The Strange and Curious Case of the Deadly Superbug Yeast
Originally posted on: Wired
A pathogen that resists almost all of the drugs developed to treat or kill it is moving rapidly across the world, and public health experts are stymied how to stop it.
By now, that’s a familiar scenario, the central narrative in the emergence of antibiotic-resistant bacteria. But this particular pathogen isn’t a bacterium. It’s a yeast, a new variety of an organism so common that it’s used as one of the basic tools of lab science, transformed into an infection so disturbing that one lead researcher called it “more infectious than Ebola” at an international conference last week.
The name of the yeast is Candida auris. It’s been on the radar of epidemiologists only since 2009, but it’s grown into a potent microbial threat, found in 27 countries thus far. Science can’t yet say where it came from or how to control its spread, and hospitals are being forced back into old hygiene practices—putting patients into isolation, swabbing rooms with bleach—to try to control it.
To a medical system that’s been dealing with worsening antibiotic resistance for decades, this chronology feels somewhat familiar: just another, potentially tougher battle to face. But the struggle to keep this resistant yeast from surging is a warning sign that relying on standard responses won't work. As the foes continue to evolve, medicine needs both new tech, and surprisingly old techniques, to fight its microbial wars.
As the foes continue to evolve, medicine needs both new tech, and surprisingly old techniques
“This bug is the most difficult we’ve ever seen,” says Dr. Tom Chiller, the chief of mycotic diseases at the CDC, who made the Ebola remark at the 20th Congress of the International Society for Human and Animal Mycology in Amsterdam. “It’s much harder to kill.”
The center of the emerging problem is that this yeast isn’t behaving like a yeast. Normally, yeast hangs out in warm, damp spaces in the body, and surges out of that niche only when its local ecosystem veers out of balance. That’s what happens in vaginal yeast infections, for instance, and also in infections that bloom in the mouth and throat or bloodstream when the immune system breaks down.
But in that standard scenario, the yeast that has gone rogue only infects the person it was residing in. C. auris breaks that pattern. It has developed the ability to survive on cool external skin and cold inorganic surfaces, which allows it to linger on the hands of healthcare workers and on the doorknobs and counters and computer keys of a hospital room. With that assist, it can travel from its original host to new victims, passing from person to person in outbreaks that last for weeks or months.
Yeast is a fungus, but C. auris is behaving like a bacterium — in fact, like a bacterial superbug. It’s a cross-species shift as inexplicable as if a grass-munching cow hopped a fence and began bloodily chomping on the sheep in the pasture next door.
The accepted narrative of new diseases is that they always take us by surprise: Science recognizes it after it has begun to move, with the second patient or the tenth or the hundredth, and works its way back to find Patient Zero. But C. auris was flagged as troublesome from its first discovery, though its identifiers didn’t understand at the time what it might be able to do.
The accepted narrative of new diseases is that they always take us by surprise
The story begins in 2009, when a 70-year-old woman already in a hospital in Tokyo developed a stubborn, oozing ear infection. The infection didn’t respond when doctors administered antibiotics, which made them think the problem might be a fungus instead. A swab of her ear yielded a yeast that appeared to be a new species. Microbiologists Kazuo Satoh and Koichi Makimura named it for the Latin word for “ear.”
That story also would have ended in 2009—new species, new nomenclature, another entry in a textbook—except for an unnerving fact. Fungal infections have never been a high priority in medical research, and as a result, there are very few drugs approved for treating them—only three classes of several drugs each, compared to a dozen classes and hundreds of antibiotics for bacteria. This novel yeast was already showing some resistance to the first-choice antifungals that would have been used against it, a family of compounds called azoles that can be given by mouth.
The back-up choice, a drug called amphotericin, is IV-only, and also so toxic—its severe fever-and-chills reactions have been dubbed “shake and bake”—that doctors try to avoid it whenever possible. That left only one set of drugs available, a new IV-only class called echinocandins. C. auris entered medical awareness accompanied by the knowledge that, if it blew up into a problem, it would be difficult to treat.
Still, at that point it had only caused an ear infection. That might have been a random occurrence; there was no reason to assume worse to come. Except, at about the same time, physicians in South Korea were called on to treat two hospital patients, a 1-year-old boy with a blood-cell disorder and a 74-year-old man with throat cancer. They both had developed bloodstream infections caused by the newly discovered yeast. And in both their cases, the organism was partially resistant to the azole class and also to amphotericin. Both died.
The same novel bug, occurring in unrelated patients, in different body systems, simultaneously in two countries, made epidemiologists wonder whether there might be more to come. There was. In just a few years, C. auris infections were recognized in India, South Africa, Kenya, Brazil, Israel, Kuwait and Spain. As with the Korean and Japanese cases, there was no connection between the different countries’ patients. In fact, the strains were genetically different on different continents—suggesting that C. auris had not begun in one place and then spread by transmission, but had arisen simultaneously everywhere, for reasons no one could discern.
But the minutely different strains had the same impact on patients: They were deadly. Depending on the country and the location of their illness in their bodies, up to 60 percent of infected patients died.
