How do hospital professionals involved in a randomised controlled trial perceive the value of genotyping vs. PCR-ribotyping for control of hospital acquired C. difficile infections?

Background: Despite scientific advances in typing of C. difficile strains very little is known about how hospital staff use typing results during periods of increased incidence (PIIs). This qualitative study, undertaken alongside a randomised controlled trial (RCT), explored this issue. The trial compared ribotyping versus more rapid genotyping (MLVA or multilocus variable repeat analysis) and found no significant difference in post 48 hour cases (C difficile transmissions). Methods: In-depth qualitative interviews with senior staff in 11/16 hospital trusts in the trial (5 MLVA and 6 Ribotyping). Semi-structured interviews were conducted at end of the trial period. Transcripts were content analysed using framework analysis supported by NVivo-8 software. Common sub-themes were extracted by two researchers independently. These were compared and organised into over-arching categories or ‘super-ordinate themes’. Results: The trial recorded that 45% of typing tests had some impact on infection control (IC) activities. Interviews indicated that tests had little impact on initial IC decisions. These were driven by hospital protocols and automatically triggered when a PII was identified. To influence decision-making, a laboratory turnaround time < 3 days (ideally 24 hours) was suggested; MLVA turnaround time was 5.3 days. Typing results were predominantly used to modify initiated IC activities such as ward cleaning, audits of practice or staff training; major decisions (e.g. ward closure) were unaffected. Organisational factors could limit utilisation of MLVA results. Results were twice as likely to be reported as ‘aiding management’ (indirect benefit) than impacting on IC activities (direct effect). Some interviewees considered test results provided reassurance about earlier IC decisions; others identified secondary benefits on organisational culture. An underlying benefit of improved discrimination provided by MLVA typing was the ability to explore epidemiology associated with CDI cases in a hospital more thoroughly. Conclusions: Ribotyping and MLVA are both valued by users. MLVA had little additional direct impact on initial infection control decisions. This would require reduced turnaround time. The major impact is adjustments to earlier IC measures and retrospective reassurance. For this, turnaround time is less important than discriminatory power. The potential remains for wider use of genotyping to examine transmission routes

Treatment of infections caused by multidrug-resistant Gram-negative bacteria:Report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use

A study of the efficacy and cost-effectiveness of MRSA screening and monitoring on surgical wards using a new, rapid molecular test (EMMS)

<p>Abstract</p> <p>Background</p> <p>MRSA is a significant contributor to prolonged hospital stay, poor clinical outcome and increased healthcare costs amongst surgical patients. A PCR test has been developed for rapid detection of MRSA in nasal swabs. The aims of this study are (1) to estimate the effectiveness of screening using this rapid PCR tests vs culture in reducing MRSA cross-infection rates; (2) to compare the cost of each testing strategy, including subsequent health care costs; and (3) to model different policies for the early identification and control of MRSA infection in surgical patients.</p> <p>Methods/Design</p> <p>The study is a prospective two-period cross-over study set in 7 surgical wards covering different surgical specialities. A total of 10,000 patients > 18 years will be tested over 16 months. The only difference between the two study periods is the method used for the detection of MRSA in each ward (rapid v conventional culture), with all other infection control practices remaining consistent between the arms. The study has been designed to complement routine practice in the NHS. Outcomes are MRSA cross-infection rates (primary outcome) and need for antibiotic therapy and MRSA-related morbidity. Parallel economic and modelling studies are being conducted to aid in the interpretation of the results and to evaluate the cost-effectiveness of the rapid PCR screening strategy.</p> <p>Discussion</p> <p>This paper highlights the design, methods and operational aspects of a study evaluating rapid MRSA screening in the surgical ward setting.</p

Acquisition and Loss of CTX-M-Producing and Non-Producing Escherichia coli in the Fecal Microbiome of Travelers to South Asia

Over 80% of travelers from the United Kingdom to the Indian subcontinent acquire CTX-M-producing (CTX-M-EC), but the mechanism of CTX-M-EC acquisition is poorly understood. We aimed to investigate the dynamics of CTX-M-EC acquisition in healthy travelers and how this relates to populations of non-CTX-M-EC in the fecal microbiome. This is a prospective observational study of healthy volunteers traveling from the United Kingdom to South Asia. Fecal samples were collected pre- and post-travel at several time points up to 12 months post-travel. A toothpicking experiment was used to determine the proportion of cephalosporin-sensitive in fecal samples containing CTX-M-EC. MLST and SNP type of pre-travel and post-travel were deduced by WGS. CTX-M-EC was acquired by 89% (16/18) of volunteers. Polyclonal acquisition of CTX-M-EC was seen in 8/15 volunteers (all had >3 STs across post-travel samples), suggesting multiple acquisition events. Indistinguishable CTX-M-EC clones (zero SNPs apart) are detectable in serial fecal samples up to 7 months after travel, indicating stable maintenance in the fecal microbiome on return to the United Kingdom in the absence of selective pressure. CTX-M-EC-containing samples were often co-colonized with novel, non-CTX-M strains after travel, indicating that acquisition of non-CTX-M-EC occurs alongside CTX-M-EC. The same pre-travel non-CTX-M strains (<10 SNPs apart) were found in post-travel fecal samples after CTX-M-EC had been lost, suggesting return of the fecal microbiome to the pre-travel state and long-term persistence of minority strains in travelers who acquire CTX-M-EC. strains which produce CTX-M extended-spectrum beta-lactamases are endemic as colonizers of humans and in the environment in South Asia. This study demonstrates that acquisition of CTX-M-producing (CTX-M-EC) in travelers from the United Kingdom to South Asia is polyclonal, which is likely due to multiple acquisition events from contaminated food and drinking water during travel. CTX-M-EC frequently persists in the fecal microbiome for at least 1 year after acquisition, often alongside newly acquired non-CTX-M strains. In travelers who acquire CTX-M-EC, pre-travel non-CTX-M remains as a minority population in the gut until the CTX-M-EC strains are lost. The non-CTX-M strains are then reestablished as the predominant population. This study has shed light on the dynamics of CTX-M-EC acquisition, colonization, and loss after travel. Future work involving manipulation of nonvirulent resident could be used to prevent colonization with antibiotic-resistant

Global Origin of Mycobacterium tuberculosis in the Midlands, UK

DNA fingerprinting data for 4,207 Mycobacterium tuberculosis isolates were combined with data from a computer program (Origins). Largest population groups were from England (n = 1,031) and India (n = 912), and most prevalent strains were the Euro-American (45%) and East African–Indian (34%) lineages. Combining geographic and molecular data can enhance cluster investigation

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Tuberculosis Microepidemics among Dispersed Migrants, Birmingham, UK, 2004-2013

MIRU-VNTR typing was supported by the Public Health England National TB Strain Typing Project. M.M. is funded by the UK Clinical Research Collaboration Modernising Medical Microbiology Consortium. C.B. is funded by the Heart of Birmingham Primary Care Trust and Public Health England