The Free-Rider Problem: Guess who else is flying with you this Thanksgiving?

airport-4

 

It’s a variation on an old theme: Travel spreads disease. We’ve known it at least since the Bubonic plague reached Turkey in 1347 via the Silk Road — an ancient trade route connecting China to the Mediterranean — following an outbreak in 1330s China. By 1348, it raged in Italy. By 1351, half of Europe lay in plague.

The Silk Road has largely been replaced by the Silver Bird. Exponentially growing air travel accelerates the spread of bacteria. JFK International Airport, for example, handled 56,827,154 passengers in 2015. Travelers sample the local microflora – often more resistant than at home – as they eat, drink and swim, returning home colonized.

And now we enter the most traveled period of the year. This Thanksgiving it’s estimated that close to 50 million Americans will travel for the holidays, more than 27 million of whom — a record for the holiday — are expected to fly. And the evidence shows that both the plane and the terminal have bad bugs willing to travel with you.

For example, a recent study found that drug-resistant bacteria from an individual traveler can be transferred to inanimate surfaces and then picked up by others. German researchers sampled 400 toilet door handles in 136 airports in 59 countries and found the handles were “loaded with germs from the skin and the intestines”. The vast majority of the bacteria were Staphylococcus aureus.

And two years ago, researchers from Auburn University found that germs on a plane –- in seatback pockets, tray tables, the metal button used to flush the toilet, etc. — can last anywhere from several days (E. coli) to a week (Methicillin-resistant Staphylococcus aureus, or MRSA). Thereby increasing the chance that one of these stowaways will hitch a ride with you when you disembark.

The good news is that researchers from both studies say there is a way to protect yourself: Always wash your hands. Professor Karsten Becker of the University Hospital Münster stresses that the best way to combat bugs hanging around on airport door handles is to simply wash your hands after you’ve been to the toilet. “No matter where you are, thorough hand washing after going to the toilet is a must,” he says. “In public toilets, any skin contact with surfaces should be kept to an absolute minimum as well.” He says using an alcoholic hand disinfectant instead of soap is also useful, but it’s only necessary in public toilets and not at home.

One more thing: Effetive hand washing does call for the right technique:

“Shorter is Better,” Revisited: A Physician-Patient Partnership on this Issue is Crucial

Brad Spellberg, MD. Chief Medical Officer and Professor of Clinical Medicine at the Los Angeles County-University of Southern California Medical Center.

Brad Spellberg, MD. Chief Medical Officer and Professor of Clinical Medicine at the Los Angeles County-University of Southern California Medical Center.

Two weeks ago, we ran an article titled “New Rule: When it Comes to the Length of Time You Should Take an Antibiotic, ‘Shorter is Better.’” The article was based on the writings of Brad Spellberg, MD, a leading world expert on infectious disease, that were recently published in JAMA Internal Medicine and Medscape News. Spellberg’s views on the subject have garnered an unprecedented amount of attention and so he responded today with a 3-page article in Medscape News that further clarifies his opinion. The short point is that he stands by what he says. Spellberg’s article can (and should) be read in full here, but there are two points we wish to emphasize. Both involve the ill-advised temptation of the patient to act as their own doctor. The bold-lettered questions were put to Dr. Spellberg by Medscape readers, typically health care professionals.

If patients do not complete their course of antibiotics, won’t they just take the leftovers in the future the next time they get sick?

Spellberg: “This is a risk, yes. But the fundamental point of busting the myth about taking antibiotics for long periods of time is that, based on many dozens of randomized clinical trials across many types of infections, giving shorter courses of therapy is effective. It will be rare that patients feel sufficiently better to stop their antibiotics before completing a short, 5-day course of antibiotics for cellulitis or community-acquired pneumonia, or 5-7 days for pyelonephritis, for example. Thus, giving evidenced-based, short-course therapies will reduce the risk of patients feeling better before completing their therapy and will minimize the number of pills they have left.

In contrast, if providers continue to prescribe 10- to 14-day courses of therapy, patients who feel better and stop taking the pills before completing the full course are more likely to end up with leftover pills.

At the time the provider gives the prescription to the patient, instructions should reiterate that the patient should not stop the medications without first consulting the provider.”

How can patients be trusted to stop their own therapies?

