2026 Southeastern Residency Conference

Authors’ Names: Madison Moncus, Ashton Dickinson, Mary Massaro, Brandon Hawkins, Alexandra McBrayer, Clark Cutrer, Samantha Walker 

Background: Febrile neutropenia is a life-threatening complication in patients with malignancy and hematopoietic stem cell transplant (HSCT) recipients. Empiric anti-pseudomonal beta-lactam therapy is recommended; however, the optimal strategy for narrowing therapy based on culture data remains uncertain.  While de‑escalation to pathogen‑directed regimens is widely endorsed when microbiologic data is available, the evidence supporting this practice remains limited. Emerging data suggests de-escalation may safely reduce broad-spectrum antibiotic exposure; though evidence in high-risk populations, such as those with hematologic malignancy and HSCT recipients, is limited. This study evaluates the safety and efficacy of narrowing empiric therapy to pathogen-directed therapy in adults with malignancy and HSCT recipients. 

Methods: This retrospective cohort evaluates adult hospitalized patients with cancer-associated febrile neutropenia between January 2020 and January 2025. Eligible patients received initial empiric antipseudomonal beta-lactam therapy and had a positive bacterial culture obtained within 72 hours of fever onset. Patients with pseudomonal infections, organisms resistant to definitive therapy, ANC recovery (ANC > 500 cells/mm³) within 72 hours of initiating antibiotic therapy, or death within 72 hours were excluded. Patients were stratified into two groups: those who remained on empiric anti-pseudomonal therapy for more than 72 hours after susceptibility results became available, and those who were narrowed to pathogen-directed therapy within 72 hours. Data was collected securely via RedCap. The primary composite outcome included escalation of antibiotic therapy or infection recurrence within 30 days. Secondary outcomes included incidence of new onset Clostridioides difficile infection (CDI), hospital length of stay, all-cause mortality at 30 days, new positive culture with resistance demonstrated to initial treatment agents within 30 days, and time to de-escalation. Data collected included baseline demographics, cancer type, culture results, antibiotic regimens, fluoroquinolone prophylaxis, resistance patterns, and readmissions. Categorical variables were analyzed using chi-square or Fisher’s exact test, and continuous variables were analyzed using the Mann-Whitney U test. Data was analyzed utilizing SPSS. 

Results: A total of 44 patients met inclusion criteria, with 32 patients in the empiric therapy group and 12 patients in the pathogen‑directed therapy group. Baseline demographics, malignancies, and microbiologic characteristics were similar between groups, with most patients having hematologic malignancies and comparable distributions of gram‑positive and gram‑negative organisms. Patients de‑escalated to pathogen‑directed therapy received significantly shorter durations of antipseudomonal therapy (median 3 vs. 18 days, p < 0.001). De‑escalation typically occurred within 24 hours of susceptibility reporting (58%). The composite primary endpoint occurred in 72% of the empiric group and 42% of the pathogen‑directed group (p = 0.085). Antibiotic escalation was more frequent among patients who remained on empiric therapy (50% vs. 8%, p = 0.015), with meropenem accounting for most escalations (94%, p = 0.003). Rates of recurrent fever, repeat positive cultures, readmission due to infection, CDI, and 30‑day mortality were low and did not differ significantly between groups. Hospital length of stay was shorter in the pathogen‑directed group (7 vs. 20 days, p = 0.005). 

Conclusions: De‑escalation of empiric antipseudomonal therapy to pathogen‑directed therapy was associated with substantially reduced broad‑spectrum antibiotic exposure and shorter hospital length of stay without increased treatment failure, recurrent infection, or mortality. These findings support the safety of culture‑guided de‑escalation in adults with malignancy‑associated febrile neutropenia, including HSCT recipients, and highlight the need for larger multicenter studies to confirm generalizability across diverse oncology populations.