Tackling Resistance And HealthCare Economics Through CPE Screening

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

Research hypotheses to be addressed through the study:

1. The implementation of rapid molecular CPE detection through the Cepheid Xpert Carba-R with an enhanced reporting workflow is associated with greater effectiveness and timeliness in IPC interventions, compared with the existing use of culture-based screening strategies alone. This will lead to reductions in in-hospital transmission of CPE and result in downstream effects for organisation and individuals.
2. In-hospital screening strategies through rapid molecular CPE testing can be cost-effective from a health economic perspective and acceptable to patient and stakeholders, given particular clinical settings and baseline local CPE prevalence.

This is a multi-centre mixed methods research study consisting of:

1. A pragmatic prospective interventional interrupted time series study to examine impact of rapid Carbapenemase producing Enterobacterales (CPE) diagnostics and an enhanced reporting workflow in parallel with screening on clinical practice and transmission.
2. A clinical observational cohort study to characterise individual risk factors for CPE colonisation, epidemiology of colonisation including point-prevalence, and subsequent in-hospital transmission dynamics.
3. A health economic modelling study utilising hospital and national data to estimate medical costs, patient experience and systems level impact of screening, CPE colonisation and acquisition

The study will take place across two hospital Trusts:

1. Imperial College Healthcare NHS Trust (ICNHT), London ii) Guy's and St Thomas NHS Foundation Trust (GSTT), London

Project 1 will implement the Cepheid Xpert Carba-R rapid test in parallel to routine culture for CPE screening at two hospital sites to understand impact on IPC practice.

Project 2 will capture transmission dynamics, healthcare cost, patient acceptability and quality of life metrics using national datasets, and de-identified healthcare data collected from Project 1. Modelling using health economics outcome research methods will be performed to evaluate CPE screening strategies for a range of scenarios and settings with a view of informing policy. Health economic costings will utilise routinely available clinical data as well as costings metrics and health related grouping code from NHS Hospital Episode Statistics.