Neonatal antimicrobial resistance

Newborn babies worldwide are dying as resistance to antibiotics increases, but a Liverpool initiative is bringing together local and international research to take a joined-up approach to a global problem that could cause millions of deaths.

The global challenge of rising antimicrobial resistance

“Neonatal infection is a huge challenge because newborn babies present with non-specific widespread blood infections which are life-threatening and many babies die as a result,” says Professor William Hope, Dame Sally Davies Chair in Antimicrobial Resistance and Director of the Centre of Excellence in Infectious Diseases Research (CEIDR).

The rise in antimicrobial resistance (AMR) where infections no longer respond to antibiotics is a global problem: “We are seeing the rise of AMR so infections are drug resistant. Especially in Asia and sub-Saharan Africa, we see babies who now have no other treatment options because drug resistance rates are over 60 per cent. So they die because there are no antibiotics suitable to treat the infection,” says Professor Hope.

“The current antimicrobial regimen recommended by the World Health Organization is increasingly ineffective in the face of drug resistance. Too many babies die because they do not receive an effective antibiotic.

Doctor listening to baby's heartbeat

“Drug resistance is one of the greatest challenges of our time. Premature and newborn babies are particularly vulnerable because they are so small and present so many issues around drug safety.” The O’Neill report commissioned by the UK government and published in 2016 suggests that without action AMR will cause the deaths of 10 million people by 2050 and result in an accumulated cost of $100 trillion for the global economy.

The Liverpool approach

“AMR does not respect borders or boundaries, so we need to tackle the problem at speed and at scale,” says Professor Hope.

In Liverpool, CEIDR is now bringing together the expertise of Liverpool School of Tropical Medicine (LSTM) and the University of Liverpool, developing partnerships with industry, and working with the Global Antibiotic Research and Development Partnership as well as the U.S. Food and Drug Administration. Liverpool now has internationally leading research to develop new antibiotics, vaccines and materials to overcome drug resistance.

“Newborn babies need personalised care, including up-to-date medicines and technology,” says Professor Mark Turner, Professor of Neonatalogy and Research Delivery at the University of Liverpool, and Consultant Neonatalogist and Director of Research at Liverpool Women’s NHS Foundation Trust. “Sadly society has neglected the needs of newborn babies when medicines have been developed, and my research aims to fill some of those gaps.”

Professor Turner, who is a CEIDR member, is tailoring new antibiotics and other medicines to premature and newborn babies as part of the EU Innovative Medicines Initiative conect4children. “Worldwide we have made some progress in neonatal mortality rates, but that depends on having effective antibiotics to treat neonatal sepsis. AMR is a huge problem: the COVID-19 pandemic spread across the world very quickly, and AMR is spreading in a similar way though more slowly. This is why we are working on new antibiotics urgently.

“Our work will mean safer healthcare for babies in Liverpool, protecting them from antimicrobial resistance, and protecting babies worldwide too. By solving local problems we are delivering global solutions.”

Researchers are using their world-class clinical pharmacology research to tailor drugs precisely, and developing new ways to deliver personalised medicine. “Currently antibiotics are administered on a ‘one dose fits all’ basis, but we are optimising the use of antibiotics to find the right dosage to deliver maximum effect,” says Professor Hope. In 2019 LSTM and UoL were awarded £3.54 million for a research project to develop a personalised health approach to AMR, measuring real-time drug concentrations in patients and performing real-time analyses of drug action in the body.

“We are taking a joined-up approach,” he adds, “and working together in Liverpool to develop a civic data cooperative so the use of antibiotics and detection of AMR can be tackled at a citywide level using state-of-the-art data and technologies.”

Technicians working on bacterial culture of pathogens in laboratory

Global reach

AMR presents different challenges in different places. In sub-Saharan Africa, fewer diagnostic tests and types of antibiotics are available. “In Malawi, we are seeing a rapid upturn in infection resistant to cephalosporins which are first-line antibiotics,” says Nicholas Feasey, Professor of Clinical Microbiology at LSTM and Head of Drug-Resistant Infections at Malawi-Liverpool Wellcome Trust Clinical Research Programme.

“Here, neonatal sepsis is frequently untreatable, and babies are dying. Around a quarter of the population here now carry cephalosporin-resistant bacteria. As bacteria evolve in response to different antibiotics, there are now multidrug-resistant strains we cannot treat,” says Professor Feasey, a CEIDR member.

The Drivers of Resistance in Uganda and Malawi (DRUM) project run by LSTM is now addressing how water, sanitation and antibiotic use contribute to antibiotic resistance and will inform government policy. “Liverpool is a global city which has a long tradition of being a leader in global health research, and through our work here in East Africa we aim to identify regionally helpful interventions, for example, local solutions to optimising antibiotic use, that will help prevent resistant bacteria from spreading further”.