It’s All In The Delivery

As legendary comedian Jack Benny used to say, it’s not so much the joke but how you deliver it that makes all the difference. As it turns out there may be a similar rule at work in the delivery of antibiotics.

The question is this: When you take an antibiotic, whether orally or by IV, how does it know where to go? The infection could be anywhere in your body; in your lungs, your nose, your knee, your ankle, etc. So when you take the antibiotic, does it go directly to the trouble spot as if it were riding in a taxi, or does it behave more like a bus, stopping at several places along the way?

The answer is bus, apparently.

“When you give antibiotics by mouth or IV, it goes through your entire body. Everywhere in the body sees it and all the bacteria that’s already in your body see it,” says Fred Sweet, MD, co-founder of the Rockford, Illinois Spine Center.

This made Sweet curious. He wanted to know if direct versus indirect delivery of the antibiotic made a difference in the ability to treat infection. His theory was that each time the antibiotic bus stopped, it off-loaded some of its potency, therefore by the time it got to the trouble spot it wouldn’t be as effective.

So he brought in the rats and loaded them up with disease-causing bacteria. One group was administered the antibiotic vancomycin (the last resort antibiotic for MRSA) through an IV. The other group was given the same amount of vancomycin that was in the IV, but all of it was applied directly to the area of infection in powder form via a patch.

The result? For the rats that got the IV, 100 percent became infected. For the vancomycin powder, none became infected.

Dr. Sweet says there are two important implications. One, by changing how antibiotics are administered, physicians could possibly reduce the rates of infection after surgery nearly tenfold. Two, lessening the antibiotic load through direct application would mean having fewer antibiotic-resistant strains of bacteria thus slowing the rising plague of antibiotic resistance – which is predicted to cause more deaths than cancer by 2050..

Sweet thinks it’ll be 15 to 20 years before the technique could become the status quo, but added that from what he could tell, “If we can reduce these systemic antibiotics, I think within just a few years after that the number of resistant organisms will fall off the charts.”

So the next time your doctor prescribes an antibiotic be sure to ask her if there’s any way it can be delivered by “taxi”!

A “smart” watch designed to promote better hand hygiene in hospital workers was voted the second most important medical advance of 2014. But should it have been?

The heat is on to deal with the rising global plague of antibiotic resistance (ABR). A problem so severe that a report just released, commissioned by UK Prime Minister David Cameron, predicted it will cause more deaths than cancer by 2050. This past September, President Obama issued an Executive Order giving the full force of law to a National Strategy on Combating ABR. And the people that oversee the prestigious Longitude Prize in science have made available all of its US $15 million prize fund to come up with solutions.

So given the worldwide push to address ABR it perhaps shouldn’t surprise us that readers of the online medical journal Medscape – doctors, nurses, and scientists – voted a smart watch, designed to encourage better in-hospital hand hygiene, to be the second most important medical advance of 2014.

The Year in Medicine 2014: News That Made a Difference. Medscape, Dec. 15, 2014

It’s a smart idea to address the issue of healthcare worker hand hygiene: “The critical thing that all of us as healthcare providers can do is clean our hands between patient contact: and that is the number one, two, and three action to keep our patient safe,” says Dr. John Embil, Director of Infection Prevention and Control at Winnipeg’s Health Sciences Centre. That’s because the contaminated hands of healthcare workers are the most common vehicles of transmission in most settings.

But we may have a problem. As we said at the time of the smart watch announcement, it’s not just that it might not solve the problem of hospital-acquired infections — it could well make it worse. A sharp-eyed microbiologist pointed out to Medscape: “You know what I never see is a comment about the watch itself (any watch). You can’t sterilize a watch, you can’t even clean most very well. You could clean and sterilize the watch band, if you want to take the time to remove the watch from it. That watch sees many patients a month. That watch can catch all types of particles [germs] …”

Indeed, earlier in the year Medscape published the recommendations of The Society for Healthcare Epidemiology of America (SHEA) regarding what healthcare professionals should wear. Chief among the recommendations is what SHEA calls the Bare Below the Elbows (BBE) policy, something the Brits, for one, have long endorsed.

