Drug-Resistant Superbugs May Be Growing Even Deadlier

The new coronavirus outbreak may have caught some public officials by surprise, but infectious disease specialists have been anticipating this worst-case scenario for decades. And they warn that the same gaps in our health care system that allowed Covid-19 to flourish could give a window for other types of pathogens to overwhelm us.

One long-standing threat is antimicrobial resistance (AMR), or when so-called superbugs evolve abilities to evade our best germ-killing drugs, whether they be antibiotics, antifungals, antivirals, or anthelmintics (which rid bodies of parasites). An AMR outbreak has some similarities to a viral outbreak like Covid-19: There aren’t many tools with which to treat drug-resistant pathogens, and they can easily jump from person to person. Both AMR outbreaks and viral outbreaks spread particularly quickly in places like nursing homes and hospitals, where there is close proximity of people with compromised immune systems.

Of course, AMR and viral outbreaks aren’t exactly the same. Unlike the novel coronavirus, AMR superbugs can also disperse through the food and water supply or as sexually transmitted diseases, and they tend to transmit more slowly than viruses. But the severity of the threat posed by an AMR outbreak can be similar to that of a viral one.

Every year, at least 700,000 deaths are caused by drug-resistant diseases globally, according to the World Health Organization (WHO), which predicts that number could jump to 10 million deaths annually by 2050.

“What we’re watching happen with Covid is not new to us in the AR arena,” says Dawn Siebert, the senior science adviser for antibiotic resistance at the Centers for Disease Control and Prevention (CDC).

There are a number of reasons why AMR is on the rise: Antibiotics are overprescribed by doctors but are also ubiquitous in factory farming and even in some pesticides. A growing body of research suggests another reason: That climate change, rather than being a separate existential hazard to AMR, is intertwined, with AMR thriving as temperatures rise and resulting desertification is clustering humans and wildlife closer together.

Dr. Hani Kaba, a biologist at University Medical Center Göttingen, is one of a number of microbiologists actively looking for the link between rising temperatures caused by climate change and AMR. Kaba and his team published a cross-sectional analysis in January in the International Journal of Hygiene and Environmental Health tracking seasonal temperatures across 30 European countries between 1991 and 2015. They also measured the prevalence of four bacterial species that have evolved problematic antibiotic resistance.

“If the relationship between minimum temperature and antibiotic resistance is, indeed, present and increasing over time, this could support a more rapid progression towards a ‘post-antibiotic era.’”

Of the four microbes, one in particular showed a significant association with climate change: Pseudomonas aeruginosa (CRPA), which is resistant to a class of antibiotics called carbapenems. These are often used as a last line of defense against only the most severe infections. Kaba and his team predict the prevalence of CRPA may even double by 2039.

The result of Kaba’s analysis suggested there is a connection between climate change and AMR, though it is still not known whether the link is casual. One possibility is that warmer temperatures and increased humidity give some bacteria and fungi more opportunity to share genetic resistant material. Like neighbors exchanging recipes, these tiny microbes can share traits with each other just by being nearby, through a process called horizontal gene transfer. It makes it easy to swap drug-resistant traits with each other so that some bugs even grow resistant to multiple drugs.

Adding strength to the theory that climate change and AMR are linked, Kaba’s team used multiple datasets and multiple models to analyze their data. They got the same result. But to be truly sure, Kaba says we need to monitor this problem closely, collect more data, and do more research. Until then, it’s too early to draw any conclusions.

Researchers in the U.S. have described similar trends. A 2018 paper in Nature Climate Change analyzed a database of 41 states between 2013 and 2015, looking for antibiotic-resistant strains of three bacteria: a pathogen commonly responsible for pneumonia, K. pneumoniae; the infamous food poisoning culprit E. coli; and Staphylococcus aureus, known for antibiotic-resistant staph infections called MRSA.

With a 10 degree Celsius increase in temperature, all three pathogens increased antibiotic resistance, each less than 5%. This suggests that forecasts of AMR fatalities — those 10 million dead per year in just three decades — could be remarkable underestimates.

“If the relationship between minimum temperature and antibiotic resistance is, indeed, present and increasing over time,” the authors wrote, “this could support a more rapid progression towards a ‘post-antibiotic era.’”

Untangling the evidence is complex because it deals with both tiny microbes and giant climate models. But even if AMR isn’t strengthening microbes directly, climate change could still be increasing the risk in other ways, first by limiting our search for new antibiotics and second by increasing outbreaks of new diseases. Climate change also affects the movements of people, dispersing more diseases.

Dr. Cassandra Quave, a medical ethnobotanist at Emory University in Atlanta, Georgia, has dedicated her life’s work to finding new ways of fighting disease in nature by analyzing herbs and shrubs to unlock their chemical defenses. “A lot of our antimicrobials are inspired by natural products, or they are natural products,” she tells OneZero. Penicillin, which is derived from mold, is the archetypal example, while antimicrobial drugs derived from soil bacteria ushered in the “Golden Age of Antibiotics.” Humans have also developed drugs from insect ooze, reptile saliva, and other icky sources.

