SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs).OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB).DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010–2012 in Tbilisi, Georgia.RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03–1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05–1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02–1.07).CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016-2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016-2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 – 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12-4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

Background While rapid molecular diagnostic tests for tuberculosis (TB) have decreased detection time of M. tuberculosis and drug resistance, whether their use improves clinical care and outcomes is uncertain. To address these knowledge gaps, we evaluated whether use of the Xpert MTB/RIF assay impacts treatment and clinical outcome metrics among patients treated for sputum smear-negative multidrug-resistant (MDR)-TB. Methods A retrospective cohort of adult patients initiating treatment for sputum smear-negative MDR-TB at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia from 2011-2016. The Xpert MTB/RIF was introduced in Georgia in 2010 and implemented into programmatic use in 2014. Exposure was availability of an Xpert result at time of diagnosis. Time to second-line treatment initiation, sputum culture conversion, and end-of-treatment outcomes were determined from. Time to event was compared using a Cox proportional hazards model. Results Among 151 patients treated for sputum smear-negative MDR-TB (96% culture positive), the Xpert was utilized in the clinical management of 78 (52%) patients and not used in 73 (48%). An adjusted analysis controlling for potential confounders found that patients in the Xpert group had shorter median time to second-line treatment (13 vs. 56 days, adjusted hazard ratio [aHR]10.21, p&lt;0.0001) and culture conversion (61 vs. 93 days, aHR 1.93, p&lt;0.001). There was no difference in treatment outcomes. Conclusions Use of the Xpert in the management of sputum smear-negative MDR-TB decreases time to second-line therapy and sputum culture conversion, providing evidence of its clinical impact and supporting its programmatic utility.

People living with the human immunodeficiency virus (PLHIV) have a higher risk of developing active tuberculosis (TB) disease, and TB remains a major cause of death in PLHIV. Uzbekistan is facing a substantial TB epidemic, which increases the risk of PLHIV developing active TB. Our retrospective cohort study aimed to evaluate the incidence rate and assess the risk factors for developing active TB among PLHIV. We collected secondary data extracted from medical charts of all patients, newly diagnosed at the AIDS Center in Tashkent, during the period of 2015–2017. The incidence rate of TB among PLHIV was 5.1 (95% CI: 4.5–6.0) per 1000 person/month. Adjusted regression analysis showed three major risk factors for TB, namely, being less than 15 years old (hazard ratio (HR) 5.83; 95% CI: 3.24–10.50, p value = 0.001),low CD4 count (adjusted hazard ratio(aHR) 21.0; 95% CI: 9.25–47.7, p value < 0.001), and antiretroviral therapy (ART) interruption/not receiving ART (aHR 5.57; 95% CI: 3.46–8.97 and aHR 6.2; 95% CI: 3.75–10.24, p value < 0.001, respectively) were significantly associated with developing active TB among PLHIV. Our findings indicate that taking prescribed ART without interruptions and maintaining CD4cell counts higher than 320 cells/μL are essential to prevent the development of active TB among PLHIV.

Tuberculosis (TB) pleural effusion (TPE) is the second most common manifestation of extrapulmonary TB (EPTB), which remains a great diagnostic challenge worldwide. In Uzbekistan, there has been no formal evaluation of the actual practices of diagnosing and treating TPE. Our cohort study therefore aimed to describe the frequency and types of different diagnostic procedures of TPE during 2017–2018 and assess the association of baseline characteristics and establish diagnostic methods with TB treatment outcomes. In total, 187 patients with presumptive TPE were assessed, and 149 had a confirmed diagnosis of TPE (other diagnoses included cancer n = 8, pneumonia n = 17, and 13 cases were unspecified). TB was bacteriologically confirmed in 22 (14.8%), cytologically confirmed in 64 (43.0%), and histologically confirmed in 16 (10.7%) patients. Hepatitis was the only co-morbidity significantly associated with unsuccessful treatment outcomes (RR 4.8; 95%CI: 1.44–15.98, p value 0.011). Multivariable regression analysis showed that drug-resistant TB was independently associated with unsuccessful TB treatment outcome. (RR 3.83; 95%CI: 1.05–14.02, p value 0.04). Multidisciplinary approaches are required to maximize the diagnostic accuracy of TPE and minimize the chances of misdiagnosis. TPE patients with co-infections and those with drug resistance should be more closely monitored to try and ensure successful TB treatment outcomes.