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Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and...
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Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and Pan-Drug-Resistant Pathogens

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 31 August 2026 | Viewed by 8034

Special Issue Editor

Dr. Larisa Ionela Miftode

E-Mail Website
Guest Editor
1. Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa” of Iași, 700115 Iasi, Romania
2. Clinic of Infectious Diseases, “Sf. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania
Interests: antibiotic resistance; urinary tract infections; carbapenem-resistant Enterobacterales; multidrug-resistant bacteria; healthcare-associated infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global rise in extensively drug-resistant (XDR) and pan-drug-resistant (PDR) pathogens marks a critical turning point in the fight against infectious diseases. Once considered rare, these “superbugs” have now breached hospitals, communities, and even the food chain, challenging the very foundation of modern medicine. Infections that were once treatable with a short course of antibiotics now linger, complicate, and often prove fatal. As traditional antimicrobial therapies lose their efficacy, the threat to global health security grows more urgent.

This Special Issue, "Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and Pan-Drug-Resistant Pathogens", collates cutting-edge research, policy perspectives, and clinical strategies aimed at confronting one of the most pressing medical crises of our time. We explore the drivers behind antimicrobial resistance, including misuse in human and veterinary medicine, and examine emerging diagnostic tools, novel therapeutic options, and global stewardship efforts.

By fostering interdisciplinary collaboration and innovation, we aim to spotlight not only the scale of the challenge but also the resilience and ingenuity of global health responses.

This Special Issue welcomes all submissions related to the epidemiology, diagnosis, treatment, surveillance, and prevention of infections caused by drug-resistant pathogens, including original research articles, reviews, and opinion papers.

Dr. Ionela-Larisa Miftode
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial resistance
  • extensively drug-resistant pathogens
  • pan-drug-resistant bacteria
  • multidrug-resistant organisms (MDROs)
  • infectious disease control
  • antibiotic stewardship
  • novel antimicrobials
  • rapid diagnostics
  • global health threats

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Published Papers (3 papers)

