Antibiotics for bronchiolitis in children

Geoffrey KP Spurling; Jenny Doust; Chris B Del Mar; Lars Eriksson

doi:10.1002/14651858.CD005189.pub3

Antibióticos para la bronquiolitis en niños

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Referencias

Referencias de los estudios incluidos en esta revisión

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estudios excluidos
otras referencias

Field C, Connolly J, Murtagh G, Slattery C, Turkington E. Antibiotic treatment of epidemic bronchiolitis ‐ a double‐blind trial. British Medical Journal 1966;1:83‐5.

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.

Kneyber M, van Woensel J, Uijtendaal 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.

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(2):63‐9.

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.

Referencias de los estudios excluidos de esta revisión

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estudios incluidos
otras referencias

Boogaard R, Hulsmann A, van Venn L, Vaessen‐Verbene A, Yap Y, Sprij A, et al. Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis. Chest 2007;131:788‐95.

Friis B, Andersen P, Brenoe E, Hornsleth A, Jensen A, Knudsen F, et al. Antibiotic treatment of pneumonia and bronchiolitis. Archives of Disease in Childhood 1984;59:1038‐45.

Referencias adicionales

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estudios incluidos
estudios excluidos

Bloomfield P, Dalton D, Karleka A, Kesson A, Duncan G, Isaacs D. Bacteraemia and antibiotic use in respiratory syncytial virus infections. Archives of Disease in Childhood 2004;89:363‐7.

Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, et al. Diagnosis and testing in bronchiolitis: a systematic review. Archives of Pediatrics & Adolescent Medicine 2004;158:119‐26.

Brook I. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. Primary Care 1998;25(3):633‐48.

Christakis D, Cowan C, Garrison M, Molteni R, Marcuse E, Zerr D. Variation in inpatient diagnostic testing and management of bronchiolitis. Pediatrics 2005;115:878‐84.

Culic O, Erakovic V, Parnham M. Antiinflammatory effects of macrolide antibiotics. European Journal of Pharmacology 2001;429:209‐29.

Fitzgerald DA, Kilham HA. Bronchiolitis: assessment and evidence‐based management. Medical Journal of Australia 2004;180:399‐408.

Glezen WP, Loda FA, Clyde WA, Senior RJ, Sheaffer CI, Conley WG, et al. Epidemiologic patterns of acute lower respiratory disease of children in a pediatric practice. Journal of Pediatrics 1971;78:397‐406.

Greenes D, Harper M. Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal 1999;18(3):258‐61.

Halna M, Leblond P, Aissi E, Dumonceaux A, Delepoulle F, El Kohen R, et al. Impact of consensus conference on the ambulatory treatment of bronchiolitis in infants. Presse Medicale 2005;34(4):277‐81.

Higgins JPT. Assessing risk of bias in included studies. Altman DG, Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. [updated March 2011] The Cochrane Collaboration. Chichester, UK: Wiley‐Blackwell, 2011.

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Ichiyama T, Nishikawa M, Yoshitomi T, Hasegawa S, Matsubara T, Hayashi T, et al. Clarithromycin inhibits NF‐kB activation in human peripheral blood mononuclear cells and pulmonary epithelial cells. Antimicrobial Agents and Chemotherapy 2001;45(1):44‐7.

Kabir M, Haq N, Hoqu M, Ahmed F, Amin R, Hossain A, et al. Evaluation of hospitalised infants and young children with bronchiolitis ‐ a multi‐centre study. Mymensingh Medical Journal 2003;12(2):128‐33.

Kneyber M, van Oud‐Alblas H, van Vliet M, Uiterwaal C, Kimpen J, van Vught A. Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease. Intensive Care Medicine 2005;31:680‐5.

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available from www.cochrane‐handbook.org. Chichester, UK: Wiley‐Blackwell, 2011.

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Levin D, Tribuzio M, Green‐Wrzesinki T, Ames B, Radwan S, Jarvis D, et al. Empiric antibiotics are justified for infants with respiratory syncytial virus lower respiratory tract infection presenting with respiratory failure: a prospective study and evidence review. Pediatric Critical Care Medicine 2010;11(3):390‐5.

Lozano J, Wang E. Bronchiolitis. Clinical Evidence 2002;8:291‐303.

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Luginbuhl, LM, Newman T, Pantell RH, Finch SA, Wasserman RC. Office‐based treatment and outcomes for febrile infants with clinically diagnosed bronchiolitis. Pediatrics 2008;122(5):947‐54.