Quave believes nature is still our best bet for developing new ways to fight stubborn diseases. Her team’s hunt for new drugs led them to the work of Francis Porcher, a slave-owning botanist who, during the American Civil War, turned to native plants in the Southeast United States to treat wounded Confederate soldiers. Porcher’s research, conducted before the introduction of germ theory, resulted in a book detailing 37 plant species that were used to treat gangrene and other infections during the war.

Yet, over a century later, many of the plants Porcher described had not been investigated for any sort of antibiotic activity. Quave’s lab chose just three to scrutinize — white oak, devil’s walking stick, and tulip tree — and tested them against several bacteria that have evolved resistance to multiple drugs. Extracts of all three plants showed some inhibitory activity, including against a strain of K. pneumoniae resistant to carbapenem, that “last resort” antibiotic.

“These medicinal plants may be useful in modern medicine as treatments for antibiotic-resistant bacteria,” Quave and her team wrote last year in Scientific Reports. Hundreds, if not thousands, of other plants could harbor other drugs useful in the fight against AMR.

But as climate change and globalization spiral out of control, we risk losing these novel solutions as they struggle to survive our boiling planet. “Preserving biodiversity is in our self-interest. Nowhere does this ring truer than in drug discovery,” an international group of 18 researchers wrote in 2017 in the Journal of Global Health. At the same time, destroying our ecosystem can make pandemics more likely.

New diseases frequently emerge from animal-to-human, or zoonotic, disease transmission. For example, the prevailing origin theory of the new coronavirus causing the current pandemic, SARS-CoV-2, is that it most likely jumped from bats to humans. It’s not the first time a deadly virus has made such a leap — and it likely won’t be the last.

As wilderness areas shrink thanks to warmer temperatures, wildfires, and melting ice, humans come into closer contact with wild animals, giving the perfect opportunity for pathogens to jump hosts. Deforestation and urbanization also contribute to the spill-over of zoonotic agents to humans, Italian researchers wrote this month in Veterinary Microbiology

For example, in the late 1990s, a tiny village of pig farmers in Malaysia became the epicenter of a deadly viral outbreak with a fatality rate that fell between 40% and 75% and nearly collapsed the local billion-dollar pork industry. The cause was Nipah virus (NiV), a terrifying pathogen that attacks the lungs and brain. In extreme cases, it creates severe respiratory problems and seizures that can lead to a coma. (NiV inspired MEV-1, the fictional virus in the 2011 blockbuster Contagion). Both spread from bats to pigs, a chain of events inflamed by anthropogenic climate change.

Specifically, between August and October 1997, Indonesia slashed and burned more than 5 million hectares of rainforest, trees that were already crushed by an El Niño-related drought, creating “the most severe haze ever known in Southeast Asia,” according to researchers at the University of Malaya in Malaysia.

“You’re going to have to make the choice: Do you get that torn ACL fixed or not? Because there’s going to be a serious risk-benefit ratio because of risk of infection.”

This carcinogenic smoke prompted bats to flee to orchards overhanging pigsties in Malaysia. From there, human transmission was just a few hops away. Today, NiV outbreaks happen regularly in Asia and have even become seasonal. The virus is far from the only one that has vaulted from animals to humans. Approximately three out of four new infectious diseases — from SARS to MERS to Ebola, but not just viruses — also originated in animals, according to the United Nations Environment Programme.

Much like Covid-19, drug-resistant diseases can upend life. If this threat isn’t taken more seriously, Quave warns, “We’re gonna be back to 1800-style medicine. Your ability to perform surgeries, to get chemo, to have an organ transplant, to have any kind of an immune-compromised state, you’re going to have to make the choice: Do you get that torn ACL fixed or not? Because there’s going to be a serious risk-benefit ratio because of risk of infection.”

Doctors around the globe are currently throwing everything they can at Covid-19, including a lot of antibiotics, which don’t kill viruses but may help patients recover in other ways. Some infectious disease specialists believe this extra antibiotic use could, like climate change, contribute to a rise in AMR because in order for a pathogen to develop drug-resistant traits, the pathogen first needs to be exposed to such a drug. The more often superbugs are exposed to antibiotics, the more likely they are to evolve these workarounds.

The good news is that even as the threat may be increasing, we’re probably more prepared for addressing antibiotic resistance than we’ve ever been before, according to Michael Craig, the senior adviser for antibiotic resistance at the CDC. In the past five years, the CDC has built a network of labs in all 50 states to monitor AMR using sophisticated genome sequencing. They’re now doing an unprecedented amount of testing.

But investment in finding new drugs to fight superbugs hasn’t been well-funded as of late. Furthermore, fighting AMR is truly a global effort, not unlike climate change, and some regions are further behind than others.

“From our perspective, a lot of other countries aren’t prepared for these threats. They aren’t in a position to be able to either detect them or to respond to them,” Craig says. “We’re trying to do more to get other countries engaged in this. I hope this will be a wake-up call.”