Integrating clinical and molecular epidemiology
to determine the effectiveness of a screen-and-treat strategy for
asymptomatic bacteriuria after kidney transplantation
Thesis submitted by Julien COUSSEMENT
in fulfilment of the requirements for the PhD Degree in Medical Sciences
(“Docteur en Sciences Médicales”)
Academic year 2019-2020
Contents
Abstract ... 1
Résumé ... 2
List of research articles related to this PhD thesis ... 3
General introduction ... 4
Clinical epidemiology and current management of symptomatic urinary tract infections and asymptomatic
bacteriuria after kidney transplantation ... 5
HISTORICAL PERSPECTIVE ... 5
WHAT IS THE SCREEN-AND-TREAT STRATEGY FOR ASYMPTOMATIC BACTERIURIA, AND HOW MIGHT IT WORK ... 8
AVAILABLE RECOMMENDATIONS ON ASYMPTOMATIC BACTERIURIA AFTER KIDNEY TRANSPLANTATION ... 9
HOW FREQUENT IS ASYMPTOMATIC BACTERIURIA AFTER KIDNEY TRANSPLANTATION? ... 10
WHY IT IS IMPORTANT TO DO THIS RESEARCH ... 11
Escherichia coli: importance in kidney transplant recipients with bacteriuria, and molecular epidemiology ... 13
E. COLI IS THE LEADING CAUSE OF URINARY TRACT INFECTION AND ASYMPTOMATIC BACTERIURIA ... 13
PATHOGENESIS OF E. COLI URINARY TRACT INFECTIONS ... 14
E. COLI IS A GENETICALLY DIVERSE SPECIES ... 15
USE OF MOLECULAR EPIDEMIOLOGY TO STUDY E. COLI STRAINS CAUSING ASYMPTOMATIC BACTERIURIA AND URINARY TRACT INFECTIONS ... 16
MOLECULAR CHARACTERISTICS OF EXTRA-INTESTINAL PATHOGENIC E. COLI (EXPEC) STRAINS ... 17
ASSOCIATION BETWEEN E. COLI MOLECULAR CHARACTERISTICS AND THE OCCURRENCE, PRESENTATION AND/OR OUTCOME OF URINARY TRACT INFECTIONS ... 18
ROLE OF E. COLI MOLECULAR CHARACTERISTICS IN KIDNEY TRANSPLANT RECIPIENTS WITH URINARY TRACT INFECTION . 20
Gaps in knowledge and research questions ... 21
Research conducted ... 22
1) COCHRANE SYSTEMATIC REVIEW AND META-ANALYSIS TO ASSESS THE BENEFITS AND HARMS OF TREATING ASYMPTOMATIC BACTERIURIA IN KIDNEY TRANSPLANT RECIPIENTS ... 22
2) EUROPEAN SURVEY TO EXPLORE CURRENT PRACTICE RELATED TO THE DIAGNOSIS AND MANAGEMENT OF ASYMPTOMATIC BACTERIURIA IN ADULT KIDNEY TRANSPLANT RECIPIENTS ... 62
3) MULTICENTER CROSS-SECTIONAL STUDY TO DETERMINE THE PREVALENCE OF ASYMPTOMATIC BACTERIURIA AMONG KIDNEY TRANSPLANT RECIPIENTS UNDERGOING ROUTINE SURVEILLANCE ... 71
4) PRAGMATIC, INVESTIGATOR-DRIVEN, RANDOMISED CONTROLLED TRIAL TO COMPARE ANTIBIOTICS WITH NO THERAPY IN KIDNEY TRANSPLANT RECIPIENTS WITH ASYMPTOMATIC BACTERIURIA (BIRT TRIAL) ... 88
5) STUDY USING WHOLE-GENOME SEQUENCING TO IDENTIFY THE HOST AND BACTERIAL FACTOR(S) THAT DETERMINE THE CLINICAL PRESENTATION (I.E., ACUTE PYELONEPHRITIS VS. ASYMPTOMATIC BACTERIURIA) IN KIDNEY TRANSPLANT RECIPIENTS WITH E. COLI BACTERIURIA ... 111
Discussion ... 120
SUMMARY OF MAIN RESULTS ... 121
VALIDITY OF THE BIRT TRIAL RESULTS ... 123
HARMS ASSOCIATED WITH SCREENING FOR AND TREATING ASYMPTOMATIC BACTERIURIA AFTER KIDNEY TRANSPLANTATION ... 127
MOVING FROM EVIDENCE TO RECOMMENDATIONS: DEVELOPING CLINICAL PRACTICE GUIDELINES ... 131
MOVING FROM EVIDENCE TO ACTION: IMPLEMENTING EFFECTIVE ANTIMICROBIAL STEWARDSHIP INTERVENTIONS TO REDUCE UNNECESSARY ANTIBIOTIC USE AMONG KIDNEY TRANSPLANT RECIPIENTS ... 133
NEED FOR INNOVATIVE MEASURES TO PREVENT URINARY TRACT INFECTIONS AFTER KIDNEY TRANSPLANTATION ... 136
RESEARCH PERSPECTIVES: EXPANDING THE USE OF ANTIMICROBIAL STEWARDSHIP IN KIDNEY TRANSPLANT RECIPIENTS BEYOND ASYMPTOMATIC BACTERIURIA ... 143
