OBJECTIVES: Clostridioides difficile infection (CDI) recurrences are associated with substantial clinical and economic burden including high mortality and high hospitalization cost. We analyzed recently available 100% Medicare Fee-for-Service (FFS) claims to assess recurrence and identify risk factors for patients experiencing 1, 2, and 3+ recurrences of CDI (rCDI) to inform CDI patient management.

METHODS: Patients aged ≥65 from 2009-2017 who were continuously enrolled in Medicare Parts A & B (medical) and Part D (pharmacy) for 12 months before and up to 12 months after index CDI (first evidence of CDI) were included. Multivariate logistic regression models were developed to assess probability of recurrence using 12-month pre-index primary CDI (pCDI) baseline demographics and healthcare resource use. Odds-ratios (OR) were estimated to assess risk of 1rCDI vs. none, 2rCDI vs. 1rCDI, and 3+rCDI vs. 2rCDI.

RESULTS: A total of 497,489 CDI patients were included; 69.5% had pCDI only, 13.7% had 1rCDI, 7.4% 2rCDI, and 9.4% 3+rCDI. Odds ratio of recurrence was highest for pre-index transplant patients (OR: 4.01 1rCDI, 4.14 2rCDI, 4.51 3+rCDI; p<0.0001), followed by pre-index antibiotics use, including rifaximin (OR: 2.18 1rCDI; 1.42 2rCDI; p<0.0001), vancomycin (OR: 1.43 1rCDI, 1.30 2rCDI, 1.13 3+rCDI; p<0.0001), and metronidazole (OR: 1.33 1rCDI, 1.20 2rCDI, 1.06 3+rCDI; p<0.001). Pre-index immunosuppressant use, inpatient stay, and enteral feeding also increased CDI recurrence significantly, with ORs 1.18 (1rCDI), 1.12 (2rCDI) (p<0.0001), 1.05 (3rCDI) (p=0.160); 1.22 (1rCDI), 1.19 (2rDI), 1.13 (3+rCDI), p<0.0001; and 1.17 (1rCDI), 1.13 (2rCDI), 1.25 (3+rCDI), p<0.0001; respectively.

CONCLUSION: Transplant was the strongest predictor of multiple CDI recurrences, followed by antibiotic use prior to an index CDI. New therapies to reduce CDI recurrences are needed to improve outcomes and reduce economic and clinical burden to patients, payers, and providers.