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Rose RM, Pinkston P, O'Donnell C. Viral infections of the lower respiratory tract. Clinics in Chest Medicine 1987;8:405‐18.

Smyth R, Openshaw P. Bronchiolitis. Lancet 2006;368:312‐22.

Thorburn K, Harigopal S, Reddy V, Taylor N, van Saene H. High incidence of pulmonary bacterial co‐infection in children with severe respiratory syncytial virus bronchiolitis. Thorax 2006;61(7):611‐5.

Vogel AM, Lennon DR, Harding JE, Pinnock RE, Graham DA, Grimwood K, et al. Variations in bronchiolitis management between five New Zealand hospitals: can we do better?. Journal of Paediatric Child Health 2003;39:40‐5.

Williams JV, Harris PA, Tollefson SJ, Halburnt‐Rush LL, Pingsterhaus JM, Edwards KM, et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. New England Journal of Medicine 2004;350:443‐50.

Wilson SD, Dahl BB, Wells RD. An evidence‐based clinical pathway for bronchiolitis safety reduces antibiotic overuse. American Journal of Quality 2002;17(5):195‐9.

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Wohl ME, Chernick V. State of the art bronchiolitis. American Review of Respiratory Disease 1978;118:759‐81.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Field 1966

Methods	Randomised controlled trial
Participants	Babies
Interventions	Ampicillin Placebo
Outcomes	Length of hospital stay Symptoms (not specified) Switch to treatment arm Death
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised
Blinding (performance bias and detection bias) All outcomes	Low risk	Patients were blinded but not doctors nor outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	No intention‐to‐treat analysis but withdrawal rates were acceptable
Selective reporting (reporting bias)	Low risk

Kabir 2009

Methods	Randomised controlled trial
Participants	Children under 2 years of age with clinical suspected bronchiolitis
Interventions	IV ampicillin (parenteral ampicillin 50 mg/kg/6‐hourly + supportive care), oral erythromycin (oral erythromycin 10 mg/kg 6‐hourly + supportive care), control
Outcomes	Respiratory rate, oxygen saturation, wheeze, fever, length of hospital stay, shortness of breath
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number table
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	High risk	Seems unlikely, not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	32 participants dropped out (10%), 17 were referred to paediatric intensive care and 15 withdrew from the study or left the recruiting hospitals
Selective reporting (reporting bias)	High risk

Kneyber 2008

Methods	Double‐blinded, placebo‐controlled, randomised controlled trial
Participants	Hospitalised infants younger than 24 months with clinically‐confirmed viral lower respiratory tract infection
Interventions	Azithromycin 10 mg/kg/day, once daily for 3 days
Outcomes	Respiratory rate, accessory muscle use, malaise severity, disease complications, use of alternative therapies, length of hospital stay, length of intensive care stay, deaths, need for NG feeding
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Adequate block randomisation
Allocation concealment (selection bias)	Low risk
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and doctors
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss to follow up
Selective reporting (reporting bias)	Low risk
Other bias	Low risk

Mazumder 2009

Methods	Randomised controlled trial
Participants	Children aged 1 month to 2 years presenting to an outpatients department in a teaching hospital
Interventions	Supportive management, supportive management plus IV ampicillin, supportive management plus oral erythromycin
Outcomes	Breathing difficulty, feeding difficulty, social smile, tachypnoea, hypoxia, wheeze, rhonchi, crepitation, WBC, Hb, ESR, CRP, X‐ray, rate of recovery
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Odds and evens
Allocation concealment (selection bias)	Unclear risk	Not discussed
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not specified
Selective reporting (reporting bias)	Unclear risk	Unsure

Tahan 2007

Methods	Double‐blind, randomised controlled trial
Participants	Infants less than or equal to 7 months with immunologically confirmed RSV infection admitted to 1 hospital
Interventions	Clarithromycin 15 mg/kg/day, once daily for 3 weeks
Outcomes	Respiratory rate, wheeze, use of supplemental oxygen, cyanosis, hospital admission, length of stay
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"... infants were randomized by a single study nurse..." "Simple randomisation was used"
Allocation concealment (selection bias)	Unclear risk	Allocation after enrolment by study nurse
Blinding (performance bias and detection bias) All outcomes	Low risk	Blinding of patients and investigators
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	30 patients were randomised, however 9 were later excluded as they received corticosteroid therapy
Selective reporting (reporting bias)	Unclear risk	Unsure if trial was registered
Other bias	Unclear risk	Unsure if there were any conflicts of interest

