HEALTH

The Attack Of The Superbugs

As the antibiotic era ends, pan-resistant bacteria are here to stay

HEALTH
Illustration: Tara Jacoby
Jan 27, 2017 at 10:55 AM ET

For all of our modern comforts, few deserve as much appreciation and praise as antibiotics do. Since their initial, almost accidental discovery in the 1920s, they’ve saved countless lives, rescued untold limbs from amputation, and wiped out entire kinds of disease from all corners of the globe. But their sway over the bacterial kingdom has slowly been fading, a reality that has led many to worry about the worst coming in the not-too-distant future — the end of antibiotics.

The end of antibiotics isn’t yet to come, though. It’s already happening right in front of our eyes. Once-easily fought infections are now Herculean struggles between bacteria and doctors across the world. And unless humanity can mount a massive global campaign to tamp down antibiotic resistance while developing effective new drugs soon, this germ warfare will only get worse.

Consider one recent case: In January, local Nevada doctors, along with the Centers of Disease Control and Prevention, reported the death of a 70-something woman in Washoe County. She was hospitalized and diagnosed with sepsis, a widespread inflammation triggered by infection that ravages the body. Despite their efforts, the woman proved unresponsive to any treatment. After falling into septic shock, her organs rapidly shut down and she soon died.

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Samples from one of her infected wounds had tested positive for a bacteria called Klebsiella pneumoniae that was at least partly resistant to all 14 available antibiotics the hospital had in stock. The CDC, brought in for more testing, additionally found her passenger was truly resistant to at least a whopping 26 antibiotics found in the U.S., including the aptly-called “last resort” drugs colistin and tigecycline. About the only good news was that, thanks to quickly isolating her away from other patients, the doctors seemingly stopped the infection from spreading any further.

“We’ve never seen that before [in our area],” Dr. Lei Chen of the Washoe County Health District told Vocativ, referring to the bacteria’s invulnerability. Antibiotic-resistant bacteria are a common enough danger in the U.S., with at least two million infections and 23,000 deaths caused by them annually, according to the CDC, but few are as hardy as the woman’s strain was, repelling both conventional and last-resort drugs.

The Nevada case is what doctors call a pan-resistant infection. And while these are still rare occurrences, no one is really sure for how long. “It underscores that this type of thing can happen,” said Dr. Randall Todd, Director of Epidemiology & Public Health Preparedness at Washoe County. “But we don’t ever want it to be common.”

If there’s any germ likely to become commonly pan-resistant in the near future, it’s something like K. pneumoniae. The bug is part of a group typically found in the gut called Enterobacteriaceae. Broader still, these bacteria are gram-negative, a term that describes their inability to be colored by a violet dye that scientists use to see bacteria under the microscope. Like a laundry load of tighty whities mixed in with your sister’s red blazer, they instead turn pinkish, but only after a second dye is added.

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Unfortunately, the same thing that leaves them pink — their unique, thicker cell walls — also gives gram-negative bacteria a built-in buffer against many antibiotics. And our ongoing antibiotic arms-race has only steeled their defenses. Enterobacteriaceae, especially, have learned to deter drug after drug thrown at them, making them one of the most serious threats out there, according to the CDC. Some strains have even picked up genes that let them resist a powerful “break glass in case of emergency” line of drugs called carbapenems, leading to Carbapenem-resistant Enterobacteriaceae (CRE). What’s worse, CREs also tend to be resistant to every other antibiotic that came before it, earning them the charming nickname of “nightmare bacteria” from former CDC Director Tom Frieden.

In our desperation, we’ve dusted off ancient drugs, like colistin, which had fallen out of favor because of their toxic side-effects and so-so performance, to use as an absolute last measure against CREs. But in recent years, bacteria have started to adapt to it too.

Last year, U.S. Army researchers confirmed the presence of a particular colistin resistance gene, MCR-1, in a sample of E. coli (another Enterobacteriaceae) collected from a woman in Pennsylvania. It was only the latest appearance of MCR-1, but the first to be found in a person within the United States. Though the patient’s strain was thankfully susceptible to standard antibiotics, MCR-1, along with a similar gene MCR-2, is troubling because of where it’s been found — on a loop of free-moving DNA called a plasmid.

Bacteria have plenty of ways to transfer genes to one another, but plasmids are their version of a private charter plane. Plasmid genes jump from one species to another with little hassle, and often through sources far away from human contact. Indeed, MCR-1 was first discovered in the farm animals of China, where colistin had frequently been used in animal feed, though it may have existed since at least the 1980s. In response, China moved to ban colistin as a feed additive in October, but the genie has long since left the bottle — MCR-1 has been spotted in over 30 countries as of now, in both meat and man.

Though the possibility of MCR-1 attaching onto a CRE bacteria is dreadful enough, the Nevada case proves that it isn’t the only route to pan-resistance. The woman in question had recently returned from a trip to India, where she was hospitalized several times for a fractured femur that turned into a bone infection over a two-year period. It’s likely that, aided by repeated antibiotic treatments and a weakened immune system, her body became a stewpot of resistance, with the strain of K. pneumoniae that eventually killed her collecting mutations like some sort of demented Katamari ball. There’s no official tally, but at least several hundred cases of CRE are detected in the U.S. annually, most often in hospitals. And while estimates are tricky, research suggests that 10 to 15 percent of CRE strains may also have pan-resistance to collistin and tigecycline.

Elsewhere, we’re on our last legs against the common STD gonorrhea. The titular bacteria that causes it, Neisseria gonorrhoeae, is now usually resistant to most front-line drugs, which prompted the CDC and other health agencies to recommend treating it with a combination therapy of one standard antibiotic mixed with another emergency antibiotic, in 2010. But there are already scattered reports of gonorrhea steadily becoming hardier against both, if not completely resistant yet, including during an outbreak in Hawaii that began last April.

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“I would not be shocked to read tomorrow that a colistin resistant CRE or N. gonorrhoeae resistant to both antibiotics used in the current combination therapy has been found,” said Dr. Anne Farewell, a bacterial geneticist at the University of Gothenburg’s Center for Antibiotic Resistance in Sweden, over email. Her message had eerily been sent mere hours before the report on the Nevada case was published.

There are other dark horse candidates for pan-resistance, like tuberculosis. Since 2007, there have been several reports of what’s being called totally drug-resistant TB, which would be the last grim stage of an ongoing evolution seen since the 1940s. But according to Dr. Mario Raviglione, director of the World Health Organization’s Global TB Program, we don’t have the resources needed to confirm if these cases are truly, completely resistant. What is known that, despite successes in driving down cases of resistant TB, there are still pockets of the world where rates continue to climb, particularly in poorer countries like India. All told, it’s estimated that around 10 percent of all resistant TB cases fall under the extensively drug-resistant TB umbrella, meaning they repel the first and second-line of drugs.

In many ways, though, looking for the single tipping point of pan-resistance is a distraction, morbidly curious about it as we might be.

“It is largely a question of semantics,” explained Farewell. “When a colistin resistant CRE arises but a doctor is able to treat it with a very toxic old drug that requires hospitalization for many months and causes significant long term damage to the patient, is that ‘The Superbug’ or not quite?”

“We are already in the middle of this crisis, not waiting for the next shoe to drop,” she added. 

Antibiotic-resistant infections kill at least 700,000 people worldwide a year right now, according to an exhaustive report commissioned by the UK in 2014, and without any substantial medical breakthroughs or policy changes that slow down resistance, they may claim some 10 million deaths annually by 2050 — eclipsing cancer in general as a leading cause. These deaths largely won’t come from pan-resistant infections, just tougher ones. A preventable death there, a preventable death here.

Leaving that aside, antibiotics, along with proper sanitation and nutrition, gird our entire way of living. Most every invasive surgery, pregnancy, organ transplant and chemotherapy session we go through will become riskier. Other diseases like HIV, malaria or influenza will become deadlier, since bacteria often exploit the opening in our immune system they leave behind. And already precarious populations like those living with cystic fibrosis, prisoners, and the poor will lose years off their lives.

