Early antimicrobial prophylaxis in autologous stem cell transplant recipients: Conventional versus an absolute neutrophil count-driven approach

Abstract

Background: Autologous hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of developing life-threatening infections. There is discordance in published recommendations for timing of pre- and post-transplant antimicrobial prophylaxis in this patient population, and these recommendations are unsubstantiated by any published comparative analyses.

Methods: An observational, pre- and post-intervention study of consecutive autologous HSCT recipients was conducted over a 2-year period. In the pre-intervention cohort, antimicrobial prophylaxis was initiated on the day prior to transplant. In the post-intervention cohort, antimicrobials were initiated once absolute neutrophil count (ANC) reached ≤500 cells/mm³ . The primary outcome assessed was frequency of febrile occurrences. Secondary outcomes included total days of prophylaxis, positive blood cultures, all-cause mortality, Clostridioides difficile infection rates, and length of stay.

Results: A total of 208 patients were included in the final analysis, with 105 and 103 patients in the pre- and post-intervention cohorts, respectively. The majority of patients included were male. Lower rates of fever occurrences were observed in the post-intervention cohort (83% pre- vs. 69% post-intervention; p = 0.019). A significant reduction in the mean antibacterial days per patient was identified (9.7 vs. 4.6 days; p < 0.001). Other than lower rates of febrile neutropenia in the post-intervention cohort, no differences were identified in secondary outcomes. In multivariable analyses, ANC-driven prophylaxis was independently associated with decreased febrile events.

Conclusions: Delaying prophylaxis until severe neutropenia was not associated with increased febrile events or other secondary clinical outcomes evaluated. This approach is associated with a significant reduction in antimicrobial exposure.

Keywords: absolute neutrophil count; antimicrobial stewardship; hematopoietic stem cell transplant; prophylaxis.