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  • Writer's pictureP.K. Peterson

Battling Antimicrobial Resistance: WHO’s on Board. Who Else?

“Antimicrobial resistance (AMR) threatens the effective treatment of an ever increasing range of infections caused by bacteria, parasites, viruses and fungi.”     

World Health Organization


“Antibiotics are among the most potent of all anxiolytics – for prescribers.”

Brad Spellberg, MD, CMO, LAC & USC Medical Center

 


The World Health Organization (WHO) defines antimicrobial resistance (AMR) “as when bacteria, viruses, fungi, or parasites change over time and no longer respond to antimicrobial medicines.” (The term “antibiotic” resistance is no longer used because antibiotics target only bacteria and other pathogens are becoming resistant to antimicrobial medicines.) Many experts consider the emergence of AMR pathogens the most serious infectious diseases threat of all.


The ARM phenomenon can happen naturally over time through genetic changes in pathogens.  It is accelerated greatly, however, by human activities such as the misuse and overuse of antibiotics, i.e., using antibiotics to treat viral infections or adding them to animal feed to promote an animal’s growth. In this week’s Germ Gems post, I discuss this global threat and mention some important strategies to counteract the development of AMR.

 AMR: a global threat. In 1928, Alexander Fleming discovered penicillin, the first true antibiotic. In his acceptance speech for the 1945 Nobel Prize for Physiology or Medicine, Fleming recognized the potential for antibiotic resistance and warned that penicillin would be used carelessly and over time become less effective in killing bacteria. Fleming was prescient.


A recent 10-year study in the U.S. reported that nearly half of Streptococcus pneumoniae, a major cause of pneumonia and meningitis, are antibiotic-resistant. Another recent study found that in the Americas, more than 40% of all infection-related deaths are associated with AMR. According to recent estimates, up to 10 million deaths due to AMR pathogens could occur annually by 2050. If left unchecked, AMR could shave $3.4 trillion off the Gross Domestic Product annually and push 24 million more people into extreme poverty in the next decade.


Who is to blame for AMR?  Bacteria, as well as other pathogens (viruses, parasites, and fungi) are incredibly ingenious creatures in developing mechanisms whereby they become resistant to antimicrobial agents. It is simply a matter of evolution—a strategy for survival.


Antibiotics fight bacterial infections and can save human lives but are not effective against viral infections. And, it is well established that the more antibiotics we add to the environment—either by physicians over-prescribing them or by farmers adding them to animal feed for growth promotion (the efficacy of which is thin)—the more antibiotic resistance we see.


In some countries, antibiotics can be purchased without a prescription, that is, over-the-counter (OTC). The OTC sale of antibiotics contributes to an antibiotic’s misuse and fosters the development of AMR.


The development of AMR in agriculture is greatly shaped by geography. China adds more than 30,000 tons of antibiotics to feed per year, followed by Brazil with 10,000 tons per year, and, in third place, the U.S. with more than 5,000 tons per year.


Weaning physicians off overprescribing antibiotics. Doctors have been overprescribing antibiotics and using them to treat viral infections. (Antibiotics only work against bacteria.) This practice was greatly magnified during the early years of the COVID-19 pandemic. (See “WHO Reports Major Overuse of Antibiotics for Treatment of COVID-19” May 1, 2024). (In defense of the physicians, it’s difficult to assess whether a patient with “sepsis”—altered vital signs due to inflammation—is suffering from a serious viral [SARS-CoV-2] infection alone vs a bacterial superinfection requiring an antibiotic.)


One of the most effective strategies to control emergence of antibiotic resistance in the U.S. has been the development of “Antibiotic Stewardship Programs” (ASPs). These programs are generally run by teams of pharmacists and infectious diseases physicians in hospital settings, especially in intensive care units, where antibiotics are routinely prescribed but subject to intensive surveillance and monitoring.

