Antibiotics and Topical Nasal Steroid for Treatment of Acute Maxillary Sinusitis: A Randomized Controlled Trial

Clinical Question

In adults with acute rhinosinusitis, is the routine use of antibiotics or nasal steroids more safe and effective at improving clinical cure?

Bottom Line

In patients 16 and older with acute rhinosinusitis, the routine use of antibiotics is safe, but not effective at improving clinical cure.

Major Points

Acute rhinosinusitis is commonly seen by primary care physicians, the United Kingdom estimates that physicians see more than 50 cases in a year. Studies suggest that only 37% to 63% of patients do not have a confirmed diagnosis of acute rhinosinusitis and still receive treatment. The common treatment for acute rhinosinusitis is prescribing a broad spectrum antibiotic or an intranasal steroid.

The Antibiotics and Topical Nasal Steroid for Treatment of Acute Maxillary Sinusitis trial evenly randomized 240 adults aged 16 years of age or older with acute nonrecurrent sinusitis and with 2 or more of the Berg and Carenfelt criteria to 4 different groups: active amoxicillin/active budesonide (n=53), active amoxicillin/placebo budesonide (n=60), placebo amoxicillin/active budesonide (n=64), and placebo amoxicillin and placebo budesonide (n=63). After 10 days, 29% of patients still had symptoms while on amoxicillin and 33.6% of patients still had symptoms without amoxicillin (95% CI, 0.57-1.73). In addition, after 10 days, 31.4% of patients still had symptoms with topical budesonide and 31.4% of patients still had symptoms without topical budesonide (95% CI, 0.54-1.62).

Antibiotics and topical nasal steroids are among common treatments for acute rhinosinusitis in practice. Antibiotics have not been shown to be effective in treating acute rhinosinusitis when compared to placebo in this RCT, but are relatively safe since there were no adverse events reported in the study. This study is one of the largest non-pharmaceutically funded, double blinded randomized controls done assessing the effectiveness of amoxicillin in patients with acute sinusitis. Although this RCT is the largest focusing on this topic, potential limitations are still relevant. The diagnostic criteria of acute rhinosinusitis was very strict, resulting in a low recruitment rate. The study also relied on subjective data from patient diaries, which may have resulted in false negative findings in the overall study.

Guidelines

Appropriate Antibiotics Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention

Antibiotic treatment for patients with acute rhinosinusitis who have had symptoms for more than 10 days, onset of severe symptoms, a high fever (>39 °C) and facial pain or purulent nasal discharge that has lasted more than 3 consecutive days.

Design

• Trial type: double-blinded, randomized, placebo-controlled factorial trial
• N = 240 adults aged 16 years of age or older with acute nonrecurrent sinusitis and had 2 or more diagnostic criteria
  • Active antibiotic and active steroid (n=53)
  • Active antibiotic and placebo steroid (n=60)
  • Placebo antibiotic and active steroid (n=64)
  • Placebo antibiotic and placebo steroid (n=63)
• Setting: 58 family practice
• Enrollment: November 2001 to November 2005
• Follow-up: 14 days
• Analysis: Intention-to-treat
• Primary outcome: proportion clinically cured at day 10 using patient symptom diaries and duration of severity of symptoms

Population

Inclusion Criteria

• Adult patients older than 15 years with uncomplicated acute illness (<28 days duration) who presented to a primary care practice with symptoms of sinusitis. Patients had to be positive for a minimum of 2 of the Berg and Carenfelt criteria:
  • Purulent nasal discharge with unilateral predominance
  • Local pain with unilateral predominance
  • Purulent nasal discharge bilaterally
  • Pus on inspection inside the nose

Exclusion Criteria

• Cases with a low probability of acute bacterial sinusitis that had less than 2 of the Berg and Carenfelt criteria
• Patients with a history of recurrent sinusitis (2 or more attacks of acute sinusitis in the previous 12 months)
• Patients with significant comorbidities (poorly controlled DM, HF, pregnant or breastfeeding)
• Allergies or history of adverse reaction to the medication
• Patients that received antibiotics or steroids in the previous month

Baseline Characteristics

• Mean age: 44 years
• Sex: 4 female to every 1 male
• Smoking
• Asthma
• Eczema
• Hay fever
• Previous sinusitis
• Number of days with symptoms
• Pus on inspection
• Initial temperature: There was a significant difference between temperature between those receiving the antibiotic and those not receiving the antibiotics

Interventions

• Randomization to a group:
  • Amoxicillin - 500 mg of amoxicillin 3 times per day for 7 days vs. placebo
  • Budesonide - 200 ug of budesonide in each nostril once per day for 10 days vs. placebo

Outcomes

Primary Outcomes

• Proportion clinically cured at day 10 using patient symptom diaries and duration of severity of symptoms
  • The proportions of patients with symptoms lasting 10 or more days were 29 of 100 (29%) for amoxicillin vs 36 of 107 (33.6%) for no amoxicillin (AOR, 0.99; 95% CI, 0.57-1.73).
  • Cox regression confirmed the lack of a significant effect of amoxicillin (hazard ratio for resolution, 1.08 [95% CI, 0.79-1.48]; P = .63)
  • The proportions of patients with symptoms lasting 10 or more days were 32 of 102 (31.4%) for topical budesonide vs 33 of 105 (31.4%) for no budesonide (AOR, 0.93; 95% CI, 0.54- 1.62).
• Sensitivity analysis including loss to followup
  • The estimated effect of amoxicillin on symptoms lasting 10 days or more (AOR, 0.90; 95% CI, 0.54-1.50)

Secondary Outcomes

• Nasal steroids were significantly more effective in patients with less severity of symptoms at baseline.
  • The effect of the steroid on the unwell group of symptoms at 10 days was −0.75 (95% CI, −1.34 to −0.14) for a baseline severity score of zero.
  • Interaction coefficient was 0.28 (95% CI, 0.10 to 0.45; P = .003; ie, the effect of the nasal steroid is reduced by 0.28 for each 1 point increase in baseline severity of sinusitis).

Subgroup Analysis

None performed

Adverse Events

No serious adverse events occurred according to trial and clinical records and case analysis at 6 weeks.

Criticisms

• Recruitment rate was low (mean value of 3 cases per family physician)
• Possibility of false negative findings
• Diagnostic criteria were strict and many patients failed to meet them
• Patient’s severity of symptoms was subjective based on their self reported patient’s diary that used a 7 point Likert scale.

Funding

This study was funded by the UK Department of Health

Further Reading

Williamson IG, Rumsby K, Benge S, et al. Antibiotics and Topical Nasal Steroid for Treatment of Acute Maxillary Sinusitis: A Randomized Controlled Trial. JAMA. 2007;298(21):2487–2496