Spellberg: “I did not suggest that patients should stop their own therapies. I indicated that patients should be encouraged to reach out to their providers and discuss the possibility of stopping if they felt better before completing the prescribed course of therapy.

Medicine in the 21st century is a team sport. I would hope that all providers would encourage partnership with their patients as a means to optimize care outcomes. I would also hope that medicine has moved past the mid-20th century paternalism when doctors were promoted as being all-knowing and patients were expected to obey without questioning […] A dialogue between patient and provider can help us move towards more prudent use of antibiotics, particularly if we are educating both patients and providers about the dangers of overuse.”

Notice that Spellberg is putting the onus on the physician: “At the time the provider gives the prescription to the patient, instructions should reiterate that the patient should not stop the medications without first consulting the provider.” But as he also points out, 21st century medicine is a “team sport.” In other words, if your physician doesn’t say anything about stopping antibiotics early, then you should. You could also bring a copy of Spellberg’s articles for your doctor to look at. It would show your knowledge of the issue, your willingness to take greater responsibility for your health, and will help forge the kind of relationship you will have with your physician: i.e. the kind where you work with him or her.

 

 

Even Proper Use of Antibiotics Results in the Emergence of Superbugs

This is a bit nuanced but it nevertheless underscores the most crucial point about antibiotics: Never take them unless your physician is sure you have to. The reason? ALL antibiotic use — appropriate or inappropriate — results in the emergence of bacteria that are resistant to them.

It’s simply a myth, says infectious disease specialist Brad Spellberg, MD, to think “that if we could eliminate inappropriate antibiotic use, resistance would no longer develop …. The difference is that we can and should stop inappropriate use because it offers no benefit. In contrast, appropriate antibiotic use is necessary to reduce [sickness and death] from bacterial infections.” Therefore, “we must seek to eliminate inappropriate antibiotic use not because this will end emergence of resistance, but because it will slow it down without forgoing any meaningful benefit of antibiotic use.”

The following video makes the point, but subtly. In explaining how superbugs are created, it says we use antibiotics to kill harmful diseases like E. coli infections. But that over time bacteria fight back. As they get exposed to more and more antibiotics –– appropriately or inappropriately, in humans and in animals (as bugs from animals transfer to humans) — bacteria find ways to protect themselves. This is called resistance. Bacteria can be resistant to one antibiotic, several, or all of them; hence the term “superbug.”

One more thing. Since it’s the case that the greater the exposure to antibiotics the greater the likelihood of superbug emergence, it follows that when it comes to how long you should take a course of antibiotics, shorter is better.

The video also nicely explains the various ways that bugs fight our drugs: for example, by building an outer shield, by building pumps that kick out an antibiotic once it breaches the bugs shield, and so on.

New Rule: When it comes to the length of time you should take an antibiotic, “Shorter is Better”

Brad Spellberg, MD. Chief Medical Officer and Professor of Clinical Medicine at the Los Angeles County-University of Southern California Medical Center.

Brad Spellberg, MD. Chief Medical Officer and Professor of Clinical Medicine at the Los Angeles County-University of Southern California Medical Center.

Neither antibiotics nor the bacteria they aim to kill are what we thought they we were. To the contrary, it turns out that antibiotics have a huge downside and bacteria have a huge upside. As a consequence, our relationship to both has changed. With respect to antibiotics we want to flip the script from Hey doc, I want an antibiotic, to Hey doc, do I really need an antibiotic? And if they answer is Yes, you do need an antibiotic, then you want to take it for as short a time as possible.

Those are the words of Brad Spellberg, MD, a leading world authority on bacterial-driven infectious disease. Writing in Medscape News this month, Spellberg says it’s a myth that “patients must complete every dose of antibiotics prescribed, even after they feel better.” He explains:

Every randomized clinical trial that has ever compared short-course therapy with longer-course therapy … has found that shorter-course therapies are just as effective … This myth needs to be replaced by a new antibiotic mantra: ‘Shorter is better!’ Patients should be told that if they feel substantially better, with resolution of symptoms of infection, they should call the clinician to determine whether antibiotics can be stopped early. Clinicians should be receptive to this concept, and not fear customizing the duration of therapy.

