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

• Published in: Journal of antimicrobial chemotherapy Vol. 52; no. 5; pp. 826 - 836
• Main Authors: Garau, Javier, Twynholm, Monique, Garcia-Mendez, Elena, Siquier, Bartolome, Rivero, Antonio
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2003; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination - administration & dosage; Amoxicillin-Potassium Clavulanate Combination - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimicrobials; Biological and medical sciences; CAP; Community-Acquired Infections - drug therapy; Community-Acquired Infections - microbiology; Double-Blind Method; Drug Therapy, Combination - administration & dosage; Drug Therapy, Combination - therapeutic use; Female; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pneumonia, Pneumococcal - drug therapy; Pneumonia, Pneumococcal - microbiology; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Treatment Outcome; Pneumonia; Clavulanic acid; Administration schedule; β-Lactamase; Penicillin derivatives; Immediate release form; Bacteria; Micrococcales; Human; Lung disease; Drug combination; Respiratory disease; Enzyme; Controlled release form; β-Lactams; Oral administration; Enzyme inhibitor; Streptococcus pneumoniae; Streptococcaceae; Antibiotic; Chemotherapy; Community acquired infection; Treatment; Amoxicillin; Dosage form; Hydrolases; Antibacterial agent
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkg458

Objectives: 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.