ABR is a Problem because we are not creating enough new antibiotics to deal with ever changing superbugs

The New England Journal of Medicine, in a 2010 study, found that “health care providers prescribed 258.0 million courses of antibiotics in 2010, or 833 prescriptions per 1000 persons”1. Over 80% of the population of the US was given a prescription for antibiotics in the year of 2010—there is no indication for a decrease in these numbers for following years. Moreover, this study found that an estimated 50% of these prescriptions were unnecessary. This overprescribing of antibiotics further strengthens the selective pressure on bacterial populations escalating the problem of antibiotic resistance or ABR. With an increase in ABR, new and alternative antibiotics must be employed to cure infections until improved methods are utilized that remedy the problem of ABR. However, the development of new antibiotics may see a bleak future.

Discovering and employing new antibiotics is slowing down. According to Brad Spellberg of the David Geffen School of Medicine at UCLA, only 2 types of antibiotics were approved from 2008 to 2012 compared to the 16 approved from 1983 to 19872. The slowdown of antibiotic research and approval is attributed to three factors: scientific, economic and regulatory2. Spellberg explains, “Drug screens for new antibiotics tend to re-discover the same lead compounds over and over again”. Finding unique antibiotic solutions is now an arduous and also expensive process—the astronomical cost of developing and approving new antibiotics provides little incentive for companies to take part in.

The current regulatory system relevant to antibiotics put in place by the FDA also inhibits the speed and efficiency at which antibiotics can be approved. The FDA approves antibiotics based on “disease state one at a time”2. This causes “companies [to] spend $100 million for a phase III program and as a result capture as an indication only one slice of the pie.”2. The problematic structure of this regulatory system strongly contributes to the overall difficulty in developing new antibiotics.

With the increasing difficulty of developing antibiotics and the associated high cost, prospecting investors in this field have little incentive to pursue this venture. New alternatives to antibiotics must be found in order to fight disease for those in need, provide economic incentive for researchers and investors, and remedy the ever-increasing threat of ABR.

85-year-old man in Brazil develops multi-drug resistant infection

Many conditions and diseases throughout the world are under-reported and worsen until the patient is forced to address the problem. Severe complications are often easily prevented if detected early. Diabetes is a disease many people live with for prolonged periods of time before proper diagnosis. For those who don’t know, Diabetes Mellitus affects the hormone insulin which influences how sugar is absorbed and transported in the body. Since sugar is the major source of fuel for all cells in the body, defects its regulation can cause major health complications, even organ failure.

A case study written by the Diabetic Foot and Ankle Journal investigated an incident of an 85-year-old man in Brazil admitted to the Emergency Room because of  “an ankle injury and a foot non-healing ulcer sustained from a drill accident 2 months prior to his visit in our hospital”. Lab results showed the ulcer colonized by several species of multi-drug resistant bacteria contributing to irreversible damage to the man’s foot. The man eventually had to undergo a lower-limb amputation. The hospital also did several blood tests, which diagnosed the man with Diabetes Mellitus—information unknown to him before the hospital visit. This case study shows the importance of education of diseases like Diabetes Mellitus as well as the dangers and virulence of multi-drug resistant bacteria.

This man had been living with Diabetes for 13 years prior to this hospital visit and had no knowledge he possessed the disease and had no means to manage and treat the complications associated with Diabetes Mellitus. His blood-work taken at the hospital showed deficiency in almost every respect—hematocrit, white blood cell, granulocyte, counts were well out of their normal ranges. Because of this, his immune system must have been greatly suppressed at the time of diagnosis as well as years prior. If his condition was detected and properly managed, health complications, like this serious infection, could have been prevented or at least mitigated. This shows the importance of education and awareness of inhibiting and life-threatening diseases.

Many aspects of the serious infection this man incurred could have been prevented by wound care as well as means to treat Diabetes. Since Diabetes Mellitus is known to be immunosuppressive, it was very hard for this man’s body to fight off the serious infection in his foot ulcer. The case study cited the man’s “denial and lack of knowledge regarding his disease and the importance of proper foot care”. The absence of education and knowledge led to a very serious, but perhaps preventable health complication.

