The Resistance Movement: Bacteria Want to Live Too

Team BT 1The vast majority of bacteria, as it turns out, are our little buddies: They help us digest food, for example milk sugars and fiber; and they help assemble nutrients, such as amino acids, the building blocks of proteins, and vitamin K, which we need to clot blood. The surprising part, however, is they actually help us fight disease, says NYU infectious disease expert, Martin Blaser, MD, in his book, Missing Microbes: How the Overuse of Antibiotics is Fueling Our Modern Plagues. They do this, for example, by sending chemical signals to our immune system to keep it on high alert; they help to metabolize needed pharmaceuticals such as the heart drug digoxin; and they even secrete substances, including their own antibiotics, which are poisonous to foreign invaders. But they can’t do this work single-handedly; instead, bacteria have to work together in huge numbers to get the job done. For example, just one milliliter of our colon — where bacteria metabolize fiber — contains more bacteria than there are people on Earth, says Martin Blaser.

And in return for all the help they give us, how do we treat these guys? Apparently, we’re slaughtering them in droves with our indiscriminate use of antibiotics. Margaret Riley, PhD, and professor of biology at the University of Massachusetts, Amherst, analogizes the taking of antibiotics to the ingestion of a hydrogen bomb on the basis that it kills all of our body’s bacteria, not just the kind that’s causing a problem.

The extent of this antibiotic “bombing” is massive: Health care providers prescribed 258.0 million courses of antibiotics in 2010, or 833 prescriptions per 1000 persons. And according to the US Centers for Disease Control, 30-50% of antibiotics prescribed in hospitals are unnecessary or inappropriate. But there’s a bigger issue: 70 – 80% of all antibiotics sold in the US are used for the single purpose of fattening up industrial farm animals. In 2011, animal producers bought nearly 30 million pounds of antibiotics for the purpose of fattening up their livestock, a practice banned in Europe.

One has survival advantage: Light- and dark- colored moths against a dark background

One has survival advantage: Light- and dark- colored moths against a dark background

So when we drop over 15 tons of antibiotics a year on our bacterial population — in the US alone — we can expect a response. And just like any other living organism being bombed, bacteria don’t want to die either, and so they fight back by developing resistance to the antibiotic bombs. This development of resistance is simply evolution at work, meaning that developing resistance is inevitable. Evolution, however, much like bacteria, is often misunderstood, so it’s worth taking a closer look at it because it shows us how we’re not going to win a “war” against disease if our strategy is based on fighting nature. So here’s the classic example of evolution in action, which is defined as the change in a characteristic (color, in our example), of a population (moths), over time, i.e. generations, in response to an environmental event (the Industrial Revolution and soot production). OK, it involves the Industrial Revolution, but nonetheless it’s a rather cool example:

Nineteenth century England spawned heavy industry and with it came chimney smoke: dark sooty pollution that covered trees and buildings. Which just happened to be where the peppered moth like to hang out. There are 2 kinds of peppered moths, one is dark-colored, the other light-colored. At the time of the IR most were light-colored. But, as the bark of trees and the sides of buildings took on black soot, the light-colored moths began to stand out thus becoming more noticeable to birds, their natural predator. As a result, their population declined and the dark-colored moth population rose, as they were now camouflaged by the darkened trees.

This is evolution by means of natural selection: the environment changes, and that change ‘selects’ for some fraction of the population — dark-colored moths, in this case — and giving that population a survival advantage and thus a reproductive advantage.

Back to our bacteria. The analogue to the IR and soot is the antibiotic. The analogue to the light-colored moth that the changed environment selected against is all our bacteria that aren’t resistant to antibiotics: i.e. the vast majority that help us live healthier lives or are at least harmless. And the analogue to the dark-colored moth that the changed environment selected for, thus giving it a survival and reproductive advantage, is the bacteria that are resistant to antibiotics.

Bacteria GT3

There is one important difference with (resistant) bacteria. They have a trick up their sleeve: the ability to transfer their genes that confer resistance to antibiotics, to other (susceptible) bacteria, in real time — nicely illustrated in the above cartoon. Think of genes, Dr. Blaser says, as a deck of cards, and the transfer of genes as swapping out of one of the cards. It would be as if the dark-colored moth could hand their genes that code for their dark color to the light-colored moth sitting sitting beside it on the tree.

The upshot of our “drug abuse” — the overuse and misuse of antibiotics on our resident bacteria — is the proliferation of bacteria that are resistant to those very same antibiotics. So much so that the US Centers for Disease Control reported that:

Antibiotic resistance is a worldwide problem. New forms of antibiotic resistance can cross international boundaries and spread between continents with ease. Many forms of resistance spread with remarkable speed. World health leaders have described antibiotic resistant microorganisms as “nightmare bacteria” that “pose a catastrophic threat” to people in every country in the world.

