More Evidence Narrow-Spectrum Antibiotics Best for ARTIs

Rabiya S. Tuma, PhD

June 12, 2017

SAN FRANCISCO — Narrow antibiotics are as effective as broad ones for treating acute respiratory tract infections (ARTIs) in children and come with fewer adverse effects, according to a large prospective study.

Current guidelines recommend the use of narrow-spectrum antibiotics for ARTIs, yet previous studies have shown that up to half of physicians still prescribe broader-spectrum antibiotics than those recommended.

The reason for that disconnect is likely multifactorial, including the lack of direct comparisons in randomized controlled trials, said Jeffrey Gerber, MD, PhD, an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia (CHOP), Pennsylvania, during a presentation at the Pediatrics Academic Societies (PAS) 2017 Annual Meeting in May.

To get around that evidence gap, Dr Gerber and colleagues performed a prospective study in a clinic setting to learn how narrow- vs broad-spectrum antibiotics perform with respect to patient- and parent-centered outcomes, including child suffering as measured by the validated PedsQL tool.

Between January 2015 and April 2016, the team enrolled children aged 6 months to 12 years from 31 primary care practices in Pennsylvania and New Jersey that are part of the CHOP network and serve a diverse group of patients.

Using the electronic medical record system, the team identified 58,488 patients seen for ARTI and prescribed antibiotics and randomly selected 10,296, whom they tried to reach by phone. Of those, the researchers successfully contacted, enrolled, and completed an interview with 2472 parents on day 5 after the child's visit. Nearly all of the participants (2096) completed an interview on day 14.

Of the children enrolled 1100 had acute otitis media, 667 had sinusitis and 705 had group A streptococcal pharyngitis (GAS). All patients with GAS were required to have a positive streptococcus test result to be eligible for the study.

Overall, 1604 (65%) received narrow-spectrum antibiotics, which included penicillin and amoxicillin, and the others received broad-spectrum antibiotics, which included amoxicillin-clavulanate, azithromycin, cefdinir, cefprozil, cefuroxime axetil, cephalexin, ceftriaxone, or sodium cefadroxil. "I know those aren't crazy broad spectrum, but for the purposes of acute respiratory infections, they are relatively broad spectrum," Dr Gerber said during his presentation.

Among the children who received narrow-spectrum antibiotics, just 77 (3.1%) received a second antibiotic prescription, which suggests a low rate of treatment failure. Moreover, just 33 of those prescriptions were a different spectrum. Dr Gerber emphasized that the low rate of second prescriptions indicates these children did well on a narrow-spectrum agent.

The average PedsQL score was 91.1 for the entire population on day 14, which was the primary endpoint. Children who received a narrow-spectrum antibiotic had a slightly higher score (91.5) than those who received broader antibiotics (90.2). "Although this was statistically significant because we had a lot of patients and a lot of power, we did not think this was a clinically significant difference. We thought these were the same," Dr Gerber said.

In terms the secondary outcomes, including missed work and school, need for additional childcare, child sleep quality, side effects, and speed of symptom resolution, the only difference between the groups was the rate of side effects.

Among children prescribed a narrow antibiotic, 25.1% experienced an adverse side effect (diarrhea, rash, upset stomach, or vomiting) vs 35.6% of those who received broad-spectrum drugs. In an adjusted analysis, stratified by diagnosis, the difference between the two groups was 11.6 percentage points, which was significant (P < .001).

Dr Gerber noted several study limitations, including reliance on the diagnosis in the electronic record. "Many were likely viral, but this was a real-world example and this is what they were treating," he said.

Also, the PedsQL instrument might not be sensitive enough to detect minor differences in symptoms, and because this was not a randomized trial, there could be unobserved confounding.

When asked during the discussion about the policy implications of the findings, Dr Gerber said, "This is another piece of evidence that might help resolve some of the conflicts that are out there among different agencies that recommend different antimicrobials."

"This study is large and it adds very important support to the guidelines themselves," Russell Steele, MD, told Medscape Medical News. "If you use cefdinir or amoxicillin-clavulanate, it's no better than amoxicillin." Dr Steele, division head of pediatric infectious diseases at Ochsner Children's Health Center and professor of pediatrics at the University of Queensland School of Medicine, Ochsner Clinical School, Australia, and clinical professor of pediatrics, at Tulane University School of Medicine, New Orleans, Louisiana, was not involved in the study.

That said, he cautioned that thinking of this as a comparison of narrow- vs broad-spectrum drugs was a bit misleading because none of the agents used are truly broad spectrum. He suggested it might be better to consider the difference as treating within the guidelines or outside of them. And these data show there is no reason to use an agent outside the guidelines for the conditions studied, he said.

For example, in the case of otitis media, some clinicians might feel the need to prescribe cephalosporins over amoxicillin to cover β-lactamase–secreting organisms, such as Haemophilus influenzae and Moraxella catarrhalis. "The lack of difference [in this study] supports that most of them do not need to be treated with an alternative to what is in the guidelines," Dr Steele said.

The study was funded by the Patient-Centered Outcomes Research Institute. The authors have disclosed no relevant financial relationships.

Pediatrics Academic Societies (PAS) 2017 Annual Meeting . Abstract 3600.1. Presented May 8, 2017.

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