Evaluation of multidrug-resistant organisms in prolonged cefepime versus levofloxacin use through engraftment in allogeneic stem cell transplant recipientsHarry Grant Woodard, PharmD1, May Aziz, PharmD, BCOP1, Rebekah Dyer, PharmD, BCPS,1 William Clark, MD2, Christina E. Maguire, PharmD, BCIDP, AAHIVP11Virginia Commonwealth University Health System Department of Pharmacy Services 2Virginia Commonwealth University Department of Hematology and Oncology
Learning objective: Audience members will be able to explain the risks and benefits of early de-escalation of antibiotic therapy for neutropenic fever in allogeneic stem cell transplant recipients.
Background: The purpose of this project is to evaluate rates of multidrug-resistant organisms (MDROs) between prolonged cefepime use through allogeneic stem cell transplant (SCT) engraftment versus de-escalation to levofloxacin to help guide clinical decisions.
Methods: This is a single-center retrospective review of SCT recipients from 7/1/23 to 10/2/25. Patients who received prophylactic levofloxacin that was escalated to cefepime at neutropenic fever (NF) onset were included. Exclusion criteria were MDRO within the past 6 months, documented source of infection, and use of gram-negative coverage other than cefepime. Patients were categorized into two groups: early de-escalation (cefepime < 7 days) versus late de-escalation (> = 7 days of empiric therapy). Statistical analyses were performed using JMP software. For normally distributed data, chi-square tests and Fischer’s exact tests were used when appropriate. For non-normally distributed data, Kruskal Willis tests were utilized. A p-value of < 0.05 was considered statistically significant. The primary outcome is rate of MDROs in the early and late de-escalation groups. Key secondary outcomes include rates of repeat NF, graft-versus-host disease (GVHD), repeat admissions, and length of stay.
Results: Forty-two of 125 patients met inclusion criteria. Baseline characteristics were well balanced between groups. There was one documented MDRO infection within each group within 90 days of fever resolution (p = 1.0). There were higher rates of repeat NF in the early de-escalation group (29.41% vs. 4%, p = 0.0318) ranging from one to eleven days after the initial NF episode. In patients treated for infection within 90 days of NF resolution, there was a numerically higher rate of culture positivity in the early de-escalation group (80% vs. 36.36%, p = 0.0805). Additionally, there was a trend towards higher rates of gut GVHD (41.67% vs 65%, p=.20) in the late de-escalation group.
Conclusions: This study found no difference in MDRO infection between SCT patients with early versus late de-escalation of antibiotic therapy, with low rates overall. Increased rates of repeat NF in the early de-escalation group and numerical increases in gut GVHD in the prolonged therapy group highlight the challenging balance between benefits and risks of prolonged antibiotic therapy after SCT. Larger studies should be completed to further characterize antibiotic stewardship in this population.
Learning Question:
What are the side effects of prolonged broad spectrum antibiotic therapy? Select all that apply.
- Gut GVHD
- Dyspnea
- Clostridium difficile infections
- Development of multi-drug-resistant organisms
