Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Aug 22;8(8):CD009834.
doi: 10.1002/14651858.CD009834.pub3.

Antibiotics for persistent cough or wheeze following acute bronchiolitis in children

Affiliations
Review

Antibiotics for persistent cough or wheeze following acute bronchiolitis in children

Gabrielle B McCallum et al. Cochrane Database Syst Rev. .

Abstract

Background: Bronchiolitis is a common acute respiratory condition with high prevalence worldwide. This clinically diagnosed syndrome is manifested by tachypnoea (rapid breathing), with crackles or wheeze in young children. In the acute phase of bronchiolitis (≤ 14 days), antibiotics are not routinely prescribed unless the illness is severe or a secondary bacterial infection is suspected. Although bronchiolitis is usually self-limiting, some young children continue to have protracted symptoms (e.g. cough and wheezing) beyond the acute phase and often re-present to secondary care.

Objectives: To compare the effectiveness of antibiotics versus controls (placebo or no treatment) for reducing or treating persistent respiratory symptoms following acute bronchiolitis within six months of acute illness.

Search methods: We searched the following databases: the Cochrane Airways Group Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), the World Health Organization (WHO) trial portal, the Australian and New Zealand Clinical Trials Registry, and ClinicalTrials.gov, up to 26 August 2016.

Selection criteria: We included randomised controlled trials (RCTs) comparing antibiotics versus controls (placebo or no treatment) given in the post-acute phase of bronchiolitis (> 14 days) for children younger than two years with a diagnosis of bronchiolitis.

Data collection and analysis: Two review authors independently assessed studies against predefined criteria, and selected, extracted, and assessed data for inclusion. We contacted trial authors for further information.

Main results: In this review update, we added one study with 219 children. A total of two RCTs with 249 children (n = 240 completed) were eligible for inclusion in this review. Both studies contributed to our primary and secondary outcomes, but we assessed the quality of evidence for our three primary outcomes as low, owing to the small numbers of studies and participants; and high attrition in one of the studies. Data show no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up (odds ratio (OR) 0.69, 95% confidence interval (CI) 0.37 to 1.28; fixed-effect model); and number of children (n = 240) rehospitalised with respiratory illness within six months (OR 0.54, 95% CI 0.05 to 6.21; random-effects model). We were unable to analyse exacerbation rate because studies used different methods to report this information. Data showed no significant differences between treatment groups for our secondary outcome: proportion of children (n = 240) with wheeze at six months (OR 0.47, 95% CI 0.06 to 3.95; random-effects model). One study reported bacterial resistance, but only at 48 hours (thus with limited applicability for this review). Another study reported adverse events from which all children recovered and remained in the study.

Authors' conclusions: Current evidence is insufficient to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute bronchiolitis phase. Future RCTs are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms. This is particularly important in populations with high acute and post-acute bronchiolitis morbidity (e.g. indigenous populations in Australia, New Zealand, and the USA).

PubMed Disclaimer

Conflict of interest statement

Three review authors (GBM, PSM, and ABC) were authors of the McCallum 2015 paper. Review author EJP, who was not involved in the McCallum 2015 trial, extracted data for this review.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.
4
4
Forest plot of comparison: 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), outcome: 1.1 Number of participants who were not cured at follow‐up (up to 6 months).
5
5
Forest plot of comparison: 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), outcome: 1.2 Number of participants who were rehospitalised within 6 months.
6
6
Forest plot of comparison: 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), outcome: 1.3 Proportion of participants with wheeze (within 6 months of intervention).
1.1
1.1. Analysis
Comparison 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), Outcome 1 Number of participants who were not cured at follow‐up (up to 6 months).
1.2
1.2. Analysis
Comparison 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), Outcome 2 Number of participants who were rehospitalised within 6 months.
1.3
1.3. Analysis
Comparison 1 Prevention of post‐bronchiolitis syndrome (antibiotics vs placebo), Outcome 3 Proportion of participants with wheeze (within 6 months of intervention).