In addition to an emphasis on health education and knowledge, this case study also demonstrated the virulence and robustness of multi-drug resistant bacteria. Many species of bacteria in biofilm—structures containing bacteria connected to a surface and to each other as well as polymeric extracellular substances. Bacteria in biofilms are known to increase the bacteria’s rate of survival in a certain environment. This makes them more resistant to treatment and contributes to the antibiotic resistance problem; many bacteria found in biofilm are resistant to different types of antibiotics. The bacteria in the man’s foot ulcer was resistant to a wide array of antibiotics and made wound healing virtually impossible—amputation was recommended in order to prevent the infection from spreading. The case study stresses the importance of antibiotic surveillance in order to mitigate the antibiotic resistance problem in order to make proper and effective treatment decisions easier for healthcare workers.

This case study is an example of two important things. Knowledge and educations in regards to health is of absolute importance especially in developing countries. Furthermore, multi-drug resistant bacteria make it incredibly difficult for healthcare workers to treat infection. Many of the complications incurred by this man could have been prevented or at lease mitigated; however, these complications also led to a significantly reduced quality of life. While not explored explicitly in this case study, a suppressed immune system over 13 years most likely led to prolonged sickness and additional health complications. In addition, the amputation doctors had to perform will inhibit the man’s way of life for the remainder of his years. Hopefully increased awareness through case studies like these in conjunction with further analysis, research and development will lead to not only more effective ways in educating and diagnosing people, but also means to treat cases like these.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384988/

The Burn Wound Problem

Burn wounds are prevalent issue in urgent care centers around the world. This issue can affect a wide array of people from household accidents to combat wounds in the battlefield. Burn patients’ exposed and injured tissue is prone to many harmful bacteria and subsequent infections. According to the American Burn Association, 486,000 people in 2016 have sought out treatment for burn wounds—a statistic that may be close to home.1 However, this problem is even more pronounced in countries elsewhere, especially where treatment is difficult to acquire and wound care is hard to carry out.  In order to better understand this problem, we should take a look at what exactly is causing complications involving burn wounds, as well as possible methods in treating burn wounds.

Most burn wound infections are caused by a handful of common organisms. A 6-year study reviewing the records of the US Army Institute of Surgical Research Burn Center found that the most common organisms infection burn patients were Acinetobacter baumanniiPseudomonas aeruginosa  , Klebsiella pneumonia and Staphylococcus aureus.2 Many of the organisms found in burn wounds tend to be multi-drug resistant making effective treatment difficult for healthcare workers.

Since the exposed tissue of burn patients is prone to harmful pathogens, most burn patients are known to experience some type of infection, especially in developing countries. A 2007 study conducted by the Ahvaz Jundi-Shapour University of Medical Sciences found that 76.9% of patients in a burn hospital acquired a burn-related infection. Of these patients, 72.5% possessed primary wound infection, 18.6% blood stream infection, and 8.9% urinary tract infection.3 While the study did not explicitly investigate the cause of high rates of infection, it stresses the need to develop methods in preventing and treating these burns. Because of the vulnerable nature of these burns, hospitals and healthcare workers need to take extra precautions with sanitation and wound surveillance; however, how will hospitals tackle multi-drug resistant bacteria?

Burn infections are known to be resistant to many types of antibiotics. This makes treatment difficult and prolonged and can lead to more severe secondary complications. However, new methods in treatment may tackle this problem. An experiment conducted by Tianhong et al of the American Society for Microbiology employed photodynamic therapy on burn infections in mice.4 For those who don’t know, antimicrobial photodynamic therapy (aPDT) involves using energetic non-thermal light in conjunction with a photosensitizer solution to battle infection. A clinical isolate of A. baumannii from Iraq was applied on burn surfaces on the mice, and aPDT was employed on the wound either directly after infection occurred, or 1 and 2 days after infection occurred.4 The study found a 3-log unit loss of bacterial infection when aPDT was employed directly after infection occurred and a 1.7-log unit loss of bacterial infection when aPDT was employed 1 to 2 days after infection.4 The experiment also mentioned, “that PDT did not lead to the inhibition of wound healing.” The results from this experiment demonstrate the effectiveness in employing aPDT as a treatment for burn infections.

