More newborn babies with sepsis are dying because their infections are not responding to the usual antibiotics, according to the biggest global study on the subject yet.

The study’s sponsor, the Global Antibiotic Research and Development Partnership (GARDP), is now designing an interventional trial to identify better treatment regimens. to combat rising resistance.

GARDP’s study, which involved over 3200 newborns diagnosed with sepsis in 11 countries, was released at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) on Tuesday.

It found that many physicians were forced to use last-line antibiotics such as carbapenems due to the high degree of antibiotic resistance in their treatment units. 

Last-line antibiotics were prescribed to 15% of babies enrolled in the study. Overall, 11% of the newborns died over the course of the study – but there was huge variation between countries and hospitals.

In 2019, nearly 1.3 million deaths – including nearly 140,000 deaths of newborns – were caused by bacterial antimicrobial resistance (AMR).   

Major threat to newborns

“Our study has shown that antibiotic resistance is now one of the major threats to newborn health globally,” said Mike Sharland from St George’s, University of London and the principal investigator. 

“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. 

The World Health Organization (WHO) recommends the standard antibiotics – ampicillin plus gentamicin – for the treatment of neonatal sepsis, but the study showed that many hospitals are using other combinations due to high levels of resistance to the WHO-recommended treatment.   

But the use of antibiotics varied noticeably across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Vietnam and Uganda, “with many different antibiotic combinations being used, often without any underlying data”, according to GARDP.  

Okwenathi Sibango, born prematurely at six and a half months, was one of the babies enrolled in the study. After fighting off an intestinal infection, the tiny boy, who weighed less than a kilogramme, picked up a life-threatening antibiotic-resistant infection in the hospital. He also developed meningitis and his doctors had to treat him with antibiotics of last resort.

“Over the past decade we have a seen a year-by-year increase in antibiotic resistance,” says Dr Angela Dramowski, Clinical Head of General Paediatrics at the Cape Town hospital that treated Sibango.

“We urgently need new antibiotic options. We are also hopeful that the study by GARDP and partners will go far in working out the best treatment options for babies, with the right dose and the least possible toxicity. This will help us in treating babies like Okwenathi.” 

Testing new antibiotic combinations

The GARDP 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 comparative efficacy of other approved but less common antibiotics and describe local patterns of antibiotic resistance.

It starts in Kenya and South Africa later this year and will expand to up to eight other countries next year.   

“There is an urgent need to develop and ensure access to novel antibiotic treatments to keep pace with rising rates of drug-resistant infections among babies with neonatal sepsis,” said GARDP Executive Director Manica Balasegaram.

 “We are incredibly grateful to our numerous partners and funders who have given us essential support to make this observational study possible. Guided by these new insights, we have the opportunity to place children at the centre of the international response to antibiotic resistance.”  

Image Credits: 20 May 2021South AfricaKL Schermbrucker/GARDP.