Antimicrobial Resistance: Too Much Study, Not Enough Action, No Time to Lose

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Antimicrobial Resistance: Too Much Study, Not Enough Action, No Time to Lose

Abstract

We have known about the threat of antimicrobial resistance (AMR) for so long that it seems as though we should have solutions in hand by now to save lives. However, news from around the world supports the assertion that we are NOT doing nearly enough to prevent this insidious threat to human life. Morbidity rates are increasing and broad efforts, such as the AMR Review, seem to have fizzled out. One thing we know for sure is that solutions must be global and multifaceted to be effective. Governments must be involved, but the effort cannot succeed unless there is also participation from the private sector, educational institutions, researchers and clinicians. Smaller studies sponsored by non-governmental organizations, consumers and civil society can also play a role in finding solutions to the AMR dilemma.

Main Article

On January 13, 2017, the CDC reported in its Morbidity and Mortality Report (MMWR) that a woman in Reno, Nevada, had died after an extensive, unsuccessful antibiotic treatment (Chen et al, 2017). She had checked into the hospital late in 2016 with a Carbapenem-resistant Enterobacteriaceae (CRE) infection, likely contracted during her travels in India. Doctors attempted to treat the infection with 26 different antibiotics – every option the hospital had on hand – but the infection shrugged off every attempt. After all this time, how could this happen? The Reno woman’s case is a visceral reminder that the threat of Antimicrobial Resistance (AMR), both personal and global, grows every day, and that the loss of life due to antibiotic resistance may soon become a common nightmare. Further inaction could result in waves of patients for whom modern medicine is largely ineffective.

In fact, we may already be there. The CDC has stated that “(a)ntibiotic resistance is one of the most urgent threats to the public’s health” (CDC, 2017a). Worse, in its 2017 report, “Antibiotic Use in the United States,” the CDC says antibiotic resistance “threatens to return us to the time when simple infections were often fatal”(CDC, 2017a).

It is inarguable that antibiotics are heavily misused worldwide; they are prescribed too often and used inappropriately

It is inarguable that antibiotics are heavily misused worldwide; they are prescribed too often and used inappropriately. More frequent exposure to the drugs leads to an increased rate of resistance, especially for the so-called “superbugs” that are completely immune to their effects. Researchers at the University of Michigan determined last November that more than 23% of antibiotics prescribed at that institution were inappropriate and unnecessary to treat patients’ illnesses. The CDC reports that the problem is particularly drastic in nursing homes, with 11% of all nursing home residents taking antibiotics on any given day, and nearly 40% of all antibiotic prescriptions lacking the proper information normally required to make a diagnosis that would indicate treatment with antibiotics (CDC, 2017b).

Even when appropriately prescribed, drugs are often misused by patients who miss doses, stop taking the medication when their symptoms clear up, or use antibiotics left over from a previous illness when they are unneeded (van Duijn, et al, 2018). Although this seems harmless, it can create a perfect environment that allows the bacteria to adapt and further spread this adaptive resistance to different people, which can easily be lethal.

Nothing is Changing: Time is Running Out

A few organized efforts have been made to find solutions to the antimicrobial resistance problem worldwide. The World Health Organization (WHO) created a “Global Action Plan on Microbial Resistance” in 2015. In a significant push towards better understanding AMR, UK Prime Minister David Cameron commissioned the “AMR Review”, which was finally published in 2016 (O’Neil, 2016). Titled “Tackling Drug-Resistant Infections Globally: Final Report and Recommendations,” the report very thoroughly compiled global data on the emergence and spread of antibiotic resistance, as well as effective and less effective strategies to mitigate the increasing number of human deaths. Among the outcomes were 10 simple recommendations that would help to ‘extend the effective shelf life’ of antibiotics, and give us more time to develop better strategies against AMR (O’Neil, 2016). These include reducing demand for antimicrobials by improving public awareness, improving sanitation, reducing unnecessary use (including use in agriculture), improving global surveillance of drug resistance, developing vaccines and other alternatives, increasing the number of people working in infectious diseases, funding research and development, and providing better incentives to find new drugs and improve existing ones (O’Neil, 2016).

In spite of these official recommendations and others, to date no organized global changes have been realized. The WHO’s Antibiotic Awareness Week underscores the growing urgency to find solutions.: “Change Can’t Wait. Our Time with Antibiotics is Running Out” (WHO, 2019). Time and time again, we are seeing that despite the best of intentions, the current efforts just are not enough. For example, here are the stories that we are seeing regularly in the global media:

Cases continue to increase

The Malaysian Ministry of Health reports skyrocketing cases of Carbapenem-resistant Enterobacteriaceae infections, from only 11 cases in 2011 to 800 in 2016. Again, there are many others (Ministry to Health Malaysia, 2019).

