Effect of Renal Function and Dialysis on Temocillin Pharmacokinetics

Boelaert, Johan R.; Daneels, R; Schurgers, M.; Mellows, G.; Swaisland, A. J.; Lambert, A; Landuyt, H. W. Van

doi:10.2165/00003495-198500295-00023

Cited by 15 publications

(4 citation statements)

References 3 publications

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“…We observed a consistently high systemic exposure to temocillin. The total volume of distribution is in agreement with literature data [25] and does not appear to be significantly affected by renal insufficiency, as previously reported [11,14]. Free AUC reaches 35-50% of total AUC depending on the dose, which is in the same range as recent observations in severely ill patients hospitalised in intensive care units [24].…”

Section: Discussionsupporting

confidence: 91%

“…Previous research on temocillin during haemodialysis was limited to two studies conducted in the 1980s with a small number (n = 5-7) of patients and using older and less efficient low-flux dialysers. The performance of these dialysers in eliminating temocillin is inferior to that of contemporary highflux dialysers, and modern pharmacokinetic/pharmacodynamic (PK/PD) insights about parameters predicting the activity of ␤lactams were not yet fully developed [11,25]. The applicability of these outdated data to current practice is therefore questionable.…”

Section: Discussionmentioning

confidence: 99%

“…In this setting, temocillin (an intravenous ␤-lactam antibiotic with a long half-life [10]) constitutes a valuable candidate as an anti-Gram-negative agent in settings where Pseudomonas aeruginosa can be excluded [11]. Moreover, the remarkable stability of temocillin against most ␤-lactamases, including AmpC, extended-spectrum ␤-lactamases and most carbapenemases, fuelled a recent interest in this antibiotic as a carbapenem-sparing agent [12].…”

Section: Introductionmentioning

confidence: 99%

“…Little is known, however, about temocillin pharmacokinetics/pharmacodynamics in ESRD patients as well as its dialysability with contemporary high-flux haemodialysers [11,14]. Its primarily renal elimination (mainly by glomerular filtration in unchanged form) and long serum half-life compared with other ␤-lactams [10] render it suitable to be administered on haemodialysis days only.…”

Section: Introductionmentioning

confidence: 99%

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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

Vandecasteele

Bastos

Capron

et al. 2015

International Journal of Antimicrobial Agents

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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.

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