IPF Linked to Higher Mortality, Costs in Hospitalized Patients With CDI

Hospitalized patients with idiopathic pulmonary fibrosis (IPF) who develop Clostridium difficile infection (CDI) may face substantially worse outcomes than patients without IPF, according to a recent retrospective analysis published in JGH Open.¹

Investigators analyzed data from the National Inpatient Sample between January 1, 2016, and December 31, 2020, identifying more than 1.48 million CDI-related hospitalizations nationwide. Among those admissions, 1600 patients had a concurrent diagnosis of IPF, a chronic and progressive interstitial lung disease associated with declining pulmonary function and a median survival of approximately 2 to 3 years after diagnosis.

Previous research has already established CDI as a major driver of hospitalization burden, mortality, and health care costs in vulnerable patient populations. CDI is the most common pathogen responsible for healthcare-associated infections.¹ Prior findings noted that patients with CDI experience significantly greater risks of mortality, readmission, longer hospital stays, and increased hospital charges, reinforcing the broader public health significance of identifying high-risk subgroups such as patients with IPF. Additional estimates suggest CDI affects approximately 500,000 patients annually in the United States and contributes to tens of thousands of deaths each year.²

This retrospective cohort study underscores the growing need to better understand how chronic pulmonary diseases shape infectious disease outcomes, particularly as patients with IPF are frequently exposed to recognized CDI risk factors, including advanced age, repeated antibiotic exposure, hospitalization, immunosuppression, and gastric acid suppression therapy.¹

After propensity score matching to balance demographics and comorbidities, IPF remained independently associated with significantly higher in-hospital mortality among patients hospitalized with CDI. All-cause mortality reached 12.2% in the IPF cohort (adjusted OR [aOR], 1.85; 95% CI, 1.25-2.75; P = 0.05) compared with 6.2% in matched patients without IPF.

The 5-year prevalence of IPF among patients with CDI was 0.11%. The percentage increased yearly from 0.09% in 2016 to 1.02% in 2020.

Patients with IPF also experienced greater health care utilization. Hospital stays were 3.76 days longer on average among the IPF cohort, and hospitalization costs were markedly higher, with mean charges at $189,308 compared with approximately $99,373 (aOR 1.90, 95% CI 1.55-2.36; P < .001) among matched controls.

Importantly, respiratory compromise appeared to drive the excess mortality burden more than fulminant gastrointestinal complications traditionally associated with severe CDI. Patients with IPF were significantly more likely to require mechanical ventilation (aOR, 1.79; 95% CI, 1.28-2.51) and vasopressor support (aOR, 2.32; 95% CI, 1.10-5.04).

However, investigators did not observe significant increases in severe sepsis, toxic megacolon, colectomy, ileostomy, or ileus after matching.

That distinction may be clinically important. These data “suggests that CDI is not directly causing excess mortality among IPF patients through gastrointestinal pathology. The excess mortality stems from respiratory and hemodynamic decompensation related to baseline IPF,” the study authors wrote. “CDI in IPF patients may serve as a marker of greater underlying illness severity, frailty, or prolonged hospitalization complexity.”

The study also raises questions surrounding antimicrobial stewardship in IPF management. Although evidence supporting routine antibiotics during acute IPF exacerbations remains limited, many patients still receive empiric antimicrobial therapy, potentially increasing susceptibility to CDI. Investigators additionally highlighted proton pump inhibitors (PPIs) as another possible contributor.

PPIs are commonly prescribed in IPF because gastroesophageal reflux disease frequently coexists with pulmonary fibrosis, yet prolonged PPI use has also been associated with CDI risk.

Still, the authors cautioned that the analysis cannot establish causality. Because the National Inpatient Sample is an administrative database, the study is vulnerable to coding inaccuracies, misclassification of IPF diagnoses, and residual confounding. The dataset also lacked detailed information on pulmonary function, disease severity, antibiotic exposure, antifibrotic therapy, and PPI use.

Despite those limitations, the findings provide an important signal for clinicians and health systems caring for patients with advanced pulmonary disease. CDI prevention strategies, antibiotic stewardship initiatives, and earlier risk stratification efforts may be particularly important in hospitalized patients with IPF, especially given the high mortality and resource utilization observed in this cohort.

“Future studies incorporating detailed medication data are needed to clarify how specific treatments, including antibiotics and PPIs, influence CDI risk in this population and to evaluate whether targeted stewardship strategies can improve clinical outcomes,” the study authors concluded.

References

1. Szeto CH, Montalvan GE, Tai CY, et al. Outcomes of Clostridium difficile infection in patients with idiopathic pulmonary fibrosis: analysis of the nationwide inpatient sample, 2016–2020. JGH Open. 2026;10(5):e70416. doi:10.1002/jgh3.70416

2. Gavidia M. Substantial health care burden linked with recurrent CDI for Medicare Advantage, commercial beneficiaries. AJMC^®. November 4, 2022. Accessed May 15, 2026. https://www.ajmc.com/view/substantial-health-care-burden-linked-with-recurrent-cdi-for-medicare-advantage-commercial-beneficiaries