Volume 1 Number 1 2025
Molecular Epidemiology and Resistance Mechanisms of Extensively Drug-Resistant Gram-Negative Bacteria: Challenges and Emerging Therapeutic Strategies
Bikom Chandra Singha1*, Abul Kalam Azad2
Paradise 1 (1) 1-8 https://doi.org/10.25163/paradise.1110358
Submitted: 01 June 2025 Revised: 17 March 2025 Published: 19 March 2025
Abstract
Background: The emergence of extensively drug-resistant (XDR) gram-negative bacteria poses a major global health challenge, contributing to increased mortality, prolonged hospital stays, and escalating healthcare costs. Over the past two decades, advances in whole-genome sequencing and genotyping have improved our understanding of the development and spread of antibiotic resistance. Resistance in XDR infections arises from mechanisms such as target site mutations, enzymatic degradation of antibiotics, and alterations in membrane permeability. Methods: This study examines the epidemiology and molecular resistance mechanisms of three clinically significant gram-negative pathogens: XDR Pseudomonas aeruginosa, XDR Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae (CRE). Literature-based evidence and molecular findings were analyzed to identify resistance patterns, emerging clones, and therapeutic challenges. Results: The findings indicate that these pathogens, classified as “critical threats” by the World Health Organization, often necessitate last-resort antibiotics such as polymyxins and novel β-lactam/β-lactamase inhibitor combinations. Resistance mechanisms differ among species but commonly involve enzymatic activity, genetic mutations, and permeability changes. Molecular diagnostics have shown promise in guiding combination therapies, particularly against metallo-β-lactamase-producing CRE, though routine use remains limited. Several novel antimicrobials—including ceftolozane- tazobactam, plazomicin, vaborbactam, and avibactam offer alternative therapeutic options. Conclusion: The growing threat of XDR gram-negative bacteria underscores the urgent need for ongoing global surveillance, improved diagnostic strategies, and deeper investigation into the molecular epidemiology of resistance. Strengthening antibiotic stewardship and advancing targeted therapies are essential to mitigate treatment challenges and control the spread of these pathogens.
Keywords: Extensively drug-resistant bacteria, Gram-negative pathogens, Antibiotic resistance mechanisms, Molecular epidemiology, Novel antimicrobials
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