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Purpose: Nosocomial bloodstream infections with multidrug-resistant microorganisms have become a common health threat in intensive care settings worldwide. Understanding antimicrobial resistance and the outcomes of these infections is crucial for addressing this issue. This study aimed to investigate the burden, antimicrobial resistance, and 28-day outcomes of nosocomial bloodstream infections in the intensive care unit. Materials and Methods: This retrospective study was conducted in a multispecialty intensive care unit at a tertiary care hospital in western India. Adult patients aged ≥18 years with bloodstream infections acquired after 48 h of admission were included in the analysis. Results: A total of 245 patients suspected of having nosocomial infections in the intensive care unit were evaluated, and 179 were included in the study. Gram-negative bacteremia was identified in the majority of cases, affecting 111 (62%) patients. Carbapenem-resistant Acinetobacter baumannii was the most prevalent pathogen, found in 21.2% (38/179) of patients. Candida species were detected in 37 (20.6%) cases, and gram-positive cocci were identified in 31 (17.3%) patients, with vancomycin-sensitive Enterococci being the most common gram-positive cocci isolated from blood. The central venous catheter was the most frequent source of bloodstream infection, identified in 66 (36.9%) patients. Among all patients, 28-day mortality was observed in 102 (57%) patients. Higher quick sepsis-related organ failure (qSOFA) scores at the onset of bloodstream infection, central venous catheters as a source of infection, inability to initiate early appropriate therapy and septic shock at the onset of bloodstream infection were identified as independent predictors of mortality in patients with nosocomial bloodstream infections. Conclusion: An increased burden of gram-negative bacilli and Candida was found to cause nosocomial bloodstream infections, with very high rates of antimicrobial resistance. Early appropriate diagnosis and treatment play a critical role in improving survival. Additionally, enhanced infection prevention and control practices are necessary to mitigate the heavy burden of infections caused by multidrug-resistant organisms in critical care settings., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.