Molecular Framework of Multidrug Resistance in Pseudomonas aeruginosa

Antimicrobial resistance (AMR) in Pseudomonas aeruginosa (PA) represents an escalating public health emergency in India, where factors such as unregulated antibiotic usage, limited infection control, and dense hospital environments have precipitated a dramatic rise in multidrug-resistant (MDR) and extensively drug-resistant (XDR) PA isolates. Recent Indian surveillance data indicate that resistance rates among clinical PA isolates often exceed 70% for key antibiotics, with carbapenem resistance surpassing 60% in intensive care settings and up to 98% for agents such as ceftriaxone in some cohorts. The World Health Organization designates PA as a critical-priority pathogen owing to its intrinsic and acquired resistance to nearly all available antibiotics, dramatically compromising patient outcomes, especially in high-burden regions like India. This review synthesizes the epidemiology of PA resistance in India, elucidating both the clinical prevalence and principal societal drivers-including over-the-counter antibiotic distribution and the prevalence of irrational fixed-dose combinations. A comprehensive analysis is provided of the molecular mechanisms underlying AMR in Indian PA isolates: the high prevalence of metallo-β-lactamases (e.g., blaNDM-1, blaVIM), overexpression of efflux pump systems (such as MexAB-OprM in over 50% of MDR isolates), porin loss (notably OprD in carbapenem-resistant strains), target site mutations, and widespread biofilm formation which affects up to 80% of device-related infections. Understanding these pathways is imperative for optimizing therapeutic regimens, informing antimicrobial stewardship, and directing research toward urgently needed new interventions for PA in India's unique clinical landscape. Additionally this review also talks about the various novel strategies which are currently in the development stages that can prove to be potent against PA in the future.