Global Threat of Carbapenem-Resistant Gram-Negative Bacteria

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

doi:10.3389/fcimb.2022.823684

Global Threat of Carbapenem-Resistant Gram-Negative Bacteria

Front Cell Infect Microbiol. 2022 Mar 15:12:823684. doi: 10.3389/fcimb.2022.823684. eCollection 2022.

Authors

Shio-Shin Jean^{1

2}, Dorji Harnod^{3

4}, Po-Ren Hsueh^{5

6

7

8}

Affiliations

¹ Department of Emergency and Critical Care Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan.
² Department of Pharmacy, College of Pharmacy and Health care, Tajen University, Pingtung, Taiwan.
³ Division of Critical Care Medicine, Department of Emergency and Critical Care Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁴ Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan.
⁶ School of Medicine, China Medical University, Taichung, Taiwan.
⁷ Ph.D Program for Aging, School of Medicine, China Medical University, Taichung, Taiwan.
⁸ Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Abstract

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.

Keywords: Acinetobacter baumannii complex; Pseudomonas aeruginosa; carbapenem-resistant; ceftazidime-avibactam; enterobacterales; extensively-drug resistant; gram-negative bacteria.

Publication types

Review

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Carbapenems* / pharmacology
Carbapenems* / therapeutic use
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria* / genetics
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Carbapenems