Some antibiotics are no longer as effective. That's as concerning as it sounds.

Immediately after penicillin became widely used some 80 years ago, bacteria started figuring out how to evade antibiotic medications. Ever since, the arms race between dangerous microbes and humans has raged. A new study shows that in crucial ways, humans keep losing.

“The very slow rolling pandemic of antibiotic resistance has been easy to ignore,” but that must change with today’s rising rates coupled with a lack of novel antibiotics that address the problem, says Christina Yek, a research physician at the National Institute of Allergy and Infectious Diseases, part of the United States National Institutes of Health.

Resistance of certain germs to antibiotics remains one of the top global public health challenges, according to the World Health Organization. These organisms kill an estimated 5 million people worldwide each year. In the U.S., more than 2.8 million antimicrobial-resistant infections occur annually, including those acquired in the hospital or picked up elsewhere. When germs become antibiotic resistant, physicians are unable to easily treat the infection 

“We have talked in the past about going into a post-antibiotic era, where we no longer have [effective] antibiotics, but in many respects we’re already there,” says Rick Martinello, an infectious diseases physician at Yale Medicine and medical director of its infection prevention program. “Without the benefit of antibiotics, the outcomes for that individual are bleaker… deaths, prolonged infection, longer hospital stays.”

Hospital-acquired infections increasing

The number of people acquiring resistant microbes in hospitals increased 32 percent during the COVID-19 pandemic, affecting 38 people for every 10,000 hospitalizations, according to a preliminary report presented this spring by Yek and other NIH researchers at the European Society of Clinical Microbiology and Infectious Diseases in Barcelona, Spain. Rates have dropped somewhat since but remain above pre-pandemic levels.

The largest increases occurred in microbes resistant to a commonly prescribed class of antibiotics called carbapenems. The study found this class of antibiotics is encountering numerous resistant bacteria, especially Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales, the cause of many severe hospital infections.

The Centers for Disease Control first raised the alarm about higher-than-normal rates during the pandemic, when more than 29,400 people died from antimicrobial-resistant infections during the first year—with nearly half acquiring the germs in hospitals.

The hope was the percentage of patients with resistant infections would return to their prior baseline, Yek says. But so far, hospital-acquired resistant infections have not.

Meanwhile, drugs have not kept pace. Nearly all new antibiotics approved by the U.S. Food and Drug Administration in recent years have been variations of prior medicines, without new mechanisms of action that target resistant microbes. “That realization has been sobering,” Yek says. “The resistance is gaining while we are staying almost stagnant.”

The socially vulnerable are most at risk

The NIH report included data on two million hospital admissions nationwide collected from insurance companies and medical systems. The researchers also sought to identify groups that are most vulnerable to these infections.

They found people with chronic diseases or more acute illnesses were more likely to acquire a resistant infection. 

In addition, Hispanics and people with lower income and educational levels also had increased rates. “What stood out from the data was that people who were more socially vulnerable were more at risk,” Yek says.

Similarly, a separate abstract presented by Duke University and other researchers at the same international meeting found that Black women in the U.S. who developed carbapenem-resistant Enterobacterales have a higher death rate than white women or men with the same condition. These women were more likely to have vascular or kidney disease before being hospitalized.

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Resistant germs acquired anywhere are a concern, but those acquired in a hospital are particularly worrisome. For one, these germs are generally more virulent and can be resistant to a wider number of antibiotics, which is why they are associated with high levels of disability and death.

Plus, “The implication is we did it to people,” Yek says. Germs can enter a patient’s body through hospital interventions, including catheters, intravenous lines, and/or surgical openings.

Other risk factors for resistance are longer stays in the healthcare facility and having taken antibiotics within the prior three months, according to a review article published in the journal Cureus.

Overused in medicine and agriculture

Scientists have known for years that resistance spreads through the indiscriminate and excessive dispensing of antibiotics, but that hasn’t sufficiently altered the situation. In addition to overuse in healthcare, antibiotics are frequently used in the veterinary and agricultural industries. “Antibiotics may be used as growth promoters in chickens and cows, and they also spray antibiotics on pear and apple trees,” Martinello says.

When exposed to antibiotics, many bacteria and fungi in the body are killed, but those with innate resistance not only survive and multiply, they pass the trait to other organisms. Over time, some germs accumulate genes for resistance not just to one antibiotic, but to many. Such multiple drug resistance microbes are especially difficult to treat.

In these situations, “the patients get the Hail Mary of multiple antibiotics in hopes there will be synergy…but on the whole, those patients don’t get cured of their infections and a lot of them probably die from their infections,” says Yak, whose specialty is infectious diseases.

Combining drugs do help some patients. Adding the antibiotic avibactam to treatment with ceftazidime, for example, boosts its effectiveness against P. aeruginosa from 65 percent to 94 percent, the Cureus review reported.

Minimizing your own use of unnecessary antibiotics

Scientists continue searching for new drugs that might prove effective. Researchers at the Massachusetts Institute of Technology recently discovered a new way to interfere with a certain bacterial enzyme that may lead to a new class of antibiotics. Others are turning to artificial intelligence to identify potential therapies.

In the meantime, many hospitals have instituted protocols to minimize resistant infections. These include strategies to prevent infections such as hand hygiene, device disinfection regimens, and improved hospital cleaning.

And it includes reducing the length of antibiotic prescribing during hospitalizations, as appropriate. Cutting back on antibiotics can shorten hospital stays without increasing mortality. 

Doctors who see patients in community practices also must resist unnecessary prescribing, which they sometimes do to placate patients, Yek says.

“Antibiotics are not always going to be the right solution,” she says. A nasal condition called sinusitis may be due to allergies; flu is caused by a virus. Neither of these improves with antibiotics. If you do have a bacterial infection and your doctor prescribes a broad-spectrum antibiotic against numerous microbe strains, ask if a more targeted medicine might be effective, she says.

Martinello advocates also buying organic foods that are less likely to contain antibiotics and pressing food companies to reduce their use in animals and agriculture.

“We need to have a great deal of respect for these medications,” Martinello says, “and understand that their benefit can be lost over time, in particular when they’re misused.”