More and more bacteria are developing resistance to common antibiotics. In contrast, too few new antibiotic agents are being developed, the World Health Organization (WHO) warns in a report. Between 2017 and 2021, only 12 new antibiotics have hit the market and only 27 are in the pipeline. Most of these are not innovative, new active ingredients, but rather further developments of existing classes of active ingredients.
The discovery of penicillin in 1928 marked a medical revolution. Previously fatal infectious diseases could be cured within a few days with antibiotics. Over time, however, it turned out that bacteria are able to develop resistance to the apparent miracle cure. Today, medical research is in a race with bacteria: new classes of antibiotics with new targets and mechanisms of action can overcome resistance for a while, but precisely when antibiotics are not used responsibly, new resistances quickly develop. Infections with multi-resistant pathogens are an increasing problem worldwide. According to estimates, five million people die every year from infections with multi-resistant germs.
Few innovations
In a report published in 2022, the World Health Organization (WHO) came to the conclusion that too few new antibiotics are currently being developed to be able to adequately counter the increasing resistance. “In the five years from 2017 to 2021 to which this report refers, only twelve antibiotics were approved, of which only one – cefiderocol – is effective against all pathogens classified as critical by the WHO,” explains Valeria Gigante, team leader of the WHO Antimicrobial Resistance Unit in Geneva. She will present the results of the report in April at a special session of the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2023) in Copenhagen.
According to the WHO, only a few innovations in antibiotics can be expected in the coming years. “Only 27 new antibiotics targeting pathogens classified as critical by the WHO are currently undergoing clinical trials,” said Gigante. “Only four of these have new mechanisms of action. Most of them are not new drug classes, but rather an evolution of existing classes.” Only two of the drugs currently in development target highly resistant bacteria. It is difficult to predict when and whether these drugs will receive market approval, since even in the final phase of clinical testing it can still turn out that a new drug does not meet the requirements for safety and efficacy.
Race against resistance
From the point of view of the WHO, various new resistances are worrying. Among other things, various types of bacteria are increasingly able to produce an enzyme called New Delhi metallo-beta-lactamase 1 (NDM-1) that allows them to break down carbapenem antibiotics. These have so far been considered reserve antibiotics and are used when other antibiotics fail. The new resistance could also render this last line of defense ineffective. The spread of resistance is promoted by the widespread inappropriate use of antibiotics. While antibiotics marketed between 1930 and 1959 took an average of 11 years before bacteria developed resistance to them, antibiotics marketed between 1970 and 2000 reduced this period to two to three years.
This means that new antibiotics with new mechanisms of action should actually be developed at an ever increasing pace. One problem, however, is that developing new antibiotics is not very profitable for pharmaceutical companies. Unlike drugs for cancer or cardiovascular diseases, for example, these are mostly short-term treatments that bring in little money for the manufacturers. In addition, most new antibiotics are classified as reserve antibiotics, i.e. they are only used when other antibiotics fail. Seven of the twelve active ingredients newly approved in recent years have already been classified as reserve antibiotics, and others are still being evaluated. This further lowers the earning potential for the developers.
Investment and collaboration required
“We lack a sustainable economic model for antibacterial innovation,” says Venkatasubramanian Ramasubramanian, President of the Clinical Infectious Diseases Society of India, who will also present at ECCMID 2023. “To make matters worse, the products currently being tested are mainly tailored to the requirements of industrialized countries, which leads to a disparity, particularly in developing countries with a high level of resistance.” private partnerships, investing more money in basic antimicrobial research, and providing more financial incentives for pharmaceutical companies.
Gigante also sees an urgent need for action: “The rapid increase in multi-resistant infections worldwide is worrying,” she says. “We are running out of time to bring new antibiotics to market and tackle this public health threat. If we don’t act now, we risk returning to a pre-antibiotic era in which common infections are fatal. With increased investment and cross-sectoral collaboration, we can make progress in the fight against antimicrobial resistance and ensure patients have equitable and global access to effective treatments for drug-resistant bacterial infections.”
Sources: European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2023, Copenhagen, April 15-18, 2023); WHO report