BBE means just that: nothing on the arms below the elbow, thus healthcare workers should wear short sleeves versus the traditional white lab coat, no wristwatch, and no jewelry. This ensures better hand and wrist hygiene, thereby minimizing the transfer of bacteria that might be contaminating HCWs attire.

Apparently BBE was a success in Britain as instances of MRSA cited on death certificates fell by 77 per cent after the policy was implemented.

So the right policy – or device – will make a difference. That makes sense. But we also have to be careful. Just because we call something “smart” doesn’t mean it is.

If only it were that easy.

A minute of your time: Here’s a 70 second video on how to stop the spread of infection in your home

In Wednesday’s blog we wrote about the disquieting fact that if you contract MRSA in the community – your home, say – it will return 40% of the time, either to the patient or to someone in their household. The main reason for this is that the bad bugs will remain on you, someone you share your home with, or on certain household surfaces.

The good news is that health authorities unanimously agree on the best way to prevent a recurrence: wash your hands – that’s the Golden Rule of infection prevention.

But there’s a problem. We mortals don’t know how to do it properly. For example, a study conducted in 2012 found that fecal strains were present on 26% of hands, with 11% of hands being comparable to a dirty toilet bowl in terms of the number of germs – yikes!

So here’s a video from our friends in Britain that shows us the right way to wash. I don’t know about you but I scored an F!

Handwashing best practice from Royal Society for Public Health on Vimeo.

MRSA – the house guest that just won’t leave

Doctors have long noticed something disquieting that happens after they successfully treat someone who contracted MRSA in the community – in their home, for example – it comes back about 40% of the time. Either to the patient or to someone in the patient’s household.

So researchers at the Harbor UCLA Medical Center looked into why MRSA is a repeat offender. They found a number of things that you’d expect and something that you wouldn’t.

The basic fact is this: in a home where someone had MRSA, and even though that person may now be better, MRSA bugs will remain in the house for 3 months or more, 50% of the time. So even though you’re now cured there’s still a coin flips chance that more of the little buggers will continue to hide out in your home for months.

Where in your home? On you, anyone that lives there, and certain household surfaces more than others.

Let’s begin with you. Let’s say a MRSA skin infection on your hand is successfully treated. Nonetheless, you may still carry MRSA elsewhere on your body, your nose in particular, and elsewhere on your skin.

You also shed the bug as you go about your business in the house. The most common off-loading places are the bathroom door handle, bathroom sink handle, toilet seat in the bathroom used most frequently by the patient, the patient’s hairbrush, kitchen counter top, kitchen sink handle, landline telephone, refrigerator door handle, television remote, and the favorite nonplush toy of any child, if it was your child that had MRSA.

The researchers found that when MRSA remained in the home at the 3 month mark it was most prevalent on the child’s favorite toy (ouch), bathroom door handles, and toilets.

The other people in the house will pick up the MRSA from these surfaces or from direct contact with the sick person.

So a good scrubbing of the house seems like the obvious answer but here’s where we run into a problem: the households that did the most cleaning were the same ones that had the most MRSA after 3 months!

So what can you do? You adapt the cop rule which says always watch the hands – no weapon can hurt you unless the bad guy has it in his hands. Similarly, medical authorities agree that a person’s hands are what most often carries and transmits the bad bugs – so always wash the hands.

As for how you get rid of your sick child’s favorite toy – well, proceed with caution!

On Antibiotics and our Responsibility to Question our Doctor about Them

As if being sick isn’t bad enough it now seems we have to do more than just tell our doctor what’s bothering us. In the context of antibiotics, at least, the new rule is that we have a responsibility to make sure our doctor is getting it right, according to highly regarded infectious disease specialist Brad Spellberg, MD.

