Prediction and Prevention of Bloodstream Infections After Kidney Transplantation

Overview

Kidney transplant recipients take medicines that suppress the immune system to prevent rejection of the transplanted kidney. As a result, they have a high risk of infections, especially urinary tract infections (UTIs). Some of these infections can spread to the bloodstream and cause serious illness, hospitalization, loss of kidney function, or death. Currently, there is no established strategy to prevent these serious bacterial infections in kidney transplant recipients who are at highest risk. The PREDICT study is investigating whether a low daily dose of the antibiotic pivmecillinam can reduce the risk of bacterial urinary tract infections and bloodstream infections after kidney transplantation. The study focuses on kidney transplant recipients who have bacteria detected in their urine during the first month after transplantation, as previous research suggests that these patients have a particularly high risk of developing serious infections later. In this randomized, double-blind, placebo-controlled trial, 180 adult kidney transplant recipients will be assigned by chance to receive either pivmecillinam or a matching placebo from 1 to 6 months after transplantation. Neither participants nor study staff will know which treatment has been assigned during the study. All participants will continue to receive standard post-transplant care and monitoring. The main goal of the study is to determine whether prophylactic pivmecillinam can reduce the occurrence of infections caused by Enterobacterales bacteria, including urinary tract infections and bloodstream infections, during the first 6 months after transplantation. The study will also evaluate the effects of treatment on serious clinical outcomes, safety, quality of life, antimicrobial resistance, and long-term kidney transplant outcomes. The study hypothesis is that targeted antibiotic prophylaxis with pivmecillinam in kidney transplant recipients at increased risk of infection will reduce the incidence of Enterobacterales urinary tract infections and bloodstream infections during the high-risk period after transplantation compared with placebo.

Background: Kidney transplant recipients are at increased risk of infectious complications because immunosuppressive treatment is required to prevent rejection of the transplanted kidney. Urinary tract infections are among the most common infectious complications after transplantation and may lead to bloodstream infections, which are associated with substantial morbidity, mortality, and risk of graft loss. Despite this burden, there is currently no established targeted strategy to prevent serious bacterial infections in kidney transplant recipients at highest risk of infection. Previous work by the investigators demonstrated that bacteriuria during the first month after kidney transplantation is an important predictor of subsequent urinary tract infections and bloodstream infections. Early bacteriuria therefore represents a clinically useful marker for identifying a high-risk subgroup that may benefit from preventive interventions. Study rationale: The PREDICT study evaluates a risk-stratified prophylactic strategy using pivmecillinam in kidney transplant recipients with early bacteriuria. Pivmecillinam is a narrow-spectrum oral antibiotic with activity against Enterobacterales, which are the predominant causes of urinary tract infections and bloodstream infections after kidney transplantation. Its pharmacological profile and extensive clinical experience make it a potential candidate for targeted prevention during the period of highest infection risk after transplantation. Objectives: The primary objective is to determine whether prophylactic pivmecillinam reduces the occurrence of Enterobacterales urinary tract infections and/or bloodstream infections in high-risk kidney transplant recipients. Secondary objectives include evaluation of all bloodstream infections, severe clinical outcomes, treatment safety, antimicrobial resistance, and patient-reported quality of life. Exploratory objectives include investigation of microbiome and resistome changes, immunological and metabolic biomarkers, and long-term transplant outcomes. Study Design: PREDICT is a Danish nationwide multicentre randomized, double-blind, placebo-controlled trial. Adult kidney transplant recipients with bacteriuria during the first month after transplantation will be randomly assigned to receive prophylactic pivmecillinam or placebo in addition to standard post-transplant care. Participants will be followed during the intervention period and for safety evaluation after treatment completion. Long-term outcomes will be assessed through national registry follow-up.