Antimicrobial resistance (AMR) long has been described as a “slow-moving tsunami,” giving the impression that while it is indeed something apocalyptic, the fallout is only going to be felt in the vague, distant future. It may seem that we do not need to take immediate action because there is still time … but is there?
Unfortunately, time is not on our side. In the backdrop of the COVID-19 pandemic, AMR, which predates COVID-19, is becoming more widespread. The fallout of AMR is felt in the present, not the future. It has the potential to affect a wide swath of the population rather than only the most severely ill. In Canada, in addition to having limited access to new antimicrobials, ongoing supply chain challenges with existing antimicrobials (for example, the current shortage of amoxicillin) also affect our ability to treat infections. In short, AMR is a global public health threat.
Antimicrobial use – antibacterials, antifungals and antivirals – has led to the emergence of AMR. The pandemic has exacerbated the situation.
Early in the pandemic, the assumption that patients with COVID-19 had a high likelihood of bacterial co-infections led to a disproportionately high prevalence of antibiotic prescribing relative to the actual prevalence of bacterial co-infections. A meta-analysis of 154 studies conducted between December 2019 and May 2020 found that three out of four patients hospitalized with COVID-19 received antibiotics, yet fewer than one in 10 had bacterial co-infections that warranted therapy.
As the pandemic evolved, evidence-supported therapies against COVID-19 became better standardized, and supportive care such as mechanical ventilation and extracorporeal membrane oxygenation (ECMO), offered life-saving benefits. However, with prolonged hospitalizations, patients are at risk of acquiring infections associated with health care as well as secondary infections that could drive the need for antimicrobial use.
Repeated exposure to antibiotics can result in the emergence of multidrug-resistant bacterial infections and invasive fungal infections, both of which are significant complications and can cause death. Considering the volume of patients who were hospitalized during the successive waves of COVID-19 locally, nationally and globally, we have seen a lot of antimicrobials being prescribed, contributing to a rise in AMR.
Globally, antibiotic resistance has increased since COVID-19 began.
Trying to save the life of a patient fighting an infection caused by extremely antibiotic-resistant bacteria is more common than one would think. It is a devastating situation for patients, their loved ones and the health-care team. To make matters worse, the impact of antibiotic resistance goes beyond the patient who received antibiotics, with implications on the resistance patterns at the ward and facility level. Globally, antibiotic resistance has increased since COVID-19 began. Since we live in a connected world, as the spread of SARS-CoV-2 has taught us, antimicrobial-resistant pathogens can spread globally and quickly. Put another way, what is happening in seemingly faraway places is already affecting us directly.
“The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.”
– Sir Alexander Fleming, Nobel Laureate
Antimicrobial resistance affects you, me – everybody
Without effective antimicrobials, the medical advances of the past few decades – many of which are life-saving miracles, and many of which we now take for granted – are at peril: a cut on the skin can cause an infection, causing someone to lose their limb or their life without effective antibiotics.
Anyone undergoing routine procedures such as C-section, hip or knee replacement face an unacceptable risk of post-surgical infections without effective antibiotics, which can lead to long term disability, poor quality of life, and even death from C-section complications. With our aging population, the number of Canadians needing hip or knee replacements will continue to increase in the next few decades. That is a huge swath of the population whose mobility may be taken away as a consequence of AMR.
Cancer treatment has advanced in leaps and bounds and more patients are being offered life-prolonging therapy than before. But cancer treatment increases one’s vulnerability to infections. Therefore, treatment cannot proceed without the support of effective antimicrobials; the last thing we want to see is patients surviving cancer only to succumb to an untreatable infection.
Solid organ transplantation gives patients a new lease on life. However, without effective antimicrobials, the surgery of transplantation cannot take place due to unacceptable risks of infections. Even if someone survives the surgery, it is not feasible to sustain the life-long immunosuppression required to prevent rejection of the transplant without effective antimicrobials.
All of us can take an active role in tackling AMR
Whether we are healthy individuals, patients, health-care professionals, health-care leaders or policy-makers, we all have a role to play to slow down the onslaught of AMR. Sir Alexander Fleming, who discovered penicillin and changed the course of human history, predicted the emergence of antibiotic resistance and its devastating effect on human life shortly after winning the Nobel Prize in 1945.
We all need to understand why antimicrobials are not necessarily the answer to all infections, and tackling AMR goes beyond optimizing antimicrobial use. Immunization against pneumococcal disease, for example, is highly effective at reducing the risk of infection, thereby reducing the need for antibiotic treatment. The annual flu shot reduces the risk of the flu, thereby reducing the risk of secondary bacterial infections following influenza and subsequent need for antibiotic treatment.