Spellberg gave further details last month in his editorial in JAMA Internal Medicine. Comparing a shorter 5 day course of antibiotics versus the standard 10 day regimen, researchers found that the “30-day rates of clinical success were significantly higher for short-course versus standard therapy,” and that “the readmission rate was significantly lower,” for the short-course therapy.

Spellberg also points out the broader societal reason for limiting antibiotic use: “We’re having a public health crisis of antibiotic resistance not just in the US but internationally: as resistance rates keep rising, as new antibiotic development declines, we’re running into patients we can’t treat, who have infections we can’t treat for the first time since 1934, and that is a very frightening thing for the medical community to confront.”

The overall equation is this: The more you use antibiotics — in people and in animals —- the more the bugs get used to them and become immune. That’s just natural selection at work. Therefore, cautions Spellberg, “Don’t take antibiotics unless you really need them.” And if you do need them, “The shorter the better.”

The Medicinal Maggot

“I love [the heart sign] maggots” is emblazoned on a t-shirt lying on a chair in the office of Dr. Yamni Nigam, Associate Professor in Biomedical Science at the College of Human and Health Sciences at Swansea University, in the U.K. We had to first tell you how qualified she is before we mention that Dr. Nigam also founded the Swansea Maggot Research Group (yes, you read that right), in 2001, “which focuses on the medicinal maggot;” i.e., it’s wound healing and antimicrobial properties, the latter of which has garnered the Swansea team worldwide attention this month.

maggotsA little background. Battlefield surgeons have long understood the wound healing properties of the maggot. By inserting “tiny clean baby medicinal maggots” into a wound, the maggots feed on dead, infected tissue, clean away wound debris, eliminate infection, and appear to promote healthy tissue formation that helps the wound heal and close.

But it’s the anti-infection properties of the insect that offer the real promise. Just last month, for example, the United Nations announced that “resistance to antibiotics … is the greatest and most urgent global risk.” That’s because antibiotic resistant infections are believed to kill 700,000 people around the world each year; it’s estimated they’ll cause more deaths than cancer by 2050; and emerging evidence suggests that deaths by infection in the U.S. may well be their number one cause of death right now.

The basic problem is this: No new class of antibiotics have been discovered since 1987. This has given bacteria time to evolve mechanisms that defeat our drugs, thus giving rise to so-called super-bacteria such as MRSA, extensively drug-resistant TB, and the possibility of pan-resistant gonorrhea, to name just a few.

So why don’t we just come up with new antibiotics? Dr. Gerry Wright, an infectious disease expert at McMaster University, explains:

Antibiotics exist in nature, mostly in organisms found in the soil. Yes, you have to extract from these organisms the molecule with the antibiotic property, and that means scientists working in their labs. But the active ingredient that becomes the antibiotic is a naturally occurring one, and therein lies the rub: we have taken from nature all the molecules known to exist that have antibiotic properties. That’s why no new classes of antibiotics have been developed since the 80s; all we’ve done since then is find the same kind of molecules over and over again. In other words, we have long-since picked all the low-hanging fruit.

Back to Dr. Nigam and the anti-infection properties of maggots. Her team found that they secrete a substance that has “excellent antibiotic activity.” What they want to do now is: (1) isolate the active ingredient (as Alexander Fleming isolated penicillin from mold, in 1928) in these secretions that is killing the bacteria, and (2) test it against a range of pathogens to see which ones it’s effective against.

Notice the other bit of good news. Unlike with wound therapy, we won’t have to actually go to the pharmacy and fetch a bag of maggots. By isolating the antibiotic molecule of interest, then synthesizing it in the lab, it will come in the more palatable tablet form.

Here’s Dr. Nigam with further details:

If you have the cold or flu, antibiotics are not for you

October is the beginning of three important seasons: professional hockey, basketball — and the flu. Although flu season typically begins right about now, it really cranks up between December and March.

All told, it affects up to 20% of the U.S. population each year. More than 200,000 people are hospitalized­ with it, and more than 36,000 people die from it. It leaves us sniffling, sneezing, coughing, achy and generally feeling miserable for anywhere from a few days to a few weeks. It jeopardizes our ability to work and study, and we’re concerned about passing it on to others, especially family and coworkers.

