An international clinical trial to evaluate desperately needed new antibiotic combinations for newborn babies with sepsis has begun in three public hospitals in South Africa and Kenya, and will be expanded to other countries and regions in 2024.
The NeoSep1 trial, which hopes to recruit up to 3 000 newborns overall, will evaluate new combinations of existing antibiotics and compare them to treatment regimens currently used in newborn babies with suspected neonatal sepsis, writes MedicalBrief.
Chris Hani Baragwanath Academic Hospital, Cape Town’s Tygerberg Hospital and KEMRI-Kilifi County Hospital in Kenya, are involved in the initial stage of the trial.
Neonatal sepsis, a life-threatening infection, affects up to 3m babies a year globally, and is exacerbated by an increasing number of newborns becoming resistant to WHO-recommended antibiotic treatments, particularly the ampicillin-gentamicin regimen.
Over the past decade, AMR has worsened to the point that around 50%-70% of common pathogens exhibit a high degree of resistance to available first- and second-line antibiotics. More than 214 000 babies die of drug-resistant neonatal sepsis every year, mostly in low- and middle-income countries (LMIC).
The trial is sponsored by the Global Antibiotic Research and Development Partnership (GARDP) in collaboration with the Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL); St George’s University of London (SGUL); and the international scientific network Penta.
“Many babies die because of limited treatment options, and the NeoSep1 trial is an opportunity to change this, to identify new antibiotic combinations we can tailor to treat neonatal sepsis where there is widespread resistance to recommended options,” said Seamus O’Brien, director of research and development at GARDP.
The trial will rank the safety and efficacy of three new combinations of older antibiotics (fosfomycin-amikacin, flomoxef-amikacin, and flomoxef-fosfomycin) against the current standard of care. It will also assess and validate the doses of two antibiotics (fosfomycin and flomoxef) for use in newborns.
A key goal is to find out whether some antibiotic treatments perform better than others, particularly in LMICs where highly resistant bacteria are common. The trial will also consider how these combination treatments can best be used in hospital settings with varying levels of antibiotic resistance.
A new way of comparing antibiotic treatments with each other, called the Personalised Randomised Controlled Trial (PRACTical) design, will be used. This allows researchers to compare many antibiotic treatments for neonatal sepsis, and will also enable doctors to choose treatment regimens that are likely to work well for newborns in their particular hospital settings.
“The development pipeline for new antibiotic treatments is limited and the lack of a universal, effective standard of care creates huge challenges in conducting research. Novel trial designs – like the PRACTical design – have been specifically developed for these challenges in important public health emergencies such as neonatal sepsis,” said Sarah Walker, professor of Medical Statistics and Epidemiology at the MRC CTU at UCL.
The NeoSep1 trial builds on findings from a global observational study of sepsis in newborn babies, conducted by GARDP and partners in 19 hospitals across 11 countries from 2018 to 2020.
GARDP published a report on the study in 2022, which had found a worryingly wide variation in treatment and frequent switching of antibiotics because of high resistance to treatments.
“We often have to treat babies with a combination of the antibiotics of last resort. On top of this we are not 100% sure about how to dose these drugs. We’re dealing with fragile newborns, so we need to be aware of the potential toxicity of the antibiotics and dosages we use. This trial … is critical as we want the best possible outcome for newborns,” said Adrie Bekker, principal investigator for the NeoSep1 trial at Tygerberg Hospital and professor in the Division of Neonatology, Department of Paediatrics and Child Health at Stellenbosch University.
Expanding the number of suitable, effective treatment regimens could be lifesaving for newborns and could also decrease the risks of neuro-developmental impairment.
“Having the right antibiotics immediately can make the difference between life and death. We are hoping the trial will provide robust evidence that the antibiotic combinations are safe and effective and that this will lead to a change in both WHO and local treatment guidelines,” said Christina Obiero, principal investigator for the NeoSep1 trial for the KEMRI-Wellcome Trust Research Programme at Kilifi County Hospital, Kenya.
See more from MedicalBrief archives:
Fosfomycin for babies with neonatal sepsis and AMR – Kenya trial
WHO urges action to stem rising AMR as experts call for new neonatal drugs
UNICEF mortality estimates: Millions of children dying of preventable causes