Treatment failure with amoxicillin-clavulanate for pediatric acute sinusitis was similar compared with amoxicillin alone, but the broad-spectrum antibiotic may be associated with more adverse events, an examination of a large commercial claims database revealed.
The two frequently prescribed antibiotics were similar in their risk for treatment failure (1.7% with amoxicillin-clavulanate vs 1.8% with amoxicillin; RR 0.98, 95% CI 0.92-1.05), reported Timothy Savage, MD, MPH, MSc, of Brigham and Women’s Hospital in Boston, and colleagues.
Overall, adverse events occurred in 2.3% of the amoxicillin-clavulanate patients and 2% of the amoxicillin patients (RR 1.15, 95% CI 1.08-1.22), with yeast infections and gastrointestinal symptoms disproportionately more common among users of the broad-spectrum antibiotic, according to the observational cohort study in JAMA.
Reached for comment, Scott Roberts, MD, of Yale School of Medicine in New Haven, Connecticut, said he was pleasantly surprised regarding the study’s findings, as he suspected amoxicillin-clavulanate users would have had better outcomes due to its wider range of activity.
“This study reassures clinicians that amoxicillin is sufficient for bacterial sinusitis in today’s era, when many have received the pneumococcal vaccine and antibiotic resistance is more widespread,” said Roberts, who was not involved in the research. “These findings provide reassurance that amoxicillin should be a core treatment option of acute sinusitis given similar outcomes data and [the] improved side effect profile.”
He also pointed to another benefit of the results. “Wearing my antibiotic stewardship hat when looking at our future of increasing antimicrobial resistance, this study is welcome news as it will avoid unnecessary antibiotic overuse and improve patient outcomes,” said Roberts.
Christopher Strother, MD, of the Icahn School of Medicine at Mount Sinai in New York City, echoed these sentiments, stating the study findings enforce his own treatment plans.
“I try to avoid giving the antibiotic in the first place,” he said. “If that child is well-appearing and can be managed with keeping their symptoms under control, my general practice is to try to give them a chance to get better on their own as long as we keep them comfortable.”
Patients who don’t appear well, or “are really uncomfortable or really sick, those are the ones that need the antibiotics, but I tend to start with amoxicillin already,” said Strother.
Savage and colleagues noted that acute sinusitis accounts for approximately 4.9 million prescriptions among children in the U.S., making it one of the most common causes of prescriptions for children — with amoxicillin and amoxicillin-clavulanate making up a majority of treatments prescribed.
There is no evidence-based consensus on the best antibiotic for pediatric acute sinusitis, as the Infectious Diseases Society of America recommends amoxicillin-clavulanate, and the American Academy of Pediatrics recommends amoxicillin with or without clavulanate.
Furthermore, few if any studies have compared the two treatments since the first introduction of conjugate pneumococcal vaccines in 2000, Savage’s group said. Since then, they added, the routine use of this vaccine and increasing antibiotic resistance have likely shifted the culprit microbiology in acute bacterial sinusitis, which may have implications for rates of treatment failure.
The present study relied on MarketScan Commercial Claims and Encounters Database, a nationwide healthcare utilization database. Investigators included 320,141 kids diagnosed with acute sinusitis who got a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin from 2017 to 2021.
Propensity score matching resulted in 99,471 matched pairs for comparison between groups. Of those matched patients, a little over half were ages 12 to 17 years, while 26% were 6 to 11 years and 23% were 5 years or younger. Girls made up just over half the cohort.
The risks of developing yeast infections (RR 1.33, 95% CI 1.16-1.54) and gastrointestinal symptoms (RR 1.15, 95% CI 1.05-1.25) were significantly greater among amoxicillin-clavulanate patients versus the amoxicillin group. Urgent care visits were also slightly more common in the amoxicillin-clavulanate group, at 9.6% compared with 5.9% in the amoxicillin group.
Strother told MedPage Today that the slight increase in these adverse events is fairly typical with many antibiotics across the board.
When “you give an antibiotic, you’re not only getting rid of whatever infection you’re trying to treat, but you’re also going to get rid of a lot of helpful, healthy bacteria that are in your body,” he said, which can result in more stomach upset, diarrhea, and yeast infections.
Savage’s group noted that data regarding race, ethnicity, and socioeconomic status were not available. Other limitations included lack of available microbiologic data, an inability to evaluate medication adherence, some missing prescriber data, and missing information regarding patient weight and weight-based dosing.
This study was supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH.
Savage reported grants from the NICHD and institutional support from UCB.
Strother and Roberts had no disclosures.
Source Reference: Savage TJ, et al “Treatment failure and adverse events after amoxicillin-clavulanate vs amoxicillin for pediatric acute sinusitis” JAMA 2023; DOI: 10.1001/jama.2023.15503.