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The Battle Is on: New Beta-Lactams for the Treatment of Multidrug-Resistant Gram-Negative Organisms

  • Mandee Noval
  • Mary Banoub
  • Kimberly C. Claeys
  • Emily HeilEmail author
Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Healthcare Associated Infections

Abstract

Purpose of Review

Resistant gram-negative infections are becoming increasingly difficult to treat, prompting increased focus on drug development. This review will focus primarily on the new beta-lactam agents developed in the past 5 years that target multidrug-resistant (MDR) gram-negative organisms, including those producing carbapenemases.

Recent Findings

Four new agents including ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), imipenem-relebactam (IMI-REL), and cefiderocol have recently been approved for the treatment of resistant gram-negative infections. CAZ-AVI remains an option for blaOXA-48–producing isolates and potentially MDR Pseudomonas aeruginosa, but the concern for resistance arises when using the agent for KPC-producing Enterobacteriales. MER-VAB appears to be more stable than CAZ-AVI in the treatment of KPC-producing Enterobacteriales but less is known about its propensity for the development of resistance and the drug does not reliably expand the coverage of meropenem-resistant P. aeruginosa isolates. IMI-REL expands the spectrum of imipenem-cilastatin to include KPC-producing Enterobacteriales as well as MDR P. aeruginosa but much less is known about its real-world clinical utility. Cefiderocol is the only of the four new agents with efficacy against metallo-beta-lactamases and resistant Acinetobacter species, but comparator studies using best available therapy for carbapenem-resistant gram-negative bacterial infections show higher mortality rates with the new drug, making its role in clinical therapy still to be determined.

Summary

The new beta-lactams differ in their mechanisms of combatting resistance and thus have unique roles in therapy. Additional evidence is needed regarding the potential for development of resistance in the newer combination agents, as well as for the role of cefiderocol in carbapenem-resistant gram-negative infections.

Keywords

Carbapenem-resistant EnterobacterialeCeftazidime-avibactam Meropenem-vaborbactam Imipenem-relebactam Cefiderocol 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Noval declares that she has nothing to disclose. Dr. Banoub declares that she has nothing to disclose. Dr. Claeys received research support from GenMark Diagnostics and BioFire Diagnostics and has served as a speaker for Luminex Corporation and GenMark Diagnostics. Dr. Heil declares that she has nothing to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Mandee Noval
    • 1
  • Mary Banoub
    • 2
  • Kimberly C. Claeys
    • 1
  • Emily Heil
    • 1
    Email author
  1. 1.Department of Pharmacy Practice and ScienceUniversity of Maryland School of PharmacyBaltimoreUSA
  2. 2.University of Maryland Medical CenterBaltimoreUSA

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