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Antimicrobials — Handle With Care

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Antimicrobial-resistant pathogens are on the rise, driven by overuse, misuse, and agricultural use of the drugs designed to kill them.

Infection with antimicrobial-resistant microbes is blamed for over 700,000 deaths per year globally, and with the continued rise of antimicrobial resistance, this number could top 10 million by 2050.1 The rise of antibiotic resistance jeopardizes our ability to treat common infections, and microbes previously considered innocuous are becoming deadly.2

A brief history of the antibiotic era

When the story of antimicrobials is told, most people think of the “antibiotic era” and begin the story with Alexander Fleming’s messy lab and the accidental discovery of penicillins in 1928. That said, there is evidence that tetracycline, an antibiotic commercialized in 1948,3 was used hundreds of years BCE, likely, as part of the diet to prevent infection.4 Similarly, the anti-malarial medication artemisinin (quinghaosu) has been used in Chinese medicine for thousands of years to treat multiple diseases.5 The first documented hospital use of an antimicrobial was by Emmerich and Löw in 1899;6 they used an extract from Pseudomonas aeruginosa that was active against multiple pathogens but was, unfortunately, highly toxic to humans.

Superbugs, strains of microbes resistant to most drugs used for treating infections, threaten our ability to treat both simple and severe infections. As early as 1945, Fleming observed bacteria becoming resistant to penicillin, stating that, “[t]he thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism”.7 Despite that warning, antibiotics are still prescribed when not needed.

In 2016, the United States Centers for Disease Control and Prevention estimated that, of the antibiotics prescribed in outpatient settings, at least 30% of them were not needed.8 Historically, factory farming9,10,11 has accounted for approximately 80% of all antibiotic use, contaminating the environment and driving the evolution of superbugs. Clinically, the majority of antimicrobial resistance comes from misuse – patient non-compliance and over prescription.

When prescribed appropriately, taking antimicrobials for infection can kill the invader, but when the full dose of the medication is not taken properly – because the patient forgets or because of adverse events – or when antibiotics are prescribed for viral infections, stronger survivors may be left behind. Any antibiotic use, whether needed or not, contributes to the rising rates of resistance.12 And the rise of resistance threatens everything from the safety
and efficacy of surgical procedures to treating infections in immunosuppressed cancer patients.13

Microbes can become resistant to antimicrobials in a variety of ways. Bacteria can share DNA, often in the form of plasmids, containing genes that break down some antibiotics. And the more antibiotic-resistant bacteria there are, the faster the population of antibiotic-resistant bacteria rises. The top antibiotic-resistant microbes on the World Health Organization (WHO) watchlist include carbapenem-resistant Enterobacteriaceae (CRE; including Escherichia coli and Klebsiella pneumoniae) and Acinetobacter (including Acinetobacter baumannii), methicillin-resistant Staphylococcus aureus (MRSA), and multi-drug resistant Neisseria gonorrhoeae, Mycobacterium tuberculosis,14 and Clostridiodies difficile.15

The future of antibiotic resistance

A good way to avoid the use of antimicrobials is to avoid infection. Two years of a pandemic brought awareness to best practices for infection control. Frequent handwashing, keeping hands away from the face, and staying at home when ill are at the base of infection control both in and out of the hospital setting. Further, taking antibiotics only when necessary not only decreases potentially negative side effects but also decreases the likelihood of resistance formation.

Much work remains to be done to fight antibiotic resistance and keep us out of a post-antibiotic era. Since the introduction of penicillin as a treatment for bacterial infections almost 80 years ago, bacteria have eventually developed resistance against every antibiotic that has been identified.16 According to the WHO, “[d]evelopment of new antibiotics is almost at a standstill and the world is running out of antibiotics.”17

But there is hope. One study18 showed that decreasing prescription of macrolide antibiotics for streptococcal infections led to a 50% reduction in macrolide resistance. And antibiotic stewardship programs have led to similar reductions in many other infectious agents.12 Further, in 2017, the Food and Drug Administration implemented a policy where antibiotics of medical importance – those that are needed for human treatment – cannot legally be given for animal growth promotion19,20 to help limit antibiotic resistance arising from food-producing animals.

WHO, along with their counterparts at the Food and Agriculture Organization of the United Nations, the United Nations Environment Programme, and the World Organisation for Animal Health, have determined that the only way to decrease antimicrobial resistance is to take steps towards improving antibiotic stewardship together.

Beckman Coulter’s contribution

Making the right decisions to support your laboratory’s antibiotic stewardship initiatives is critical to combating emerging resistant threats. Our specialized panels* feature drugs recommended by the Infectious Disease Society of America (IDSA) to treat pyelonephritis and complicated urinary tract infections caused by ESβLs (Extended-Spectrum beta-lactamase producing E. coli) which include ertapenem, meropenem, imipenem-cilastatin, ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole.21

For gram-positive infections, we feature important drugs like vancomycin and ceftaroline which can help to combat Methicillin-resistant Staphylococcus aureus (MRSA) infections. 22 Our solutions and variety of panels can help your laboratory get in front of the most prevalent and dangerous multi-drug resistant organisms (MDROs) and help in the fight against antimicrobial resistance.

To download the latest Beckman Coulter panel brochure, please visit: 2022 Beckman Coulter Panel Brochure Download

This article has been paid for by Beckman Coulter.

