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

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 sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. Results 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 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention 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 (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.

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

“…The high risk of invasive infections in recipients colonized by MRSA [ 47 , 48 ] or KPC [ 7 , 8 ] commonly increases morbidity and mortality. In patients with CRE, BSI conferred a significantly lower survival rate [ 7 , 85 , 86 ].…”

“…Liver transplantation is a lifesaving treatment for acute and chronic end-stage liver diseases. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80% [ 6 , 7 , 8 ] despite advanced surgical techniques, new immunosuppressive drugs, prophylactic antibiotics, vaccination, and infection control strategies. The increasing incidence of MDR infections has raised clinical needs in terms of infection control strategies and empiric and targeted antibiotic and antiviral therapies.…”

“…Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80% [ 6 , 7 , 8 ], despite advanced surgical techniques, new immunosuppressive drugs, prophylactic antibiotics, vaccination, and infection control strategies [ 1 ]. Bacterial infections represent up to 70% of all infections in liver transplants, followed by fungal and viral infections [ 9 ].…”

Proposing a Framework to Assess the Methodological Quality of Prognostic Models

“…The liver transplantation (LT) community is already familiar with this concept. Recently, Kim et al showed that “MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women.” ( 8 ) Furthermore, the decision curve analysis helped a multinational cohort study of consecutive adult LT patients to detect cabapenem‐resistant Enterobacteriacae infection after LT. ( 9 ) Although these tools may be a priori complicated, authors publishing in Liver Transplantation should be encouraged to follow them for a comprehensive score evaluation.…”

“…detect cabapenem-resistant Enterobacteriacae infection after LT. (9) Although these tools may be a priori complicated, authors publishing in Liver Transplantation should be encouraged to follow them for a comprehensive score evaluation.…”