The same CDC report said that MRSA poses a serious public health threat. The agency conservatively estimated that it caused 80,461 invasive infections and 11,285 related deaths in 2011, the last year for which statistics were available. The report also said that a much higher number of less severe infections occurred in both the community and in healthcare settings.

So here’s a question. We have two examples of evolution where organisms successfully adapted to environmental pressures: dark-colored moths and bacteria that are resistant to drugs — in each case conferring a survival advantage. But what about humans: can we think of a case where we have evolved, say over the last 50 to 100 years, in a way that has conferred a survival advantage? If so, what is our newly acquired trait that’s analogous to the dark-color in the moths or the drug-resistance in the bacteria, that gives us that advantage?

Put another way, if we can’t specify such a trait, does that mean humans have stopped evolving?

 

 

 

 

 

The Secret World Inside You

Our understanding of the natural world and, crucially, how we get that understanding, is changing rapidly.

A perfect example is the current exhibition at the American Museum of Natural History, in New York, called The Secret World Inside You, which runs until August 14 this year.

What’s on display there is you and me; specifically, our microbiome – that vast array of microbes living in and upon us that outnumber our “human” cells, collectively weighs about three pounds, and, we are learning, greatly affects our health in ways that, until recently, we had no idea about. For example, our microbiome – “good” bacteria, in this case – play important roles in digestion and nutrition, obesity, mood, and immune function, among other things.

Rob DeSalle, Research Scientist in Residence at the AMNH, believes this change in our way of looking at microbes will change the way we think about ourselves and our health. It will shift medicine away from an attitude of “let’s just kill these things” to understanding how these beneficial microbes interact with us.

One example of the beneficial role played by of our microbes — and utterly counterintuitive — is the research showing that antibiotic use actually increases our risk for a future infection. That’s because antibiotics kill both good and bad bacteria. Since good bacteria help fight infection, the less we have — they’re killed by the antibiotic — the less able we are to fight off germs we encounter. The same reasoning holds for antibiotic use and an increased risk for clostridium difficile infection, a pernicious diarrhea which kills about 29,000 people within 30 days of diagnosis, each year in the United States.

However, it is one thing to know something, but it is often quite another thing to be persuaded by it and to act on it. Stanford University biophysicist Manu Prakash, in a recent interview with The New Yorker, explains how seeing is believing: “It’s not good enough to read about [the microbiome] … You have to experience it …Unless you get people curious about the small-scale world, it’s very hard to change mind-sets about diseases [and] … There’s a very deep connection between science education and global health.” To let everyone see this microworld in action, Prakash has developed a bookmark-size largely paper microscope, available to everyone this summer for the mere cost of a dollar (see preceding link).

And therein lies the value of The Secret World Inside You exhibit at the AMNH — it makes the invisible world real and meaningful. It has done so, commendably, by coming up with entertaining teaching games, quizzes, life-size animation and compelling visual effects, attractive to people of all ages (as is the website itself).

Here’s one way to gauge its effectiveness: How would you get your child to develop the habit of washing their hands so as to prevent the colonization and spread of disease-causing germs; MRSA, say? You could try a rational discussion backed up with data from the Centers for Disease Control that says it kills over 11,000 people a year in the US. Or you could have your child walk around and inspect a colorful and compelling life-size model of MRSA being attacked by a macrophage, and let that lead to a discussion about the microbial world and your health. Which do you think would do the trick? Which method of persuasion would stick with your child and perhaps even inspire him or her to become interested in the world of science and disease?

At the AMNH: An immune cell (yellow) on the attack against a swarm of disease-causing Staphylococcus bacteria (red).

At the AMNH: An immune cell (yellow) on the attack against a swarm of disease-causing Staphylococcus bacteria (red).

Getting High on Antibiotics

Direct from the department of the unexpected:

Scientists have discovered an unrecognized cause of “delirium or alterations of cognition or consciousness” in hospital patients: Antibiotics — in any one of 54 different antibiotics, including penicillin, covering 12 different drug classes. The effects often “closely resemble drug-induced psychotic syndromes caused by … [such things as] cocaine [and] amphetamines,” says Shamik Bhattacharyya, MD, from the Harvard Medical School, and lead author of the study.

How prevalent is the effect? We’re not sure. The Harvard study was a literature review that identified 391 cases from 1946 through 2013 involving patients experiencing delirium. While that number appears low we have to remember that, until now, when patients on antibiotics became delirious, antibiotics were simply never considered as a possible cause.

DeliriumAnother study, for example, has reported the number to be as high as 15%; however, that refers to a skewed patient population: critically ill patients with chronic kidney disease.

Dr. Bhattacharyya says the takeaway from his study should be this: “There are instances when antibiotics are overlooked as a potential treatable cause of delirium. [And so] the primary message … is that when patients become confused when suffering from infections, antibiotics should be included in the list of many potential causes.”

