Antimicrobial Resistance Is A Global Crisis

Antimicrobial resistance is recognized as a global health crisis. In the most recent United Nations Interagency Coordination Group (IACG) Report on Antimicrobial Resistance,1 there is significant urgency in the messaging to focus efforts on reducing misuse of antimicrobials in order to avoid disastrous impacts of drug resistance and global economic effects. There’s a need to shine a light on this important topic to improve education and mobilize those who can affect change. Unnecessary and broad antimicrobial use contributes to an ever-growing global push towards antimicrobial resistance.

Inappropriate or unnecessary antimicrobial use has been shown to be between 30-50%. The Centre for Disease Control (CDC) reports that at least 30% of prescribed antimicrobials in the outpatient setting are considered inappropriate.2 When considering a wider definition of unnecessary use, inappropriate selection, dosing, and duration, the rate approaches 50% of all prescribed outpatient antibiotics. A Summary of antibiotic use in Long Term Care (LTC) in Ontario, Canada by Public Health Ontario (PHO) notes that 50% of prescribed antibiotic courses in this setting are unnecessary.3

The growing concerns associated with antimicrobial resistance are seen in the resulting complex infections that precede morbidity and mortality due to difficult to treat infections worldwide. In the US alone, more than 2.8 million individuals have infections with antimicrobial-resistant organisms, and of those approximately 35,000 die as a result.4 In some high-income OECD countries, about 35% of common infections are resistant to available antimicrobials and in low to middle income countries, resistance rates are as high as 80 to 90%.1 Globally, drug resistant infections cause more than 700,000 deaths.1

Drug resistance not only affects capacity to combat infectious diseases in humans, but also in other terrestrial and aquatic life, where antimicrobials are becoming increasingly ineffective due to a myriad of factors, including inappropriate use.1 Therefore, it is imperative that antimicrobials be valued and protected as critical tools for fighting infectious diseases. One of the ways to ensure antimicrobials are used appropriately is through implementation of Antimicrobial Stewardship (ASP) principles.

The Intersection of Antimicrobial Resistance and Stewardship Throughout History

The mechanisms of antimicrobial resistance are complex and made up of a range of biochemical and physiologic processes that contribute to the outcome of resistance.5 At the forefront of the discovery of bacteria in the late 19th century was a perpetual search for appropriate treatment alternatives. In 1928 the discovery of penicillin was a pivotal moment in this journey followed by discovery of penicillinase producing bacteria later that century.5 The development of antimicrobials followed by resistance mechanism discovery continued with the introduction of sulfonamides in the 1930s and resistance mechanisms seen later that century.5 This process has persisted throughout the history of antimicrobial discovery and use. The review “Origins and Evolution of Antimicrobial Resistance” provides a fantastic overview of the modes of action and resistance mechanisms of commonly used antimicrobials.5

With the rise of antimicrobial resistance and recognition that appropriate antimicrobial use is necessary to preserve efficacy arose the concept of antimicrobial stewardship. As early as the 1990s, programs began to be developed and were often led by specialists, including pharmacists, in infectious disease or clinical microbiology that focused on antimicrobial use and stewardship.67 Stewardship grew into an approach or set of methods that aim to optimize antimicrobial therapy and minimize toxicity to patients while always considering global impact of resistance.68 This principle of antimicrobial stewardship persists today and its implementation is sought with more urgency as the global crisis related to antimicrobial resistance becomes globally overwhelming.

Defining Antimicrobial Stewardship Around the World: Common Goals

Global

The World Health Organization (WHO) provides a toolkit for antimicrobial stewardship programs in healthcare environments in low- and middle-income countries.9 The toolkit defines antimicrobial stewardship to include a set of actions that are intended to promote responsible antimicrobial use and definitions of stewardship herein apply at the individual, national and global level across human, animal and environmental use.

United States of America

The Infectious Diseases Society of America (IDSA) & Society for Healthcare Epidemiology of America (SHEA)’s joint guideline on “Implementing an Antibiotic Stewardship Program” defines ASP as multiple coordinated strategies to improve and measure the appropriateness of antimicrobial use through selection of the optimal antimicrobial, and ensuring the best evidence is applied to other aspects of stewardship such as duration, and route of administration.10

Canada

The Pan-Canadian Public Health Network’s Communicable and Infectious Diseases Steering Committee Task Group on Antimicrobial Use Stewardship defines stewardship as a coordinated set of efforts and interventions to promote, improve monitor and evaluate the judicious use of antimicrobials with a focus on preserving future effectiveness and promoting human health.11

Europe

The European Centre for Disease Prevention and Control (ECDC) links to a 2017 European Commission guideline for product use of antimicrobials in human health that defines antimicrobial stewardship programs as coordinated efforts that focus on implementing interventions that improve appropriate antimicrobial prescribing.12

Australia

The Australian Commision on Safety and Quality in Health Care defines antimicrobial stewardship as including a range of different activities that promote and provide support that optimizes antimicrobial prescribing. Some of the suggested services include antimicrobial stewardship policy, reviews of prescribing and use, program evaluation for performance and providing implementation strategies to improve appropriateness of prescribing.13

All of these definitions from around the globe, and I suspect many more, echo the themes grouping antimicrobial stewardship interventions into the following goals: A coordinated effort with multiple services or initiatives brought together to improve appropriateness of antimicrobial prescribing, and, Simplification and optimization of antimicrobial regimens selected as well as choosing the most appropriate route, dose and duration of therapy are at the core of stewardship initiatives.

