Akram, A.Kawshalya, I.2026-01-082025-10-10978-624-6010-09-62783 – 8862https://rda.sliit.lk/handle/123456789/4462Klebsiella pneumoniae functions as a major pathogenic microorganism that causes pneumonia infections, urinary tract infections, and bloodstream infections. The advanced resistance of K. pneumoniae against ciprofloxacin presents medical professionals with significant management issues for treatment strategies.This research examined ciprofloxacin resistance-related genetic mutations and alterations in K. pneumoniae through detailed analysis of essential DNA gyrase and topoisomerase IV genes: gyrA, gyrB, parC, and parE. The research analysed alterations between resistant and susceptible microbial strains through bioinformatics methodology. The scientific confirmation established that ciprofloxacin resistance exhibits a strong relationship with gyrA mutations at Ser83, along with Asp87 positions. Research confirms thatenzyme structure changes caused by these alterations lead to decreased ciprofloxacin binding effectiveness. The mutation of Ser359Ala and Ser367Thr in gyrB increased bacterial resistance slightly when compared to gyrA mutations. Ser80Ile and Glu84Val parC mutations showed a reduction in ciprofloxacin binding ability, thus causing an increase in resistance. The drug-binding site of ciprofloxacin became stronger through parE mutations that included Ile529Leu and Ser458Ala, which reinforced ciprofloxacin resistance. Genomic surveillance must remain active because these research results verify the contribution of these mutations to ciprofloxacin resistance. Research into K. pneumoniae resistance molecular pathways becomes vital for developing antimicrobial strategies as well as for stopping resistance strain proliferation.enAntimicrobial resistanceciprofloxacingene mutationsKlebsiella pneumoniaArticlehttps://doi.org/10.54389/SUTK4844