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Antibiotics
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Proceedings from the 3rd International Conference on Polymyxins
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Proceedings from the 3rd International Conference on Polymyxins

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 55969

Special Issue Editors

Dr. Keith S. Kaye

E-Mail Website
Guest Editor
University of Michigan Medical School, Ann Arbor, MI 48109, USA
Interests: antimicrobial resistance, particularly among gram-negative bacilli; optimizing use of polymyxin antimicrobials; prevention of healthcare associated infections including Clostridium difficile, multi-drug resistant organisms, central-line associated infections and surgical site infections; innovative approaches to antimicrobial stewardship
Dr. Brian T. Tsuji

E-Mail Website
Guest Editor
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14203, USA
Interests: Dr. Tsuji’s research aims to optimize the exposure-response relationship for a number of antimicrobial agents including colistin, polymyxin B, vancomycin, and beta-lactams against clinically challenging pathogens. His ongoing projects explore novel pharmacokinetic/pharmacodynamic approaches for polymyxin combinations against multidrug resistant Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa
Dr. Zackery P. Bulman

E-Mail Website
Guest Editor
College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
Interests: Dr. Bulman’s laboratory investigates innovative polymyxin-based combination treatment strategies to combat carbapenem-resistant Enterobacteriaceae. He is also interested in understanding the relationship between polymyxin resistance and bacterial virulence. His current projects aim to target antimicrobial therapies to the infecting pathogen in an attempt to understand bacterial contributions to resistance and treatment failure
Dr. Justin R. Lenhard

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Guest Editor
California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA
Interests: Dr. Lenhard’s research endeavors focus on the rational design and optimization of polymyxin combinations against carbapenem-resistant and polymyxin-resistant A. baumannii. Ongoing investigations seek to identify optimal antibacterial regimens in the face of polymicrobial infections characterized by bacterial cooperation and modulated antimicrobial activity

Special Issue Information

Dear Colleagues,

The polymyxin antibiotics (polymyxin E (colistin) and polymyxin B) have seen a recent resurgence in clinical use due to the sharp rise in infections caused by multidrug-resistant Gram-negative pathogens that are not susceptible to most antimicrobial agents. This important role, as a last-line antibiotic, has recently led the World Health Organization to add the polymyxins to their “Highest Priority” tier of critically important antimicrobials for human medicine. However, since the polymyxins became available in the 1950s when there was substantially less regulatory rigor needed for drug approval than today, significant opportunity and need remains to optimize the use of polymyxins to improve patient care.

The International Conference on Polymyxins is a gathering of the world’s leading opinion-leaders to discuss the cutting-edge of polymyxin research and clinical use. Recently, the 3rd iteration of this conference occurred from April 25–26, 2018, in Madrid, Spain. Over 30 presentations by world leaders were provided to: highlight recent accomplishments in the field, deliver updates on toxicity, describe advances in the use of polymyxin-based combinations, summarize regulatory and world health perspectives of polymyxin use, discuss recent discoveries in polymyxin resistance, provide updates regarding susceptibility testing, project the future role of polymyxins, and provide a roadmap for future research.

In this Antibiotics Special Issue, we aim to highlight the proceedings from the 3rd International Conference on Polymyxins. We have procured a collection of articles from the perspectives of the world’s leading experts that review recent advances in polymyxin research and clinical use and provide an overview of the conference. In addition to providing highlights from the conference, articles also speculate on the future of polymyxin research and novel approaches to polymyxin therapy in the clinic. Through this 3rd International Conference on Polymyxins Special Issue, we hope to both reflect on, as well as stimulate, constructive discussion and research regarding the polymyxins so that this important antimicrobial class can be best used to benefit patients in need for many years to come.

Sincerely,

Dr. Keith S. Kaye
Dr. Brian T. Tsuji
Dr. Zackery P. Bulman
Dr. Justin R. Lenhard
Guest Editors

Conference Website:

https://medicine.umich.edu/dept/intmed/education-training/cme/3rd-international-conference-polymyxins