From the study discussed above,  aPDT has the potential to be an effective method in treating burn infections. An important point to take away from the experiment is the timing of the aPDT treatment—it was most effective the sooner it was carried out on the burn wound. This is important for patients to seek out medical assistance when acquiring a burn-related injury so that they may be monitored for infection and treatment is administered right away. This would aid greatly both on the infection prevention front and the treatment front.

Burn wounds and infections are a serious issue facing people around the world. The culprits of infection have become resistant to many forms of conventional antibiotics, and thus, new methods must be developed and employed. While this article discussed specific examples in developing countries and military hospitals, it is imperative to know that these issues exist close to home. Burns can happen anywhere at home or in the workplace, and multi-drug resistant bacteria are prevalent everywhere. Everyone can benefit from knowing about the issue and aiding in the development of prevention and treatment.

References:
1http://www.ameriburn.org/resources_factsheet.php

2http://www.burnsjournal.com/article/S0305-4179(09)00521-X/abstract

3http://search.proquest.com/openview/809eb975465fd106336f1bea71ffd5ab/1?pq-origsite=gscholar

4http://aac.asm.org/content/53/9/3929.short

Ondine Biomedical Goes to China!

Ondine Biomedical is proud to announce its expansion into the China market. We are doing so by forming a Joint Venture with Henan Zhengzhou Zhenghe Medical Device Co., Ltd. of China, called PDT Medical.

The JV calls for Ondine to provide the technical know-how for its two products that PDT Medical will be manufacturing: MRSAid and Periowave. Zhenghe will be responsible for the product registration with the China Food and Drug Administration, plus the manufacturing, distribution and sale of the product in China.

We would also like to thank the province of British Columbia’s International Trade and Investment Office for East China. They were instrumental in this deal by bringing the two parties together in Vancouver, and acting throughout as an independent third party vouching for the bona-fides of us and Zhenge: Thank you so much Ellen Xin for your great work!

Here is a sample of what Ondine is bringing to China:

Myths About Antibiotics

Here’s a very useful primer on antibiotics published just last week in Consumer Reports. It’s so good we’re leaving it in the original and will add just a few words, which are these: The crucial Myths are numbers 1 and 2, and we’ve written in greater detail on these subjects before.

With respect to Myth 1 – Antibiotics Can Cure Colds and the Flu, further information can be found here, A Message from the Harvard School of Public Health: Please Stop Asking for Antibiotics.

With Respect to Myth 2 – Antibiotics Have Few Side Effects, we’d refer you to our report on the work of New York University’s Martin Blaser, MD, Can Antibiotics Increase Your Chance of Getting an Infection?

And for those that want the video version of the 5 Myths, here you go:

Myth 1. They Can Cure Colds and the Flu:

Not so. Antibiotics work against only bacterial infections, not viral ones such as colds, the flu, most sore throats, and many sinus and ear infections.

Myth 2. They Have Few Side Effects:

Almost 1 in 5 emergency-room visits for drug side effects stems from antibiotics. In children, the drugs are the leading cause of such visits. Those side effects include diarrhea, yeast infections, and in rare cases, nerve damage, torn tendons, and allergic reactions that include rashes, swelling of the face or throat, and breathing problems. And the drugs can kill off good bacteria, increasing the risk of some infections, including C. difficile. At least 250,000 people a year now develop C. diff. infections linked to antibiotic use, and 14,000 die as a result.

