Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?

The current clinical practice guideline from the American Academy of Pediatrics for the
Diagnosis and Management of Acute Bacterial Sinusitis recommends that the diagnosis of acute
sinusitis is made when symptoms of an upper respiratory infection (URI) persist beyond 10
days without showing signs of improvement (persistent presentation), when symptoms appear to
worsen (on the 6th to 10th day) after a period of improvement (worsening presentation), or
when both high fever and purulent nasal discharge are present concurrently for at least 3
consecutive days (severe presentation). In studies to date, children with persistent and
worsening presentations comprise >95% of cases. The investigators preliminary data and the
available literature suggest that only a subset of children being diagnosed with acute
sinusitis on the basis of current criteria are likely to have bacterial disease. This is not
entirely surprising because current criteria rely solely on the duration and the quality of
respiratory tract symptoms (which are both common and non-specific). Accordingly, it seems
likely that many children currently being diagnosed as having acute sinusitis actually have
an uncomplicated upper respiratory infection. This is important because acute sinusitis is
one of the most common diagnoses for which antimicrobials are prescribed for children in the
United States, accounting for 7.9 million prescriptions annually. A critical need thus exists
to establish which subgroups of children currently being diagnosed with acute sinusitis
actually benefit from antimicrobial therapy.

The objective of this trial is to determine whether certain subgroups of children with acute
sinusitis exist in whom antibiotic therapy can be appropriately withheld. This objective will
be achieved by conducting a large, randomized, double-blind, placebo-controlled clinical
trial in children 2 to 12 years of age with persistent or worsening presentations of acute
sinusitis. Based on the investigators preliminary data, the investigators hypothesize that
only certain subgroups of children currently being treated for acute sinusitis actually
benefit from antimicrobial therapy. By identifying, in a large placebo-controlled trial,
subgroups of children who respectively do and do not benefit from antimicrobial therapy, the
investigators will be better able to determine which children should be classified as having
acute bacterial sinusitis. Accordingly, the results of this trial may impact not only the
treatment guidelines for acute sinusitis but also the diagnostic criteria, and will help
ensure that, to the extent possible, antibiotic use is limited to appropriate patients. This,
in turn, will maximize the likelihood of achieving optimal outcomes and minimize the risk of
promoting antibiotic resistance.

Inclusion Criteria:

- Meets criteria for "persistent" or "worsening" presentations of sinusitis

- Baseline score ≥9 on the Pediatric Rhinosinusitis Symptom Scale

Exclusion Criteria:

- Severe presentation (≥3 days of colored nasal discharge and fever ≥39°C

- Asthma/allergic rhinitis explains symptoms

- Allergy to amoxicillin-clavulanate

- Immotile cilia syndrome

- Cystic fibrosis

- Immunodeficiency

- Parental inability to read/write English or Spanish

- Other concurrent infection (e.g., pneumonia, acute otitis media, streptococcal
pharyngitis)

- Systemic toxicity

- Wheezing on exam

- Antibiotic use within 15 days