What Is Antimicrobial Resistance (AMR)?

History of the AMR Problem

The history of the AMR problem dates back to the era of penicillin’s development. Alexander Fleming, who discovered penicillin in 1928, stated in his 1945 Nobel Prize in Physiology or Medicine acceptance speech: “A time may come when penicillin can be bought by anyone in a store.At that time, there is a risk that uninformed people might take it in doses below the required amount, exposing the microorganisms in their bodies to a non-lethal dose of the drug and thereby creating drug-resistant bacteria.”

In fact, as early as 1940—five years before Fleming made this remark—penicillinase, an enzyme that inactivates penicillin, was discovered in bacteria resistant to penicillin. Just as Fleming predicted, it is no exaggeration to say that the remarkable history of antibiotic development after World War II has been a history of the battle against drug resistance.In the 1960s, a series of new antibiotics were developed, including methicillin—effective against penicillin-resistant Staphylococcus aureus—as well as aminopenicillins (ampicillin) and aminoglycosides (gentamicin), which were effective against Gram-negative bacteria. Consequently, the perception that bacterial infections were no longer incurable diseases became widespread.

At the same time, as developed countries acquired powerful weapons to combat infectious diseases—such as vaccines and antimicrobial agents—and the leading causes of death shifted from infectious diseases to noncommunicable diseases (NCDs), the focus of pharmaceutical companies’ research and development also shifted. Consequently, the development of new antimicrobial agents has been on a steady decline since the 1980s.At the same time, the threat of new drug-resistant bacteria began to rise, particularly within hospitals. This was due to an increase in healthcare-associated infections (HAIs) related to surgeries and medical devices, driven by advances in medical technology.
In Japan as well, healthcare-associated infections caused by drug-resistant Gram-positive cocci—such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE)—and subsequently by multidrug-resistant Pseudomonas aeruginosa (MDRP),multidrug-resistant Acinetobacter (MDRA)—are spreading and remain a major problem in healthcare facilities.Furthermore, community-acquired drug-resistant infections outside of healthcare facilities have also been on the rise recently

. Additionally, regarding the issue of drug-resistant bacteria in animals, it has been pointed out that, in addition to reducing the therapeutic efficacy of treatments in the veterinary field, if drug-resistant bacteria are transmitted to humans via livestock products and cause infections, the therapeutic effects of antimicrobial drugs may not be fully achieved.

Looking abroad, the problem of antimicrobial resistance is expanding beyond infections caused by common bacteria, as evidenced by the emergence of malaria parasites resistant to artemisinin—a drug specifically effective against malaria—and the global spread of multidrug-resistant and extensively drug-resistant tuberculosis (mycobacteria).

Estimates of the disease burden and economic burden caused by drug resistance have been conducted in Europe and the United States, andand according to the Jim O’Neill Report, if no measures are taken, the number of deaths caused by drug-resistant bacteria worldwide is estimated to reach 10 million annually by 2050—exceeding the current number of cancer-related deaths—and result in a loss of 100 trillion dollars in gross domestic product.In today’s increasingly globalized world, this is not merely a problem for other countries; measures

to combat

antimicrobial resistance are an issue that every nation must address.

Reference: Action Plan for Antimicrobial Resistance (AMR) 2016–2020, “Introduction”

Addressing New Drug-Resistant Bacteria and Developing New Antimicrobials

Since Alexander Fleming’s discovery of penicillin, numerous antimicrobial drugs have been developed, significantly reducing the number of deaths caused by infectious diseases. However, research and development of new antimicrobial drugs has stalled significantly in recent years. One reason for this is that even if a new antimicrobial drug is successfully developed, there is little prospect of recouping the investment required to bring it to market.In the United States, there was even a case where a company responsible for developing treatments for antimicrobial resistance (AMR) went bankrupt despite successfully developing a new drug and bringing it to market.

To address this pressing issue, in 2020, 24 pharmaceutical companies worldwide—including members of the JPMA—partnered with non-governmental stakeholders to launch the AMR Action Fund, a $1 billion research and development support fund aimed at bringing up to four new antimicrobial drugs to market over a 10-year period.From Japan, five companies—Eisai, Shionogi & Co., Daiichi Sankyo, Takeda Pharmaceutical, and Chugai Pharmaceutical—are contributing to and supporting this fund.Furthermore, to create a new framework for attracting sustainable and robust investment in antimicrobial R&D, the JPMA, as a member of the AMR Alliance Japan, is promoting pull-type incentives ^※ and is contributing to the advancement of AMR policies and the concrete implementation of countermeasures. Since bacteria are constantly mutating, if new antimicrobial drugs are not continuously developed, we risk being thrust back to an era when even a simple cut could be fatal—an era when infectious diseases were the leading cause of death.We need to have AMR treatments ready before drug-resistant bacteria become widespread—and this is achievable.

Future Challenges

In response to a request from the “National Public Awareness Council for Promoting Measures Against Antimicrobial Resistance (AMR),” the JPMA is conducting a wide range of activities aimed at raising awareness and promoting AMR countermeasures.The number of drug-resistant (AMR) bacteria—which render antimicrobials (including antibiotics) that should normally be effective useless—is increasing, posing a global threat. To prevent the spread of drug-resistant bacteria, we will continue our public awareness activities.

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