An antibiotic rarely used in infants admitted to hospitals could be a safe and affordable, life-saving treatment for neonatal sepsis, in the face of growing resistance to other drugs, a study finds.
Neurological experts say the burden of neonatal sepsis — a blood infection that occurs in infants younger than 90 days old — is high in Sub-Saharan Africa where it affects an estimated 605,750 babies a year, resulting in up to 302,870 deaths.
According to the study published in Archives of Diseases in Childhood, the antibiotic fosfomycin has "significant potential" for the safe treatment of sepsis in infants, as antimicrobial resistance threatens the efficacy of other commonly used drugs.
The study aimed to develop an antimicrobial regimen for low-and middle-income countries for neonatal sepsis treatment in locations with increasing resistance to current treatments recommended by the World Health Organization (WHO), says study coauthor Borna Nyaoke.
"Studies have demonstrated 95 per cent and 60 per cent resistance rates to amoxicillin and gentamicin respectively in gram-negative bacteria causing neonatal sepsis," explains Nyaoke, who is also clinical project manager for the non-profit Global Antibiotic Research and Development Partnership.
Researchers conducted a randomized controlled trial to assess the safety of fosfomycin given by injection and orally to newborns with clinical sepsis.They screened newborns on admission at the Kilifi County Hospital in Kenya between March 2018 and February 2019.
All newborns were treated with standard-of-care antibiotics, namely ampicillin, benzylpenicillin, flucloxacillin and gentamicin, according to the WHO and Kenya national pediatric guidelines.
We randomly assigned half of the participants to receive additional IV [intravenous or injection] followed by oral fosfomycin at 100 milligrams twice daily for up to seven days."
Christina Obiero, lead author of the study, and clinical investigator based at KEMRI-Wellcome Trust Research Programme, Kenya
According to the study, there was no evidence that fosfomycin given by mouth and injection led to adverse side effects such as stomach pain, though it says further trials are needed to confirm the results.
"We anticipate better treatment outcomes with fosfomycin given its limited use in babies and developing countries," says Obiero.
She adds that fosfomycin was previously patented, leading to limited production, availability and affordability but it is now off-patent, and this assures its availability for use.
According to Obiero, laboratory-based studies have shown that fosfomycin combined with amikacin has enhanced efficacy compared with fosfomycin alone. A future clinical trial is currently in the planning stage to assess combinations of fosfomycin with other antibiotics such as amikacin.
Angela Dramowski, a pediatric infectious diseases specialist and clinician researcher at Stellenbosch University in South Africa, tells SciDev.Net: "This is a very important and relevant study, particularly for babies in Sub-Saharan Africa that face a triple challenge."
In Sub-Saharan Africa, you find the highest-burden of serious bacterial infections and infection-related newborn deaths globally, some of the highest rates of antibiotic resistance worldwide, and a shortage of effective antibiotics to treat these infections, she explains.
"The problem of lack of access to effective antibiotics is also multi-factorial," Dramowski adds. "Few new antibiotics brought to market and almost no data on safety and effectiveness of new and many 'old' antibiotics in neonates, and lack of finances to procure these antibiotics for newborns with resistant bacterial infections in countries with competing health challenges.
"Given the major contribution of neonatal sepsis to global mortality, much more research funding and advocacy are needed to develop new infection prevention, diagnosis and treatment options for this vulnerable population."
Obiero, C.W et al. (2022) Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload. Archives of Disease in Childhood. doi.org/10.1136/archdischild-2021-322483.