Research output

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Research output: Contribution to journalArticleAcademicpeer-review

Associated researcher

  • Haeseker, M.
  • Havenith, T.
  • Stolk, L.
  • Neef, C.

  • Bruggeman, C.
  • Verbon, A.

Associated organisations

Abstract

Background: The pharmacodynamic (PD) efficacy target of amoxicillin is 40% time above the minimal inhibition concentration (40% T > MIC). Recent studies of other antibiotics have shown that PD-efficacy targets are not always reached. The aim of this study was to evaluate the percentage of hospitalised patients, using amoxicillin/clavulanic acid intravenously (iv), that reach the pharmacodynamic efficacy target 40% T > MIC. Additionally, the association of demographic anthropomorphic and clinical parameters with the pharmacokinetics and pharmacodynamics of amoxicillin were determined.

Methods: In serum of 57 hospitalised patients amoxicillin concentrations were measured using high performance liquid chromatography. Patients were older than 18 years and most patients had an abdominal infection. The standard amoxicillin/clavulanic acid dose was 4 times a day 1000/200 mg iv. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\Pharm 3.60). A one-compartment open model was used. Individual dosing simulations were performed with MW\Pharm.

Results: In our study population, the mean (+/- SD) age was 67 (+/- 16) years and the mean clearance corrected for bodyweight was 0.17 (+/- 0.07) L/h/kg. Only, 65% of the patients reached the proposed amoxicillin 40% T > MIC with amoxicillin/clavulanic acid for bacterial MICs of 8 mg/L. A computer simulated increase of the standard dose to 6 times daily, increased this percentage to 95%. In this small study group 40% T > MIC was not associated with clinical or microbiological cure.

Conclusion: A substantial proportion of the hospitalised patients did not reach the 40% T > MIC with the standard dose amoxicillin/clavulanic acid for a bacterial MIC of 8 mg/L. Therefore, we suggest increasing the standard dose of amoxicillin/clavulanic acid to 6 times a day in patients with severe Enterobacteriaceae infections.

    Research areas

  • Amoxicillin, Clavulanic acid, Pharmacokinetics, Age, CRITICALLY-ILL PATIENTS, DOSAGE REGIMENS, LIVER-INJURY, PHARMACOKINETICS, PHARMACODYNAMICS, COMBINATION, AMPICILLIN, SERUM
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Details

Original languageEnglish
Article number38
Number of pages8
JournalBMC Pharmacology and Toxicology
Volume15
DOIs
Publication statusPublished - 21 Jul 2014