ASPs have been shown to curtail AMR. These programs are now expanding into nursing homes where, according to the Centers for Disease Control and Prevention (CDC), 40-75% of the antibiotics prescribed may be unnecessary.


But, a big problem is that most antibiotics are actually prescribed for outpatients—a situation that can’t be easily monitored let alone controlled.

The pipeline is running dry. In the early years of the antibiotic era, the pharmaceutical industry was adept at developing new antibiotics to thwart AMR. But in the late 20th century,  the “antibiotic pipeline” slowed to a mere trickle. Now, approvals of new antibiotics have become exceedingly rare events.


According to Dr. Valeria Gigante, Team Lead of  WHO’s Antimicrobial Resistance Division, in the years from 2017 to 2021 only12 antibiotics were approved and only one of these was “able to target all the pathogens deemed critical by WHO.” (The WHO’s “2021 Antibacterial agents in clinical and preclinical development: an overview and analysis,” was published in March 2023.) As Dr. Gigante stated, “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.”


What pathogens are involved? The WHO maintains a list of “priority pathogens”—microbes for which there is a need for an antibacterial. WHO rates the pathogens as “critical,” “high,” or “medium” based on the urgency of the need for new antibiotics Those pathogens deemed “critical” are considered the most dangerous and include Acinetobacter baumanii, carbapenem-resistant Psuedomonas aeruginosa, and Enterobacteriaceae. WHO’s list of “high” pathogens includesmethicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus, while its “medium” list includes penicillin-resistant Streptococcus pneumoniae as well as antifungals for Aspergillus fumigatus, Candida albicans, C. auris, and Cryptococcus neoformans. (On May 17, 2024, the WHO updated its list of priority pathogens. To me, it would seem prudent that several parasites, like Plasmodium falciparum, and also viruses, like HIV, be added to WHO’s list.)


Who are the partners in battling AMR? Quite appropriately, the WHO plays a leadership role in the global arena in battling AMR. In the U.S., the CDC serves as a driving force in the guidance of physicians and hospitals in antimicrobial use. The CDC works closely with the WHO as well as hand-in-hand with the U.S. Food and Drug Administration (the organization tasked with providing oversight of antibiotics that are added to the feed of food-producing animals) to combat AMR.


In addition, the Antibacterial Resistance Leadership Group (ARLG), a National Institute of Allergy and Infectious Diseases-sponsored group of experts constituted in 2013, plays a pivotal role in AMR research. (See “The Antibacterial Resistance Leadership Group (ARLG)” in the October 2023 Clinical Infectious Disease Supplement.)


Moreover, there is a bill before Congress that could aid in the battle against AMR. The Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act looks very promising. (The bill is awaiting action by the 2023-2024 118th Congress.) This federal regulation would delink companies’ profits from the volume of antibiotics sold to help solve market challenges that led many pharmaceutical companies to abandon antibiotic development. 

What can we all do to stall AMR? Urge Congress to pass the PASTEUR Act. This bipartisan legislation is supported by the patient, infectious diseases physician, and research communities. Were it to pass, it would go a long way toward unclogging the antibiotic development pipeline.


Should that bill stall or fail, there are other activities you might consider doing now that would play a part, albeit small, in the battle against AMR. For example, when your doctor informs you that you will not be prescribed an antibiotic to treat your viral infection, say “thank you.”


But if you have been prescribed an antibiotic to treat a bacterial infection, take it exactly as prescribed—for the full course of treatment even if you feel better sooner. If you fail to do that and have some antibiotic left, dispose of it properly. Do not use it in the future to treat another infection that you self-diagnose as “bacterial.” Approximately, three-quarters of Americans save their antibiotics and use them indiscriminately in the future. Recent studies suggest “leftover antibiotics” are a major barrier to antimicrobial stewardship.  


Finally, given the enormity and complexity of the problem of AMR, we should thank those in industry, academia, and government who are searching for innovative solutions to this formidable global crisis. The lives of millions of people across the globe depend on their success.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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