Cigarette Smoking Enables MRSA

Dr. Laura E. Crotty Alexander. Her research establishes that cigarette smoking causes your MRSA bacteria to become way more virulent.

Let’s start with what we know. The number one way to legally ruin your health is to smoke cigarettes. However strong your body was before you took up the habit, you are only half as strong now because smoking weakens the immune system. So for example, smokers are two to four times more likely to develop pneumonia than non-smokers. You will get the flu more often and it will be more severe, and so on.

But Laura E. Crotty Alexander, M.D., assistant professor of medicine at the University of California, San Diego, had another idea. What if the problem isn’t just that cigarette smoke weakens the immune system, what if it actually makes your bacteria stronger? In other words, does cigarette smoking both weaken your body and strengthen your bad bugs at the same time?

Apparently so. Dr. Alexander tested her idea with MRSA. She found that when you inoculated mice who had MRSA in their lungs with cigarette smoke, that the MRSA bacteria had a survival rate four times greater than the MRSA in mice who weren’t given the cigarette smoke. Thus you are better able to establish infection in the body and cause more severe disease in mice who “smoked.”

And because of the booming market in e-cigarettes, Alexander wondered if e-cigarette vapor would have the same effect. So she ran parallel studies and found the same pattern of increased virulence: MRSA bacteria in mice inoculated with the vapor had a survival rate three-times greater than mice that weren’t inoculated with the cigarette vapor.

Dr.Alexander reasons that cigarette smoke puts stress on bacterial cells, just as it does on human cells, and that the bacteria respond by protecting and arming themselves, thus becoming less vulnerable to attack.

Smoking, then, is a triple-whammy. First, it weakens your immune system. Second, as Dr. Alexander’s work shows, it strengthens the bad bugs that invade your body. Thus, these first two cases increase the likelihood you’ll need an antibiotic. Third, a newly discovered side-effect of taking antibiotics is that it leaves you more vulnerable to infection because it kills not just your “bad” bugs, but you “good” ones too, those that help fight infection.

So then, what’s the true cost of that pack of cigarettes?

Annals of Evolution: From the Handshake to the Fist Bump as a Way to Prevent the Transmission of Disease in Hospitals

Seth Meyers and Amy Poehler demonstrating proper doctor patient contact. Who knew?

So it has come to this: in what conjures up images of a sketch on Saturday Night Live, the prestigious Journal of the American Medical Association this month recommended the banning of the handshake between doctors and patients. Instead, JAMA says, we should replace it with the fist bump, or a wave (think of the Queen as she passes by in her motorcade), by placing your hand on your heart, or bowing, or … well, this is where SNL could surely offer up something good.

What’s going on? It’s not just that health care workers’ hands are hotbeds for germs and so they end up spreading disease throughout the hospital, it’s also the fact that doctors (especially) and nurses aren’t following hand hygiene rules: JAMA reports compliance rates as low as 40%. One of the best known superbugs, MRSA, is alone estimated to kill around 19,000 people every year in the United States – far more than HIV and AIDS – and a similar number in Canada and Europe. And the problem is likely to get worse. Three weeks ago the World Health Organization released a landmark report saying we’re headed for a post-antibiotic era (i.e., we have overused antibiotics for so long now that germs have found ways to overcome them) in which common infections and minor injuries which have been treatable for decades can once again kill.

So because antibiotics are failing us, we’re scrambling to figure out other ways to prevent the spread of infectious disease. However, the proposed handshake ban does not look promising. In an online pole of healthcare workers seeking a response to the JAMA article, 54% of them said that they “Should not stop shaking hands” with their patients. Which is suspiciously close to the 60% who already don’t comply with existing hospital hand hygiene rules.

So if we can’t rely on health care workers who can we turn to? The JAMA article recommends “widespread media and educational efforts, as well as the development and promotion of effective alternatives,” as a way of overcoming resistance to their proposal to ban the handshake. And who are the Masters of the Media? Well, here’s the contact information for SNL. Since Seth Meyers and Amy Poehler were ahead of the curve on the fist bump, perhaps they and their colleagues could lend us a hand (again).

Pet-MRSA

Guess who else has MRSA?

We have just learned that our cats and dogs can get MRSA. And they get it not just from other animals but from you, their owner; and, should your pet contract MRSA from somewhere out there, it can then be passed on to you.

And it’s not just cats and dogs, it’s all “companion animals:” your pet rabbit, parrot, and turtle; horses and, um, your bats (bats?).

