title: Efficacy and safety of twice-daily pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg) in the treatment of adults with community-acquired pneumonia in a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.
abstract: OBJECTIVE
  This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.
  
  
  METHODS
  Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192).
  
  
  RESULTS
  Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain).
  
  
  CONCLUSIONS
  Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.
authors.affiliation: Emergency Room, Hospital Son Dureta, Palma de Mallorca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Siquier
authors.forename: J
authors.initials: J
authors.lastname: Sánchez-Alvarez
authors.forename: E
authors.initials: E
authors.lastname: García-Mendez
authors.forename: M
authors.initials: M
authors.lastname: Sabriá
authors.forename: J
authors.initials: J
authors.lastname: Santos
authors.forename: R
authors.initials: R
authors.lastname: Pallarés
authors.forename: M
authors.initials: M
authors.lastname: Twynholm
authors.forename: R
authors.initials: R
authors.lastname: Dal-Ré
mesh_terms: D000328:Adult; D000368:Aged; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D013030:Spain / Q000453:epidemiology; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination