The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?

Samuel L Aitken; Virginia M Pierce; Jason M Pogue; Ellen G Kline; Frank P Tverdek; Ryan K Shields

doi:10.1093/cid/ciae229

The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?

Clin Infect Dis. 2024 Oct 15;79(4):834-837. doi: 10.1093/cid/ciae229.

Authors

Samuel L Aitken^{1

2}, Virginia M Pierce^{3

4}, Jason M Pogue^{1

2}, Ellen G Kline⁵, Frank P Tverdek^{6

7}, Ryan K Shields⁵

Affiliations

¹ Department of Pharmacy, Michigan Medicine, Ann Arbor, Michigan, USA.
² Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
³ Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁴ Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁵ Division of Infectious Diseases, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA.
⁶ Department of Pharmacy, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
⁷ Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, Washington, USA.

PMID: 38661186
DOI: 10.1093/cid/ciae229

Abstract

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.

Keywords: CMY; New Delhi metallo beta-lactamase; aztreonam; cefiderocol; zidebactam.

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Publication types

Case Reports

MeSH terms

Aged
Anti-Bacterial Agents* / pharmacology
Anti-Bacterial Agents* / therapeutic use
Azabicyclo Compounds* / pharmacology
Azabicyclo Compounds* / therapeutic use
Aztreonam / pharmacology
Cefiderocol
Cephalosporins / pharmacology
Cephalosporins / therapeutic use
Drug Combinations
Escherichia coli Infections* / drug therapy
Escherichia coli Infections* / microbiology
Escherichia coli Proteins / genetics
Escherichia coli Proteins / metabolism
Escherichia coli* / drug effects
Escherichia coli* / enzymology
Escherichia coli* / genetics
Female
Humans
Male
Microbial Sensitivity Tests*
Middle Aged
Mutation*
Penicillin-Binding Proteins* / genetics
Penicillin-Binding Proteins* / metabolism
United States
beta-Lactamase Inhibitors / pharmacology
beta-Lactamase Inhibitors / therapeutic use
beta-Lactamases* / genetics
beta-Lactamases* / metabolism

Substances

beta-Lactamases
Anti-Bacterial Agents
Penicillin-Binding Proteins
Azabicyclo Compounds
beta lactamase NDM-5, E coli
beta-Lactamase Inhibitors
Aztreonam
Cephalosporins
Drug Combinations
Cefiderocol
Escherichia coli Proteins

Grants and funding

Innoviva Specialty Therapeutics