So says a study out of Cambridge University in England published this week. Researchers gathered MRSA samples from animals in veterinary hospitals throughout the United Kingdom over a 4 year period and compared them to human cases of MRSA.

Two other findings from the study are interesting because they also show similarity between us and our pets.

Even though there are hundreds of strains of MRSA in the environment, each veterinary hospital the researchers drew samples from had its own unique strain, “suggesting that as in human hospitals, MRSA can be readily transmitted in veterinary hospital settings.” And, “It’s a reminder that constant vigilance and high levels of hygiene are just as important when treating cats and dogs as with humans.” Thus proving once again that the hospital – whether human or animal – is an inherently dangerous place.

Second, just as with humans, the study says that it’s the vulnerable who are at risk. Healthy pets are not likely to become infected with MRSA from their human companions unless their health is already compromised. Conversely, vulnerable humans – the elderly, infants, or someone who is ill – are more at risk from becoming infected from a pet carrying MRSA.

One more thing. MRSA has traditionally been associated with hospitals, and now with this Cambridge study, veterinary hospitals. But U.S. research published last month makes it abundantly clear that MRSA should no longer be thought of as just a hospital-bound phenomenon – simply put, it has also taken root in our homes. Specifically, the researchers found that MRSA had become “endemic,” i.e. regularly found, in private homes, and that the home plays a critical role as “reservoirs for transmission and diversification.”

So as it turns out we share more than just the house with our cats and dogs, we also share each other’s germs; in this case, MRSA. It’s what we have suspected all along: they are part of the family.

Bioprospecting

The new age prospectors - bioprospectors - Drs. Lauren Paul and William Fenical went to the ocean floor to discover anthracimycin, which might be effective against MRSA and anthrax.

There’s an interesting report by the BBC about the recent discovery of a potentially new antibiotic, anthracimycin, that “seems to be” effective against MRSA and anthrax. The antibiotic was extracted from bacteria that had been collected from the bottom of the Pacific Ocean off the coast of California.

But what are scientists doing making the grand effort to dig up bacteria buried in muddy ocean floors? They call it “bioprospecting,” which is the search in far flung places (think of prospecting for gold in the 1800s) like caves, rain forests, and ocean floors, for natural occurring organisms that have medicinal properties. In this case the naturally occurring organism is a kind of bacteria whose medicinal property fights MRSA and anthrax.

The reasons scientists are engaged in bioprospecting in the first place are important to understand. It’s not because it offers them an exciting life and makes for good conversation over a round of beer. It’s because, contrary to conventional thought, most drugs are not made from scratch in the lab. They’re found in nature and “refined” for popular use in the lab. For example, most antibiotics are extracted from tiny creatures found in the soil. And if you look at the 10 best-selling drugs last year – for things like cancer, arthritis, heart disease, and so on – you find that 7 of those drugs come from nature, not the lab.

But there’s a problem. Why are infectious disease scientists having to scour the ends of the earth to find compounds with antibiotic properties? If most of them are found in the soil, why can’t they just go and dig up the backyard? The answer is because the backyard has been picked clean over a roughly 40 year period beginning in the 1930s. This explains 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 antibiotic fruit.

Which leads us to the next problem: antibiotic resistance. Since we’ve been using variations of the same antibiotics for decades now, the bad bugs have figured out ways to beat these drugs thereby rendering them useless. So much so that the World Health Organization announced last week that we’re on the cusp of a worldwide post-antibiotic era in which even common infections and minor injuries which have been treatable for decades can once again kill.

Hence the urgent need for our scientists to pack up their tools and head for some deep cave in an Amazon rain forest to find us some brand new molecule with antibiotic properties. After all, these hidden organisms haven’t been exposed to antibiotic drugs so we know they couldn’t possibly have developed resistance to them … right?

Well that was the theory and a pretty reasonable one at that – until yesterday when we got some bad news: it turns out that most of these exotically located organisms cut off from the rest of the world are in fact already resistant to our antibiotics; it’s as if they were just “born” that way, millions of years ago.

The researchers looked at data from 71 places around the world, everywhere from Antarctic ice to the bottom of the ocean and found antibiotic resistance in every location. A similar study carried out by Dr. Gerry Wright, a self-proclaimed bioprospector and microbiologist at McMaster University in Ontario, dug up bacteria in a New Mexico cave stretching some 1,600 feet underground. He found that, as reported in the New York Times, most of the bacteria were resistant to some antibiotic and others could resist 14 commercially available antibiotics. In other words, antibiotic-resistant bacteria are not just the product of modern medicine, they’re an ancient part of nature.

