Nader Shaikh, MD, MPH

Credit: Pitt Pediatrics

Treatment with antibiotics of children with acute sinusitis shows minimal benefits in those without nasopharyngeal bacterial pathogens at the time of their condition’s presentation, according to new findings, and the effects did not depend on nasal discharge’s color.¹

These findings resulted from research into the overlap between symptoms of viral upper respiratory tract infection and acute sinusitis, an occurrence which the investigators indicate some subgroups of younger patients with acute sinusitis and given antibiotics may not benefit from the use of such treatment.

The investigators conducted their analysis to determine if therapy with antibiotics could be appropriately withheld in prespecified subgroups. The research was authored by Nader Shaikh, MD, MPH, from the UPMC Children’s Hospital of Pittsburgh in Pennsylvania.

“This multicenter, double-blind, placebo-controlled, randomized clinical trial addressed these 2 questions by comparing treatment with amoxicillin and clavulanate potassium vs matching placebo in children aged 2 to 11 years meeting clinical criteria for the diagnosis of acute sinusitis,” Shaikh and colleagues wrote.

Background and Findings

The study investigators conducted the trial between February of 2016 and April of 2022 at several different primary care offices affiliated with different institutions, including the Children’s Hospital of Philadelphia, the UPMC Children’s Hospital of Pittsburgh, Kentucky Pediatric and Adult Research, the University of Wisconsin–Madison, West Virginia University Children’s, and Cyn3rgy Research.

The trial protocol received approval from the respective institutional review boards and is detailed in Supplement 1. The investigators aimed to enroll children aged 2 to 11 years who met the clinical practice guideline from the American Academy of Pediatrics for acute sinusitis.

The participants deemed as eligible by the team had either persistent symptoms lasting 11 - 30 days without improvement or worsening, also characterized by improvement and then a relapse between days 6 - 10 following a viral upper respiratory infection. The investigators noted that children with scores of 9 or more on the Pediatric Rhinosinusitis Symptom Scale (PRSS) were included, and race data was gathered for reporting purposes to the National Institutes of Health.

Research assistants involved in the study questioned parents on their child's upper respiratory tract infection symptoms to determine their eligibility. If children met the criteria for acute sinusitis and the diagnosis was confirmed by the clinician, written consent was obtained from the parent.

Children with wheezing, severe sinusitis, asthma, cough as the only symptom, allergic rhinitis without worsening respiratory symptoms, cystic fibrosis, immunodeficiency, immotile cilia syndrome, concurrent infections, amoxicillin and clavulanate allergies, systemic toxicity, prior sinus surgery, recent antibiotic use, or language or phone use limitations were excluded.

Participants were categorized into 2 arms based upon colored nasal discharge presence and randomly given either oral amoxicillin and clavulanate or a placebo for 10 days. The study was double-blind, ensuring treatment assignments were undisclosed to research personnel, parents, and non-study clinicians.

An interim evaluation was used if a child showed treatment failure signs or if parental concerns became apparent, and treatment was adjusted as needed. Nasopharyngeal specimens were collected at the beginning and end of the study to identify bacterial cultures using standard microbiological techniques.

The main focus of the study was to assess symptom burden using daily symptom scores on a validated scale (ranging from 0 - 40) during the 10-day period following diagnosis. Other outcomes considered were adverse events (including clinically significant diarrhea), treatment failure, and resource utilization by families.

The investigators used 510 children, and most of these participants were aged 2 - 5 years (64%), male (54%), White (52%), and not Hispanic (89%). Those treated with amoxicillin and clavulanate showed substantially lower mean symptom scores (9.04 [95% CI, 8.71 - 9.37]) versus those given a placebo (10.60 [95% CI, 10.27 - 10.93]), and this led to an in between-group difference of -1.69 (95% CI, -2.07 to -1.31).

The investigators reported that the antibiotic group was shown to have also experienced a shorter time to resolution (7.0 days) compared to the placebo group (9.0 days) (P = 0.003). For children without detected nasopharyngeal pathogens, the benefit of antibiotic treatment was not as pronounced as those with pathogens identified.

The team added that the between-group difference in mean symptom scores was -0.88 (95% CI, -1.63 to -0.12) for those without detected pathogens, whereas it was -1.95 (95% CI, -2.40 to -1.51) for participants with detected pathogens. That said, the team found that the presence of colored nasal discharge did not substantially affect treatment efficacy.

The research team noted that the between-group difference for colored nasal discharge was -1.62 (95% CI, -2.09 to -1.16), while for clear nasal discharge, it was -1.70 (95% CI, -2.38 to -1.03) (P = 0.52 for the interaction between treatment arm and the presence of colored nasal discharge).

“In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens on presentation, and its effects did not depend on the color of nasal discharge,” they wrote. “Testing for specific bacteria on presentation may represent a strategy to reduce antibiotic use in this condition.”

References

1. ^{Shaikh N, Hoberman A, Shope TR, et al. Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial. JAMA. 2023;330(4):349–358. doi:10.1001/jama.2023.10854.}