Anti-endotoxin Properties of Polymyxin B-immobilized Fibers

Tani, Tohru; Shimizu, Tomoharu; Tani, Masaji; Shoji, Hiromichi; Endo, Yuichi

doi:10.1007/978-3-030-16373-0_19

Cited by 17 publications

(12 citation statements)

References 64 publications

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“…Toraymyxin, a blood purification cartridge containing polymyxin B–immobilized fibers, has been developed for the removal of endotoxin from blood in humans ( Tani et al, 2019 ). The first clinical data with Toraymyxin were reported in 1994, showing a decreased level of circulating endotoxin and an improved hyperdynamic state in patients with septic multiple organ failure ( n = 16) ( Aoki et al, 1994 ).…”

Section: Antiendotoxin Properties Of Polymyxinsmentioning

confidence: 99%

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Nang

Azad

Velkov

et al. 2021

Pharmacological Reviews

260

172

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Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of “safer” antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative “superbugs,” every effort must be made to improve the clinical utility of the last-line polymyxins. Significance Statement Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.

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Section: Antiendotoxin Properties Of Polymyxinsmentioning

confidence: 99%

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Nang

Azad

Velkov

et al. 2021

Pharmacological Reviews

260

172

View full text Add to dashboard Cite

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“…PMB has a unique advantage in Gram-negative sepsis therapy, due to its bacterial endotoxin LPS-binding ability 233 . Since 1994, PMB has been well applied for immobilization in columns to remove endotoxins from the bloodstream, for the treatment of severe sepsis and septic shock 234 , 235 , 236 , 237 , 238 . Recently, the development of nano-drug delivery systems has led to significant improvements in the bioavailability and safety of AMPs in vivo .…”

Section: Mdps-based Formulations and Their Applicationsmentioning

confidence: 99%

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

Lin

Chi

Yan

et al. 2021

Acta Pharmaceutica Sinica B

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Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

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“…The anti-endotoxin activity of polymyxins has been considered as a potential treatment of sepsis [58]. Hemoperfusion using a polymyxin B-immobilized fiber blood purification column was developed in Japan in the nineties and proposed to remove circulating endotoxin in sepsis and shock [59].…”

Section: Anti-endotoxin Activitymentioning

confidence: 99%

Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

et al. 2021

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Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.

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Anti-endotoxin Properties of Polymyxin B-immobilized Fibers

Cited by 17 publications

References 64 publications

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

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