Journal Article

Global Threat of Carbapenem-Resistant Gram-Negative Bacteria

Jean, Shio-Shin, Harnod, Dorji, Hsueh, Po-Ren

2022

Overview

Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly bla KPC , bla NDM , and bla OXA-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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Anti-Bacterial Agents - pharmacology / Anti-Bacterial Agents - therapeutic use / Antibiotics / carbapenem-resistant / Carbapenems / Carbapenems - pharmacology / Carbapenems - therapeutic use / Catheters / Ceftazidime / ceftazidime-avibactam / Cellular and Infection Microbiology / Drug resistance / Drug Resistance, Multiple, Bacterial / enterobacterales / extensively-drug resistant / Gram-negative bacteria / Gram-Negative Bacteria - genetics / Hospitalization / Microbial Sensitivity Tests / Minimum inhibitory concentration / Mortality / Multidrug resistance / Multidrug resistant organisms / Nosocomial infections / Pediatrics / Pharmacokinetics / Pneumonia / Polymyxin B / Pseudomonas aeruginosa / Public health / Tazobactam / Tigecycline / Trends