Impact of broad-spectrum antibiotic exposures and multidrug-resistant gram-negative bacteremia on hematopoietic cell transplantation outcomes.

Abstract

There is a close association between the use of broad-spectrum antibiotics, gut microbiome alteration, multidrug resistant (MDR) gram-negative bacilli (GNB) bacteremia, graft versus host disease (GVHD), and mortality post-allogeneic hematopoietic cell transplantation (allo-HCT). This study reports the impact of the high use of carbapenems and colistin and MDR bacteremia pre- and post-HCT on HCT outcomes. This was a single-center, partial retrospective, and prospective study from 2016 to 2020. Both pre- and post-HCT antibiotic exposures and blood culture/sensitivity were recorded. MDR GNB was defined as either non-susceptibility to third-generation cephalosporin or carbapenems. In the absence of positive cultures, the treating physician escalated antibiotics from third-generation cephalosporins to carbapenem and/or colistin as per clinical discretion. De-escalation policy was not strictly enforced. MDR GNB bacteremia was seen in 29 of 76 (38%) of patients peri-HCT. The utilization rates for carbapenems and colistin was significantly higher in the cohort with MDR GNB bacteremia pre-HCT (70%vs. 32%, p=0.002 and 31%vs. 6.4%, p=0.007, respectively) and post-HCT (100%vs. 74.5%, p=0.002, and 55.2%vs. 8.5%, p<0.0001, respectively). The cohort with MDR GNB bacteremia had significantly more severe acute GVHD at day+100 (45%vs. 17.5%, p=0.009). The median survival was 204 days compared to not reached in the cohort without any MDR GNB bacteremia (p=0.005). This study shows pre- and post-HCT MDR GNB bacteremia is associated with an increased risk of severe acute GVHD and mortality. Patients with MDR GNB bacteremia had higher exposure to pre- and post-HCT carbapenems and colistin.