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Too few antibiotics in pipeline, World Health Organization review warns

A new analysis of of antibiotics being developed shows that too few are in the pipeline, particularly ones needed to target potentially dangerous pathogens. File Photo by John Angelillo/UPI
1 of 3 | A new analysis of of antibiotics being developed shows that too few are in the pipeline, particularly ones needed to target potentially dangerous pathogens. File Photo by John Angelillo/UPI | License Photo

March 15 (UPI) -- A new analysis of of antibiotics being developed shows that too few are in the pipeline, particularly those needed to target potentially dangerous pathogens.

The update on the landscape for new antibiotics was published online Wednesday in advance of the European Congress of Clinical Microbiology & Infectious Diseases in Copenhagen, Denmark, that runs from April 15 to 18.

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The review from WHO shows that just 12 new antibiotic shave entered the market over the five-year period from 2017 to 2021. There are 27 under development in clinical trials against pathogens considered "critical," such as Acinetobacter baumannii and Pseudomonas aeruginosa.

Of these 27 under development, only six are considered 'innovative' enough to be capable of overcoming antibiotic resistance. Two of the six are targeting highly drug resistant forms of microbes.

"In the five years covered by this report, we have had just 12 antibiotics approved, with only one of these -- Cefiderocol -- able to target all the pathogens deemed critical by WHO," Dr. Valeria Gigante said in a statement.

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"And there are only 27 more currently under development in phase 1 to 3 clinical trials, with little innovation. Only four of the 27 have new mechanisms of action, and most are not new drug classes, but the evolution of existing classes," said Gigante, the team lead in the World Health Organization's Antimicrobial Resistance Division in Geneva, Switzerland.

Researchers said one antibiotic, Solithroymcin, can be used to treat community-acquired pneumonia and other infections. It is in the new drug application stage, meaning it passed through clinical trials and awaiting market authorization. Seven other antibiotics are in phase 3 trials, having their efficacy assessed.

Difficult to predict

Gigante said, though, it is difficult to predict if and when a market authorization will be granted for these drugs because failure is still possible in late-stage trials.

Antimicrobial resistance, which kills an estimated 5 million people a year, disproportionately harms the poor, who often don't have the resources to access second-line, more expensive antibiotics that could work when first-line drugs fail, scientists said.

Pharmaceutical companies often are not as motivated to develop antimicrobials because those treatments are often more short-term and less lucrative, the WHO report said, noting that they make up a fraction of the revenue generated compared to treatments for cancer and cardiology.

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Calling it the "silent pandemic of antibiotic resistance," researchers warned of a "doomsday scenario" in which routine medical procedures would no longer be effective, and a growing number of people will start dying from what was previously non-threatening treatable infections.

Major gap

"There is a major gap regarding products addressing multi-drug resistant pathogens such as Acinetobacter baumannii and Pseudomonasaeruginosa (just one agent authorized against all the critical pathogens and few in the pipeline)," Gigante wrote.

"The rapid increase of multidrug-resistant infections worldwide is concerning. Time is running out for us to bring new antibiotics to market and combat this urgent threat to public health. Without immediate action, we risk returning to a pre-antibiotic era where common infections become deadly."

She said that while challenges remain, there are developments in coming up with new, innovative antimicrobial agents that have shown some promising results.

"With increased investment and collaboration across sectors, we can make progress in the fight against antimicrobial resistance and ensure that patients have equitable and global access to effective treatments for drug-resistant bacterial infections," she said.

Dr. Venkatasubramanian Ramasubramanian, president of the Clinical Infectious Diseases Society of India and consultant for Infectious Diseases & Tropical Medicine at Apollo Hospitals in Chennai, India, said the world already is living in a "post-antibiotic era." He also will make a presentation at the conference.

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Pipeline insufficient

"The current antibacterial pipeline is woefully insufficient to make a difference in tackling the ongoing threat of antibiotic resistance," Ramasubramanian said. He will highlight challenges in innovation including the withdrawal of large companies from the antibacterial research space.

"We lack a sustainable economic model for anti-bacterial innovation. To exacerbate the issue, the current products under evaluation mainly cater to the requirements of the developed nations, resulting in a mismatch, especially in developing countries with a high burden of resistance," he said.

Ramasubramanian will highlight the discrepancy in the priority pathogen list between WHO and the U.S. Centers for Disease Control and Prevention.

"This incongruity is magnified in the list of certain countries like India, who have a high burden of drug-resistant organisms," he said. "A further twist to the story is when new molecules are developed for resistant organisms, that have shown promise during the developmental stage, fail to perform when strains unique to certain countries are tested.

"This is due to newer mechanisms of resistance that seem to be continually evolving in high-burden countries."

The Centers for Disease Control and Prevention said last year that the progress made against drug-resistant infections slowed during the height of the COVID-19 pandemic. The CDC reported that hospital-related infections and deaths grew by 15% during the pandemic's first year, from 2019 to 2020.

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