FDA approved antibacterial drugs: 2018-2019

Andrei, Ștefan; Droc, Gabriela; Ștefan, Gabriel

doi:10.15190/d.2019.15

Cited by 81 publications

(69 citation statements)

References 47 publications

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“…Even though several new antibiotics have been approved by the US Food and Drug Administration (FDA) over the last few years, emergence of resistance has already been reported ( Abdallah et al, 2015 ; de Man et al, 2018 ; Giddins et al, 2018 ; Karaiskos et al, 2019 ; Morrissey et al, 2020 ). Many clinicians worldwide have been forced to use polymyxins as the last-line therapy to treat life-threatening infections caused by the three aforementioned Gram negative “superbugs” because of their resistance to all currently available antibiotics ( Wertheim et al, 2013 ; Andrei et al, 2019 ; Zhang et al, 2020 ). Polymyxins (i.e., polymyxin B and colistin) are an “old” class of lipopeptide antibiotics that were approved in the late 1950s ( Li et al, 2006b ).…”

Section: Introductionmentioning

confidence: 99%

Rescuing the Last-Line Polymyxins: Achievements and Challenges

et al. 2021

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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: Introductionmentioning

confidence: 99%

Rescuing the Last-Line Polymyxins: Achievements and Challenges

et al. 2021

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“…However, most of these products are not very innovative, being derivatives of known classes, such as the tetracycline derivatives eravacycline, omadacycline, or sarecyclin, the cephalosporin derivative cefiderocol and the combination therapy imipenem-cilastatin-relebactam. Sarecycline is indicated for moderate to severe acne caused by Cutibacterium acnes while the combination therapy imipenem-cilastatin-relebactam and cefiderocol were approved for complicated urinary tract infections (Andrei et al 2019 ; EMA 2020 ; FDA 2020 ).…”

Section: Background: the Antibiotic Resistance Global Threat And Currmentioning

confidence: 99%

Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities

et al. 2021

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The global public health threat of antimicrobial resistance has led the scientific community to highly engage into research on alternative strategies to the traditional small molecule therapeutics. Here, we review one of the most popular alternatives amongst basic and applied research scientists, synthetic antimicrobial peptides. The ease of peptide chemical synthesis combined with emerging engineering principles and potent broad-spectrum activity, including against multidrug-resistant strains, has motivated intense scientific focus on these compounds for the past decade. This global effort has resulted in significant advances in our understanding of peptide antimicrobial activity at the molecular scale. Recent evidence of molecular targets other than the microbial lipid membrane, and efforts towards consensus antimicrobial peptide motifs, have supported the rise of molecular engineering approaches and design tools, including machine learning. Beyond molecular concepts, supramolecular chemistry has been lately added to the debate; and helped unravel the impact of peptide self-assembly on activity, including on biofilms and secondary targets, while providing new directions in pharmaceutical formulation through taking advantage of peptide selfassembled nanostructures. We argue that these basic research advances constitute a solid basis for promising industry translation of rationally designed synthetic peptide antimicrobials, not only as novel drugs against multidrug-resistant strains but also as components of emerging antimicrobial biomaterials. This perspective is supported by recent developments of innovative peptidebased and peptide-carrier nanobiomaterials that we also review.

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“…Even more troublesome is the ability of these Tet X variants to degrade other next-generation tetracyclines such as eravacycline [ 25 ] and omadacycline [ 26 ]. In 2018, the FDA approved the former drug for therapy of complex intra-abdominal infections, and the latter — for treatment of community-acquired bacterial pneumonia and acute skin and skin structure infections [ 27 ]. For example, tet (X5), which was detected in a clinical A. baumannii isolate from China in 2017, confers universal resistance to all classes of tetracyclines, including tetracycline, doxycycline, minocycline, tigecycline, eravacycline, and omadacycline [ 28 ].…”

Section: Present Situation With Tet (X)mentioning

confidence: 99%

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

Aminov

2021

IJMS

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Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal.

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FDA approved antibacterial drugs: 2018-2019

Cited by 81 publications

References 47 publications

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Rescuing the Last-Line Polymyxins: Achievements and Challenges

Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

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