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Online ISSN 1827-1596
Breilh D. 1, Fleureau C. 2, Gordien J.-B. 1, Joanes-Boyau O. 2, Texier-Maugein J. 3, Rapaport S. 2, Boselli E. 4, Janvier G. 2, Saux M.-C. 1
1 EA 2968 Pharmacokinetics and Clinical Pharmacy, Victor Segalen Bordeaux 2 University, Hôpital Haut–Lévêque CHU de Bordeaux, Pessac, France;
2 Departement of Anesthesia and Resuscitation, Hôpital Haut-Lévêque CHU de Bordeaux, Pessac, France;
3 Laboratory of Microbiology, Haut-Lévêque Hospital CHU de Bordeaux, Pessac, France;
4 Department of Anesthesiology and Intensive Care, Édouard Herriot Hospital, Lyon, France
BACKGROUND: The aim of this paper was to compare the pharmacokinetic and pharmacodynamic (PK/PD) parameters of continuous (CI) and intermittent infusion (ITI) of ertapenem into critically ill patients with severe abdominal infections.
METHODS:Twenty septic patients hospitalized in a university hospital intensive care unit were enrolled in the study. Half of the patients received ertapenem as an ITI 1 g bolus once daily, and the other half of the patients received the same dose via CI over 24 h following a 1-g loading dose. Blood was drawn 1, 12 and 24 h after terminating ITI or on days 2, 3 and 5 after starting CI for each patient. After centrifugation, the drawn blood was frozen at -80 °C until being examined by high-performance liquid-chromatography analysis.
RESULTS: Median serum-free ertapenem concentrations were as follows: ƒCmax = 98.9 mg/L and ƒCmin = 2.5 mg/L for ITI, and ƒCss=15.9 mg/L for CI. The ITI and CI median total clearance and volumes of distribution were 2.2 L/h vs. 2.5 L/h and 15.4 L vs. 21.0 L, respectively. The ertapenem MIC ranges were as follows: Escherichia coli (0.006 to 0.5 mg/L), Enterobacter cloacae (0.023 to 0.5 mg/L), Klebsiella oxytoca (0.023 to 0.5 mg/L), Staphylococcus aureus (0.38 to 3 mg/L), Streptococcus viridians (0.38 to 3 mg/L) and Enterococcus faecalis (0.38 to 3 mg/L). ITI and CI provided steady-state serum-free ertapenem concentrations constantly above the MIC for all bacteria.
CONCLUSION:Ertapenem exhibited satisfactory PK/PD parameters and achieved serum-free concentrations 100% of the time, above even the high MIC of extracellular pathogens normally encountered during severe abdominal infections. CI administration resulted in equally effective PK/PD parameters as ITI in normal weight, good renal-function patients.