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Polymyxins: To Combine or Not to Combine?
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Shifting Gears: The Future of Polymyxin Antibiotics

1
Department of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA
2
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
3
Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics and Life Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, NY 14215, USA
4
Department of Internal Medicine; Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA
*
Authors to whom correspondence should be addressed.
The authors both contributed equally to the present work.
Antibiotics 2019, 8(2), 42; https://doi.org/10.3390/antibiotics8020042
Received: 28 February 2019 / Revised: 5 April 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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Abstract

The manuscripts contained in this special edition of Antibiotics represent a current review of the polymyxins as well as highlights from the 3rd International Polymyxin Conference, which was held in Madrid, Spain, 25 to 26 April 2018. The role of the polymyxin antibiotics has evolved over time based on the availability of alternative agents. After high rates of nephrotoxicity caused the drug class to fall out of favor, polymyxins were once against utilized in the 21st century to combat drug-resistant pathogens. However, the introduction of safer agents with activity against drug-resistant organisms has brought the future utility of polymyxins into question. The present review investigates the future niche of polymyxins by evaluating currently available and future treatment options for difficult-to-treat pathogens. The introduction of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin are likely to decrease polymyxin utilization for infections caused by Enterobacteriaceae. Similarly, the availability of ceftolozane-tazobactam will reduce the use of polymyxins to counter multidrug-resistant Pseudomonas aeruginosa. In contrast, polymyxins will likely continue be an important option for combatting carbapenem-resistant Acinetobacter baumannii until better options become commercially available. Measuring polymyxin concentrations in patients and individualizing therapy may be a future strategy to optimize clinical outcomes while minimizing nephrotoxicity. Inhaled polymyxins will continue to be an adjunctive option for pulmonary infections but further clinical trials are needed to clarify the efficacy of inhaled polymyxins. Lastly, safer polymyxin analogs will potentially be an important addition to the antimicrobial armamentarium. View Full-Text
Keywords: polymyxins; Acinetobacter baumannii; Klebsiella pneumoniae; Pseudomonas aeruginosa; carbapenem resistance; β-lactamase inhibitors; avibactam; ceftolozane; cefiderocol; inhaled antibiotics polymyxins; Acinetobacter baumannii; Klebsiella pneumoniae; Pseudomonas aeruginosa; carbapenem resistance; β-lactamase inhibitors; avibactam; ceftolozane; cefiderocol; inhaled antibiotics
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lenhard, J.R.; Bulman, Z.P.; Tsuji, B.T.; Kaye, K.S. Shifting Gears: The Future of Polymyxin Antibiotics. Antibiotics 2019, 8, 42.

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