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

Leonard B. Bacharier, Theresa W. Guilbert, David T. Mauger, Susan Boehmer, Avraham Beigelman, Anne M. Fitzpatrick, Daniel J. Jackson, Sachin N. Baxi, Mindy Benson, Carey Ann D. Burnham, Michael Cabana, Mario Castro, James F. Chmiel, Ronina Covar, Michael Daines, Jonathan M. Gaffin, Deborah Ann Gentile, Fernando Holguin, Elliot Israel, H. William KellyStephen C. Lazarus, Robert F. Lemanske, Ngoc Ly, Kelley Meade, Wayne Morgan, James Moy, Tod Olin, Stephen P. Peters, Wanda Phipatanakul, Jacqueline A. Pongracic, Hengameh H. Raissy, Kristie Ross, William J. Sheehan, Christine Sorkness, Stanley J. Szefler, W. Gerald Teague, Shannon Thyne, Fernando D. Martinez

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION Participants were randomly assigned to receive azithromycin (12mg/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. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, thatwould in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngealsamples, alongwithadverseevents,wereamongthesecondaryoutcomemeasures. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

Original languageEnglish (US)
Pages (from-to)2034-2044
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume314
Issue number19
DOIs
StatePublished - Nov 17 2015
Externally publishedYes

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Azithromycin
Preschool Children
Respiratory System
Randomized Controlled Trials
Placebos
National Heart, Lung, and Blood Institute (U.S.)
Virus Diseases
Signs and Symptoms
Prescriptions
Adrenal Cortex Hormones
Outcome Assessment (Health Care)
Anti-Bacterial Agents
Bacteria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Bacharier, Leonard B.; Guilbert, Theresa W.; Mauger, David T.; Boehmer, Susan; Beigelman, Avraham; Fitzpatrick, Anne M.; Jackson, Daniel J.; Baxi, Sachin N.; Benson, Mindy; Burnham, Carey Ann D.; Cabana, Michael; Castro, Mario; Chmiel, James F.; Covar, Ronina; Daines, Michael; Gaffin, Jonathan M.; Gentile, Deborah Ann; Holguin, Fernando; Israel, Elliot; William Kelly, H.; Lazarus, Stephen C.; Lemanske, Robert F.; Ly, Ngoc; Meade, Kelley; Morgan, Wayne; Moy, James; Olin, Tod; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A.; Raissy, Hengameh H.; Ross, Kristie; Sheehan, William J.; Sorkness, Christine; Szefler, Stanley J.; Gerald Teague, W.; Thyne, Shannon; Martinez, Fernando D.

In: JAMA - Journal of the American Medical Association, Vol. 314, No. 19, 17.11.2015, p. 2034-2044.