The need for relief is therefore strong and so we often reach for that favorite catch-all remedy, an antibiotic.

 

flu

 

But we now know that’s a bad move, and for two reasons. An antibiotic (read: an anti-bacterial) has no efect whatsoever on a viral-driven illness. And that’s exactly what the flu is, an illness caused by the influenza virus — not by the influenza bacteria (there is no such thing).

In fact, the U.S. Centers for Disease Control reminds us that for the same reason, antibiotics cannot cure the common cold, are almost never needed for bronchitis, are not recommended to treat many ear infections, and are typically not needed to treat a sinus infection (sinusitis).

The second reason we don’t want an antibiotic is they have serious side effects.  A notable one is a Clostridium difficile infection (CDI): profuse diarrhea, abdominal pain and fever, that’s contracted by more than 250,000 people in the U.S. each year, and kills at least 14,000.

CDI normally occurs after antibiotic use. That’s because antibiotics are indiscriminate killers: they kill our beneficial bacteria too — the vast majority of our microorganisms — such as the ones that prevent infection. These infection-preventing bugs work in two ways. They use up nutrients thus making them unavailable to C. diff, or other disease-causing bugs, which are normally present in your gut, but in small numbers. And some of our normal microbiota make compounds that are toxic to C. diff. Thus with beneficial bugs out of the way, C. diff has food to eat, room to grow, and isn’t being knocked-off by toxic chemicals.

So if we don’t reach for an antibiotic to cure the flu, what do we do? The CDC says the best medicine is prevention: i.e., the flu shot. Should we nevertheless come down with the flu, the CDC also reminds us:

Most people with the flu have mild illness and do not need medical care or antiviral drugs. If you get sick with flu symptoms, in most cases, you should stay home and avoid contact with other people except to get medical care.

If, however, you have symptoms of flu and are in a high risk group, (including young children, people 65 and older, pregnant women and people with certain medical conditions), or are very sick or worried about your illness, contact your health care provider.

How we Think: The United Nations Addresses Silent Violence

At the United Nations in New York this week, as the heads of state of 140 nations gather to address the pressing issues of the day — growing armed conflict, terrorism, and the massive refugee crisis — they will also spend a full day confronting the harm caused by the emerging global crisis of antibiotic-resistant infections.

 

bullet-bacteria

 

One reason for the UN action is the sheer size of the number of people affected. The worldwide carnage of death caused by resistant infections is conservatively estimated at 700,000 people. In the US alone, the annual number is put at 23,000. But a compelling new investigation called “The Uncounted,” says that number grossly underestimates actual deaths — “a tiny fraction of the actual toll” — mainly because states simply do not record deaths by resistant infections, do so for only a few types of drug-resistant infections, or do not record consistently. Instead, the death will be listed as organ failure or simply as an infection that couldn’t be treated.

The near future is even more worrying. According to a widely-accepted study by the UK government, drug-resistant infections will kill an extra 10 million people a year worldwide – more than currently die from cancer – by 2050.

The second reason for the UN concern is less obvious but more insidious: Antibiotics have to be used in the treatment of most immunocompromised patients who, by definition, face a higher risk of infection. For example, burn victims, cancer patients undergoing chemotherapy, women undergoing c-sections, organ transplant patients, and even people undergoing routine surgery. And in all cases, the elderly, especially, are at risk. And so without effective antibiotics these procedures become even more dangerous.

Addressing this second issue three years ago the chief medical officer of Britain, Sally Davies MD, described it as “a ticking time bomb,” and that “the growing resistance to antibiotics should be ranked along with terrorism on a list of threats to the nation.”

The UN sees it that way too and thus their action today in putting harm caused by bacteria on equal footing with harm caused by bullets and bombs.

Notice that in all three cases the harm is broader than just death. Antibiotic-resistant infections don’t just kill you, they also do you violence: they scar, cause amputations, necessitate multiple surgeries, stays in the ICU, repeated hospitalizations, and cause infections that once “treated” can lay dormant and strike again at any time even years later. That translates into a lot of pain and suffering, for both the affected individual and for their families. In the US alone, for example, the Centers for Disease Control says at least 2,000,000 people contract resistant-infections every year.

So when Dr. Davies, head of the conservative British medical establishment, publicly states that resistant infections should be ranked with terrorism as a national threat is she exaggerating or does she have it about right?

