Thursday, April 18, 2024
4/18/2024
¿ DESCRIPTION (provided by applicant): Multidrug-resistant (MDR), community-acquired urinary tract infections (UTI) contribute to severe medical complications, including sepsis. Of particular concern is the rising resistance against third generation cephalosporins (3GC) and carbapenems. A large proportion of community-acquired UTI in most regions of the world are caused by a limited set of multi-drug resistant E. coli strains belonging to related lineages, or E coli strains that harbor drug resistance genes shared by pathogenic and environmental Gram negative bacteria. Studies have shown that MDR uropathogenic E. coli (UPEC) share the same genetic lineages with E. coli causing infection in poultry, indicating potential foodborne transmissions of antibiotic resistant UPEC. However, additional research is required to accurately quantify the contribution of food and food animals as reservoirs for E. coli pathogens that cause drug-resistant UTI. Our project will examine the transmission dynamics of MDR UPEC in Dhaka, Bangladesh as a paradigm of how UPEC clonal lineages and their drug-resistance determinants disseminate in community as opposed to healthcare settings. We plan to do this project in Bangladesh as this country along with other countries in the sub-continent appear to be an important reservoir of many multidrug-resistant Enterobacteriaceae organisms and lineages that are observed globally. We will do this study in 3 phases: first we will determine the trend in prevalence of MDR E. coli in patients with UTI (yr1 to yr3.5) and identify risk factor associated with MDR UTI. Second, we will study the retail food, water and poultry sources for MDR UPEC (yr1.5-yr3.5). Finally, we will compare the antibiotic resistance profiles and genotypic characteristics of isolates from UTI and food sources to track mode of transmission of UPEC associated with community acquired UTI (yr2-yr4.5). Whole genome sequencing of isolates sharing their genetic lineages (based on PFGE and MLST data) will be used to determine the direction of transmission. Altogether, the project will take 60 months. This project will enable us to quantitatively determine the impact, if any, of food and food-producing animals as reservoirs for E. coli pathogens on an important and common community-acquired infection-UTI. If such reservoirs turn out to be a major source of these infections, we will be able to devise more focused public health interventions to prevent them.
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