title: Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: a comparison of 0.5-h and 3-h infusions.
abstract: In critically ill patients, pathophysiological changes alter the pharmacokinetics of antibiotics. Imipenem exhibits primarily time-dependent killing. Its administration by prolonged infusion may increase the time for which its plasma concentration exceeds the minimum inhibitory concentrations (MICs) of suspected pathogens. The objectives of this study were to compare the pharmacokinetic parameters of imipenem administered by standard short infusion (1g imipenem/1g cilastatin over 30min three times daily) and by extended infusion with a reduced total dose (0.5g imipenem/0.5g cilastatin over 3h four times daily) and to compare the target pharmacokinetic/pharmacodynamic indices, namely percentage of the dosing interval for which the free plasma concentration of imipenem exceeds the MIC and 4× MIC (%fT>MIC and %fT>4×MIC) of 0.5, 1, 2 and 4mg/L, for these two regimens in critically ill adult patients with nosocomial pneumonia on Day 2 of empirical antibiotic therapy. The study included 22 patients. Whilst no significant differences were found between both groups for %fT>MIC, %fT>4×MIC was 87.4±12.19%, 68.6±15.08%, 47.31±6.64% and 27.81±9.52% of the 8-h interval in the short infusion group for MICs of 0.5, 1, 2 and 4mg/L, respectively, and 85.15±17.57%, 53.14±27.27%, 13.55±24.47% and 0±0% of the 6-h interval for the extended infusion group. In conclusion, administration of 0.5g of imipenem by a 3-h infusion every 6h does not provide sufficient drug concentrations to treat infections caused by pathogens with a MIC of ≥2mg/L.
authors.affiliation: Department of Anaesthesiology and Intensive Care, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, Prague 2, 128 08, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Lipš
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc, 775 15, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Siller
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc, 775 15, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Strojil
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc, 775 15, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Urbánek
authors.affiliation: Department of Anaesthesiology and Intensive Care, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, Prague 2, 128 08, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Balík
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc, 775 15, Czech Republic. Electronic address: hana.suchankova@fnol.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Suchánková
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem
keywords: ICU; Imipenem; PK/PD; Pneumonia; Prolonged infusion