Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England.

BACKGROUND: Marked increases in Clostridium difficile infection (CDI) incidence, driven by epidemic strain spread, is a global phenomenon. METHODS: The Clostridium difficile Ribotyping Network (CDRN) was established in 2007 as part of enhanced CDI surveillance in England, to facilitate the recognition and control of epidemic strains. We report on changes in CDI epidemiology in England in the first 3 years of CDRN. RESULTS: CDRN received 12,603 fecal specimens, comprising significantly (P < .05) increasing numbers and proportions of national CDI cases in 2007-2008 (n = 2109, 3.8%), 2008-2009 (n = 4774, 13.2%), and 2009-2010 (n = 5720, 22.3%). The C. difficile recovery rate was 90%, yielding 11,294 isolates for ribotyping. Rates of 9 of the 10 most common ribotypes changed significantly (P < .05) during 2007-2010. Clostridium difficile ribotype 027 predominated, but decreased markedly from 55% to 36% and 21% in 2007-2008, 2008-2009, and 2009-2010, respectively. The largest regional variations in prevalence occurred for ribotypes 027, 002, 015, and 078. Cephalosporin and fluoroquinolone use in CDI cases was reported significantly (P < .05) less frequently during 2007-2010. Mortality data were subject to potential reporting bias, but there was a significant decrease in CDI-associated deaths during 2007-2010, which may have been due to multiple factors, including reduced prevalence of ribotype 027. CONCLUSIONS: Access to C. difficile ribotyping was associated with significant changes in the prevalence of epidemic strains, especially ribotype 027. These changes coincided with markedly reduced CDI incidence and related mortality in England. CDI control programs should include prospective access to C. difficile typing and analysis of risk factors for CDI and outcomes.

Detection of Clostridium difficile infection: a suggested laboratory diagnostic algorithm.

Currently, the diagnosis of Clostridium difficile infection (CDI) relies on the detection of toxins A and B in faeces but the sensitivity of these tests has been questioned, particularly in advanced disease. In this context, additional methods to enhance the diagnosis of C. difficile have been investigated. In this study, 1007 faecal samples are tested using toxigenic culture, an immunoassay for toxins AB and the C. difficile-specific glutamate dehydrogenase (GDH) test. Samples positive by any of the above tests are evaluated for the presence of faecal lactoferrin as an indicator of intestinal inflammation. Patients with evidence of inflammation but with negative toxin AB tests are followed up to assess clinical outcome. The toxin AB test was positive in 35 samples (3.4%), while 121 (12%) samples were culture-positive, 87 (8.6%) of which were toxigenic. Glutamate dehydrogenase proved to be a sensitive and specific marker of C. difficile with a negative predictive value of 99.3% (95% CI: 0.98-1.00). Faecal lactoferrin was positive in 52/129 (40.3%) samples tested. A cohort of 15 patients with a negative faecal toxin AB and a positive lactoferrin test was C. difficile culture-positive with a toxigenic isolate; clinically, all had advanced CDI. All demonstrated faecal toxin between five and 41 days later on repeat testing. It is suggested that a two-step algorithm be used to include screening faecal samples for GDH, with positive samples tested for faecal toxin AB and lactoferrin. Patients who present with a negative faecal toxin AB test and a positive lactoferrin test were serially tested for faecal toxin AB every five to seven days until a diagnosis was established. More sensitive tests than enzyme-linked immunosorbent assay (ELISA) for the detection of faecal toxin, or the use of a rapid specific test for the presence of a toxigenic strain, must be considered in such patients.

Audit of laboratory diagnostic methods for syphilis in England and Wales.

OBJECTIVES: The number of cases of infectious syphilis is increasing rapidly across England and Wales. Concern has been expressed about diagnostic delay and its potential impact on patient care. A standard operating procedure for the serological diagnosis of syphilis has recently been developed by the Health Protection Agency. This study aimed to audit clinical and laboratory practice in England and Wales against this standard. METHODS: All microbiology departments, genitourinary medicine (GUM) clinics and antenatal clinics in England and Wales were invited to complete a web-based questionnaire. RESULTS: The overall response rate was 76%. Practices varied between laboratories. The proportion of microbiology departments performing enzyme immunoassay (EIA), Treponema pallidum particle agglutination assay/T pallidum haemagglutination assay, rapid plasma reagin/Venereal Disease Reference Laboratory and EIA IgM were 94%, 34%, 41% and 10%, respectively. Of these, 57% only perform a single screening assay. The turnaround time for negative results was less than 1 week for 84% of microbiology departments. For positive samples, turnaround times varied from less than 1 week to 6-8 weeks, with 19% of GUM clinics reporting turnaround times of over 3 weeks. Notably, 26% of GUM clinics and 6% of antenatal clinics reported that delays in turnaround time had adversely affected patient management in the past year. CONCLUSION: This study suggests that there is significant room to improve laboratory turnaround times for the diagnosis of syphilis in England and Wales, and such improvements would be a positive step in limiting the spread of infection and of congenital syphilis.

