Correlation of in-vitro activity and pharmacokinetic parameters with in-vivo effect of amoxycillin, co-amoxiclav and cefotaxime in a murine model of pneumococcal pneumonia

J Antimicrob Chemother. 1996 Aug;38(2):227-36. doi: 10.1093/jac/38.2.227.

Abstract

In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacokinetics
  • Amoxicillin / therapeutic use*
  • Amoxicillin-Potassium Clavulanate Combination
  • Animals
  • Cefotaxime / pharmacokinetics
  • Cefotaxime / therapeutic use*
  • Cephalosporins / pharmacokinetics
  • Cephalosporins / therapeutic use*
  • Clavulanic Acids / pharmacokinetics
  • Clavulanic Acids / therapeutic use
  • Disease Models, Animal
  • Drug Therapy, Combination / pharmacokinetics
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • Mice
  • Microbial Sensitivity Tests
  • Penicillins / pharmacokinetics
  • Penicillins / therapeutic use*
  • Pneumonia, Pneumococcal / drug therapy*
  • Streptococcus pneumoniae / drug effects

Substances

  • Cephalosporins
  • Clavulanic Acids
  • Penicillins
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin
  • Cefotaxime