Antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO-defined non-severe pneumonia and wheeze.

Abstract

Worldwide, pneumonia is the leading cause of death amongst children under five years of age, and accounts for approximately two million deaths annually. Pneumonia can be classified according to the World Health Organization (WHO) guidelines. Classification includes assessment of certain clinical signs and symptoms, and the severity of the disease. Treatment is then tailored according to the classification. For non-severe pneumonia, the WHO recommends treatment with oral antibiotics. We used the 2014 WHO definition of non-severe pneumonia for this review: an acute episode of cough, or difficulty in breathing, combined with fast breathing and chest indrawing. The WHO recommends treating non-severe pneumonia with oral antibiotics. Pneumonia is more commonly caused by viruses that do not require antibiotic treatment, but pneumonia caused by bacteria needs management with antibiotics to avoid complications. There is no clear way to quickly distinguish between viral and bacterial pneumonia. It is considered safe to give antibiotics, however, this may lead to the development of antibiotic resistance, and thus, limit their use in future infections. Therefore, it is essential to explore the efficacy of antibiotics for children with WHO-defined non-severe pneumonia and wheeze. To evaluate the efficacy of antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO-defined non-severe pneumonia and wheeze. We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers (December 2020). We included randomised controlled trials (RCTs) evaluating the efficacy of antibiotic therapy versus no antibiotic therapy for children, aged 2 to 59 months, with non-severe pneumonia and wheeze. We defined non-severe pneumonia as 'a cough or difficulty in breathing, with rapid breathing (a respiratory rate of 50 breaths per minute or more for children aged 2 to 12 months, or a respiratory rate of 40 breaths per minute or more for children aged 12 to 59 months), chest indrawing and wheeze'. We excluded trials involving children with severe or very severe pneumonia, and non-RCTs. Our primary outcomes were clinical cure and treatment failure; secondary outcomes were relapse, mortality, and treatment harms. We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Two review authors independently assessed the search results, extracted data, assessed risk of bias and the certainty of the evidence. We contacted the authors of two included trials and the author of the trial awaiting classification to obtain missing numerical outcome data. We included three trials involving 3256 children aged between 2 to 59 months, who exhibited features of non-severe pneumonia with wheeze. The included trials were multi-centre, double-blind, randomised, placebo-controlled trials carried out in Malawi, Pakistan, and India. The children were treated with a three-day course of amoxicillin or placebo, and were followed up for a total of two weeks. We assessed the included trials at overall low risk of bias for random sequence generation, allocation concealment, blinding, attrition bias, and selective reporting. Only one trial was assessed to be at high risk for blinding of outcome assessors. One trial is awaiting classification Antibiotic therapy may result in a reduction of treatment failure by 20% (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.68 to 0.94; three trials; 3222 participants; low-certainty evidence). Antibiotic therapy probably results in little or no difference toclinical cure (RR 1.02, 95% CI 0.96 to 1.08; one trial; 456 participants; moderate-certainty evidence), and in little or no difference to relapse (RR 1.00, 95% CI 0.74 to 1.34; three trials; 2795 participants; low-certainty evidence), and treatment harms (RR 0.81, 95% CI 0.60 to 1.09; three trials, 3253 participants; low-certainty evidence). Two trials (2112 participants ) reported on mortality; no deaths occurred in either group. One trial reported cases of hospitalisation, diarrhoea (with and without dehydration), rash (without itch), tremors, mild nausea and vomiting. We do not currently have enough evidence to support or challenge the continued use of antibiotics for the treatment of non-severe pneumonia. There is a clear need for RCTs to address this question in children aged 2 to 59 months with 2014 WHO-defined non-severe pneumonia and wheeze.