JJust minutes from the turquoise waters of Kenya's Kilifi Creek, far from the tourists enjoying the estuary, a team of doctors, technicians and microbiologists are helping to shape a new era of newborn care.
NeoSep1 – a groundbreaking clinical trial the purpose of which is to identify effective and safe combinations of antibiotics for the treatment of sepsis in newborns. One of the centers leading the second phase of this research is the Kemri-Wellcome Trust Research Program (KWTRP) in Kilifi.
Newborn babies are especially vulnerable to sepsis, a life-threatening infection, because their underdeveloped immune systems have difficulty fighting off pathogens. Every year, neonatal sepsis is the cause about 800,000 deaths worldwidewhereas in Africa it accounts for 28% of all neonatal deaths.
Many of these newborns die because of the antibiotics recommended to treat sepsis. no longer effective: The errors evolved and became stable over the years. To 214,000 neonatal deaths worldwide are caused by antimicrobial resistant infections (AMR).
NeoSep1, led by the Global Antibiotic Research and Development Partnership (GARDP), aims to combat growing drug resistance by testing new combinations of existing antibiotics and comparing them with regimens currently used to treat neonatal sepsis.
GARDP Study in 2023 found that more than 200 different antibiotic combinations are used worldwide to treat neonatal sepsis. Sally Ellis, project manager for the pediatric antibiotic program at GARDP, says this variety of antibiotics “encourages bacteria to become resistant.”
Early in the project, the NeoSep1 research teams confirmed the correct dosages for three new combinations of existing antibiotics and identified five other regimens that are recommended for the treatment of neonatal sepsis or routinely used in various hospitals around the world. They narrowed the options down to eight in total.
Christina Obiero, principal investigator of the study at Kilifi County Hospital, said: “We were pleased to find that the doses we used were safe and effective. The second part of the study will further use these treatments to treat sepsis in newborns.”
Ellis says the research strategy is to attack the disease in several ways. “We are committed to improving information about the dosing of each antibiotic combination, identifying the type of microorganism causing the infection, and identifying potential or new treatment options,” she says.
Running in Eight Countries – South AfricaKenya, Ghana, India, Bangladesh, Pakistan, Malaysia and Vietnam – the study will enroll 3,000 babies by 2029, including 600 children under 28 days of age at three Kenyan clinics in Mombasa, Nairobi and Kilifi.
One of the most significant innovations of this work, developed by several international research partners is the inclusion of two antibiotics that have been around for many years but have never been used in Africa to treat sepsis: fosfomycin and flomoxef.
“These drugs were developed back in the 1970s and 1980s, respectively,” Ellis says. “Fosfomycin is widely used in Europe, mainly for urinary tract infections, but increasingly as part of combination therapy for difficult-to-treat infections. Flomoxef is also an older drug that is used almost exclusively in East Asia.”
Development of new antibiotics is expensive and slow, leaving few treatment options for newborns. “Now that fosfomycin and flomoxef are generics, they are much more affordable. We are repurposing them to treat sepsis,” says Obiero.
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Alexander Makazi, coordinator of the NeoSep1 study at the Kenya Medical Research Institute (Kemri), says that to understand how eight combinations, including first- and second-line treatments, as well as new options such as fosfomycin combined with flomoxef, responded to different bacteria, “we exposed the bacteria to a group of different antibiotics… If they couldn't spread, we knew that particular drug was killing them.”
Immediately identifying and prescribing appropriate treatment is one of the most important tasks for the Kemri team. Sepsis may develop suddenly and the newborn's condition may worsen within seconds, making rapid response and prompt initiation of antibiotic treatment critical.
However, determining which bacteria may be affecting a baby “can take about five days from the time the blood sample is taken until the laboratory gets the results,” says Robert Mwakesi, manager of the KWTRP laboratory, located next to the critical care unit at Kilifi County Hospital, where babies are cared for by a medical team under the watchful eye of their families.
Obiero says: “If we know exactly which bacteria are causing the infection and which treatment works best, we can act quickly and save more lives.”
In Africa, NeoSep1, part of a five-year project by a consortium of partners called Snip-Africa, brings together health professionals from different sectors working towards the same goal: ranking eight antibiotic combinations to determine which are most effective and safe for every newborn baby with sepsis.
“As soon as we receive the ranking results, we will try to inform the world Health Organizations and national governments should reconsider existing recommendations,” says Obiero. “In addition to determining the best treatment option for each infection, the goal is also to minimize infants' exposure to unnecessary antibiotics, as this is what ultimately leads to resistance.”
“If we achieve this, it will be a game changer,” adds Makazi, who recalls the relief he felt when one child responded successfully to treatment for sepsis. “The look on a mother's face when she saw her sick baby improve – now strong enough to latch on to the breast – was incredibly moving,” he says.
“Moments like these remind us that our work truly makes a difference.”
