Children hospitalised with severe pneumonia can safely switch from injectable to oral antibiotics once they begin to recover, allowing many to return home sooner and complete treatment outside hospital. This is according to a major international clinical trial led by researchers from City St George's, University of London, UCL Innovative Clinical Trials Unit, and partners across Africa and Europe, with results published today in The Lancet.
Pneumonia remains one of the leading infectious killers of children worldwide, particularly in low- and middle-income countries. Current World Health Organization (WHO) guidelines recommend five days of injectable antibiotics for children hospitalised with severe community-acquired pneumonia, often requiring them to stay in hospital even after they have already substantially improved.
Longer hospital stays are more expensive, placing a higher burden on already pressurised healthcare systems and facilities, whilst increasing the risk of hospital-acquired antibiotic-resistant infections and impacting the wellbeing of the children and their families.
The PediCAP trial is one of the largest studies to assess antibiotic treatment for severe childhood pneumonia in Africa. The study enrolled 1,101 children aged two months to six years with community-acquired pneumonia that developed outside hospital but was severe enough to require hospital treatment. Thirteen hospitals across South Africa, Uganda, Zambia, Zimbabwe and Mozambique contributed to the study.
All children in the trial began treatment with a WHO-recommended injectable antibiotic. Some were assigned to switch to either oral amoxicillin or oral amoxicillin-clavulanate when their condition had improved, as confirmed by a healthcare worker. Researchers compared these children to those who received the WHO-recommended injectable treatment for the full five days.
Children who switched to oral antibiotics recovered just as well as those who remained on injectable treatment for five days. Rates of hospital readmission or death within 28 days were similar across all groups - 6% for oral amoxicillin, 7% for oral amoxicillin-clavulanate and 6% for injectable antibiotics - showing that an early switch to oral treatment is a safe and effective strategy.
The standard amoxicillin performed just as well as the broader-spectrum antibiotic amoxicillin-clavulanate, supporting the use of a treatment that is cheaper and widely available.
Researchers also compared how well children recovered with different durations of antibiotic treatment, ranging from four to eight days in total. A total antibiotic course of four to five days was as effective as longer courses of seven or eight days, suggesting many children can be treated successfully with substantially less antibiotic exposure than is often used in practice.
Children who switched to oral antibiotics left hospital around one day earlier compared to those who remained on injectable treatment for the full five days.
Professor Julia Bielicki, Professor of Paediatric Infectious Diseases at City St George's, University of London and co-lead author of the study, said:
"Every year millions of children around the world are admitted to hospital with severe pneumonia. Our study shows that once a child is clinically improving, it is safe to switch from injectable to oral antibiotics, and complete treatment at home.
"This simple change could help children get back to their families sooner, reduce pressure on busy hospitals, lower healthcare costs and avoid sometimes catastrophic financial impacts on families from lost caregiver earnings. Because amoxicillin is affordable and widely available, these findings have the potential to change clinical practice and improve care for children around the world."
Dr Michelle Clements, Principal Statistician at UCL Innovative Clinical Trials Unit and co-lead author, said:
"PediCAP is the first large-scale study to use our innovative multi-arm trial design to evaluate different antibiotics and treatment durations at the same time. Rather than simply comparing one short course with one longer course, this approach allowed us to establish that the shortest studied treatment strategy was effective and safe, while also helping us to understanding the relationship between treatment length and effect.
"By generating robust evidence more efficiently, this trial design has helped answer questions that we hope will support changes to global treatment guidelines and improve care for millions of children with pneumonia worldwide."
The trial was funded by the European Union's EDCTP2 programme and sponsored by the Penta Foundation.