The Harvard study stands for something else too: it’s yet another example of a growing list of ill effects of antibiotics.

Barbara Warner, MD, professor of pediatrics at the St. Louis Children’s Hospital, puts it this way: “The conventional wisdom has been antibiotics can’t hurt and they might help. But our new study demonstrates that wide-scale use of antibiotics in this population does not come without cost,” says. The population Warner is talking about is preterm infants. Because they’re more prone to infection they’re routinely given antibiotics whether they’re showing signs of infection or not. But her new study found that by doing so (1) you increased resistance not just to the prescribed antibiotic but to other antibiotics as well, and (2) the routine administration of antibiotics killed “good” bacteria in the infants’ GI tract; bacteria that are needed to play vital roles in infant nutrition, bone development, and immune function.

That we need our gut bacteria for healthy immune function accounts for perhaps the most surprising ill effect from antibiotic use: an increased risk for infection. That’s the conclusion of infectious disease specialist Martin Blaser, MD, of the NYU School of Medicine, and Director of the Human Microbiome Program. His reasoning is similar to Warner’s: Good bacteria operate in conjunction with your immune system to protect you from disease. So if you knock them out with an antibiotic and are then exposed to a disease-causing germ, your chances of that germ making you sick go up – way up.

Notice that all of these ill effects occur even when the patient needs an antibiotic to treat a threatening infection. So in those cases you simply have to take the risk of delirium, and so on. What’s truly unfortunate, however, is something else entirely: that in 30 – 50 per cent of the cases where antibiotics are prescribed in hospitals, they are either unnecessary or inappropriate, according to the US Centers for Disease Control and Prevention.

The Reader’s Debate: Should you always take a course of antibiotics through to the end, or should you stop when you feel better?

The practice of medicine and the science it’s based on, like most things, changes over time.

An excellent example of this comes by way of a reader’s thoughtful question that goes to the very heart of an issue we all face: What’s the proper way to take a course of antibiotics? Is it always through to the end until all the pills are gone, or should we stop when we begin to feel better?

The reader’s letter in full:

Here’s an antibiotic question I have. If you have a bacterial infection, the dr prescribed antibiotics. The label says to take all the pills. Usually a 10 day course. The thinking is that you don’t want to leave any of the “biotics” to live to attack another day. It makes sense. I have a friend who takes the drugs only until the symptoms go away. No problem. Could that be the better way? Give your own immune system a kick in the pants to fight off the bad bugs? That would support your own system. I don’t know which is right. I’ve always taken the full course (although I don’t take antibiotics unless I’m dying) and thought it made sense. My smart friend swears by her method. Who is right?

The “right” answer seems to depend on who you ask. Historically, the weight of opinion has been squarely on the side of taking each and every pill until they’re all gone, a view that’s still backed by our institutional heavyweights. The World Health Organization, for example, issued a news release last November in an effort to correct public misconceptions about antibiotics, saying, in part:

“… 64% of respondents believe antibiotics can be used to treat colds and flu, despite the fact that antibiotics have no impact on viruses. Close to one third (32%) of people surveyed [wrongly] believe they should stop taking antibiotics when they feel better, rather than completing the prescribed course of treatment.”

Similarly, the Mayo Clinic consumer health web site says: “It is tempting to stop taking an antibiotic as soon as you feel better. But the full treatment is necessary to kill the disease-causing bacteria.”

The US Centers for Disease Control and Prevention offer the same advice, with one caveat: “Never … stop taking an antibiotic early unless your healthcare professional tells you to do so.”

Which brings us to where we confront the issue: at our doctor’s office or with a hospital physician. And as we know they typically, if not always, warn us to complete the full course of antibiotics –– until recently.

Dr. Spellberg: That you have to keep taking your antibiotics even after you fell better "is old wives’ tale."

Dr. Spellberg: That you have to keep taking your antibiotics even after you feel better “is an old wives’ tale.”

Meet infectious disease specialist Brad Spellberg, MD, clinician, professor of medicine, researcher, author of the book Rising Plague, and Chief Medical Officer of the LA County and USC Medical Center. He represents an emerging school of thought that says you should stop taking antibiotics when your symptoms disappear. In an interview with the science magazine Discover, he sums it up nicely:

“The science is clear. Every study that has been done comparing longer versus shorter antibiotic therapy has found shorter therapy just as effective. The issue of continuing therapy until all doses are done is an old wives’ tale. There’s no data to support it. You can’t make a cured patient better.”

Effectiveness, then, is one factor to consider on the question of how long to an antibiotic. But there’s another important factor in play here too: harm. Like all drugs, even aspirin, antibiotics come with unwanted side effects. So the more antibiotics you take the greater the chance you will experience some of them including, paradoxically, increasing your risk for infection down the road.

