Category: MRSA

Side Effects: The shorter is better rule may also apply to one type of breast cancer therapy

The new rule in antibiotic therapy is the shorter the duration the better: “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.” And crucially, shorter courses reduce your risk of adverse side effects such as life-threatening allergic reactions, super infections, nausea and rash.

It turns out that this very same idea may apply with equal force to cancer therapy. NPR reports that a new study out of Cambridge University found women who were diagnosed with early-stage HER2-positive breast cancer did just as well with 6 months of treatment with the drug Herceptin (trastuzumab) as did women who received a 12-month course of this treatment. Specifically, survival was nearly identical after five years. And women with the shorter treatment also had fewer side-effects such as heart damage, fatigue and pain.

So why on earth would we be doubling up on treatment length when it doesn’t help and it exposes us to serious health risks and greater costs? NPR:

This kind of question — of whether the standard, established dose could be reduced to good effect — is one that drug manufacturers don’t go out of their way to answer once a drug is on the market, because the result could reduce the amount of drugs they sell.

The American Society of Clinical Oncology told NPR they found the Cambridge study “quite compelling” and “it is likely that it will signal a shift” in how doctors prescribe this drug to their early-stage breast cancer patients.

Here’s a brief video and accompanying article that nicely explain Herceptin therapy and HER2-breast cancer. Notice at the end of the video the long list of side effects that the drug therapy exposes you to. It’s precisely this that the ‘shorter is better’ mantra is trying to avoid.

 

How Herceptin Works: the Mechanism of Action from Breastcancer.org on Vimeo.

Doctors work under a lot of pressure and it can undermine their decision-making. The better we understand that pressure, the better our care.

Why would our best and brightest get it wrong half the time? As many as 1 in every 2 antibiotics prescribed in the U.S. are unnecessary or inappropriate. Is that because doctors are incompetent, or don’t care if they get it right? Or is something else going on?

That’s what researchers at the University of Pennsylvania wanted to know and so they went directly to clinicians and asked them. And what they found is that these “well-intentioned individuals” work under crippling emotional pressure which in turn drives poor decision making. Lead investigator Julia Szymczak, PhD:

One of the most common and repeated themes that occurred across the data … was … this constant emotional experience of fear; fear of something happening to the patient, fear of being wrong, fear of being sued. And to alleviate that fear they [doctors] said, ‘we use antibiotics to comfort ourselves.’

In the following video and accompanying article, Dr. Szymczak explains how the burden of caring for sick people when too often doctors don’t know what’s wrong, and providing that care under the watchful eye of colleagues, patients and their families, triggers a “very strong emotional reaction to do something.” And how that ‘something’ invariably translates into “quickly put[ting] a patient on a broad-spectrum antibiotic in an almost automatic and unquestioned way.”

Szymczak’s insightful work isn’t about blame; it’s a plea for understanding, premised on the idea that understanding begins the road to better treatment – writ large. Because her work immediately invites a crucial question: If the pressures she identifies are indeed systemic as the physicians themselves say they are, then shouldn’t we be asking if medical decision-making is being compromised across the board?

 

Routinely giving antibiotics to preemies can cause immediate, lifelong harm

Preemie 6

 

If you’re wondering whether antibiotics have a dark side, take a look at a report in Science this month called A Delicate Balance – Routinely giving antibiotics to premature babies may do more harm than good.

Preemies are the hospital’s most vulnerable patients. Sometimes weighing less than a pound and protected in cases of clear plastic, preterm birth is the most common cause of death of infants worldwide.

Their underdeveloped immune system is one problem. But it’s compounded by the fact that we’re often fooled by what appears to be good health: “Infants and neonates have a relatively stable system that can maintain itself through quite a bit of stress but ultimately it can fail – suddenly and catastrophically,” says Greg Large, MD, a family physician at the Western Medical Clinic in Brandon, Manitoba.

That’s why, according to Science, the vast majority of the nearly half-million infants born prematurely in the United States are routinely given antibiotics even without evidence of infection, and why they are kept on the drugs even after blood tests say they aren’t sick. Neonatologists do so because they “are unable to shake the fear that a baby may die on their watch.”

Yet this understandable practice of blanket antibiotic dosing is being challenged because “We’re beginning to recognize that the risk of giving that antibiotic may actually outweigh the benefit,” says Josef Neu, a neonatologist at the University of Florida in Gainesville.

The risk is that antibiotics wipe out an infant’s developing gut microbiome: trillions of microbes that synthesize vitamins, prime our immune systems and produce just as many neurotransmitters as the brain. Because preemies “may never truly catch up” the concern is we’re promoting a host of problems later in life such as asthma, autoimmune disease, and adult and even childhood obesity.

But serious problems arise immediately as well. Antibiotics can increase babies’ risk of the very afflictions the drugs aim to protect against – such as fungal infections, late-onset sepsis, and a deadly intestinal disorder called necrotizing enterocolitis. In fact, a seminal 2009 study found that “each additional day of antibiotics significantly increased the odds that a preemie would develop necrotizing enterocolitis or die.”

Moreover, 2- and 3-year-olds with prior antibiotic exposure developed a “who’s-who list of bad gut pathogens … resistant to every antibiotic … tested…. Their guts had basically become a breeding ground for antibiotic-resistant microorganisms … potentially endangering not only themselves, but also the wider population.”

UF’s Dr. Neu hopes to provide hard evidence of these risks by conducting a clinical trial: A random selection of 150 premature infants who would have been given antibiotics automatically will instead be placed in a nontreatment control group. For 2 years, his team will track the microbiomes and health of the preemies. Some of Neu’s colleagues feel uneasy about withholding antibiotics, but he says answers are needed: “What can we do to use these antibiotics more intelligently?”

I asked Dr. Large, a father of 3, if he would enroll his child in such a study. After a long pause he said “I would be willing to consider it. You just have to watch’em real close.”

 

Wrong Directions: Pathogens are up, specialists are down

The hot paper we reported on yesterday said that you can reduce the 30-day mortality rate for hospitalized MRSA patients by more than half (from 23% to 10%) if you involve an infectious disease specialist in your care (along with your GP). According to the study’s lead author, having an ID consult is an absolute game changer: If there were a medicine that had such a dramatic effect, he said, “every patient would be on it.”

But there’s a problem – a lack of ID specialists. This has been reported on for several years now and various reasons are offered. Then just last week a report in Medscape addressed the issue again, identifying yet another reason for the shortage – a difficult diagnostic coding system used for tracking antibiotic-resistant infections is missing nearly 9 out of every 10 cases. And this has a domino effect: Grossly understating the problem of resistant infections means funding for research and treatment isn’t provided, which in turn “creates a strong disincentive for physicians to specialize in infectious diseases.”

So the researchers used a different method for identifying resistant infections – looking at evidence of treatment failure, defined as use of two or more therapeutic subclasses of prescription antibiotics to treat a bacterial infection – and found an 88% increase in the number of cases.

 

Rise in ABR infections

 

Looking at this new data over a 14-year period beginning in 2000, the authors conclude:

  • Rates of antibiotic-resistant infections have roughly doubled since 2002. “That while the overall number of [susceptible] bacterial infections remained relatively constant between 2002 and 2014, rising from 13.5 million to 14.3 million annually, the proportion that were antibiotic resistant rose dramatically, from 5.2% to 11.0%.”
  • The cost of care now tops $2 billion per year in the US. “Antibiotic resistance added $1,383 to the cost of treating a patient with a bacterial infection. Using an estimate of the number of such infections in 2014, this amounts to a national cost of $2.2 billion annually.”

They admit that even this is an undercount because they didn’t include data for institutionalized patients, such as those in nursing homes (a huge source of resistant infections), other long-term care facilities, prisons, and military or Veterans Affairs facilities, all of which typically have higher rates of antibiotic-resistant infections. Nor did the analysis include children, who, they say, “are the primary carriers of methicillin-resistant Staphylococcus aureus and pneumococcus in the community.”

In other words, resistant infections are on the rise, yet the very people who are able to cut by half the 30-day mortality rate in MRSA cases are on a relative decline, especially when you factor in one huge demographic: the aging thus increasingly vulnerable-to-disease baby boomer generation.

 

Hospital patients with a MRSA infection require an infectious disease specialist

ID consult

 

If you’re a hospital patient under the care of a GP and have a MRSA infection, your chance of dying or being sent to hospice within a month is just over 23% – that’s almost 1 in every 4 patients. And further, within the first year of a MRSA infection that risk of mortality goes up to 44% – approaching 1 in every 2 patients.

But here’s the crucial bit: You can cut the risk of death in the first month by more than half; and the 1-year mortality figure by 13% – if you involve an infectious disease specialist in your care (in addition to your primary care doctor).

That’s the new and important finding by researchers at the Washington University School of Medicine in St. Louis, Missouri, in their 10-year retrospective study involving 4,214 adult patients in 13 academic medical center hospitals (they have sicker patients) in and around St. Louis.

In addition to the MRSA numbers, they also found that an ID consultation was associated with similar reductions in 30-day and 1-year mortality for drug-resistant Enterobacteriaceae infections (a family of microbes that includes E. coli and Salmonella) and for drug-resistant polymicrobial infections – infections caused by more than one bug.

Lead author of the study, Jason Burnham, MD, offered his perspective in an interview with Consumer Reports: If there were a medicine that had such a dramatic effect “every patient would be on it.”

He explains why you should be seen by an infectious disease doctor:

They do more than simply suggest that a particular antibiotic would work well for particular bacteria. While a nonspecialist can, for example, write you a prescription for an infection you pick up in the hospital, an infectious-disease doctor can help you launch a more comprehensive treatment plan – using multiple antibiotics in combination when needed, draining abscesses where infections can hide, removing infected central lines, checking for pernicious complications such as endocarditis (an infection of the heart valves), and monitoring you for potential side effects to potent antibiotics.

But there’s a problem of invisibilty.

As patient advocate Lisa McGiffert told Consume Reports, people with resistant infections often “don’t know to ask for a specialist…. [as they] probably don’t even know these kinds of doctors exist.” But “[i]f you have a heart condition, you’re going to want a cardiologist. This is the same kind of thing.”

And so asking for a specialist, McGiffert says, could “make a difference in a person living or dying.”

 

 

 

 

 

 

 

 

 

 

 

When a skin infection is as deadly as a heart attack

In an epic webinar last week on why it’s important to focus on antibiotic stewardship and why it’s important to save these “frankly miraculous therapeutics” (antibiotics), Brad Spellberg, MD, Chief Medical Officer at the Los Angeles County-University of Southern California Medical Center, began his address by reminding us, using a true story, of how bad things were before we had these miracle drugs.

In December of 1942 a healthy 4-year old girl tripped while going downstairs. She cut her cheek and developed a Staphlococcal infection on her face which spread to her blood. The infection on her face spread relentlessly over 3 days. The evening of the third night her face and neck became so swollen she couldn’t swallow her own saliva. On the morning of the fourth day when she was gasping for breath her parents in a panic rushed her to the Mayo Clinic. This is what she looked like on arrival at the hospital. These are the actual photographs taken on admission to the Mayo Clinic.

Spellberg W3

Her admitting physician told her parents she would be dead within 2 days and there wasn’t anything anybody could do to stop that. Imagine, said Spellberg, being told that about your 4-year old who 4 days earlier had been perfectly well.

But she was very lucky because the treating doctor was one of the very few people who could access penicillin before the end of WWll. It was all going to the army. But he had experimental vials in his lab and so he grabbed those vials and began to treat her with penicillin. And you can see in the bottom pictures what she looked like after a few days of penicillin therapy.

Antibiotics, Spellberg emphasized, are the only drugs, the only medical intervention, that can take a girl that looks like this on the top panel and turn them into a patient who looks like the little girl on the bottom panels, in just a few days.

In fact, in the pre-antibiotic era a simple cellulitis (a skin infection) had an 11% mortality rate – an 11% chance of death. By comparison, a 1988 study found that death by myocardial infarction (a heart attack) was 12%. Which means, Spellberg says:

[T]hat the death rate from cellulitis in the pre-antibiotic era was the same as the death rate from myocardial infarction. Who remembers that? Who remembers that a simple skin infection was as deadly as an MI? That the reduction in death you get when using a beta-lactam to treat a skin infection is far greater than the reduction in deaths you get from aspirin or clot-busting drug treatment of MI.

Just think about how insane that is compared to what we see today with effective therapy. And the reduction of death that you got with penicillin was immediate and dramatic.

Drug resistance was always with us, but Spellberg warns it has caught up with us now that we’ve stopped coming out with the next generation of “gorillacillin.” So much so that with respect to some gram-negative pathogens:

We have organisms that have become resistant to almost all available therapies and, in some cases, quite literally to all available therapies.… [T]he reality is…. [w]e are making things up. We are putting together regimens that we know will not work individually and hoping by some magical combination phenomena that we can treat an otherwise untreatable infection. And that’s not the way medicine is supposed to be in the 21st century …. This is 1934 medicine. We have set the clock back 80 years to the pre-antibiotic era.

An era when a skin infection was as deadly as a heart attack.

The Long Arm of the Flu Virus

Flu report

 

Last Friday’s weekly flu report from the Centers for Disease Control (above) told us what we didn’t want to hear:

… that influenza activity is still on the rise overall. In fact, we may be on track to beat some recent records … we could potentially see several more weeks of activity … one out of 10 people who died in the week that has passed died from influenza or pneumonia … these viruses are often linked to more severe illness, especially among children and people age 65 and older.

 

The link to more severe illness can refer to the onset secondary infections, meaning the virus “opens the floodgates for … bacteria to invade their body,” as happened to this woman with MRSA. An example of this writ large is the influenza pandemic of 1918-1919 (the so-called Spanish Flu) where “the majority of deaths were not caused by the influenza virus.… Instead, most victims succumbed to bacterial pneumonia following influenza virus infection.”

Second, the flu can exhaust healthcare resources allowing superbugs to breach infection control barriers. For example, this month’s VRE outbreak at an Ontario hospital was attributed to the virus:

We had a flood of influenza cases into the hospital and emergency department, and also there were a number of sister institutions that ended up having influenza outbreaks which meant long-term care nursing homes couldn’t take patients, chronic care facilities couldn’t take patients from our hospital so we had a back-up of patients and basically it put a lot of stress on our infection control practices.

 

The third way the flu virus reaches into our lives is more subtle: we’ll prescribe the wrong treatment for it – namely, an antibiotic – and suffer a severe side effect as a result. For example, the painful and often deadly C. difficile-caused diarrhea; irregular heartbeats and sudden death; tendon rupture; and drug interactions that have people end up in the emergency room.

This is especially so for seniors: As the CBC reports, a recent study found that nearly half of 185,014 Canadians aged 66 or older who go to a family doctor about a cold or other non-bacterial respiratory infection leave with a prescription for an unnecessary antibiotic.

It may sound trite but it’s also true: If you have the cold or flu, antibiotics are not for you. Here’s a chart from the CDC that nicely summarizes things:

 

ABX relevance 4

 

 

 

 

 

 

 

What’s a Scientist?

BlackberryMeet Simon Meehan, an engaging 15-year old high school student from County Cork, Ireland, who was just awarded the top prize at the prestigious BT Young Scientist & Technology Exhibition, beating out 1,100 students involved in some 550 projects.

Simon’s interest is in how we can use common plants to treat antibiotic-resistant infections driven by ubiquitous bugs such as Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa.

His project is called “Investigation of the antimicrobial effects of both aerial [leaf] and root parts of selected plants against Staphylococcus aureus.” It looked at nine locally sourced plants such as asparagus, nettles and blackberries to test for the presence of chemicals which could potentially be used to control bacterial infection. In the end, he found two plants that did the trick, leaf and fruit extracts from the common blackberry plant (pictured), and a root extract from Mare’s tail. In Simon’s words:

My major conclusion is that I have found an organic non-toxic and locally abundant herb that has antioxidant and antimicrobial effect against MRSA … Staphylococcus aureus, and also Pseudomonas aeruginosa, a potentially deadly bug, especially for those with cystic fibrosis.

I have found an antibiotic that is organic, non-toxic and antimicrobial. And this is in the blackberry of all plants. I mean, you hear of people going to the Amazonian Rainforest, whereas [I] found something outside [my] back door. And I feel, without disrespecting the scientific community too much, there should be some conclusion drawn from this – that we are over-thinking science in too many ways.

 

Not content to leave it there, Simon wants to extend his research by testing the plant extracts on other bacteria. And he also wants to explore his curious finding that there was “a major difference” in the effectiveness of the blackberry plant depending on the time of year he picked it, June versus August.

Because of Simon’s youthfulness we might conclude that he will be a future force in science. But given what his rigorous research has already uncovered and the further work he has planned, we may want to think about his observation in the video below:

“Science appears to be seen in a much more sophisticated way than necessary. And I feel that we don’t sometimes see what is right in front of our eyes.” (Italics added.)

Mr. Simon Meehan is now waiting on a patent for his extraction method for the blackberry bush that could lead to its widespread use as an antibiotic.

