Why some infections are getting harder to treat

In 1910, the very first manufactured antibiotic came into use. Called salvarsan, it was used to treat syphilis. Less than two decades later, in 1928, the discovery of penicillin truly launched the antibiotic era.

Since then, antibiotics have saved the lives of countless people who would otherwise have died of infections. Now, though, many experts are worried that we have begun to live in an era in which bacteria become more and more resistant to drugs, and standard infection treatments no longer reliably work.

In 2022, the World Health Organization (WHO) classified antimicrobial resistance (AMR) as a top global health threat. (Antimicrobials include antibiotics.) The agency estimated that, in 2019, AMR caused 1.27 million deaths globally and contributed to nearly 5 million more.

What is antibiotic resistance and how does it happen? What bacteria have stopped responding to drugs? And what’s being done to address the problem?

What causes resistance?

Antibiotic resistance happens when bacteria evolve so that antibiotic drugs can’t kill them anymore.

“Every type of bacteria has its own genome,” or set of genes and DNA, says Seema Shah, MD, an infectious disease specialist in Houston, Texas.

“Mutations can occur in one bacterium that make it resistant to a type of antibiotic. Those start to multiply even if you’re taking antibiotics because they’re not affected. And they can transfer that resistance to other bacteria,” Dr. Shah explains.

In other words, unnecessary use of antibiotics kills the bacteria that are not resistant. But the types that are resistant stay alive. These survivors can then multiply, increasing the likelihood for antibiotic resistant infections in humans.

About 28 percent of antibiotic prescriptions are unnecessary, according to the Centers for Disease Control and Prevention (CDC). In 2022, healthcare providers in the United States wrote 236.4 million outpatient oral antibiotic prescriptions. Using the CDC’s estimate, that means about 66 million of those may not have been needed.

While this is cause for serious concern, it’s small compared to the amount of antibiotics used for livestock and agriculture. Bacteria in farm animals exposed to these antibiotics can develop resistance over time. When humans eat the farm animals or produce grown in soil that used their manure as fertilizer, they may pick up the resistant bacteria.

A 2023 study published in PLOS Global Public Health noted that as of 2017, antibiotics given to livestock accounted for 73 percent of all antibiotics used worldwide.

Which bacteria are resistant to antibiotics?

Each year in the U.S., more than 2.8 million people become ill and 35,000 die from antibiotic-resistant infections, according to the CDC. Here are the antibiotic-resistant bacteria strains that the organization deemed to be urgent or serious threats in a 2024 report:

• Carbapenem-resistant Enterobacterales (CRE), including E. coli
• Carbapenem-resistant Acinetobacter
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant Enterococcus (VRE)
• Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales
• Multidrug-resistant (MDR) Pseudomonas aeruginosa

The fungus Candida auris (C. auris) also made the list. (Fungus is not bacteria.)

What’s being done?

To reduce overuse of antibiotics and lower the number of bacteria that become resistant to them, the WHO’s Essential Medicines List divides the drugs into three classes:

• The “access” group consists of the most commonly used antibiotics, such as amoxicillin and cephalexin. They’re used to treat a wide variety of illnesses and should be available at all times.
• The “watch” group includes first- or second-line treatments for a smaller number of infections. They’re at high risk of becoming resistant.
• The “reserve” group consists of last-resort treatments for when other antibiotics have failed to work.

The CDC has a similar effort with its hospital-based antibiotic stewardship programs.

As for antibiotics on farms, the European Union outlawed their use to promote growth in animals in 2006. In the U.S., antibiotics considered “not medically important” for treating human illnesses may still be used for animal growth. They can also be used on farm animals for treatment, prevention, or control of a specific disease.

Worldwide, overuse of antibiotics on farm animals is widespread in low- and middle-income countries, however, and recent research has detected “hotspots” of antibiotic resistance in India, China, and many other countries.

In 2020, the U.S. government released a multi-year plan to combat antibiotic-resistant bacteria. It aimed to better detect resistant bacteria, speed up research, and improve collaboration among the many groups involved with this problem, including healthcare and veterinary professionals, farmers, researchers, and industry.

Ongoing barriers

Addressing antibiotic resistance is methodical work, and the pace of developing new antibiotic drugs has been slow. In recent years, other global health emergencies, including COVID-19, have diverted public health resources away from the problem. Money issues present another obstacle.

“There’s not a lot of incentive for drug companies to make these new antibiotics,” says Shah. Many invest cautiously because there’s less profit potential compared to developing other types of drugs.

Some new antibiotics have been approved in recent years, including new oral antibiotics for gonorrhea, a common sexually transmitted infection. But innovation generally hasn’t kept pace with resistance, and efforts to address the root causes of the problem are ongoing.