Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study

Author:

Giannella Maddalena12,Freire Maristela3,Rinaldi Matteo12ORCID,Abdala Edson4,Rubin Arianna1,Mularoni Alessandra5,Gruttadauria Salvatore6,Grossi Paolo7,Shbaklo Nour8,Tandoi Francesco9,Ferrarese Alberto10,Burra Patrizia10,Fernandes Ruan11,Aranha Camargo Luis Fernando11,Asensio Angel12,Alagna Laura13,Bandera Alessandra13,Simkins Jacques14,Abbo Lilian15,Halpern Marcia16,Santana Girao Evelyne17,Valerio Maricela18,Muñoz Patricia18,Fernandez Yunquera Ainhoa19,Statlender Liran20,Yahav Dafna21,Franceschini Erica22,Graziano Elena23,Morelli Maria Cristina24,Cescon Matteo225,Viale Pierluigi12,Lewis Russell12,Bartoletti Michele,Pascale Renato,Campoli Caterina,Coladonato Simona,Cristini Francesco,Tumietto Fabio,Siniscalchi Antonio,Laici Cristiana,Ambretti Simone,Romagnoli Renato,De Rosa Francesco Giuseppe,Muscatello Antonio,Mangioni Davide,Gori Andrea,Antonelli Barbara,Dondossola Daniele,Rossi Giorgio,Invernizzi Federica,Peghin Maddalena,Cillo Umberto,Mussini Cristina,Benedetto Fabrizio Di,Terrabuio Débora Raquel Benedita,Bittante Carolina D,Toniolo Alexandra do Rosário,Balbi Elizabeth,Garcia José Huygens Parente,Morrás Ignacio,Ramos Antonio,Cruz Ana Fernandez,Salcedo Magdalena,

Affiliation:

1. Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, Bologna, Italy

2. Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy

3. Working Committee for Hospital Epidemiology and Infection Control, Hospital das Clinicas, Universidade de São Paulo, São Paulo, Brazil

4. Infectious Diseases Department, Hospital das Clinicas, Universidade de São Paulo, São Paulo, Brazil

5. Infectious Diseases, ISMETT IRCCS, Palermo, Italy

6. Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS, ISMETT-UPMC, Palermo, Italy

7. Infectious and Tropical Diseases Department, University of Insubria, Varese, Italy

8. Infectious Disease, Department of Medical Sciences University of Turin AOU Città della salute e della Scienza, Turin, Italy

9. Liver Transplant Center, General Surgery Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza, Molinette Hospital, University of Turin, Turin, Italy

10. Multivisceral Transplant Unit (Gastroenterology), Department of Surgery Oncology and Gastroenterology, Surgical and Gastroenterological Sciences, Padua University Hospital, Padua, Italy

11. Infectious Diseases Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil

12. Preventive Medicine Department, Puerta de Hierro-Majadahonda University Hospital, Majadahonda, Madrid, Spain

13. Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

14. Transplant Infectious Diseases and Immunocompromised Host Service, Division of Infectious Diseases, University of Miami/Miami Transplant Institute, Miami, Florida, USA

15. Department of Medicine, Division of Infectious Diseases, University of Miami, Miami, Florida, USA

16. Liver Transplant Unit, Quinta D’Or Hospital, Rio de Janeiro, Brazil

17. Infectious Diseases Unit and Liver Transplant Unit of Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, Brazil

18. Department of Clinical Microbiology and Infectious Diseases, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain

19. Department of Gastroenterology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain

20. Intensive Care Unit, Rabin Medical Center, Petah Tikva, Israel

21. Infectious Disease Unit, Beilinson Hospital, Petah Tikva, Israel

22. Infectious Diseases Unit, Department of Nephrology Dialysis and Transplant Unit, University Hospital of Modena, Modena, Italy

23. Infectious Disease Clinic, ASUFC, Udine, Italy

24. Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, Bologna, Italy

25. Liver and Multiorgan Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, Bologna, Italy

Abstract

Abstract Background Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. Methods Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. Results A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9–42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11–24) and 21% (IQR, 15–33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. Conclusions Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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