Head of Infection Prevention at Bern University Hospital
University of Bern
Adjunct Faculty, Division of Infectious Diseases
Washington University School of Medicine
When he joined the BIRCWH program, Dr. Marschall was an Assistant Professor of Medicine in the Division of Infectious Diseases at Washington University School of Medicine and was pursuing a career in patient-oriented, translational research. His focus was the epidemiology of hospital infections and their management and he was particularly interested in causes and treatment of urinary tract infections. He was the recipient of an institutional career development award (KL2) to study the relationship between E. coli urinary tract infections and bloodstream infections in hospitalized patients, including an analysis of bacterial virulence factors. After his first year in the BIRCWH, he was recruited to a prestigious position in his home country of Switzerland. He is the Head of Infection Protection at Bern Hospital in Bern, Switzerland.
BIRCWH Scholar from 07/01/2012 until 06/30/2013
Host and microbial factors associated with E. coli urinary tract infection
The purpose of this proposal for a BIRCWH award is to provide additional education, resources, and protected time to ensure my transition to an independent clinical researcher studying E. coli urinary tract infections. I will take coursework in lab methodology, statistics, microbial pathogenesis, and immunology, and obtain a Master of Science in Clinical Investigation. I have chosen a clinical research mentor, Dr. David K. Warren, and a basic science mentor, Dr. Jeffrey P. Henderson. My research interest is focused on risk factors for and outcomes of urinary tract infections in the hospital setting. E. coli bacteriuria is common and can be either asymptomatic or present with symptoms. Symptomatic urinary tract infections can progress to kidney and bloodstream infections, which are associated with increased morbidity and mortality. Specific risk factors for symptomatic urinary tract infection are poorly understood, both in terms of patient factors and bacterial factors. In order to improve the treatment and prevention of these infections, basic data are needed. The specific aims of his research project are to: 1) Determine patient risk factors for developing symptomatic urinary tract infection in hospitalized patients with E. coli bacteriuria. We will assemble a prospective cohort and perform stratified analyses by gender, urinary catheter-association, and location of acquisition. We hypothesize that male gender and patients with obstruction and urinary stasis are at increased risk for symptomatic urinary tract infection. 2) Determine patterns of E. coli virulence factors associated with symptom development in bacteriuria. Bacterial genomes will be interrogated for the presence of approximately 20 virulence genes and compared in symptomatic versus asymptomatic patients from the cohort in aim 1. We hypothesize that a specific virulence factor pattern (p-fimbriae, afimbrial adhesin, yersiniabactin) is associated with progression to symptomatic urinary tract infection. 3) Determine the levels of a urinary antimicrobial peptide, cathelicidin, and serum vitamin D levels (cathelicidin is regulated by vitamin D), and compare them between symptomatic patients, asymptomatic patients, and healthy volunteers. We hypothesize that lower vitamin D levels lead to lower cathelicidin levels correlating with a higher likelihood of progression to symptoms. For statistical analyses, we will use logistic regression and multilevel modeling (for aims 1 and 2), and ANOVA (for the nested case-control study in aim 3). The overarching goal is to elucidate risk factors for symptomatic E. coli urinary tract infection in a multi-faceted manner in order to lay the groundwork for innovative prevention and treatment trials.