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Is the standard dose of amoxicillin-clavulanic acid sufficient?

Haeseker M, Havenith T, Stolk L, Neef C, Bruggeman C, Verbon A - BMC Pharmacol Toxicol (2014)

Bottom Line: A computer simulated increase of the standard dose to 6 times daily, increased this percentage to 95%.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. NTR1725 16th march 2009.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands. m.haeseker@mumc.nl.

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 number: NTR1725 16th march 2009.

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The measured concentrations of amoxicillin plotted against the time after amoxicillin administration.
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Figure 1: The measured concentrations of amoxicillin plotted against the time after amoxicillin administration.

Mentions: The measured concentrations of amoxicillin were plotted against the sampling times in Figure 1. There was a good linear correlation (R2 = 0.96) between the amoxicillin actual measured concentration and estimated concentration with MAP Bayesian fitting (MW/Pharm 3.60, Mediware, the Netherlands), Figure 2. The amoxicillin efficacy target (40%T > MIC) was reached in 100% of patients with a bacterial MIC ≤ 2 mg/L of Gram negative bacteria, in 93% of patients with a MIC = 4 mg/L and in 65% of patients with a MIC = 8 mg/L (Figure 3). When divided in age categories, arbitrarily set at 70 years; all patients older than 70 years reached the 40%T > MIC with a MIC of 4 mg/L and 87% of the patients younger than 70 years. For a MIC of 8 mg/L, the 40%T > MIC was reached in 81% of the patients older than 70 years and in 52% of the patients younger than 70 years (Figure 3).


Is the standard dose of amoxicillin-clavulanic acid sufficient?

Haeseker M, Havenith T, Stolk L, Neef C, Bruggeman C, Verbon A - BMC Pharmacol Toxicol (2014)

The measured concentrations of amoxicillin plotted against the time after amoxicillin administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4129431&req=5

Figure 1: The measured concentrations of amoxicillin plotted against the time after amoxicillin administration.
Mentions: The measured concentrations of amoxicillin were plotted against the sampling times in Figure 1. There was a good linear correlation (R2 = 0.96) between the amoxicillin actual measured concentration and estimated concentration with MAP Bayesian fitting (MW/Pharm 3.60, Mediware, the Netherlands), Figure 2. The amoxicillin efficacy target (40%T > MIC) was reached in 100% of patients with a bacterial MIC ≤ 2 mg/L of Gram negative bacteria, in 93% of patients with a MIC = 4 mg/L and in 65% of patients with a MIC = 8 mg/L (Figure 3). When divided in age categories, arbitrarily set at 70 years; all patients older than 70 years reached the 40%T > MIC with a MIC of 4 mg/L and 87% of the patients younger than 70 years. For a MIC of 8 mg/L, the 40%T > MIC was reached in 81% of the patients older than 70 years and in 52% of the patients younger than 70 years (Figure 3).

Bottom Line: A computer simulated increase of the standard dose to 6 times daily, increased this percentage to 95%.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. NTR1725 16th march 2009.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands. m.haeseker@mumc.nl.

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 number: NTR1725 16th march 2009.

Show MeSH
Related in: MedlinePlus