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Therapeutic Options for Metallo-β-Lactamase-Producing Enterobacterales

Authors Tan X, Kim HS, Baugh K, Huang Y, Kadiyala N, Wences M, Singh N, Wenzler E, Bulman ZP

Received 2 November 2020

Accepted for publication 22 December 2020

Published 18 January 2021 Volume 2021:14 Pages 125—142

DOI https://doi.org/10.2147/IDR.S246174

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Suresh Antony


Xing Tan, 1 Hwan Seung Kim, 1 Kimberly Baugh, 2 Yanqin Huang, 1 Neeraja Kadiyala, 1 Marisol Wences, 1 Nidhi Singh, 1 Eric Wenzler, 1 Zackery P Bulman 1

1Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA; 2Franciscan Health Hammond/Dyer, Hammond, IN, USA

Correspondence: Zackery P Bulman Department of Pharmacy Practice
College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Room 164 (M/C 886), Chicago, IL 60612, USA
Tel +1 312-996-1415
Fax +1 312-413-1797
Email bulman@uic.edu

Abstract: The spread of metallo-β-lactamase (MBL)-producing Enterobacterales worldwide without the simultaneous increase in active antibiotics makes these organisms an urgent public health threat. This review summarizes recent advancements in diagnostic and treatment strategies for infections caused by MBL-producing Enterobacterales. Adequate treatment of patients infected with MBL-producing Enterobacterales relies on detection of the β-lactamase in the clinic. There are several molecular platforms that are currently available to identify clinically relevant MBLs as well as other important serine-β-lactamases. Once detected, there are several antibiotics that have historically been used for the treatment of MBL-producing Enterobacterales. Antimicrobials such as aminoglycosides, tetracyclines, fosfomycin, and polymyxins often show promising in vitro activity though clinical data are currently lacking to support their widespread use. Ceftazidime-avibactam combined with aztreonam is promising for treatment of infections caused by MBL-producing Enterobacterales and currently has the most clinical data of any available antibiotic to support its use. While cefiderocol has displayed promising activity against MBL-producing Enterobacterales in vitro and in preliminary clinical studies, further clinical studies will better shed light on its place in treatment. Lastly, there are several promising MBL inhibitors in the pipeline, which may further improve the treatment of MBL-producing Enterobacterales.

Keywords: metallo-β-lactamase, Enterobacterales, carbapenemase, ceftazidime-avibactam, aztreonam, rapid diagnostics

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