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JAMA. 2015 Nov 17;314(19):2034-2044. doi: 10.1001/jama.2015.13896.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.

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Department of Pediatrics, Washington University in St Louis School of Medicine, St Louis, Missouri (Bacharier, Beigelman, Castro); Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio (Guilbert); Department of Public Health Sciences, Pennsylvania State University, Hershey (Mauger, Boehmer); Department of Pediatrics, Emory University, Atlanta, Georgia (Fitzpatrick); Pediatrics Section of Allergy, Immunology, and Rheumatology, University of Wisconsin School of Medicine and Public Health, Madison (Jackson); Division of Allergy/Immunology, Boston Children's Hospital, Boston, Massachusetts (Baxi, Phipatanakul, Sheehan); Benioff Children's Hospital, Oakland, California (Benson, Meade); Department of Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, Missouri (Burnham); University of California, San Francisco, Medicine, San Francisco (Cabana, Lazarus); Rainbow Babies and Children's Hospital, Cleveland, Ohio (Chmiel, Ross); Department of Pediatrics, National Jewish Health, Denver, Colorado (Covar, Olin); University of Arizona, Arizona Respiratory Center, Tucson (Daines, Morgan); Division of Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts (Gaffin); Department of Pediatrics, Allegheny General Hospital, Pittsburgh, Pennsylvania (Gentile); The University of Pittsburgh Asthma Institute, Pittsburgh, Pennsylvania (Holguin); Brigham and Women's Hospital, Boston, Massachusetts (Israel); Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico (Kelly); Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison (Lemanske); Airway Clinical Research Center, University of California, San Francisco, San Francisco, California (Ly); Stroger Hospital of Cook County Pediatric Services, Chicago, Illinois (Moy); Wake Forest University School of Medicine, Winston-Salem, North Carolina (Peters); Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois (Pongracic); Department of Pediatrics/Pulmonary, University of New Mexico, Albuquerque (Raissy); University of Wisconsin-Madison, Madison (Sorkness); The Breathing Institute, Children's Hospital Colorado, Denver (Szefler); University of Virginia School of Medicine, Charlottesville (Teague); Department of Pediatrics, San Francisco General Hospital, San Francisco, California (Thyne); Arizona Respiratory Center, University of Arizona, Tucson, Arizona (Martinez).
Contributed equally

Erratum in



Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed.


To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes.


A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment.


Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period.


The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures.


A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed.


Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy.

TRIAL REGISTRATION: Identifier: NCT01272635.

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