Myth 3. A ‘Full Course’ Lasts at Least a Week:

Not always. A shorter course can work for some infections, such as certain urinary tract, ear, and sinus infections. So ask your doctor for the shortest course and lowest dose of antibiotics necessary to treat your infection

Myth 4. It’s Okay to Take Leftover Medication:

Nope. First, you may not need an antibiotic at all. And if you do, the leftovers may not be the right type or dose for your infection. Taking them could allow the growth of harmful and resistant bacteria. Return unused antibiotics to the pharmacy or mix them with coffee grounds or cat litter and toss in the trash.

Myth 5. All Bacterial Infections Require Drugs:

Mild ones sometimes clear up on their own. So ask your doctor whether you could try waiting it out.

The Devil and the Angels are in the Details: Healthcare Worker Personal Protective Equipment, Designed to Prevent the Spread of Infection, is Failing Us – And the Problem isn’t With the Equipment

The continuing Ebola outbreak in West Africa has so far infected more than 800 doctors and nurses, killing close to 500 of them, despite the fact that they wore personal protective equipment (PPE) – gowns, gloves, goggles, and masks.

The problem isn’t confined to Africa. Cases where PPE-wearing nurses have contracted Ebola in top notch US and Spanish hospitals reveals an underlying and tricky issue: The equipment isn’t protecting us, it’s because of improper use not the gear itself, and the problem extends to bad bugs in general, not just to Ebola.

PPEJust last week at a medical conference in Orlando, Florida, researchers presented a study which found that contamination occurred almost 50% of the time in PPE-wearing US healthcare workers.

Myreen Tomas, MD, and her colleagues at the Cleveland Veterans Affairs Medical Center, enlisted in their study, nurses, nurses aids, phlebotomists, radiology technicians, physical and occupational therapists, and other healthcare personnel who use PPE and interact with patients.

In 435 simulations they had them remove gowns and gloves that were “contaminated” with a fluorescent lotion. They used black light to identify sites on skin and clothing contaminated with the lotion.

“We were very surprised by what we found,” said Dr. Thomas: Of the 435 PPE removal simulations, there were 200 instances (46%) of contamination, mostly to the hands and neck.

Here’s the good news. If healthcare workers paid attention to the details of using PPE, Dr. Thomas says they could reduce contamination rates to as low as 5%. For example: ensure the gown and gloves are the right size because they come prepackaged so often times they’re too large for most nurses and techs; put the gown on before the gloves; ensure the wrists are completely covered by the gown and that there is no exposed skin; and remove the gown by pulling it away from the body instead of over the head.

This matters because the wearing of PPE is standard practice for dealing with the vast number of people who contract contagious disease. A conservative estimate by the Centers for Disease Control and Prevention says that every year in the US more than two million people are sickened with antibiotic-resistant infections, with at least 23,000 dying as a result. MRSA alone is responsible for almost half of those deaths (p.77). The Canadian rates, population adjusted, are similar.

It’s understood that well-meaning healthcare workers are major conveyers of infectious disease simply because they are so exposed to it.

Thus the question: How much of this harm could we avoid if we paid attention to the details of PPE usage – and thereby reduced worker contamination rates to near 5% – as suggested by Dr. Thomas?

 

 

 

 

 

 

 

What’s For Breakfast?

pancakes 2When we were kids, my sisters and I loved it when our grandmother came by to make us breakfast. Our favorite dish was her pancakes, made from scratch of course, which we smothered in good old fashioned maple syrup. And as it turns out we may have been on to something quite healthy: the maple syrup.

Researchers at McGill University in Montreal say they have discovered an ingredient in 100% pure Canadian maple syrup that helps antibiotics to more easily kill bacteria, and also helps render those bad bugs less toxic in the first place.

They found something else too: the maple syrup extract makes bacteria less able to build biofilms, and it also breaks down biofilms already formed. These are the yucky greasy films you find on various surfaces. One very common example of a biofilm just happens to be — the plaque that forms on your teeth.

See where is this going? If you were to “agree” to have extra pancakes and maple syrup for breakfast — does that mean you wouldn’t have to brush your teeth?

Probably not. But had I ever put that argument to my grandmother I’m pretty sure it would have been met with a smile and something like: “Well, okay … but just this once, mind you!”

