title: 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 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 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.
authors.affiliation: Nephrology and Infectious Diseases Department, AZ Sint-Jan Brugge-Oostende AV, AV Ruddershove 10, 8000 Brugge, Belgium.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Vandecasteele
authors.affiliation: Pharmacologie cellulaire et moléculaire (LDRI/FACM), Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium; Clinical Pharmacy Research Group (LDRI/CLIP), Av. E Mounier 72, bte 01.72.02, B-1200 Brussels, Belgium.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Miranda Bastos
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Av. Hippocrate 10, B-1200 Brussels, Belgium; Louvain Center for Toxicology and Applied Pharmacology, Université catholique de Louvain, Av. E. Mounier 53, Box B1-52-12, B-1200 Brussels, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Capron
authors.affiliation: Clinical Pharmacy Research Group (LDRI/CLIP), Av. E Mounier 72, bte 01.72.02, B-1200 Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Spinewine
authors.affiliation: Pharmacologie cellulaire et moléculaire (LDRI/FACM), Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.affiliation: Pharmacologie cellulaire et moléculaire (LDRI/FACM), Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Av. E. Mounier 73, bte B1.73.05, B-1200 Brussels, Belgium. Electronic address: francoise.vanbambeke@uclouvain.be.
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D010406:Penicillins; C031367:temocillin
keywords: ESRD; Gram-negative infection; Intermittent haemodialysis; Pharmacodynamics; Pharmacokinetics; Temocillin