Global Study Provides High-Quality Data to Improve Treatment of Newborns with Sepsis

A global observational study of more than 3,200 newborns suffering from sepsis in 19 hospitals in 11 countries found that many newborns died because the antibiotics used to treat sepsis were becoming ineffective. It was shown that

The study, conducted from 2018 to 2020, found that infants with culture-positive sepsis had a high mortality rate (almost 1 in 5 hospital-wide) and a significant burden due to antibiotic resistance.

This study provided a wealth of high-quality data aimed at improving the treatment of neonates with sepsis.

The survey results are PLOSMedicine Co-authored by a global team of over 80 researchers across four continents. This study was carried out in collaboration with the Global Antibiotics Research and Development Partnership (GARDP) and St George’s University of London (SGUL). Penta – Child Health Research; Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL). The research team led the data analysis. and the University of Antwerp.

This observational study helped provide the high-quality data needed to design trials of appropriate treatments for neonatal sepsis. This is the result of a great collaboration of researchers and clinicians from Africa, Asia, Latin America and Europe. “

Dr. Neil Russell, Senior Research Fellow, St George’s, University of London

Manika Balasegaram, Executive Director of GARDP, said: “What types of infections are occurring in newborns seen in hospitals, what insects cause the infections, what treatments are used, and what is being used? “It was very important to do this research to better understand the treatments available.” “Why are deaths increasing? This study provides us with important information to help us better design clinical trials and ultimately improve care and outcomes for infants with neonatal sepsis.” gave.”

Sepsis is a life-threatening bloodstream infection that affects up to 3 million infants annually worldwide. Each year, 214,000 newborns, mostly in low- and middle-income countries (LMICs), die from sepsis that has become resistant to antibiotics. Newborns are at particular risk of serious infections due to their immature immune systems.

Mortality among the 19 hospitals studied varied widely, ranging from 1.6% to 27.3%, with significantly higher mortality in LMIC. Leading clinicians from hospitals in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Vietnam and Uganda participated in the study.

Saisemviso Bellafi, Head of Pediatrics at Chris Hani Balagwanas Academic Hospital, Johannesburg, South Africa, said:

“This study reveals the stark reality of antibiotic-resistant infections, especially in LMIC hospitals, which often face shortages of nurses, beds and space. Infections are resistant to antibiotics: “Antibiotics don’t work and babies often die. This situation needs to change urgently. We need antibiotics to cover all bacterial infections.”

The study highlights an alarmingly wide range of treatment modalities. More than 200 different antibiotic combinations were used in the hospital in this study, with frequent antibiotic switching due to high resistance to treatment.

Many physicians have been forced to use antibiotics such as carbapenems due to high antibiotic resistance to treatments recommended on their wards. These are classified as “watchful” antibiotics by the World Health Organization. They must be preserved and are only recommended for certain limited indications. However, in many cases these were the only antibiotics available to treat infections.

Fifteen percent of infants with neonatal sepsis enrolled in this study were prescribed last-line antibiotics. Klebsiella pneumoniae It was the most commonly isolated pathogen. Usually associated with nosocomial infections.

Using the data collected, the team developed two tools that can be used in clinical trials and neonatal intensive care units around the world. The NeoSep Severity Score is based on 10 clinical signs and symptoms and can be used by clinicians to identify neonates at high risk of death so they can receive specialized treatment more quickly. The NeoSep Recovery Score uses many of the same clinical signs and symptoms and may provide important information to clinicians about whether to escalate treatment.

This study also aims to inform WHO guidelines for the treatment of newborns with sepsis.

Wolfgang Stöhr, MRC Observational Studies Statistician at UCL, said: Organisms evolve and drug resistance changes. That is why clinical guidelines for neonatal sepsis must always be adapted. This observational study represents an important step towards better treatment, as guideline updates depend on the latest and greatest evidence. “

The results of this study are being used to design a pivotal strategic public health clinical trial to find better treatments for neonatal infections amid growing resistance to existing treatments.

The Neonatal Sepsis Trial (NeoSep1) is led by GARDP and the MRC CTU of SGUL and UCL and is being conducted at Chris Hani Balagwanas Academic Hospital, Soweto, Johannesburg, Tigerberg Hospital, Cape Town, and Kilifi County Hospital, Kenya. . The trial will also look at the appropriate formulation and dosage for newborns. The trial will be expanded to other countries and regions from 2024, with a goal of recruiting up to 3,000 newborns overall.

Alessandra Nardon, clinical project manager at Penta Child Health Research, said: “Working on prescribing and dose adequacy is essential. Children are not small adults. Medicines meet their needs in a safe and effective way. It has to be prescribed to meet the needs,” he said.

The new trial will benefit from significant laboratory work done during the observational study.

Survi Malhotra-Kumar, Director of the Institute for Medical Microbiology, University of Antwerp, said: “The Laboratory for Medical Microbiology (LMM LAB-Net) acted as a central laboratory and supported local laboratory analyzes for observational studies. A detailed molecular analysis of the pathogen.Together, these results provide valuable information for the NeoSep1 trial.”