli; their meropenem minimal inhibitory concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem plasma levels which exceeded the MIC for the whole dosing interval. When pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices were lower.
authors.affiliation: Clinical Pharmacology and Infectious Diseases Unit, The Rappaport Faculty of Medicine, Carmel Medical Center, 7 Michal St., Technion, 34362, Haifa, Israel. kitzes@netvision.net.il
authors.forename: Ruth
authors.initials: R
authors.lastname: Kitzes-Cohen
authors.forename: Dina
authors.initials: D
authors.lastname: Farin
authors.forename: Guillermo
authors.initials: G
authors.lastname: Piva
authors.forename: Sylvie Anne
authors.initials: SA
authors.lastname: De Myttenaere-Bursztein
mesh_terms: D000368:Aged; D003404:Creatinine / Q000378:metabolism; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013845:Thienamycins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D013845:Thienamycins; D003404:Creatinine; D000077731:Meropenem