Colistin Resistance in Klebsiella pneumoniae: Mechanisms, Detection, and Clinical Impact

Klebsiella pneumoniae (K. pneumoniae ​​​​​) is a Gram-negative, encapsulated opportunistic pathogen causing pneumonia, urinary tract infections, bloodstream infections, and ventilator-associated pneumonia. Carbapenem resistance has made colistin a last-resort antibiotic for multidrug-resistant Gram-negative infections, but increased colistin use has driven resistance emergence. Resistance occurs through chromosomal mutations (mgrB, phoPQ, pmrAB) causing lipid A modification that reduces colistin binding, and plasmid-mediated mcr genes (especially mcr-1) encoding phosphoethanolamine transferase that spread horizontally across strains and species, making it a critical public health concern. Broth microdilution is the reference standard for susceptibility testing, while disk diffusion is unreliable. Molecular methods (polymerase chain reaction (PCR), sequencing) detect resistance genes and distinguish chromosomal versus plasmid-mediated mechanisms, providing comprehensive characterization for surveillance and outbreak investigation. Colistin-resistant K. pneumoniae is predominantly healthcare-associated, linked to ICU admission, prolonged hospitalization, broad-spectrum antibiotic exposure (carbapenems, colistin), and invasive devices (central venous catheters, urinary catheters, ventilators). Infections cause delayed effective therapy, prolonged hospital stay, increased complications, and higher mortality, particularly in critically ill patients with bloodstream infections or sepsis. India faces a high burden of carbapenem- and colistin-resistant isolates in tertiary care hospitals, yet molecular characterization data from regional hospitals remain limited. Rapid molecular diagnostics detecting mcr genes enable earlier appropriate therapy. Antimicrobial stewardship combined with infection control measures (contact precautions, hand hygiene, active surveillance, environmental cleaning) is essential to preserve colistin effectiveness and limit resistance spread, maintaining it as a last-line therapeutic option.