It goes like this. The majority of the antibiotics prescribed, like amoxicillin, for example, are “broad-spectrum”: they go after all the bacteria in you, not just the bug causing the problem. So whether you have a strep, staph, or E coli, infection, say, the antibiotic will eliminate it because it kills all susceptible bacteria, including — and here’s the rub — your “good” bacteria. These good bacteria operate in conjunction with your immune system to protect you from disease. So if you knock them out with an antibiotic and are then exposed to a disease-causing germ, your chances of that germ making you sick go up.

That’s the conclusion of infectious disease specialist Martin Blaser, MD, director of the Human Microbiome Program, researcher and professor of medicine at New York University, and author of the book Missing Microbes. As he candidly challenges: “Has any health-care professional ever told you that taking antibiotics would increase your susceptibility to infection?”

Dr. Blaser: The paradox of taking antibiotics is that it actually increases your risk of infection.

Dr. Blaser: The paradox of taking antibiotics is that they actually increase your risk of infection.

Where this increased susceptibility issue gets overlooked is its effect on kids. Early life is a vulnerable time and a critical period for development. Yet, cautions Blazer, “We have been using antibiotics as if there was no biological cost.” The average child in the United States, he says, receives 10 courses of the drugs by the age of 10, setting them up for such things as obesity, impaired metabolic function, and impaired bone growth, i.e., height. And the effects of antibiotics, his research shows, are cumulative: the more you take, the greater the risk of one or more of these “side effects.”

So, for how long should you take that antibiotic? For as short a time as possible, and for two reasons: short courses are just as effective as longer courses (Spellberg); and the more antibiotics you take the greater the chance that something will go wrong, including, oddly, the increased risk of infection (Blaser).

There’s a third and crucial point to consider, which is really the threshold question: Whether we should we even be taking an antibiotic in the first place. Antibiotics only work on infections caused by bacteria, not viruses. According to the CDC, infections caused by viruses include the stuff we all experience: colds, the flu, most sore throats, most coughs and bronchitis (“chest colds”), many sinus infections, and many ear infections — and for all these things, antibiotics have no role to play. So going after virus with an antibiotic would be like hunting bear with a fishing rod: in neither case will you get the job done, and in both cases you could get hurt.

Notice the CDC’s use of the words “most” sore throats, “many” sinus infections, and so on. Some sore throats, etc., are therefore caused by a bacterium for which an antibiotic should prove effective: but how do you distinguish a bacterial from a viral-based infection? The sure way is take a sample from the infected area and send it to the lab for analysis – which will take a few days – or, as is most often the case, your physician will exercise their clinical judgment to determine where the probabilities lie. And “lie” they might, because it is, after all, an exercise in professional guesswork.

So back to our reader’s question. It seems they both have valid points well-supported by the evidence. Recent clinical trials and the voice of leader’s in the field of infectious disease such as Brad Spellberg suggest that stopping antibiotics as soon as your symptoms disappear is where we’re headed. And the reader who said “I don’t take antibiotics unless I’m dying,” would have the support of everyone, especially Dr. Blazer and his colleagues.

The medical evidence, then, tells us 3 things: Be sure an antibiotic is the right tool for the job; if it is, a short course will be just as effective as a long course; and a short course will also minimize your risk of antibiotic harm, such as obesity or becoming more vulnerable to infection down the road.

Knowing all this, let’s see how it plays out in the real world.

You’re at your pediatrician’s office. Your 5-year old boy has come down with some kind of infection, again. Your doctor examines him and says in her opinion your child probably has a touch of bronchitis. She hands you a prescription for a broad-spectrum antibiotic and says, like most doctors will, be sure that your son completes the full 10-day course. She smiles warmly and begins to usher you out of her office. It’s late in the day and the waiting room is full of sick kids and anxious parents.

This is your son. You’ve done your homework and you know the issues.

What do you do?

 

Department of Disbelief: Things We Don’t See We Don’t Take Seriously – Such as MRSA Bacteria. But A New Technology May Have The Cure

The well-known phrase “seeing is believing,” i.e., only physical or concrete evidence is convincing, is more than just a 17th C proverb: scientific research tells us it’s true. What’s more, it’s corollary, “not seeing is not believing,” is apparently also true. In fact, Israeli-American psychologist Daniel Kahnemen won the 2002 Nobel Prize in economic sciences for proving just that: we decide what’s important based on what comes to mind; and what comes to mind is vivid visual imagery – think 9/11 imagery – and not (boring) data.

This two-minute video nicely illustrates the point by posing the question: Which should we be more afraid of, sharks or horses?

