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Thrice-weekly temocillin administered after each dialysis session is appropriate for the treatment of serious Gram-negative infections in haemodialysis patients.
Int J Antimicrob Agents. 2015 Oct 9;
Authors: Vandecasteele SJ, Miranda Bastos AC, Capron A, Spinewine A, Tulkens PM, Van Bambeke F
Abstract
In patients with end-stage renal disease (ESRD) treated with intermittent haemodialysis, a limited number of antibiotics have been studied for their suitability for parenteral administration after dialysis sessions only in a thrice-weekly regimen. Temocillin is a β-lactam antibiotic with a long half-live and enhanced activity against most Gram-negative bacteria, including extended-spectrum β-lactamase-producers, thus making it an ideal candidate for use in this setting. This study aimed to evaluate the reliability of thrice-weekly parenteral temocillin in haemodialysis patients by characterising the pharmacokinetics of total and free temocillin. Free and total temocillin concentrations were determined with a validated HPLC method in 448 samples derived from 48 administration cycles in 16 patients with ESRD treated with intermittent haemodialysis and temocillin. Pharmacokinetics were non-linear partly due to saturation in protein binding. Median clearance and half-life for the free drug during intradialysis and interdialysis periods were 113mL/min vs. 26mL/min and 3.6h vs. 24h, respectively, with dialysis extracting approximately one-half of the residual concentration. The free temocillin concentration remained >16mg/L (MIC90 threshold for most Enterobacteriaceae) during 48%, 67% and 71% of the dosing interval for patients receiving 1g q24h, 2g q48h and 3g q72h, respectively, suggesting appropriate exposure for the two latter therapeutic schemes. Temocillin administered on dialysis days only in a dosing schedule of 2g q48h and 3g q72h is appropriate for the treatment of serious and/or resistant Gram-negative infections in patients with ESRD undergoing intermittent haemodialysis. These doses are higher than those previously recommended.
PMID: 26603304 [PubMed - as supplied by publisher]