1. J Antimicrob Chemother. 2015 Mar;70(3):891-8. doi: 10.1093/jac/dku465. Epub 2014 
Nov 27.

Temocillin (6 g daily) in critically ill patients: continuous infusion versus
three times daily administration.

Laterre PF(1), Wittebole X(1), Van de Velde S(2), Muller AE(3), Mouton JW(4),
Carryn S(2), Tulkens PM(5), Dugernier T(6).

Author information: 
(1)Department of Critical Care Medicine, St Luc University Hospital, Université
catholique de Louvain, Brussels, Belgium. (2)Pharmacologie cellulaire et
moléculaire, Louvain Drug Research Institute, Université catholique de Louvain,
Brussels, Belgium. (3)Department of Medical Microbiology, Medical Centre
Haaglanden (MCH), Den Haag, The Netherlands. (4)Department of Medical
Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
(5)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium tulkens@facm.ucl.ac.be.
(6)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.

OBJECTIVES: 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.
PATIENTS AND 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.

© The Author 2014. Published by Oxford University Press on behalf of the British 
Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions,
please e-mail: journals.permissions@oup.com.

PMID: 25433006  [PubMed - in process]