Bactericidal activity of amoxicillin against non-susceptible Streptococcus pneumoniae in an in vitro pharmacodynamic model simulating the concentrations obtained with the 2000/125 mg sustained-release co-amoxiclav formulation

J Antimicrob Chemother. 2004 Dec;54(6):1148-51. doi: 10.1093/jac/dkh463. Epub 2004 Oct 15.

Abstract

Objectives: To investigate the bactericidal activity against Streptococcus pneumoniae of simulated amoxicillin serum concentrations obtained in humans after 2000/125 mg sustained-release (SR) and 875/125 mg co-amoxiclav administered twice and three times a day, respectively.

Methods: An in vitro computerized pharmacodynamic simulation was carried out and colony counts were determined over 24 h. Ten strains non-susceptible to amoxicillin (four of them exhibiting an MIC of 4 mg/L, five strains with an MIC of 8 mg/L and one strain with an MIC of 16 mg/L) were used.

Results: With amoxicillin 2000 mg, an initial inoculum reduction >99.99% was obtained for strains with an MIC of 4 mg/L, > or =99% for strains with an MIC of 8 mg/L and 70.6% for the strain with an MIC of 16 mg/L at 24 h sampling time. At this sampling time, no reduction of initial inocula was obtained with amoxicillin 875 mg/8 h for two of the four strains with an MIC of 4 mg/L, three of the five strains with an MIC of 8 mg/L or for the strain with an MIC of 16 mg/L.

Conclusions: The new co-amoxiclav 2000/125 mg SR formulation appears to offer advantages versus previous formulations with respect to bactericidal activity against current amoxicillin non-susceptible strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacokinetics
  • Amoxicillin / pharmacology*
  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics
  • Amoxicillin-Potassium Clavulanate Combination / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Humans
  • Microbial Sensitivity Tests
  • Models, Biological
  • Penicillin Resistance
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / growth & development*

Substances

  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin