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. 2024 May 10:15:1385475.
doi: 10.3389/fmicb.2024.1385475. eCollection 2024.

Friends or foes? Novel antimicrobials tackling MDR/XDR Gram-negative bacteria: a systematic review

Mihai Octavian Dan  1 , Daniela Tǎlǎpan  1   2
Affiliations

Friends or foes? Novel antimicrobials tackling MDR/XDR Gram-negative bacteria: a systematic review

Mihai Octavian Dan et al. Front Microbiol. .

Abstract

Gram-negative bacteria have been one of the most studied classes in the field of microbiology, especially in the context of globally alarming antimicrobial resistance levels to these pathogens over the course of the past decades. With high numbers of these microorganisms being described as multidrug-resistant (MDR), or even extended-drug-resistant (XDR) bacteria, specialists in the field have been struggling to keep up with higher prevalence of difficult-to-treat infections caused by such superbugs. The FDA approval of novel antimicrobials, such as cefiderocol (FDC), ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), imipenem/relebactam (IMR), sulbactam/durlobactam (SUL-DUR) and phase 3 clinical trials' results of aztreonam/avibactam (ATM-AVI) has proven that, while all these substances provide encouraging efficacy rates, antibiotic resistance keeps up with the pace of drug development. Microorganisms have developed more extensive mechanisms of resistance in order to target the threat posed by these novel antimicrobials, thus equiring researchers to be on a constant lookout for other potential drug candidates and molecule development. However, these strategies require a proper understanding of bacterial resistance mechanisms to gain a comprehensive outlook on the issue. The present review aims to highlight these six antibiotic agents, which have brought hope to clinicians during the past decade, discussing general properties of these substances, as well as mechanisms and patterns of resistance, while also providing a short overview on further directions in the field.

Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, Identifier CRD42024505832.

Keywords: antibiotic resistance; aztreonam/avibactam; cefiderocol; ceftazidime/avibactam; ceftolozane/tazobactam; imipenem/relebactam; salvage therapy; sulbactam/durlobactam.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of data collection, adapted from the PRISMA 2020 flow diagram.
Figure 2
Figure 2
Chemical structures of cefiderocol (A), ceftolozane/tazobactam (B), ceftazidime/avibactam (C), aztreonam (D), imipenem/relebactam (E), and sulbactam/durlobactam (F) (Avycaz, 2024; Aztreonam, 2024; Cefiderocol, 2024; Ceftolozane-Tazobactam, 2024; Durlobactam, 2024; Imipenem, 2024; Relebactam, 2024; Sulbactam, 2024).
See this image and copyright information in PMC

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