In this video which runs less than 5 minutes, Dr. Spellberg lays out the issues around antibiotics beginning with what they are: “Antibiotics are just poisons that kill bacteria,” he says. And that fundamental fact – that they’re far from harmless – is what needs to guide our behavior. After the video we’ll discuss Spellberg’s crucial message.

So the point is that since antibiotics can hurt us the trick is to use them only when we have to – which is less often than we think.

Here’s Brad Spellberg on taking an antibiotic: “The key is you only take it when you have a bacterial infection. If you don’t have a bacterial infection and you take an antibiotic all you’re doing is killing off the good bacteria in and on your body and then you’re allowing resistant bacteria to set up shop. Next time you get an infection you now may be infected with the resistant bacteria.” (‘Resistant bacteria’ are those bugs that antibiotics have no effect on thus prolonging your illness, or worse.)

To ensure we take antibiotics only when our illness is bacterial and not viral – viruses cause the flu, most colds, sore throats, earaches, and a lot of bronchitis and pneumonia – Spellberg prescribes 2 rules for us to follow:

(1) “Should you question your doctor? Absolutely. What I would say is the first thing you say is, ‘Jeez Doc do I really need the antibiotic?’” And,

(2) “If the doctor’s clinical judgment is that you have a bacterial infection then you ask a second question, namely ‘Can you give me something that’s narrow? Do you have to give me something that’s so broad?’ Because different antibiotics kill different types of bacteria. You really want to hone in on the most likely bacterial cause.” In other words, you want an antibiotic that works like a laser not a hand grenade.

So when we’re sick and our energy’s down, when we can’t thinking straight and we feel pressure to get back to work and so on, the unfortunate fact is that just getting ourselves to the doctor isn’t enough. Once there we have to get it right, and, says Brad Spellberg, that involves asking his colleagues those two critical questions anytime we find ourselves in antibiotic territory.

And one more thing. As the Harvard School of Public Health cautions us, please stop asking for antibiotics!

The Antibiotic Reflex

Lost in the numerous daily stories about Ebola is this gem: When Thomas Duncan, the first Ebola patient to enter the U.S. undetected, first presented himself to a hospital in Dallas, he and his fiancée told staff more than once that he had been to Liberia. And even though his presenting symptoms were consistent with Ebola, that disease was never considered. Instead, he was diagnosed with a low-grade viral infection, given a prescription and sent home. Three days later he returned to the hospital in worse shape and was diagnosed with Ebola virus disease. The following week Thomas Duncan died.

Subsequent news stories about Mr. Duncan focused largely on two things: How on Earth did hospital workers not consider Ebola when he first appeared there (his family is understandably angry about this). And did he infect other people during that 3 days before he went back to the hospital and was finally admitted (so far, no).

But let’s back up. That prescription he was sent home with when he first went to the hospital – it was for an antibiotic. Never mind that they fumbled the Ebola ball, they also prescribed an antibiotic because they thought he had a low-grade viral infection. Which is like giving a fishing rod to a deer hunter: antibiotics treat bacterial-based infections only, not viral-based ones – so what were they thinking when they prescribed an antibiotic for a viral problem?

Thomas Duncan had the Ebola virus. But he was sent home from the hospital with an antibiotic.

Here’s the thing. Wrongly prescribing antibiotics happens far too often – about 40% of the time according to the US Centers for Disease Control: when presented with illness, the reflex to both seek and prescribe an antibiotic is common to both patient and doctor.

More often than not when you or your child have an ear ache, a sore throat, or cold, flu, or bronchitis-like symptoms, it is some virus that’s doing it to you. Nevertheless, people reflexively seek, and receive, antibiotics.

The physician reflex to over-prescribe is due to patient pressure, the fear patients will go elsewhere, not wanting to bother with lab tests, fear of being sued in the event that an antibiotic should indeed have been described, and, the big catch-all – even if antibiotics aren’t warranted, at least they’ll do no harm.

