title: 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.
abstract: 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.
authors.affiliation: Service de Pneumologie, Hôpital André Mignot, Le Chesnay, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Petitpretz
authors.forename: Christian
authors.initials: C
authors.lastname: Chidiac
authors.forename: Francisco
authors.initials: F
authors.lastname: Soriano
authors.forename: Javier
authors.initials: J
authors.lastname: Garau
authors.forename: Katharine
authors.initials: K
authors.lastname: Stevenson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rouffiac
mesh_terms: D000328:Adult; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010403:Penicillin Resistance; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination