Infectious Disease

No antibiotic in development is sufficiently effective against drug resistance

April 17, 2021

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None of the 43 traditional antibiotics in the clinical pipeline that target WHO priority pathogens, Clostridioides difficile or tuberculosis, treat drug resistance adequately, according to a new report.

The WHO’s annual Antibacterial Pipeline Report reviews antibiotic candidates in the early development or clinical trial phases to assess progress, identify drug resistance gaps, and promote action to address those gaps.

Antibiotic pills

According to the WHO, the antibiotic pipeline is insufficient to combat the increasing incidence and spread of antibiotic resistance.
Source: Adobe Stock.

This year’s report revealed a “near static” pipeline, the WHO said. 43 traditional antibiotics and combinations have been described in development – 26 targeting WHO priority pathogens, 12 targeting TB, and seven targeting C. difficile.

The report states that “antibacterial agents in clinical development unfortunately do not address the problem of largely or pan-drug resistant Gram-negative bacteria. There is still a lack of novel antibiotics targeting the WHO’s critical priority pathogens. “

“In particular,” the report said, carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa “continue to be inadequately treated”. The pipeline is also insufficiently addressing oral antibiotic treatment options for expanded spectrum beta-lactamases and carbapenem-resistant enterobacterales “that could allow treatment outside of a health facility or reduce the duration of treatment in the facility”.

The report notes that only two new antibiotics for the treatment of multi-drug resistant tuberculosis have hit the market in over 70 years and that investment in research and development for tuberculosis agents is at its lowest since 2008.

According to the report, there are 27 non-traditional antibacterial agents in the clinical pipeline, including nine antibodies, four bacteriophage and phage-derived enzymes, eight microbiological modulators, two immunomodulatory agents, and four agents in the miscellaneous category that contain antivirulants.

Most non-traditional products are currently being tested and are intended to be used in combination with standard antibiotics, the report said. Four are in phase 3 of development.

Most drugs in clinical development “offer limited clinical benefit over existing treatments, with 82% of recently approved antibiotics being derivatives of existing classes of antibiotics with well-established drug resistance,” said the WHO.

According to the report, there are more than 290 different antibacterial agents in the preclinical pipeline.

“The ongoing failure to develop, manufacture and commercialize effective new antibiotics is compounding the effects of antibiotic resistance and jeopardizing our ability to successfully treat bacterial infections.” Hanan Balkhy, MD, The WHO deputy director general for antibiotic resistance said in a press release.

The report also found that there are some “promising” products in the pipeline, but only a fraction of them will hit the market due to the economic and scientific challenges of drug development.

“Opportunities arising from the COVID-19 pandemic must be used to emphasize the need for sustainable investment in research and development of new and effective antibiotics.” Haileyesus Done, MD, MPH, PhD, The press release states who is leading WHO’s global coordination efforts against antibiotic resistance. “Antibiotics are the Achilles’ heel for universal health insurance and our global health security. We need sustained efforts worldwide, including mechanisms for pooling funding and new and additional investment, to address the scale of the AMR threat. “

References:

Press release.

WHO. 2020 Antibacterial Agents in Clinical and Preclinical Development: Overview and Analysis. https://www.who.int/publications/i/item/9789240021303. Accessed April 15, 2021.

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