Resistance of Gram-Negative Bacteria to Last-Resort Antibacterials

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 1697

Special Issue Editor


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Guest Editor
Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", Patr. Gregoriou E & 27 Neapoleos Str, 15341 Agia Paraskevi, Greece
Interests: resistance mechanisms of gram-negatives; carbapenemase detection; carbapenem resistance; carbapenemase-producing organisms; resistance genomics; in vitro pk/pd
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Special Issue Information

Dear Colleagues,

Infections due to multi-drug-resistant (MDR), extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negatives are increasing worldwide, forcing clinicians to use last-resort antimicrobials for their management. These salvage treatment options include the few new antibacterials developed recently (cefiderocol, ceftolozane-tazobactam meropenem-vaborbactam, imipenem-relebactam, ceftazidime- and aztreonam-avibactam, cefepime-taniborbactam, eravacycline and omadacycline) and older antibacterials, like polymyxins and tigecycline. Unfortunately, resistance to last-resort agents is also reported, putting in danger their use and making infections due to these pathogens practically untreatable.

The scope of this Special Issue is to update knowledge on resistance of Gram-negative pathogens to last-resort antimicrobials through manuscripts highlighting their epidemiology, resistance mechanisms and genomics, but also manuscripts addressing alternative treatment options or reversal of resistance methods, like combination therapy, phage therapy, antimicrobial peptides, CRISPR-cas system and PK/PD studies. Finally, manuscripts describing new microbiological tools for resistance detection are also welcome.

Dr. Sophia Vourli
Guest Editor

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Keywords

  • last-resort antimicrobials
  • mechanisms of resistance to new antimicrobials
  • PK/PD of new and old antimicrobials
  • combination therapy
  • resistance genomics

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Published Papers (1 paper)

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Review

28 pages, 2243 KB  
Review
Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies
by Shah Zeb, Arzoo Nazir, Muhammad Fazal Hameed, Sadia Ikram, Syed Zeeshan Haider Naqvi, Muhammad Shoaib, Patrick Butaye, Zhiqiang Wang, Ruichao Li and Xiaoyu Lu
Microorganisms 2026, 14(1), 173; https://doi.org/10.3390/microorganisms14010173 - 13 Jan 2026
Cited by 2 | Viewed by 1196
Abstract
Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to [...] Read more.
Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. Full article
(This article belongs to the Special Issue Resistance of Gram-Negative Bacteria to Last-Resort Antibacterials)
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