Why new children’s antibiotics matter
Antibiotic resistance disproportionately affects children, especially newborns (babies under 28 days old). In 2019, over 560,000 neonatal deaths were associated with AMR, including nearly 140,000 deaths directly attributable to AMR.
Despite the urgent need for antibiotics that meet the unique needs of children, the development of new treatments and expansion of access to existing antibiotics continue to be neglected. GARDP created its children’s antibiotics programme to address this crucial gap in antibiotic R&D, with a particular focus on developing new antibiotic treatments for newborn babies who are most at risk from drug-resistant infections.
In 2019, over 560,000 neonatal deaths were associated with AMR, including nearly 140,000 deaths directly attributable to AMR.
Our priority
Reduce mortality from neonatal sepsis
Neonatal sepsis is a life-threatening condition often associated with a bacterial bloodstream infection that affects up to 3 million newborns every year.
WHO estimates that early diagnosis and treatment could prevent around 84% of deaths from neonatal sepsis. However, high rates of drug resistance often complicate treatment, with up to 40% of bacterial infections in hospitalized babies now resistant to standard treatments.
As such, we urgently need effective new antibiotics for this vulnerable population.
Neonatal sepsis is a life-threatening condition often associated with a bacterial bloodstream infection that affect up to 3 million newborns every year.
Antibiotic resistance affects especially newborns
Antibiotic resistance affects especially newborns
Most childhood deaths from blood infections occur in newborns up to 28 days old.
BEHIND THE SCENES
Treating babies with neonatal sepsis in South Africa
Dr. Tanusha Ramdin, a senior neonatalogist at Charlotte Maxeke Johannesburg Academic Hospital, is passionate about working with GARDP and its partners to give more babies with neonatal sepsis a fighting chance to survive.
"I work with very tiny babies, who are especially vulnerable to infections because of their underdeveloped immune systems. If they pick up an infection, their chances of dying are high. Most childhood deaths from blood infections occur in newborns up to 28 days old.
In these situations, we have to administer antibiotics to babies very quickly. It’s often a life-and-death situation. If a baby responds well to an antibiotic, it can be lifesaving. It’s an incredible relief.
Antibiotic resistance is a major problem, and superbugs have made the situation much worse. In our ward, we only have one antibiotic that still works against these superbugs. We are running out of options. If we don’t get more antibiotics soon, more babies are going to die. We desperately need research and investment into new, safe, and effective antibiotics for our newborns, who have different needs than adults. The treatments, formulations, and dosages all need to be tailored to neonates."
2021 Progress
Our achievements
neonatal sepsis
We identified five antibiotics as potential treatments for neonatal sepsis, with three showing particular promise.
identified
three potential combination
treatments for neonatal sepsis
ADVANCED
the clinical development of cefepime taniborbactam for children
INITIATED
collaborations to develop access to antibiotics
R&D progress in neonatal sepsis
In 2020, GARDP worked with Penta - Child Health Research, the University of Antwerp, the Medical Research Clinical Trial Unit at University College London, and St. George's, University of London to complete the global neonatal sepsis observational study, one of the largest ever on the care of babies with sepsis.
This research, which looked at over 3,200 newborns across 19 sites in 11 countries, provided evidence that will fill gaps in our knowledge, transform treatments, and save lives. GARDP presented preliminary conclusions at the European Society of Clinical Microbiology and Infectious Diseases (ECCMID) conference in July 2021 and plans to publish the full results in 2022.
We identified five antibiotics as potential treatments for neonatal sepsis, with three showing particular promise when evaluated in combination using the Hollow Fibre Infection model: amikacin, fosfomycin, and flomoxef.
In 2022, GARDP is planning to launch a strategic public health clinical trial that will validate the flomoxef–fosfomycin dosage and evaluate and rank the three new combinations (fosfomycin–amikacin, flomoxef–amikacin, and flomoxef–fosfomycin) alongside currently used combinations of antibiotics as reported from the neonatal observation study. These existing combinations include the WHO standard-of-care for neonatal sepsis: ampicillin–gentamicin, cefotaxime, piperacillin–tazobactam with or without amikacin, ceftazidime with or without amikacin, and meropenem. The trial, which aims to enrol over 3,000 babies globally, will start in three hospitals in 2022—one in Kenya and two in South Africa—with additional hospitals to follow in up to ten countries.
bringing a new treatment to children
In 2020, GARDP joined forces with Venatorx Pharmaceuticals to study the use of cefepime–taniborbactam in children and newborns. Cefepime–taniborbactam is an investigational combination of cefepime, an existing antibiotic, and taniborbactam, a novel, broad-spectrum beta-lactamase inhibitor that restores the activity of cefepime against carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA).
GARDP and Venatorx have started the paediatric programme focusing on the required non-clinical studies. Three of those studies were completed in 2021, and the definitive study is planned for 2022.
New collaborations to expand access to children’s antibiotics
Access is a crucial aspect of GARDP’s partnerships, including those around children’s antibiotics. It is central to our planned agreements with InfectoPharm and Shionogi to develop new antibiotic treatment combinations for neonatal sepsis, as well as our collaboration with Venatorx to enable the use of cefepime–taniborbactam for children.
It was also a key component of our discussions with Shionogi on cefiderocol, where we agreed to work together to bring cefiderocol to patients in LMICs for both adults and children. Shionogi is conducting the initial paediatric development programme, and two of the three studies in children aged three months to 18 years are ongoing. The final study, which will establish the correct dose for infants under three months old, is currently planned to start in late 2022.
Our next challenge?
“
In 2022, we will focus our efforts on using what we learned in our neonatal observational study to pursue clinical research around the three antibiotic combinations that show promise in treating newborns with sepsis. This will include identifying new study sites and building on the strong framework for our clinical trials. We will also continue to strengthen our collaborations around accelerating access to existing antibiotics for children.
