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.
Author(s): Sethi S, Breton J, Wynne B.
Affiliation(s): University of Buffalo, 3495 Bailey Ave., Medical Research 151, Buffalo, NY 14215,
USA. ssethi@buffalo.edu
Publication date & source: 2005, Antimicrob Agents Chemother. , 49(1):153-60
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.
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