Thrice-weekly temocillin administered after each dialysis session is appropriate for the treatment of serious Gram-negative infections in haemodialysis patients.

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 ß-lactam antibiotic with a long half-live and enhanced activity against most Gram-negative bacteria, including extended-spectrum ß-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 113 mL/min vs. 26 mL/min and 3.6 h vs. 24 h, respectively, with dialysis extracting approximately one-half of the residual concentration. The free temocillin concentration remained >16 mg/L (MIC90 threshold for most Enterobacteriaceae) during 48%, 67% and 71% of the dosing interval for patients receiving 1 g q24h, 2 g q48h and 3 g q72h, respectively, suggesting appropriate exposure for the two latter therapeutic schemes. Temocillin administered on dialysis days only in a dosing schedule of 2 g q48h and 3 g 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.