Dataset Information

Rescuing the Last-Line Polymyxins: Achievements and Challenges.

ABSTRACT: 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.

SUBMITTER: Nang SC

PROVIDER: S-EPMC7911091 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Birth cohorts are those among observational studies that provide understanding of the natural history and causality of diseases since early in life. Discussions during an International Association for Dental Research symposium in London, United Kingdom, in 2018, followed by a workshop in Bangkok, Thailand, in 2019, concluded that there are few birth cohort studies that consider oral health and that a broader discussion on similarities and differences among those studies would be valuable. This article aims to 1) bring together available long-term data of oral health birth cohort studies from the low, middle, and high-income countries worldwide and 2) describe similarities and differences among these studies. This work comprises 15 studies from all 5 continents. The most studied dental conditions and exposures are identified; findings are summarized; and methodological differences and similarities among studies are presented. Methodological strengths and weaknesses are also highlighted. Findings are summarized in 1) the negative impact of detrimental socioeconomic status on oral health changes over time, 2) the role of unfavorable patterns of dental visiting on oral health, 3) associations between general and oral health, 4) nutritional and dietary effects on oral health, and 5) intergenerational influences on oral health. Dental caries and dental visiting patterns have been recorded in all studies. Sources of fluoride exposure have been documented in most of the more recent studies. Despite some methodological differences in the way that the exposures and outcomes were measured, some findings are consistent. Predictive models have been used with caries risk tools, periodontitis occurrence, and permanent dentition orthodontic treatment need. The next steps of the group's work are as follows: 1) establishing a consortium of oral health birth cohort studies, 2) conducting a scoping review, 3) exploring opportunities for pooled data analyses to answer pressing research questions, and 4) promoting and enabling the development of the next generation of oral health researchers.

Dataset Information

Rescuing the Last-Line Polymyxins: Achievements and Challenges.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets