Henry DC, Riffer E, Sokol WN, Chaudry NI, Swanson RN. Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis. Antimicrob Agents Chemother 2003; 47: 2770-2774.
* PRACTICE RECOMMENDATIONS
It is reasonable to try a 3-day course of azithromycin (Zithromax) 500 mg/d for patients with a firm diagnosis of acute bacterial sinusitis.
However, keep in mind that antibiotics in general do not provide a clinically meaningful advantage when compared with placebo. Azithromycin is well tolerated, and patients are more likely to complete a 3-day course than a 10-day one. Recall that amoxicillin is as effective as macrolides clinically, and that most cases of sinusitis are not bacterial.
Sinusitis is frequently treated with 7- to 14-day courses of antibiotics in primary care; however, several trials have shown success with shorter regimens. This randomized controlled trial compared treatment efficacy using azithromycin for 3 and 6 days with amoxicillin-clavulanate for 10 days.
* POPULATION STUDIED
This manufacturer-sponsored, multicenter study, performed in the United States, enrolled 941 adults with acute bacterial sinusitis, defined clinically as presence of either purulent nasal discharge or facial pain, pressure, or tightness for more than 7 but fewer than 28 days, as well as an abnormal plain radiograph. Patients were excluded if they had hypersensitivity to macrolides or penicillins, were receiving systemic antibiotic therapy within 2 weeks prior to enrollment, or had a history of chronic sinusitis.
The average age of the subjects was 41 years; 41% were female; 86% were white, 6% black, and 1% Asian. Most patients had sinusitis symptoms primarily consisting of postnasal purulent discharge, facial pain, and nasal congestion for 13 days prior to enrollment.
* STUDY DESIGN AND VALIDITY
This was a double-blind randomized controlled study. Allocation concealment is uncertain. Subjects were assigned to receive azithromycin 500 mg/d for 3 days (AZM-3), azithromycin 500 mg/d for 6 days (AZM-6), or amoxicillin-clavulanate 500 mg/125 mg 3 times daily for 10 days (AMC). The subjects were assessed clinically at baseline, by telephone at day 4, and again clinically at days 10 and 28. Analysis of data was done on an intention-to-treat basis.
The study methodology was fair. Statistically, this study was adequately powered to detect efficacy equivalence rather than superiority between AZM and AMC (the 2 AZM groups were not compared). The researchers did not assess the validity of the criteria used for diagnosis and did not include a placebo arm; nor did they specify the method of allocation.
The fact that the researchers did not include a placebo arm is a severe limitation of this study. Without a placebo arm, there is no way to know if antibiotics were necessary in the first place. A recent double-blind randomized placebo-controlled trial comparing amoxicillin-clavulanate with placebo in adults with acute sinusitis in general practice demonstrated no benefit with antibiotic therapy. (1) (Level of evidence: 1b)
* OUTCOMES MEASURED
The primary outcome was cure at the end of trial (28 days), defined as resolution of signs and symptoms to the level that existed prior to the occurrence of the acute illness. Secondary outcomes were adverse reaction to medication and compliance.
The groups were similar at baseline, and 93.1% followed up at 28 days. In the intention-to-treat population (920 patients), clinical success at 28 days was equivalent among AZM-3 (71.5%), AZM-6 (74.1%), and AMC (71.5%).
Subjects treated with AMC reported a higher incidence of treatment-related adverse events than AZM-3 (51.1% vs 31.1%; P=.001; number needed to treat [NNT]=5) or AZM-6 (51.1% vs 37.6%; P=.001; NNT=7). Diarrhea was the most frequently reported adverse event, occurring in 17% to 21% of patients treated with azithromycin and 32% of patients treated with AMC. Compliance was significantly better in the AZM groups compared with the AMC group (AZM-3: 99.2%; AZM-6: 93.9%; and AMC: 82.1%).
(1.) Bucher HC, Tschudi P, Young J, et al. Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice. Arch Intern Med 2003; 163:1793-1798.
R. Marc Via, MD, Department of Family and Community Medicine, Scott & White Memorial Hospital, Texas A & M University System Health Science Center College of Medicine, Temple, Tex. E-mail: email@example.com.
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