Does Evidence Fully Support Antibiotic Use for Acute Sinusitis in Kids?

Use of antibiotics for acute sinusitis in children reduces treatment failures, a meta-analysis showed, but the results may also support initial observation given the natural history of the condition, according to the study authors.

Based on pooled data of more than 950 patients from six randomized trials, moderate-certainty evidence showed a significant benefit for antibiotic treatment, with absolute treatment failure rates of 23% for antibiotic-treated patients versus 40.8% for placebo recipients (risk ratio [RR] 0.59, 95% CI 0.49-0.72), reported Nader Shaikh, MD, of the Children's Hospital of Pittsburgh, and colleagues.

The results "clearly demonstrate the efficacy of antibiotics," the researchers concluded in Pediatrics, but given that none of the 431 placebo-treated children developed major sequelae, "our results could also be viewed as supporting observation, provided that close follow-up with families could be ensured."

High-certainty evidence from three of the trials included in the meta-analysis showed a higher risk for diarrhea with antibiotics versus placebo (13.4% vs 7.2%; RR 1.62, 95% CI 1.04-2.51).

Overall, six children needed to receive antibiotics to prevent one additional treatment failure, the study found, while one additional case of diarrhea would occur for every 16 patients treated.

"Approximately 7.5% of upper respiratory tract infections in children are complicated by acute sinusitis, and, as such, it represents one of the most common indications for antibiotic prescription in children," explained Shaikh and coauthors.

"Antibiotics are currently recommended for children with severe or worsening symptoms of acute sinusitis," they continued. "In children with persistent symptoms, defined as lasting more than 10 days without improvement, either immediate treatment or observation are acceptable treatment options. Children observed are recommended to receive antibiotics if they fail to improve within 72 hours."

For their meta-analysis, the researchers aimed to examine the efficacy of antibiotics for acute sinusitis, given that new trials had been conducted since the last meta-analysis on the subject was performed in 2013. They included six randomized placebo-controlled studies. All told, these included 956 pediatric participants assigned to either antibiotics (low-dose amoxicillin with or without clavulanate; cefuroxime; or high-dose amoxicillin or clavulanate) or placebo. In all studies, treatment was prescribed for 10 to 14 days.

Identifying which children will most likely benefit from antibiotics remains a challenge, noted Timothy Savage, MD, of Harvard Medical School in Boston, and Matthew Kronman, MD, of Seattle Children's Hospital, in an invited commentary.

They noted that in one recent trial included in the current analysis, sterile culture specimens showed that antibiotics provided no benefit among patients meeting the American Academy of Pediatrics' (AAP) diagnostic criteria for acute sinusitis.

"This finding is an enticing first hint that rapid tests with a high negative predictive value and specificity may allow clinicians to discriminate patients with sinusitis who could benefit from antibiotics from those unlikely to benefit," wrote Savage and Kronman. "Until such a cheap, accurate, and rapid test is widely available, however, clinicians must weigh the potential benefits of improved symptom duration with antibiotic treatment among patients meeting the AAP diagnostic criteria against the increased risk of diarrhea and the potential (but unmeasured) microbiome disruption among treated patients."

Ultimately, the editorialists said, the current study does indicate that antibiotics have a role in managing acute sinusitis in children, "but questions of how to optimize this treatment through using the narrowest spectrum agent and shortest effective treatment duration remain."

"Although high-dose amoxicillin-clavulanate demonstrated the greatest benefit over placebo, high-dose amoxicillin may have been equally effective, a conclusion supported by a recent study of >300,000 children," wrote Savage and Kronman. "Similarly, determining whether 5 to 7 days of treatment, as recommended in the current RedBook, has equal effectiveness to 10 days as recommended in guidelines will be essential."

Study Details

All but one of the six trials included in the meta-analysis from Shaikh and colleagues were determined to have a low-risk of bias. Treatment failure in the trials was defined as worsening at any time or a lack of substantial improvement either while on therapy or by days 10-18, depending on the trial -- assessed either by a validated scale, unvalidated scales, or clinical status.

Primary outcome analyses that excluded the study with a high risk of bias showed a similar benefit of antibiotic treatment, with a 36% reduced risk of treatment failure (RR 0.64, 95% CI 0.53-0.79). Similar results were observed in an analysis restricted to the three trials that used AAP's diagnostic criteria (RR 0.66, 95% CI 0.54-0.82).

As for other adverse events, the researchers also looked at rash (reported in two studies), but found no significant difference in rates between groups: 3% with antibiotics and 2.3% with placebo (RR 0.92, 95% CI 0.37-2.24).

There are several limitations to the meta-analysis, the authors said. Notably, the studies included varied in their methodology, as well as their categorizations of treatment failure and sinusitis diagnosis. Other limitations included the small number of studies included and a lack of studies examining the impact of antibiotics on the nasal or gut microbiomes.

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