title: Is the standard dose of amoxicillin-clavulanic acid sufficient?
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  
  
  
  BACKGROUND
  NTR1725 16th march 2009.
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands. m.haeseker@mumc.nl.
authors.forename: Michiel
authors.initials: M
authors.lastname: Haeseker
authors.forename: Thomas
authors.initials: T
authors.lastname: Havenith
authors.forename: Leo
authors.initials: L
authors.lastname: Stolk
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.forename: Cathrien
authors.initials: C
authors.lastname: Bruggeman
authors.forename: Annelies
authors.initials: A
authors.lastname: Verbon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D065093:beta-Lactamase Inhibitors; D019980:Amoxicillin-Potassium Clavulanate Combination