This matters because it’s not just you and me who think this way; we all do, including government policy makers. As the video points out, more money is allocated for fighting terrorism than cancer even though cancer kills 2,000 times as many people. Similarly, with respect to infectious disease, there was a shift of tens of millions of dollars of federal research money since 2001 away from pathogens that cause major public health problems to obscure germs that the government fears might be used in a bioterrorist attack. Yet, conservative estimates have MRSA alone killing over 11,000 Americans every year and seriously injuring over 80,000 more – and this sentence is Exhibit A for the kind of rational data that doesn’t convince people of anything.

Conventional wisdom holds that the cure for this faulty way of thinking – this cognitive disability we all share — is to be aware of it and to make a concerted effort to rely on the evidence instead of impressionable events. (Good luck with that.)

Manu Prakash and Foldscope

Manu Prakash and Foldscope

Which brings us to Stanford University biophysicist Manu Prakash and his effort to bring the miniscule world of microorganisms – he calls it the microcosmos – to the masses. He wants us to be able to see the microcosmos just as we see the everyday things in the world we inhabit: to see bacteria as easy as we see a building.

To do this he invented the Foldscope, a microscope made almost entirely from a sheet of paper, plus a tiny lens, and is the size of a large bookmark. It comes in a kit and performs most of the functions of a high-school lab microscope. He plans to make the Foldscope available for purchase by the summer – for the cost of $1.00!

In a recent interview with The New Yorker, Prakash explained his thinking: “It’s not good enough to read about [the microcosmos] … You have to experience it …Unless you get people curious about the small-scale world, it’s very hard to change mind-sets about diseases [and] … There’s a very deep connection between science education and global health.” Experience what you see through Foldscope:

Aside from having your own Foldscope, you’d have them available in hospitals, doctor’s offices, health clinics, schools, libraries, and so on, so everyone could experience the microcosmos and thus be persuaded it’s real. This is how you change behavior. Anyone going to any health facility, and this would include staff, could be asked to scrape their hands and see what’s there. This, for example, would be a way to overcome the notoriously difficult problem of getting hospital staff to comply with their own hand-washing rules.

The Foldscope (or perhaps something similar as a Google Glass app) is the portal into the microcosmos, a world teeming with “many very little living animalcules, very prettily a-moving … which bent their bodies into curves.” Those were the words of the inventor of the microscope, Dutch scientist Antoni van Leeuwenhoek, describing what he saw the first time he scraped off some of his own dental plaque and put it under his microscope.

Interestingly, when Leeuwenhoek announced his discovery of the microcosmos, few of his contemporaries were willing to believe it even existed. That was 1683. According to the Pulitzer Prize-winning research of Daniel Kahneman, when it comes to the microcosmos, for practical purposes, the majority of us haven’t moved much beyond that: that’s just who we are.

A Pentagon Biotech Unit Targets MRSA

Al Gore didn’t invent the Internet. It was the Pentagon’s biotech strike force, DARPA, whose research gave rise to such things as the Internet, GPS monitoring, and stealth aircraft.

DARPA stands for the Defense Advanced Research Projects Agency. Their mission isn’t to do ordinary science, it’s to forge quantum leaps in technology. For example, technology to immediately translate languages for online and in-person communications; the Spiderman project to enable soldiers to walk up walls; robotic arms that can be controlled by a person’s mind; prosthetic hands that can “feel” things, and so on. In other words, their job is to make science fiction real.

DARPA at work

DARPA at work

The DARPA project that interests us is disease detection: the development of pathogen identification technology that tells you immediately whether you’re dealing with a bacteria or a virus, and which one.

The way we figure that out now doesn’t cut it. We still use the Louis Pasteur-era ‘culture’ method: you take a sample from the affected area and send it to the lab, they look at it under a microscope and send you a report. That can take several days to a week assuming you’re near a hospital. But if you’re in a remote area, an underdeveloped country, a war zone, and so on, it’ll take longer and sometimes it can’t even be done. And that’s all a bad bug needs to do you irreversible harm.

That’s why DARPA is funding research to make pathogen detection as simple as a pregnancy test. One effort underway is the development of a small, light-weight paper-based device without complex instrumentation. The test is activated once exposed to a nasal swab, and in less than an hour, will change color to indicate the presence of different target diseases. They’re after the usual suspects like the flu, the Middle East Respiratory Syndrome or MERS, malaria, dengue fever, sexually transmitted diseases, and Ebola.

However, the first pathogen researchers will target is methicillin-resistant Staphylococcus aureus, or MRSA. That’s because MRSA is especially problematic in institutional settings like hospitals, military bases, and prisons; or in refugee camps or crowded urban settings where people generally live in close quarters (MRSA is spread by contact). So fast diagnosis is key because MRSA infections can worsen rapidly, and in less than a week, take hold in human tissue and become very difficult to treat or even untreatable: In the U.S. alone MRSA causes more than 11,000 deaths a year (linked report, p.77).

