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Thoracic Transplantation on the Cusp of the Post-Antibiotic Era


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Stephanie Pouch, MD
The Ohio State University
Columbus, OH, USA
Stephanie.pouch@osumc.edu



The lead article in the May 21, 2016 issue of The Economist, entitled "When the Drugs Don't Work," was, in my opinion, brilliant [1]. As a transplant infectious diseases specialist, I think about antimicrobial resistance on a daily basis. I often find myself needing to use older, toxic antimicrobials in combinations that have not been systematically evaluated in clinical trials in an attempt to manage multidrug resistant infections, such as those due to carbapenem-resistant Enterobacteriaceae. We are often able to effectively treat these infections; however, antimicrobials such as the polymyxins and aminoglycosides, especially when used in conjunction with calcineurin inhibitors, can lead to toxicities such as kidney injury, which may in turn have deleterious downstream effects on patient and graft outcomes. While there are a few newer agents currently available, including ceftazidime-avibactam and ceftolozane-tazobactam, as well as a small number of additional agents in development, the pipeline remains relatively dry. Compound these issues with more recently described mechanisms of antibiotic resistance, including the MCR-1 gene conveying resistance to colistin, it becomes apparent that we are headed towards a post-antibiotic era.

So why was the article in The Economist so remarkable? It highlighted the need to fight antimicrobial resistance on several fronts, including policy change, encouragement of innovation by decoupling payments from sales, focusing on the cost of antibiotic resistance to society as a whole, and most importantly emphasizing behavioral changes among physicians, patients, and the agricultural industry [1]. At the end of the day, we are all stakeholders in this issue.

My message is not one of doom and gloom. Rather, I prefer to look at the current state of affairs as an opportunity to impact change on a global scale.

In March 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria, which stated that "antibiotic resistance is a global health problem that requires international attention and collaboration because bacteria do not recognize borders." It recommended formalized stewardship programs to reduce antimicrobial resistance and stressed the urgent need for global collaboration [2]. Solid organ transplant recipients are particularly vulnerable to the acquisition of multidrug-resistant organisms (MDROs) due to poor functional status, prolonged hospitalization, previous colonization and/or infection with MDROs, and the excessive and often protracted use of broad-spectrum antimicrobials [3]. Stewardship programs have been effective in decreasing the inappropriate use of antibiotics and limiting the evolution of antimicrobial resistance without negatively altering clinical outcomes [4]. However, while our patients likely benefit from the downstream effect of hospital-wide stewardship initiatives, there is currently no formal guidance on antimicrobial stewardship for organ transplant recipients [5].

As healthcare providers, I challenge us, regardless of specialty, to be an antibiotic steward. We should use rapid diagnostic testing as available, review antibiotic use on a daily basis, work together in an interdisciplinary manner to ensure that the choice of antibiotic, dose, and duration are appropriate for each patient we treat. Globally, we, as members of the International Society for Heart & Lung Transplantation, have a unique opportunity to pioneer thoracic transplant stewardship. The evolution of antibiotic resistance is real, but we can be the drivers of major change now and ensure that not only our patients, but our society agriculturally and environmentally from hospitals to homes will continue to thrive in the future. ■

Disclosure Statement: The author has no conflicts of interest to disclose.


References:

  1. http://www.economist.com/news/leaders/21699116-how-combat-dangerous-rise-antibiotic-resistance-when-drugs-donu2019t-work
  2. https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf
  3. Patel G, Rana MM, Huprikar S. Multidrug-resistant bacteria in organ transplantation: an emerging threat with limited therapeutic options. Curr Infect Dis Rep 2013; 15: 504-13.
  4. Kaki R, Elligsen M, Walker S, et al. Impact of antimicrobial stewardship in critical care: A systematic review. J Antimicrob Chemother 2011; 66: 1223-1230.
  5. Aitken SL, Palmer HR, Topal JE, et al. Call for antimicrobial stewardship in solid organ transplantation. Am J Transplant 2013; 13: 2499.



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