1. Int J Antimicrob Agents. 2015 Dec;46(6):660-5. doi:
10.1016/j.ijantimicag.2015.09.005. Epub 2015 Oct 9.

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

Vandecasteele SJ(1), Miranda Bastos AC(2), Capron A(3), Spinewine A(4), Tulkens
PM(5), Van Bambeke F(6).

Author information: 
(1)Nephrology and Infectious Diseases Department, AZ Sint-Jan Brugge-Oostende AV,
AV Ruddershove 10, 8000 Brugge, Belgium. (2)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.
(3)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. (4)Clinical Pharmacy Research Group (LDRI/CLIP), Av. E 
Mounier 72, bte 01.72.02, B-1200 Brussels, Belgium. (5)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. (6)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.

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.

Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All
rights reserved.

PMID: 26603304  [PubMed - in process]