Name Marjolein Kluytmans
Date defended March 29, 2019
(Co-) Supervisors Prof. Dr M.J.M. Bonten, Dr P.C.J.L. Bruijning-Verhagen
Title of thesis Extended-spectrum beta-lactamase-producing Enterobacteriaceae in Dutch hospitals

Thesis summary
Across the globe, care-related infections are a key cause of morbidity and mortality, and are increasingly caused by resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). ESBL-E are resistant to the main categories of antibiotics, which interferes with the treatment of infections by these bacteria. To limit the spread of ESBL-E in hospitals, infection prevention guidelines recommend taking contact isolation measures in addition to the standard precautions for patients colonized or infected with ESBL-E, preferably by placing them in a single room.

This thesis describes the development of a laboratory method that improves the detection of rectal carriage of ESBL-E; the use of whole-genome sequencing (WGS) data for the high-throughput detection of new resistance mechanisms in existing collections of Enterobacteriaceae; and the development of a high-resolution typing method based on WGS data, which can be used to determine the transfer of ESBL-E between patients. The main study of this thesis is a multicenter cluster-randomized trial demonstrating that a strategy of contact isolation in a shared room is not inferior to a strategy of contact isolation in a single room in terms of transmission of ESBL-E to other patients. This finding justifies reconsideration of the current preference for the use of single rooms for contact isolation of ESBL-E-positive patients and enables expansion of the control measures for ESBL-E in daily clinical practice. Finally, this thesis provides proof of the effectiveness of contact isolation as a control measure for ESBL-E and demonstrates that the spread of ESBL-E in Dutch hospitals can be managed.