Although antimicrobial stewardship programs have been established in many acute-care hospitals and complex continuing-care facilities, they receive limited resources. Furthermore, outpatient antimicrobial stewardship remains under-developed in Canada. Given the bulk of antimicrobials are prescribed in outpatient settings, especially in walk-in clinics where many Canadians rely on for health-care access due to national shortage of family physicians, dedicated resources such as the Four Moments of Antibiotic Decision-Making from the U.S. AHRQ and the outpatient toolkit from Public Health Ontario are helpful to primary-care clinicians. A vital aspect of the outpatient interventions is to empower patients to better understand the benefits and harms of antimicrobial use, which remains an unmet need.
For policy-makers, a timely, robust surveillance system of antimicrobial resistance, coupled with efficient tracking of antimicrobial consumption will help direct antimicrobial stewardship efforts in a coordinated fashion across Canada and at the global stage.
Antimicrobial resistance is not a slow-moving tsunami. Rather, it is a public health threat that is fast and furious. Everyone has a role to play to mitigate against this threat, and we must act now. Nov. 18-24 is World Antimicrobial Awareness Week – let’s spread awareness, not resistance.
Antibiotics are still some of the best tools available in medicine. The golden era of major discoveries in medicine is over and it’s too bad that medicine has lost its way. Shareholder preferences now control medicine. In 2018 Goldman Sachs said it’s official, shareholders are no longer interested in cures, new antibiotics or vaccines. The paradigm of modern medicine is to palliate with treatments that provide lifetime annuities to the pharmaceutical industry. The invention of powerful immunosuppressants is responsible for an epidemic of autoimmune diseases. The neurologist is not interested in what is causing the patients MS nor is the rheumatologist interested in the root cause of rheumatoid arthritis. Historically infection was usually found to be the root cause of inflammation.
Long-COVID has knocked physicians out of their comfort zone, perhaps they will have a second look at other stigmatized invisible diseases such as fibromyalgia, long-Lyme and ME/ CFS. It is now felt that many of the causative microbes live on in tissue reservoirs, biofilm or are neuroinvasive. The immune system can detect, but can’t clear the infection. Unfortunately, there are no medical sleuths being trained to do the fine tissue work required to do follow up work. In the case of ME/ CFS they don’t know what they are looking for and looking in the wrong places. In medicine the dead shall speak to the living, but autopsies are seldom done anymore and searching for Borrelia in the brains of Alzheimer’s victims is quickly discouraged.
Government incentives are required to get things moving. Private foundations and patient groups are funding research and making progress. Professor Kim Lewis has rediscovered Hygromycin A, an antibiotic that was first discovered in 1952 but was abandoned after it was determined that it was only effective against spirochetes. This is a selective antibiotic that will leave the microbiome alone and will likely be able to treat Lyme and syphilis at any stage.
Most physicians are not aware that 80% of chronic infections are biofilm, everything from otitis media, urinary track and MRSA infections are biofilm composed of non-dividing cells that are 1,000 times more difficult to treat than acute infections caused by planktonic organisms and yet there are no FDA approved biofilm agents which could re-potentiate older antibiotics. Dr. Garth Ehrlich explores his findings from 20 years of research on YouTube.
Bacterial phage have been used with great success to treat infections but are difficult to patent. Medical specialists work in silos but a lot can be learned form precision medicine use in cancer treatments. Identifying molecules from searches of the FDA data bank that interfere with critical metabolic pathways of pathogens offers another route to effective treatment particularly if these molecules can penetrate biofilm to kill their target.
The Public Health Agency of Canada [PHAC] is now headed by two infectious disease doctors. PHAC has prioritized the preservation of the antibiotic supply over returning Canadians to health. PHAC’s goals are now those of a private organization, the Association of Medical Microbiologists and Infectious Disease [AMMI] Canada who maintain very close ties with industry. Self-regulation is a privilege, not a right and only works if everyone is being altruistic. It’s likely some degree of civilian oversight is urgently needed to see that PHAC and its branches are working for the public good and not just industry’s.
Slow moving or fast and furious, antimicrobial resistance is simple, complex, and dynamic, following the rules of the new science of complexity, also the science of tsunamis.
While raising awareness of antimicrobial awareness we can also raise awareness of complexity and its applicability to medicine and health in general, and how we can reduce antibiotic resistance through the science of complexity, the science of change in complex systems.
Tsunamis generally move fast – about 500 mph, but in shallow water can slow to 50 mph, but its amplitude increases, potentially causing as much trouble – (source Wikipedia).
We can raise awareness of antibiotic resistance and reducing it, by also raising awareness of complexity.
For free book online – Tsunami, Chaos and Global Heart: using complexity science to rethink and make a better world, and a poster on learning/teaching complexity.
Vivian S Rambihar MD. Toronto.