Update of

Similar articles

Cited by

References

References to studies included in this review

McCallum 2015 {published data only}
    1. McCallum GB, Morris PS, Grimwood K, Maclennan C, White AV, Chang AB, et al. Three‐weekly doses of azithromycin for indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo‐controlled trial. Frontiers in Pediatrics 2015;3:1‐9. - PMC - PubMed
Tahan 2007 {published data only}
    1. Tahan F, Ozcan A, Koc N. Clarithromycin in the treatment of RSV bronchiolitis: a double‐blind, randomised, placebo‐controlled trial. European Respiratory Journal 2007;29:91‐7. - PubMed

References to studies excluded from this review

Beigelman 2015 {published data only}
    1. Beigelman A, Isaacson‐Schmid M, Sajol G, Baty J, Rodrigues OM, Leege E, et al. Randomized trial to evaluate azithromycin's effects on serum and upper airway IL‐8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis. Journal of Allergy and Clinical Immunology 2015;135(5):1171‐8e1. [CN‐01087161; CN‐01130880; CN‐01136644; P30 CA091842] - PMC - PubMed
Friis 1984 {published data only}
    1. Friis B, Anderson P, Brenoe E, Hornsleth A, Jensen A, Knudsen F, et al. Antibiotic treatment of pneumonia and bronchiolitis ‐ a prospective randomised study. Archives of Disease in Childhood 1984;59:1038‐45. - PMC - PubMed
Kabir 2009 {published data only}
    1. Kabir A, Mollah A, Anwar K, Rahman A, Amin R, Rahman M. Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh. Acta Paediatrica 2009;98:1593‐9. - PubMed
Kneyber 2008 {published data only}
    1. Kneyber MC, Woensel JB, Uitjendaal E, Uiterwaal C, Kimpen J. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial. Pediatric Pulmonology 2008;43:142‐9. - PubMed
Mazumder 2009 {published data only}
    1. Mazumder M, Hossain M, Kabir A. Management of bronchiolitis with or without antibiotics ‐ a randomized control trial. Journal of Bangladesh College of Physicians and Surgeons 2009;27:63‐9.
McCallum 2013 {published data only}
    1. McCallum GB, Morris PS, Chatfield MD, Maclennan C, White AV, Chang AB. A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis: a randomised, placebo‐controlled trial. PloS One 2013;8(9):1‐9. - PMC - PubMed
Pinto 2012 {published data only}
    1. Pinto LA, Pitrez PM, Luisi F, Mello PP, Gerhardt M, Marostica PJ. Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes: a randomized, double‐blinded, and placebo‐controlled clinical trial. Journal of Paediatrics 2012;161(6):1104‐8. [RBR‐257ZBC; SN‐1099‐0496] - PubMed