The assumption of no harm, however, has proven flat-out wrong. Because when you’re improperly prescribed an antibiotic two things happen: your bugs, not wanting to die, fight back and evolve into “superbugs” that are able to resist antibiotics in the future. So the next time you get a bacterial infection and really do need that prescription it won’t help you. Second, you don’t keep those superbugs to yourself. Instead, you spread them to the people closest to you, like family and friends. And like you – and because of you – should these people eventually need an antibiotic the chance of it not working has now increased.

We don’t know whether or not Mr. Duncan asked for an antibiotic. What we do know is that when he first went to the hospital the world in general and health care workers in particular were on notice (2d para below the Gov. Perry video) that a deadly viral outbreak in West Africa was just one flight away from our doorstep. Despite that, and despite having all the evidence it needed to treat Mr. Duncan as a possible Ebola case, the Dallas hospital antibiotic reflex sprang into action with dire consequences: Thomas Duncan died, his family are mourning, the hospital staff who got it wrong are surely not feeling good about themselves, and the nation is scared.

Preventing Infections With Universal Decolonization is the Smart Way to Extend the Useful Lifetime of Antibiotics

Eight days ago, the United States government rolled out its National Strategy to fight the growing crisis of antibiotic resistant bacteria. It is a crisis because at least 2 million Americans are severely wounded and at least 23,000 are left dead (about half are due to MRSA alone), every year, by infections that antibiotics no longer cure. As antibiotics continue to lose their usefulness, these numbers will grow.

MRSA (red) growing in the fibers of a wound bandage.

A key component of the White House Strategy is to try and extend the useful lifetimes of the antibiotics we have now by restricting their use – this is called “stewardship.” We’re familiar with the principle from our own lives.

For example, antibiotics are just like a community car: the more everybody uses it the more run down it gets until eventually it’s no good to anybody. So to extend the useful lifetime of the car restrict its use to necessary things like going to work, but no more drag racing and trips to the beach. With antibiotics, continue to use them to treat serious infections but stop prescribing them for things they don’t work on like the common cold and the flu, or because patients pressure you for them.

Back in July, when the president’s science advisors tabled their report that became the basis of the National Strategy, it received unanimous and enthusiastic approval. There was, however, one elegant and very subtle partial dissent from Christine Cassel, MD, a member of the President’s Council of Advisors on Science and Technology (PCAST).

Dr. Christine Cassel: Recognized by the NIH as one of the leading women leaders in science, and was the first woman to be President of the American College of Physicians and to be Chair of the American Board of Internal Medicine.

She began : “… [M]y congratulations … on a masterful and really thorough look at the original literature about this. I just wanted to – and this is not really I think in the report yet … – add to the definition of stewardship in two ways.  One is we think of stewardship as not prescribing antibiotics unnecessarily. But there’s another kind of stewardship which is reducing the risk of infection so the person doesn’t need the antibiotic … if you think about American hospitals … Medicare & Medicaid, and in particular the innovation center programs have incentives in place … to reduce HAIs, which is where some of the more dangerous ones are.

And we learned just in the last year that’s down 10%. You may say 10% is not a lot, 10% is half a million adverse events and 15,000 lives. Not to mention lots of dollars, but also lots of avoided need for antibiotics in the first place, and for exposing those bacteria to more antibiotics. So I think there’s a way in which looking at prevention is an important thing.” (My emphasis.) (Webcast, Antibiotic Resistance Report Discussion, 39 minute mark.)

Dr. Elizabeth Bryce: Her work embodies the philosophy of Dr. Cassel, and is supported by the latest research.

In other words – less elegantly – we need to double down on prevention. A prime example of prevention in action was just reported in The Journal of Hospital Infection. In a study led by Elizabeth Bryce, MD, the Vancouver General Hospital, concerned about the overuse of antibiotics yet needing to reduce infections that arise during surgery, replaced the standard antibiotic ointment with a universal decolonization method using a novel light-based disinfection therapy. They found a “significant reduction” in the overall surgical site infection rate and the greatest decreases were a 42% drop in orthopedic and spinal patients. (This work received an international innovation award.)

