Summaries of recent research projects
Syndromic testing for infective gastroenteritis
Diarrhoea is a common symptom amongst hospitalised patients, only a relatively small proportion is caused by an infectious agent. Those pathogens that do cause gastroenteritis are difficult to distinguish on clinical symptoms alone. Laboratory testing for infectious gastroenterits is often slow, sometimes taking up to 3 or more days which is wasteful of infection control resources. We have evaluated a number of multiplex panels that can simultaneously detect a wide range of bacteria, viruses and parasites and undertook an 8 month clinical study involving over 200 patients to understand how patient pathways could benefit and result in potential cost savings to the wider NHS. We have also introduced an in-house PCR test for norovirus which is currently in routine use providing a rapid and accurate result for the benefit of our patients.
Testing for respiratory pathogens
Laboratory based testing for Influenza and RSV can take up to 12 hours, since these viruses are spread easily, there is a risk of cross-transmission if symptomatic patients are not isolated pre-emptively. There is the potential for isolation rooms to become quickly overwhelmed in the winter months, thus there is a need for a more rapid test which could guide clinicians decisions about patient isolation and treatment with antiviral drugs. We have been working with Enigma Diagnostics Ltd to validate a rapid point of care PCR test which can be operated by non experts at the point of care, providing a result in under 80 minutes. There are a number of other tests for respiratory pathogens which have become available recently, we plan to prioritise these new technologies and perform pilot studies to investigate their potential use in the clinical areas such as the Emergency Department, paediatrics and ICU.
Improving testing for sexually transmitted infections
We have modelled the cost effectiveness and patient pathway benefits of decentralising tests for Chlamydia and gonorrhoea. Our work has shown how a rapid, highly sensitive PCR test can save genitourinary medicine service delivery costs and improve patient care by improving patient contact tracing and reducing long term sequelae.
Screening for MRSA colonisation
We have worked with a number of diagnostics companies to help develop and evaluate new technologies to screen for MRSA. These range from high throughput automated molecular tests to random access rapid point of care tests. We have also evaluated the cost effectiveness of screening, isolation and decolonisation strategies in high risk settings such as ICU.
We undertook a 22month pilot study to investigate the potential clinical utility of ward based, rapid testing for Clostridium difficile infection and the role of the colonised patient in ward based transmission.
We have evaluated new technologies for the detection of common agents of blood stream infections, from pre-incubated blood culture samples. Some of these emerging technologies offer the potential to detect several antimicrobial resistance genes, in addition to providing species level identification. The potential use of the technologies in terms of improved antimicrobial stewardship (cessation or de-escalation of therapy) was compared to standard culture-based identification methods.
Smart Phone app for Infections
We are developing an antimicrobial prescribing smart phone app (for iOS and Android) which can be used by clinicians to help guide choice of empiric antimicrobial therapy and guide appropriate selection of laboratory tests. This will allow doctors and nurses easy and rapid access to key policies and guidelines at the time they are needed. This may help to improve antimicrobial stewardship and in the long term, limit the impact of antimicrobial resistance. The app is due to launch in Spring 2014.
MRSA was a major problem for the Trust during the 2000s. Since the widespread emergence of MRSA in our Trust, we preformed extensive studies to evaluate the clinical and molecular epidemiology of MRSA in the patients served by the Trust and in the local community. We have used molecular tools, including whole genome sequencing, to define the population structure of key MRSA clones and clonal groups. This has helped to shed new insight on MRSA, with local and international impact. We have also applied molecular tools in real-time to assist with investigation of several high-profile outbreaks. One outbreak in particular, of so-called ‘TW’ MRSA on the ICU has provided novel data on strain-specific transmissibility and virulence potential. A number of outbreaks have implicated contaminated surfaces and equipment in transmission, and we have performed several prospective studies evaluating the role of contaminated surfaces in transmission.
We have performed a number of studies evaluating therapeutic aspects of MRSA treatment and control. The implementation of universal use of chlorhexidine decolonization is likely to have been a major factor in the reductions of MRSA achieved by the Trust. However, recent work has demonstrated a subtle, gradual reduced susceptibility to both chlorhexidine and vancomyin, which remains the mainstay of MRSA therapy. We have also discovered that reduced susceptibility to chlorhexidine and vancomycin is more relevant clinically in a particular clone.
During the 2000s, we noted the early emergence of community-associated MRSA (CA-MRSA) in the UK, and have continued to carefully monitor the prevalence of CA-MRSA, which has become endemic in many countries. We are currently performed detailed in vitro analysis of a range of healthcare- and community-associated MRSA to evaluate potential differences in virulence potential.
