Received: 13 July 2021 Revised: 10 August 2021 Accepted: 15 August 2021 DOI: 10.1111/tid.13717 ORIGINAL ARTICLE Impact of broad-spectrum antibiotic exposures and multidrug-resistant gram-negative bacteremia on hematopoietic cell transplantation outcomes Shaweta Kaundal 1 Aditya Jandial 1 Harmandeep Singh 1 Madhu Chopra 1 Kripa Shanker Kasudhan 2 Niranjan Khaire 1 Alka Khadwal 1 Gaurav Prakash 1 Arihant Jain 1 Vikas Suri 1 Amol Patil 2 Amit Arora 3 Vishal Sharma 4 Pallab Ray 3 Pankaj Malhotra 1 Deepesh P. Lad 1 1 Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India 2 Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 3 Department of Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 4 Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Correspondence Deepesh P. Lad, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Email: lad.deepesh@pgimer.edu.in Twitter: @Lad_Deepesh Funding information Indian Council of Medical Research, Grant/Award Number: IRIS ID 2020-0664 Abstract Introduction: There is a close association between the use of broad-spectrum antibi- otics, 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. Methods: This was a single-center, partial retrospective, and prospective study from 2016 to 2020. Both pre- and post-HCT antibiotic exposures and blood cul- ture/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. Results: 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 sur- vival was 204 days compared to not reached in the cohort without any MDR GNB bacteremia (p = 0.005). Conclusion: 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. Abbreviations: CRE, carbapenem-resistant Enterobacterales; ESBL, extended-spectrum β-lactamase; GNB, gram-negative bacilli; GVHD, graft versus host disease; HCT, hematopoietic cell transplantation; MDR, multidrug resistance Transpl Infect Dis. 2021;23:e13717. © 2021 Wiley Periodicals LLC 1 of 6 wileyonlinelibrary.com/journal/tid https://doi.org/10.1111/tid.13717