Given that one of the controls was the 12,387 surgery patients over the 4 years prior to the study who received the standard antibiotic therapy, the reduced infection numbers would have translated, over those years, into a lot of saved lives, needles trauma, and antibiotics that needn’t have been dispensed.

Indeed, as The Lancet reported yesterday, “findings from large randomised trials show that decolonisation of nasal carriers of S aureus, irrespective of sensitivity to meticillin, can reduce postoperative wound infections, and that universal decolonisation is more effective than targeted decolonisation on intensive care units.” (My emphasis.)

Nothing Spreads Like Fear: President Obama Sounds the Alarm on Antibiotic Resistance (And Gets a Little Help from Hollywood)

Antibiotic resistance (ABR) is now on the map in the United States. Last Thursday, President Obama issued an Executive Order giving the full force of law to a National Strategy on Combating Antibiotic Resistance. The Strategy adopted the report by the President’s Council of Advisors on Science and Technology (PCAST), Combating Antibiotic Resistance, which was unanimously and enthusiastically approved by its members at a public meeting July 11.

But why the need for a national strategy now; and, tellingly, why the rush to give it immediate legal effect by Executive Order?

Let’s begin in the frontlines of medicine: Doctors are flat-out scared – for their own health. They’re afraid to go to work at the hospital because they might catch an infectious disease which can’t be treated because antibiotics have become increasingly useless.

Dr. Barbara Murray: I'm scared. I don't want to go to the hospital.

Barbara Murray, MD, (who was not involved in the PCAST report), president of the Infectious Diseases Society of America, who practices in Houston, Texas, puts it this way: “I’ve been [treating infectious diseases] for years, and I’m scared,” she said. “I don’t want to go to the hospital. This is the first time I’ve felt this way.”

Eric Lander, PhD, founding director of the Broad Institute of MIT and Harvard, and co-chair of PCAST, agrees: “Members of PCAST have commented to me, ‘I now worry when I go to a hospital whether I might get an ABR infection.’” (Comments by Dr. Lander are from this Webcast, July 11, where he unveiled the PCAST report.)

The number of dead and wounded support Murray and Lander: At least 2 million people become severely infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections – half of those deaths due to MRSA alone. Many more people die from other conditions that were complicated by an antibiotic-resistant infection.

Second, ABR infections eviscerate the practice of medicine: “The safety of many modern medical procedures – including cancer chemotherapy, complex surgery, dialysis for renal disease, and organ transplantation – relies on effective antibiotics. These interventions become significantly more dangerous as bacterial resistance rises. Indeed, the World Health Organization recently warned that we risk entering a ‘post-antibiotic’ era unless we act now,” says Eric Lander.

Third, a post-antibiotic era would have devastating social consequences: “Bacteria for which there is no effective antibiotic pose a national security threat, says John Holdren, director of the White House Office of Science and Technology Policy.  “What we see … is the potential for [a] runaway spread of infection, which ultimately, as they go to very large scale, undermines social stability.” (Emphasis mine.)

Disease resulting in social instability to the degree that it morphs into a national security threat is the thesis of the film “Contagion,” starring Matt Damon. According to this United Nations/World Bank public health expert, the filmmakers get it exactly right and therefore “you should rush to see [it]” and witness “how, in the new phase of globalization—large-scale movements of people, goods, and services, and shortened geographical distances due to the dramatic growth and improvement of air transportation—the rapid spread of viruses and bacteria is a clear and present danger.”

In fact, ABR already has a global footprint: “The yearly death toll from antibiotic-resistant infections is roughly equivalent to one jumbo jet crash every week,” says John Rex, a member of the PCAST Working Group. As Thomas Frieden, director of the Centers for Disease Control and Preventions, says, “A disease outbreak anywhere is a risk everywhere.”

Dr. Eric Lander: It's just plain scary.