Here’s a brief video of the McGill researcher who put in the work on this and gives us a fuller explanation of the science behind it.

Lost and Found: A rediscovered medicine first used 1,000 years ago turns out to be more effective against MRSA than the antibiotics we have today

The scientist: Disease Warrior by day, Viking Warrior by night

The Scientist: Disease Warrior by day, Viking Warrior by night

It’s not often that a woman who dresses up as a Viking Warrior to reenact ancient battles on weekends teams up with a mild-mannered historian to solve one of our great medical problems.

Meet Freya Harrison, PhD, Research Fellow at the University of Nottingham’s Faculty of Medicine & Health Sciences – by day – warrior princess by night.

Of course, if you’re going to act the part of Viking Warrior it only makes sense that you learn to speak the language – Anglo-Saxon – which no one has much bothered to do since about 1066. Which is not a problem, you simply join the University of Nottingham Anglo-Saxon book reading club! And that’s where Ms. Harrison ran into history professor of Viking Studies, Christina Lee.

Coincidentally, Professor Lee had her own agenda on the boil: Her belief that the Medieval Era, the so-called Dark Ages, unfairly suffers a bad rap. Her theory is that it was actually a very rational era and one way to prove that would be to look at how they did scientific experiments.

The Historian: The Dark Ages had a Renaissance quality to them and she  would prove it

The Historian: The Dark Ages had a Renaissance quality to them and she needed a scientist to help her prove it

It just so happened that she was in possession of those Medieval Era experiments by way of one of the earliest known medical textbooks ever published, the 9th C Bald’s Leechbook, which Christina had been studying for years. Full of “recipes” for different ailments, she was interested in the one for a lump on the eye which she translated to mean a stye, which her research told her was usually caused by a staph bacteria, often drug resistant ones called MRSA.

Wouldn’t it be a great idea, Christina thought, if she could find someone willing to carry out this 1,000 year old experiment to see if it actually worked – to see if the ancient recipe could function as an antibiotic and kill today’s MRSA. And lo and behold in walks the Viking Warrior who immediately said yes to Christina’s proposed scientific adventure!

The age-old potion called for a precise ratio of garlic + onion or leek + wine + cow bile. “Pound them well together,” strain through a cloth, let stand for 9 days. No, they didn’t have to mash-up a cow; they managed to find the animal bile at a chemist shop. And for the wine, they got it from a vineyard that had been in the area since the 9th C!

Now for the first big test. Throw the recipe into a test tube full of bacteria, let stand for 24 hours, check to see if there’s any effect. There were sleepless nights leading up to that first morning when they looked to see if any of the germ cells were still alive: What Freya Harrison discovered was that the recipe had “a massive, massive killing ability. When we got the first results,” she said, “We were just absolutely dumbfounded. We did not see this coming at all.”

But success in the test tube is one thing, the trick is to make it work in real-life MRSA-infected wounds. So Harrison contacted colleague Dr. Kendra Rumbaugh who was already doing work on MRSA-infected skin wounds in mice at Texas Tech University in the United States.

After using Harrison’s recipe on the MRSA-mice, Dr Rumbaugh reports: “We know that MRSA-infected wounds are exceptionally difficult to treat in people and in mouse models. We have not tested a single antibiotic or experimental therapeutic that is completely effective; however, this ‘ancient remedy’ performed as good if not better than the conventional antibiotics we used.” (My emphasis)

The results matter because antibiotic resistant infections are predicted to cause more deaths than cancer by the year 2050. MRSA, in particular, is particularly deadly (p.77), responsible for about half of all deaths in the U.S. caused by germs resistant to our dwindling supply of antibiotics.

Initially, this was thought to be one of those Friday afternoon just-before-you-head-out-to-the-local-pub kind of experiment. But that’s not at all how it turned out. Dr. Freya Harrison: “The potential of this to work on people as an antibiotic is just beyond my wildest dreams to be honest.”

