A Stratified Approach to Carbapenem Resistance Management

Multi-drug resistant bacteria are a global threat to public health. In order to improve patient management and to provide information for infection control and prevention there is a pressing need for tools that rapidly stratify patients as colonised or infected by drug resistant bacteria in order to minimise the risk of transfer and outbreak. Carbapenemase-producing Enterobacteriaceae (CPE) present an urgent public health risk. These organisms are resistant to the carbapenem class of antibiotics, often considered the “last resort” in the treatment of many bacterial infections. CPEs restrict treatment options and are associated with increased morbidity and mortality. They are readily transmissible in healthcare settings and countries such as Greece and Italy are already considered endemic for some classes of CPE. Public Health England (PHE) guidelines recommend that high risk patients (those previously admitted to hospital within specific geographical areas both inside and outside the UK, or who have been previously identified as CPE-positive) should be immediately isolated from the general patient population upon hospital admission. These patients should undergo screening for CPE, typically via culture on a commercially-produced chromogenic agar designed for isolation of CPE. These tests can take up to 72 hours to produce a result, with testing recommended on days 0, 2 and 4 after admission, meaning that patients can often be isolated for over a week upon admission, in most cases unnecessarily. This project seeks to improve the stratification of the “at risk” cohort of patients by the introduction of a rapid test for the detection of the major carbapenemase gene families. In the UK, 5 carbapenemase gene families account for > 99 % of all carbapenamases found in Enterobacteriaceae referred to as KPC, NDM, IMP, VIM and OXA-48. From a single sample, the test will stratify patients according to the presence or absence of any of the 5 key carbapenemases in a few hours rather than days. Such a test offers the potential to aid earlier diagnosis, facilitating appropriate patient management while allowing prompt deployment of infection prevention and control measures. Phase 1 of the proposed project will focus on the final development of a polymerase chain reaction (PCR) based test for CPE, including testing of simulated samples in collaboration with the Newcastle Freeman hospital. An economic model will also be developed to confirm the cost effectiveness of using a PCR based diagnostic test to identify CPE carriers upon admission to UK hospitals. Phase 2 would address full commercialisation of the product including clinical evaluation towards appropriate regulatory approval, and further clinical utility studies to generate sufficient diagnostic evidence for inclusion within routine testing in healthcare settings.