This article was originally published at https://www.beckmancoulter.com/en/blog/diagnostics/the-importance-of-antibiotic-stewardship.

*Not available for sale in all countries. Please check with your sales representative.

References:
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1. New Report Calls for Urgent Action to Avert Antimicrobial Resistance Crisis.
(2019, April 29). Retrieved October 14, 2022, from https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis
2. Van Tyne, D. et al. (2019). Impact of Antibiotic Treatment and Host Innate Immune Pressure on Enterococcal Adaptation in the Human Bloodstream. Science Translational Medicine, 11(487). https://doi.org/10.1126/scitranslmed.aat8418
3. Nelson, M. L., & Levy, S. B. (2011). The History of the Tetracyclines. Annals of the New York Academy of Sciences, 1241, 17–32. https://doi.org/10.1111/j.1749-6632.2011.06354.x
4. Aminov R. I. (2010). A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future. Frontiers in Microbiology, 1,134. https://doi.org/10.3389/fmicb.2010.00134
5. Cui L., Su X. Z. (2009). Discovery, Mechanisms of Action and Combination Therapy of Artemisinin. Expert Rev. Anti. Infect. Ther. 7, 999–1013 10.1586/eri.09.68
6. Emmerich R., Löw O. (1899). Bakteriolytische Enzyme Als Ursache der Erworbenen Immunität und die Heilung von Infectionskrankheiten Dch Dieselben. Z. Hyg. 31, 1–65 10.1007/BF02206499
7. Tay, K. et al. (2019). Multi-Faceted Intervention to Improve the Antibiotic Prescriptions among Doctors for Acute URI and Acute Diarrhoea Cases: The Green Zone Antibiotic Project. The Malaysian Journal of Medical Sciences: MJMS, 26(4), 101–109. https://doi.org/10.21315/mjms2019.26.4.12
8. Harris, A. et al. (2016). Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention. Annals of
Internal Medicine, 164(6), 425. https://doi.org/10.7326/m15-1840
9. Tollefson, L. et al. (1997). Therapeutic Antibiotics in Animal Feeds and Antibiotic Resistance. Revue Scientifique et Technique (International Office of Epizootics), 16(2), 709–715. https://doi.org/10.20506/rst.16.2.1054
10. Wegener H. C. (2003). Antibiotics in Animal Feed and Their Role in Resistance Development. Current Opinion in Microbiology, 6(5), 439–445. https://doi.org/10.1016/j.mib.2003.09.009
11. Kurenbach, B. et al. (2015, May). Sublethal Exposure to Commercial Formulations of the Herbicides Dicamba, 2,4-Dichlorophenoxyacetic Acid, and Glyphosate Cause Changes in Antibiotic Susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium. MBio, 6(2). https://doi.org/10.1128/mbio.00009-15
12. David C. et al. (2017). Antibiotic Overprescribing: Still a Major Concern. Journal of Family Practice, 66(12), 730–
736. https://pubmed.ncbi.nlm.nih.gov/29202142/
13. Teillant, A. et al. (2015). Potential Burden of Antibiotic Resistance on Surgery and Cancer Chemotherapy Antibiotic Prophylaxis in the USA: A Literature Review and Modelling Study. The Lancet. Infectious diseases, 15(12), 1429–1437. https://doi.org/10.1016/S1473-3099(15)00270-4
14. Antimicrobial resistance. (2021, November 17). Retrieved October 21, 2022, from https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
15. Wickramage, I. et al. (2021, July 23). Mechanisms of Antibiotic Resistance of Clostridioides difficile. Journal of Antimicrobial Chemotherapy, 76(12), 3077–3090. https://doi.org/10.1093/jac/dkab231
16. Fair, R. & Tor, Y. (2014). Antibiotics and Bacterial Resistance in the 21st century. Perspectives in Medicinal Chemistry, 6, 25–64. https://doi.org/10.4137/PMC.S14459
17. World Antimicrobial Awareness Week 2022- Spread Awareness, Stop Resistance. (2022, November 18). Retrieved October 14, 2022, from https://www.who.int/news-room/events/detail/2022/11/18/default-calendar/world-antimicrobial-awareness-week-2022
18. Seppälä, H. et al. (1997). The Effect of Changes in the Consumption of Macrolide Antibiotics on Erythromycin Resistance in Group A Streptococci in Finland. New England Journal of Medicine, 337(7), 441–446. https://doi.org/10.1056/nejm199708143370701
19. Federal Register, Volume 76 Issue 246 (Thursday, December 22, 2011). (2011, December 22). https://www.govinfo.gov/content/pkg/FR-2011-12-22/html/2011-32775.htm
20. Recommendations for Sponsors of Medically Important Antimicrobial Drugs Approved for Use in Animals to Voluntarily Bring Under Veterinary Oversight All Products That Continue to be Available as Over the Counter; Guidance for Industry; Availability. (2021, June 11). U.S. FDA. Federal Register/Vol. 86, No. 111 / June 7, 2021 /Notices. https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry
21. https://www.idsociety.org/practice-guideline/amrguidance/#Table1.%C2%A0Suggesteddosingofantibioticsforthetreatmentofinfectionscausedbyantimicrobial-resistantorganisms
22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204005/

This article was originally published at https://www.beckmancoulter.com/en/blog/diagnostics/the-importance-of-antibiotic-stewardship.

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