Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

OBJECTIVES: Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. METHODS: Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. RESULTS: Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20-39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival. CONCLUSIONS: Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

Assessing the effect of foreign travel and protection by BCG vaccination on the spread of tuberculosis in a low incidence country, United Kingdom, October 2008 to December 2009.

The contribution of travel to high incidence countries and the impact of the discontinuation of universal Bacillus Calmette­Guérin (BCG) vaccination to there cent rise in tuberculosis (TB) in the United Kingdom remain unclear. An outbreak in a college presented an opportunity to assess these. A cohort of students answered a questionnaire assessing risk factors for TB.Participants were screened with an interferon gamma release assay (IGRA). Unadjusted and adjusted odds ratios (OR) were calculated using logistic regression.Among 2,284 students, 400 (17.5%) were diagnosed with TB infection. A higher risk was noted for travel to a high incidence area in the past two years (OR: 1.39;95% confidence interval (CI): 1.04­1.89) and among those with the greatest exposure to the index case(OR: 3.94; 95% CI: 2.60­5.97). There was no association between BCG and risk of infection (OR: 1.05; 95%CI: 0.80­1.39). The lack of a protective effect by BCG on TB infection supports the discontinuation of universal vaccination. The association with foreign travel suggests the need to assess the cost-effectiveness of serial IGRA testing and treatment of positive persons among returning travellers.

Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries.

NICE (National Institute for Health and Clinical Excellence) guidelines for new entrant tuberculosis (TB) screening recommend chest x ray (CXR) for immigrants from countries with TB incidence >40/10(5), and tuberculin skin test (TST) for people with normal CXR from very high TB prevalence countries. A revised screening policy using first-line QuantiFERON-TB Gold (QFT) in high risk immigrants was piloted in 2007. Initially, TST was offered to immigrants from countries with TB incidence 200-339/10(5), and QFT to those from countries with incidence >340/10(5). When increased resources became available, all immigrants from countries with TB incidence >200/10(5) had QFT. Those with positive QFT were invited for CXR. 1336 immigrant were invited for screening, with a 32% attendance rate. 280 patients had QFT, of which 38% were positive, with <2% being indeterminate. Using the NICE approach, the cost of screening these 280 immigrants would be pound 13,346.75 ( pound 47.67 per immigrant) and would identify 83 cases of latent TB infection (LTBI). Using first-line QFT followed by CXR the cost was pound 9781.82 ( pound 34.94 per immigrant) and identified 105 cases of LTBI. The cost to identify one case of LTBI following NICE guidelines would be pound 160.81 and using the present protocol was pound 93.16. For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI.

Use of QuantiFERON-TB Gold test in the investigation of unexplained positive tuberculin skin tests.

OBJECTIVES: To investigate the use of new gamma-interferon (IFN-gamma)-based blood tests to determine whether or not a higher-than-expected proportion of positive tuberculin skin tests (TSTs) were due to tuberculosis infection. STUDY DESIGN: When an unexpectedly high proportion of children in a high school in Leeds were found to have positive TSTs, a cohort study was undertaken based on blood tests and long-term follow-up of the affected children. IFN-gamma-based blood tests are reported to be more specific for tuberculosis infection than TSTs. METHODS: One hundred and ninety children, aged 13-14 years, were screened and 28 (15%) had a positive TST. None had any known risk factor for tuberculosis infection. Parental consent was requested for testing with QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia). Active cases of tuberculosis with any possible connection to the school or the children were sought through the routine diagnosis and reporting service over the next 36 months. RESULTS: Consent was given for 26 children with Heaf Grade 2 results to be tested using QuantiFERON-TB Gold, and blood was obtained from 24 of these children. All tested negative. None of these children developed active tuberculosis, and no cases of active tuberculosis were identified with any connection to the children or the school. CONCLUSION: QuantiFERON-TB Gold testing appeared to identify false-positive TSTs correctly in this group. This supports the recent recommendation to use IFN-gamma-based blood tests in people with positive TSTs to confirm or refute the diagnosis of tuberculosis infection.

The treatment of spinal tuberculosis: a retrospective study.

BACKGROUND: There are conflicting guidelines and variations in clinical practice in the management of bone tuberculosis (TB), including spinal TB. A case who received 6 months of treatment in line with current British Thoracic Society (BTS) guidelines, and subsequently relapsed, prompted a survey of treatment and outcomes of spinal and other bone TB. METHODS: A retrospective study examining the clinical features, treatment duration and outcome of patients presenting with spinal and other bone TB to the Leeds Teaching Hospitals National Health Service Trust, between 1998 and 2002. RESULTS: Forty-two patients were identified. Notes from 34 patients with spinal TB and four patients with TB of other bones were reviewed. Of eight patients who received 6 months of therapy, five relapsed. Of 30 patients who received treatment for 9 months or longer, none relapsed (P < 0.05). CONCLUSION: Six months of treatment, as currently recommended by the BTS, may be inadequate for bone TB, including spinal TB.

