Impact of neutropenia on clinical outcomes in myelodysplastic syndrome patients hospitalized with sepsis: Insights from a national inpatient sample (2016–2022)

Abstract Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders often complicated by infections due to cytopenias. Sepsis is a frequent cause of hospitalization and mortality in MDS patients. Neutropenia, a common feature in MDS, may predispose patients to specific infectious complications, but its impact on sepsis-related outcomes remains poorly characterized. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2016 to 2022. Adult hospitalizations with co-diagnoses of MDS and sepsis were identified using ICD-10-CM codes. Patients were stratified based on the presence or absence of neutropenia. Multivariable logistic regression models were used to evaluate the association between neutropenia and specific in-hospital outcomes, including Clostridioides difficile infection, fungal sepsis, and disseminated intravascular coagulation (DIC). Models were adjusted for age, sex, comorbidities, hospital characteristics, and illness severity. Results: A total of 78,549 hospitalizations involving MDS patients with sepsis were identified, including 11,295 (14.4%) with neutropenia. Neutropenic patients had significantly higher odds of C. difficile infection (adjusted odds ratio [aOR] 1.61, 95% CI 1.30–1.99, p < 0.001) and fungal sepsis (aOR 2.08, 95% CI 1.22–3.54, p = 0.007) compared to those without neutropenia. However, neutropenia was not significantly associated with DIC (aOR 0.84, 95% CI 0.59–1.19, p = 0.322). Conclusion: In this large national cohort, neutropenia was associated with a significantly increased risk of C. difficile infection and fungal sepsis among MDS patients hospitalized with sepsis. These findings highlight the need for early recognition and targeted antimicrobial strategies in neutropenic MDS patients. No significant association was observed between neutropenia and DIC. Future studies should explore preventive strategies and risk stratification tools tailored to this high-risk population. Keywords: Myelodysplastic syndromes, neutropenia, sepsis, NIS, Clostridioides difficile, fungal sepsis, outcomes