A new front opens up in germ warfare — the nursing home

Underneath the tranquil exterior of the nursing home lies a thriving community of new-found members whose presence poses an imminent threat to our elderly: i.e., multi-drug resistant organisms (MDROs) — aka “superbugs,” bad bugs, germs, or pathogens. Those invisible creatures that, in gangs of tens of millions or more, are in us, on us, and around us, and drive those nasty infections that antibiotics increasingly have no control over. So much so that:

“Current data suggests that here are nearly 3 million infections in nursing homes every year, resulting in 150,000 hospital admissions and 300,000 deaths.  As the US nursing home population is expected to increase from 3 to 5 million by 2030, we can expect to see a larger burden of these types of infection.”

The stunning quotation is from James A. McKinnell, MD, (email correspondence, 6/22), an Infectious Disease specialist at the Harbor-UCLA Medical Center and the Los Angeles Biomedical Research Institute. He is also the co-lead author of an eye-opening new study that says there’s significantly more of these drug-resistant pathogens in our nursing homes than we knew. For example:

1) Almost half (47.5%) of the people in nursing homes are colonized with at least one superbug.

2) Nursing homes themselves are awash with superbugs: 88% of the rooms are contaminated with at least one. And watch out for the bedside table/bedrails as 86% of them are contaminated with at least one superbug.

3) The big dog is Methicillin-resistant staphylococcus aureus (MRSA). They were found in almost 2/3 of the rooms (65.2%); followed by VRE (46.4%), ESBL (26.4%), and CRE (5.1%).

4) We also know that these 4 bugs aren’t the only ones living in nursing homes. The Centers for Disease Control tells us there are 18 superbugs whose threat to our health is either “urgent” (such as CRE), “serious” (MRSA, ESBL, and CRE), or “concerning.” In other words, Mckinnell’s team, looking for less than ¼ of the known threats (a demanding task in itself) found almost 9 in 10 rooms colonized with these disease-causing drug-resistant pathogens.

5) Interestingly, the bugs in the room don’t always match the bugs on you. For example, among MRSA carriers, almost 2/3 of them (64.1%) had their rooms contaminated with non-MRSA bugs, thus exposing them to new and different superbug acquisition.

elderly 2

Dr. Mckinnell’s study matters because his group did something different: they looked harder. Investigators typically check for pathogens in just the nose — but why stop there? Using the so-called Zorro technique (the search mimics the motion the fictional character Zorro makes with his sword) his team checked the left armpit, right armpit, left groin, and right groin.

And voila, detection increased by 20%. In an interview with Medscape, Mckinnell reports that “We found 160 patients with MRSA. If we had only done nares, we would have only found 121; we would have missed 39 carriers.” Thus, he says, “When a facility tells me their rates are 6%, I usually add 30% to account for all the missed and untested multidrug-resistant organisms.”

The upshot is that “Nursing homes are the perfect storm of patients carrying pathogens and at the same time at [an increased] risk of getting sick if they are exposed to them.” The elderly have weaker immune systems, are more likely to have a history of MDRO carriage, be bed-bound, or be in need of a catheter, each one a risk factor for infection.

And the risk spreads. As others have pointed out, in the revolving door between the nursing home and the hospital, if colonized individuals are admitted to the hospital without having been screened, a silent transmission of pathogens can emanate throughout the healthcare system.

Estimates vary, but there seems to be at least twice as many people in nursing homes as there in hospitals in the US. The point of intervention, then, is clear: you want to debug — decolonize — people at the nursing home.

But there’s a trick to it. Targeted prevention becomes difficult when nearly half the patients in a nursing home are colonized with a MDRO, says Dr. McKinnell. Therefore, “We need universal interventions that protect everyone, and enhanced ones for those who need more protection.”

There’s one more consideration, captured in the dictum attached to Dr. Mckinnell’s emails, which reads: “Pick your travel partners wisely. You walk this road only once.” Sage words indeed; which assume, of course, that we have the ability to pick our partners in the first place — and thankfully, most of us do.