Beneficial Outcomes of Antimicrobial Stewardship

Beyond the global collaborative goals discussed above, some of the other broader benefits linked to ASP include:1 10 14 Combating misuse and overuse of antimicrobials by instilling evidence-based and judicial use of antimicrobials, Improved patient outcomes for treatment of infection by optimizing antimicrobials, Reduced adverse outcomes such as selection for multidrug resistant organism (MDROs) or Clostridium difficile infection, and, Sustainability of antimicrobial susceptibility by optimizing resource utilization across an entire continuum of care.

6 Great Antimicrobial Stewardship Resources

As you work to build and/or improve your antimicrobial stewardship program, here are 5 more handy resources that you may find useful.

1. This is a fantastic introductory course on antimicrobial use and prescribing for clinicians with a focus on stewardship: Antimicrobial Stewardship: A Competency-Based Approach (WHO)

2. Action plan created in 2015 as a result of growing antimicrobial resistance: Global Action Plan on Antimicrobial Resistance (WHO)

3. Below is a checklist that I created to help you make an impact on your ASP practice. Download the PDF here.



Spectrum ASP Tool

How can I start to make an impact in my practice?

Where to start
✓ Is this antimicrobial or antimicrobial regimen indicated (is there an active infection)?
✓ Have cultures been drawn based on the most likely source of infection?
✓ Is the selected antimicrobial therapy an empiric therapy? What is the plan for targetted therapy?

Focus on the pharmacotherapy details
✓ Is this the most appropriate therapy?
✓ Does it take into consideration comorbidities?
✓ Does it take into concomitant therapies (prescribed and non-prescribed)?
✓ Is the dose suited for renal and hepatic function?
✓ Is the dosing optimized to the suspected infectious pathogen and illness?
✓ Has risk of adverse events due to antimicrobial use been considered?
✓ What parameters are in place to monitor for efficacy and safety?

Follow Up and De-escalation
✓ Has renal function been reassessed
✓ Are cultures now available?
✓ Can therapy be narrowed or targeted?
✓ If antimicrobial is parenteral can stepdown to oral therapy be made?
✓ Is a multidisciplenary team involved in patient’s therapy? Should this be in place?
✓ How can we limit societal or braoder impact of antimicrobial use?

Reference:
Antimicrobial Stewardship: A competency-based approach



4. The Infectious Diseases Society of America (IDSA) & Society for Healthcare Epidemiology of America (SHEA) have assembled detailed and incredibly well-written guidelines for implementing an Antimicrobial Stewardship Program

5. Dr. Brad Spellberg is an Infectious Diseases Physician who publishes the Shorter Is Better list of resources in a fantastic repository of information to help optimize antimicrobial duration backed with evidence-based data

6. Dr. Timothy Gauthier is a Pharmacist and Editor-In-Chief of IDStewardship, which is another great resource where experts in Antimicrobial Stewardship & Infectious Diseases share educational material in a fun and easy to read manner.

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Biography:

Dr. Mira Maximos (PharmD) completed a hospital pharmacy residency at London Health Sciences Centre concomitantly with a Master of Science in Pharmacy and went on to pursue a Doctor of Pharmacy degree at the University of Waterloo. Dr. Maximos works at Woodstock Hospital in Ontario as an inpatient and antimicrobial stewardship pharmacist specializing in infectious diseases, with @Spectrum as the Knowledge Mobilization pharmacist and is a research associate with the Centre of Excellence for Women’s Health. You can follow her on Twitter @miramaximos.@miramaximos.

Conflicts of Interest: Mira Maximos is employed with Spectrum Mobile Health as a Knowledge Mobilization pharmacist

This blog post is for information/educational purposes only, and does not substitute professional medical advice. Also please note that opinions are those of the authors and do not necessarily reflect that of their employers.

References

  1. UN Interagency Coordination Group (IACG) on Antimicrobial Resistance. 2019. World Health Organization. “No Time to Wait: Securing the Future from Drug Resistant Infections.” (Accessed February 26, 2021).  2 3 4 5

  2. Centre for Disease Control. 2020. “Measuring Outpatient Antibiotic Prescribing”. (March 12, 2021). 

  3. Public Health Ontario. 2021. “Antibiotic overuse in Ontario’s long-term care homes”. (May 6, 2021). 

  4. Centre for Disease Control. 2020. “Antimicrobial Resistance.” Centre for Disease Control. (Accessed May 1, 2021). 

  5. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 2010;74(3):417-433.  2 3 4

  6. Dyar, O. J., B. Huttner, J. Schouten, and C. Pulcini. 2017. “What Is Antimicrobial Stewardship?” Clinical Microbiology and Infection 23(11): 793–98.  2

  7. Plachouras, D and Hopkins S. 2017. “Antimicrobial Stewardship: We Know It Works; Time to Make Sure It Is in Place Everywhere.” The Cochrane database of systematic reviews 2: ED000119.

  8. Doron S, Davidson LE. Antimicrobial stewardship. Mayo Clin Proc. 2011;86(11):1113-1123. 

  9. Antimicrobial Stewardship Programmes in Health-Care Facilities in Low-and Middle-Income Countries. A WHO Practice Toolkit. World Health Organization (WHO). (Accessed March 12, 2021). 

  10. Barlam TF et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016 May 15;62(10):e51-77.  2

  11. Pan-Canadian Public Health Network. The Communicable and Infectious Disease Steering Committee Task Group on Antimicrobial Use Stewardship. 2016. 

  12. European Union guidelines for the prudent use of antimicrobials in human health. Official Journal of the European Union. 2017. 

  13. Australian Commission on Safety and Quality in Health Care. Antimicrobial Stewardship. 2019. (Accessed May 10, 2021). 

  14. George P, Morris AM. Pro/con debate: Should antimicrobial stewardship programs be adopted universally in the intensive care unit? Crit Care. 2010;14(1):205.