Remember, too, the dictum of the Director of the U.S. Centers for Disease Control and Prevention, Thomas Frieden, MD, who said that because of rapid global travel of people and goods “a disease outbreak anywhere is a risk everywhere.” Last year’s Ebola outbreak is an example of this, and it’s also an example of the need for rapid diagnostics: the first U.S. Ebola patient who presented himself at the Dallas hospital with flu-like symptoms was sent home with antibiotics – which fight bacterial-based diseases only. Ebola, however, is a virus thus unresponsive to antibiotics. Had there been rapid diagnostics available he wouldn’t have been turned away to wander the streets of Dallas for days, possibly infecting others, before he returned to the hospital in much worse shape and finally admitted.

Here’s one of the DARPA-funded disease detectives discussing their groundbreaking work:

The Resistance Movement: Cancer, like infectious disease, also develops resistance to the drugs used to treat it

Infectious Disease is not alone in its resistance to therapeutic drugs: cancer behaves much the same way. For instance, when we say that a chemotherapy patient relapses, what’s happening is that the cancer cells have developed resistance to the chemo drug, thus rendering it useless, allowing the cancer cells to grow back.

The relationship between antibiotic therapy and chemotherapy dates back to the origins of chemotherapy, some 70 years ago. Sid Mukerjee, M.D., in his 2011 Pulitzer prize-winning book, The Emperor of All Maladies – A Biography of Cancer explains that in the late 1940s, the idea of chemotherapy – a drug that could cure cancer – began to take hold. The timing was no accident. This was on the heels of the birth of the Antibiotic Age that began with the widespread use of penicillin by American and British Forces during WW ll. The use of the drug was so successful that it spawned the idea in oncologists to look for “a penicillin for cancer.”

Cancer cells mutate quickly in response to chemotherapy, thus a never-ending “cat-and-mouse game” between the two. And so “we are forced to keep running merely to keep still.”

Cancer cells mutate quickly in response to chemotherapy, thus it’s a never-ending “cat-and-mouse game” between the two. 

Cancer cells mutate quickly in response to chemotherapy, thus a never-ending “cat-and-mouse game” between the two. “This is our predicament with cancer: we are forced to keep running merely to keep still.”

So it came as little surprise that the first ant-cancer drug was, in fact, an antibiotic – actinomycin D – that was repurposed to act as an anti-cancer agent. This was the summer of 1955 and the drug worked – to a degree. It caused remissions that lasted months – but only months – in a rare form of kidney cancer in children.

More drugs soon followed that treated other cancers. However, not only did the problem of resistance always emerge, something even worse happened: In one trial, for example, people treated with multi-drug chemotherapy for Hodgkin’s disease would relapse; not with Hodgkin’s disease, but with a second and different cancer – typically an aggressive drug resistant leukemia – caused by the chemotherapy.

The lesson soon leaned by the cancer community was the one already learned by the infectious disease community: the cell – whether it’s a human cell, a cancer cell, or a bacterial cell such as MRSA, – is built to adapt and survive, even when attacked by poisons such as antibiotics or chemotherapeutics.

The chart on drug resistance is instructive. While it focuses on bacterial mutation and resistance, it works the same way with cancer cell mutation and the resulting resistance to chemotherapy:

drug resistance

Author, researcher, and infectious disease specialist Brad Spellberg, M.D., in an interview with NPR, “Bacterial Infections Defy Treatment,” echo’s Mukerjee’s sentiments on the “cat-and-mouse game” of drug resistance. He phrases it as a constant trade-off between “our wits versus their genes”:

So let’s quote Joshua Lederberg, Nobel laureate, who in 2000 wrote that the future of humanity and microbes would likely evolve as episodes of our wits versus their genes.

This is what bacteria [e.g. MRSA] do. They’re just being bacteria. They become resistant to stuff, they adapt. We have to accept that’s never going to stop. No matter how perfect our stewardship is, no matter how prefect our infection control is, they’re always going to adapt. So, yes, we are never going to win in the end. But … we know steps that we can [adopt] to get back ahead in the race.

 

 

 

The Crime Boss, Part 4: Mr. Parnell Goes to Prison

This past Monday, Stewart Parnell, former head of the Peanut Corporation of America, was sentenced by a federal court judge in Georgia to 28 years in prison. At age 61, Parnell will spend the rest of his life behind bars. (Two others at PCA were also sent to prison, one for 20 years, the other for 5 years.)

This case directly implicates how we treat people colonized with infectious pathogens such as MRSA. It suggests that the law could play a greater role in policing the problem, not just in the traditional sense of using the civil law to sue, but there’s now more than a hint that the criminal law could be used as well. But first, some background.

