Efficacy and safety of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 milligrams twice daily for 5 days versus amoxicillin-clavulanate at 875/125 milligrams twice daily for 7 days in the treatment of acute exacerbations of chronic bronchitis.

Abstract

This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h dosing interval, compared with conventional formulations, to eradicate bacterial strains for which amoxicillin MICs were < or =4 microg/ml while retaining efficacy against beta-lactamase-producing pathogens. A total of 893 patients were randomized and received study medication (amoxicillin-clavulanate at 2,000/125 mg for 443 patients and 875/125 mg for 450 patients). Overall, 141 patients receiving amoxicillin-clavulanate at 2,000/125 mg and 135 receiving the comparator formulation had at least one pathogen identified at screening. Amoxicillin-clavulanate at 2,000/125 mg was as effective clinically in the per-protocol (PP) population at the test of cure (days 14 to 21, primary efficacy endpoint) as amoxicillin-clavulanate at 875/125 mg (clinical success rates of 93.0 and 91.2%, respectively; treatment difference, 1.8; 95% confidence interval [CI], -2.2, 5.7). Bacteriological success in the bacteriology PP population was high for both formulations (amoxicillin-clavulanate at 2,000/125 mg, 76.7%; amoxicillin-clavulanate at 875/125 mg, 73.0%; treatment difference, 3.8; 95% CI, -7.5, 15.0). Both therapies were well tolerated, with a similar incidence of adverse events. Fewer than 5% of patients in each group withdrew from the study due to adverse events. The shorter, 5-day course of amoxicillin-clavulanate at 2,000/125 mg was shown to be as effective clinically as a longer, 7-day course of amoxicillin-clavulanate at 875/125 mg, with high bacteriological efficacy and no difference in tolerability.

• Authors: Sanjay Sethi, John Breton, Brian Wynne
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 1 Pg. 153-60 (Jan 2005) ISSN: 0066-4804 [Print] United States
• PMID: 15616290 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Anti-Bacterial Agents
• Amoxicillin-Potassium Clavulanate Combination

Topics

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Amoxicillin-Potassium Clavulanate Combination (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Bacterial Infections (drug therapy, microbiology)
• Bronchitis, Chronic (complications, drug therapy, microbiology)
• Double-Blind Method
• Female
• Haemophilus influenzae (drug effects, isolation & purification)
• Haemophilus parainfluenzae (drug effects, isolation & purification)
• Humans
• Male
• Middle Aged
• Moraxella catarrhalis (drug effects, isolation & purification)
• Streptococcus pneumoniae (drug effects, isolation & purification)
• Treatment Outcome