By Clifford Akumu

A safe dose of an antibiotic rarely used in infants admitted in hospitals, could be used to treat babies with neonatal sepsis signaling a major boost to cut infant mortality rates in the country,a study finds.

Researchers say they conducted the trial to determine which dose to use or safety of the antibiotic in treating babies- 28 days and below – who are hospitallised with clinically diagnosed sepsis.

“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.We now have an option and steps ahead in treatment,”said Borna Nyaoke,Clinical Trial Manager at the Drugs for Neglected Diseases initiative (DNDi) who was also part of the study.

“The study provides crucial evidence of the correct dosage of fosfomycin for newborns.”

The NeoFosfo trial was conducted among 120 babies at the Kilifi County Hospital in Kenya.It was sponsored by the Global Antibiotic Research and Development Partnership (GARDP),DNDi and supported by key partners.

Neonates-babies under the age of 28 days-are particularly susceptible as their underdeveloped immune systems battle to fight off infections. A baby with sepsis-an infection of the blood-could lead to a life-threatening situation.

Nyaoke explains that when such babies pick up an infection,doctors have to administer antibiotics very quickly or the baby could die. But doctors are often faced with a heartbreaking reality-as up to 40 percent of bacterial infections in hospitalized babies are resistant to standard treatments.

There are very few antibiotics specifically licensed to treat multidrug-resistance infections in babies.

Currently there are two treatments approved by the World Health Organisation for the treatment of sepsis; ampicillin and gentamicin. But even doctors who use these drugs within the clinical setting are now reporting resistance,noted Nyaoke.

Experts say the burden of neonatal sepsis-a blood infection that occurs in neonates-is high in Sub-Saharan Africa where it affects an estimated 605,750 babies a year,leading in up to 302,870 deaths.

In Kenya,according to statistics,there are more than 22 neonatal deaths per 1000 live births.Nyaoke noted that, “Antimicrobial resistance has since crept in and is affecting treatments that are effective.”

And the lack of research and development to develop new treatment options is putting neonates lives at risk.

The outcome of the trial titled Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload and published recently 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.

“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).

In 2016,newborn deaths in Kenya accounted for approximately 46 percent of all under five deaths.Birth asphyxia/trauma accounted for 31.6 percent,prematuriy with 24.6 percent and sepsis with 15.8 percent are cited as the leading causes of neonatal mortality.

Nyaoke said that the trail therefore does not give leaway to any change in the current WHO guidelines on neonatal sepsis treatment.

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.

“This first trial does not give us leeway to go to the Ministry of Health,WHO to change the guidelines for neonatal sepsis treatment.It only shows us that we have a drug that is safe and can be used at a particular dosage.We will be working on a bigger clinical trial to compare the fosfomycin with the current drugs being used in neonatal sepsis treatment,”Nyaoke told Science Africa in an interview.

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.