Characterization and risk factors for recurrence of Clostridioides (Clostridium) difficile infection in Japan: A nationwide real-world analysis using a large hospital-based administrative dataset

Objective: Recurrent Clostridioides (Clostridium) difficile infection (rCDI) is common and increases healthcare resource utilization. In this study, we assessed rCDI risk factors using an up-to-date, Japanese national hospital-based database. Methods: C. difficile infection (CDI) episodes, occurring July 2014-June 2017, in patients aged >= 18 years were extracted from the database and a nested case-control analysis was performed. Cases were defined as rCDI episodes which required re-initiation of oral vancomycin or oral/intravenous metronidazole treatment within 8 weeks from the start of initial treatment. Cases were matched to 4 non-rCDI episodes at the timing of rCDI occurrence. Adjusted odds ratios (ORs) were estimated using multivariate conditional logistic regression model. Results: Of 18,246 initial CDI episodes, 3250 (17.8%) had at least one rCDI. Approximately 90% of episodes occurred in inpatients and 65% were treated with metronidazole. Older age (<75 years vs 75-84 years and vs 85 thorn years) was associated with higher risk of rCDI (OR = 1.27, 95% confidence interval [1.15, 1.41] and 1.45 [1.30, 1.61], respectively). Use of systemic antibiotics (3.16 [2.90, 3.44]), probiotics (2.53 [2.32, 2.77]), chemotherapy (1.28 [1.08, 1.53]), or proton pump inhibitors (PPIs) (1.17 [1.07, 1.28]), and prior CDI history (1.22 [1.03, 1.43]) were also identified as rCDI risk factors. Vancomycin reduced the risk of rCDI compared with metronidazole treatment (0.83 [0.76, 0.91]). Conclusion: This large, multicenter, nationwide study confirmed that older age, PPIs, antibiotics, probiotics, chemotherapy, and prior CDI history are risk factors for rCDI in Japan. There was a 17% decrease of rCDI risk with vancomycin vs metronidazole treatment. Clinical trial registration number: N/A. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd.