POST-AnTibiOTic APOcAlyPSE wiTh ThE ‘SUPERbUg’

ever consider a world where surgery was no longer an option? It is the unfortunate truth that if society does not slow the progression rate of antimicrobial resistance, life as we have come to know it will no longer be our future.

Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. Without such means of effective treatment, it will compromise therapies that have been used for decades in healthcare and puts society in a very precarious position. Treatments such as major surgery or chemotherapy may fade into the background.

As we stand on the precipice of a postantibiotic apocalypse, this global concern has researchers all over the world clamouring to find a solution before this issue gets out of hand. Kevin Schwartz, an infection prevention and control and antimicrobial stewardship physician from Public Health Ontario is one of those researchers seeking a strategy.

“Antimicrobial resistance is going to be one of the biggest future challenges and it really threatens the way that we practice medicine,” says Kevin Schwartz, also an assistant professor at the Dalla Lana School of Public Health, University of Toronto. “We take for granted some of the modern advances of technology that we will really jeopardize if the trend of antimicrobial resistance continues.”

Antimicrobial resistance happens when microorganisms change from exposure to antimicrobial drugs. It is a natural process that happens over time, but, unfortunately, that timeline has been accelerated due to the misuse and overuse of antibiotics in people and animals. Whether it stems from prescribing patients’ antibiotics for things such as a cold or flu, or when they are given as growth promoters in animals or used to prevent disease in healthy animals, the truth is that we need to find a solution to contend with these “superbugs” – and fast.

Antimicrobial resistant-microbes are found in people, animals, food, and the environment (water, soil, and air.) They can transfer from person to person, from person to animal and animal to person – that includes food of an animal origin – and is present in every country worldwide.

“It’s such a huge global overwhelming problem. From hospital settings to nonhospital settings, and we use more antibiotics than we probably need to,” states Schwartz. “There are a variety of reasons for that. Antibiotics are effective and life-saving, and often patients present with unclear diagnoses so antibiotics are often used to be on the safe side and so we are not missing a potentially treatable illness.”

“So, I think a lot of this stems from that. Fields of antimicrobial stewardship are trying to develop ways to help physicians and prescribers use the antibiotics more appropriately. There’s probably depending on the study and the area being treated, inappropriately prescribed 30-50 per cent of the time. So, there is lots of room to improve our antibiotic use,” Schwartz adds.

However, there isn’t one strategy that is applicable across all patient settings and types of conditions and there is a lot of variability as to how antimicrobial stewardship can be implemented. For instance, the approach to improving antibiotics is going to be quite different depending on the setting. Some examples would be the difference in the intensive care unit compared to hospitalized

patients, compared to patients treated in the emergency room, compared to patients treated in family doctor offices.

“My focus is mainly on the out-patient setting,” says Schwartz. “So, how can we approach family physicians and community prescribers to use antibiotics more appropriately? Some of the strategies to do this would be to provide feedback to family physicians. Some of the stuff that we are scaling up to do is to be able to give doctors some comparisons and feedback. For example, how much antibiotics are they prescribing compared to their peers? Then by identifying those doctors that are high prescribers we can have a significant impact to decrease overall prescribing.”

He goes on to suggest that there are other simple measures that can be implemented, such as a study done in the US that monitored how a poster mailed to family doctor clinics and signed by the corresponding physician with the intent to use antibiotics appropriately displayed in the waiting room affected overall usage. The study showed that even this simple measure decreased over-prescribing by 20 per cent. “We have done something similar in Ontario over the last year, so we partnered with Choosing Wisely Canada, which is an organization to decrease waste and improve healthcare efficiency. So, we sent the poster to about 13,000 doctors in Ontario to hang in their offices for a similar purpose,” Schwartz says.

There are discrepancies in the system across the country, however, about the amount of antibiotics being prescribed by population and contrasting health regions. This could be due to the variance of practice of physicians in different geographical locations. Some prescribe more, while others tend to prescribe less – allocating education and feedback as one of the best means to observe overprescribing.

There are notable differences between ur-

ban and rural environments prescription and usage, but through multi-variable modelling incorporating these variables as predictors, it is still undetermined why some prescribe more over others.

“We want to make sure people are using the appropriate medicine for the appropriate condition. So, we’re not using overly broad, overly toxic medication when we do not need to,” comments Schwartz.

A study that was done in the UK highlighted what would happen if the course of action did not change over time. They estimated that there are roughly 700,000 deaths a year from antibiotic resistant infections, and that if we do not do anything by the year 2050, that number could reach a high of 10,000,000. To put that number in another light, the death toll will surpass cancer and motor accidents combined.

“This is a major global problem that needs a major global response to it. It highlights the important work we need to do in antimicrobial stewardship to improve antibiotic use,” states Schwartz. “It is complicated in that, most antibiotics by weight are used in animals, not in humans, and there’s lots of antibiotics in the environment and in other parts of the population. So, there’s all these different approaches where we need to combine – animal veterinary health with human health with environment – and all these different things need to come together so we can decrease antibiotic exposure and an element of resistance.”

