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

Shally Awasthi,P Raghupathy,Stephen D Walter,Abhimanyu Niswade,Vaishali More,Girdhar Agarwal,Madhuri Kulkarni,Ravi Luke,Sunit Singhi,Raj Mohan Pillai,Saradha Suresh,R Lodha,Valsan P Verghese,Sushil K Kabra,Neeraj M Srivastava,Tammy Clifford

doi:10.1371/journal.pone.0001991

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

Highlights

Acute lower respiratory infections (ALRI) are a leading cause of morbidity and mortality in children under five years of age in developing countries and are responsible for an estimated 2.6 million deaths annually [1,2,3]
The current Integrated Management of Childhood Illness (IMCI) algorithm prescribes that children with wheeze and fast breathing presenting to first level health facilities be given antibiotics if they continue to have fast breathing after two doses of bronchodilators [7]
The goal of this trial was to assess whether children of non-severe pneumonia with wheeze can be effectively managed without antibiotics and to identify which sub-group of cases do require antibiotics

Summary

Introduction

Acute lower respiratory infections (ALRI) are a leading cause of morbidity and mortality in children under five years of age in developing countries and are responsible for an estimated 2.6 million deaths annually [1,2,3]. The current Integrated Management of Childhood Illness (IMCI) algorithm prescribes that children with wheeze and fast breathing presenting to first level health facilities be given antibiotics if they continue to have fast breathing after two doses of bronchodilators [7]. An unknown proportion of children managed will have viral related wheezing illness like bronchiolitis and asthma rather than pneumonia, where antibiotics may not alter the course of disease. 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. 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

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Results

Conclusion