Stewart Parnell

Stewart Parnell

Parnell’s company caused a U.S.-wide salmonella outbreak in 2008 – 09 that killed 9 people, including children, and infected over 700 more. Parnell was more than just the guy in charge; internal company documents show that he knew they were shipping peanut butter laced with a bacterial poison – salmonella — to retailers across the country. What’s more, when he found out, he didn’t care: “… just ship it,” he said, “… these lab tests are breaking me/us.”

U.S. District Judge W. Louis Sands wanted to hear from the victims and their families before he pronounced sentence on Monday. Gabriel Meunier, on behalf of her son Christopher told Judge Sands, “My 7-year-old son told me that he was in so much pain that he wanted to die.” Jeff Almer, who attended most of the trial hearings last summer, stared at and talked directly to Parnell. In a haunting tone, he said, “Stewart Parnell, you killed my mom [Shirley Mae Almer].” Peter Hurley, whose son, Jacob, was sickened by PCA peanuts, flew in from Portland, Oregon, to say, “Stewart Parnell, you gave some people deathsentences. Luckily, you are not being sentenced to death.”

The idea that a corporate executive, in the context of causing infectious illness, could be thought of as a murderer and thus eligible for the death penalty is gaining currency with more people than just the victims and their families. For example, award-winning science journalist Julia Belluz, the 2013-14 Knight Science Journalism Fellow at MIT, asked attorney Bill Marler, who represented some of the victim families:

If someone took a gun and killed seven people, he would get the death penalty. Why did Stewart Parnell get away with 28 years?

Get away with 28 years?”

U.S. Attorney Michael Moore of Georgia’s Middle District, whose office prosecuted the case, called it “a landmark [case] with implications that will resonate not just in the food industry but in corporate boardrooms across the country.” (My emphasis.)

Which brings us to the question: Which boardrooms?

Take a look at this study of people colonized with MRSA and what happens to them. It says that 1 in 7 people who acquire the bug at the hospital become infected by it: i.e., they get sick, require surgery, multiple readmissions to the hospital, stays in the ICU, and many die. This happens fast, usually within a month. Here’s a similar study, but it says the infection rate is actually much greater, that 1 in every 4 people who are MRSA-colonized get sick.

So when a hospital discovers that a patient is colonized with MRSA they do the prudent thing and “decolonize” them, right?

Surprisingly, most don’t even though they could; moreover, the patient is neither warned of the risks nor involved in the decision making. Various reasons are given including the fact that “it taxes hospital resources.” And there’s the rub.

Shirley Mae Almer (in the chair)

Shirley Mae Almer (in the chair)

So here’s what we’ve got: An inherently dangerous situation; that puts completely unaware and innocent people at grave risk of life and limb; the ability to do something about it; and the refusal to do so. Are we talking about Parnell, poisoned peanuts, and the public; or hospitals, pathogens, and patients? The answer is both, but there is one crucial difference: foodborne illnesses hospitalize 100,000 people a year and kill 3,000; but infectious illnesses resistant to antibiotic treatment exact a far greater toll. They hospitalize 3 million people a year and kill over 23,000. MRSA alone is responsible for almost half of those deaths.

So let’s rephrase Julia Belluz’s question. Let’s say you’re a doctor or you’re in hospital management. You know or should know that between 1 in 4 and 1 in 7 people who are colonized with MRSA become infected; i.e., they get sick, some seriously, some will die. Nevertheless you don’t decolonize. Instead, you discharge them knowing the risk they face. So here’s the question – the kind of question that lawyer’s ask at trial:

What’s the difference between that and giving a patient a gun with a bullet in 1 of the 6 chambers and telling them to go home and play with it? If they shoot themselves, shouldn’t you go to prison? More to the point, suppose you did this year in and year out, and as the body count mounted you still didn’t change your polcy. Shouldn’t you go to prison now?

No, the analogy to Parnell’s case isn’t exact. But the relationship between law and medicine is shifting. Doctors and hospitals aren’t as immune to the law as they once were. So before another forward-thinking prosecutor considers whether or not to reach into your office, you may want to look at any policy affecting people’s lives that’s driven by anything that resembles “it taxes hospital resources.”

It’s not an argument that sits well with jury’s, not when it’s balanced against the life of a child.

We have followed the Parnell case and its implications for the practice of medicine since its inception. Earlier columns are The Crime, The Victims, and Rethinking Crime.

 

 

 

 

 

 

 

What’s the Greatest Threat That We Face?

The New York Times ran an interesting piece yesterday asking who, or what, threatens the U.S. the most. It offered up the usual suspects: the Joint Chiefs of Staff say it’s Russia, the FBI says it’s the Islamic State, and President Obama says it’s nuclear terrorism.

However, the president of the Council on Foreign Relations, Richard Haas, weighed in with an unusual suspect, saying that it might be, among other things, “an Ebola-like pandemic.” He didn’t elaborate and the implication was that whatever this pandemic might be we haven’t yet seen it.

