title: Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration.
abstract: OBJECTIVE
  The growing incidence of infections caused by Enterobacteriaceae producing ESBLs has led to increased use of carbapenems. Temocillin, which resists most β-lactamases, may be a useful alternative. The aim of this study was to assess the pharmacokinetics and target attainment rates of 6 g of temocillin daily divided into three administrations every 8 h (three times daily) or administered by continuous infusion in critically ill patients.
  
  
  METHODS
  This was a prospective, two-centre, randomized, controlled study in patients with intra-abdominal or lower respiratory tract infections caused by Enterobacteriaceae.
  
  
  RESULTS
  Thirty-two patients were included and analysed for clinical efficacy, and pharmacokinetics were measured in 29 of them. Four patients undergoing continuous veno-venous haemofiltration (CVVH) were analysed separately. Mean, median and range of percentages of the dosing interval during which the free drug concentration remained >16 mg/L were 76.4, 98 and 18.7-98.9 in patients treated three times daily and 98.9, 89.7 and 36.4-99.9 in patients with continuous infusion, respectively. Clinical cure rates were 79% and 93% in each of these groups, respectively (not significant). Patients with CVVH received a daily dose of 750 mg given by continuous infusion and had a mean free drug concentration of only 13.8 ± 1.9 mg/L. No adverse event attributable to temocillin was observed.
  
  
  CONCLUSIONS
  Temocillin (6 g daily) given by continuous infusion allows a larger proportion of critically ill patients to have free drug serum concentrations covering infections caused by Enterobacteriaceae with an MIC of 16 mg/L compared with administration three times daily. Clinical efficacy compared with carbapenems in documented severe infections needs to be further studied.
authors.affiliation: Department of Critical Care Medicine, St Luc University Hospital, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.affiliation: Department of Critical Care Medicine, St Luc University Hospital, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Wittebole
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Van de Velde
authors.affiliation: Department of Medical Microbiology, Medical Centre Haaglanden (MCH), Den Haag, The Netherlands.
authors.forename: Anouk E
authors.initials: AE
authors.lastname: Muller
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Carryn
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium tulkens@facm.ucl.ac.be.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.affiliation: Department of Critical Care Medicine, St Luc University Hospital, Université catholique de Louvain, Brussels, Belgium Department of Critical Care Medicine, St Pierre Hospital, Ottignies, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dugernier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009934:Organization and Administration; D010406:Penicillins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; C031367:temocillin
keywords: ESBLs; Monte Carlo simulations; continuous veno-venous haemofiltration; free concentration; target attainment rate; tolerance