The results of a large observational study in children show no difference in treatment failure rates between the two most commonly prescribed antibiotics for pediatric acute sinusitis, researchers reported today in JAMA.

Overall, treatment failure for sinus infections was rare in children treated with amoxicillin or amoxicillin-clavulanate. But the latter was associated with more adverse events, a finding the study authors say could inform prescribing decisions.

Lack of consensus on optimal antibiotic

The observational cohort study, led by researchers from Brigham and Women's Hospital in Boston, measured rates of treatment failure among children ages 17 and under who received either amoxicillin or amoxicillin-clavulanate for acute sinusitis, which is one of the most common indications for antibiotic prescribing in children. Roughly 85% of children diagnosed as having acute sinusitis receive an antibiotic, even though the condition can sometimes be caused by viruses.

Amoxicillin and amoxicillin-clavulanate account for 65% of antibiotics prescribed empirically for pediatric acute sinusitis, but clinicians don't agree on which is the optimal choice. The primary difference between the two is that clavulanate (clavulanic acid) inhibits certain beta-lactamase enzymes, which allows amoxicillin-clavulanate to target beta-lactamase–producing strains and a broader spectrum of bacteria than amoxicillin alone. 

The authors note that while two small randomized clinical trials conducted in 1986 and 2001 found no difference on cure rates for pediatric acute sinusitis between the two antibiotics, comparative effectiveness and safety hasn't been assessed since the introduction of conjugate pneumococcal vaccines in 2000.

"Since that time, the routine use of this vaccine and increasing antibiotic resistance rates may have shifted the microbiology of acute bacterial sinusitis, with reports of reductions in the contributions of S pneumoniae and increases in the rates of β-lactamase–producing H influenzae," they wrote.

Using data from a large commercial insurance database, the researchers assessed 320,141 children with acute sinusitis for treatment failure 1 to 14 days after enrollment. They defined treatment failure as an aggregate of new antibiotic dispensation, emergency department (ED) or inpatient encounter for acute sinusitis, or inpatient encounter for sinusitis complication. They also assessed adverse events.

No difference in treatment failure

Among the children enrolled, 198,942 were matched by propensity score, with 99,471 in each antibiotic group. More than 90% of patients were dispensed 10 or more days' worth of antibiotics. Treatment failure occurred in only 1,718 (1.7%) patients overall and was mostly handled on an outpatient basis, with ED and inpatient encounters rarely reported.

Analysis of the propensity score-matched patients showed no difference in the risk of treatment failure between the amoxicillin and amoxicillin-clavulanate groups (relative risk [RR], 0.98; 95% confidence interval [CI], 0.92 to 1.05).

But the risk of gastrointestinal symptoms (RR, 1.15; 95% CI, 1.05 to 1.25) and yeast infections (RR, 1.33; 95% CI, 1.16 to 1.54) was higher with amoxicillin-clavulanate.

Based on these data, physicians should seriously consider prescribing amoxicillin as a first line of defense against acute sinusitis.

After stratification by age, the RR of treatment failure with amoxicillin-clavulanate was 0.98 (95% CI, 0.86. to 1.12) for ages 0 to 5 years, 1.06 (95% CI, 0.92 to 1.21) for ages 6 to 11 years, and 0.87 (95% CI, 0.79 to 0.95) for children ages 12 to 17 years. The age-stratified RR for adverse events after amoxicillin-clavulanate was 1.23 (95% CI, 1.10 to 1.37) for ages 0 to 5, 1.19 (95% CI, 1.04 to 1.35) for ages 6 to 11, and 1.04 (95% CI, 0.95 to 1.14) for ages 12 to 17.

The study's lead author says the good news is that, regardless of which of the two antibiotics is used, most children with acute sinusitis will get better. But he says the increased risks of gastroenteritis and yeast infection associated with amoxicillin-clavulanate tilts the risk-benefit calculation in amoxicillin's favor.

"Our study shows that there are more adverse events when amoxicillin-clavulanate is used," Timothy Savage, MD, MPH, an associate epidemiologist at Brigham and Women's, said in a hospital press release. "Based on these data, physicians should seriously consider prescribing amoxicillin as a first line of defense against acute sinusitis."

In addition to the higher risk of side effects, Savage and his colleagues also say the results need to be interpreted within the context of other studies that have found that exposure to broad-spectrum antibiotics, including amoxicillin-clavulanate, can increase the risk of antibiotic-resistant infections.