On 15 April, the World Health Organization published the annual review on antibacterial agents in clinical and preclinical development. The analysis focuses on agents in the pipeline and recently approved drugs that might be useful for treating WHO priority pathogens, Mycobacterium tuberculosis and Clostridioides difficile. The findings of this review highlight the need for improvements in drug development in order to effectively tackle the emergence and spread of antibiotic resistance.
Of the 43 new agents in clinical development, 26 are targeting WHO priority pathogens but only seven fulfil at least one of the four WHO innovation criteria (defined as not having any cross-resistance to other antibiotics, belonging to a new chemical class, having a new target or a new mode of action). Further limitations discussed by the authors of the review are the insufficient effect of these drugs on extensively- or pan-resistant Gram-negative bacteria. Additionally, there is a lack of oral options for the treatment of extended-spectrum beta-lactamase producing organisms or those with carbapenem resistance. Oral options are essential for facilitating outpatient treatment, for allowing an earlier switch to oral therapy and for reducing the duration of hospitalisation.
Among the 11 antibiotics that have received regulatory approvals since 2017, only two represent a new class. According to the report the other newly approved antibiotics, which are derivatives of existing drug classes, have a limited additional clinical benefit when compared to existing drug treatment in scenarios where organisms already have multiple resistance mechanisms.
The pre-clinical pipeline shows more promise with considerably more agents under development however, it will take time and likely only a small fraction of these drug candidates will finally be available for patient treatment.
Finally, the review discusses a number of ‘non-traditional’ approaches to treatment such as bacteriophages and phage-derived enzymes, antibodies, microbiome- and immune-modulating agents and anti-virulence agents.
Other interesting reads:
European Commission: Antimicrobial resistance among biggest global health threats
BSAC – Vanguard Report: Antimicrobial resistance and the future of diagnostic testing
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