Comparative in vitro activity of a pharmacokinetically enhanced oral formulation of amoxicillin/clavulanic acid (2000/125 mg twice daily) against 9172 respiratory isolates collected worldwide in 2000

Int J Infect Dis. 2004 Nov;8(6):362-73. doi: 10.1016/j.ijid.2004.02.005.


Objectives: A new, pharmacokinetically enhanced, oral formulation of amoxicillin/clavulanic acid has been developed to overcome resistance in the major bacterial respiratory pathogen Streptococcus pneumoniae, while maintaining excellent activity against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase producing strains. This study was conducted to provide in vitro susceptibility data for amoxicillin/clavulanic acid and 16 comparator agents against the key respiratory tract pathogens.

Methods: Susceptibility testing was performed on 9172 isolates collected from 95 centers in North America, Europe, Australia, and Hong Kong by broth microdilution MIC determination, according to NCCLS methods, using amoxicillin/clavulanic acid and 16 comparator antimicrobial agents. Results were interpreted according to NCCLS breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral dosing regimens.

Results: Overall, 93.5% of Streptococcus pneumoniae isolates were susceptible to amoxicillin/clavulanic acid at the current susceptible breakpoint of < or =2 microg/mL and 97.3% at the PK/PD susceptible breakpoint of < or =4 microg/mL for the extended release formulation. Proportions of isolates that were penicillin intermediate and resistant were 13% and 16.5%, respectively, while 25% were macrolide resistant and 21.8% trimethoprim/sulfamethoxazole resistant. 21.9% of Haemophilus influenzae were beta-lactamase producers and 16.8% trimethoprim/sulfamethoxazole resistant, >99% of isolates were susceptible to amoxicillin/clavulanic acid, cefixime, ciprofloxacin and levofloxacin at NCCLS breakpoints. The most active agents against Moraxella catarrhalis were amoxicillin/clavulanic acid, macrolides, cefixime, fluoroquinolones, and doxycycline. Overall, 13% of Streptococcus pyogenes were resistant to macrolides.

Conclusion: The extended release formulation of amoxicillin/clavulanic acid has potential for empiric use against many respiratory tract infections worldwide due to its activity against species resistant to many agents currently in use.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics
  • Amoxicillin-Potassium Clavulanate Combination / pharmacology*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Australia
  • Drug Resistance, Bacterial
  • Europe
  • Haemophilus influenzae / drug effects*
  • Haemophilus influenzae / isolation & purification
  • Hong Kong
  • Humans
  • Microbial Sensitivity Tests
  • Moraxella catarrhalis / drug effects*
  • Moraxella catarrhalis / isolation & purification
  • North America
  • Population Surveillance*
  • Respiratory Tract Infections / microbiology*
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / isolation & purification


  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination