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THE POST-ANTIBIOTIC ERA IS HERE NOW WHAT?

abeland1

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#1
From WIRED
WHEN ALEXANDER FLEMING came back from a Scottish vacation in the summer of 1928 to find his London lab bench contaminated with a mold called Penicillium notatum, he kicked off a new age of scientific sovereignty over nature. Since then, the antibiotics he discovered and the many more he inspired have saved millions of lives and spared immeasurable suffering around the globe. But from the moment it started, scientists knew the age of antibiotics came stamped with an expiration date. They just didn’t know when it was.

Bacterial resistance to antibiotics is both natural and inevitable. By the luck of the draw, a few bacteria will have genes that protect them from drugs, and they’ll pass those genes around—not just to their progeny, but sometimes to their neighbors too. Now, computational epidemiologists are finally getting the data and processing to model that phenomenon. But no one’s using these tools to predict the end of the antibiotic era—because it’s already here. Instead, they’re focusing their efforts on understanding how soon resistant bacteria could be in the majority, and what, if anything, doctors can do to stop them.

In 2013, then-director of the Centers for Disease Control and Prevention Tom Frieden told reporters, “If we’re not careful, we will soon be in a post-antibiotic era.” Today, just four years later, the agency says we’ve arrived. “We say that because pan-resistant bacteria are now here” says Jean Patel, who leads the CDC's Antibiotic Strategy & Coordination Unit. “Folks are dying simply because there is no antibiotic available to treat their infection, infections that not too long ago were easily treatable.”

Last August, a woman in her 70s checked into a hospital in Reno, Nevada with a bacterial infection in her hip. The bug belonged to a class of particularly tenacious microbes known as carpabenem-resistant Enterobacteriaceae, or CREs. Except in addition to carpabenem, this bug was also resistant to tetracycline, and colistin, and every single other antimicrobial on the market, all 26 of them. A few weeks later she developed septic shock and died.

For public health officials like Patel, that case marks the end of an era, and the beginning of a new one. Now, the question is: How fast is that kind of pan-resistance going to spread? “When does it get to the point where it’s more common to have an infection that can’t be treated with antibiotics than one that can?” says Patel. “That’s going to be a very hard thing to predict.”


She knows because she’s tried before. Back in 2002, the first vancomycin-resistant staph infection showed up in a 40-year old Michigan man with a chronic foot ulcer. That seemed really bad: Staph is one of the most common bacterial infections in humans, and vancomycin its most common antibiotic adversary. Plus, the resistance gene was located on a plasmid—a free-floating circle of DNA that makes it easy to get around. Epidemiologists at the CDC worked with microbiologists like Patel to build a model to predict how far and how fast it would spread. While Patel couldn’t remember the exact output, she recalls that the results were scary. “We were very, very concerned about this,” she says.

Luckily in this case, their models were completely mistaken. Since 2002 there have been only 13 cases of vancomycin-resistant staph, and no one has died.

Being so wrong baffled the teams. But biology can be complicated like that. “I’ve worked with these bacteria in labs where they grow just fine, but they don’t seem to spread from one person to another,” says Patel. And while they still don’t know why, one hypothesis is that these particular resistance genes came with a cost. They might have made the staph capable of standing up to its antibiotic archnemesis, but the same bits of DNA also might have made it harder to survive outside a human body. Hospital protocols, time of year, and geography could have also had an effect on transmission rates. It’s more like trying to predict the weather than anything else.

“You can’t do it on paper or by just sitting there and thinking about it. You need simulation models to make it all fit together,” says Bruce Lee, a public health researcher at Johns Hopkins. He works with healthcare networks in Chicago and Orange County to predict the most likely paths that CREs—the kind of bacteria that killed the woman in Nevada—will take, should they show up in a hospital system. In the past, like when Patel was trying to plot the spread of resistant staph, these models were based exclusively on equations. Pretty complicated ones, granted. But not the sort of thing that can take into account human behavior and bacterial biology and interactions of both with the surrounding environments. “There’s increasingly been a realization in our field that to understand the spread of antibiotic resistant bacteria in any amount of detail you have to have these very data-driven simulation models where you can look at millions of different scenarios, just like a meteorologist,” says Lee.

In a study Lee published last year, he looked at the likelihood of CRE spreading through Orange County’s 28 acute-care hospitals and 74 nursing homes. In his model, each virtual facility has a number of beds based on its actual bed count, as well as information about how connected each facility is. The model represents each patient as a computational agent, that on any given day either carries or doesn’t carry CRE. Those agents all move around the healthcare ecosystem, interacting with doctors and nurses and beds and chairs and doors, hundreds of millions of times, with parameters tweaked a little bit each simulation. He found that without increased infection control measures, like regularly testing patients for pandemic resistance, and quarantining anyone who’s a carrier, CRE would be endemic—i.e. living full-time—at nearly every Orange County health care facility within a decade.

And once CRE is in a health care system, it’s really hard to pull out. “It’s like trying to extract termites from a house,” says Lee. “Once it’s in there where everything’s connected, it becomes an intractable part of the ecosystem.” So if doctors and nurses had a way to figure out sooner who was going to pass CRE around, they could at least contain the threat. Even if they might not have much to offer the patient.

For now, it’s good news that the only person-to-person transmission of 100 percent resistant bacteria is taking place inside Lee’s supercomputer. There haven’t yet been any documented cases in the real world. But that’s what Patel and the CDC are looking for. That’s what takes things to the next level, says Patel. To keep a better eye on things, last year the agency spent $14.4 million to create a network of seven regional labs with increased capacity to run genetic testing on bacterial samples taken from hospitals. And they’re currently piloting a program that might one day connect every hospital in the US directly to the CDC’s surveillance system, to automatically flag every serious resistance event around the country in near to real-time.

The other eye, Patel–and arguably, the rest of the world–is keeping trained on the antibiotic pipeline. But things don’t look great there either. Just last week, the World Health Organization released a report analyzing all the antibacterial agents currently in clinical development. Its conclusions were grim: not enough drugs, not enough innovation. There’s already some amount of pre-existing resistance to just about every one of the 51 treatments coming down the line. Researchers like Patel and Lee are hoping their work can help minimize the threats that are out there now, discover new ones as they emerge, and buy pharma companies some time to develop novel drugs. The antibiotic age might be over. But there’s still a lot to say about what comes next.
 

Weatherman

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I wonder how long it will be before hospitals and nursing homes discover they need to have silver ions in water for drinking, bathing, and laundry. They also need silver or copper plating on exposed surfaces that people touch.
 

Buck

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so, what's it take to spread some of those microbes into Mr Soro's tea?
 

abeland1

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From WIRED
PEER INTO THE POST-APOCALYPTIC FUTURE OF ANTIMICROBIAL RESISTANCE
ABOUT 4 MILLION years ago, a cave was forming in the Delaware Basin of what is now Carlsbad Caverns National Park in New Mexico. From that time on, Lechuguilla Cave remained untouched by humans or animals until its discovery in 1986—an isolated, pristine primeval ecosystem.

When the bacteria found on the walls of Lechuguilla were analyzed, many of the microbes were determined not only to have resistance to natural antibiotics like penicillin, but also to synthetic antibiotics that did not exist on earth until the second half of the twentieth century. As infectious disease specialist Brad Spellberg put it in the New England Journal of Medicine, “These results underscore a critical reality: antibiotic resistance already exists, widely disseminated in nature, to drugs we have not yet invented.”

The origin story of antibiotics is well known, almost mythic, and antibiotics, along with the other basic public health measures, have had a dramatic impact on the quality and longevity of our modern life. When ordinary people called penicillin and sulfa drugs miraculous, they were not exaggerating. These discoveries ushered in the age of antibiotics, and medical science assumed a lifesaving capability previously unknown.


LITTLE, BROWN
Note that we use the word discoveries rather than inventions. Antibiotics were around many millions of years before we were. Since the beginning of time, microbes have been competing with other microbes for nutrients and a place to call home. Under this evolutionary stress, beneficial mutations occurred in the “lucky” and successful ones that resulted in the production of chemicals—antibiotics—to inhibit other species of microbes from thriving and reproducing, while not compromising their own survival. Antibiotics are, in fact, a natural resource—or perhaps more accurately, a natural phenomenon—that can be cherished or squandered like any other gift of nature, such as clean and adequate supplies of water and clean air.

Equally natural, as Lechuguilla Cave reminds us, is the phenomenon of antibiotic resistance. Microbes move in the direction of resistance in order to survive. And that movement, increasingly, threatens our survival.

With each passing year, we lose a percentage of our antibiotic firepower. In a very real sense, we confront the possibility of revisiting the Dark Age where many infections we now consider routine could cause severe illness, when pneumonia or a stomach bug could be a death sentence, when a leading cause of mortality in the United States was tuberculosis.

The Review on Antimicrobial Resistance (AMR) determined that, left unchecked, in the next 35 years antimicrobial resistance could kill 300,000,000 people worldwide and stunt global economic output by $100 trillion. There are no other diseases we currently know of except pandemic influenza that could make that claim. In fact, if the current trend is not altered, antimicrobial resistance could become the world’s single greatest killer, surpassing heart disease or cancer.

In some parts of the United States, about 40 percent of the strains of Streptococcus pneumonia, which the legendary nineteenth and early twentieth century physician Sir William Osler called “the captain of the men of death,” are now resistant to penicillin. And the economic incentives for pharmaceutical companies to develop new antibiotics are not much brighter than those for developing new vaccines. Like vaccines, they are used only occasionally, not every day; they have to compete with older, extremely cheap generic versions manufactured overseas; and to remain effective, their use has to be restricted rather than promoted.

As it is, according to the CDC, each year in the United States at least 2,000,000 people become infected with antibiotic-resistant bacteria and at least 23,000 people die as a direct result of these infections. More people die each year in this country from MRSA (methicillin-resistant Staphylococcus aureus, often picked up in hospitals) than from AIDS.

If we can’t—or don’t—stop the march of resistance and come out into the sunlight, what will a post-antibiotic era look like? What will it actually mean to return to the darkness of the cave?

Without effective and nontoxic antibiotics to control infection, any surgery becomes inherently dangerous, so all but the most critical, lifesaving procedures therefore would be complex risk-benefit decisions. You’d have a hard time doing open-heart surgery, organ transplants, or joint replacements, and there would be no more in vitro fertilization. Caesarian delivery would be far more risky. Cancer chemotherapy would take a giant step backwards, as would neonatal and regular intensive care. For that matter, no one would go into a hospital unless they absolutely had to because of all the germs on floors and other surfaces and floating around in the air. Rheumatic fever would have lifelong consequences. TB sanitaria could be back in business. You could just about do a post-apocalyptic sci-fi movie on the subject.

To understand why antibiotic resistance is rapidly increasing and what we need to do to avert this bleak future and reduce its impact, we have to understand the Big Picture of how it happens, where it happens, and how it’s driven by use in humans and animals.

Human Use
Think of an American couple, both of who work fulltime. One day, their 4-year-old son wakes up crying with an earache. Either mom or dad takes the child to the pediatrician, who has probably seen a raft of these earaches lately and is pretty sure it’s a viral infection. There is no effective antiviral drug available to treat the ear infection. Using an antibiotic in this situation only exposes other bacteria that the child may be carrying to the drug and increases the likelihood that an antibiotic resistant strain of bacteria will win the evolutionary lottery. But the parent knows that unless the child has been given a prescription for something, the daycare center isn’t going to take him and neither partner can take off from work. It doesn’t seem like a big deal to write an antibiotic prescription to solve this couple’s dilemma, even if the odds the antibiotic is really called for are minute.

While the majority of people understand that antibiotics are overprescribed and therefore subject to mounting resistance, they think the resistance applies to them, rather than the microbes. They believe that if they take too many antibiotics – whatever that unknown number might be—they will become resistant to the agents, so if they are promoting a risk factor, it is only for themselves rather than for the entire community.

Doctors, of course, understand the real risk. Are they culpable to the charge of over- and inappropriately prescribing antibiotics? In too many cases, the answer is Yes.

Why do doctors overprescribe? Is it about covering their backsides in this litigious society? Is it a lack of awareness of the problem? According to Brad Spellberg, “The majority of the problem really revolves around fear. It’s not any more complicated than that. It’s brain stem level, sub-telencephalonic, not-conscious-thought fear of being wrong. Because we don’t know what our patients have when they’re first in front of us. We really cannot distinguish viral from bacterial infections. We just can’t.”

Spellberg cited a case, one he heard at an infectious disease conference he attended. A 25-year-old woman came into the urgent care facility of a prominent health care network complaining of fever, sore throat, headache, runny nose and malaise. These are the symptoms of a classic viral syndrome and the facility followed exactly the proper procedure. They didn’t prescribe an antibiotic, but instead told her to go home, rest, keep herself hydrated, maybe have some chicken soup, and they would call her in three days to make sure she was all right.

She came back a week later in septic shock and died soon after.

“It turns out she had Lemierre’s disease,” says Spellberg. “It clotted her jugular vein from a bacterial infection that spread from her throat to her bloodstream. This is about a one-in-10,000 event; it’s pretty darn rare. But it’s a complication of an antecedent viral infection, and it’s a known complication. So this patient, ironically, would have benefitted from receiving inappropriate antibiotics. How many times do you think doctors need to have those things happen before they start giving antibiotics to every person who walks in the door?”

As much difficulty as we’re having controlling antibiotic resistance in the First World, for the rest, we believe the situation to be a whole lot worse.

In many of these countries, antibiotics are sold right over the counter just like aspirin and nasal spray; you don’t even need a doctor’s prescription. While we in the public health community would certainly like to see a complete cessation of antibiotic use without a prescription, how do we tell sick people in developing countries that they first have to see a doctor, when there may be no more than one or two physicians for thousands of individuals, and even if they could find one, they couldn’t afford the visit in the first place? Taking an action in a vacuum, such as banning over-the-counter sales without improving infrastructure, simply isn’t viable.
 

the_shootist

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#5
We kill ourselves as other civilizations before us have killed themselves on this rock!