UCL: Three days of antibiotics is ‘safe and effective’ for children leaving hospital with pneumonia

Children being discharged from hospital with pneumonia can be treated with three days of antibiotics rather than seven, finds a large UK-wide trial led by UCL researchers.

The results of the multi-site CAP-IT trial, published in the Journal of the American Medical Association, show that the number of doses given to children at home can be reduced safely, without impacting recovery.

Researchers say the findings should influence national and international guidelines for treating children who attend hospital with pneumonia, reducing the treatment burden for children and their caregivers.

Pneumonia (sometimes called chest infection) is common in young children and is usually treated with the antibiotic drug amoxicillin. But, until now, there has been little evidence to guide how long treatment should be given for, or what dose should be used.

CAP-IT found that a shorter duration of treatment of three days of amoxicillin was as good as a longer duration of seven days.

Joint first author, Dr Julia Bielicki, (MRC Clinical Trials Unit at UCL & St George’s, University of London) said: “Amoxicillin is the commonest antibiotic children receive globally, with hundreds of millions of courses given every year.

“However, there is surprisingly limited evidence of the optimal dose and duration that should be used to make sure children are treated safely, minimising the impact from side effects and antibiotic resistance, while making it simpler for families to give their child the medicines they need.

“The CAP-IT study provides family-friendly evidence that shorter durations of amoxicillin given twice daily are safe and effective even in young children with serious chest infections attending hospital. It has also demonstrated again that large strategic trials that inform the optimal choice of drug, dose and duration of antibiotics to treat common infections are feasible and critical to tackling antibiotic resistance.”

For the CAP-IT clinical trial, 824 children were recruited between Feb 2017 and April 2019 at emergency children’s departments and on children’s wards in 29 hospitals the UK and Ireland. Children who took part were aged six months or over, weighing between 6 and 24kg and the decision to treat their chest infection with amoxicillin had been made. The average age was 2.5 years. They were randomised to receive a lower vs higher dose of amoxicillin and a shorter vs longer duration of treatment.

The study was double-blind and placebo-controlled, with half the participants receiving seven days of amoxicillin and the other half receiving three days of amoxicillin and four days of placebo. As well as comparing duration, dosing was also studied, with half the participants in each duration group receiving a lower dose (35-50 mg/kg) and the other half a higher dose (70-90 mg/kg).

Researchers found the shorter course of treatment was no less effective than the longer course, and that the lower dose was no less effective than a higher dose, in terms of children needing further antibiotic treatment within four weeks. Further, it found that a lower dose of amoxicillin was as good as a higher dose.

The study also used a dosing schedule of only giving amoxicillin in two doses per day, rather than three, suggesting the total number of doses required to treat pneumonia could be reduced from 15-21 doses over 5-7 days (UK guidelines currently recommend three times daily dosing for five days) to the simpler six doses over three days.

The number of adverse events, such as diarrhoea, thrush and skin rash, was also comparable between groups. There was no evidence that using shorter course or lower dose amoxicillin led to increased resistance to the pneumococcus bacteria, the leading bacterial cause of pneumonia globally, with low resistance levels overall in the UK.

Between the study arms, there was no indication of differences in time to return to normal activities for parents and children or in additional use of healthcare services.

Joint last author, Professor Diana Gibb, (Medical Research Council Clinical Trials Unit at UCL) said: “CAP-IT is one of the largest antibiotic trials involving children globally, and clearly shows that for children leaving hospital with a diagnosis of pneumonia, three days of amoxicillin is safe and effective. We are immensely grateful to all the children and their families who joined the trial; for the work done by nurses and doctors at the participating hospitals, and to the PERUKI and GAPRUKI networks who helped make the trial a success.”

UK Special Envoy on Antimicrobial Resistance, Dame Sally Davies, said: “I welcome the CAP-IT trial results for adding to the increasing evidence on optimal prescribing. Thanks to the UK National Institute for Health Research, CAP-IT gives information that can be used in the real world by families, doctors and policymakers to improve health outcomes, whilst contributing to global stewardship efforts. We need many more studies in adults and children globally to ensure that we can continue to tackle the global challenge of AMR.”

Dr William van’t Hoff, Chief Executive Officer at the NIHR Clinical Research Network Coordinating Centre, said: “Each year, nearly half of all children under 2 years receive antibiotics, commonly for acute respiratory infections. I am delighted to see that the CAP-IT study has provided key evidence on the best use of antibiotics for community-acquired pneumonia which is really important to improving care for so many children. It’s a trial that has been supported across the UK and in Eire, demonstrating the power of collaborative research in tackling major health questions.

The trial did not include children with complicated chest infections needing to be in hospital for long periods of time or children receiving different types of antibiotics. Therefore, our results cannot be generalised to more severely ill children or those being treated for atypical chest infections.

The CAP-IT trial was funded by the NIHR’s Health Technology Assessment programme.