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Global Threat of Carbapenem-Resistant Gram-Negative Bacteria.

Abstract
Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
AuthorsShio-Shin Jean, Dorji Harnod, Po-Ren Hsueh
JournalFrontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 12 Pg. 823684 ( 2022) ISSN: 2235-2988 [Electronic] Switzerland
PMID35372099 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2022 Jean, Harnod and Hsueh.
Chemical References
  • Anti-Bacterial Agents
  • Carbapenems
Topics
  • Anti-Bacterial Agents (pharmacology, therapeutic use)
  • Carbapenems (pharmacology, therapeutic use)
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria (genetics)
  • Microbial Sensitivity Tests

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