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Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms.

Abstract：

:There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections. Enzymatic inhibitors, such as the derivatives of the β-lactamase inhibitor avibactam, are closer to the clinic than other molecules. For example, MK-7655, in combination with imipenem, is in clinical development for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa, which are difficult to treat. In addition, other molecules targeting multidrug-resistance mechanisms, such as efflux pumps, are under development and hold promise for the treatment of multidrug resistant infections.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Schillaci D,Spanò V,Parrino B,Carbone A,Montalbano A,Barraja P,Diana P,Cirrincione G,Cascioferro S

doi

10.1021/acs.jmedchem.7b00215

subject

Has Abstract

pub_date

2017-10-26 00:00:00

pages

8268-8297

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

60

pub_type

杂志文章

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