Combination β-lactam, Macrolide Pneumonia Therapy in Children Not More Effective

The results of this study question the routine empirical use of macrolide combination therapy in this population.

The use of an added macrolide in combination with the recommended narrow spectrum β-lactam therapy vs β-lactam monotherapy for children with pneumonia did not significantly reduce length of hospital stay, according to a comparative study published in JAMA Pediatrics.

Using data from the Centers for Disease Control and Prevention (CDC)’s Etiology of Pneumonia in the Community (EPIC) surveillance study, β-lactam monotherapy, defined as children receiving β-lactam and oral or parenteral second- or third-generation cephalosporins (excluding anti-pseudomonal cephalosporins), as well as penicillin, ampicillin, ampicillinsulbactam, amoxicillin,andamoxicillin-clavulanate, was compared with β-lactam combination therapy, defined as patients receiving a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin), in children younger than 18 with pneumonia confirmed by radiograph and receiving antibiotics during the first 2 calendar days of hospitalization.

A total of 1019 children in the EPIC study received monotherapy and 399 received combination therapy. No significant difference in length of stay between the groups was found overall (unadjusted hazard ratio [HR], 1.01; 95% CI, 0.90-1.14), using a multivariate analysis, accounting for demographic factors, medical history or prior antibiotic treatment (adjusted HR, 0.87; 95% CI, 0.74-1.01) or using a propensity score-matched analysis (HR, 0.88; 95% CI, 0.74-1.03). Furthermore, no significant difference in length of stay was found in subgroups identified as potentially having an impact on antibiotic selection or length of stay such as, age 5 or older, detection of atypical bacteria, wheezing, and admission to intensive care.  

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Combination therapy was concluded to be no more effective than monotherapy, even in situations in which macrolides are presumed to be beneficial, making this an important target area for improved antibiotic stewardship.

Disclosures: Dr Self reports payment for participation in a scientific advisory board meeting for Cempra Pharmaceuticals, Dr Anderson for consulting for AbbVie and research funding from Regeneron and MedImmune, and, Dr Pavia for participation on data safety and monitoring boards for Alios Pharmaceuticals and Janssen Pharmaceuticals.


Williams DJ, Edwards KM, Self WH, et al. Effectiveness of β-Lactam monotherapy vs macrolide combination therapy for children hospitalized with pneumonia [published online October 30, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.3225