Additional references

Bailey 2009
    1. Bailey EJ, Maclennan C, Morris PS, Kruske SG, Brown N, Chang AB. Risks of severity and readmission of indigenous and non‐indigenous children hospitalised for bronchiolitis. Journal of Paediatrics and Child Health 2009;45:593‐7. - PubMed
Blom‐Danielle 2007
    1. Blom‐Danielle JM, Ermers M, Bont L, van‐Woensel‐Job BM, van‐Aalderen‐Wim MC. Inhaled corticosteroids during acute bronchiolitis in the prevention of post‐bronchiolitic wheezing. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD004881.pub3] - DOI - PubMed
Carroll 2009
    1. Carroll N, Wu P, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, et al. The severity‐dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma. Journal of Allergy and Clinical Immunology 2009;123:1055‐61. - PMC - PubMed
Chang 2009
    1. Chang AB, Chang CC, O'Grady K, Torzillo PJ. Lower respiratory tract infections. Pediatric Clinics of North America 2009;56(6):1303‐21. - PubMed
Chang 2017
    1. Chang AB, Oppenheimer JJ, Weinberger M, Rubin BK, Weir K, Irwin RS. Management of children with chronic wet cough and protracted bacterial bronchitis: CHEST Guideline and Expert Panel Report. Chest 2017;151(4):884‐90. - PubMed
Didierlaurent 2008
    1. Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, et al. Sustained desensitization to bacterial Toll‐like receptor ligands after resolution of respiratory influenza infection. Journal of Experimental Medicine 2008;205(2):323‐9. - PMC - PubMed
Fox 1999
    1. Fox GF, Everard ML, Marsh MJ, Milner AD. Randomised controlled trial of budesonide for the prevention of post‐bronchiolitis wheezing. Archives of Disease in Childhood 1999;80(4):343‐7. - PMC - PubMed
Giamarellos‐Bourboulis 2008
    1. Giamarellos‐Bourboulis EJ. Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. International Journal of Antimicrobial Agents 2008;31(1):12‐20. - PubMed
GRADEpro GDT 2015
    1. GRADEpro GDT. GRADEpro Guideline Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). gradepro.org.
Halfhide 2008
    1. Halfhide C, Smythe RL. Innate immune response and bronchiolitis and preschool recurrent wheeze. Paediatric Respiratory Reviews 2008;9(4):251‐62. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [March 2011]. The Cochrane Collaboration, 2011. www.cochrane‐handbook.org.
Kim 2010
    1. Kim CK, Choi J, Kim HB, Callaway Z, Shin BM, Kim JT, et al. A randomized intervention of montelukast for post‐bronchiolitis: effect on eosinophil degranulation. Journal of Pediatrics 2010;156(5):749‐54. - PubMed
Leach 1994
    1. Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatric Infectious Disease Journal 1994;13(11):983‐9. - PubMed
Leconte 2008
    1. Leconte S, Paulus D, Degryse J. Prolonged cough in children: a summary of the Belgian primary care clinical guideline. Primary Care Respiratory Journal 2008;17(4):206‐11. - PMC - PubMed
Marchant 2005
    1. Marchant JM, Morris P, Gaffney J, Chang AB. Antibiotics for prolonged moist cough in children. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD004822.pub2] - DOI - PubMed
Marchant 2012
    1. Marchant JM, Masters IB, Champion A, Petsky HL, Chang AB. Randomised controlled trial of amoxycillin‐clavulanate in children with chronic wet cough. Thorax 2012;67(8):689‐93. [DOI: 10.1136/thoraxjnl-2011-201506] - DOI - PubMed
McCallum 2012
    1. McCallum GB, Morris PS, Chang AB. Antibiotics for persistent cough or wheeze following acute bronchiolitis in children. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.CD009834.pub2] - DOI - PubMed
McCallum 2016
    1. McCallum GB, Chatfield MD, Morris PS, Chang AB. Risk factors for adverse outcomes of Indigenous infants hospitalized with bronchiolitis. Pediatric Pulmonology 2016;51:613‐23. - PMC - PubMed
McCullers 2006
    1. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clinical Microbiology Reviews 2006;19:571‐82. - PMC - PubMed
NICE 2015
    1. National Institute for Health and Care Excellence (NICE). Bronchiolitis: diagnosis and management in children. www.nice.org.uk/Guidance/NG9 2015. - PubMed
Ralston 2014
    1. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014;134:e1474‐e1502. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
SIGN 2006
    1. Scottish Intercollegiate Guidelines Network (SIGN). Bronchiolitis in children: a national clinical guideline. Archives of Disease in Childhood Education and Practice Edition 2006;91:1‐46. - PubMed
Sigurs 2000
    1. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. American Journal of Respiratory and Critical Care Medicine 2000;161:1501‐7. - PubMed
Spurling 2011
    1. Spurling GK, Doust J, Mar CB, Eriksson L. Antibiotics for bronchiolitis in children. Cochrane Database of Systematic Reviews 2011, Issue 6. [DOI: 10.1002/14651858.CD005189.pub3] - DOI - PubMed
Su 2014
    1. Su SC, Chang AB. Improving the management of children with bronchiolitis: the updated American Academy of Pediatrics clinical practice guideline. Chest 2014;6:1428‐30. - PubMed
Swingler 2000
    1. Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Archives of Pediatrics and Adolescent Medicine 2000;154:997‐1000. - PubMed
Wong 2005
    1. Wong JY, Rutman A, O'Callaghan C. Recovery of the ciliated epithelium following acute bronchiolitis in infancy. Thorax 2005;60(7):582‐7. - PMC - PubMed
Zarogoulisidis 2011
    1. Zarogoulidis P, Papanas N, Kioumis I, Chatzaki E, Maltezos E, Zarogoulidis K. Macrolides: from in vitro anti‐inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. European Journal of Clinical Pharmacology 2011;67:1‐25. - PubMed

MeSH terms

LinkOut - more resources