The most appropriate screening methods and regimen for MRSA has been a contentious issue, with the advent of rapid molecular tests for MRSA and the Government’s mandate to screen all admissions for MRSA. We have performed a randomised cross-over study demonstrating that the introduction of a rapid laboratory-based molecular test for MRSA does not result in reduced transmission. Current work indicates that the prevalence of MRSA identified on admission is low, but that reverting to our previous targeted screening approach would miss a substantial number of carriers, particularly those carrying CA-MRSA strains. Thus, we are generating data that will contribute to the debate and national policy about the most appropriate MRSA screening methods and regimen.
Multidrug-resistant Gram-negative rods (MDR-GNR)
Pilot Evaluation of a Whole Genome Sequencing Service to Track Transmission of Methicillin Resistant Staphylococcus aureus (MRSA) and Target Infection Control Interventions across South London
MDR-GNR, including Enterobacteriaceae such as Klebsiella pneumoniae and non-fermenters such as Acinetobacter baumannii are emerging rapidly worldwide. These problematic pathogens are multidrug-resistant leaving few, if any, therapeutic options, and are a particular risk to the local population due to ethnic mix and travel to high-prevalence areas, which are risk factors for MDR-GNR. MDR-GNR present unique challenges to infection prevention and control. First, unlike MRSA and C. difficile, MDR-GNR can be caused by multiple genes in multiple species and genera. The combination of resistance genes and species may have distinct characteristics with transmission and control implications. Further, there is a larger pool of resistance genes for horizontal transfer. Second, MDR-GNR often colonize the gastrointestinal tract, so decolonization therapy is likely to be limited to suppressing the amount of MDR-GNR in the gut; elimination of the carrier state, which has been a central component of prevention and control interventions for MRSA, seems unlikely. Third, pan-drug resistant MDR-GNR has already been reported and the pipeline for new agents is virtually empty, meaning that effective therapeutic options will be increasingly limited.
We have begun a series of studies to understand the current epidemiology of MDR-GNR. These include enhanced surveillance, evaluation of transmission routes and factors influencing extended colonization. These studies will help to guide the most effective control strategies
This BRC funded project is investigating how MRSA transmits within hospitals, across hospitals and between hospitals and the community to improve the rationalisation and cost-effectiveness of prevention and control resources. To achieve this, we are using whole genome sequencing to characterise the genetic profile of MRSA isolates obtained at five hospitals which provide microbiology diagnostic services for inpatients, outpatient clinics and community patients in Lambeth, Southwark and Lewisham London boroughs. We are also investigating whether there exists a spatial structure to MRSA population genetics and how this relates to social and economic inequalities in the South London community.
Transmission Models for MRSA clones in Hospitals
We are investigating the distribution and risk factors for low and high level resistance to mupirocin based decolonising agents in the range of MRSA clones that co-circulate in the South London community and our hospitals. In addition, the Modelling & Economics Unit, PHE, is developing transmission models for mupirocin resistance based on the comprehensive dataset provided by the 'the Pilot Evaluation of a WGS Service to Track Transmission of Methicillin Resistant Staphylococcus aureus (MRSA)'.
Spatial-temporal patterns of antimicrobial resistance outbreaks in hospitals
The School of Mathematical Sciences (University of Nottingham), Nuffield Department of Medicine (University of Oxford) and Mahidol-Oxford Tropical Medicine Research Unit collaborating centres have recently developed state-of-the-art transmission models that combine WGS and epidemiological hospital data. We are applying these new methods to comparatively describe the transmission rates of endemic and epidemic MRSA clones in hospitals where application of chlorhexidine based decolonising agents is common place in collaboration with the above centres and the Sanger Institute.
The CLAHRC Infection Theme
We recently described a pattern of frequent temporal clustering of antimicrobial resistance outbreaks across multiple bacterial groups in an eight-year retrospective study of ICU data. We also found evidence that most resistance outbreaks go undetected and that current standard infection control interventions have resulted in decreased incidence of bacterial species outbreaks but have had no apparent impact on the incidence of transmission clusters of resistance. We are collaborating with the Department of Pathogen Molecular Biology at London School of Hygiene and Tropical Medicine (LSHTM) to determine whether clustering of resistance outbreaks arises from horizontal transfer of MGEs and to determine whether this is the predominant mechanism of resistance emergence and spread in the ICU.
We are part of the new CLAHRC Infection Theme, lead by Professor Mike Sharland, St George's University hospital. We are collaborating with the Primary Care and Public Health Sciences Department and the Centre for Host-Microbiome Interactions, King's College London, to bring about a series of projects to investigate transmission of antibiotic resistant gram-negative bacteria (ARGNB) in our community in relation to population and host traits. We are planning population-based studies to determine the geographical distribution of ARGNB in our community, and the potential for the existence of transmission clusters in population subgroups. We are also planning prospective cohort studies of gut carriage of carbapenem resistant gram-negative bacteria (GNB) and GNB resistant to third generation cephalosporins to determine the relationship between the human colonic microbiome profile, the resistant bacteria colonic load and the within-household transmission probability of resistant bacteria.