If your loved-one has died, or is missing a limb, or has been traumatized, should it matter whether it was caused by a bullet, a bomb, or bacteria?

In marshaling our resources to combat harm should it matter any less that with bacteria the violence is silent and unseen?

Seeing Evolution in Action

It’s one thing to hear or read about evolution, and quite another thing to actually watch it in action. In fact, it’s pretty much impossible to do since by definition evolution occurs over generations, not a single lifetime. But a powerful new video from the Harvard Medical School lets us do just that: Watch bacteria as they evolve and move across a 4 foot long petri dish — it looks like a mini-football field — through increasing concentrations of an antibiotic that would ordinarily kill them. (Here is the full report from the Harvard Gazette.)

So why aren’t the bacteria killed by the drug? Because each time the bugs reach a higher concentration of antibiotic they stop, change their DNA (they mutate), thereby developing resistance to the drug. The mutants with the higher drug resistance reproduce and then continue their trek across the antibiotic field.

By the time they reach the middle of the field they have become resistant to 1,000 times as much antibiotic as would have killed them before their first mutation. In similar research at Harvard, bacteria developed resistance to 100,000 times as much antibiotic as would have killed them initially.

The real-world experiment took place over 11 days. The time-lapse video captures the whole process in 2 minutes.

There’s a few things to notice. When bacteria evolve they don’t remain stationary, they spread: here they moved a distance of 2 feet as they developed their drug resistance. Second, the bacteria continue to press forward in the direction of the drug that should kill them, rather than sitting still or heading to safer territory. It’s almost as if they want a fight! And third, the experiment shows us how easily bacteria evolve mutations that are resistant to extremely high concentrations of an antibiotic in just a short period of time.

It is because bacteria spread and mutate so easily — that is who they are — that the UN General Assembly has convened a one-day high-level meeting on Antimicrobial Resistance this-coming September 21 at the UN Headquarters in New York. Since seeing is believing, if the UN hasn’t seen the film we hope that someone brings this remarkable work to their attention.

Annals of Antibiotics: What has the human race gone and done this time?

You’d be forgiven for overlooking it: In the middle of a 6-page report (unfortunately, a subscription is required) about the large number of people using antibiotics without a prescription, is the rundown of where people are getting them:

“The major source of antibiotics used without a prescription was a store or pharmacy in the United States (40%), followed by antibiotics obtained from another country (24%), antibiotics obtained from a relative or friend (12%), antibiotics left over from previous prescriptions (12%), and veterinary antibiotics (4%).”

Dog confusedVeterinary meds? It wasn’t until I came across a CNN interview with one of the lead authors of the study, Dr. Barbara Trautner, that I understood the significance: We’re stealing antibiotics from our pets!

The researchers at the Baylor School of Medicine in Houston, Texas, didn’t anticipate this finding either. That’s why they didn’t even bother to ask about it in their survey. The only reason they discovered the “thefts” is that people who took the survey actually wrote it into their answers, saying it is one way they get off-prescription antibiotics.

Four percent of people using pet meds may not sound like much, but consider the math. The researchers randomly surveyed 400 people from 3 outpatient public health clinics in Harris County, Texas, and found that 5% of them were using nonprescription antibiotics. Harris County has an adult population of 3,285,000, and therefore, the researchers say, the 5% figure suggests that 131,400 primary care patients are using nonprescription antibiotics. And 4% of that figure — the percentage of people taking pet meds — is 5,256. Now multiply that number by the adult primary care patient population across the country — and you get a whopping number of people doing this.

And even that large number is likely to be an underestimate because, as mentioned, the survey didn’t provide for that answer, and because, quoting from the study, “Respondents might deny practicing self-medication, especially if they are aware that this is inappropriate behavior and if they are interviewed in a health care setting.”

Dr. Trautner warns us that we don’t want to be taking pet meds: “We metabolize things differently than animals do, and these drugs are formulated for animals.”

If a patient were ever to ask her about taking their pet’s medication, she said, she would compare it with how chocolate can be poisonous for dogs but fine for humans. Similarly, it may be dangerous for humans to take drugs that are created for an animals’ system.