But not everyone. When you’re in a nursing home a great many of your partners are picked for you. We can’t see them, but we know they’re there — in the tens of millions — because they’re killing us. That’s not hyperbole. Look again at the number of nursing home infections, hospital admissions, and deaths, in the block quotation of Dr. Mckinnell, above. Now look at the three ladies in the picture and let’s ask ourselves a question: Do we owe them a duty of care?

 

 

Good medicine: It’s time for doctors and lawyers to work together to reduce the risk of medical error

Two months ago, physician Richard Horton, editor-in-chief of The Lancet, a United Kingdom-based medical journal, published a piece called “The rule of law: an invisible determinant of health.” In it, Horton says that “Public health advocates do not typically see the law as a critical influence on health. They are wrong.”

Horton’s Exhibit A in support of his thesis might well be its application to medical error.

Earlier this month a couple of physicians from the Johns Hopkins University School of Medicine in Baltimore, published a landmark analysis of medical care gone wrong, concluding: “If medical error was a disease it would rank as the third leading cause of death in the United States,” behind only heart disease and cancer.

Law & medicine, united, could be a formidable team

Law & medicine, united, could be a formidable team

Yet the astronomical 251 000 deaths a year they attribute to medical error “probably underestimates the scope of the problem,” say the authors, because (1) they used conservative numbers in their analysis (2) they counted hospital figures only, thus excluding doctor’s offices, ambulatory care centers, nursing homes, and so on (3) harm less than death was not counted, and (4) the problem is worldwide; Canada and the UK were specifically singled out as likely to be on par with the US.

There’s also a certain slight-of-hand going on with respect to medical error: it’s not just that over 250 000 such deaths aren’t being reported each year — it’s that virtually no such cases are being reported. And for one very good reason: death certificates do not have a category for human or systemic error. In other words, statistically speaking, medical error simply does not exist.

The failure to admit medical error is driven by something else too — fear of lawsuits. Martin Makary, MD, professor of surgery at Johns Hopkins and lead author of the report on error, says fear of the law drives discussion of error underground into “locker rooms, doctor’s lounges, and nursing stations … where they live in the form of stories and not in epidemiological numbers … We have created this wall of silence where we don’t talk openly and honestly about the problems … and that’s why we haven’t even begun to recognize the third leading cause of death in the United States.” (My emphasis)

To better appreciate just how, in Makary’s words, “vastly underappreciated and not even recognized” medical error is, imagine, for example, that every time there was an airline crash we refused to discuss it or, worse, we simply pretended there was none. That’s basically where we’re at with medical error today. The way out, Makarey says, is to address error the way the airline industry addresses pilot error:

“We don’t have a standardized system like aviation. When a plane crashes there’s an investigation. And the entire pilot community worldwide learns something from the crash. But yet in health care the same mistakes happen again and again, and many of them are never investigated … We need solid legal protections for a reporting system … that allows clinicians, coroners, and ME’s, to say this [medical error] was the true cause of death … [to] allow us to finally measure the problem.” (My emphasis)

The “solid legal protections” Makary is asking for already exist in a rule of evidence called “subsequent remedial measures.” It says that when measures are taken that would have made an earlier harm less likely to occur, evidence of the subsequent measures is not admissible to prove fault in a civil lawsuit.

For example, suppose the National Transportation Safety Board investigates an airline crash and determines that a faulty rudder mechanism is responsible. It then submits a report to the Federal Aviation Authority saying so. In turn, the FAA issues a directive to airline companies mandating a change in all aircraft with that kind of rudder. In response, the airlines comply.

Applying the remedial measures rule to this case would mean that in a lawsuit brought against the airline company whose plane crashed, the following could not be used as evidence to prove fault: the fact that there was a NTSB investigation; the NTSB investigative report; the FAA directive based on the report; the subsequent remedial measures taken by the airlines in response to the directive, i.e. replacing the faulty rudder with a safe one.

The reason for the rule is grounded in public safety: in balancing the need to remedy a problem that can affect us all, against the need of a plaintiff in a lawsuit to have all relevant evidence at his disposal, the courts have long since decided that the need for public safety is more important.

