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Open Access Research article

Is the standard dose of amoxicillin-clavulanic acid sufficient?

Michiel Haeseker135*, Thomas Havenith2, Leo Stolk2, Cees Neef2, Cathrien Bruggeman13 and Annelies Verbon4

Author Affiliations

1 Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands

2 Department of Clinical Pharmacy, Maastricht University Medical Centre, Maastricht, the Netherlands

3 Care and Public Health Research Institute (CAPHRI), Maastricht, the Netherlands

4 Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands

5 Present address: Maastricht University Medical Centre, P. Debyelaan 25, PO Box 58006202 AZ Maastricht, the Netherlands

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BMC Pharmacology and Toxicology 2014, 15:38  doi:10.1186/2050-6511-15-38

Published: 21 July 2014

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.

Trial registration

Trial registration number: NTR1725 16th march 2009.

Keywords:
Amoxicillin; Clavulanic acid; Pharmacokinetics; Age