The situation looked so alarming that the public health authorities of England and the European Union rushed out urgent bulletins, warning hospitals to look for the arrival of the bug. The CDC, whose main responsibility is monitoring and preventing diseases within US borders, took the unusual step of publishing a warning before the resistant yeast even arrived in this country. “We wanted to get out ahead of the curve, to try to inform our healthcare community,” Chiller told me at the time.
Now there have been 340 cases recorded in the US, in 11 states—and the behavior of the bug in this country is teaching microbiologists more about how the new yeast behaves. It seems that not every continent develops its own strain. Instead, the U.S. is playing host to several micro-epidemics, each of which was sparked by one or several travelers from somewhere else. Cases found in New York, New Jersey, Oklahoma, Connecticut, and Maryland bear the genetic pattern of South Asia. Illinois, Massachusetts, and Florida’s cases show South America’s genetic pattern. And randomly, the few cases recorded in Indiana seem to be linked to a South African strain.
Wherever they come from, the subtle variants of C. auris share an important characteristic: They are highly drug resistant. Last year, the CDC disclosed an analysis of isolates from the US and the 26 other countries where C. auris has surfaced. More than 90 percent were resistant to azoles; 30 percent were resistant to the class that contains amphotericin; and globally, up to 20 percent were resistant to the last-ditch echinocandins. In the United States, 3 percent have been.
They also pose another challenge: long-lasting hospital outbreaks. One London hospital, the Royal Brompton, began finding the resistant yeast in early 2015. To try to stop its spread, the hospital put patients into isolation; regularly swabbed any other patient who had been in the same room as the infected persons, and all of the staff who had any contact with them; required every healthcare worker, janitor, or visitor to wear gowns, gloves, and aprons; bathed the patients twice a day with disinfectant, administered disinfectant mouthwash and dental gel, and washed the rooms three times per day with diluted bleach. When the patients moved out, the rooms they had stayed in and any equipment that had been used on them were bombed with hydrogen peroxide vapor.
Despite all those precautions, the yeast caused a 50-person outbreak that lasted more than a year. It survived the disinfectant baths and found places to hide from the bleach. And it stubbornly persisted on bodies. One patient tested negative for the bug three times, and then, on a fourth screen, tested positive again.
In April a year ago, a hospital in Oklahoma perceived that a single patient was carrying C. auris. To keep it from spreading, the hospital slammed the patient into isolation and enforced strict infection control. It also called in a CDC team, which took 73 samples from the patient, his room, other rooms where he had stayed, and other patients he might have been in contact with, and hauled them all back to Atlanta for genomic analysis. Their quick action kept the deadly yeast from spreading elsewhere in the hospital—but it represented an emergency expenditure of resources and time that no hospital could make routine.
There aren’t many bright spots in the looming battle against C. auris. One may be this: Most of the patients so far, and all of those who have died, have been people who were hospitalized because they were already somehow ill—with diabetes, cardiovascular disease, cancers, and other illnesses. They were on ventilators, threaded with IVs and catheters, and receiving multiple drugs that undermined their immune systems’ competence.
That means there’s a limited population who may be at risk, which also means there’s a limited group for whom the most costly protections should be necessary. But patients that ill are often cared for, not in hospitals, but in nursing homes and skilled nursing facilities—and those institutions tend not to hire or empower the sharp-eyed infection-prevention practitioners that hospitals do. So that raises the question of how to detect the yeast in a patient before that person enters an institution. Must every patient be interrogated for a recent history of foreign travel? Should every new arrival be checked, with skin and gut swabs and lab tests, as part of hospital admission?
Screening won’t be a perfect defense, because clinical microbiology is struggling with this bug. Multiple accounts written over the past few years reveal that most of the patients who carried C. auris—more than 80 percent in one paper—were misidentified at first, judged on laboratory assays to have other, less risky forms of yeast. Recently the CDC published a lengthy guidance for laboratories, explaining in detail the mistakes that seven separate testing methods make in identifying it, and urging labs to contact the agency whenever it is suspected or diagnosed.
It’s critical that medicine develop better tests and routine practices, and that sluggish development of new antifungal drugs be speeded up. In the absence of new tech, what seems to be helping is one of the oldest practices in medicine—but even that requires scrutiny to be sure it is done well.
Where outbreaks have been stopped, it has been due to hard efforts in hospital cleanliness: not sharing equipment between sick people; not taking rolling computers into patients’ rooms; scrubbing the walls and floors and bedrails, and checking afterward to make sure that cleaning solutions actually kill the bug. (There is some early evidence that quarternary ammonium cleansers, the most commonly used hospital disinfectants, don’t kill C. auris; but everyday chlorine bleach can.)
The most important steps may be the low-tech ones that are hardest to enforce routinely: wearing gloves, wearing gowns, washing hands. Ignaz Semmelweis, who was born 100 years ago last week, spent his life insisting that hygiene is the most essential act in medicine. The most resistant superbugs remind us that it may be the last protection that we have.