Feeling Confused? It could be the antibiotic

confused

 

Antibiotics are not who we thought they were: a wonder drug without consequences. For the last ten years or so evidence has been pouring out of our best institutions that antibiotics will harm you. For example, NYU’s Martin Blaser, MD, argues in his book Missing Microbes: How the Overuse of Antibiotics is Fueling Our Modern Plagues, that antibiotic use actually increases your risk for infection, especially over the long run, and for such other things as obesity, diabetes, asthma, food allergies, and esophageal reflux.

Now comes a report in Medscape News that antibiotics can compromise mental function as well. They can leave you feeling confused, sedated or delirius, and prone to seizures, mood changes, psychosis, and hallucinations. The elderly, especially, are at risk, as are those with central nervous system disorders, and renal dysfunction – both of which are more common in older people.

The incidence varies from a few isolated cases to, in one study, over 50% of elderly patients receiving high-dose clarithromycin (used to treat such common ailments as strep throat, pneumonia, and skin infections).

Researchers aren’t sure why this is. They think it may be due to the antibiotic adversely interacting with other medications the patient is on, or by interfering with neurotransmitter function.

Antibiotic-driven mental impairment is usually overlooked because of what psychologists call faulty attribution: attributing some effect or symptom to an easily recognized characteristic of a person – old age, say – rather than looking for some other, sometimes deeper, explanation. Fancy words for thinking that since this person is old and perhaps sick, that must be why they’re confused.

Here’s why this matters: By not considering the antibiotic as the real cause for mental impairment we’re missing an opportunity to correct it. For instance, by decreasing the drug dose, changing the antibiotic, or eliminating it when possible, researchers say that the confusion, etc. will usually resolve itself within 48 hours.

From Farm to Fork: How does giving antibiotics to livestock result in superbugs on your plate?

Of the more than 8 billion food animals — mostly cattle, pigs, chickens, and turkeys — raised for consumption in the U.S. every year, most receive some antibiotics during their lifetimes. The antibiotics are given for two reasons: to make the animals grow faster and to prevent them from getting sick (called ‘prophylactic use’). This confers a financial benefit to people who raise the animals. But with that benefit comes a hidden cost to the rest of us: more bacteria that are resistant to antibiotics. This makes infections harder, or even impossible, to treat. In other words, with more resistant bacteria in the environment, people remain sicker, longer.

But how does that work? How does putting antibiotics in the feed for cows on an industrial farm in Iowa increase the risk of an antibiotic resistant infection for someone living in Portland?

The basic equation is this: Antibiotics in, antibiotic resistant bugs (i.e. bacteria) out. When you expose bacteria – which line the gut of animals — to antibiotics, you create the risk that you kill off the susceptible bacteria and leave the resistant ones. The resistant ones quickly reproduce (e.g. a single E. coli bacterium can produce 69 billion progeny in just 12 hours) and fill up the spaces formerly occupied by the susceptible bacteria. During the slaughtering process these resistant bacteria enter the food chain and thus, eventually, our homes. The following graphic illustrates the point:

 

livestock

 

Infectious disease specialist Brad Spellberg, MD, Chief Medical Officer at the Los Angeles County-University of Southern California Medical Center, explains:

I think the real concern is not so much that there is residual antibiotics in the meat. The concern is that during the butchering process there is almost invariably some degree of contamination of bacteria in the meat. And those bacteria that were exposed to antibiotics are often antibiotic resistant. So the concern is transmission of antibiotic resistant bacteria, from the meat, from the excrement of the animals which is used to fertilize crops, which can get into ground water, which has been shown possibly to even be spread by airborne ways. So it’s more about the spread of bacteria that are bred to be resistant by exposure to the antibiotics.

 

Notice something. The issue is not that antibiotics get into the flesh of animals, which we then eat. Rather, it’s that the routine use of antibiotics in food animals increases the number of antibiotic resistant bacteria in the environment, which in turn increases the chance we’ll be made sick by them.

