Evaluating antimicrobial duration for Gram‐negative bacteremia in patients with neutropenia due to hematologic malignancy or hematopoietic stem cell transplantation

Nischal Ranganath, Zachary A. Yetmar, Audrey R. McCandless, Christina G. Rivera, Brian D. Lahr, Aaron J. Tande, Aditya S. Shah

In the management of Gram-negative bloodstream infection (GN-BSI), short antimicrobial courses have been increasingly demonstrated to be non-inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi-drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11-14 days), and prolonged (≥15 days) antimicrobial durations for GN-BSI in neutropenic patients. A retrospective cohort study was conducted on neutropenic patients with monomicrobial GN-BSI between 2018 and 2022. The primary outcome was a composite of all-cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90-day CDI and development of MDR-GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups. A total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra-abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS-adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39-2.03) or prolonged versus short therapy (PS-aHR 1.20; 95% CI 0.52-2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR-GN emergence. Our data suggest that short antimicrobial courses had comparable 90-day outcomes as intermediate and prolonged regimens for GN-BSI among immunocompromised patients with neutropenia.