Journal Club Usha Niranjan SPR Paediatrics/ Diabetes & Endocrine

Rationale Bronchiolitis season Several children (< 2yrs) with bronchiolitis Develop fever with occasional crackles more on one side of the chest. Chest X-ray - bilateral perihilar changes ? to start antibiotics ? large proportion get antibiotics

What are we concerned about In a child presenting with fever and clinical symptoms and signs of bronchiolitis –? risk of serious complications such as pneumonia, septicaemia. Is there any added benefit? –Macrolides  thought to have anti-inflammatory activities + immune modulatory effects.

What is known on the topic? Antibiotics are not recommended for bronchiolitis unless –Concerns about secondary bacterial lobar pneumonia. –Respiratory failure. It is widely accepted in the literature that chest radiographs cannot reliably differentiate viral from bacterial aetiology of pneumonia. –Harris M, Clark J, Coote N, Fletcher P, Harnden A, et al. (2011) British Thoracic Society guidelines for the management of community acquired pneumonia in children: update Thorax 66 Suppl 2: ii1–23

Accuracy of the interpretation of chest radiographs for the diagnosis of paediatric pneumonia. Elemraid M.A., et al. PLoS ONE, August 2014, 9/8, An 18-month prospective aetiological study of pneumonia (Northern England). CXR done - children aged <16 years with clinical features of pneumonia. Reported independently by 2 x radiologists. Significant disagreement between the first and second reports (P=0.001), notably in those aged < 5 years (26%, P=0.001). The most frequent sources of disagreement were the reporting of patchy and peri-hilar changes. They did not significantly affect –the clinical outcomes. –management decisions of pneumonia in children.

PICO P: In children with bronchiolitis or viral wheeze I: Antibiotics C: placebo O: rapid improvement

NHS evidence database searches Medline Embase Cochrane database None focussing on the aspect of chest X-ray changes

Article Antibiotics for bronchiolitis in children under two years of age. Farley R, Spurling GKP, Eriksson L, Del Mar CB. The Cochrane Library 2014, Issue 10

Study Cochrane Systematic review of –RCTs comparing antibiotics to placebo in children < 2yrs with bronchiolitis using clinical criteria (respiratory distress preceeded by coryzal symptoms with or without fever). Included 7 studies – 824 participants Primary outcome –Duration of oxygen requirement and symptoms(O 2 requirement, wheeze, fever) Secondary outcome –Length of hospital stay, re-admission,

The included studies

Low income country – Bangladesh (blinding not described & high risk of reporting bias)

High income country (Netherlands)

Low income country (Bangladesh) - high risk of selection bias

Primary outcome- Days of supplemental oxygen The three studies  adequate data  showed no difference between antibiotics and placebo (pooled MD -0.20; 95% CI to 0.33)

Primary outcome – O 2 Saturation One study – Majumder 2009 (children <24 months) I.V ampicillin (n=29), oral erythromycin(n=32) No antibiotics - Control (n=43) No significant difference in O 2 saturation for the antibiotics group combined or individually with the control.

Primary outcome - Wheeze One study – Majumder 2009 On day 3 – fewer children with wheeze in the combined antibiotics arm vs control ( Chi 2 test = 24.82) P value < On day 5 - more children had wheeze in the antibiotic arm (Chi 2 test = 5.69 (P value = 0.058))

Kabir 2009 (Children <2yrs) –Symptom resolution rapid ( 4 days) –None of symptoms including fever on day 2 were significantly different among the i.v ampicillin, oral erythromycin or control group (Chi 2 = 0.38 (P value = 0.83)) Kneyber 2008 –Azithromycin vs placebo –No significant difference in duration of fever. –MD 0.47 (95% CI to 1.06); (P = 0.12) Primary outcome - Fever

Secondary outcome Duration of admission/ time to discharge – 3 x studies pooled (Kneyber 2008; McCallum 2013; Pinto 2012) –No difference between antibiotics (azithromycin) and placebo –MD – 0.58; 95% CI (-1.18 to 0.02) –Chi 2 test = 0.40, df = 2 (P value = 0.82) Re-admissions –Two studies (McCallum 2013; Tahan 2007)  sufficient data –found no significant difference. –Data not pooled  due to substantial risk of heterogeneity. Complications/ adverse events – none Radiological findings- not reported.

Critical appraisal Validity 1) Did the review address a clearly focused question? Yes 2) Did the authors look for the appropriate sort of papers? Yes

Validity Do you think the important, relevant studies were included? –YES personal contact with experts search for unpublished as well as published studies search for non-English language studies

Did the review’s authors do enough to assess the quality of the included studies? –Yes If the results of the review have been combined, was it reasonable to do so? – Yes

What are the overall result of the reviews? Primary outcomes: –Duration of oxygen requirement – no significant difference. –Wheeze –mixed results for effects of antibiotics( study - high risk of bias). –Fever – no difference in duration of fever or the presence of fever on day 2. Secondary outcomes: –6 x studies –no difference in length of illness or hospital stay –Length of hospital stay – No significant difference between azithromycin and placebo. –Hospital readmission – No significant difference. –Radiological findings were not reported as an outcome in any of the included studies. What are the results?

Results Were the results precise? Yes –Pooled data – sufficient to assess effect –Confidence intervals reported.

Applicability Can the results be applied to the local population? –Yes

Applicability Were all the clinically important outcomes considered? Yes Are the benefits worth the harm and costs? Yes

Conclusion: The review highlights: –No evidence to support the use of antibiotics for bronchiolitis. –No RCTs  assessing the usefulness of antibiotics for bronchiolitis in an intensive care setting. Further research  focused on determining the reasons that clinicians use antibiotics in bronchiolitis. how to reduce clinician anxiety about not using antibiotics Further research to identify the subgroup –At risk of secondary bacterial infection following bronchiolitis especially in the context of respiratory failure.

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