 

When you use antibiotics you affect the lives of others

The Government of Canada announced this week that farmers – from the small farm to the increasingly prevalent industrial scale “factory farms” – will need a prescription before they can use antibiotics on their food-producing animals. The new rule takes effect this coming December.

Ottawa grounds the need for the rule on:

[T]he emergence of so-called ‘superbugs’ … one of the most significant health threats to Canadians.… [where] The overuse or inappropriate use of antibiotics contributes to the development of [antibiotic resistance] in people and animals. Examples [of inappropriate use] include giving antibiotics to … animals when they are not needed.

Targeting agriculture stops the disease threat at its source. As the chart below demonstrates, bad bugs created on the farm make their way through the environment into your home and community.

Notice the fine print: the use of antibiotics by one person (or group) can adversely affect the health of another person because (1) antibiotics give rise to harder to treat illness and (2) the antibiotics themselves become less effective over time.

No other drug does this. For example, taking aspirin, insulin, or hypertension medication only affects the person taking them and the drugs retain their potency over generations.

Commenting on the government’s new rule and the unique societal feature of antibiotics, John Prescott, retired professor of pathobiology at the University of Guelph, told the CBC that “Farmers need to see this as part of their societal obligation. They need to understand why it’s being done, accept it, embrace it and work with it.”

Prescott notes that it’s not just farmers who have this obligation to others to use antibiotics appropriately: “Everybody has to reduce their use of antibiotics to preserve the effectiveness of antibiotics. This is agriculture stepping up to the plate.” (Emphasis added.)

Livestock 3

 

 

 

 

A Plea for Plain Language

Tara Smith, PhD, Professor of Epidemiology at the Kent State University College of Public Health.

Tara Smith, PhD, Professor of Epidemiology at the Kent State University College of Public Health.

Be honest. When was the last time you discussed the rising tide of antibiotic-resistant disease, say over coffee at work or over dinner at home?

You know, the issue the World Health Organization says is “a global health crisis … [where] interventions, like organ transplantation, joint replacement, cancer chemotherapy, and care of preterm infants, will become more difficult or even too dangerous to undertake.”

Here’s the thing: It’s not so much that we don’t discuss it – it’s that we can’t discuss it – because we don’t really know what antibiotic resistance means.

That’s what a survey of over 10,000 people conducted by the World Health Organization told us just two years ago: Up to 75% of the people were found to be “confused about this major threat to public health and do not understand how to prevent it from growing.”

So is there a way to engage the public in a conversation about a critical health issue that the majority of us are “confused” about?

Kent State’s Dr. Tara Smith did something refreshingly unique with a paper she published last month – in an open access journal – about the unexpected prevalence of MRSA on public beaches in Ohio. She added this:

Plain Language Summary

Previous studies have examined the presence of the bacterium Staphylococcus aureus on marine beaches, but a rigorous study of freshwater beaches was lacking. We investigated S. aureus presence and proximity to wastewater treatment plants on 10 beaches in Northeast Ohio. We found S. aureus in 22.8% of our samples (64/280). Prevalence was higher in summer than fall. Prevalence was also higher in sites with wastewater treatment plants close to the beaches.

 

Plain Language/Plain English summaries are making their way into legal reporting too. For instance, the preeminent website for the U.S. Supreme Court is SCOTUSblog. One of its attractions is its Plain English/Cases Made Simple feature. It’s by no means law for dummies: it’s legally reasoned analysis of important cases before the court – without the jargon. For example, in “Wedding Cakes v. Religious Beliefs?: In Plain English,” you’ll find their breakdown of the pending and highly important “cake case” which asks the question, Can a maker of wedding cakes refuse service to a gay couple because of his religious belief that marriage should be limited to opposite-sex couples?

A few years ago in front of a live audience at the Harvard School of Public Health, Stuart Levy, MD, a pioneer in the field of antibiotic-resistant infections, made a rather bold statement. He said that if he had $800,000 to spend on fighting infectious disease, he’d spend $700,000 of it on educating the community because “They need to be a partner in using antibiotics properly.” A co-panelist agreed, saying “We’re all in this together.”

We’re all in this together but unfortunately we’re not all on board. So maybe the thinking of Dr. Levy, and the examples of Dr. Smith and and the U.S. Supreme Court reporters publishing plain language summaries, are worth a serious look.

Because with the ever-increasing presence of genetics (what is the difference between a gene, DNA, and a chromosome?) in science and medicine, this issue will only become more important over time.

 

 

 

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