The importance of this issue can not be understated. All the advances that have been accomplished in health care will be for naught if antimicrobial resistance continues down this path. Successfully taking care of premature babies, organ transplant, bone marrow transplant, and complex cancer therapies are all prime examples of procedures that will become incredibly difficult or impossible to achieve. They all rely on the fact that we can treat the complications that go hand in hand with the procedure – namely infections. These patients are more susceptible to bacterial infection, and without effective antibiotics the procedure may be too risky.

“I think people don’t really realise the huge impact that the spread of antimicrobial resistance will have on all aspects of healthcare that have been advancing over the last 50 years. It really does threaten the way we live our lives and the way we get looked after in the healthcare system,” says Schwartz. “We think back to the way things were during WWI when there was no antibiotics and even a small wound in battle could be life-threatening or limb-threatening. We really take for granted what we now consider a simple condition, where in the past they were lifethreatening. They will become life-threatening again in the absence of effective antibiotics for these problems.”

Physicians and dentists are examples of prescribers that need to prescribe antibiotics appropriately, and for the public to have an awareness of the risks of taking antibiotics unnecessarily over time. This awareness needs to be spread before the world turns into a post-antibiotic era. Antimicrobial resistance is an inevitable process. The bacteria are alive, and they will evolve to survive.

Dr. Kevin Schwartz. Photo: Public Health Ontario “we really take for granted what we now consider a simple condition, where in the past they were life-threatening. They will become life-threatening again in the absence of effective antibiotics for these problems.”

To see this story online visit https://biotechnologyfocus.ca/post-antibiotic-apocalypse-with-the-superbug/

| BY DON BOCCHINFUSO, ASSOCIATE AND NOEL COURAGE, PARTNER BERESKIN & PARR LLP

GETTING MAXIMUM IP FROM R&D

IP protection allows creators to gain the full economic benefit of their innovations. This promotes reinvestment in R&D, leading to further innovation. For many companies, a strong IP portfolio covering key markets is their most valuable asset. This article demonstrates how different forms of IP can be combined to protect life sciences innovations, using the example of a mass spectrometer.

Patents

A patent grants an exclusive right to manufacture, use, or sell an invention. In life sciences, patents may be granted on inventions such as new and inventive drug compounds, genetically modified cells, medical devices, methods of synthesis, hardware, and computerimplemented processes. Our mass spectrometer example shows how a single product may be covered by multiple patents. There may be inventions in reagents, chemical processes, mechanics, processors and software. The entire machine may be patented as a system. A patent may also be granted for an individual component such as a liquid chromatography input. Other patents can cover disposable products, operational processes, assays, and certain processes of analysis. For example, in 2017, Thermo Fisher was granted patents related to a method of operating a mass filter in a mass spectrometry system. In situations where a company decides not to file a patent, keeping an innovation as a trade secret may provide an advantage.

Industrial Designs

Industrial designs provide narrow protection on the look (aesthetic) of objects such as shape and pattern. The sleek design of a mass spectrometer casing may be registered. For example, Shimadzu Corporation, has registered the specific ornamental design of its mass spectrometer. An industrial design may even cover simple components such as a sample tube rack. The industrial design can be registered in addition to filing for conventional utility patents on function.

Trademark

Trademark protection grants the exclusive right to use a brand. Like most products, mass spectrometers bear the name or logo of their manufacturer. This mark serves as a clear indication of the source of the machine, and is a tool used by companies to build and protect goodwill (ie. distinguish their goods or services). “Orbitrap,” “Thermo Fisher,” and “Sciex” are examples of registered trademarks.

Copyright

Copyright grants the exclusive right to reproduce a protected work. Unlike other forms of IP, copyright need not be registered; it exists automatically as soon as work is created (registration does provide additional advantages). The mass spectrometer itself is not eligible for copyright protection. However, instruction manuals, software code, product images, and laboratory notes are all protected by copyright and extend IP protection beyond the device itself. Many examples of copyrighted works can be seen on mass spectrometer company websites.

Licensing

IP rights may be economically exploited by way of licensing to others that want permission to use the IP rights. Licences are particularly attractive for companies that do not have the interest or means to profitably exploit an IP right themselves. Patents covering mass spectrometry innovations have been licensed by significant industry players for both device components and assay methods. As an example, in 2017, SISCAPA Assay Technologies Inc. licensed their mass spectrometry assay calibration technology to Waters Corp.

Litigation

IP litigation enforces IP rights against an infringer. In Canada, a patent owner may seek a permanent injunction preventing an infringer from selling infringing products. A court may also award compensatory damages, or an accounting of profits. An example of patent litigation is the U.S. lawsuit in which Waters Corp paid Applera Corp $18M to settle Applera’s allegations that Waters infringed Applera’s mass spectrometry patent.

Companies should use a wide range of IP tools to protect their innovations, as shown by the mass spectrometer industry. IP supports your own company’s growth and products, but can also be commercially exploited by licensing or enforcement.