Linezolid use for drug-resistant tuberculosis in Georgia: a retrospective cohort study.

SETTING: Data on the long-term use of linezolid (LZD) in the treatment of drug-resistant pulmonary tuberculosis (DR-PTB) are limited.OBJECTIVE: To assess safety, tolerability and efficacy of LZD-containing regimens for the treatment of DR-PTB in the country of Georgia.DESIGN: A retrospective study was conducted among DR-PTB patients receiving LZD 600 mg/day as part of newly implemented regimens (bedaquiline or delamanid, repurposed and second-line drugs) from July 2014 to October 2015 in programmatic conditions and following WHO recommendations.RESULTS: One hundred mostly male (82%) patients with a median age of 33 years received LZD. Most patients (77%) had previously been treated for TB; 57% had extensively drug-resistant TB. The median duration of LZD use was 503 days (interquartile range 355-616). LZD-associated adverse events occurred in 12 patients, leading to discontinuation in 4 (2 each due to peripheral neuropathy and cytopenias), and dose reduction to 300 mg/day in 6 cases (4 due to peripheral neuropathy and 2 for cytopenias). Almost all patients (95%) achieved culture conversion and 79% had a successful treatment outcomes.CONCLUSION: Treatment regimens including lengthy LZD use showed fairly good safety and tolerability and were associated with high rates of culture conversion and favorable outcomes.

[FREQUENCY OF POLYMORPHIC VARIANTS OF GSTT1 AND GSTM1 GENES IN PATIENTS WITH PULMONARY TUBERCULOSIS IN GEORGIAN POPULATION].

A study was made for determining the frequencies of polymorphic variants of GST genes - GSTM1 and GSTT1, both among healthy individuals of the Georgian population (the Tbilisi population, populations of Eastern and Western Georgia), and among patients with tuberculosis; was also conducted a study on the relationship of certain genotypes with hepatotoxicity in patients taking anti Pulmonary Tuberculosis (PT) treatment. As a result of the analysis, it turned out that the general population indicator for healthy individuals for GSTT1 and GSTM1 positive variants of GST genes was 82%; for GSTT1 (-) / GSTM1 (+) variant was 13%; The GSTT1 (+) / GSTM1 (-) genotype was observed in 2%; as for the double null genotype - GSTT1 (-) / GSTM1 (-), the total population indicator was 3%. As for individuals suffering pulmonary tuberculosis, it turned out that 79% of studied patients revealed positive genotypes by the studied genes - GSTT1 (+)/GSTM1 (+); 3% have the GSTT1(-)/GSTM1(+) genotype; the genotype GSTT1(+)/GSTM1(-) was observed in 6% of investigated individuals, and the double null genotype - GSTT1 (-) / GSTM1 (-) - in 12%, which significantly exceeds the general population indicator for healthy individuals. The results of the studies also showed that there is a relationship between the double null genotypes of GSTM1 and GSTT1 genes and drug induced liver injury in patients with pulmonary tuberculosis, in Georgian population. It has been suggested that it is possible to recommend a preliminary analysis of the polymorphism of GSTM1 and GSTT1 genes in patients with pulmonary tuberculosis, before starting antituberculotic treatment, for preventive measures in the case of detection of double null genotypes. It should be noted, that this study has been conducted in Georgia first time.

Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia.

BACKGROUND AND SETTING: Bedaquiline (BDQ) was initially only available through compassionate use programmes. OBJECTIVE: To assess the effectiveness and safety of multidrug-resistant tuberculosis (MDR-TB) treatment containing BDQ. METHOD: Retrospective analysis of data from patients receiving BDQ through compassionate use in Armenia and Georgia from April 2013 to April 2015. Logistic regression was used to assess the risk factors associated with unsuccessful treatment outcomes. RESULTS: Of 82 patients included, 84.2% (69/82) had fluoroquinolone-resistant MDR-TB and 43.4% (23/53) were seropositive for the hepatitis C virus (HCV). The culture conversion rate was 84.4% (54/64), and 18.5% (10/54) reverted back to positive. In total, 79.3% (65/82) of the patients reported at least one adverse event. Serious adverse events were reported in 14 patients, with 10/14 patients experiencing fatal outcomes-6/10 related to advanced TB and 2/10 assessed as possibly related to BDQ. Treatment outcomes were as follows: 58.5% treatment success, 12.2% deaths, 7.3% failures and 21.9% lost to follow-up. HCV coinfection was associated with unsuccessful outcomes (adjusted OR 4.45, 95%CI 1.23-16.13). CONCLUSION: BDQ through compassionate use showed relatively good success rates and safety profiles in a cohort with difficult-to-treat MDR-TB. High rates of reversion may indicate that >24 weeks of BDQ is necessary in some cases. HCV coinfection should be diagnosed and treatment considered in MDR-TB patients.