So if we’ve pretty much found all the molecules in nature that have antibiotic properties and the once promising hope of bioprospecting is not only coming up empty but is uncovering a world full of organisms already resistant to our antibiotics where does that leave us? In polite terms we’ll just say we’re not sure, other than to observe that no antibiotic cavalry seems likely to be coming to our rescue any time soon.

As for the discovery of anthracimycin, that rare and recent bioprospecting success story – it’s still undergoing testing to see if it can be developed as a drug for general use.

We Were Warned

Britain's Chief Medical Officer, Dame Sally Davies, warned us a year and a half ago of a post-antibiotic era that would involve an "apocalyptic scenario."

We have now been officially warned by the World Health Organization of a coming post-antibiotic era where our ability to perform surgery and treat cancer is severely compromised, and where common infections and minor injuries which have been treatable for decades can once again kill.

But how is the average person supposed to evaluate such a claim? Is it to be believed in whole or in part or is it hyperbole? After all, we live in an Age of Suspicion where the pathology of politics distorts even the sciences, from the debate on man-made climate change to whether human genes can be patented, thus turning them into  private property and vehicles for corporate profit.

One way to evaluate the WHO claim of a coming post-antibiotic era is to understand that they’re not saying anything new; rather, they have merely – and finally – put their seal of approval to a position that has been staked out for years by leading scientists around the world.

For example, Britain’s most senior medical adviser, Dame Sally Davies, has warned that the rise in drug-resistant diseases could trigger a national emergency comparable to a catastrophic terrorist attack, pandemic flu or major coastal flooding. She said the threat from infections that are resistant to frontline antibiotics is so serious that the issue should be added to the government’s national risk register of civil emergencies. She describes what she calls an “apocalyptic scenario” where people going for simple operations die of routine infections “because we have run out of antibiotics.” And she has been saying this since at least January, 2013.

In the United States, the Centers for Disease Control & Prevention issued Antibiotic resistance threats in the United States, 2013, a first-ever snapshot of the burden and threats posed by the antibiotic-resistant germs having the most impact on human health. The report begins with these introductory remarks: “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.”

In Canada, the Chief Public Health Officer’s Report on the State of Public Health, 2013, called infectious disease, “the never-ending threat,” noting that more than 200,000 patients get infections every year while receiving healthcare in Canada; more than 8,000 of these patients die as a result, and that these numbers are rising. For example, the healthcare-associated MRSA rate increased more than 1,000% from 1995 to 2009 (the last year for which numbers are available).

Sir Alexander Fleming, the guy who ushered in the antibiotic age, warned us right from the start not to become addicted to antibiotics.

Canadian scientists are even more pointed. For example, Dr. Bob Hancock, Professor and Canada Research Chair in Microbiology at the University of British Columbia, in an interview this March on the CBC science program Quirks and Quarks, was asked by the host what he thought the odds are of facing a worst-case scenario of a life “beyond antibiotics.” His reply: “I would say right now, unless something changes it looks inevitable.

Let’s remember, these scientists and their organizations are notoriously cautious entities. For example, when the CDC Threat Report says that 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections, they emphasize that these are the “minimum numbers.”

Let’s end at the very beginning with the words of an internationally renowned scientist given in his Nobel Lecture: “But I would like to sound one note of warning … It is not difficult to make microbes resistant to penicillin … The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily … by exposing his microbes to … the drug make them resistant.”

These are the words of warning of none other than Sir Alexander Fleming, the scientist who discovered penicillin and who launched the antibiotic era.

The year was 1945.

So yes, we were warned.

Low-Hanging Fruit

What do you do after you've picked all the low-hanging fruit?

The ground shifted beneath our feet yesterday with the release of the World Health Organization Report warning us that we’re entering a post-antibiotic era in which common infections and minor injuries which have been treatable for decades can once again kill. That’s because antibiotics have become increasingly ineffective due to chronic overuse over the past 70 years in both medicine and agriculture. It’s simply evolution at work: the more you try to kill a microbe with antibiotics the more it will evolve to not be killed by it. Hence the development of MRSA, which has hundreds of known mutations and has even begun to defeat drugs of last resort which have previously been able to treat it – but no more.