Treatments are not working

The Journal of Clinical Microbiology reported on a study of CRE infections in a hospital in Henan, China, the country’s most populous province. These researchers, and many alike in different countries are seeing a significant increase in the prevalence of CRE isolates in hospitals, suggesting that carbapenems may no longer be considered to be an effective treatment for infections caused by Klebsiella pneumoniae (Li et al, 2018).

The long-term outlook does not look good

It is estimated that by the year 2050 AMR could be responsible worldwide for one human death every three seconds (O’Neil, 2016).

What has been done to generate those specific solutions since the review was completed? Unfortunately, very little. There is a tendency to downplay the significance of these infections to the general public. The New York Times recently discussed a case of Candida auris (a highly resistant fungus) in hospitals (Adams et al, 2018). Similar to another case in the United Kingdom, no information was released to the public while the problem was handled. The hospitals quietly cleaned and disinfected potentially-contaminated wards and are reported to have employed further precautionary measures to prevent another outbreak. This secrecy was likely meant to protect the hospitals’ reputations (Richtel and Jacobs, 2019).

secrecy benefits no one

However, this secrecy benefits no one; we need to shine a bright light on these challenges, because without attention, nothing will progress. The best we can hope for is continuous research and small improvements. It is not enough to only understand the problem and have an idea how the problem might worsen in the future. We must have a plan to do enough to stop it. Why? Because people are dying now, and the longer we wait, the more complex and insidious the challenge could become.

Whose Job is Mitigation of Antimicrobial Resistance?

If we are to solve the problem of antibiotic resistance before time does indeed run out, it is clear that a much larger-scale effort is needed.  As Dr. Margaret Chen of the World Health Organization said in 2015 when addressing the G7 Health Ministers, “The World Economic Forum has identified antibiotic resistance as a global risk beyond the capacity of any one organization or nation to manage or mitigate alone” (World Health Organization, 2015). What does this mean? In part, it means no one – no country, government or institution – can operate in isolation. Any solution needs to be undertaken on a global level to be effective. Efforts must be coordinated, because any previous work done in one region to mitigate a problem could be undone when a different, highly-resistant pathogen is introduced. We live in a smaller, more connected world, and physical borders and vast distances mean much less to emerging pathogens.

This global need for coordination might lead some to believe it is the responsibility of the world’s governments to solve the problem. However, due to the nature of government studies and the constantly changing cast of leaders, government efforts have a tendency to fizzle out when new priorities take center stage, such as the case with the AMR Review. Government efforts are indeed important, but they are not going to be enough to tackle this impending disaster. It is important that the private sector rolls up its sleeves as well.

Dr. Chen said, “Consumer groups and civil society can play an important role in combating antimicrobial resistance. They are important movers, shakers, and front-line players, especially in this age of social media.” This was the precise call to action that inspired myself and others to roll up our sleeves and get involved in creating The Infection Prevention Strategy (TIPS). Through this non-profit organization, we “created a model of information sharing that makes the process of vetting new technologies, implementing successful programs and inspiring innovation more efficient, more accessible and more collaborative.” In short, TIPS is one of those “movers, shakers, and front-line players” Dr. Chen was looking for to raise the profile of AMR efforts through innovative services, diverse outreach, and social media strategies to reach a broad audience of researchers, clinicians, industry innovators and laypeople.

The TIPS network and series of websites most notably, InfectionControl.tips (https://www.IC.tips) have become the world’s largest global platform for infection prevention and control. The websites were launched to provide an easily-accessible hub for standard best-practices in infection prevention – a hub that can be accessed by anyone, including private citizens, medical personnel, researchers and government officials.

Funding for promising front-line projects

Through the TIPS Sudden Science Program, the organization is also providing funding for promising front-line projects in the field to help the world find solutions more quickly, because the faster we find solutions, the more lives we can save. Patients like the woman in Nevada are dying right now and do not have years to wait for solutions.

A recently-funded TIPS study is led by Dr. Sergio Borgia and Dr. Allison McGeer from the William Olser Health System and Sinai Health System in Canada. The purpose of the study is to determine the effectiveness of chemical and physical disinfection of hospital drains in preventing the drains from harboring these kinds of antibiotic-resistant diseases. It is already known that carbapenemase-producing Enterobacteriaceae (CPE) inhabit hospital drains and that is one of the ways the pathogen is spread, but limited evidence is available to address whether current procedures are effective at reducing their populations in these drains. The infected sinks are in patient rooms and with very few antibiotics that can help if a patient contracts the disease, the importance and urgency of studying such a specific threat becomes apparent.