CRP: C reactive protein
ESR: erythrocyte sedimentation rate
Hb: haemoglobin
IV: intravenous
NG: nasogastric
RSV: respiratory syncytial virus
WBC: white blood count

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Boogaard 2007	Did not study antibiotics
Friis 1984	The patient selection criteria were fine crepitations or consolidation on chest radiograph which was not consistent with our inclusion criteria of a purely clinical presentation of bronchiolitis

Data and analyses

Open in table viewer

Comparison 1. Length of symptoms (not specified)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Duration of symptoms Show forest plot	2	123	Mean Difference (IV, Fixed, 95% CI)	0.32 [‐1.14, 1.78]
Open in figure viewer Analysis 1.1 Comparison 1 Length of symptoms (not specified), Outcome 1 Duration of symptoms.
2 Duration of fever (days) Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.47 [‐0.12, 1.06]
Open in figure viewer Analysis 1.2 Comparison 1 Length of symptoms (not specified), Outcome 2 Duration of fever (days).

Open in table viewer

Comparison 2. Death

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deaths Show forest plot	5	543	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
Open in figure viewer Analysis 2.1 Comparison 2 Death, Outcome 1 Deaths.

Open in table viewer

Comparison 3. Length of hospital stay

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Length of hospital stay Show forest plot	3	288	Mean Difference (IV, Random, 95% CI)	0.34 [‐0.71, 1.38]
Open in figure viewer Analysis 3.1 Comparison 3 Length of hospital stay, Outcome 1 Length of hospital stay.

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Comparison 4. Use of alternative therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Use of alternative therapy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 4.1 Comparison 4 Use of alternative therapy, Outcome 1 Use of alternative therapy.
1.1 Oxygen	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Bronchodilator use	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Corticosteroid use	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Naso‐gastric feeding	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Duration of bronchodilator use Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐1.25, 0.91]
Open in figure viewer Analysis 4.2 Comparison 4 Use of alternative therapy, Outcome 2 Duration of bronchodilator use.
3 Days of supplementary oxygen Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐0.46, 1.18]
Open in figure viewer Analysis 4.3 Comparison 4 Use of alternative therapy, Outcome 3 Days of supplementary oxygen.
4 Days of tube feeding Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.98, 1.12]
Open in figure viewer Analysis 4.4 Comparison 4 Use of alternative therapy, Outcome 4 Days of tube feeding.

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Comparison 5. PICU admission

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PICU admission Show forest plot	1	71	Odds Ratio (M‐H, Fixed, 95% CI)	0.39 [0.02, 10.03]
Open in figure viewer Analysis 5.1 Comparison 5 PICU admission, Outcome 1 PICU admission.

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Comparison 6. Re‐admission

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Re‐admission Show forest plot	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 1.29]
Open in figure viewer Analysis 6.1 Comparison 6 Re‐admission, Outcome 1 Re‐admission.

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Comparison 7. Symptoms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Wheeze Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.1 Comparison 7 Symptoms, Outcome 1 Wheeze.
1.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Shortness of breath Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.2 Comparison 7 Symptoms, Outcome 2 Shortness of breath.
2.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Oxygen saturation (< 96%) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.3 Comparison 7 Symptoms, Outcome 3 Oxygen saturation (< 96%).
3.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Not smiling socially Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.4 Comparison 7 Symptoms, Outcome 4 Not smiling socially.
4.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Feeding difficulties Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.5 Comparison 7 Symptoms, Outcome 5 Feeding difficulties.
5.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Fever Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.6 Comparison 7 Symptoms, Outcome 6 Fever.
6.1 Day 2	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Cough Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.7 Comparison 7 Symptoms, Outcome 7 Cough.
7.1 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Analysis 1.1

Comparison 1 Length of symptoms (not specified), Outcome 1 Duration of symptoms.

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Analysis 1.2

Comparison 1 Length of symptoms (not specified), Outcome 2 Duration of fever (days).

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Analysis 2.1

Comparison 2 Death, Outcome 1 Deaths.

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Analysis 3.1

Comparison 3 Length of hospital stay, Outcome 1 Length of hospital stay.

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Analysis 4.1

Comparison 4 Use of alternative therapy, Outcome 1 Use of alternative therapy.

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Analysis 4.2

Comparison 4 Use of alternative therapy, Outcome 2 Duration of bronchodilator use.

