Objectives: The growing incidence of infections caused by Enterobacteriaceae producing ESBLs has led to increased use of carbapenems. Temocillin, which resists most b-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.

Continuous veno-venous haemofiltration, ESBLs, Free concentration, Monte Carlo simulations, Target attainment rate, Tolerance
dx.doi.org/10.1093/jac/dku465, hdl.handle.net/1765/88131
Journal of Antimicrobial Chemotherapy
Department of Medical Microbiology and Infectious Diseases

Laterre, P.-F, Wittebole, X, Van De Velde, S, Muller, A.E, Mouton, J.W, Carryn, S, … Dugernier, T. (2015). Temocillin (6 g daily) in critically ill patients: Continuous infusion versus three times daily administration. Journal of Antimicrobial Chemotherapy, 70(3), 891–898. doi:10.1093/jac/dku465