 

The House Guest

"Bob"

“Bob”

In the 1991 comedy What About Bob? Bill Murray plays Bob Wiley, a psychiatric patient who not only befriends the family of his psychiatrist played by Ricard Dreyfus, Murray turns into that dreaded house guest who just won’t leave. To make matters worse, Murray ends up marrying into the family notwithstanding Dreyfus’s numerous efforts to get him out of there including “death therapy” – placing 20 pounds of explosives in Murray’s backpack on a hiking trip. I’m reminded of the film by research published this week that casts MRSA in the Bill Murray role.

Investigators visited the homes of 350 people in Chicago and Los Angeles who had come to the hospital with skin infections. At these home visits investigators looked at family members’ noses, throats and groins for MRSA colonization. Of the 812 household members studied they found that MRSA colonized one or more of the body sites in 50% (405) of the cases.

Using fancy genome sequencing techniques they also found that: (1) MRSA persisted within the households from 2.3 to 8.3 years before their samples were collected (2) MRSA is transmitted from person to person within households that contain an individual with a skin infection, and (3) MRSA can evolve so that it becomes genetically unique to that particular household. Similar research has found that these newer strains are more drug resistant and dangerous than earlier strains thus making the MRSA harder, or even impossible, to treat.

How MRSA got into those households in the first place was not part of the study. But we know from other research that, ironically, hospitals themselves are implicated. That’s because when hospitals discover a patient is colonized with MRSA they don’t treat it – they don’t “decolonize” that person. Instead, so long as the person isn’t infected (sick) they’ll send them home once their primary illness permits.

But given that MRSA colonization is the greatest risk factor for MRSA infection, and because the researchers involved in today’s study conclude: “Decolonization of household members may be a critical component of prevention programs to control MRSA spread in the United States,” it seems time to reconsider the wisdom of sending MRSA-colonized patients home untreated.

The good news is you don’t need 20 pounds of explosives to it. We have the technology.

“The longer they stay, the longer they stay”

If you think people are being pushed out of hospitals sooner than they used to be you’d be right, but not necessarily because of long wait times and bed shortages. Rather, it’s because hospitals can do something to you that’s utterly counterintuitive – they can make you sicker. The chief concern is that you’ll pick up a serious infection.

mrsa 4For example, a recent study found that 1 in 12 adults in hospitals across Canada are either colonized or infected with a “superbug.” And that’s an underestimate because the researchers only looked at 3 superbugs: MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant Enterococci), and Clostridium difficile.

Dr. Brad Spellberg, an infectious disease specialist and the Chief Medical Officer for Los Angeles County-University of Southern California, explains the issue.

To begin with, Spellberg says, understand that hospitals are a place where the sickest people in society are gathered together. Therefore, there’s lots of antibiotics being used and so you’re breeding superbugs that become resistant to the antibiotics. And so the bacteria you encounter in the hospital are a lot nastier than the stuff you’re going to pick up at home.

In other words, patients come into the hospital for whatever ails them and while there they pick up an infection, and the next thing you know that 1 or 2 day hospital stay turns into a week or a month. Hence the saying among physicians, “The longer the stay, the longer they stay.” Hence the new thinking, “get people out of the hospital before they get a complication of being in the hospital.”

There’s two interesting sidebars to this.

One, these nasty hospital superbugs are seen more in developed countries than in underdeveloped countries. These superbugs and the infections you get in the hospital are side effects of modern medical therapy. For example, all those lines and tubes that permit various medicines to get into your body also give bacteria easy access to your body. Before they had to fight through your skin. Now they have a direct route into your bloodstream through these “super-highways.”

Two, your lifestyle matters. For example, wear a seat belt so if you’re in a car accident you don’t end up in the ICU with a head injury, but in the ER with minor cuts and bruises.

Dr. Spellberg’s remarks can be found in the following interview. Most of the good stuff is explained in just the first 3 minutes. Aside from being a leading world authority on the subject, Spellberg is a compelling speaker and writer. Anything from this guy is well worth checking out.

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