Extended-spectrum beta-lactamase-producing Enterobacteriaceae in Dutch hospitals

Abstract

Healthcare-associated infections are a leading cause of morbidity and mortality worldwide and are increasingly caused by antimicrobial resistant bacteria, including extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). ESBL-E are resistant to the most important class of antibiotics, which limits therapeutic options. To control the spread of ESBL-E within hospitals, infection control guidelines recommend applying contact precautions in addition to standard precautions for patients who are colonised or infected with ESBL-E, preferably in a single-bed room. This thesis describes the development of a laboratory method that improves the detection of ESBL-E rectal carriage; the use of whole-genome sequencing (WGS) data for high-throughput detection of novel resistance mechanisms in existing collections of Enterobacteriaceae; and the development of a high-resolution WGS-based typing method for ESBL-E that can be used to identify nosocomial transmission of ESBL-E. The main study described in this thesis is a multicentre, cluster-randomised study that provides evidence that an isolation strategy of contact precautions in a multiple-bed room is non-inferior to a strategy of contact precautions in a single-bed room in terms of transmission of ESBL-E to other patients. Non-inferiority of the multiple-bed room strategy may change the current single-bed room preference for the isolation of ESBL-E-positive patients and thus broaden infection control options for ESBL-E in daily clinical practice. Finally, this thesis provides evidence for the effectiveness of contact precautions in the control of ESBL-E, and demonstrates that it is possible to control the nosocomial transmission of ESBL-E in Dutch hospitals.