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Review
. 2025 May;109(3):735-747.
doi: 10.1016/j.mcna.2025.01.003. Epub 2025 Feb 28.

Management of Severe Infections: Multidrug-Resistant and Carbapenem-Resistant Gram-Negative Bacteria

Affiliations
Review

Management of Severe Infections: Multidrug-Resistant and Carbapenem-Resistant Gram-Negative Bacteria

Federico Perez et al. Med Clin North Am. 2025 May.

Abstract

This article provides an overview of the mechanisms behind carbapenem resistance and the antibiotic management for severe infections caused by key carbapenem-resistant gram-negative bacteria, specifically Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. For Enterobacterales, it highlights the relative advantages of meropenem-vaborbactam and imipenem-relebactam in treating Klebsiella pneumoniae carbapenemase (KPC)-producing strains with resistance to ceftazidime-avibactam, the preference for ceftazidime-avibactam in addressing oxacillin-hydrolyzing carpapenemase (OXA)-48-like -producing organisms, and the combination of ceftazidime-avibactam with aztreonam for metallo-β-lactamase (MBL)-producing Enterobacterales. Regarding A baumannii, sulbactam-durlobactam is identified as the preferred treatment, while ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam are viable options for P aeruginosa. Additionally, cefiderocol is presented as an alternative for MBL-producing carbapenem-resistant gram-negative bacteria.

Keywords: Acinetobacterbaumannii; Carbapenem-resistant Enterobacterales; Carbapenemase-producing Enterobacterales; Carbapenems; Cefiderocol; Metallo-β-lactamase; Pseudomonasaeruginosa; β-lactam/β-lactamase inhibitors.

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Conflict of interest statement

Disclosures Previous research funding from Merck, United States, Pfizer, United States, and Accelerate to Federico Perez.

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