The number of antibacterial agents in preclinical and clinical development worldwide rose from 80 to 97 from 2021 to 2023 and new antibiotics are urgently needed to combat severe infections and those tied to antimicrobial resistance (AMR), the World Health Organization (WHO) advises in a report released late last week.
The report, the first published since 2017, assesses whether antibiotics in the pipeline will likely address infections caused by WHO priority pathogens, which are drug-resistant bacteria posing the greatest risk to human health.
"Antimicrobial resistance is only getting worse yet we're not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria," Yukiko Nakatani, MD, PhD, interim WHO assistant director-general for antimicrobial resistance, said in a WHO news release. "Innovation is badly lacking yet, even when new products are authorized, access is a serious challenge."
Gaps across the pipeline
Thirteen antimicrobials have been authorized by the US Food and Drug Administration, the European Medicines Agency, or other stringent regulatory organization since July 2017, the report said.
But only two are in a new chemical class and considered innovative, which the authors said highlights the challenges of discovering new effective and safe antibacterials. Three nontraditional drugs to restore gut microbiota in adults have also been authorized to prevent recurrent Clostridioides difficile infection (CDI) after antibiotic treatment.
Of the 97 in-development antibiotics, 57 are traditional antibacterials, including 12 new products that entered the pipeline since 2017. Of the 57 traditional antibiotics, 56% are intended for use against highest-risk WHO priority pathogens (eg, Acinetobacter baumannii, carbapenem-resistant Enterobacterales), and 33% are designed to combat drug-resistant Mycobacterium tuberculosis. Also, five traditional drugs (9%) are being developed against CDI, and one targets Heliobacter pylori.
Of the 32 in-development antibiotics against bacterial priority pathogens, only 12 are considered innovative, and only 4 of the 12 are active against at least one WHO critical pathogen included in the highest-risk category. The antibiotic-development pipeline is lacking medications for children, convenient oral formulations for non-hospitalized patients, and drugs designed to fight drug resistance, the authors said.
Of the 40 nontraditional antibiotics, 30 are intended against WHO critical high-priority pathogens, 9 are directed against CDI, and 1 targets H pylori.
Need for greater collaboration, access
While progress is being made in terms of nontraditional drugs such as bacteriophages, antibodies, anti-virulence agents, immune-modulating drugs, and microbiome-modulating agents, further research is needed to determine how they can be used in the clinical setting.
Policy efforts on R&D and use should focus on financial and non-financial incentives and efforts to optimize the use of authorized antibiotics, develop novel antibacterial agents and explore new fixed-dose combinations of antibiotics for treating serious bacterial infections such as neonatal sepsis.
The preclinical pipeline is more active and innovative, the report said, with many non-traditional drugs and a continued focus on gram-negative bacteria that are resistant to last-resort antibiotics. But the development of antibiotics targeting a single type of bacteria has leveled off. These drugs, the report said, require broadly available and affordable rapid tests to confirm that the target bacteria are present.
The authors called for greater transparency into the pipeline to enable collaboration on challenging projects, help researchers and drug developers, and interest potential funders. The resulting drugs need to be accessible to all, especially those in low- and middle-income countries, they added.
"Policy efforts on R&D [research and development] and use should focus on financial and non-financial incentives and efforts to optimize the use of authorized antibiotics, develop novel antibacterial agents and explore new fixed-dose combinations of antibiotics for treating serious bacterial infections such as neonatal sepsis," the researchers wrote.
