From the Guidelines
Azithromycin is not recommended as a first-line treatment for acute sinusitis due to its limited coverage of common bacterial pathogens and increasing resistance rates. The most recent and highest quality study, 1, suggests that amoxicillin-clavulanate is the preferred agent for empirical antibiotics in acute bacterial rhinosinusitis (ABRS). While azithromycin has activity against some respiratory pathogens, it does not adequately cover the most common bacteria that cause sinusitis, particularly Streptococcus pneumoniae and Haemophilus influenzae.
Key Points to Consider
- First-line antibiotic therapy for bacterial sinusitis typically includes amoxicillin (500-875 mg three times daily) or amoxicillin-clavulanate (875/125 mg twice daily) for 5-10 days.
- For patients with penicillin allergies, alternatives include doxycycline (100 mg twice daily) or a respiratory fluoroquinolone like levofloxacin (750 mg daily for 5 days).
- Many cases of acute sinusitis are viral and resolve without antibiotics within 7-10 days.
- Antibiotics should be reserved for patients with severe symptoms, symptoms lasting more than 10 days, or worsening symptoms after initial improvement, as recommended by 1.
Important Considerations
- The observation option for ABRS refers to deferring antibiotic treatment of selected patients for up to 7 days after diagnosis and limiting management to symptomatic relief, as suggested by 1.
- Patients with nonsevere illness at presentation are candidates for observation when follow-up is ensured, and a system is in place that permits reevaluation if the illness persists or worsens.
- Patients with severe illness are treated initially with oral antibiotics, and the clinician should consider the patient’s age, general health, cardiopulmonary status, and comorbid conditions as part of the decision-making process, as recommended by 1.
From the FDA Drug Label
In a randomized, double blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg tid for 10 days). Clinical response assessments were made at Day 10 and Day 28. The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28 For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71. 5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of –8.4 to 8. 3, for 10 days of amoxicillin/clavulanate.
In an open label, noncomparative study requiring baseline transantral sinus punctures the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens: PathogenAzithromycin (500 mg per day for 3 Days) Day 7Day 28 S. pneumoniae23/26 (88%)21/25 (84%) H influenzae28/32 (87%)24/32 (75%) M. catarrhalis14/15 (93%)13/15 (87%)
Azithromycin is effective for treating acute sinusitis. The clinical cure rates for azithromycin were comparable to those of amoxicillin/clavulanate, with cure rates of 71.5% at Day 28 in the comparative study 2. Key points include:
- Clinical cure rates: 88% at Day 10 and 71.5% at Day 28 for azithromycin in the comparative study
- Pathogen-specific cure rates: 84-93% for S. pneumoniae, H. influenzae, and M. catarrhalis in the noncomparative study
- Treatment duration: 3 days of azithromycin was compared to 10 days of amoxicillin/clavulanate in the comparative study
From the Research
Efficacy of Azithromycin in Treating Acute Sinusitis
- Azithromycin has been shown to be effective in treating acute sinusitis in several studies 3, 4, 5, 6, 7.
- A 5-day course of azithromycin was found to be effective in treating patients with acute sinusitis, with 26.5% of patients cured and 67.6% improved on days 5 to 7, and 86.3% having a favorable clinical response at days 12 to 16 3.
- A 3-day course of azithromycin was compared to a 10-day course of amoxicillin/clavulanate and was found to be as effective and well tolerated, with a significantly faster resolution of signs and symptoms of sinusitis 4.
- Azithromycin extended release was found to be an effective and generally well tolerated treatment for patients with acute bacterial sinusitis, with clinical cure rates noninferior to those obtained with a 10-day regimen of levofloxacin 5.
- A 5-day course of azithromycin was compared to a 10-day course of amoxicillin and was found to have equal efficacy, safety, and tolerability in the treatment of acute bacterial sinusitis 6.
- Two azithromycin regimens, 500 mg/day once daily for 3 days or 6 days, were compared to an amoxicillin-clavulanate regimen of 500-125 mg three times daily for 10 days, and were found to be equivalent in efficacy and better tolerated than amoxicillin-clavulanate 7.
Comparison to Other Antibiotics
- Azithromycin was compared to amoxicillin/clavulanate in several studies and was found to be as effective and well tolerated, with a simpler dosage regimen and faster clinical effect 4, 7.
- Azithromycin was compared to amoxicillin and was found to have equal efficacy, safety, and tolerability in the treatment of acute bacterial sinusitis 6.
- Azithromycin extended release was compared to levofloxacin and was found to have noninferior clinical cure rates 5.
Safety and Tolerability
- Azithromycin was found to be well tolerated in all studies, with mild and moderate adverse events reported in a small percentage of patients 3, 4, 5, 6, 7.
- The most common adverse events reported were gastrointestinal disturbances, such as diarrhea 4, 7.
- Azithromycin was found to have a better safety and tolerability profile than amoxicillin/clavulanate in several studies 4, 7.