Research output: Contribution to journalArticle

Bacharier, LB, Guilbert, TW, Mauger, DT, Boehmer, S, Beigelman, A, Fitzpatrick, AM, Jackson, DJ, Baxi, SN, Benson, M, Burnham, CAD, Cabana, M, Castro, M, Chmiel, JF, Covar, R, Daines, M, Gaffin, JM, Gentile, DA, Holguin, F, Israel, E, William Kelly, H, Lazarus, SC, Lemanske, RF, Ly, N, Meade, K, Morgan, W, Moy, J, Olin, T, Peters, SP, Phipatanakul, W, Pongracic, JA, Raissy, HH, Ross, K, Sheehan, WJ, Sorkness, C, Szefler, SJ, Gerald Teague, W, Thyne, S & Martinez, FD 2015, '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', JAMA - Journal of the American Medical Association, vol. 314, no. 19, pp. 2034-2044. https://doi.org/10.1001/jama.2015.13896
Bacharier, Leonard B. ; Guilbert, Theresa W. ; Mauger, David T. ; Boehmer, Susan ; Beigelman, Avraham ; Fitzpatrick, Anne M. ; Jackson, Daniel J. ; Baxi, Sachin N. ; Benson, Mindy ; Burnham, Carey Ann D. ; Cabana, Michael ; Castro, Mario ; Chmiel, James F. ; Covar, Ronina ; Daines, Michael ; Gaffin, Jonathan M. ; Gentile, Deborah Ann ; Holguin, Fernando ; Israel, Elliot ; William Kelly, H. ; Lazarus, Stephen C. ; Lemanske, Robert F. ; Ly, Ngoc ; Meade, Kelley ; Morgan, Wayne ; Moy, James ; Olin, Tod ; Peters, Stephen P. ; Phipatanakul, Wanda ; Pongracic, Jacqueline A. ; Raissy, Hengameh H. ; Ross, Kristie ; Sheehan, William J. ; Sorkness, Christine ; Szefler, Stanley J. ; Gerald Teague, W. ; Thyne, Shannon ; Martinez, Fernando D. / 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. In: JAMA - Journal of the American Medical Association. 2015 ; Vol. 314, No. 19. pp. 2034-2044.
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abstract = "IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION Participants were randomly assigned to receive azithromycin (12mg/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. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, thatwould in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngealsamples, alongwithadverseevents,wereamongthesecondaryoutcomemeasures. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.",
author = "Bacharier, {Leonard B.} and Guilbert, {Theresa W.} and Mauger, {David T.} and Susan Boehmer and Avraham Beigelman and Fitzpatrick, {Anne M.} and Jackson, {Daniel J.} and Baxi, {Sachin N.} and Mindy Benson and Burnham, {Carey Ann D.} and Michael Cabana and Mario Castro and Chmiel, {James F.} and Ronina Covar and Michael Daines and Gaffin, {Jonathan M.} and Gentile, {Deborah Ann} and Fernando Holguin and Elliot Israel and {William Kelly}, H. and Lazarus, {Stephen C.} and Lemanske, {Robert F.} and Ngoc Ly and Kelley Meade and Wayne Morgan and James Moy and Tod Olin and Peters, {Stephen P.} and Wanda Phipatanakul and Pongracic, {Jacqueline A.} and Raissy, {Hengameh H.} and Kristie Ross and Sheehan, {William J.} and Christine Sorkness and Szefler, {Stanley J.} and {Gerald Teague}, W. and Shannon Thyne and Martinez, {Fernando D.}",
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TY - JOUR

T1 - 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

AU - Bacharier, Leonard B.

AU - Guilbert, Theresa W.

AU - Mauger, David T.

AU - Boehmer, Susan

AU - Beigelman, Avraham

AU - Fitzpatrick, Anne M.

AU - Jackson, Daniel J.

AU - Baxi, Sachin N.

AU - Benson, Mindy

AU - Burnham, Carey Ann D.

AU - Cabana, Michael

AU - Castro, Mario

AU - Chmiel, James F.

AU - Covar, Ronina

AU - Daines, Michael

AU - Gaffin, Jonathan M.

AU - Gentile, Deborah Ann

AU - Holguin, Fernando

AU - Israel, Elliot

AU - William Kelly, H.

AU - Lazarus, Stephen C.

AU - Lemanske, Robert F.

AU - Ly, Ngoc

AU - Meade, Kelley

AU - Morgan, Wayne

AU - Moy, James

AU - Olin, Tod

AU - Peters, Stephen P.

AU - Phipatanakul, Wanda

AU - Pongracic, Jacqueline A.

AU - Raissy, Hengameh H.

AU - Ross, Kristie

AU - Sheehan, William J.

AU - Sorkness, Christine

AU - Szefler, Stanley J.

AU - Gerald Teague, W.

AU - Thyne, Shannon

AU - Martinez, Fernando D.

PY - 2015/11/17

Y1 - 2015/11/17

N2 - IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION Participants were randomly assigned to receive azithromycin (12mg/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. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, thatwould in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngealsamples, alongwithadverseevents,wereamongthesecondaryoutcomemeasures. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

AB - IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION Participants were randomly assigned to receive azithromycin (12mg/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. MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, thatwould in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngealsamples, alongwithadverseevents,wereamongthesecondaryoutcomemeasures. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

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