For all the warranted gloom, though, Farewell does think there are reasons to be hopeful. “I don’t think we are doing enough, but the scientific community along with many governmental and private foundations are very actively involved in finding not only new antibiotics, but new solutions to this problem,” she said. There’s been a noticeable change in attitude and increased urgency surrounding antibiotic resistance, she said, one that she hadn’t seen even five years ago, let alone twenty. 

Until recently, that attitude change could be seen from places as high up as the U.S. federal government. In 2014, former President Obama issued an executive order aimed at addressing antibiotic resistance, the first real acknowledgement of the problem from an administration, devoting funding and outlining a national action for combatting resistance. Through its federal agencies, the administration pushed to reduce antibiotic use on farms and encouraged doctors to stop using them in excess.

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“There has been a lot of work done the last couple of years, much of it spurred by [Obama’s] National Action Plan,” said Dr. David Hyun, a senior officer for Pew Charitable Trusts’ Antibiotic Resistance Project. The CDC, in particular, has used its funding to open up regional labs that allow them to better detect and respond to antibiotic-resistant outbreaks like the Nevada case, he said. They ultimately hope to create an expansive surveillance system that can easily keep track of resistance rates on a national, state and regional level. A parallel system also exists for monitoring resistance in the food chain, shepherded by the CDC and the U.S. Department of Agriculture.

In fact, it was this sort of cooperation between national and local health agencies that enabled Nevada doctors to stop the worst from happening, said Dr. Lei Chen. The swift identification of a possible CRE strain by the hospital, coupled with the woman’s medical history, led to a precautionary quarantine, while also prompting Chen’s public health department and eventually the CDC into action. And it may help prevent future cases from spilling into the public. According to Chen, the CDC has allocated funding this year to all of Nevada’s state public health departments so they can better detect CRE and other dangerous resistant strains.

Under the Trump administration, there’s no telling how these small victories will hold up or whether they will advance. All references to antibiotics once found on the Whitehouse.gov site have been removed, including a link to the Obama administration’s national action plan, and the fact that they’re already tried to bar USDA scientists from discussing their work with the public while stripping funding from other public health agencies isn’t encouraging. 

Even with the best public policy, however, there’s no clear light at the end of the tunnel. Antibiotic resistance has gradually been worsening, even within the last 15 to 20 years, when superbugs like methicillin-resistant Staphylococcus aureus (MRSA) first became widely known, said Hyun. The effort needed to develop new drugs has been in short supply, hamstrung by pharmaceutical companies’ inability to recoup the costs of bringing new antibiotics to market. That’s because, unlike the latest heart medication, any new antibiotics will have to be treated like the last drops of water during a drought, used as little as possible — the exact opposite way to make money off a new product. Yet, much like climate change, the financial toll of not doing anything will total in the trillions years down the road. And it already numbers in the billions now, according to the CDC.

Of course, we need bacteria to survive. And most need or pay no mind to us in return. Even pan-resistant bacteria don’t really mean harm. Some have been found in perfectly healthy people, a fact that’ll either comfort you or keep you awake at night, only causing problems when our immune system wavers. There’s no army of sentient E. coli that will rise up and someday overthrow the human race.

But barring the cavalry showing up, a new fear of ours will learn to settle in, almost unnoticed. It’ll creep in when we pick our heads up from a nasty fall that scrapes our skin open or breaks our bones; when we wave goodbye to our loved ones before they enter an operating room, or when we cradle our newborns into a world teeming with the living infinitesimal, wishing there was still a way to shield them from it as our parents once could for us. A fear of naked vulnerability.

The antibiotic apocalypse will be gentle, if it fully arrives, but it won’t be any less devastating to the human spirit.

What’s the worst that can happen? This week, Vocativ explores the power of negative thinking with our look at worst case scenarios in politics, privacy, reproductive rights, antibiotics, climate change, hacking, and more. Read more here