Epidemiology of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp.: a nested case-control study from a tertiary hospital in London.

Information on risk factors for acquisition of extended-spectrum ss-lactamase (ESBL)-producing organisms and their outcomes in patients with invasive infections is scant. The objectives of this study were to evaluate risk factors and all-cause mortality associated with infection due to ESBL-producing organisms using a nested case-control design, and to document transmission within a hospital employing molecular and conventional epidemiological methods. From December 2003 to April 2005, 50 patients with bloodstream infections (BSIs) due to ESBL-producing E. coli and Klebsiella spp. were recruited. Controls (N=50) were chosen, within the same period, from patients with non-ESBL-producing BSIs by simple random sampling; account was taken of potential confounding factors. Cases and controls were followed-up until November 2005, and outcomes were recorded as discharged or deceased. Molecular methods, supported by conventional epidemiology, were used to study the transmission of organisms. Logistic regression analyses showed prior ss-lactam antibiotics [odds ratio (OR) 11.57; 95% confidence intervals (CI) 2.31-51.15; P=0.003], hospital stay >15 days (OR 2.63; 95% CI 1.01-6.89; P=0.04) and prior admission to the intensive care unit (OR 13.98; 95% CI 1.88-19.15; P=0.006) to be independent risk factors for the acquisition of ESBL-producing organisms. In the first 15 days of follow-up, a significant proportion of patients with ESBL-producing organisms died; however, there was no difference in mortality between cases and controls at the end of the follow-up period. Molecular epidemiology identified five clusters amongst the ESBL-producing isolates. Conventional epidemiological analyses supported the evidence of transmission in three of these clusters.

Laboratory diagnosis of bloodstream infections caused by extended-spectrum beta-lactamase-producing E. coli and Klebsiella species.

Extended-spectrum beta-lactamase (ESBL)-producing organisms are resistant to the third-generation cephalosporins commonly used as empirical therapy for a wide range of serious infections. It is therefore important for laboratories to offer reliable ESBL detection methods. This study compares two combination disc methods (Oxoid and Mast Diagnostics) containing cepodoxime with and without clavulanate with Vitek 2 for routine detection of ESBLs in Escherichia coli and Klebsiella spp. isolated from blood cultures. From December 2003 to April 2005, a total of 58 potential ESBL-producing isolates (resistant to cefotaxime and/or ceftazidime) by BSAC disc susceptibility were tested by the combination discs and Vitek 2. The Advanced Expert System, a feature of Vitek 2 reports possible mechanisms of resistance, based on interpretive reading of MICs. This study detected 7.4% more ESBL-producing isolates by Vitek 2 than by Oxoid disc testing (95% CI: 0.15-14.7%; P < 0.2) and 31.6% more ESBL-producing isolates were detected by Vitek 2 than by Mast disc testing, (95% CI: 16.2-46.96%; P < 0.001). Batch-to-batch variation was evident in disc performance for both disc types. Thus, use of appropriate controls is recommended when testing by the combination disc methods. Although no phenotypic test is 100% sensitive and specific, the Vitek 2 was a reliable system for ESBL detection; however, it is expensive and interpretation of results can be confusing to inexperienced users. Further studies to compare Vitek 2 with cefotaxime and ceftazidime combination discs may reveal disc methodology for ESBL detection to be a more reliable alternative than using cefpodoxime combination discs alone.

An epidemiological evaluation of risk factors for tuberculosis in South India: a matched case control study.

