New Drugs for Multidrug-Resistant Gram-Negative Organisms

Time for Stewardship

International Society of Antimicrobial Chemotherapy (ISAC)

研究成果: 雜誌貢獻文章

2 引文 (Scopus)

摘要

A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.
原文英語
期刊Drugs
DOIs
出版狀態已發佈 - 一月 1 2019

指紋

Enterobacteriaceae
Anti-Bacterial Agents
Carbapenems
Pharmaceutical Preparations
Lactams
meropenem
Pseudomonas aeruginosa
Enterobacteriaceae Infections
Integrons
Aztreonam
Colistin
Acinetobacter baumannii
Multiplex Polymerase Chain Reaction
Enzymes
United States Food and Drug Administration
Delivery of Health Care
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology (medical)

引用此文

New Drugs for Multidrug-Resistant Gram-Negative Organisms : Time for Stewardship. / International Society of Antimicrobial Chemotherapy (ISAC).

於: Drugs, 01.01.2019.

研究成果: 雜誌貢獻文章

International Society of Antimicrobial Chemotherapy (ISAC). / New Drugs for Multidrug-Resistant Gram-Negative Organisms : Time for Stewardship. 於: Drugs. 2019.
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abstract = "A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.",
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