That’s what Makary is asking for with respect to medical error: to be able to openly investigate it, truthfully document error when they find it, especially on the death certificate, and to have these things off limits to the courts.

Reducing medical error benefits everyone

Reducing medical error benefits everyone

The reason to truthfully document — to measure — medical error, Makary emphasizes, is because you need good data. Imagine, for example, if there were no category for deaths caused by cancer. If that were so then no government policy, research efforts, or dollars, would flow to combat it. That’s what we have with medical error: since it seemingly doesn’t exist (outside of the domain of lawsuits) the government has no reason to address the error-driven 250 000-plus deaths a year by way of policy, research, or the allocation of funds.

But to begin to honestly measure this error, doctors and hospitals need the “solid legal protections” that Makary is asking for. These legal protections would be local, not federal, and so each state or province would want to draft their own.

This has already been done in many jurisdictions with what’s called the “law of apology.” When a doctor or nurse makes a mistake they can admit it to the patient and their family, and apologize for it, without those statements being used against them in a subsequent lawsuit. Again, we have the threat of suit preventing people from doing the right thing. Yet, nicely, it was the law itself that was used to remove that threat. (Another reason for the rule is that it significantly reduces the number of suits to begin with.)

Notice one more thing: These rules of exclusion (of documents recording error and doctor’s statements) are based on the rules of evidence. They are not based on “tort reform,” a politically charged, divisive topic that seldom leads to anything productive. Rules of evidence, on the other hand, almost by definition invite rational discussion and, more importantly, can be narrowly tailored to fit the facts at hand.

Law and medicine share a bedrock principle: they are both evidence-based professions. That implies a shared way of thinking, and a shared way of practicing law and of practicing medicine. Makary’s plea necessitates that these two like-minded professions finally unite to tackle a problem that doesn’t have to exist, at least to the extraordinary degree that it seemingly does.

The following audio is Dr. Makary’s interview with the British Medical Journal, from which the above quotes have been taken. It’s a rare insider’s account of medicine gone wrong from someone at the top of his profession:

Medical error is the third leading cause of death in the United States — but it’s not something that health care workers feel free to discuss

If medical error was a disease it would rank as the third leading cause of death in the United States, concludes a study just published in the British Medical Journal.

The report pegs the number of deaths at 251 000 a year, a full 100 000 deaths ahead of respiratory illness, which is next in line. Moreover, as high as this number is, it probably underestimates the scope of the problem: “That’s using some of the most conservative numbers in the literature,” says lead author Martin Makary, MD, MPH, and professor of surgery at Johns Hopkins University School of Medicine in Baltimore.

Others agree. Jim Rickert, MD, who was not involved in the study, is an orthopedist in Bedford, Indiana, and president of the Society for Patient Centered Orthopedics. He told Medscape Medical News he was not surprised medical error came in at number 3 and that even those calculations don’t tell the whole story. For example, he notes that the 251 000 figure “doesn’t even include doctors’ offices and ambulatory care centers.” “That’s only inpatient hospitalization resulting in errors,” he says.

And then there’s this: Medical error causing patient death is apparently medicine’s dirty little secret. In an interview with the BMJ, Dr. Makary says: “These are issues that have lived in locker rooms and doctor’s offices and nursing stations where people talk about [these] stories. And it’s almost as if everyone knows of examples they’ve witnessed or know of. But they live in the form of stories and not in epidemiological numbers.”

Notice something else, too: the 251,000 figure refers to medical error causing death. Medical error also causes patient harm that falls short of death. For example: a needlessly prolonged illness, multiple hospital readmissions, the need for surgery, placement in the ICU, further physical and emotional suffering, and so on.

The following chart is taken from the study:

 

Error

 

Makary defines medical error in the traditional sense, for instance: a misdiagnosis, a medication mistake, bad judgment, inadequate skill, poorly coordinated care, or a communication breakdown. But he notes that these traditional categories are expanding to include, for example, preventable factors and events, i.e. acts of omission, such as the failure to treat.