“We looked at a bunch of drains, screened them, and discovered about 50 that had the organisms in our hospital,” said Dr. Borgia. “We’ve divided them into two groups that will be sampled over the next year. Half will get regular treatment, and half will get an intensive treatment. The hypothesis is that the drains that get the intense treatment will lose colonization of the organisms.” This research is “granular,” as Dr. Borgia describes it, but it is important and can lay the foundation for further study and solutions.

Dr. Borgia praised the availability of research funding through TIPS, as it “allows places like ours to tap into some resources we wouldn’t have otherwise had access to.” He added, “We won’t get a silver bullet overnight.” In other words, many more efforts like this study are needed to clear up the blind spots in antibiotic resistance and move forward.

We are now aware of the threat of AMR, but awareness is only one part of a full solution. We must proceed with a sense of urgency as we press ahead to develop global standards and procedures for handling incidents, preventing antibiotic misuse and, most importantly, saving lives. For those who face the current hopelessness of AMR, such as the woman in Nevada and her family, there is no time to lose.

Join. Contribute. Make A Difference. 
Contact Michael Diamond to get involved with TIPS and Make A Difference

References

Adams, E., Quinn, M., Tsay, S., Poirot, E., Chaturvedi, S., Southwick, K., … & Haley, V. (2018). Candida auris in healthcare facilities, New York, USA, 2013–2017. Emerging infectious diseases24(10), 1816.

Center for Disease Control and Prevention (2017a) Antibiotic Resistance Questions and Answers. CDC. Accessed Apr 22, 2019. https://www.cdc.gov/antibiotic-use/community/about/antibiotic-resistance-faqs.html

Centers for Disease Control and Prevention. (2017b). Antibiotic use in the United States, 2017: progress and opportunities. Atlanta: US Department of Health and Human Services. CDC. Accessed Apr 22, 2019. https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf

Chen, L., Todd, R., Kiehlbauch, J., Walters, M., & Kallen, A. (2017). Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae-Washoe County, Nevada, 2016. MMWR. Morbidity and mortality weekly report66(1), 33-33.

Chua KP, Fischer MA, Linder JA. Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. BMJ: British Medical Journal (Online). 2019 Jan 16;364.

Li, Y., Sun, Q. L., Shen, Y., Zhang, Y., Yang, J. W., Shu, L. B., … & Wang, S. (2018). Rapid increase in prevalence of carbapenem-resistant enterobacteriaceae (CRE) and emergence of colistin resistance gene mcr-1 in CRE in a hospital in Henan, China. Journal of clinical microbiology56(4), e01932-17.

Ministry of Health Malaysia (2019) Ministry of Health Malaysia. Accessed Apr 22, 2019. http://www.moh.gov.my/index.php

O’Neil, J (2016). Tackling drug-resistant infections globally: Final report and recommendations. Review on Antimicrobial Resistance. Accessed 19 Apr, 2019. https://amr-review.org/Publications.

Richtel M; Jacobs A (2019) A Mysterious Infection, Spanning the Globe in a Climate of Secrecy. New York Times. Published Apr 6, 2019. Accessed Apr 22, 2019  https://www.nytimes.com/2019/04/06/health/drug-resistant-candida-auris.html

Van Duijn, P. J., Verbrugghe, W., Jorens, P. G., Spöhr, F., Schedler, D., Deja, M., … & Misset, B. (2018). The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial. The Lancet Infectious Diseases18(4), 401-409.

World Health Organization (2019). World Antibiotic Awareness Week. Accessed Apr 22, 2019. https://www.who.int/campaigns/world-antibiotic-awareness-week

World Health Organization (2015) Global Action Plan On Antimicrobial Resistance. World Health Organization. Accessed Apr 22, 2019 http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf

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Co-founder of The Infection Prevention Strategy (TIPS) Michael Diamond is the co-founder of The Infection Prevention Strategy (TIPS), a non-profit organization that has contributed millions in Scientific Impact since 2016. Michael is devoted to advancing information and science to address the myriad issues relating to infection prevention and global health. Mr. Diamond is driven by the firm belief that we should not have to wait years for promising technology, ideas and processes to be implemented and accepted. Michael has created a model of information sharing that makes the process of vetting new technologies, implementing successful programs and inspiring innovation, more efficient, more accessible, more global and more collaborative. Michael’s most notable achievement to date is the TIPS online journal, www.IC.tips, a Pan-Access, worldwide collective that extends globally and touches locally. Michael leads teams around the world to develop trials and pilot studies to aid in the discovery of successful research-to-market technological advancements. His global team includes engagers and implementers. Currently represented in 38 countries, and well-established as the world’s largest engagement network, the TIPS motto is: Join. Contribute. Make A Difference.

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