Antibiotic Resistance

Have you ever had to pay multiple visits to a doctor because the prescribed medication for illness just wasn’t working? This might occurred because of a natural phenomenon termed ABR or antibiotic resistance. So what is ABR? According to the Alliance for the Prudent Use of Antibiotics of the Tufts University Medical School, antibiotic resistance “occurs when an antibiotic has lost its ability to effectively control or kill bacterial growth”1. The bacteria become resistant to certain antibiotics and such therapy is rendered ineffective.

Bacteria achieve antibiotic resistance through natural phenomenon related to genetics and evolutionary mechanisms. Some bacteria in a population appear to be resistant to a specific type of antibiotic (or multiple antibiotics) due to random genetic mutation. Once antibiotics are deployed on the site of infection, the non-resistant bacteria are eliminated and the resistant bacteria are left alive. The antibiotics create a “selective pressure” that promote the survival of the resistant bacteria1. Furthermore, these bacteria will reproduce and their offspring inherit the resistant traits thus creating a new fully resistant population.

Bacteria also have multiple robust mechanisms that enable the proliferation of ABR. Their offspring can inherit resistant traits “vertically”, or they can share genetic information with other bacteria “horizontally” through a process termed conjugation1. Adding to the fact that bacteria can survive on many surfaces and travel easily on unsuspecting flights and water travel, ABR is able to spread amongst bacteria quickly.

Studies conducted by the World Health Organization show that ABR is not only a concern for the future, but also a very current worldwide issue. In 2013, there were approximately 480,000 cases of multi-drug resistant Tuberculosis evident in around 100 countries2. Like other cases of antibiotic resistant bacteria, multi-drug resistant Tuberculosis requires extended and arduous methods of treatment as the bacteria is stubborn to common antibiotic treatment.

Evidently, ABR is a current real-world issue with the potential to further escalate. This issue should be studied and better understood in order to develop alternatives to remedy the problems ABR creates.


1 “General Background: About Antibiotic Resistance.” APUA. 2014. Accessed June 08, 2016.

2 “Antimicrobial Resistance.” World Health Organization. Accessed June 08, 2016.

Overuse of Antibiotics in Livestock contributes to ABR trends

Farmers use antibiotics to ensure harmful pathogens like bacteria do not go on to live on the shelves of grocery stores and on the dinner table. While this may be comforting, there is an unfortunate overuse of antibiotics in livestock farming. This overuse contributes to the escalation of the ABR issue and can lead to infections of humans by resistant bacteria.

Livestock is often treated with antibiotics to prevent illness but overuse promotes an increased risk of ABR. The Beef Cattle Research Council explains that an antibiotic Metaphylaxis must often be used to combat respiratory illness with new feedlot calves due to high stress and confined spaces1. Antibiotics like these are often necessary to keep feedlot cattle healthy and prevent further transmission of bacteria to other cattle and even humans. Unfortunately, farmers often use antibiotics in a non-therapeutic matter. According to an article from the Union of Concerned Scientists, antibiotics are sometimes employed to fatten up livestock and increase feeding efficiency2. Antibiotics are also used liberally in a preventive manner in an attempt to prevent bacterial infection in livestock.

The overuse of antibiotics in livestock, like the over prescription of antibiotics in humans, fosters the growth of resistant bacteria. Irresponsibly deployed antibiotics in livestock farming promote the survival of resistant bacteria. These bacteria is often able to survive on the animals after they have been slaughtered and can even make their way to grocery stores and dinner tables. This can potentially lead to the infection of humans by drug resistant bacteria—infections requiring extensive time and therapy to treat.

How do we minimize the damage done by the use of antibiotics in livestock? Obviously the must be employed in some capacity to keep our food clean and healthy, but there must be methods in administering antibiotics responsibly and sparingly. The Beef Cattle Research Council advises farmers to follow certain measures that prevent ABR. Examples include treating infections promptly, obtaining the proper diagnoses before using antibiotics and ensuring the proper dose are given to the animals. The use of antibiotics in livestock must be monitored and better practices be put in place in order to deescalate ABR.

