Antibiotics in childhood pneumonia: how long is long enough?

Improved access to healthcare, vaccines and treatment with antibiotics has reduced global mortality from childhood community-acquired pneumonia. However, as respiratory viruses are responsible for most episodes of pneumonia, important questions remain over who should receive these agents and the length of each treatment course. Worldwide concerns with increasing antibiotic resistance in respiratory pathogens and appeals for more prudent antibiotic prescribing provide further urgency to these clinical questions. Unfortunately, guidelines for treatment duration in particular are based upon limited (and often weak) evidence, resulting in national and international guidelines recommending treatment courses for uncomplicated pneumonia ranging from 3 to 10 days. The advantages of short-course therapy include a lower risk of developing antibiotic resistance, improved adherence, fewer adverse drug effects, and reduced costs. The risks include treatment failure, leading to increased short- or long-term morbidity, or even death. The initial challenge is how to distinguish between bacterial and non-bacterial causes of pneumonia and then to undertake adequately powered randomised-controlled trials of varying antibiotic treatment durations in children who are most likely to have bacterial pneumonia. Meanwhile, healthcare workers should recognise the limitations of current pneumonia treatment guidelines and remember that antibiotic course duration is also determined by the child’s response to therapy.Griffith Health, School of MedicineFull Tex

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

Background: 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.Objectives: 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.Search methods: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers (December 2020).Selection criteria: 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 \u27a 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\u27. We excluded trials involving children with severe or very severe pneumonia, and non-RCTs.Data collection and analysis: 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.Main results: 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 to clinical 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.Authors\u27 conclusions: 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