Neonatal sepsis.
AMR and sepsis in newborns and children.
Children are highly vulnerable to drug-resistant bacteria. This is especially true of newborns: their immune systems are immature, they deteriorate quickly and clinicians often must start antibiotics immediately, before reliable microbiology results are available. One out of every five deaths caused by antibiotic resistance occur in children under the age of five – 99.7% in low- and middle-income countries (LMICs) – and every year up to three million newborns get serious infections that lead to sepsis, a life-threatening bloodstream infection.
Despite their greater need for protection, hardly any antibiotics are developed and made available for newborns or children. Only four of the 40 new antibiotics approved since 2000 have dosing information for newborns in their labelling. The development of antibiotics for children, if undertaken at all, trails behind that of adults by nearly a decade, usually because of the added complexity, cost and time it entails. This puts children across the world at risk, especially those in LMICs, with nearly half a million children dying each year from lack of access to effective antibiotics.
How is GARDP addressing this need?
GARDP is rethinking how antibiotic treatments are developed for children and how their access can be improved, especially newborns facing life-threatening sepsis. We are exploring a range of different new antibiotic treatment options for newborns and children, including the use of combination treatments. At the same time, GARDP is looking at how existing treatments can be used to reduce child mortality and improve outcomes for survivors.
Programme goals
GARDP aims to demonstrate how its unique antibiotic R&D partnership model can help to address the global AMR public health failure by enabling the right antibiotic treatments to be developed and made available to people who need them.
The Neonatal Sepsis programme has therefore set the following goals:
Goal 1
Identify and improve access to new treatment regimens for newborns with life-threatening infections that can cause sepsis.
Goal 2
Reduce child mortality and improve outcomes for survivors of sepsis.
Goal 3
Develop new treatments for carbapenem-resistant infections in newborns.
Our neonatal sepsis projects
Global neonatal sepsis observational study (NeoOBS)
Working with partners, GARDP has conducted one of the largest ever observational studies on over 3,200 newborns across 19 sites in 11 high-, middle- and low-income countries across four continents. The aim was to assess which antibiotics are currently being used for neonatal sepsis, and to what extent resistance makes these treatments ineffective.
The study findings provided a wealth of high-quality data which has helped inform the design of the NeoSep1 trial.
NeoSep1 trial
Launched in South Africa and Kenya in early 2023, the NeoSep1 trial is evaluating new combinations of existing antibiotics and comparing them to treatment regimens that are currently used to treat newborn babies with suspected sepsis. It is also looking at the appropriate dose and formulation for newborns.
The innovative trial design ensures that the trial will generate actionable evidence regardless of the outcome. The trial will be expanded to other countries in Africa and the Asia-Pacific region with the expected target of enrolling more than 3,000 newborns by end 2028.
Development of new treatments for carbapenem-resistant infections in newborns
Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Enterobacterales (CREs) cause infections for which there are very limited or no safe and effective treatment options for children and newborns. A novel antibiotic in GARDP’s portfolio that can tackle these infections is cefiderocol.
While this drug is currently only licensed for adults, Shionogi, the pharmaceutical company that developed it, is completing regulatory trials to establish the paediatric dose. GARDP will initially investigate its use in treating neonatal sepsis when used alone and then in combination with other antibiotics.
GARDP policy paper: Survive and Thrive.
While under-five AMR mortality has fallen in recent decades, children and newborns continue to be one of the most at-risks groups. The decline in mortality reflects a broader global trend of increases in child survival, thanks largely to improved access to childhood immunization.
However, mortality reduction in newborns has been much slower than for under-fives. Moreover, given that they are too young to receive most vaccines, newborns are particularly vulnerable and expected to make up a significant proportion of AMR-related deaths. Even though children and newborns are disproportionately affected by drug-resistant infections, they are being left behind in the current global AMR response.
GARDP’s paediatric policy paper examines the reasons and extent of the crisis, and provides recommendations to put this vulnerable population at the centre of the global AMR response.
Prioritize
development of new tools and other measures for diagnosis, treatment and care of children and newborns with drug-resistant infections.
Improve
collaboration to accelerate
paediatric development and regulatory approval.
Integrate
the needs of children of all
ages into AMR National Action Plans.
Improve
surveillance and data collection.
