Should children be prescribed antibiotics for uncomplicated chest infections?

Antibiotic (ie, amoxicillin) treatment for children presenting with uncomplicated (ie, non-pneumonic) lower respiratory tract infections (LRTIs) in primary care does not appear to be effective, suggests findings from the UK ARTIC PC* trial.

“Parents want help in managing symptoms and improving the course of illness [of their children] … Prescribing antibiotics [might also] reduce societal costs (eg, out-of-pocket expenses and time off work),” said the researchers. However, evidence supporting the efficacy of antibiotics for LRTIs in children is scarce. [Cochrane Database Syst Rev 2017;6:CD000245; JAMA 2005;293:3029-3035]

The researchers sought to evaluate whether a 7-day course of antibiotics would benefit children presenting in primary care with acute uncomplicated LRTI (acute cough as predominant symptom, with other signs/symptoms localized to the lower respiratory tract, ie, sputum, shortness of breath, or pain) lasting <21 days. A total of 432 children (median age 3.2 years, 54 percent male) were randomized 1:1 to receive either amoxicillin 50 mg/kg/day or placebo oral suspension in three divided doses. [Lancet 2021;doi:S0140-6736(21)01431-8]

“[We chose amoxicillin] because it is the first-choice antibiotic in UK national guidance for use in LRTIs among children … and with current levels of intermediate resistance, should cover most susceptible organisms,” said the researchers.

Median durations of moderately bad or worse symptoms were similar with amoxicillin vs placebo (5 vs 6 days; hazard ratio [HR], 1.13; p=0.1). “[This] suggests that antibiotics do not provide a clinically important benefit on average for symptom reduction nor symptom severity,” the researchers explained. “[Although] the question remains whether there are some children who receive a meaningful benefit … the benefit is diluted by large numbers of children who receive no benefit.”

Subgroup analysis yielded similar median durations of moderately bad or worse symptoms across all five prespecified subgroups comprising children with abnormal chest signs (6 days in both amoxicillin and placebo arms), sputum or chest rattle (5 vs 7 days), fever (5 vs 6 days), physician rating of unwell (5 vs 6 days), and shortness of breath (5 vs 6 days).

“[A]lthough we did not have the power to exclude more moderate benefits … our subgroup analysis results suggest that none of the groups we specified were likely to achieve substantial benefits in terms of symptomatic improvement from antibiotics,” said the researchers.

Contrary to the theory that antibiotic prescriptions might entail health or societal resource savings, the findings showed similar societal costs due to time off work or privately purchased remedies between the amoxicillin and the placebo arms (£32.90 vs £32.70) and slightly higher total NHS costs per child with amoxicillin vs placebo (£29.40 vs £25.80). “If the costs of antibiotic resistance were included, the adverse effect on health and societal resource use [might have been] higher,” said the researchers.

The study was designed to be able to detect a clinically important 3-day improvement in symptom duration or about a 20-percent improvement for an illness lasting 14 days, the researchers noted. “A 3-day improvement in a subgroup was [deemed] important enough to be worth prescribing an antibiotic, given the public health issue of antibiotic resistance.”

“[However,] our results showed that, for children presenting to primary care with uncomplicated acute LRTI, there is unlikely to be a clinically relevant effect of [a 7-day course of] amoxicillin treatment on symptom burden, both overall and for key patient subgroups, in whom antibiotics are commonly prescribed,” they continued.

“Unless pneumonia is suspected, clinicians should provide a so-called safety-netting advice, but not prescribe antibiotics for most children presenting with chest infections,” the researchers concluded.