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

Giusy Tiseo; Dafna Yahav; Alaa Atamna; Tomer Avni; Manuel Causse; Elena Pérez-Nadales; Alessandra Mularoni; Elena Reigadas; María Olmedo-Samperio; Mario Fernández-Ruiz; Zaira R Palacios-Baena; Jesus Rodríguez-Baño; Paolo De Simone; Giandomenico Biancofiore; Eman Fares Sabik; Mical Paul; José María Aguado; Ugo Boggi; Patricia Muñoz; Julián Torres-Cisneros; Alessio Farcomeni; Marco Falcone; ESCMID Study Group for Infections in the Elderly (ESGIE)

doi:10.1016/j.jinf.2024.106306

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

J Infect. 2024 Oct 5;89(6):106306. doi: 10.1016/j.jinf.2024.106306. Online ahead of print.

Authors

Giusy Tiseo¹, Dafna Yahav², Alaa Atamna³, Tomer Avni³, Manuel Causse⁴, Elena Pérez-Nadales⁴, Alessandra Mularoni⁵, Elena Reigadas⁶, María Olmedo-Samperio⁶, Mario Fernández-Ruiz⁶, Zaira R Palacios-Baena⁷, Jesus Rodríguez-Baño⁷, Paolo De Simone⁸, Giandomenico Biancofiore⁹, Eman Fares Sabik¹⁰, Mical Paul¹⁰, José María Aguado⁶, Ugo Boggi¹¹, Patricia Muñoz⁶, Julián Torres-Cisneros⁴, Alessio Farcomeni¹², Marco Falcone¹³; ESCMID Study Group for Infections in the Elderly (ESGIE)

Affiliations

¹ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
² Infectious Diseases Unit, Sheba Medical Center, Ramat Gan, Israel.
³ Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
⁴ CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Clinical Units of Microbiology and Infectious Diseases, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Department of Agricultural Chemistry, Edaphology and Microbiology and Department of Medical and Surgical Science, University of Cordoba, Cordoba, Spain.
⁵ Infectious Diseases Unit, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy.
⁶ Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Health Research Institute Hospital "12 de Octubre" (imas12), Department of Medicine, School of Medicine, Universidad Complutense, CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
⁷ CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Infectious Diseases and Microbiology Clinical Unit, University Hospital Virgen Macarena, Instute of Biomedicine of Seville (IBiS)/CSIC, Department of Medicine, University of Seville, Seville, Spain.
⁸ Liver Transplant Program, University of Pisa Medical School Hospital, Pisa, Italy.
⁹ Division of Transplant Anesthesia and Critical Care, Department of Anesthesia, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
¹⁰ Infectious Diseases Instute, Rambam Health Care Campus, Haifa, Israel.
¹¹ Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.
¹² Department of Economics and Finance, Tor Vergata University of Rome, Rome, Italy.
¹³ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Electronic address: marco.falcone@unipi.it.

PMID: 39374859
DOI: 10.1016/j.jinf.2024.106306

Abstract

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.

Keywords: Bezlotoxumab; Clostridioides difficile; Metronidazole; Recurrence; Solid organ transplant.