So the WHO report understandably received worldwide attention yesterday. A common thread throughout the coverage was to offer this solution: “[G]overnments have to find ways to encourage research and development into new antibiotics … given that pharmaceutical companies don’t have a financial incentive to develop new drugs for infections that just last for a week or two,” as the CBC reported on the National.

However, the assumption that new antibiotics can be found given sufficient time, money, and government support turns out to be a tragically flawed one because there may not be any more antibiotics to be discovered.

Dr. Gerry Wright, an infectious disease expert at McMaster University, in an interview with CBC’s science program Quirks and Quarks, explains the problem this way: 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.

These magic molecules that exist in nature and exhibit antibiotic properties are hard to come by because they have to be able to do something very special: they have to kill bacterial cells but not human cells – they have to be toxic to bacteria but not toxic to us. Remember, bacteria are “us” in the sense that we have 10 times as many naturally occurring bacterial cells in our body than we do human cells. So the line between destroying a bacterial cell wall versus a human cell wall is a fine one. That’s why antibiotics of “last resort” are given that ominous sounding name – because they attack us along with the bacteria, and so it becomes a war of attrition within to see which side is left standing.

So if all the low-hanging antibiotic fruit has been picked, where does that leave us? How about “Bio-prospecting” – looking for antibiotic molecules in remote locations like caves, rain forests, and the ocean floor. That’s something Dr. Wright does and he concedes nothing is on the horizon.

So where that really leaves us is turning to prevention strategies through better hygiene and other infection control practices such as decolonization, especially in health-care facilities. The sooner we plant those seeds, the sooner we bear our treatment fruit of the future.

Landmark WHO Report: We’re Entering A Post-Antibiotic Era

What happens when antibiotics no longer work?

The World Health Organization released a major report today that says we’re headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill

In real-world terms it goes like this. It will start with something as simple as a blister on the foot. Staphylococcus bacteria will infiltrate the open wound causing infection. The staph is of a kind that’s resistant to antibiotics (MRSA), so surgery is required to remove that part of the foot that’s infected. Nerves are permanently damaged leaving the patient in pain for the rest of their life. This isn’t a hypothetical case, it’s what Carl Nicks of pro football’s Tampa Bay Buccaneers is going through right now, and it has put his career in jeopardy.

The case of Mr. Nicks illustrates the most crucial point: medicine these days is wrapped around the ability to control infection by the use of antibiotics, without which much of what we do – and take for granted – gets put on hold.

For example, you’re restricted in your ability to treat cancer because the basic nature of cancer therapy is to knock out the immune response. So if you have no antibiotics to protect you, you’re left more susceptible to bacterial infection.

Surgery is impaired because antibiotics prevent patients from succumbing to bacteria. Thus the ability to do organ transplants, hip replacements, and so on is compromised.

Not to mention the inability to treat pneumonia; and the everyday, cuts and scratches that offer bacteria the chance to enter the body and cause an infection.

The inability to do all these things because antibiotics have been rendered useless is what is meant by a “post-antibiotic” era. And it will change the way we live.

So how did we get there? In a word – evolution: microbes such as the staphylococcus aureus bacterium have pressure put on them from the overuse of antibiotics drugs. The microbes respond to that by surviving and not being killed by these antibiotics so therefore they evolve in ways that make them resistant.

The WHO report says this threat of antibiotic resistance is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country … and the implications will be devastating.

Antibiotic resistance is the number one problem in global health. It’s a topic that has many related issues and is getting global media coverage today by outlets such as the BBC, CTV, the Guardian, and Salon.

We will spend the rest of the week digging deeper into the issue.

Dirty Money

As it turns out, "filthy lucre" is indeed filthy.

It has long been recognized in public health circles that socioeconomic status affects health (the link is to an interesting discussion on why it’s often called the “Titanic Effect”). Anyway, the rule is simple: the greater your wealth the greater your health. That’s because wealthier people have access to better healthcare options and can more easily afford related health care costs, such as co-payments, transportation to and from care, and optional or elective tests and procedures. And wealthier people live in safer communities, have healthier food options, can better afford healthier lifestyles such as engaging in proper exercise, and so on.

Now comes a new study adds an interesting wrinkle to this: namely, that money itself – paper currency and coins – carry pathogens. That’s because our hands are full of germs and so everything we handle, money included, can potentially become contaminated.

