The World Health Organization (WHO) has updated its list of antibiotic-resistant bacteria that pose the greatest threat to human health, ranking the 15 families of bacteria that feature as “critical”, “high” and “medium” threats. 

The Bacterial Priority Pathogens List (BPPL) 2024’s “critical” list features bacteria that are high burden, can resist treatment and spread resistance to other bacteria.

A new entrant on the “critical” list is a third-generation cephalosporin-resistant Enterobacterales. It joins tuberculosis resistant to rifampicin, and gram-negative bacteria resistant to last-resort antibiotics.

Gram-negative bacteria have built-in abilities to find new ways to resist treatment and can pass along genetic material that allows other bacteria to become drug resistant as well.

“The list provides guidance on the development of new and necessary treatments to stop the spread of antimicrobial resistance (AMR),” according to the WHO

AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to medicines. It is driven largely by the misuse and overuse of antimicrobials.

High priority bacteria include fluoroquinolone-resistant salmonella and shigella; gonorrhoeae that is resistant to third-generation cephalosporin and/or fluoroquinolone, and Staphylococcus aureus that is methicillin-resistant

“Antimicrobial resistance jeopardises our ability to effectively treat high-burden infections, such as tuberculosis, leading to severe illness and increased mortality rates,” said Dr Jérôme Salomon, WHO’s Assistant Director-General for Universal Health Coverage.

Not enough support for new drugs

But there is not enough support for the development of new antibiotics, according to a new report released this week by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)

The report reviews the antibiotic pipeline data against bacterial pathogens identified by the WHO and other public health agencies as of the greatest concern. 

Only 10 new antibiotics or combinations were approved by stringent regulatory authorities between 2017 and 2023, and only two of these are defined as innovative by the WHO. None constitute a new class of antibiotics. 

There is currently just one antibiotic candidate in Phase III clinical trials across the four bacterial pathogens defined as a critical priority by WHO. Only two of the seven high-priority pathogens have innovative candidate antibiotics in development, with five having three or fewer candidates at any stage of clinical development.

James Anderson, IFPMA’s Executive Director of Global Health acalled for “urgent action” to reinforce the pipeline of antibiotics and protect the world from rising drug resistance. 

“Robust pull incentives are crucial in encouraging the research and development investment needed, and by demonstrating the impact that these can have, this report underscores the economic and health imperative for governments to act boldly in a year when the UN is focused on combatting AMR,” said Anderson.

Using predictive health intelligence and data analytics experts from Airfinity, the report found that, if no new incentives are introduced that could encourage investment into antibiotic R&D, the pipeline will continue to decline, delivering only eight approvals by 2033. Under this scenario, in 10 years’ time, the pipeline is expected to contain 26 treatments, of which only 6 are in late stages of development.

However, if “effective incentives” are introduced by 2025, 19 new antibiotics could be approved and a pipeline of 72 treatments in 2033.

Some of the examples the IFPMA cites as promising incentives include a novel subscription model being rolled out in the UK. This involves paying companies a fixed annual fee for antimicrobials based primarily on their value to the National Health Service (NHS), as opposed to the volumes used. 

Last year, Japan announced that it will pilot a revenue guarantee model to help subsidies companies that work to address AMR.

The Japanese government is moving forward with their pull incentive, called the "Antimicrobial Securement Project" [抗菌薬確保支援事業]. This is a revenue guarantee pull incentive, akin to Sweden, but higher in funding amount. pic.twitter.com/43ojdKjzT4

— Kevin Outterson (@koutterson) February 13, 2023

However, the IFPMA wants a global model to reward the successful development of new antibiotics. 

“There needs to be a level of global coordination and enough countries involved to make sure that the total economic package is sufficient to attract the necessary R&D investment,” according to the IFPMA.

Image Credits: DFID/ Will Crowne, IFPMA.