title: Pharmacokinetics of free ertapenem in critically ill septic patients: intermittent versus continuous infusion.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: EA 2968 Pharmacokinetics and Clinical Pharmacy, Victor Segalen Bordeaux 2 University, Hôpital Haut-Lévêque CHU de Bordeaux, Pessac, France. dominique.breilh@chubordeaux.fr
authors: D
authors: D
authors: Breilh
authors: C
authors: C
authors: Fleureau
authors: J B
authors: JB
authors: Gordien
authors: O
authors: O
authors: Joanes-Boyau
authors: J
authors: J
authors: Texier-Maugein
authors: S
authors: S
authors: Rapaport
authors: E
authors: E
authors: Boselli
authors: G
authors: G
authors: Janvier
authors: M C
authors: MC
authors: Saux