Predominant VNTR family of strains of Mycobacterium tuberculosis isolated from South Asian patients.

SETTING: Despite the low incidence of tuberculosis in the UK, some minority ethnic groups, particularly those originating from South Asia, experience very high incidence rates. OBJECTIVE: Comparison of the variable number tandem repeat (VNTR) profiles of strains of Mycobacterium tuberculosis circulating in an immigrant community in the UK with those found in the country of ethnic origin. DESIGN: Isolates of M. tuberculosis were collected from samples obtained from patients attending clinics in Leeds and Bradford, UK and Rawalpindi, Pakistan. Strains were compared using VNTR analysis and mixed-linker PCR. RESULTS: Comparison of VNTR profiles found that one profile (42235) represented 37% of patient isolates from Rawalpindi and 23% of patient isolates in Leeds and Bradford, where it was associated exclusively with patients with South Asian names. A second profile (02235) represented 15% of patient isolates in Leeds and Bradford, and was also exclusively associated with the South Asian community. These profiles could be subdivided by mixed-linker PCR analysis. CONCLUSION: The VNTR profile 42235 may represent a family of strains commonly found in communities associated with South Asia.

Rapid identification of laboratory contamination with Mycobacterium tuberculosis using variable number tandem repeat analysis.

Compared with solid media, broth-based mycobacterial culture systems have increased sensitivity but also have higher false-positive rates due to cross-contamination. Systematic strain typing is rarely undertaken because the techniques are technically demanding and the data are difficult to organize. Variable number tandem repeat (VNTR) analysis by PCR is rapid and reproducible. The digital profile is easily manipulated in a database. We undertook a retrospective study of Mycobacterium tuberculosis isolates collected over an 18-month period following the introduction of the BACTEC MGIT 960 system. VNTR allele profiles were determined with early positive broth cultures and entered into a database with the specimen processing date and other specimen data. We found 36 distinct VNTR profiles in cultures from 144 patients. Three common VNTR profiles accounted for 45% of true-positive cases. By combining VNTR results with specimen data, we identified nine cross-contamination incidents, six of which were previously unsuspected. These nine incidents resulted in 34 false-positive cultures for 29 patients. False-positive cultures were identified for three patients who had previously been culture positive for tuberculosis and were receiving treatment. Identification of cross-contamination incidents requires careful documentation of specimen data and good communication between clinical and laboratory staff. Automated broth culture systems should be supplemented with molecular analysis to identify cross-contamination events. VNTR analysis is reproducible and provides timely results when applied to early positive broth cultures. This method should ensure that patients are not placed on unnecessary tuberculosis therapy or that cases are not falsely identified as treatment failures. In addition, areas where existing procedures may be improved can be identified.

Comparison of agar-based media for primary isolation of glycopeptide-resistant enterococci.

OBJECTIVE: To compare four vancomycin-containing agar media for the isolation of glycopeptide-resistant enterococci (GRE) from clinical fecal specimens: kanamycin---aesculin---azide (KAA) agar; bile---aesculin---polymixin (BAP) agar; aztreonam---amphotericin blood (CBAA) agar; and neomycin blood (CBN) agar. METHODS: Fecal specimens from 125 patients were inoculated onto each medium. Media were examined for enterococci after incubation for up to 48 h. Enterococci were identified to species level, and glycopeptide phenotypes were determined by measuring minimum inhibitory concentrations of vancomycin and teicoplanin. RESULTS: GRE were isolated from 44/125 samples. Enterococcus faecalis and Enterococcus faecium isolates, expressing glycopeptide resistance of the VanA or VanB phenotypes, were recovered from 27/33 (82%) specimens on BAP medium, 26/33 (79%) on KAA medium, and 21/33 (64%) on CBN and CBAA media. Enterococcus gallinarum and Enterococcus casseliflavus isolates expressing low-level glycopeptide resistance (VanC phenotype) were recovered from 14/15 (93%) specimens on CBAA medium, 7/15 (47%) on KAA and CBN media, and 6/15 (40%) on BAP medium. CONCLUSIONS: The media tested in this study, with the exception of CBN medium, detected at least 75% of patients colonized by GRE. Further development of BAP, CBAA and KAA media is warranted to improve growth and selectivity.