Burden of Difficult-to-Treat Resistant Organisms in Gram-Negative Bloodstream Infections: A Retrospective Observational Study From Eastern India.

Background Gram-negative bacteria (GNB) are responsible for about one-third to nearly half of adult bloodstream infections, resulting in higher rates of morbidity and mortality. Difficult-to-treat resistance (DTR), among GNB, is characterised as being intermediate or resistant to all β-lactam classes (including carbapenems) and fluoroquinolones, thus constituting a clinically significant resistant phenotype. This study aims to ascertain the prevalence and antibiotic susceptibility pattern of DTR organisms isolated from Gram-negative bloodstream infections (GNBSIs) at a tertiary-level hospital in eastern India. Methods This retrospective observational study was conducted in the Department of Microbiology of a tertiary care hospital in eastern India from June 2024 to May 2025. Blood samples were collected in age-specific blood culture bottles and incubated at 37°C. Positive blood cultures were subcultured to obtain pure isolates. Identification and antimicrobial susceptibility testing (AST) were performed using the VITEK 2 Compact automated system. The results were interpreted according to Clinical Laboratory and Standards Institute (CLSI) M100, 2026, 36th edition. Demographic characteristics, comorbidities, risk factors, and in-hospital mortality rates were collected from hospital records. Univariate and multivariate analyses were used to test the association of the variables with DTR GNBSIs. Results Among 202 patients with GNBSIs, 67 (33.17%, 95% CI: 26.7-39.7%) exhibited the characteristics of DTR. The most common DTR pathogens were Klebsiella pneumoniae, 27 (40.3%, 95% CI: 28.6-52.0%), followed by Acinetobacter baumannii, 19 (28.36%, 95% CI: 17.6-39.2%), and Escherichia coli, 10 (14.9%, 95% CI: 6.4-23.5%). The majority of the DTR organisms from GNBSIs were isolated from male patients (41, 61.19%) as compared to female patients (26, 38.81%), with maximum occurrence in the age group >60 years (25, 37.3%). Factors such as arterial line, liver disease, dialysis, prior antibiotic use, and prior carbapenem use exhibited statistically significant associations with DTR GNBSIs in univariate analysis. Prior antibiotic use was identified as the independent predictor of DTR GNBSIs in multivariate analysis. AST revealed maximum resistance of DTR isolates to amikacin (39/63, 61.9%) followed by gentamicin (31/59, 52.54%) and co-trimoxazole (29/59, 49.15%). In terms of susceptibility, maximum susceptibility was marked towards tigecycline (37/44, 84.09%), followed by co-trimoxazole (30/59, 50.85%) and gentamicin (28/59, 47.46%), with (63/63, 100%) of the DTR isolates being intermediate to colistin. Conclusion The occurrence of DTR and their non-susceptibility to first-line drugs raises serious concern due to the limited availability of effective treatment options. Therefore, active surveillance, strict infection control practices, and antibiotic stewardship are necessary to tackle this situation in hospitals.