Antibiotic Exposure Patterns and Clinical Outcomes Preceding Clostridioides difficile Infection: A Retrospective...

Background Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated morbidity and mortality, with antibiotic exposure recognized as the principal modifiable risk factor. Variability in antibiotic class, duration, and overlap may influence CDI risk and clinical severity. Local audits of prescribing patterns are essential to inform antimicrobial stewardship strategies. Objective The objective of the study was to characterize antibiotic exposure patterns preceding laboratory-confirmed CDI and to describe associated clinical outcomes, including disease severity, recurrence, and CDI-attributable mortality in hospitalized patients. Methods This retrospective observational study was conducted at Kalinga Institute of Medical Sciences, Bhubaneswar, India, between January 2023 and December 2024. Adult inpatients (≥18 years) with glutamate dehydrogenase (GDH)- and toxin-positive CDI were included. Antibiotic exposure within the preceding 60 days was analyzed for class, duration, number of agents, overlap, and time to CDI. High-risk antibiotic classes were predefined. CDI severity was graded according to the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) 2021 criteria. Outcomes assessed included recurrence and CDI-attributable mortality. Data were analyzed using descriptive statistics. Results Twenty-seven patients were included (mean age 54.26 ± 14.03 years; 59.3% male). The median cumulative antibiotic exposure was 41 days (Q1-Q3: 20.25-129), and 63.0% of patients had overlapping antibiotic therapy. The median interval from first antibiotic exposure to CDI diagnosis was 12 days (Q1-Q3: 8-30.25). Exposure to high-risk antibiotic classes ranged from zero to five, with 29.6% receiving two classes and 11.1% receiving four or more. Non-severe CDI was observed in 55.6% of patients, severe CDI in 37.0%, and fulminant CDI in 7.4%. No recurrence was documented. CDI-attributable mortality was 18.5%. Conclusion Prolonged and multi-class antibiotic exposure, including frequent use of high-risk agents and overlapping therapy, was common among hospitalized patients who developed CDI. The notable mortality observed underscores the importance of targeted antimicrobial stewardship interventions aimed at minimizing unnecessary broad-spectrum and concurrent antibiotic use.