Results from a clinical trial completed in Kenya have determined that a safe dose of the antibiotic, fosfomycin, can be used to treat babies with neonatal sepsis. This is a significant development, as there are very few antibiotics specifically licensed to treat multidrug-resistant infections in babies.

The NeoFosfo trial investigated the pharmacokinetics (PK) and safety of fosfomycin in 120 babies aged under 28 days who were hospitalized with clinically diagnosed sepsis at the Kilifi County hospital in Kenya. The PK studies define which dose to use in babies.

The trial was sponsored by the Global Antibiotic Research and Development Partnership (GARDP) and the Drugs for Neglected Diseases initiative (DNDi) and supported by key partners.

“This is a very encouraging outcome for the treatment of neonatal sepsis and the care of babies who are hardest-hit by rising antimicrobial resistance (AMR),” said Neonatal Sepsis Project Leader for GARDP, Sally Ellis. “The study provides crucial evidence of the correct dosage of fosfomycin for newborns.”

A paper on the outcome of the trial, which was recently published in the global paediatric journal, Archives of Diseases in Childhood, indicated that fosfomycin offered significant potential as part of a combination antibiotic regimen for newborns, which is safe, easily administered, and affordable.

The paper comes after recent data showed that Sub-Saharan Africa has the highest overall burden of AMR in the world, and that babies in particular are most affected. The GRAM study, published in The Lancet in January 2022, revealed that children under five years old made up over half of the 255,000 people in Sub-Saharan Africa who died in 2019 because of AMR.

Neonatal sepsis is a life-threatening condition that requires prompt detection and treatment. Newborns — babies under 28 days old — are particularly vulnerable as their underdeveloped immune systems struggle to fight infections. This is complicated by drug resistance, as up to 40% of bacterial infections are resistant to standard treatments. Many newborns die if they don’t get timely treatment, while others may have significant long-term consequences.

“Currently there are very limited antibiotics in the pipeline. Safe and affordable antibiotic combinations effective against bacteria causing sepsis in babies are needed to improve survival. Our results are significant as they provide evidence that fosfomycin is safe and can now be taken forward into further clinical trials focusing on improving mortality outcomes for sepsis in babies,” said clinical investigator on the trial, Christina Obiero of the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya.

Fosfomycin is an antibiotic that is used in some countries to treat serious bacterial infections but has rarely been used for treatment of serious infection in babies admitted to hospitals. It is an off-patent antibiotic and thus potentially inexpensive, and has been identified as “critically important” by the World Health Organization (WHO).

The results of the NeoFosfo trial will be followed by a large GARDP-led international clinical trial, NeoSep, which will enrol three thousand babies, including in Kenya and South Africa. It will obtain robust evidence of the safety and efficacy of new antibiotic combinations including fosfomycin, compared to other WHO-recommended and existing antibiotic combinations, for the treatment of neonatal sepsis.

It is expected that results obtained from this trial could inform WHO and local antibiotic treatment guidelines, as partners aim to demonstrate which combinations are safe and effective in treating neonatal sepsis.

GARDP is committed to accelerating the development of lifesaving treatments for drug-resistant infections and transforming the care of babies with sepsis.

About GARDP

The Global Antibiotic Research and Development Partnership (GARDP) is a Swissnot-for-profit organization developing new treatments for drug-resistant infections that pose the greatest threat to health.GARDP was created by the World Health Organization (WHO) and the Drugs for Neglected Diseases initiative (DNDi) in 2016 to ensure that everyone who needs antibiotics receives effective and affordable treatment, no matter where they live. We aim to develop five new treatments by 2025 to fight drug-resistant infections, focusing on sexually transmitted infections, sepsis in newborns and infections in hospitalized adults and children. GARDP is funded by the governments of Germany,Japan,Luxembourg, Monaco, Netherlands,South Africa,Switzerland, United Kingdom,as well asMédecins SansFrontièresandprivate foundations.GARDP is registered under the legal name GARDP Foundation. www.gardp.org

About the partners

The Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme was formally established in 1989, and is a partnership between KEMRI, Oxford University and the Wellcome Trust. It conducts basic, epidemiological and clinical research in parallel, with results feeding directly into local and international health policy and aims to expand the country’s capacity to conduct multidisciplinary research that is strong, sustainable and internationally competitive. www.kemri-wellcome.org

The UCL Great Ormond Street Institute of Child Health (GOS ICH) which, together with its clinical partner Great Ormond Street Hospital for Children (GOSH), forms the largest concentration of children’s health research in Europe. Its mission is to improve the health and wellbeing of children, and the adults they will become, through world-class research, education and public engagement.

The Centre for Tropical Medicine and Global Health is a world leading centre within the Nuffield Department of Clinical Medicine, University of Oxford, comprised of research groups who are permanently based in Africa and Asia as well as across two sites in Oxford. Its research ranges from clinical studies to behavioural sciences, with capacity building integral to all of our activities.

The Paediatric Infectious Disease Research Group (PIDRG) based at St George’s, University of London, is internationally recognised as a leading centre for PID research and is led by Professor Mike Sharland. This research is focused on optimising the antibiotics we give children and babies.

InfectoPharm Arzneimittel und Consilium GmbH specializes in the further development of medicines for children. For over 30 years, this family-owned German company has distinguished itself as a groundbreaking pioneer in the industry. The portfolio currently comprises around 130 preparations with numerous innovations in the fields of pediatrics, infectious diseases, pneumology, dermatology and allergology, which are increasingly attracting international attention. The consilium service is available free of charge to professionals as a product-neutral consulting and knowledge transfer service in Germany. InfectoPharm employs more than 240 people at its headquarters in Heppenheim, located at the south of Frankfurt.