Double-blind, randomized study of the efficacy and safety of oral pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 milligrams) versus those of amoxicillin-clavulanate (875/125 milligrams), both given twice daily for 7 days, in treatment of bacterial community-acquired pneumonia in adults.
This randomized, double-blind, noninferiority trial was designed to demonstrate that pharmacokinetically enhanced amoxicillin-clavulanate (2,000/125 mg) was at least as effective clinically as amoxicillin-clavulanate 875/125 mg, both given twice daily for 7 days, in the treatment of community-acquired pneumonia in adults. In total, 633 clinically and radiologically confirmed community-acquired pneumonia patients (intent-to-treat population) were randomized to receive either oral amoxicillin-clavulanate 2,000/125 mg (n = 322) or oral amoxicillin-clavulanate 875/125 mg (n = 311). At screening, 160 of 633 (25.3%) patients had at least one typical pathogen isolated from expectorated or invasive sputum samples or blood culture (bacteriology intent-to-treat population). Streptococcus pneumoniae (58 of 160, 36.3%), methicillin-susceptible Staphylococcus aureus (34 of 160, 21.3%), and Haemophilus influenzae (33 of 160, 20.6%) were the most common typical causative pathogens isolated in both groups in the bacteriology intent-to-treat population. Clinical success in the clinical per protocol population at test of cure (days 16 to 37), the primary efficacy endpoint, was 90.3% (223 of 247) for amoxicillin-clavulanate 2,000/125 mg and 87.6% (198 of 226) for amoxicillin-clavulanate 875/125 mg (treatment difference, 2.7; 95% confidence interval, -3.0, 8.3). Bacteriological success at test of cure in the bacteriology per protocol population was 86.6% (58 of 67) for amoxicillin-clavulanate 2,000/125 mg and 78.4% (40 of 51) for amoxicillin-clavulanate 875/125 mg (treatment difference, 8.1%; 95% confidence interval, -5.8, 22.1). Both therapies were well tolerated. Amoxicillin-clavulanate 2,000/125 mg twice daily was shown to be as clinically effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia, without a noted increase in the reported rate of adverse events.
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Summa Health System, Akron, OH 44304, USA. filet@summa-health.org
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Kurz
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Kozak
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Xie
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Berkowitz
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D000293:Adolescent; D000328:Adult; D000368:Aged; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D013183:Sputum / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects; D016896:Treatment Outcome
D019980:Amoxicillin-Potassium Clavulanate Combination