Examples of bedaquiline introduction for the management of multidrug-resistant tuberculosis in five countries.

BACKGROUND: For the first time in almost 50 years, there are new drugs available for the treatment of tuberculosis (TB), including bedaquiline (BDQ) and delamanid (DLM). The rate of introduction, however, has not kept pace with patient needs. It is estimated that as many as 23% of multidrug-resistant TB (MDR-TB) patients have an indication for receiving BDQ. As this is the first time the MDR-TB community is introducing new medications, it is important to understand how implementation can be developed in a variety of settings. METHODS: A qualitative assessment of country TB programs in which more than 5% of MDR-TB patients were started on BDQ under program conditions. RESULTS: National TB programs in Belarus, France, Georgia, South Africa, and Swaziland all started sizeable cohorts of patients on BDQ in 2015. Common factors observed in these programs included experience with compassionate use/expanded access, support from implementing partners, and adequate national or donor-supported budgets. Barriers to introduction included restriction of BDQ to the in-patient setting, lack of access to companion drugs, and the development of systems for pharmacovigilance. CONCLUSION: The five countries in this paper are examples of the introduction of new therapeutic options for the treatment of TB.

TB/HIV co infection in Georgia.

HIV and TB co-infection is a considerable problem worldwide. HIV significantly increases the morbidity and mortality from TB and often makes the diagnosis more challenging. In this study we attempted to evaluate the prevalence of TB among newly diagnosed HIV infected persons and determine the rate of HIV infection among active TB patients in Georgia. The prospective observational study has been conducted in Georgia since January 01, 2006. All newly diagnosed HIV positive persons were screened for active and latent TB infection and the prevalence of TB was identified. During the same time period HIV screening was performed in all identified active TB cases. Up to 22% (16.7 to 22%) of HIV positive individuals were found to have active TB, and 22.4 to 32.6% had LTBI. The prevalence of HIV among TB patents ranged from 1.7 to 2.2%. The study showed significant prevalence of TB (both active and latent TB) among HIV patients. Because of problems with TB diagnosis in HIV patients, the real prevalence may be underestimated. The alarming statistical data should force us towards meticulous and scrupulous screening for tuberculosis among HIV positive individuals. The prevalence of HIV among TB patents was not very high, ranging from 1.7 to 2.2%, but we recommend routine screening for HIV in all active TB patients.

Argyrophilic nucleolar organizer regions in benign and malignant mesothelial lesions.

The aim our study was to assess the usefulness of AgNOR stain in distinguishing between benign and malignant mesothelial lesions. The patients were divided into three groups: group I -- reactive mesothelium (71 cases), group II -- hyperplastic mesothelium (66 cases), group III -- epithelial type mesothelioma (52 cases). Smears were stained by Pap and AgNOR methods. After staining, all cases were randomized for blind evaluation. Each case was viewed independently by two observers. AgNORs were identified as black, usually spheric particles observed within the nucleolus. For each cell, the number of AgNOR-positive cells and the number of AgNOR-dots per nucleus were counted. Our results show that AgNOR staining is useful to differentiate epithelial type mesothelioma and benign mesothelial lesions such as reactive and hyperplastic mesothelium. This differentiation is based primarily on the mean number of AgNOR-dots per cell rather than number of AgNOR-positive cells. AgNOR is highly sensitive, specific and cost-effective technology which can be used as an ancillary diagnostic approach for distinguishing between reactive and/or hyperplastic changes of mesothelium as well as in differential diagnosis of epithelial type mesothelioma.