Multi-centre Evaluation of Carbapenemase-producing Enterobacterales (CPE) Prevalence and Transmission Dynamics, Recommendations on Screening Strategies, and Health Economics Outcomes Research Impact to Inform Policy Change

Carbapenemase-producing Enterobacterales (CPE) are a significant threat to healthcare through their ability to cause drug-resistant infections. These group of bacteria posses enzymes which break down and inactivate carbapenems, a broad spectrum class of antibiotics reserved for severe infections. Transmission of CPEs between patients occur through proximity / contact within their environment in hospital - and is therefore preventable.

Within the individual, initial colonisation with CPE is an important risk factor for development of multi-drug resistant infections which are associated with significant mortality and high hospital costs. The in-hospital transmission of CPE exerts a complex burden across almost all healthcare domains - for example, CPE infection or colonisation renders common surgical antibiotic prophylaxis ineffective, increases morbidity and mortality in vulnerable patient groups such as intensive care, places burdens on the use of single occupancy beds and imposes considerable cost and disruption to care pathways through outbreaks.

Existing microbiological diagnoses of CPEs vary, but commonly involve bacterial culture of a sample such as a rectal swab in laboratory settings followed by phenotypic testing and characterisation of common antibiotic resistant genes (ARGs) through molecular or immunochromatographic approaches, mostly focusing on the "big 5" mechanisms of CPE. Such testing pathways can however be time-consuming, with the median result turnaround time to be between 24-48 hours. Rapid molecular testing for CPE bypasses the bacterial culture step and may allow for robust IPC measures to be implemented in a near real-time fashion including rapid risk stratification of CPE carriage status. Where transmission is suspected, contact tracing using rapid testing early in the transmission cascade could reduce unwanted impact and be cost-effective.

The proposed study examines the utility, cost-benefit in adoption of a rapid based screening approach using rapid CPE testing coupled with an enhanced reporting workflow operating 24 hours a day, compared with existing standard practice. Given the complex interactions of AMR and CPE acquisition and transmission within hospital settings, a comprehensive approach including clinical, epidemiological and health economic costings will be utilised and modelled in order to accurately understand impact. Rapid CPE screening will be incorporated into clinical processes to minimise adverse impact and the research conducted as a pragmatic study.

The rapid test for use in this study is the Cepheid Xpert Carba-R which can detect genes in 5 most prevalent Carbapenemase gene families (including KPC, NDM, VIM, IMP and OXA classes) directly from a rectal swab sample in 50 minutes - this technology is CE-mark approved as an in vitro diagnostic and has undergone NICE technological appraisal