Early Antimicrobial De-escalation and Stewardship in Adult Hematopoietic Stem Cell Transplantation Recipients: Retrospective Review

Abstract

Abstract Background Antimicrobial stewardship in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients remains underutilized in North America. European guidelines advise de-escalation of broad-spectrum therapy after 72 hours in select patients with neutropenic fever of unknown origin. This is not commonplace in the United States, as current guidelines recommend broad-spectrum therapy until neutrophil engraftment. If de-escalating after at least 5 days of broad-spectrum therapy and defervescence in neutropenic allo-HSCT recipients does not predispose them to recurrent fever or infection, the practice could afford several benefits. Methods The primary end point was rate of recurrent fever. Secondary outcomes included Clostridium difficile–associated infections, length of stay, intensive care unit (ICU) admission incidence, in-hospital mortality rate, need for re-escalation of therapy, rate of positive blood cultures for patients who had recurrent fevers, overall antimicrobial utilization from neutropenic fever onset, and pharmacoeconomic impact. Results A total of 120 patients were assessed in 2 groups as cohort 1 (n = 46), which received early de-escalation, and cohort 2 (n = 74), which did not. The primary end point met criteria for noninferiority, as 7 patients (15%) in cohort 1 had recurrent fever within the specified time frame compared with 14 (19%) in cohort 2 (90% CI, –0.0878 to 0.1629, P = .026). Patients in cohort 1 received significantly less gram-positive broad-spectrum antimicrobials, with trends toward lower use of broad-spectrum gram-negative agents and lower associated costs and no differences in length of stay, ICU admission incidence, need for re-escalation of therapy, rate of culture-positive bacteremia after de-escalation or discontinuation of broad-spectrum therapy, or in-hospital mortality rate. Conclusions De-escalating after at least 5 days of broad-spectrum therapy and defervescence did not appear to affect the rate of recurrent fever. This allowed for significant reductions in gram-positive broad-spectrum antimicrobial utilization, with trends toward lower use of broad-spectrum gram-negative agents and associated costs and no difference in clinical outcomes compared with those continuing such therapy until neutrophil engraftment.