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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Gram negative; antimicrobial stewardship; duration; immunocompromised; neutropenia; sepsis.