Delafloxacin: design, development and potential place in therapy

Candel, Francisco Javier; Peñuelas, Marina

doi:10.2147/dddt.s106071

Cited by 50 publications

(46 citation statements)

References 57 publications

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“…Major milestones achieved and efforts made in developing phage therapy. Approvals for new chemical entities (NCE) ( blue ) and development of drug resistance (orange) is also mapped in chronological order .…”

Section: Phage Therapy—clinical Talesmentioning

confidence: 99%

Ameliorating the antimicrobial resistance crisis: phage therapy

Saha

Mukherjee

2019

IUBMB Life

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Propelled by the overuse and inappropriate use of antibiotics, antimicrobial resistance is now widespread in the environment, leaving us with limited drugs for treating a large number of resistant pathogens. The use of bacteriophages that kill bacteria has come up as a viable alternative to circumvent the antimicrobial resistance crisis, and phage therapy‐based approaches are fast advancing in recent times. In this minireview, we try to describe the advantages associated with phage therapy and update the latest developments in the field including the clinical trials that are underway. Particularly, we highlight the synergistic bactericidal effect of phages in the presence of sub‐lethal dose of antibiotics and the potency of lytic phages, and their hydrolytic enzymes in expunging pathogens from drug‐tolerant biofilms and animal farm produce. We also discuss how major challenges, including human immune response to phage components, development of bacterial resistance and elimination of intracellular pathogens, presented as potential setbacks to the implementation of phage therapy is being removed using engineered phages and novel formulations. © 2019 IUBMB Life, 2019

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Section: Phage Therapy—clinical Talesmentioning

confidence: 99%

Ameliorating the antimicrobial resistance crisis: phage therapy

Saha

Mukherjee

2019

IUBMB Life

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“…First, it has a novel mechanism of action with activity against multi-drug resistant organisms. 47 Along these lines, in-vitro studies have shown that the development of resistance to Delafloxacin is difficult since it requires the accumulation of several mutations that collectively affect both its targets (topoisomerase IV and DNA gyrase). 47 Furthermore, it does not seem to be a good substrate for bacterial efflux pumps.…”

Section: The Next Generation Of New Antibioticsmentioning

confidence: 99%

“…47 Along these lines, in-vitro studies have shown that the development of resistance to Delafloxacin is difficult since it requires the accumulation of several mutations that collectively affect both its targets (topoisomerase IV and DNA gyrase). 47 Furthermore, it does not seem to be a good substrate for bacterial efflux pumps. 47 Second this antibiotic has minimal interactions without metabolism in the cytochrome P450 system or any human hepatic microsomal system.…”

Section: The Next Generation Of New Antibioticsmentioning

confidence: 99%

“…47 Furthermore, it does not seem to be a good substrate for bacterial efflux pumps. 47 Second this antibiotic has minimal interactions without metabolism in the cytochrome P450 system or any human hepatic microsomal system. 45, 47 Its safety and tolerance profile is consequently also favorable, with only minimal amounts of minor side-effects.…”

Section: The Next Generation Of New Antibioticsmentioning

confidence: 99%

“…47 Second this antibiotic has minimal interactions without metabolism in the cytochrome P450 system or any human hepatic microsomal system. 45, 47 Its safety and tolerance profile is consequently also favorable, with only minimal amounts of minor side-effects. 45 Third it has a favorable PK and PD profile, with high potency for common and resistant CAP pathogens, especially in acidic environments.…”

Section: The Next Generation Of New Antibioticsmentioning

confidence: 99%

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Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Amalakuhan

Echevarria

Restrepo

2017

Expert Opinion on Pharmacotherapy

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INTRODUCTION Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns. AREAS COVERED After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly. EXPERT OPINION All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.

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Darobactine mit Überlegener Antibiotischer Aktivität Generiert durch Strukturgeleitetes Kryo‐EM‐Biosynthese‐Design**

et al. 2022

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In den letzten Jahrzehnten ist die Entwicklungspipeline neuer Antibiotika gegen Gram‐negative Bakterien nahezu zum Erliegen gekommen, da die meisten entdeckten Kandidaten Defizite im Bereich der Wirksamkeit, ihrer pharmakokinetischen Eigenschaften oder eine zu hohe Toxizität aufwiesen. Die Darobactine, eine vielversprechende neue Peptid‐Klasse, binden an BamA, ein zuvor von Antibiotika nicht adressiertes Zielprotein der äußeren Membran. Wir haben bereits gezeigt, dass durch Biosynthese‐Modifikationen in einem heterologen Wirt neuartige Darobactine mit erhöhter antibakterieller Aktivität erzeugt werden können. Nun verwenden wir eine optimierte Reinigungsmethode und präsentieren Kryo‐EM‐Strukturen des Bam‐Komplexes mit Darobactin 9 (D9), welche als Basis für die biotechnologische Herstellung von zwanzig neuen Darobactinen, einschließlich halogenierter Analoga, dient. Das neu entwickelte Darobactin 22 bindet enger an BamA und übertrifft das bereits hohe Aktivitätsprofil von D9 gegen klinisch relevante Krankheitserreger, wie Carbapenem‐resistente Acinetobacter baumannii, um das bis zu 32‐fache, ohne erkennbare Anzeichen von Toxizität.

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Delafloxacin: design, development and potential place in therapy

Cited by 50 publications

References 57 publications

Ameliorating the antimicrobial resistance crisis: phage therapy

Ameliorating the antimicrobial resistance crisis: phage therapy

Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Darobactine mit Überlegener Antibiotischer Aktivität Generiert durch Strukturgeleitetes Kryo‐EM‐Biosynthese‐Design**

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