title: Oral pharmacokinetically enhanced co-amoxiclav 2000/125 mg, twice daily, compared with co-amoxiclav 875/125 mg, three times daily, in the treatment of community-acquired pneumonia in European adults.
abstract: OBJECTIVE
  Pharmacokinetically enhanced co-amoxiclav 2000/125 mg was designed to achieve high serum concentrations of amoxicillin over the 12 h dosing interval to eradicate Streptococcus pneumoniae with amoxicillin MICs of at least 4 mg/L.
  
  
  METHODS
  This randomized, double-blind, double-dummy, multicentre study compared the efficacy and safety of oral co-amoxiclav 2000/125 mg twice daily versus co-amoxiclav 875/125 mg three times daily, for 7 or 10 days, in the treatment of community-acquired pneumonia (CAP).
  
  
  RESULTS
  The per-protocol (PP) population at follow-up (Days 18-39) comprised 114 patients receiving co-amoxiclav 2000/125 mg and 116 receiving co-amoxiclav 875/125 mg. Clinical success at follow-up (primary efficacy endpoint) in the clinical PP population was 94.7% (108/114) for co-amoxiclav 2000/125 mg versus 88.8% (103/116) for co-amoxiclav 875/125 mg [treatment difference (TD) = 5.9%, 95% CI: 1.1, 13.0]. Bacteriological success in the bacteriology PP population at follow-up was 85.0% (17/20) for co-amoxiclav 2000/125 mg versus 77.3% (17/22) for co-amoxiclav 875/125 mg (TD = 7.7%, 95% CI: 15.8, 31.2). Penicillin-resistant S. pneumoniae (PRSP) were isolated in three patients (including two with bacteraemia) in the co-amoxiclav 2000/125 mg group (amoxicillin MICs 8 mg/L, penicillin MICs 4 mg/L) and one in the comparator group; all were clinical and bacteriological successes. Co-amoxiclav 2000/125 mg and co-amoxiclav 875/125 mg were associated with adverse events leading to withdrawal in 6.3% and 6.2% of patients, respectively.
  
  
  CONCLUSIONS
  Co-amoxiclav 2000/125 mg twice daily was at least as effective clinically as co-amoxiclav 875/125 mg three times daily in the treatment of CAP. Although few patients in this study had PRSP infection, 3/3 were successfully treated with co-amoxiclav 2000/125 mg.
authors.affiliation: Department of Medicine, Hospital Mutua de Terrassa, Barcelona, Spain. jagarau@terra.es
authors.forename: Javier
authors.initials: J
authors.lastname: Garau
authors.forename: Monique
authors.initials: M
authors.lastname: Twynholm
authors.forename: Elena
authors.initials: E
authors.lastname: Garcia-Mendez
authors.forename: Bartolome
authors.initials: B
authors.lastname: Siquier
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination