Updated on November 6, 2024.
Throughout history, various cultures, such as the ancient Egyptians, used molds to treat injuries and illnesses, though they didn’t yet know about bacteria. In 1910, the very first manufactured antibiotic came into use. Called salvarsan, it was used to treat syphilis. 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 concerned that we have begun to live in an era in which bacteria become more and more resistant to drugs, and some standard infection treatments no longer reliably work.
The World Health Organization (WHO), in its 2022 Global Antimicrobial Resistance and Use Surveillance System (GLASS) report, noted high rates of resistance to drugs called antimicrobials (these drugs are also called antibiotics) that treat bacterial infections. Classifying antimicrobial resistance (AMR) as one of the top 10 global health threats, the WHO estimates that in 2019, AMR was the direct cause of 1.27 million global deaths, and a contributing factor to nearly five million deaths.
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? We asked infectious disease specialist Seema Shah, MD, of Texas Orthopedic Hospital in Houston for her insights.
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 Dr. Shah.
“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.”
In other words, inappropriate and overuse of antibiotics kills the bacteria that are not resistant but the types that are resistant stay alive. These survivors can then expand in numbers so that more of these types of resistant germs are around, increasing the likelihood for antibiotic resistant infections in humans.
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. The good news is that this number is down from 258.9 million prescriptions in 2018, and 268.6 million prescriptions in 2013. The bad news is that the CDC estimates that about 28 percent of antibiotic prescriptions are unnecessary.
While this is cause for serious concern, it’s still a pretty small chunk 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 meat from these farm animals or eat produce grown in soil that used manure from these animals 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?
The CDC estimates that more than 2.8 million people per year in the U.S. get sick and 35,000 die from resistant infections. Here are four antibiotic-resistant bacteria strains that the CDC deems to be among the most urgent threats as of 2019. The fungus Candida auris is also on the “urgent threats” list.
Acinetobacter
These bacteria can live for a long time on surfaces, and most people who are infected had recently been cared for in a healthcare facility, usually in an intensive care unit. Acinetobacter can cause infections in wounds, the blood, and the urinary tract, as well as pneumonia. Strains of Acinetobacter bacteria that are resistant to a class of antibiotics called carbapenems (which treat severe infections), caused about 700 deaths in 2017. Some strains are resistant to almost all antibiotics, not just carbapenems.
Clostridioides difficile (C. diff)
This bug usually infects people after they’ve taken antibiotics (like fluoroquinolones) for a separate and unrelated condition. Although antibiotics are generally helpful for treating illness, they can have the side effect of causing a person’s microbiome (beneficial bacteria that live in the gut and other areas of your body like the skin) to become unbalanced. C. diff infections caused at least 12,800 deaths in 2017, many of them in older people. More than half of all the approximately 223,900 cases in 2017 were in people living in long-term care facilities who had recently been staying in a hospital.
Enterobacteriaceae
The group of bacteria called Enterobacteriaceae includes many potentially dangerous germs, such as:
- E. coli, which has many different types, most of which are harmless. One type of E. coli, though, is a common cause of food poisoning, as well as urinary tract and deadly bloodstream infections.
- Klebsiella pneumoniae, which can lead to pneumonia, meningitis, and blood infections
In 2017, about 1,100 deaths in the U.S. were caused by carbapenem-resistant Enterobacteriaceae. Those most at risk include people who use catheters or who need to take long courses of antibiotics. Some strains of these bacteria are resistant to the antibiotic carbapenem, and other strains are resistant to almost all antibiotics.
Neisseria gonorrhoeae
This bacterium causes the sexually transmitted infection (STI) gonorrhea, which can itself cause infertility and ectopic pregnancy (when a fertilized egg implants outside the uterus), and it can put an infected person at higher risk of HIV. Certain strains of this STI have become resistant to all but one class of antibiotics. About 550,000 drug-resistant infections are estimated in the U.S. each year. “I don’t think it’s fair to say that resistant gonorrhea is common, but it’s becoming more and more of a problem in the last few years,” Shah says. Treatment is made more difficult because this bacterium is especially difficult to detect without regular screening, as it may not cause symptoms.
Other resistant bacteria that are a priority
An additional 11 resistant bacteria and fungi made the CDC’s “serious threats” list, including strains of:
- Campylobacter
- Candida
- Enterobacteriaceae
- Enterococci
- Pseudomonas aeruginosa
- Salmonella (two strains)
- Shigella
- Staphylococcus aureus
- Streptococcus pneumoniae
- Tuberculosis
Two more strains of Streptococcus are listed as “concerning threats.” A fungus and two additional bacteria strains are listed on the “watch list.”
What’s being done?
In an effort to reduce overuse of last-resort antibiotics and lower the number of bacteria that become resistant to them, the WHO’s Essential Medicines List, updated in 2023, divides antibiotics 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 the use of antibiotics to promote growth in animals in 2006. In the past, in the U.S., farm animals were frequently given antibiotics to grow faster—a common effect of some of these drugs. In 2017, however, the Food and Drug Administration (FDA) implemented a rule against certain antibiotics for purposes of production (like growth). Now it’s illegal to use them except for treatment, prevention, or control of a specific disease. However, antibiotics considered “not medically important” for treating human illnesses may still be used for animal growth. The FDA is continuing to work to curb antimicrobial resistance.
Worldwide, overuse of antibiotics on farm animals is widespread in low- and middle-income countries. Recent research has detected “hotspots” of antibiotic resistance in India, China, and many other countries.
And despite the 2017 FDA restriction, in 2020, the U.S. still ranked in the top five countries in the world for the most antibiotics used in these animals. Researchers predict that between 2020 and 2030, global usage of antibiotics for sheep, cattle, pigs, and chickens will increase by eight percent.
On October 8, 2020, the U.S. government released a five-year plan to combat antibiotic-resistant bacteria. It aims 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
Fighting antibiotic resistance is slow work, and meanwhile, the pace of developing new antibiotic drugs has also been slow. One reason was the global COVID-19 pandemic, according to a special 2022 report by the CDC. This massive health crisis diverted public health resources away from tracking antimicrobial resistance and toward tracking the spread of COVID.
And unfortunately, prescriptions of antibiotics were often given as a first line of treatment for COVID, even though they’re ineffective against a virus. The high rates of hospitalization also meant that more legitimately-needed antibiotics were being prescribed to treat hospital-onset bacterial infections.
Another reason progress is slow is financial. “There’s not a lot of incentive for drug companies to make these new antibiotics,” says Shah. Drug companies haven’t been heavily investing in the research since there’s less financial incentive compared to developing other types of drugs.
In recent years, some new antibiotics have arrived. But this type of research is not keeping pace with the global scale of bacterial resistance, and efforts to get at the root of the problem are continuing.
