Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study

Objective: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. Methods: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. Results: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77–9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64–8.14, p = .001) were factors independently associated with recurrence. Conclusions: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.