TITLE

Is the standard dose of amoxicillin-clavulanic acid sufficient?

AUTHOR(S)
Haeseker, Michiel; Havenith, Thomas; Stolk, Leo; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies
PUB. DATE
July 2014
SOURCE
BMC Pharmacology & Toxicology;2014, Vol. 15 Issue 1, p38
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
110347135

 

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