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Analysis 4.3

Comparison 4 Use of alternative therapy, Outcome 3 Days of supplementary oxygen.

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Analysis 4.4

Comparison 4 Use of alternative therapy, Outcome 4 Days of tube feeding.

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Analysis 5.1

Comparison 5 PICU admission, Outcome 1 PICU admission.

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Analysis 6.1

Comparison 6 Re‐admission, Outcome 1 Re‐admission.

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Analysis 7.1

Comparison 7 Symptoms, Outcome 1 Wheeze.

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Analysis 7.2

Comparison 7 Symptoms, Outcome 2 Shortness of breath.

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Analysis 7.3

Comparison 7 Symptoms, Outcome 3 Oxygen saturation (< 96%).

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Analysis 7.4

Comparison 7 Symptoms, Outcome 4 Not smiling socially.

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Analysis 7.5

Comparison 7 Symptoms, Outcome 5 Feeding difficulties.

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Analysis 7.6

Comparison 7 Symptoms, Outcome 6 Fever.

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Analysis 7.7

Comparison 7 Symptoms, Outcome 7 Cough.

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Table 1. Kneyber: azithromycin versus placebo for bronchiolitis

Variable	Azithromycin (n = 32)	Placebo (n = 39)	Outcome	Significance level
Days of symptoms	4.94 (SD 3.78)	4.62 (SD 2.05)	Mean difference 0.32 (95% CI ‐1.14 to 1.78)	P = 0.65
Days in hospital	5.5 (SD 2.54)	5.82 (SD 1.98)	Mean difference ‐0.32 (95% CI ‐1.40 to 0.76)	P = 0.56
Duration of fever (days)	1.47 (SD 1.41)	1.00 (SD 1.08)	Mean difference 0.47 (95% CI ‐0.12 to 1.06)	P = 0.12
Duration of bronchodilator use	2.79 (SD 2.49)	2.96 (SD 2.06)	Mean difference ‐0.17 (95% CI ‐1.25 to 0.91)	P = 0.81
Bronchodilator use	17	23	Odds ratio 0.79 (95% CI 0.31 to 2.02)	P = 0.62
Supplementary oxygen	20 (62.5%)	31 (79.49%)	Odds ratio 0.43 (95% CI 0.15 to 1.24)	P = 0.11
Days of extra oxygen	3.75 (SD 1.74)	3.39 (SD 1.78)	Mean difference 0.36 (95% CI ‐0.46 to 1.18)	P = 0.48
PICU admission	0 (0%)	1 (2.56%)	Odds ratio 0.39 (95% CI 0.02 to 10.03)	P = 1.00
Tube feeding	16 (50.00%)	16 (41.03%)	Odds ratio 1.44 (95% CI 0.56 to 3.69)	P = 0.45
Days of tube feeding	1.90 (SD 2.13)	1.83 (SD 2.36)	Mean difference 0.07 (95% CI ‐0.98 to 1.12)	P = 0.90
PICU: paediatric intensive care unit SD: standard deviation CI: confidence interval

Table 1. Kneyber: azithromycin versus placebo for bronchiolitis

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Table 2. Mazumder: IV ampicillin versus oral erythromycin versus control

Variable

Day 1

Outcome

Day 3

Outcome

Day 5

Outcome

IV ampicillin

Oral erythromycin

Control

Chi² test (P value)

IV ampicillin

Oral erythromycin

Control

Chi² test (P value)

IV ampicillin

Oral erythromycin

Control

Chi² test

(P value)

Wheeze

29/29 (100%)

32/32 (100%)

43/43 (100%)

N/A

16/29 (55%)

2/32 (6%)

26/43 (60%)

24.82 (P < 0.001)

6/29 (21%)

7/32 (22%)

2/43 (5%)

5.69 (P = 0.058)

Shortness of breath

29/29 (100%)

32/32 (100%)

43/43 (100%)

N/A

18/29 (62%)

16/32 (50%)

27/43 (63%)

1.97 (P = 0.37)

8/29 (28%)

8/32 (25%)

15/43 (35%)

0.95 (P = 0.62)

Oxygen saturation (< 96%)

18/29 (62%)

15/32 (47%)

23/43 (53%)

1.42 (P = 0.49)

8/29 (28%)

7/32 (22%)

5/43 (12%)

3.05 (P = 0.22)

2/29 (7%)

3/32 (9%)