The way to deal with this global and growing threat of ABR is “… sort of simple at some level,” according to Dr. Lander. “There are really 3 things that have to be done … If we can surveil and see what’s going on, and we can slow down the rate at which we lose antibiotics, through stewardship, and speed up the rate at which we create new antibiotics or equivalent therapies … we stay ahead; we win.

But Lander warns us: “There is no permanent victory against microbes. If you use antibiotics, whether in human health care or in agriculture, you will over time see resistance. If we fail, if we fall behind in our stewardship, in our creation [of new antibiotics or equivalent therapies], or if we fail to surveil to understand what’s going on, it’s a very real risk to see a resurgence of what life looked like a century ago when we had bugs we could not treat. It’s a terrifying prospect. Now … it doesn’t help to do scare tactics around these things but it’s just plain scary.”

The tag-line of the film Contagion is “Nothing Spreads Like Fear.” How, as bad as these outbreaks are in and of themselves, our human responses to these types of public health crises make matters even worse.

So we hope the Obama Strategy works. We don’t want to wake up one day to find ourselves cast in a real-life Contagion: we don’t want life to imitate art – not in this case.

The Struggle for Survival

This 4 ½ minute animated video is just too good to pass over.

Engaging and viewer-friendly, it explains the biological basis – Darwin’s theory of natural selection – of the global crisis of antibiotic resistance.

It will either shore up what you know or, better yet, answer a question you might have. The crux of it begins at the 1:35 mark. Here’s the verbatim:

Just like any other organism, individual bacteria can undergo random mutations [changes]. Many of these mutations are harmful or useless but every now and then one comes along that gives its organism an edge in survival. And for a bacterium, a mutation making it resistant to a certain antibiotic gives quite the edge.

As the non-resistant bacteria are killed off which happens especially quickly in antibiotic rich environments like hospital there is more room and resources for the resistant ones to thrive, passing along the mutated genes that help them do so.” (Emphasis mine.)

We humans are a biological “organism” too. The beauty of natural selection is that it explains not just how bacteria are engaged in – and will win – their struggle to survive against the onslaught of antibiotics; but how we humans, too, struggle to survive against such things as disease, famine, and war.

Enjoy:

The Resistance Movement

Here’s a neat graphic on how antibiotic resistance happens, courtesy of the US Centers for Disease Control and Prevention. It nicely illustrates how the use of an antibiotic – or any antimicrobial, such as soaps and cleaners – does something quite unintended and counter-intuitive: it drives resistance.

A few brief comments:

Step 1. Bad to the bone: How did those resistant bugs get there in the first place? Aside from being the product of modern medicine, bacteria are “born” resistant. From Antarctic ice to the bottom of the ocean to deep underground caves – places where man has not yet set foot – scientists are finding bacteria that are already resistant to our drugs: they’re simply an ancient part of nature.

Step 2. Thanks for telling us: If antibiotics kill good bacteria that protect our body from infection, does that mean antibiotics leave us more vulnerable to infection? Yes, according to New York University infectious disease specialist Martin Blaser, MD. As he candidly puts it:  “Has any health-care professional ever told you that taking antibiotics would increase your susceptibility to infection?”

Step 3. Fast and furious: Humans take 20 – 30 years to produce a new generation; bugs do it in 20 – 30 minutes. So for example, by reproducing every 20 minutes a single E. coli bacterium can create 69 billion progeny in just 12 hours of growth. Kill one, and as many as 69 billion more can pop up in 12 hours! (Brad Spellberg, MD, Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them. (New York: Prometheus Books, 2009))

Step 4. Clever critters: Not only will the bug fight off the antibiotic you’re taking, penicillin say, but at the same time the bug will develop the ability to fight off other antibiotics too; for example, methicillin, amoxicillin, and tetracycline. The bug will then transfer the resistances it developed to those 4 antibiotics, to all his little bug buddies. This transfer will take place not just within a single species, E. coli to E. coli for example, but also between species, say from E. coli to Salmonella to Shigella (a bug that causes dysentery). In other words, when you take an antibiotic a whole other world of bugs that become resistant to multiple antibiotics develop inside you.

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