The most common contaminants on the money were found to be Staphylococcus aureus, E. coli (a food pathogen), Klebsiella (causes pneumonia, urinary tract infections, diarrhea, and soft tissue infections), and Enterobacter (commonly affects the immunocompromised and those on mechanical ventilation).

The study also found that banknotes recovered from hospitals were highly contaminated by Staphylococcus aureus; that bacterial isolates from currency exhibited a high incidence of antibiotic resistance, such as MRSA; and that S. aureus can survive for months on the surface of the currency.

And there was one other finding that was especially interesting because it says that pathogens, too, have their own way of conforming to the wealth rule: i.e. pathogens treat different currencies differently. Specifically, (1) the lower the economic status of a country, the greater the concentration of bacteria on the currency, (2) the lower the denomination of the note the more likely it was to be contaminated; for example, 94% of US $1 bills had bacterial contamination, and (3) the longer the paper bill remains in circulation, the more opportunity there is for it to become contaminated.

So what do you do after you handle dirty money? The researchers recommend that you wash your hands, especially when simultaneously handling food and money.

Either that, or you launder the money.

Are Hospitals Spreading MRSA Back Into the Community?

This question was posed in some really important research published this week which was the focus of yesterday’s blog. But one aspect of the study – hospital to community transmission – is so important it warrants separate consideration.

The researchers were trying to figure out why there was a MRSA outbreak in homes in 2 boroughs of New York City. They documented how it was, in part, brought in from other states; but it was another area of the study that caught my eye, as reported in the journal Nature: “’Further studies are needed to evaluate how hospitals might be involved in spreading the bacteria back into the community,’ say the study authors.”

How so? Well, hospitals might be spreading MRSA back into the community due to their policy of not treating MRSA-colonized patients. Instead, they and their MRSA are sent home – which means the patient has an increased risk of getting infected, and that the patient becomes a vector for spreading the bug, especially to their family. The issue is set out in full here.

But at the time that was written I did not have a study (1) saying MRSA is prevalent in private homes, and is spread from person to person in those homes, and (2) that put front and center the issue that hospitals may well be contributing to the prevalence of community-based MRSA.

Now we have that evidence.

“The Times They Are A-Changin’” – and so is MRSA.

The many faces of MRSA: they change over time and place and the newer ones are increasingly virulent and drug resistant.

We tend to think of MRSA as a single organism that remains the same over time. But that’s far from the truth and it’s also dangerously misleading. The fact is, there are hundreds of different strains of MRSA – and counting. Which strains predominate will change over time and also over place – not just between hospitals and communities but also between countries. What’s more – and this is key – many of the newer strains are more drug resistant and virulent (toxic) than earlier strains thus making MRSA harder, or even impossible, to treat.

So says Dr. David Coleman at Trinity College, Dublin, whose research team studied a large sample of sporadically occurring MRSA in patients in hospitals over a decade.

There are 2 inter-related issues at work here. One is that society is literally on the move like never before and as we reported last month, bugs don’t have borders. As Professor Coleman puts it: “It is not a phenomenon unique to Ireland,” because “international travel increases the mixing of different community strains, helping to cause the very high level of [MRSA] diversity.”

The second issue has to do with how MRSA, like all microbes, respond to antibiotics, which literally are out to capture and kill them. So MRSA, like a bad guy on the run and to avoid being caught will not only change its identity it may change its “weaponry” too – knowing that the heat is on it will upgrade from a pistol to a machine gun.

And this is exactly what happened to a 35 year old male hospital patient in Brazil, where a new and highly resistant form of MRSA infected the man’s blood, killing him. (The case was reported in the New England Journal of Medicine last week but a more readable version can be found here.)

So why did he die?  He became infected only after he was admitted to the hospital. The staff knew it was MRSA and so they began treating him timely with a number of drugs including the powerful MRSA antibiotic of last resort, vancomycin. So what happened? The patient developed resistant to the vancomycin while he was being treated with it – that’s how fast MRSA can change its identity. And it upgraded its “weaponry” too, changing into an aggressive and lethal bloodstream infection.

Which brings us back to the first issue of microbe mobility. “If the vancomycin-resistant superbug were to break out, it wouldn’t stay confined to one region or country,” says Dr. Cesar Arias, a professor of medicine at the University of Texas and one of the researchers of the study in the NEJM. “Bugs don’t have passports. They don’t respect borders. They can travel very easily. And, in fact, this has been shown for MRSA.”

And so the times, like MRSA, are a-changin’.

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