And that’s on top of the fact that we don’t want to be taking (human) antibiotics in the first place without having seen a doctor because, as the study points out, we may not even need them. So without even any upside, the study points out that a number of things could go wrong, such as: an adverse drug reaction, a superinfection, the masking of an underlying infectious process, and harm to the bacteria in our body that we need for good health.

And should we actually require an antibiotic, we will need the right kind, taken at the right dosage level, at the right frequency, and for the right duration — none of which can be figured out through self-help.

Meanwhile, if our pets could talk we can imagine what they might say about our misusing antibiotics — especially if they caught us taking theirs … “Bad Human,” comes to mind.

 

 

 

 

 

The Smartest Guys in the Room

The Mayo Clinic just published Ten Things You Should Know About Antibiotic Resistance. The interesting thing about the article is that all ten things actually refer to just one thing: the mcr-1 gene.

Mcr-1 has become the gene of interest in antibiotic circles because (1) it has already conferred resistance on colistin, an antibiotic of last resort and (2) it’s promiscuous: it easily goes from one bacterium to the next leaving “superbugs” in its wake. The upshot, warns the CDC, is that this gypsy gene could turn all species of bacteria into superbugs thereby rendering our antibiotics useless.

Bacteria GT3

 

To really appreciate what’s happening here we turn to Columbia School of Medicine oncologist, and Pulitzer prize-winning author, Siddhartha Mukherjee MD, and his new and important book, The Gene: An Intimate History. He explains how genes “travel”:

Throughout the biological world genes generally travel vertically — i.e., from parents to children … the gene never leaves the living organism or cell [the body].

Rarely, though, genetic material can cross from one organism to another — not between parent and child, but between two unrelated strangers. This horizontal exchange of genes is called transformation. Even the word signals our astonishment: humans are accustomed to transmitting genetic information only through reproduction — but during transformation, one organism seems to metamorphose into another.

Transformation almost never occurs in mammals. But bacteria, which live on the rough edges of the biological world, can exchange genes horizontally. To fathom the strangeness of the event, imagine two friends, one blue eyed and one brown eyed, who go out for an evening stroll — and return with altered eye colors having exchanged genes.

 

In fact, it’s even stranger than that. Since bacteria exchange genes between different species, it would be as if, to continue Mukherjee’s analogy, we took our dog out for an evening stroll, and returned with altered eye colors having exchanged genes. Bacteria, writes Mukherjee, are “capable of trading genetic material like gossip, with scarcely an afterthought; free trade in genes [is] a hallmark of the biological world.”

So why are bacteria able to trade genes like gossip while we humans can only do it so cumbersomely through reproduction? For reasons of self-defense and species survival, says MIT-Harvard professor of medical biology, Eric Lander, PhD.

Bacteria have been around for some 3 billion years Lander reminds us. And for that whole time they have been at war with each other as well as with viruses. And what is a bacteria’s weapon of choice? Antibiotics: It is bacteria and other microorganisms that invented them (penicillin from mold, for example); we humans merely discovered their existence. And to defend against these antibiotics — to stay alive — bacteria have had to evolve various mechanisms to defeat them: what we call antibiotic resistance.

And not only have bacteria been perfecting and evolving these resistance mechanisms for 3 billion years, they turn over new generations — new genetic variants — every 20 – 25 minutes.

That’s why, Lander says, when it comes to genetic engineering we sit at the feet of bacteria — they are the experts. You see it in the contrast with us mortals: Our current version, H. sapien, has been around a mere 100,000 or so years. It takes a relative eternity, 20 – 25 years or so, to produce a new generation (of genetic variants), and we have zero ability to trade genes horizontally, i.e., between one person and another.

So back to mcr-1, an antibiotic weapon that has evolved in bacteria. What if it “escapes”? So far it has been found in E. coli in the gut of hospital patients and has defeated colistin, a “last resort” antibiotic.

But what if E. coli engages in genetic “free trade” and hands over its mcr-1 gene to one of our biggest threats, the common hospital and nursing home bug, MRSA, conferring even further antibiotic resistance on this superbug?

What then?

(Dr. Lander’s comments are available online at: https://www.edx.org/course/introduction-biology-secret-life-mitx-7-00x-3, Lecture 15: Cloning: Purifying a Gene.)

 

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