Macrolides vs. Beta-Lactams in Pediatric Community-Acquired Pneumonia

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SAN DIEGO—Macrolides might involve a lower risk of treatment failure than beta-lactams among children with community-acquired pneumonia (CAP), according to a 31-pediatric practice, retrospective cohort database analysis reported at IDWeek 2017.

“While rates of treatment failure in children diagnosed with CAP in the outpatient setting were low, macrolides were associated with a lower failure rate than treatment with beta-lactams,” reported study coauthor Lori Handy, MD, MSCE, of the Division of Infectious Diseases, The Children’s Hospital of Philadelphia in Philadelphia, and the Nemours/A.I. duPont Hospital for Children in Wilmington, DE.

“This may be due to residual confounding by indication or changing epidemiology of outpatient pneumonia,” Dr. Handy warned. Subtherapeutic dosing of amoxicillin might also be an issue, she acknowledged.

Amoxicillin is a first-line treatment for mild CAP in healthy, immunized children because it is effective against S. pneumoniae, Dr. Handy noted. But in clinical practice, macrolides, which have inferior anti-pneumococcal activity, are more frequently prescribed against outpatient CAP.

“Up to 40% of S. pneumoniae isolates are resistant to macrolides,” Dr. Handy said. 

The study authors compared beta-lactam vs. macrolide antibiotic effectiveness in The Children’s Hospital of Philadelphia (CHOP) primary care network. 

Data was compiled from electronic records for patients aged 3 months to 18 years who were diagnosed with CAP between 2009 and 2013 and prescribed monotherapy of amoxicillin, broad-spectrum beta-lactam antibiotics, or macrolides.

Multivariate analyses revealed that of 10,470 children who received antibiotics for pneumonia, 40.6% received amoxicillin, 42.6% received macrolides, and 16.8% received broad-spectrum beta-lactams.

The groups differed by age, proportion of African-American patients, insurance type, documented fever, chest x-ray orders, and antibiotic history. The study was not randomized, Dr. Handy cautioned.

“Treatment failure in 2 weeks following diagnosis occurred in 634 children (6.1%); 418 required a change in antibiotic by the pediatrician, 169 required an ED visit, and 47 required hospitalization,” she reported. 

Treatment failure occurred in 9.8% of children receiving amoxicillin, 3.2% of those receiving a macrolide (adjusted odds ratio [OR] vs. amoxicillin: 0.32; 95% CI: 0.25–0.41), and 10.4% on broad-spectrum antimicrobials (adjusted OR 1.05; 95% CI: 0.79–1.39).

The study was retrospective and nonrandomized, and confounding by indication could not be ruled out, cautioned Dr. Handy. Furthermore, CAP is a clinical diagnosis and there exists no rapid confirmatory lab test, she added. Randomized controlled trials are needed before revisions to treatment guidelines are contemplated, she said.

“In healthy children with CAP, use of macrolide antibiotics compared with either amoxicillin or broad-spectrum beta-lactams decreased odds of treatment failure,” she concluded. “Results were more pronounced for school-aged children.”

The study authors disclosed a research grant from Merck and consulting fees from Astellas and Nabriva.

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Reference:

Handy L, Gerber JS, Bryan M, Zaoutis T, Feemster K. Comparative effectiveness of beta-lactams versus azithromycin for treatment of outpatient pediatric community-acquired pneumonia. Poster presented at IDWeek; October 4–8, 2017; San Diego, CA. http://www.idweek.org