Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia | Pediatrics | JAMA Pediatrics | JAMA Network
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Original Investigation
December 2017

Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia

Author Affiliations
  • 1Division of Hospital Medicine, Monroe Carell Jr. Children’s Hospital, Vanderbilt University Medical Center, Nashville, Tennessee
  • 2Division of Infectious Diseases, Monroe Carell Jr. Children’s Hospital, Vanderbilt University Medical Center, Nashville, Tennessee
  • 3The Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center, Nashville
  • 4Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  • 5Division of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
  • 6Division of Infectious Diseases, Le Bonheur Children’s Hospital, Memphis, Tennessee
  • 7Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis
  • 8Division of Infectious Diseases, Primary Children’s Medical Center, Salt Lake City, Utah
  • 9Department of Pediatrics, University of Utah School of Medicine, Salt Lake City
  • 10Division of Infectious Diseases, Departments of Medicine and Pediatrics, Emory University School of Medicine, Atlanta, Georgia
  • 11Centers for Disease Control and Prevention, Atlanta, Georgia
  • 12Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
JAMA Pediatr. 2017;171(12):1184-1191. doi:10.1001/jamapediatrics.2017.3225
Key Points

Question  Is treatment with a β-lactam antibiotic in combination with a macrolide more effective than β-lactam monotherapy among children hospitalized with pneumonia?

Findings  In this prospective cohort of more than 1400 children hospitalized with pneumonia, there were no significant differences in length of stay, intensive care admission, rehospitalizations, or recovery at follow-up among children receiving β-lactam plus macrolide combination therapy compared with β-lactam monotherapy.

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


Importance  β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches.

Objective  To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia.

Design, Setting, and Participants  We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children’s hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017.

Main Outcomes and Measures  We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients’ length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up.

Results  Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the Etiology of Pneumonia in the Community Study with radiographically confirmed pneumonia in the study period; 1019 (71.9%) received β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes.

Conclusions and Relevance  Empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population.