A 10-day course of amoxicillin does not reduce symptoms of acute rhinosinusitis at day 3 of treatment
- 1University of Pittsburgh School of Medicine Department of Otolaryngology, Pennsylvania, USA
- 2University of Pittsburgh School of Medicine, Department of Otolaryngology, Pittsburgh, Pennsylvania, USA
- 3Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
- Correspondence to: Jack Anon
University Pittsburgh School of Medicine, 580 Peach St, Erie, Pittsburgh, Pennsylvania, USA;
Despite the controversy regarding their clinical benefit and concerns about resistance, the use of antimicrobials for rhinosinusitis (RS) accounts for one in five prescriptions for adults in the USA. However, we lack a simple diagnostic or predictive tool for determining whether acute viral RS has progressed to secondary bacterial RS, and must therefore rely on a patient's history and limited physical findings to diagnose RS. Using guidelines recommended by a small expert panel and partially funded by the US Centers for Disease Control and Prevention, this study attempts to answer the question of whether amoxicillin is an effective treatment for acute RS?
This was a randomised, blinded, placebo-controlled, multi-centre study undertaken between November 2006 and May 2009. Study participants between 18 and 70 years of age were enrolled if they had a history of acute viral RS with tenderness in the face or teeth and purulent nasal secretions lasting for >7 days but <28 days that had not improved or was worsening, or symptoms lasting for less than 7 days that had significantly worsened. Exclusion criteria included allergy to penicillin or amoxicillin or prior antibiotic treatment within 4 weeks. No diagnostic studies such as x-rays, endoscopic examination or cultures were used to confirm the diagnosis. Patients were randomised 1:1 to either a 10-day course of amoxicillin (500 mg three times a day) or placebo. The primary outcome measure was the effect of treatment on a disease-specific quality of life instrument, determined using a modified Sinonasal Outcome Test-16 (SNOT-16) at day 3. This test uses a 0–3 scale (not a problem (0) to severe problem (3)) for questions such as: (1) need to blow nose, (2) sneezing, (3) runny nose, (4) postnasal discharge, (5) thick nasal discharge, (6) headache and (7) facial pain/pressure. Improvement in the disease-specific quality of life was assessed as the reduction in SNOT-16 scores from day 0 to days 3, 7 and 10.
Of 244 screened adults, 166 were enrolled and received amoxicillin (n=85) or placebo (n=81). The mean change in SNOT-16 scores was similar in both groups at day 3 and at day 10 but differed at day 7, favouring amoxicillin (mean difference between groups of 0.19 (95% CI 0.024 to 0.35)). Likewise, a 7-point Likert analysis also showed significant symptom improvement for the amoxicillin group at day 7, but no significant difference at day 3 or 10.
Multiple studies have shown that based solely on clinical characteristics, it is impossible to know which patients have a bacterial component to their RS and could benefit from the use of an appropriate antibiotic.1 The reference cited by the authors to support the criteria they used to diagnose likely bacterial RS does not provide diagnostic criteria for acute bacterial sinusitis as the patients studied did not present with acute RS and no microbiologic testing was performed.2
The limitations of the study by Garbutt et al are revealed by comparison with a recent study by Wald et al. This placebo-controlled study of acute RS in children, based on clinical criteria but using stringent entry requirements, required over 2100 children to be screened to obtain 139 (6.5%) eligible children. With this degree of rigour in enrolling patients with a high probability of having bacterial RS, they showed that amoxicillin–clavulanate indeed shortened the duration of disease.3 Two recent studies of acute otitis media with stringent enrolment criteria also showed superiority of active treatment (amoxicillin–clavulanate) over placebo.
The present study is a reiteration of many other small studies that enrolled patients with RS without a high probability of bacterial RS. A more rigorous study, such as that conducted by Wald et al would have yielded more useful clinical information. We continue to see a need for an inexpensive tool to determine appropriateness of antimicrobials. Culture-directed therapy based upon microbiologic findings is still the gold standard. Two recent double-blind, placebo-controlled trials have shown that antimicrobials given to adults with cold are significantly more likely to improve faster in patients with nasopharyngeal cultures yielding bacterial pathogens. Further studies are needed to validate these findings and determine if better clinical findings predictive of bacterial infection can be developed.