So in this emerging category of acts of omission causing harm, consider this fairly typical example of failure to treat in the context of infectious illness. Do you think it constitutes medical error today, and if not, should it?

Imagine, then, you’re in charge of a patient who you know to be colonized with the “superbug” methicillin-resistant staphylococcus aureus (MRSA). Your patient’s name is Sue, a 40-year old single mother of three, aged 7, 10, and 12. She’s been successfully treated for a pneumonia and is about to be discharged. She’s not infected by the MRSA but you’re aware of an important study reported in Clinical Infectious Diseases that says there’s a 1 in 4 chance that she could become infected. And you know that infection leads to the type of harm described two paragraphs above, i.e. multiple hospital readmissions, the need for surgery, etc., which, aside from her own suffering, would jeopardize her income and thus her ability to care for her children. Further, you’re aware of another study that says there’s even a 1 in 7 chance your patient will die if, in fact, she were to become infected with MRSA. So you’re faced with a question: Do you “decolonize” her? That is, do you get rid of the MRSA residing on her skin or in her nostrils, where it’s typically found, thereby removing the foreseeable risk of infection and consequent harm?

The obvious answer would be to decolonize. However, and surprisingly, that is actually not done in most jurisdictions. And here’s the thing: should Sue become MRSA-infected and get sick, or perhaps die, your decision not to treat would not (yet) be considered medical error — at least by health care providers — because non-treatment is the standard of care throughout the land: i.e. that’s how most providers handle a case like this. (But whether a court of law would see it as medical error — as medical negligence — is quite another matter: If your mechanic knew that your car had somewhat faulty brakes and failed to fix them, or failed to even tell you about them, and you crashed as a result, you would have an actionable claim against your mechanic.)

Makary says that “most people underestimate the risk of error when they seek medical care,” calling it a problem that is “vastly underappreciated and not even recognized.” Sue’s case may very well fall within the scope of these statements. If so, her plight is yet further proof of the “vastly underappreciated” nature of this problem.

Ultimately, though, how much harm we can attribute to medical error is unknown, and to some degree probably unknowable. Nevertheless, “the same mistakes happen again and again,” says Dr. Makary, in his interview with the BMJ; and, what’s more, “they’re never investigated.” Which leads us to what he considers the most surprising thing about medical error, what he calls the “Wall of Silence”: the fact that “We haven’t even begun to recognize the third leading cause of death in the United States.”

Makary is right, of course: We haven’t publicly recognized it. But inside those locker’s rooms, doctor’s offices, and nursing stations that he mentions above, are a host of dedicated people who, my guess would be, want to give voice to the issue, both within their ranks, and publicly. But they operate inside what’s been called an “environment of fear.” And so the question becomes: What will it take to change that culture to permit a much-needed open and honest exchange about an issue that in one way or another affects each one of us?

What do you think?

 

 

 

 

 

 

 

 

 

 

Cells of Resistance: All life forms fight to survive

The struggle for life is a trait shared by all living organisms, not just humans; from the biggest to the smallest, from bears to bacteria. A corollary to our shared struggle for life is a built-in resistance to death: when any form of life is threatened by an enemy, a serious injury, or disease, it fights back. The interesting thing is that regardless of which kind of life is under threat, the fight back — the resistance response — is remarkably similar. You can see this in 3 cases: bacteria’s resistance to antibiotics; cancer’s resistance to chemotherapy; and the French Resistance to the Nazi German occupation during the Second World War. There are dissimilarities too, certainly moral ones, but the value of the comparison is that it offers a crucial lesson about bacteria: they harm that they cause is probably more our doing than theirs.

French Resistance 2We begin with the heroic French Resistance because it offers a helpful perspective, one that is too seldom taken into account in health circles: looking at resistance from the point of view of the “organism” under threat, in this case the French citizenry.

The Nazi German invasion and occupation of France during the Second World War constituted an existential threat to French nationhood. In response, resistance cells of small groups of armed men and women sprang up and fought back. They were few in number at first, but their numbers grew as the Occupation became increasingly unbearable. For instance, due to collective punishment — the taking of thousands of hostages from the general population and the shooting deaths of an estimated 30,000 of them — the number of resistance fighters grew to over 400,000 by the last year of the war. And as we know, the Resistance prevailed, the Occupier defeated.

