Causal_pathways_to_colonisation_with_extended_spectrum_beta_lactamase_producing_Enterobacteriaceae_during_hospitalisation_in_a_low_income_setting__CAPSULE_

Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) pose a major threat to health, especially in sub-Saharan Africa (sSA) where treatment options are limited or unavailable and ESBL-E infections are associated with high mortality. Lack of evidence on the real causal factors and routes of ESBL-E transmission in sSA limits the prioritisation and implementation of interventions for controlling further spread. I will investigate the pathways to colonisation with ESBL-E at the Queen Elizabeth Central Hospital (QECH), focusing on the roles of hospital environment, antimicrobial use (AMU), gut microbiome diversity and patient-carer interactions in influencing hospital acquisitions of ESBL-E. Aims i. To characterise changes in patient and carer gut microbiota during hospitalisation; ii. To determine hospital reservoirs of ESBL-E and routes of transmission to initially non-colonised patients and carers during hospitalisation; iii. Explore the causal relationships of AMU, patient and hospital hygiene factors with gut microbiota diversity and their influence on acquisition of ESBL-E Materials and methods Stool samples, socio-demographic and clinical data will be prospectively and longitudinally collected from 300 adult patients admitted to the medical ward of QECH for non-bacterial infection conditions, and their carers. Stool samples will be screened for ESBL-E and whole genomes of ESBL-E isolates will be sequenced. A pair of stool samples from each participant, and 150 ESBL-E positive environmental samples will be selected for shotgun metagenomic sequencing. A combination of bioinformatics and causal modelling approaches will be used to determine reservoirs and routes of ESBL-E transmission and causal effects of AMU, hospital contamination and gut microbiome diversity on ESBL-E