Outcomes of Clostridium difficile Infection in Patients With Idiopathic Pulmonary Fibrosis: Analysis of the Nationwide Inpatient Sample, 2016–2020

Background Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Patients with IPF are frequently exposed to risk factors for Clostridium difficile infection (CDI), such as advanced age, antibiotic use, and gastric acid suppression. However, the outcomes of CDI in hospitalized IPF patients remain unclear. Methods We conducted a retrospective cohort study using the National Inpatient Sample (2016–2020) to compare outcomes among hospitalized CDI adults with or without IPF as a pre‐existing comorbidity. Hospitalizations were identified using ICD‐10 codes. Propensity score matching (1:4) was performed to balance demographics and comorbidities. The primary outcome was all‐cause in‐hospital mortality; secondary outcomes included length of stay, hospitalization costs, mechanical ventilation, vasopressor use, and major adverse events. Results Of 1 450 860 CDI hospitalizations, 1600 (0.11%) had IPF. After matching, IPF was independently associated with higher in‐hospital mortality (aOR 1.85, 95% CI 1.22–2.76), longer hospital stays, and increased hospitalization costs. IPF patients were more likely to require mechanical ventilation (aOR 1.79, 95% CI 1.27–2.52). However, rates of fulminant CDI complications (severe sepsis, toxic megacolon, ileus, colectomy, ileostomy) were not significantly increased in the IPF cohort after matching. Conclusions Hospitalized CDI patients with IPF experience significantly higher mortality and resource utilization compared to those without IPF. The absence of increased fulminant CDI complications suggests that CDI may act as a marker of underlying disease severity in IPF rather than a direct cause of death. These findings highlight the need for risk stratification in CDI patients with chronic lung diseases.