The emergence and spread of antimicrobial resistance (AMR) poses a significant challenge to the safe delivery of modern medical care. Multidrug-resistant organisms (MDRO) are found more commonly in healthcare settings where they contribute to the burden of healthcare-associated infections (HCAI). Patients in intensive care units are particularly vulnerable to HCAI as they are critically ill, have multiple invasive medical devices and are frequently treated with broad-spectrum antibiotics (which select antibiotic resistant organisms). Several outbreaks of infection caused by MDRO in intensive care units have been reported. They are often identified late, and are associated with high mortality. Microbial whole-genome sequencing (WGS) is an emerging technology that will transform the practice of clinical microbiology. We have previously conducted one of the first studies to demonstrate the potential utility of WGS in a nosocomial outbreak investigation, involving an MRSA outbreak at Addenbrooke’s Hospital. A number of other studies have used WGS retrospectively to investigate nosocomial outbreaks caused by MDROs. Our study will focus on the prevalence and transmission of vancomycin-resistant enterococci (VRE) and multidrug-resistant Gram negative bacilli. We will conduct a prospective surveillance study of MDRO in adults admitted to an intensive care unti at Addenbrooke’s Hospital. This will enable us to determine the rates of carriage, infection and transmission in this vulnerable patient population, and to identify possible intervention and control strategies. We will compare standard epidemiological investigation / typing with WGS in the investigation of suspected MDRO outbreaks, along with a health economic evaluation between these methods.