Study finds two antibiotics equally effective against sinusitis in children, but one has fewer side effects

In a new study published in Journal of the American Medical Association The study, led by researchers at Brigham and Women’s Hospital, found that patients taking amoxicillin-clavulanic acid had higher rates of gastrointestinal symptoms and yeast infections than those taking amoxicillin.

Acute sinusitis is one of the most common reasons children take antibiotic medications, with nearly 5 million antibiotic prescriptions written to treat this condition in the United States each year. The majority of these prescriptions are for the drugs amoxicillin and amoxicillin-clavulanic acid, but there is a lack of consensus on which drug should be used as first-line therapy in children.

Scientists analyzed the outcomes of more than 300,000 children who took both drugs. They found no difference in treatment failure rates (i.e., having to receive a new course of antibiotics or seek additional treatment for sinusitis or complications) between patients taking amoxicillin and amoxicillin-clavulanic acid.

In fact, treatment failure was so rare that the study’s authors said doctors should trust both drugs to cure acute sinusitis that requires antibiotics. However, patients taking amoxicillin-clavulanic acid were at higher risk for adverse events, particularly gastrointestinal symptoms and yeast infections.

“This study adds recent, actionable data and evidence to inform clinicians about which antibiotics they should choose to treat children with acute bacterial sinusitis,” said lead author, M.D., M.P.H., M.S., said Timothy Savage, associate epidemiologist in the Brigham’s Division of Pharmacoepidemiology. Pharmacoeconomics. “What you can see from this study is that there is no difference in treatment failure rates no matter which of the two antibiotics you choose.”

Amoxicillin-clavulanic acid is thought to treat a wider range of bacteria than amoxicillin, but it is also associated with more gastrointestinal side effects. Scientists are also concerned that over-dosing with amoxicillin-clavulanic acid may accelerate the rate at which infectious bacteria develop antimicrobial resistance in the long term. Therefore, doctors want to know whether the benefits of prescribing amoxicillin-clavulanic acid to children with acute sinusitis outweigh the short- and long-term risks.

Researchers extracted data from 320,141 clinical cases of children diagnosed with acute sinusitis and compared whether children taking amoxicillin or amoxicillin-clavulanic acid were more likely to experience treatment failure. They found no difference in treatment failure rates between the two drugs.

Generally speaking, treatment failure is extremely rare. Less than 2% of prescriptions failed, most of which were corrected through outpatient medication changes. In only 0.1% of children, failure is severe enough to require a trip to the emergency room or hospitalization.

Clinical data showed that adverse events were rare but more common in patients treated with amoxicillin-clavulanic acid, occurring in 2.3% of patients treated with amoxicillin-clavulanic acid and 2% of patients treated with amoxicillin. Patients who received amoxicillin-clavulanic acid had a 15% increased risk of gastrointestinal side effects and a 33% increased risk of yeast infections compared with patients who received amoxicillin. The study’s authors concluded that narrow-spectrum amoxicillin may be the best first-line option against acute sinusitis.

“Our study shows that there are more adverse events when amoxicillin-clavulanic acid is used,” Savage said. “Based on these data, physicians should seriously consider prescribing amoxicillin as a first line of defense in preventing acute sinusitis.”

Not all cases of acute sinusitis are caused by bacterial infections; a previous study found that up to 32% of cases may be caused by viruses. Still, because the symptoms of bacterial and viral sinusitis are nearly indistinguishable, many doctors choose to first treat patients with antibiotics and monitor whether the infection clears up.

Approximately 85% of children with acute sinusitis are treated with antibiotics, with amoxicillin and amoxicillin-clavulanic acid accounting for 65% of these prescriptions. The current study did not include microbiological data, and the authors were unable to discern whether the diagnosis of acute sinusitis was caused by a viral or bacterial infection.

Because this was not a randomized clinical trial, the study authors acknowledged that residual bias may have affected the results, and although they reanalyzed the data in several different ways to try to mitigate this effect, there was no difference in the results.

Two previous studies comparing the clinical outcomes of these two drugs were conducted more than 20 years ago. These analyzes showed that both drugs relieved symptoms at a similar rate, but both studies were limited by a combined sample size of less than 300 patients. The fact that bacterial species have evolved significantly over the past two decades prompted Savage and his team to launch a new, larger study to compare the treatment failure rates of the two drugs.

“If a doctor was trying to decide between these two drugs, they could look at these results and find that 98 percent of the kids got better regardless of whether they were taking amoxicillin or amoxicillin-clavulanic acid,” Savage said. “With these drugs, the chance of a child ending up in the hospital is less than 1 in 1,000. This should provide reassurance that the child will do well regardless of which antibiotic is used.”