NeoSep1 Part 1 study shows promising antibiotic options for newborns with suspected sepsis
22 Jan 2026
A paper published in the journal Antimicrobial Agents and Chemotherapy (AAC) reports that off-patent antibiotics, fosfomycin and flomoxef, when used at standard doses, were safe in newborn babies with suspected sepsis. Importantly, antibiotic levels at these doses are considered sufficient to expect good clinical effectiveness, highlighting their potential as urgently needed, affordable alternative treatments for neonatal sepsis worldwide.
The paper, co-authored by the NeoSep1 study team, presents results from Part 1 of the GARDP-sponsored NeoSep1 clinical trial. It provides the first evidence for sufficient antibiotic concentrations and for the safety of clinically relevant doses of fosfomycin and flomoxef used together, or in combination with amikacin, in the empiric treatment of neonatal sepsis in predominantly preterm babies weighing more than 1,000 grams.
In 2023, 65 newborns were enrolled in Part 1 of NeoSep1 at three hospitals (2 in South Africa and 1 in Kenya): Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa; Tygerberg Hospital in Cape Town, South Africa; and Kilifi County Hospital in Kilifi, Kenya. Newborns were assigned to one of three antibiotic treatment groups and were followed for 28 days.
Infections are one of the leading causes of death in newborns worldwide, particularly during the first month of life. The burden is especially high in sub-Saharan Africa and Asia, where antimicrobial-resistant Gram-negative bacteria, such as Klebsiella pneumoniae, are common.
NeoSep1 Part 1 showed that the antibiotic combinations tested were safe and well tolerated in both sick full-term newborns and preterm newborns, even though many babies were critically ill and at moderate to high risk of death. A key strength of the clinical trial was that most participants were preterm infants in their first week of life. Collecting pharmacokinetic (PK) and safety data in this group helps address important evidence gaps and allows more accurate predictions of drug exposure for fosfomycin and flomoxef.
These findings are particularly important because very few neonatal PK studies have been carried out to determine optimal dosing of antibiotics, including fosfomycin and flomoxef, in newborns. This work builds on the earlier NeoFosfo trial conducted in Kenya which focused on more mature neonates.
Part 2 of the NeoSep1 trial started in South Africa in June 2025 and will expand to Kenya, Ghana, Uganda, India, Bangladesh, Pakistan, Malaysia and Vietnam, with a target of enrolling 3,000 newborns by 2028. The aim is to identify optimal antibiotic treatment regimens that could reduce deaths from neonatal sepsis in regions with high levels of antimicrobial resistance. The trial will compare the new antibiotic combinations not previously used for sepsis with five treatments currently in use.
Through NeoSep1, GARDP and its partners aim to generate evidence to inform WHO guidance and national and institutional policies on effective empiric antibiotic treatment for newborns with sepsis.
NeoSep1 is sponsored by the Global Antibiotic Research & Development Partnership (GARDP) in collaboration with the Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL), City St George’s, University of London (SGUL), and Fondazione Penta ETS.
The NeoSep1 trial also forms part of the five-year SNIP-AFRICA project, which brings together a consortium of African and European partners. Funded by EDCTP3 and led by Penta, SNIP-AFRICA aims to reduce mortality among newborns with sepsis in hospitals in Africa.
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