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Review

13 pages, 269 KiB  
Review
Shifting Gears: The Future of Polymyxin Antibiotics
by Justin R. Lenhard, Zackery P. Bulman, Brian T. Tsuji and Keith S. Kaye
Antibiotics 2019, 8(2), 42; https://doi.org/10.3390/antibiotics8020042 - 12 Apr 2019
Cited by 24 | Viewed by 6827
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
13 pages, 246 KiB  
Review
Polymyxins: To Combine or Not to Combine?
by Federico Perez, Nadim G. El Chakhtoura, Mohamad Yasmin and Robert A. Bonomo
Antibiotics 2019, 8(2), 38; https://doi.org/10.3390/antibiotics8020038 - 10 Apr 2019
Cited by 35 | Viewed by 5309
Abstract
Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads [...] Read more.
Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads to better outcomes remains unknown. This review discusses the limitations of observational studies that suggest a benefit of combinations of colistin and carbapenems to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, and summarizes the results of randomized controlled trials in which treatment with colistin in combination with meropenem or rifampin does not lead to better clinical outcomes than colisitn monotherapy in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). Although the introduction of new antibiotics makes it possible to treat certain strains of CRE and carbapenem-resistant P. aeruginosa (CRPA) with polymyxin-sparing regimens, the use of polymyxins is, for now, still necessary in CRAB and in CRE and CRPA harboring metallo-beta-lactamases. Therefore, strategies must be developed to optimize polymyxin-based treatments, informed by in vitro hollow fiber models, careful clinical observations, and high-quality evidence from appropriately designed trials. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
21 pages, 1588 KiB  
Review
Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria
by Emily M. Eichenberger and Joshua T. Thaden
Antibiotics 2019, 8(2), 37; https://doi.org/10.3390/antibiotics8020037 - 06 Apr 2019
Cited by 142 | Viewed by 22764
Abstract
Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of large sets of clinical bacterial isolates [...] Read more.
Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of large sets of clinical bacterial isolates has greatly expanded our understanding of how antibiotic resistance develops and transmits among bacteria and between patients. Diverse mechanisms of resistance, including antibiotic degradation, antibiotic target modification, and modulation of permeability through the bacterial membrane have been demonstrated. These fundamental insights into the mechanisms of gram-negative antibiotic resistance have influenced the development of novel antibiotics and treatment practices in highly resistant infections. Here, we review the mechanisms and global epidemiology of antibiotic resistance in some of the most clinically important resistance phenotypes, including carbapenem resistant Enterobacteriaceae, extensively drug resistant (XDR) Pseudomonas aeruginosa, and XDR Acinetobacter baumannii. Understanding the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterials and for individual treatment decisions, which often involve alternatives to β-lactam antibiotics. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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11 pages, 298 KiB  
Review
A Review of the Clinical Pharmacokinetics of Polymyxin B
by Sean N. Avedissian, Jiajun Liu, Nathaniel J. Rhodes, Andrew Lee, Gwendolyn M. Pais, Alan R. Hauser and Marc H. Scheetz
Antibiotics 2019, 8(1), 31; https://doi.org/10.3390/antibiotics8010031 - 22 Mar 2019
Cited by 66 | Viewed by 7396
Abstract
Polymyxin B remains an antibiotic of last resort because of its toxicities. Although newer therapies are becoming available, it is anticipated that resistance to these agents will continue to emerge, and understanding the safest and most efficacious manner to deliver polymyxin B will [...] Read more.
Polymyxin B remains an antibiotic of last resort because of its toxicities. Although newer therapies are becoming available, it is anticipated that resistance to these agents will continue to emerge, and understanding the safest and most efficacious manner to deliver polymyxin B will remain highly important. Recent data have demonstrated that polymyxin B may be less nephrotoxic than colistin. Pharmacokinetically, polymyxin B is primarily eliminated via non-renal pathways, and most do not recommend adjusting the dose for renal impairment. However, some recent studies suggest a weak relationship between polymyxin B clearance and patient creatinine clearance. This review article will describe the clinical pharmacokinetics of polymyxin B and address relevant issues in chemistry and assays available. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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22 pages, 656 KiB  
Review
A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia
by Mark Biagi, David Butler, Xing Tan, Samah Qasmieh and Eric Wenzler
Antibiotics 2019, 8(1), 27; https://doi.org/10.3390/antibiotics8010027 - 16 Mar 2019
Cited by 13 | Viewed by 6133
Abstract
Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the [...] Read more.
Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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18 pages, 526 KiB  
Review
Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity
by Roger L. Nation, Maria Helena P. Rigatto, Diego R. Falci and Alexandre P. Zavascki
Antibiotics 2019, 8(1), 24; https://doi.org/10.3390/antibiotics8010024 - 14 Mar 2019
Cited by 70 | Viewed by 6702
Abstract
Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and [...] Read more.
Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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