In the same interview, Spellberg warns us of a trick used by food producers. They’ll label the meat with something like “Antibiotics not used for growth promotion.” What’s missing, he says, is the likelihood that they’re still using them for prophylactic use. Giving healthy animals antibiotics is no more acceptable than giving healthy people antibiotics, Spellberg says, as the above graphic suggests.

So, about that Christmas turkey. Be sure to read the labels, but even that can be tricky. For example, the labels “Antibiotic Free” or “Natural” can be meaningless. Here’s a useful guide from Consumer Reports on what to look for. This brief video from the report tells you a lot:

Follow the Money

Dr. Brad Spellberg

Dr. Brad Spellberg

Antibiotics are different than other drugs in one crucial respect: the more you use them, the less effective they become. That’s because the target of antibiotics – bad bacteria – are living organisms, and as such they, like humans, also struggle to survive. When they reproduce, for example, (bacteria can produce 500,000 generations in just 1 human generation) they do so in ways that fight our drugs, rendering them increasingly ineffective. This is the problem of antibiotic resistance, that the United Nations recently declared to be “the greatest and most urgent global risk.”

What’s less well known is that the great majority (~80%) of all antibiotic use in the United States is in food animal agriculture, where they’re routinely given to the animals to speed their growth and to prevent them from getting sick, what the medical community calls ‘prophylactic use’. The question is, are those legitimate medical reasons to dispense antibiotics? Or are they simply economic expedients that leave the rest of us unnecessarily exposed to harm, i.e. to an infection from bacteria that is resistant to treatment by antibiotics? The answer, according to one leading expert, is decidedly the latter.

Brad Spellberg, MD, is the Chief Medical Officer at the Los Angeles County-University of Southern California Medical Center, one of the largest public hospitals in the United States. Dr. Spellberg still sees patients, teaches clinical medicine, runs a research lab, and is a prolific author: in addition to his ongoing contributions to the medical literature on his research and on the public policy of antibiotic resistance, he wrote the uniquely informative book Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them.

What’s not on Spellberg’s resume but what’s abundantly clear from listening to him is that he’s refreshingly plain spoken. In an interview with PRI’s Science Friday, Spellberg took on the issue of our routine use of antibiotics in food animal agriculture.

Inside The Van Ommering Dairy As U.S. Milk Production Declines

“Resistance continues to spread,” he says, “because we continue to so badly abuse antibiotics and overuse them …. Four times as many antibiotics are purchased for use in livestock than for use in human beings in the U.S. It is true that we cannot say definitively what proportion of resistant infections in humans is attributable to the use of antibiotics in animals. But we can say there is a contribution. And so societally, rather than getting into a debate on the minutiae of what proportion of this causes that, the point really is, since we know it contributes – and that’s a serious societal negative, or con – what is the pro that it offers society that should allow us to want to put up with that con?” Here’s where the plain talking Dr. Spellberg hits his stride (the bold emphases are mine):

And the pro really is, the people who use antibiotics in livestock believe that it allows them to make more money. So one group in society believes it can make more money by putting antibiotics into livestock – which does create a risk of harm to other people in society. Why our society chooses to tolerate that remains unclear to me.”

Should we as a society decide that a small economic advantage to a small group of people in our society is a reason we should accept [for] creating a risk of harm to everyone else in this society? Does that make sense from a societal policy perspective?

When patients die of resistant infections … people say well I don’t know what proportion of those infections are caused by routine use of antibiotics. But when 80% of our antibiotic use is in livestock we have to acknowledge that we’re saying it’s okay that we know people will be harmed, because we don’t know how many and because some people are making money off it. To me, that equation does not add up.

The thing is, this routine use of antibiotics in agriculture may not even be delivering the financial benefit we thought. Spellberg: “… there have already been multiple countries that have already banned growth promotion and routine prophylactic use of antibiotics. And not only have farmers not been harmed economically, they have expanded their herds after the ban …. Denmark had a marked expansion in its pig production after they did the ban.”

And so we continue to engage in this risky behavior because?

 

 

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?

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