Background: Intensive care units have become hotspots for antimicrobial resistance, particularly concerning colistin resistance, posing a threat of untreatable infections. Aim: This study aims to analyze the epidemiological and clinical aspects of patients carrying colistin-resistant organisms. It focuses on identifying risk factors, the microbiological profile, susceptibility patterns, and treatment outcomes. Materials and methods: Isolates with colistin MIC >2 µg/mL, identified via BD PHOENIX, were subjected to colistin broth disc elution testing (as per CLSI guidelines) in our Microbiology Department between January and December 2022. Results: Among the 30 patients, colistin-resistant gram-negative isolates were found predominantly in blood cultures (50%), followed by ET/TT cultures (23.3%), urine cultures (10%), and other sites (16.7%). Klebsiella pneumoniae was the most common organism (80%), showing the highest sensitivity to Ceftazidime-avibactam + Aztreonam (CAZ-AVI + ATM) (76.7%). Of these patients, 66.7% recovered and were discharged, while 33.3% succumbed during hospitalization despite treatment. Conclusion: The study underscores a notable presence of colistin-resistant gram-negative isolates, predominantly in blood cultures, with K. pneumoniae being predominant. The combination of CAZ-AVI + ATM exhibited the highest sensitivity. However, the mortality rate of 33.3% despite sensitive antibiotic treatment highlights the urgency for ongoing vigilance and research to combat colistin-resistant infections and improve patient outcomes.