Looking at antibiotic resistance through the same lens, the organism under threat is bacteria. Let’s remember, we live in a bacterial world and the vast majority of them either help us, with things like digestion and immune function, or are harmless. The invader/occupier in this case is the antibiotic; the word means, literally, ‘anti-life’ (bios, from Ancient Greece, means ‘life’). As the NEJM reminds us, antibiotics en masse constitute a huge assault: In 2009, more than 3 million tons of antibiotics were administered to human patients in the United States alone; in 2010, a staggering 13 million tons were administered to animals.

weaponry

When you’re hit hard like this, you fight back, and so the “bacterial resistance” evolved against all major antibiotics pretty much from the get-go. For example, staphylococcus bacteria developed resistance to penicillin when it was first used in the 1940s; staph then developed resistance to the penicillin-derived methicillin about a year after it was first used in 1960; hence the origin of methicillin-resistant Staphylococcus aureus (MRSA).

However, unlike the French Resistance, the bacterial resistance was slow moving for a quite a number of years. For example, the US death toll from MRSA as recent as 1999 may have been as low as 4 (children). But just over a decade later and commensurate with the antibiotic onslaught mentioned above, the Centers for Disease Control tells us that the bacterial resistance spread across the country and so MRSA now kills more than 11,000 Americans every year and seriously wounds more than 80,000. If you add in other resistant bacteria and cases where “the use of antibiotics was a major contributing factor leading to the illness,” the annual American death toll is close to 40,000 people.

Cancer cells, too, develop resistance to the “assault” from chemotherapy drugs. (There’s certainly nothing beneficial about cancer cells, as there is with bacteria, let alone something heroic about them, as with the French Resistance, but we include them because they also illustrate the principle that all living organisms respond to serious threats by developing resistance to overcome them.)

With cancer cells, as with bacterial cells, drug therapy — chemotherapy and antibiotic therapy, respectively — kills the drug-sensitive cells, but leaves behind a higher proportion of drug-resistant cancer cells. As the tumor begins to grow again, chemotherapy may fail and the patient relapses because the remaining tumor cells are now resistant. In fact, one way cancer cells resist chemotherapy is similar to how bacterial cells resist antibiotic therapy: molecular “pumps” actively expel drugs from the interior of the cell.

The lesson in all of this is explained by infectious disease specialist Brad Spellberg, MD, chief medical officer of the Los Angeles County and University of Southern California Medical Center. His point is that we have to change how we think about the bacterial world. We need to shift our approach from one based on confrontation to one based on co-existence. Thus, for example, the language of war metaphors of invasion, defense, destroying the enemy, and so on, should be abandoned because those words fundamentally misdiagnose what bacteria are about. Instead, Dr. Spellberg suggests this approach:

I like to go back to first principles before I tackle complex problems. This whole thing about winning the war against microbes … nah!

We’re not going to win a war against organisms that outnumber us by a factor of 1022 , outweigh us by a hundred million-fold, replicate 500,000 times faster than we do, and have been doing this for 10,000 times longer than our species has existed!

So what we need to do is flip it around. We’re not at war with them. What we need to do is, in the immortal words of Dave Gilbert, achieve peaceful coexistence. The question is, what strategy do we deploy to achieve peaceful coexistence?

I think we need to start thinking of infections, by and large, in most cases, as accidents. There is no advantage for bacteria in most cases to infect us. They are much better off being non-infectious commensals in our gut.

In this sense, then, our massive overuse of antibiotics is simply fertilizing disease, death, and pain. So much so that the figure mentioned above of 40,000 American deaths a year caused by the “bacterial resistance,” rivals the annual death rate of any war the US has ever been in with the exception of their Civil War.

At the end of the day, says Dr. Spellberg, it comes down to “our wits versus their genes,” and the job of our collective wits is simply to come to grips with one fundamental truth about resistance:

This is what bacteria 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 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:

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