Globally, infectious diseases such as pneumonia and sepsis are the leading cause of death and disability in children under five and are responsible for more than 3 million deaths a year. The situation is worsened by drug-resistant infections, as the limited number of treatments for children and babies are becoming less effective. More than 214,000 babies die each year from drug-resistant infections. Most of these deaths occur in low- and middle-countries.
Transforming care of babies with sepsis
Antibiotic resistance is a leading threat to child survival and development. Babies are a particularly vulnerable population as their underdeveloped immune systems struggle to fight infections. A recent study has found that 140,000 newborn deaths were directly attributable to bacterial antimicrobial resistance in 2019. Yet children and babies are not prioritised in terms of investment in research and development.
GARDP—together with the Penta–Child Health Research, St George’s, University of London, the Medical Research Council Clinical Trials Unit at University College London, and the University of Antwerp—has completed one of the largest ever observational studies on the care of babies with sepsis. The study looked at looked at over 3200 newborns at 19 sites in 11 countries on 4 continents. It found that newborns with neonatal sepsis are increasingly dying because of drug-resistant bacterial infections. GARDP released the study findings at ECCMID 2021 and 2022 and has submitted the clinical paper to a scientific journal. Download Report on Neonatal Sepsis Observational Study
GARDP has used the data from neonatal sepsis observational study to design an upcoming interventional trial, which plans to identify better treatment regimens to overcome resistance to the current recommended treatment regimens. The NeoSep1 trial will test the safety and effectiveness of three potential new antibiotic combination treatments, ranking them against existing commonly used antibiotic regimens for neonatal sepsis. It will also look into the relative effectiveness of other approved but less commonly used antibiotic treatments and describe local patterns of antibiotic resistance. The trial will begin in Kenya and South Africa later this year and will be expanded in up to eight additional countries in 2023.
Treatments for children
Children are not small adults and their bodies react differently to antibiotics. It is critical to establish the correct dose for children and confirm safety and effectiveness. Even though children are disproportionately affected by drug resistance, there has been little effort to make antibiotics available for them. To address this lack of treatments, GARDP worked with partners in Kenya to evaluate the dosage and safety of the antibiotic fosfomycin for use in children. Results from the clinical trial indicated that a safe dose of fosfomycin can be used to treat babies with neonatal sepsis.
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.
Evaluating safety and effectiveness
Although regulatory agencies require pharmaceutical companies to develop plans to evaluate new antibiotics for use in children, these are generally not started until after drugs are registered for use in adults. Many plans are delayed for years after licensing in adults, if they are developed at all. A recent study found that of 37 new antibiotics being developed in adults, just 2 were being studied in children. GARDP is working with partners to ensure the research and development of new and improved treatments includes evaluating them for use with babies and children.
Sustainable Development Goals
GARDP’s work to develop new and improved treatments for children is critical to achieving Sustainable Development Goal 3: Ensure healthy lives and promote well-being for all at all ages. Targets within this goal include ending the preventable deaths of newborns and children and ensuring access to effective medicines for everyone who needs them. With sepsis a leading cause of death in babies and children, the World Health Organization have called for urgent action on this infection to achieve SDG3.
In some countries, nearly half of antibiotics given to children are prescribed off-label, meaning children are prescribed drugs licensed for different infections or for use with different age groups. This places enormous pressure on doctors and a heavy reliance on specialist knowledge, which may be limited. It also contributes to the increase in drug resistance. GARDP is working with partners to improve guidance on treatments for children and babies.
“There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections. This is a major problem for babies in all countries, both rich and poor. Our study has shown that antibiotic resistance is now one of the major threats to newborn health globally. It has allowed us to design a major new global trial of new treatments with a goal to reduce mortality from neonatal sepsis.”
– Mike Sharland, Principal Investigator St George’s, University of London & AMR Programme Lead, Penta