SETTING: There are limited data on risk factors associated with tuberculosis (TB) in India. OBJECTIVES: To evaluate potential socio-demographic risk factors for TB. DESIGN: Matched case-control. Cases were all new diagnoses of pulmonary TB attending as out-patients at St John's Medical College Hospital, Bangalore, India, from October 2001 to October 2003. Age- and sex-matched controls, one for each case (n = 189), were recruited among relatives accompanying non-TB in-patients in the hospital. RESULTS: Significant risk factors were low education level (OR 0.30; 95%CI 0.11-0.82), not having a separate kitchen (OR 3.26; 95%CI 1.25-8.46) and chronic disease, mainly diabetes (OR 2.44; 95%CI 1.17-5.09). High income, cooking with biomass fuels, history of smoking and alcohol consumption were not significant on multivariate analysis. Patients were respectively 11 and seven times more likely to have a BMI <18.5 (95%CI 5.62-21.98) and mid-arm circumference <24 cm (95%CI 3.87-11.89). CONCLUSIONS: In our study, TB was associated with low education level, kitchen type and diabetes, reflecting the complex interaction between non-communicable disease, urbanisation and a changing economic climate in Bangalore. The relationship between TB, the use of biomass cooking fuels and gender differentials related to fuel exposure merit further exploration. The study underscores the poor nutritional status of patients.

Molecular epidemiology of Mycobacterium tuberculosis in patients of Somalian and white ethnic origin attending an inner London clinic.

BACKGROUND: In 2002, 6891 and 2850 tuberculosis (TB) notifications were received respectively for England and Wales and London. TB is an important public health problem in the Somalian population of inner London. SETTING: An inner London TB clinic. OBJECTIVE: To study the epidemiology, genetic diversity and clustering of tuberculosis in Somalian and white patients. MAIN OUTCOME METHODS: In a cross sectional study from June 1998 to June 2001, IS6110 restriction fragment length polymorphism (RFLP) and secondary spoligotyping was performed on 57 M. tuberculosis isolates from 40 Somalian and 17 white patients. Contact tracing of patients provided epidemiological information. RESULTS: In the Somalian group, using RFLP and spoligotyping, there were three clusters. Routine contact tracing confirmed one household cluster (two siblings). Spoligotyping yielded one cluster of two white patients who were patrons of a local pub. The rates of recent transmission were respectively 10.0% and 5.9% in the Somalian and white groups. CONCLUSIONS: Heterogeneous RFLP patterns in both groups showed a predominance of reactivation disease. Clustering as evidence of recent transmission has public health implications for enhanced contact tracing and active intervention.

Knowledge, attitudes and practices regarding tuberculosis among immigrants of Somalian ethnic origin in London: a cross-sectional study.

The objectives were to study knowledge, attitudes, and practices (KAP) regarding tuberculosis (TB) among Somalian subjects in inner London. We administered structured, fixed response KAP questionnaires to 23 patients (culture proved TB), and two groups of controls: 25 contacts (family members) and 27 lay controls (general Somali immigrant population). Responses were summed on a five-point scale. Most were aware of the infectious nature of TB but uncertain of other risk factors. Many were uncertain about coping with the disease and its effect on lifestyle. Belief in biomedicine for TB was unequivocal with men having a significantly higher belief score than women (p = 0.02); the need to comply with TB medication was unambiguously understood. Somalians interviewed were educated, multilingual, and aware of important health issues. Uncertainties in core TB knowledge need to be addressed with direct educational input, especially in women and recent entrants into the country. Volunteers from the established Somalian community could play a valuable part as links in the community to fight TB.

Is the detection of Mycobacterium tuberculosis DNA by ligase chain reaction worth the cost: experiences from an inner London teaching hospital.

AIMS: To evaluate the clinical usefulness and the costs of using a rapid, commercial ligase chain reaction test (LCx) to detect Mycobacterium tuberculosis directly from clinical samples. METHODS: A prospective study of 2120 routine clinical specimens from 1161 patients over a 13 month period. Investigations for mycobacterial disease by microscopy, culture, and the Abbott LCx assay were performed. Sequential LCx assays were monitored in a cohort of patients undergoing treatment. The costs of the assay were calculated using the WELCAN system. Sensitivity, specificity, and positive and negative predictive values of the LCx assay were compared with conventional tests. The performance of the assay in patients undergoing treatment and cost in terms of WELCAN units converted to pounds/annum was studied. RESULTS: The assay was 85%/88% sensitive and 98%/100% specific in culture confirmed/clinically confirmed cases of tuberculosis, respectively. The assay was not useful for the measurement of treatment outcomes. The test cost approximately 42,500 Pounds/annum. CONCLUSIONS: The assay is a rapid, sensitive, and specific adjunct to clinical diagnosis, especially in differentiating non-tuberculous mycobacteria. However, it does not differentiate old and treated tuberculosis from reactivated disease, it is not useful to monitor adherence to treatment, and it is expensive.