Dr. Davies: The risk of antibiotic resistance is "just as important and deadly as international terrorism."

Dr. Davies: The risk of antibiotic resistance is “just as important and deadly as international terrorism.”

But the health community say otherwise. For example, the UK’s chief medical officer, Dr. Sally Davies, said in an interview with the CBC this year that antibiotic resistance (ABR) – the idea that bacteria are so adaptable they have developed immunity to drugs (antibiotics) devised to kill them – is at least on par with our top threats.

CBC host Michael Enright: “You’ve compared the threat of ABR to the threat of terrorism … and nation-states are activating their resources to counter that. Why are governments so slow to seriously tackle this problem?”

“Let’s be clear,” said Dr. Davies, “In the West and actually across the world far more people are dying of ABR than of terrorism. But somehow it doesn’t seem so shocking. Already, about 50,000 people in Europe and the United States are killed each year by bacteria and other microbes that have developed resistance to the drugs we throw at them.”

And these numbers are expected to climb Davies says: by the year 2050 drug-resistant bacteria could cause as many as 10 million extra deaths globally, surpassing cancer deaths.

Commenting on these numbers, Mr. Enright offered an astute perspective: “If the headlines were about Ebola and not ABR that was going to kill 10m people a year, surely to God there’d be global governmental action.”

“Absolutely,” said Davies. “And if you look at the number dying every year of ABR – how have we let the public become complacent about it? We need to do something.”

But Davies cautioned that solutions won’t come easy.

“What we have to do – it’s a complex, wicked problem – is work on every level: public awareness, government awareness, with the professionals so they don’t overprescribe, the public education about not demanding them when they don’t need them, and see how we can resolve that market failure in the R&D pipeline. This is a really difficult problem.”

“I sometimes lie in bed at night,” Davies continued, “and wonder whether the families of these people who died knew that these were needless deaths, that we should have done something about it.”

Germ Warfare

The most combat deaths that the United States ever suffered — by far — was during World War ll. Almost 292,000 troops died from the time the US entered the war after the bombing of Pearl Harbor on December 7, 1941, to war’s end in 1945. Averaged over the 4 years that’s almost 73,000 American deaths a year.

Now take a look at the number of deaths that occur each year in US hospitals due to infections that patients acquire while there: 75,000. Add to that 573,000 people who will develop hospital infections and will not die, but who will undergo surgeries, lengthy and repeated hospital admissions, limb germ warfareamputations, physical and psychological suffering, and so on.

Simply put, “Hospitals need to stop infecting their patients,” says Doris Peter, PhD, director of the Consumer Reports Health Ratings Center. “Until they do, patients need to be on high alert whenever they enter a hospital even as visitors.” What’s more, “We’ve reached the point where patients are dying of infections in hospitals that we have no antibiotics to treat,” says Arjun Srinivasan, MD, who oversees the CDC’s efforts to prevent hospital-acquired infections.

But what does “high alert” mean? Are there actually concrete things that patients and their families can do to make a hospital stay safer?

The answer is an unqualified Yes: According to this month’s excellent cover story in Consumer Reports, America’s Antibiotic Crisis – How hospitals can make you sick, there are 10 things patients have to take the initiative on:

Consider MRSA testing. A nasal swab can detect MRSA and allow medical staff to take precautions, such as having you wash with a special soap before your procedure.

Insist on cleanliness. Ask to have your room cleaned if it looks dirty.

Take bleach wipes for bed rails, doorknobs, and the TV remote. Insist that everyone who enters your room wash their hands.

Keep your own hands clean. Wash regularly with soap and water.

Question antibiotics. Make sure that any anti­biotics prescribed to you in the hospital are needed and appropriate for your infection.

Watch out for heartburn drugs. Medications such as Nexium and Prilosec increase the risk of developing C. difficile symptoms by reducing stomach acid that appears to help keep the bug in check. So ask whether the drug is needed and request the lowest dose for the shortest possible time.

Ask every day whether ‘tubes’ can be removed. The risk of infection increases the longer items such as catheters and ventilators are left in place. If you’re not able to ask, be sure a friend or family member does.

Say no to razors. If you need to be shaved, use an electric hair remover, not a razor, because any nick can provide an opening for infection.

And when you return home from the hospital:

Watch for warning signs. They include fever, diarrhea, worsening pain, or an incision site that becomes warm, red, and swollen. People at particular risk include adults older than 65 as well as infants, anyone on antibiotics, and people with a compromised immune system.

Practice good hygiene.  Take extra precautions to make sure that your infection doesn’t spread. So clean frequently touched surfaces with 1 part bleach mixed with 10 parts water. Reserve a bathroom for the infected person. If that’s not possible, use the bleach solution to disinfect surfaces between uses. And don’t share toiletries or towels; use paper towels rather than cloth hand towels.

This 5 minute video dives deeper into the above points:

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