Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in... more
Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB. Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes. Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients. To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first- and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drug-resistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.
The main university hospital in Iasi, Romania. To assess whether health care workers (HCWs) have a higher risk of acquiring tuberculosis (TB) than the general population, and if TB incidence varies between departments, to develop adequate... more
The main university hospital in Iasi, Romania. To assess whether health care workers (HCWs) have a higher risk of acquiring tuberculosis (TB) than the general population, and if TB incidence varies between departments, to develop adequate infection control measures. All records of TB cases among HCWs were reviewed by cross-checking laboratory and medical records (retrospectively, 1971--1996; prospectively 1997--2003, following the implementation of the first World Health Organization pilot project in Romania). Annual TB incidence rates among HCWs were calculated and compared with those of the general population; relative and attributable risk with 95% confidence intervals (CI) were calculated. Fifty TB cases were diagnosed in HCWs; 42% were nurses, 24% ancillary staff, 12% physicians, 10% laboratory staff, 10% administrative staff and 2% radiology technicians. The mean incidence of TB in Romania during the study period was 96.8 per 100,000 persons/year (95%CI 83.5-110.1); the mean i...
Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease... more
Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.
SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46 major clinical units and 22 laboratories nationwide in Italy. To determine the main features, adherence to WHO guidelines and the outcomes of multidrug-resistant... more
SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46 major clinical units and 22 laboratories nationwide in Italy. To determine the main features, adherence to WHO guidelines and the outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled from January 1995 to December 1999. Observational study, preceded by proficiency testing, according to WHO recommendations. Results were stratified by appropriate and inappropriate regimens (< three active drugs). Analysis of the outcomes was performed according to adequacy of treatment. Analysis of risk factors and factors predicting treatment outcomes was performed using univariate and multivariate analysis (level of significance P < 0.05). One hundred and twenty-seven MDR patients were diagnosed. The overall success rate was low (39%). Seventy per cent of cases were treated with at least three active drugs. Factors predicting treatment success were new MDR-TB cases (OR 3.45; 95% CI 1.22-9.78; P < 0.05) and treatment for > or = 12 months (OR 5.03; 95% CI 1.65-15. 31; P < 0.05). Immigration and HIV infection were the main risk factors among new MDR-TB cases. The best available treatment should be provided to all newly diagnosed MDR-TB patients, avoiding the use of poorly modified regimens. MDR-TB patients should be referred to highly specialised centres.
Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test... more
Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown. Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (kappa = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (kappa = 0.16) or QFT-IT (kappa = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001). Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.
Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower... more
Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower respiratory tract infections and tuberculosis are presented through analysis of some of the best abstracts presented at the 19th European Respiratory Society Congress in Vienna (Austria). Pathogenesis, diagnosis, treatment, prognostic factors and novel diagnostic techniques relevant for bacterial and viral infections, as well as new tools for the diagnosis of latent and active tuberculosis in different sub-groups of patients, are discussed. The growing epidemiological threat represented by multidrug-resistant and extensively drug-resistant tuberculosis cases is presented and its impact analysed.
Respiratory tract infections and tuberculosis are among the leading reasons for seeking medical care. In this report the most recent advances in the field of clinical research and basic sciences of respiratory infections and tuberculosis... more
Respiratory tract infections and tuberculosis are among the leading reasons for seeking medical care. In this report the most recent advances in the field of clinical research and basic sciences of respiratory infections and tuberculosis are presented through the analysis of some of the best abstracts presented at the 20th European Respiratory Society Congress in Barcelona, Spain and their subsequent publications in major journals. The role of viruses in chronic obstructive pulmonary disease exacerbations, the importance of new biomarkers in the management and risk assessment of lower respiratory tract infections, new modalities of treatment of respiratory infections as well as new tools for the diagnosis of latent and active tuberculosis in special subgroups of patients (children and immunocompromised individuals), and the new epidemiological threat of multidrug-resistant and extensively drug-resistant tuberculosis cases are discussed.