Optimizing Newborn Care: Inside the NeoSep1 trial
Newborn infections remain one of the leading causes of infant deaths globally, and antimicrobial resistance is worsening the situation. In Kenya and across Africa, neonatal sepsis continues to claim thousands of lives each year, often due to bacteria that no longer respond to standard treatments. As part of World AMR Awareness Week (WAAW) 2025, we spoke with Dr Christina Obiero, Research Scientist at the Kenya Medical Research Institute (KEMRI), to explore how the NeoSep1 Trial is reshaping newborn treatment and strengthening the global fight against antimicrobial resistance (AMR).
Neonatal sepsis is a severe bloodstream infection that occurs within the first 28 days of life and, when not treated quickly, can lead to inflammation, organ failure, and death. Complicating this challenge is AMR, the ability of bacteria to adapt and withstand medicines that once effectively killed them. The antibiotics previously used to treat neonatal sepsis are losing effectiveness due to rising resistance and there is limited evidence on the best combinations or dosing for newborns, and the pipeline for new neonatal antibiotics is extremely thin. “AMR makes infections harder or sometimes even impossible to treat, threatening decades of progress in newborn survival,” Dr Obiero explains.
The NeoSep1 Trial aims to fill this gap. The multi-country study led by the Global Antibiotic Research & Development Partnership(GARDP) in partnership with national research institutions, including KEMRI, is being conducted to ensure findings are relevant to low- and middle-income settings. The trial seeks to optimize antibiotic treatment for newborns with sepsis through evidence tailored to these contexts. NeoSep1 takes a modern, tailored approach; instead of evaluating single drugs, the study tests optimized antibiotic combinations and carefully adjusted dosing regimens suitable for newborns. These include newer combinations such as flomoxef plus fosfomycin, administered alone or with amikacin, and compared with current standard therapies. Each participating hospital uses a site-specific randomization list developed around local treatment protocols, patient populations, and local AMR trends.
In Kenya alone, researchers aim to enroll around 600 newborns across Kilifi County Referral Hospital, Coast General Teaching and Referral Hospital, and Mbagathi Hospital, contributing to a global target of 3,000 infants. The first phase of the trial, conducted in Kenya and South Africa, focused on the pharmacokinetics and safety of flomoxef and fosfomycin in newborns with sepsis. Sixty-five infants were enrolled across three sites: Kilifi County Referral Hospital, Tygerberg Hospital, and Baragwanath Hospital. “These early results confirmed the doses to be evaluated in the second phase,” says Dr Obiero. “We will now randomize newborns with clinical sepsis who are at moderate to high risk of death, assigning them to one of eight antibiotic combinations.”
The evidence generated from NeoSep1 will inform the design of future trials on antibiotic dosing, treatment duration, and combination therapy in newborns. “Ultimately, this research will support updates to WHO guidelines for neonatal sepsis treatment,” Dr Obiero explains. “The goal is to ensure that newborns receive treatments that are both effective and minimize the risk of resistance.” As principal investigator, Dr Obiero highlights the need for stronger surveillance systems, rapid diagnostic tools, sustained investment in newborn health services, and continued support for clinical trials and local research capacity. “NeoSep1 is helping us move closer to that vision by generating local evidence and building scientific capacity,” she says.
NeoSep1 is led by the Global Antibiotic Research & Development Partnership (GARDP) and embedded within the Severe Neonatal Infection Adaptive Platform Trials in Africa (SNIP-Africa) project. SNIP-Africa brings together partners in the Global South and North to address neonatal sepsis and AMR through clinical trials, surveillance, capacity building, and stakeholder engagement. These collaborations are strengthening regional research infrastructure and ensuring long-term sustainability for neonatal sepsis research in Africa.
By testing antibiotic combinations in diverse African settings, the project aims to ensure future treatments are affordable, accessible, and adaptable especially in contexts with high disease burden and limited resources.