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

Abstract

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 2014eJune 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 75e84 years and vs 85 þ years) was associated with higher risk of rCDI (OR ¼ 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.

Excess length of hospital stay, mortality and cost attributable to Clostridioides (Clostridium) difficile infection and recurrence: a nationwide analysis in Japan

“…low sensitivity of diagnosis code-based definition) [36] and (2) EIA test results were available from only nine hospitals and the majority of CDI was defined by diagnosis and CDI treatment, while acknowledging that not all CDI cases in Japan are managed with VCM or MNZ (e.g. some cases are managed by stopping antibiotic treatment) [31]. Any misclassified false-negative cases would bias towards a smaller difference between CDI and non-CDI (i.e.…”

Clostridioides (Clostridium) difficile infection in Japanese hospitals 2008–2017: A real-world nationwide analysis of treatment pattern, incidence and testing density

“…We consider that our incidence is underestimated for the following reasons: 1) Diagnosis code: even if CDI was diagnosed in the clinical setting, the diagnosis code may not be recorded if it is not essential for reimbursement purposes. We previously reported that half of the patients treated with oral VCM or oral/IV MNZ did not have a CDI diagnosis code in this database [6]. Therefore, there are likely to be CDI cases without a diagnosis code and, thus, not defined as CDI in this study; 2) Treatment: in addition to diagnosis code, patients had to have either CDI treatment or a positive EIA test in this study.…”

“…Our study found that probiotics were used in approximately three-quarters (74.2%) of CDI-associated hospitalizations. Increased probiotic use was observed in cases with subsequent rCDI (85.7%), which likely reflects an attempt to protect patients with known risk factors for recurrence, for example older age, prior CDI or those treated with proton pump inhibitors [6].…”

“…We acknowledge that not all CDI cases in Japan are managed with VCM or MNZ (e.g. some cases are managed by stopping antibiotic treatment) [6]. Therefore, there are likely to be CDI cases that were not treated and so not defined as CDI in this study.…”

“…CDI is a leading cause of hospital-acquired infection that places a considerable burden on health-care systems across the globe [1e3]. Recurrence of CDI is common [4e6], particularly in older patients [6]; a recent study using Japanese hospital data estimated the recurrence rate as 17.8% within 8 weeks of the start of prior CDI treatment [6].…”