Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

Frontiers in Microbiology, Journal Year: 2019, Volume and Issue: 10

Published: April 1, 2019

The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa Enterobacter spp. Persistent use of antibiotics has provoked the emergence resistant (MDR) extensively drug (XDR) bacteria, which render even most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development novel therapeutics to treat infections, especially those caused by is need hour. Alternative therapies such in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles photodynamic light therapy are widely reported. Many reviews published till date describe these respect various agents used, their dosage details mechanism action against MDR but very few focused specifically on ESKAPE. objective this review alternative reported advantages limitations, potential application vivo status clinical trials. further highlights importance a combinatorial approach, wherein two more used order overcome individual additional studies warranted, before translating them into practice. These advances could possibly give alternate solution extend lifetime current antimicrobials.

Language: Английский

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The global preclinical antibacterial pipeline

Nature Reviews Microbiology, Journal Year: 2019, Volume and Issue: 18(5), P. 275 - 285

Published: Nov. 19, 2019

Antibacterial resistance is a great concern and requires global action. A critical question whether enough new antibacterial drugs are being discovered developed. review of the clinical drug pipeline was recently published, but comprehensive information about preclinical unavailable. This Review focuses on discovery development projects has found, as 1 May 2019, 407 from 314 institutions. The focus Gram-negative pathogens, particularly bacteria WHO priority list. characterized by high levels diversity interesting scientific concepts, with 135 direct-acting small molecules that represent classes, targets or mechanisms There also strong trend towards non-traditional approaches, including diverse antivirulence microbiome-modifying strategies, engineered phages probiotics. number pathogen-specific adjunctive approaches unprecedented in antibiotic history. Translational hurdles not adequately addressed yet, especially pathways to show impact approaches. innovative potential compared encouraging fragile. Much more work, funding needed for novel result effective therapies sustainably combat resistance.

Language: Английский

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Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era

Medicinal Research Reviews, Journal Year: 2018, Volume and Issue: 39(3), P. 831 - 859

Published: Oct. 24, 2018

Abstract Antimicrobial peptides (AMPs), critical components of the innate immune system, are widely distributed throughout animal and plant kingdoms. They can protect against a broad array infection‐causing agents, such as bacteria, fungi, parasites, viruses, tumor cells, also exhibit immunomodulatory activity. AMPs exert antimicrobial activities primarily through mechanisms involving membrane disruption, so they have lower likelihood inducing drug resistance. Extensive studies on structure‐activity relationship revealed that net charge, hydrophobicity, amphipathicity most important physicochemical structural determinants endowing with potency cell selectivity. This review summarizes recent advances in development respect to characteristics, relationships, functions, mechanisms, expression regulation, applications food, medicine, animals.

Language: Английский

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Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli

Drugs, Journal Year: 2019, Volume and Issue: 79(3), P. 271 - 289

Published: Feb. 1, 2019

Language: Английский

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Antibiotic Adjuvants: Make Antibiotics Great Again!

Journal of Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 62(19), P. 8665 - 8681

Published: May 7, 2019

Multiple approaches have been developed to combat bacterial resistance. However, the combination of antibiotic resistance mechanisms by bacteria and limited number effective antibiotics available decreases interventions for treatment current infections. This review covers many ways that resist including target modification, use efflux pumps, inactivation. As a pertinent example, beta lactamase inhibitors in with β-lactam containing is discussed detail. The solution emerging may involve therapies existing potentiating adjuvants, which re-empower agent become efficacious against resistant strain interest. We report herein reasoned adjuvant design permits one perform polypharmacy on not only providing greater internal access codosed but also de-energizing pumps used escape action.

Language: Английский

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Antibiotic resistance: turning evolutionary principles into clinical reality

FEMS Microbiology Reviews, Journal Year: 2020, Volume and Issue: 44(2), P. 171 - 188

Published: Jan. 24, 2020

Antibiotic resistance is one of the major challenges facing modern medicine worldwide. The past few decades have witnessed rapid progress in our understanding multiple factors that affect emergence and spread antibiotic at population level individual patient. However, process translating this into health policy clinical practice has been slow. Here, we attempt to consolidate current knowledge about evolution ecology a roadmap for future research as well environmental control resistance. At level, examine emergence, transmission dissemination resistance, patient adaptation involving bacterial physiology host resilience. Finally, describe new approaches technologies improving diagnosis treatment minimizing

Language: Английский

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Antibacterial and antioxidant activities for natural and synthetic dual-active compounds

European Journal of Medicinal Chemistry, Journal Year: 2018, Volume and Issue: 158, P. 91 - 105

Published: Sept. 5, 2018

Language: Английский

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Antibiotic adjuvants: an alternative approach to overcome multi-drug resistant Gram-negative bacteria

Critical Reviews in Microbiology, Journal Year: 2019, Volume and Issue: 45(3), P. 301 - 314

Published: April 15, 2019

Antibiotic resistance in Gram-negative pathogens has emerged and constituted a global crisis, thereby novel antibiotics other anti-infective strategies are urgently needed. However, the growing gap between clinical need drug innovation, coupled with membrane permeability barrier bacteria restricts discovery of antibiotics. adjuvants approach provides an alternative complementary strategy for new antibiotic discovery. These compounds restore or potentiate activity commonly used against multi-drug resistant (MDR) by targeting enhancing action In this review, we first provide brief overview mechanism bacteria, which can be to guide development adjuvants. Additionally, summarize recent achievements search based on their modes action. Lastly, discuss our perspectives developing next-generation such as broad-spectrum hybridization approach, would contribute enrich arsenal MDR bacteria.

Language: Английский

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Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria

Theranostics, Journal Year: 2021, Volume and Issue: 11(10), P. 4910 - 4928

Published: Jan. 1, 2021

Antimicrobial resistance has been a global health challenge that threatens our ability to control and treat life-threatening bacterial infections. Despite ongoing efforts identify new drugs or alternatives antibiotics, no classes of antibiotic their have clinically approved in the last three decades. A combination antibiotics non-antibiotic compounds could inhibit determinants enhance activity offers sustainable effective strategy confront multidrug-resistant bacteria. In this review, we provide brief overview co-evolution discovery development resistance. We summarize drug-drug interactions uncover art repurposing as potential adjuvants, including discussing classification mechanisms action, well reporting novel screening platforms. pathogen-by-pathogen approach is then proposed highlight critical value drug its therapeutic potential. Finally, general advantages, challenges trends are discussed.

Language: Английский

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Crossroads of Antibiotic Resistance and Biosynthesis

Journal of Molecular Biology, Journal Year: 2019, Volume and Issue: 431(18), P. 3370 - 3399

Published: July 6, 2019

Language: Английский

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