Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

Abstract

BackgroundWHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.MethodologyThis multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2–59 months of age, who received either oral amoxycillin (31–54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.Principal FindingsWe randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).ConclusionsTreating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.Trial RegistrationClinicalTrials.gov NCT00407394

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011

“…[II] 126 [II] However, both enrolled many children who, in the UK, would have bronchiolitis not pneumonia. One was a randomised controlled trial of 136 young Danish children aged 1 month to 6 years, either with pneumonia or bronchiolitis, with 84% RSV positive.…”

“…[II] The other in India enrolled children aged 2–59 months with cough, rapid breathing or difficulty breathing, audible or auscultatory wheeze, non-response to bronchodilator without chest radiographic changes. There was a non-significant difference in failure rate of 24% with placebo and 19.9% with amoxicillin for 3 days 126. [II] Unfortunately, as most children in these studies appeared to have bronchiolitis rather than pneumonia, it is not possible to draw conclusions from them regarding whether young children with pneumonia benefit from antibiotics.…”

Pertinent issues in diagnosis and management of wheezing in under-five children at community level

“…Another option is to give therapeutic trial with inhaled bronchodilators before assigning the diagnosis of pneumonia or severe pneumonia in all children with 'fast breathing' or 'chest indrawing.' Among cases of non-severe pneumonia and wheeze, the respiratory rate is known to come back below age specific cut-offs in 46%-62% children (7,8). The response rate in children with lower chest indrawing is somewhat lower (8).…”

“…In a study from Delhi hospital, audible wheeze was appreciated in only 44 of the 150 cases (29.3%) with an auscultable wheeze(3). In a recent multicentric study evaluating the role of antibiotics in treatment of wheezy pneumonia in under-five Indian children, audible wheeze was found in only 17% of cases where it was present on auscultation (7). The multicentric study enrolling children with severe pneumonia from Pakistan also documented a prevalence of audible wheeze in only 17% (261 out of 1545) of the total wheezy children (6).…”

Acute respiratory infection and pneumonia in India: A systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India

“…In a large, multi-centric trial across 8 public sector hospitals in India [121], 3487 children (2-59 months) with non-severe pneumonia were first nebulized with salbutamol to assess response to bronchodilator. Among them, 46% responded in terms of normalization of respiratory rate, suggesting that a large proportion of children who have non-severe pneumonia (by the WHO criteria) do not require antibiotic therapy.…”