The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults

Int J Antimicrob Agents. 2002 Aug;20(2):119-29. doi: 10.1016/s0924-8579(02)00126-7.


This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S. pneumoniae strains with high-level penicillin resistance.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects*
  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / pharmacology
  • Community-Acquired Infections / drug therapy*
  • Community-Acquired Infections / microbiology
  • Double-Blind Method
  • Drug Therapy, Combination / administration & dosage
  • Drug Therapy, Combination / adverse effects*
  • Drug Therapy, Combination / pharmacokinetics
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / isolation & purification
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Penicillin Resistance
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Pneumococcal / drug therapy
  • Pneumonia, Pneumococcal / microbiology
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / isolation & purification
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Amoxicillin-Potassium Clavulanate Combination