ABR affects Non users as much as users of antibiotics

If you are not a frequent user of antibiotics, then ABR should not be a concern, correct? This is not true. In reality, ABR (antibiotic resistance) affects everyone—non-users and users of antibiotics alike. The biotechnical nature of ABR allows for a sharing of resistant traits amongst bacteria and populations of bacteria. In other words, ABR in bacteria elsewhere can exchange information through several pathways with bacteria that could ultimately affect you.

“Horizontal” transmission of ABR amongst bacteria is a common way for ABR to spread amongst bacteria and across bacterial populations. A study conducted by Cecilia Dahlberg et al of the University of California explored the mechanism in which bacteria transmit and receive genetic information. They found that bacteria could exchange segments of their DNA through a process termed conjugation *. Bacteria are able to transmit and receive plasmids (vehicles for DNA transport) that often carry sequences that code for antibiotic resistance. ABR can be exchanged between bacteria through this mechanism frequently. Furthermore, conjugation was observed to occur between different species of bacteria illustrating the robustness of ABR through this method of transmission *.

Mechanisms like conjugation enable the spread of ABR from populations of bacteria exposed to antibiotics to other populations of bacteria not necessarily exposed to the same environment. This means that ABR is an issue not limited to communities and environments surrounding frequent users of antibiotics—it affects everyone.

* Dahlberg, Cecilia, Maria Bergstro¨m,, Margit Andreasen, Bjarke B. Christensen, Søren Molin, and Malte Hermansson. “Interspecies Bacterial Conjugation by Plasmids from Marine Environments Visualized by Gfp Expression.” Oxford Journals. December 12, 1997. Accessed June 9, 2016.

Antibiotic Resistance is expected to take more lives than cancer

Antibiotic resistance or ABR is a current real-world issue and is escalating with time. As of 2014, ABR was estimated to be responsible for 700, 000 deaths annually1. The implications of antibiotic resistance are also important to discuss. Countries around the world are expected to incur a high economic cost with the rise of ABR and there is little incentive for entrepreneurs and researchers to develop more antibiotics. Furthermore, left unsolved, experts believe antibiotic resistance to take more lives than cancer in the near future.

According to a study chaired by internationally published economist and antibiotic resistance expert Jim O’Neill, ABR is expected to take 10 million lives annually by the year 2050. The current conservative estimate for ABR-associated deaths is 700,000. This illustrates the growing problem of ABR and the need to find viable solutions. 10 million deaths per year are more than the 8.2 million annual deaths attributed to cancer.

There are several reasons why ABR is a pressing issue and continues to be a problem. Firstly, antibiotics are usually overprescribed and foster conditions that lead to antibiotic resistance through evolutionary mechanisms in bacteria. This problem is especially prevalent in third world countries. Secondly, researchers and investors have little economic incentive to produce antibiotics. Antibiotics are difficult to research and develop and regulatory approval is challenging. Additionally, the venture is not very profitable. According to the US National Library of Medicine National Institutes of Health, the net present value (NPV) of a new antibiotic is about $50 million compared to an NPV of $1 billion for a drug that treats neuromuscular disease.2

Fortunately, many distinguished scientists and institutions around the world recognize the problem of ABR. New technologies like antimicrobial Photodynamic Therapy (aPDT) are providing alternatives to antibiotics that are both economically viable and counter the problem of antibiotic resistance. Plenty of evidence shows that ABR should be a concern to everyone, can affect everyone. and will ultimately lead to many deaths in the near future if left alone. Efforts should be focused in developing alternatives to antibiotics and solving the ABR problem.

1“The Review on Antimicrobial Resistance.” AMR-Review. 2014. Accessed June 15, 2016. Review Paper – Tackling a crisis for the health and wealth of nations_1.pdf.

2Ventola, C. Lee. “The Antibiotic Resistance Crisis: Part 1: Causes and Threats.” Pharmacy and Therapeutics. 2015. Accessed June 15, 2016.

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.


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.





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?








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