You Know You Got 'Bad Bugs'

In response to the serious global concern of growing drug-resistant “superbugs,” thirteen leading pharmaceutical companies have pledged to clean up pollution from company factories and prevent overuse of antibiotics.

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Industries will collaborate with independent experts to establish new factory standards and keep antibiotic waste from entering into the water supply to preserve the growth of drug resistance. Measures in effort to prevent antibiotic overuse, including removal of incentives for selling drugs in large bulk and raise awareness on antibiotic overuse for humans and livestock, are to be implemented by 2020.

Global pharmaceutical companies participating in this effort include Pfizer, Novartis, GlaxoSmithKline, Allergan, Germany’s Merck, India’s Cipla and Wockhardt. This pledge parallels with the declaration made at the General Assembly of the United Nations (UN) held in New York mid-September this year.

Prior to this meeting, there had been only three major health issues discussed at general assembly high-level meetings—HIV/AIDS, non-communicable diseases (such as hypertension and diabetes), and Ebola. On Wednesday, September 21, 2016, all 193 nations at the General Assembly declared, in reaffirmation with the World Health Organization global action plan, to combat the “nightmare” and “catastrophic threat” of antibiotic resistance.

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Efforts will be continued on a national level, as outlined in the 2015 National Action Plan for Combating Antibiotic Resistant Bacteria.

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In support of activities in the Centers for Disease Control and Prevention (CDC) Antibiotic Resistance Solutions Initiative, over $14 million have recently been awarded to fund 34 innovative projects.

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These research efforts, primarily being conducted at multiple universities across the country, will focus on understanding the role of the microbiome in predicting antibiotic resistance.

Since Alexander Fleming discovered penicillin in 1928, the role of antibiotics has been vital in saving millions of lives.

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However, as a result of multiple disruptions in the global microbiome, including antibiotic overuse and misue, we are now seeing the emergence of “superbugs.” In a recently published JAMA article, it was estimated that 30% of outpatient oral antibiotics were inappropriately prescribed.

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Other contributory factors include the widespread use of antibiotics in livestock which affects the environmental microbiome, as well as the lack of research and development of new antibiotics.

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Fifteen out of the 18 largest pharmaceutical companies have abandoned the antibiotic field due to lack of profit and economic incentives in comparison to drug development in chronic conditions.

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The UN addressed these concerns in their political declaration, by stating the need for increasing “measures for strengthening appropriate antibiotic use in humans and animals” as well as “mobiliz[ing] funding… of research and development on existing and new antimicrobial medicines, diagnostics, vaccines.”

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At least 2 million Americans become infected with drug-resistant bacteria annually, directly causing over 23,000 deaths.

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In addition, multidrug-resistant organisms cause more than 700,000 deaths globally each year.

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A recent British study estimated that 10 million people worldwide will die from an antimicrobial-resistant infection by 2050.

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This amount would exceed the current number of deaths caused by cancer each year.

Other concerning issues of emerging antimicrobial resistance are also occurring with infections such as tuberculosis and gonorrhea. Annually, about 480,000 people are infected with drug-resistant tuberculosis worldwide.

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The impact of this in the United States is observed in the direct cost of treatment for the disease, which is approximately $150,000 per case in multidrug-resistant tuberculosis and up to $482,000 in extensively drug-resistant tuberculosis. In comparison, drug-susceptible tuberculosis costs $17,000 per case.¹⁰

When looking at gonorrhea, most recently, the CDC and Hawaii’s Department of Health reported alarming news of cases of highly-resistant infections.

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Strains of Neisseria gonorrhoeae were found to be resistant to azithromycin and partially resistant to ceftriaxone. Combination therapy with these agents, which have been recommended by CDC since 2010 because of the increase in drug-resistant strains over the last several decades, are now being threatened by emerging resistant N. gonorrhoeae strains.

“Superbugs” have reached marked resistance which healthcare providers may not be able to treat. Over the past year, there have been four patients identified with isolates positive for the colistin-resistance mcr-1 gene in the United States, raising alarm for “superbugs,” to which very few options are feasible.¹² Enterobacteriaceae with this gene were first discovered in China in 2015,

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and many similar strains were increasingly found in other countries worldwide.

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With the alliance of the Food and Agriculture Organization of the United Nations, the World Health Organization, and pharmaceutical firms, antimicrobial resistance is now being directly challenged in cohesive battle against a global threat. The extent to which these efforts will make a positive impact will be seen in the coming months and years as we face this global enemy with a united front.

Betty Vu, PharmD, is a PGY2 infectious diseases pharmacy resident in the Department of Pharmacy at Midwestern University, Chicago College of Pharmacy. Her clinical pharmacy practice site is at RUSH University Medical Center in Chicago, IL. She completed her PGY1 pharmacy residency at Montefiore Medical Center in Bronx, NY and her Doctor of Pharmacy degree at the University at Buffalo. She is an active member of ACCP, IDSA, and SIDP.

References

1. Hirschler B. Drugmakers pledge to clean up antibiotic factories, curb overuse. Reuters website. www.reuters.com/article/us-un-assembly-antibiotics-idUSKCN11Q1AA. Published September 20, 2016. Accessed September 28, 2016.
2. General Assembly of the United Nations. Draft political declaration of the high-level meeting of the General Assembly on antimicrobial resistance. UN website. www.un.org/pga/71/wp-content/uploads/sites/40/2016/09/DGACM_GAEAD_ESCAB-AMR-Draft-Political-Declaration-1616108E.pdf. Published September 21, 2016. Accessed September 29, 2016.
3. National Action Plan for Combating Antimicrobial Resistance. Washington, DC: The White House; March 2015. www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf.
4. CDC funds 34 innovative projects to combat antibiotic resistance [press release]. Atlanta, GA: Centers for Disease Control and Prevention; October 6, 2016. www.cdc.gov/media/releases/2016/p1006-cdc-antibiotic-resistance-research.html. Accessed October 7, 2016.
5. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17):1864-1873.
6. Bartlett JG, Gilbert DN, Spellberg B. Seven ways to preserve the miracle of antibiotics. Clin Infect Dis. 2013;56(10):1445-1450.
7. CDC. Antibiotic resistance threats in the United States, 2013. CDC website. www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Published April 23, 2013. Accessed September 28, 2016.
8. Review on Antimicrobial Resistance. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Review on Antimicrobial Resistance website. https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf. Published December 2014. Accessed September 29, 2016.
9. World Health Organization. Global tuberculosis report 2015. WHO website. www.who.int/tb/publications/global_report/en/. Published 2015. Accessed September 28, 2016.
10. Marks SM, Flood J, Seaworth B, et al; TB Epidemiologic Studies Consortium. Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007. Emerg Infect Dis. 2014;20(5)812-821.
11. New warning signs that gonorrhea treatment may be losing effectiveness [press release]. Atlanta, GA: Centers for Disease Control and Prevention; September 21, 2016. http://www.cdc.gov/nchhstp/newsroom/2016/2016-std-prevention-conference-press-release.html.
12. Vasquez AM, Montero N, Laughlin M, et al. Investigation of Escherichia coli harboring the mcr-1 resistance gene— Connecticut, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(36):99-980.
13. Liu YY, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161-168.
14. Castanheira M, Griffin MA, Deshpande LM, Mendes RE, Jones RN, Flamm RK. Detection of mcr-1 among Escherichia coli clinical isolates collected worldwide as part of the SENTRY Antimicrobial Surveillance Program in 2014 and 2015. Antimicrob Agents Chemother. 2016;60(9):5623-5624.
15. Skov RL, Monnet DL. Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds. Euro Surveill. 2016;21(9).