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Review

31 pages, 1131 KB  
Review
Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions
by Ionela-Larisa Miftode, Viorel Dragoș Radu, Raul-Alexandru Jigoranu, Daniela-Anicuța Leca, Cristian Sorin Prepeliuc, Maria Antoanela Pasare, Radu-Stefan Miftode, Maria Gabriela Grigoriu, Tudorița Gabriela Parângă and Egidia Gabriela Miftode
Antibiotics 2026, 15(3), 270; https://doi.org/10.3390/antibiotics15030270 - 5 Mar 2026
Cited by 1 | Viewed by 2608
Abstract
Carbapenems are essential for the treatment of severe infections caused by Gram-negative bacteria, particularly in critically ill and immunocompromised patients. However, the global rise of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii has significantly eroded their effectiveness, and the phenomenon is [...] Read more.
Carbapenems are essential for the treatment of severe infections caused by Gram-negative bacteria, particularly in critically ill and immunocompromised patients. However, the global rise of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii has significantly eroded their effectiveness, and the phenomenon is now recognized as a major public health threat. Resistance is driven by the complex and evolving interplay of enzymatic and non-enzymatic mechanisms, occurring within highly successful clonal lineages and mobile genetic platforms. This review summarizes advances since 2020 in the molecular basis of carbapenem resistance, integrating enzymatic mechanisms across Ambler classes A, B, C, and D with emerging non-enzymatic contributors, including porin remodeling, efflux pump upregulation, target-site alterations, and outer-membrane adaptations. Particular attention is given to adaptive genome dynamics, such as IS26-mediated gene amplification, plasmid multimerization, and heteroresistance, that generate unstable resistance phenotypes and complicate routine susceptibility testing. Newly introduced β-lactam/β-lactamase inhibitor combinations exert distinct selective pressures: ceftazidime–avibactam favors KPC Ω-loop variants and permeability defects, often restoring carbapenem susceptibility, whereas meropenem–vaborbactam and imipenem–relebactam resistance is driven mainly by porin loss and β-lactamase gene amplification. Cefiderocol resistance is multifactorial, frequently involving impaired siderophore uptake and heteroresistance, while sulbactam–durlobactam remains active against OXA-producing A. baumannii but is compromised by metallo-β-lactamases and PBP3 alterations. Carbapenem resistance is increasingly characterized by convergent, multi-layered adaptations that undermine both established and novel therapies. While high-level randomized evidence remains limited for some resistance mechanisms, emerging mechanistic, microbiological, and clinical data support the need for mechanism-aware diagnostics, repeated susceptibility assessment during therapy, and stewardship strategies informed by resistance biology. Integrating molecular context into routine practice will be critical to preserving emerging treatment options and limiting the global impact of carbapenem resistance. Full article
(This article belongs to the Special Issue Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and Pan-Drug-Resistant Pathogens)
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22 pages, 570 KB  
Review
Colistin Resistance: From Laboratory Research to Modern Clinical Management
by Hakan Erdem and Gulden Yilmaz-Tehli
Antibiotics 2026, 15(3), 259; https://doi.org/10.3390/antibiotics15030259 - 2 Mar 2026
Viewed by 1409
Abstract
Background/Objectives: Colistin, a polymyxin antibiotic introduced in the mid-20th century, has regained clinical importance as a last-resort agent for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. The global dissemination of carbapenem-resistant pathogens has intensified colistin use, leading to a concerning [...] Read more.
Background/Objectives: Colistin, a polymyxin antibiotic introduced in the mid-20th century, has regained clinical importance as a last-resort agent for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. The global dissemination of carbapenem-resistant pathogens has intensified colistin use, leading to a concerning rise in resistance. This review aims to provide a comprehensive and up-to-date synthesis of colistin’s pharmacological characteristics, resistance mechanisms, epidemiology, and current and emerging therapeutic strategies. Methods: A narrative review of the literature was conducted, encompassing studies on the chemistry, mechanism of action, pharmacodynamics, clinical use, dosing, and resistance to colistin. Data on chromosomal and plasmid-mediated resistance mechanisms, detection methodologies, epidemiological trends, and clinical outcomes were examined. In addition, evidence on colistin-based treatment strategies and novel non-antibiotic approaches was analyzed. Results: Colistin remains active against many MDR Gram-negative pathogens, including Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii; however, resistance is increasingly reported worldwide. Both chromosomally mediated modifications of lipid A and plasmid-mediated mcr genes contribute to resistance, with heteroresistance posing diagnostic and therapeutic challenges. Carbapenem resistance has emerged as a major driver of colistin use and subsequent resistance selection. Combination therapies, inhaled formulations, and guideline-directed use may improve outcomes, while emerging alternatives such as antimicrobial peptides, bacteriophages, nanoparticles, photodynamic therapy, and CRISPR-based technologies show promise. Conclusions: The escalating prevalence of colistin resistance threatens the effectiveness of this critical last-line antibiotic. Optimized use, robust resistance surveillance, accurate detection methods, and the development of innovative therapeutic strategies are essential to preserve colistin’s clinical utility and address the growing burden of MDR Gram-negative infections. Full article
(This article belongs to the Special Issue Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and Pan-Drug-Resistant Pathogens)
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19 pages, 1030 KB  
Review
Multidrug-Resistant Acinetobacter baumannii: Resistance Mechanisms, Emerging Therapies, and Prevention—A Narrative Review
by Ioana Adelina Stoian, Bianca Balas Maftei, Carmen-Elena Florea, Alexandra Rotaru, Constantin Aleodor Costin, Maria Antoanela Pasare, Radu Crisan Dabija and Carmen Manciuc
Antibiotics 2026, 15(1), 2; https://doi.org/10.3390/antibiotics15010002 - 19 Dec 2025
Cited by 4 | Viewed by 3395
Abstract
Acinetobacter baumannii is a leading intensive care unit (ICU) pathogen associated with high rates of carbapenem resistance and poor clinical outcomes. This narrative review synthesizes recent clinical, microbiological, and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding resistance mechanisms and therapeutic strategies. A literature review was performed [...] Read more.
Acinetobacter baumannii is a leading intensive care unit (ICU) pathogen associated with high rates of carbapenem resistance and poor clinical outcomes. This narrative review synthesizes recent clinical, microbiological, and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding resistance mechanisms and therapeutic strategies. A literature review was performed in PubMed, Scopus, and Web of Science (January 2015–August 2025), focusing on multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, ICU-acquired infections, and pivotal trials involving cefiderocol and sulbactam–durlobactam. Resistance is driven by OXA-type carbapenemases (notably OXA-23/24/58), efflux systems (AdeABC/IJK/FGH), porin alterations (CarO, Omp33–36), and lipopolysaccharide (LPS) modifications conferring colistin resistance. Management options include polymyxins, optimized tigecycline dosing, β-lactam/β-lactamase inhibitors, and newer agents such as cefiderocol and sulbactam–durlobactam, though mortality and safety outcomes vary across trials. A comparative table is included, summarizing antimicrobial mechanism coverage, PK/PD parameters, and adverse effects to support regimen selection in ventilator-associated pneumonia (VAP) and bacteremia. Optimized, multimodal approaches integrating timely diagnostics, targeted combination therapies, infection prevention, and antimicrobial stewardship are essential to improve outcomes and limit the spread of MDR and XDR A. baumannii. Full article
(This article belongs to the Special Issue Superbugs Unleashed: Global Challenges and Solutions for Extensively Drug-Resistant and Pan-Drug-Resistant Pathogens)
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