2/43 (5%)

0.65 (P = 0.72)

Not smiling socially

19/29 (66%)

21/32 (66%)

30/43 (70%)

0.20 (P = 0.90)

3/29 (10%)

3/32 (9%)

5/43 (12%)

0.10 (P = 0.95)

0/29 (0%)

0/32 (0%)

0/43 (0%)

N/A

Feeding difficulty

12/29 (41%)

13/32 (41%)

25/43 (58%)

2.98 (P = 0.23)

3/29 (10%)

3/32 (9%)

5/43 (12%)

0.10 (P = 0.95)

0/29 (0%)

0/32 (0%)

0/43 (0%)

N/A

IV: intravenous

Table 2. Mazumder: IV ampicillin versus oral erythromycin versus control

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Table 3. Kabir: IV ampicillin versus oral erythromycin versus control

Variable	Intervention			Outcome
	IV ampicillin	Oral erythromycin	Control	Chi² test (P value)
Day 2
Oxygen sats (< 90%)	2/99 (2%)	6/99 (6%)	6/97 (6%)	2.45 (P = 0.29)
Fever	5/99 (5%)	6/99 (6%)	4/97 (4%)	0.38 (P = 0.83)
Day 7
Wheeze	8/99 (8%)	9/99 (9%)	4/97 (4%)	2.04 (P = 0.36)
Shortness of breath	8/99 (8%)	9/99 (9%)	2/97 (2%)	4.68 (P = 0.10)
Cough	10/99 (10%)	9/99 (9%)	3/97 (3%)	4.06 (P = 0.13)
IV: intravenous PICU: paediatric intensive care unit SD: standard deviation CI: confidence interval

Table 3. Kabir: IV ampicillin versus oral erythromycin versus control

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Comparison 1. Length of symptoms (not specified)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Duration of symptoms Show forest plot	2	123	Mean Difference (IV, Fixed, 95% CI)	0.32 [‐1.14, 1.78]

2 Duration of fever (days) Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.47 [‐0.12, 1.06]

Comparison 1. Length of symptoms (not specified)

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Comparison 2. Death

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Deaths Show forest plot	5	543	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Death

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Comparison 3. Length of hospital stay

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Length of hospital stay Show forest plot	3	288	Mean Difference (IV, Random, 95% CI)	0.34 [‐0.71, 1.38]

Comparison 3. Length of hospital stay

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Comparison 4. Use of alternative therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Use of alternative therapy Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Oxygen	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Bronchodilator use	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Corticosteroid use	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Naso‐gastric feeding	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Duration of bronchodilator use Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐1.25, 0.91]

3 Days of supplementary oxygen Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐0.46, 1.18]

4 Days of tube feeding Show forest plot	1	71	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.98, 1.12]

Comparison 4. Use of alternative therapy

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Comparison 5. PICU admission

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PICU admission Show forest plot	1	71	Odds Ratio (M‐H, Fixed, 95% CI)	0.39 [0.02, 10.03]

Comparison 5. PICU admission

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Comparison 6. Re‐admission

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Re‐admission Show forest plot	1	21	Odds Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 1.29]

Comparison 6. Re‐admission

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Comparison 7. Symptoms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Wheeze Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Shortness of breath Show forest plot	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.4 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Oxygen saturation (< 96%) Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Not smiling socially Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Feeding difficulties Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5.1 Day 1	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 Day 3	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Day 5	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Fever Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.1 Day 2	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Cough Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.1 Day 7	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 7. Symptoms

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Referencias

Referencias de los estudios incluidos en esta revisión

Field 1966 {published data only}

Kabir 2009 {published data only}

Kneyber 2008 {published and unpublished data}

Mazumder 2009 {published data only}

Tahan 2007 {published and unpublished data}

Referencias de los estudios excluidos de esta revisión

Boogaard 2007 {published data only}

Friis 1984 {published data only}

Referencias adicionales

Bloomfield 2004

Bordley 2004

Brook 1998

Christakis 2005

Culic 2001

Fitzgerald 2004

Glezen 1971

Greenes 1999

Halna 2005

Higgins 2011

Ichiyama 2001

Kabir 2003

Kneyber 2005

Lefebvre 2011

Levin 2010

Lozano 2002

Luginbuhl 2008

RevMan 5.1 [Computer program]

Rose 1987

Smyth 2006

Thorburn 2006

Vogel 2003

Williams 2004

Wilson 2002

Wohl 1978

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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