Xpert MTB/RIF use is associated with earlier treatment initiation and culture conversion among patients with sputum smear-negative multidrug-resistant tuberculosis

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<0.0001) and culture conversion (61 vs. 93 days, aHR 1.93, p<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.

Factors Associated with Acid Fast Bacilli and Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis in Surabaya

Introduction: Indonesia is a high incidence country of multidrug-resistant tuberculosis. There are approximately 11,000 MDR TB cases, 2.8% of them are new cases and 16% of them are relapse cases. Although guidelines for MDR-TB are frequently designed, medication freely provided, and centers for treatment duly expanded, studies on time to sputum culture conversion have been very limited in Indonesia. Therefore the aim of the study is to identify risk factors that effect on sputum and culture conversion.Methods: Data on short-term regimen for MDR TB in Dr. Soetomo General Hospital from January 1st – December 31st, 2018 were collected with a total sampling approach, and fulfill the inclusion and exclusion. Data were analyzed by computer software IBM SPSS Statistic 24 for windows. Results: Male is more likely to have delayed sputum conversion and culture conversion but no statistical difference is observed (p>0.05). Smoking history is more likely to have delayed sputum and culture conversion but only in sputum smear test shows a significant difference (p≤ 0.05). Alcohol consumption has delay effect on sputum and culture conversion but there is statistically difference in only culture conversion (p<0.05). The high baseline smear test also affects delay the sputum and culture conversion but only in sputum smear reveals a significant effect (p<0.05).Conclusion: In this present study, we identified sex, smoking history, high bacillary loads as significant factors on sputum conversion. In addition, we revealed that alcohol-consumption history is a significant factor affecting on culture conversion.

9-12 months short treatment for patients with MDR-TB increases treatment success in Kyrgyzstan

Introduction: MDR/RR-TB is a growing problem in Kyrgyzstan. In 2005, the country introduced standard or individualized treatment for 20-24 months. Because of poor treatment outcomes, in 2017 a short treatment with strict eligibility criteria was introduced. The aim of this study was to compare characteristics and treatment outcomes of MDR/RR-TB patients receiving short (9-12 months) treatment in 2017 with those receiving standard or individualized (20-24 months) treatment in 2016/2017. Methodology: A comparative cohort study using routine programmatic data. Characteristics, sputum culture conversion and treatment outcomes were compared between those on short treatment with those on standard/individualized treatment using the chi-square test, crude and adjusted risk ratios (RR and aRR). Results: The study included 274, 82 and 132 patients on standard, individualized and short treatment, respectively. There were more females, fewer migrants/homeless and unemployed and more new TB patients on short treatment compared with the other two groups. A favorable outcome (cure and treatment completed) was significantly higher in short treatment patients (83%) compared with those on standard (50%) or individualized (59%) treatment (p < 0.001). There was higher 1-month sputum culture conversion with short treatment (35%) compared with the other two groups (19% and 24%, p < 0.05). Short treatment (aRR 1.6, 1.4-1.8), female gender (aRR 1.2, 1.1-1.4), not being homeless (aRR 12.9, 4.5-17.3) and having new TB (aRR 1.3, 1.0-1.5) were independently associated with a favorable outcome. Conclusions: The treatment success was higher in selected MDR-TB patients given short treatment in Kyrgyzstan: this regimen should be scaled-up to all MDR-TB patients.

Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study

BackgroundTuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment.MethodsThis multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA.FindingsBetween December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p &lt; 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (&lt;14%) or high neutrophil percentages (&gt;79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (&lt;30%).ConclusionWe showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.

Factors associated with culture conversion among adults treated for pulmonary extensively drug-resistant tuberculosis during 2018-2019 in the Russian Federation: an observational cohort study

Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens. We conducted a retrospective cohort study using health records from 54 patients with pulmonary XDR-TB treated at a tertiary level facility in the Russian Federation. The study population included adult patients with culture-positive pulmonary XDR-TB who started treatment between 1 January 2018-30 June 2019. Culture conversion was defined as two consecutive negative cultures, collected at least 30 days apart. The date of sputum culture conversion was taken from the first of two consecutive negative sputum cultures fulfilling these criteria. We measured time to culture conversion using cumulative incidence functions accounting for competing risks and applied binary cause-specific Cox regressions to assess associated factors. Sputum culture conversion was recorded for 43 (79.6%) patients. Median time to culture conversion adjusted for competing risk of loss to follow up was 4 months [95% confidence interval (CI): 2–5]. The number of patients who had culture converted by treatment months 2, 4, and 6 were 12 (22%), 29 (54%) and 38 (70%) respectively. In unadjusted analysis, positive baseline sputum smear microscopy [hazard ratio (HR): 0.34, 95% CI: 0.18-0.66; p=0.001), hepatitis C (HR: 0.35, 95% CI: 0.14-0.89; p=0.023], and human immunodeficiency virus (HR: 0.30 95%, CI: 0.09-0.97; p=0.045), and receipt of fewer than 4 effective drugs in the treatment regimen (HR: 0.13, 95% CI: 0.03-0.60; p=0.009) were associated with delayed culture conversion. When compared to their combined use, patients receiving regimens with bedaquiline only (HR: 0.12, 95% CI: 0.03-0.49; p=0.003) or linezolid only (HR: 0.21, 95% CI: 0.06-0.69; p=0.010) were less likely to achieve timely culture conversion. Factors delaying sputum culture conversion should be considered in the management of patients with XDR-TB and considered by clinicians for regimen design and treatment strategies. Our study outlines the importance of simultaneous inclusion of bedaquiline and linezolid in treatment regimens for patients with XDR-TB to reduce time to sputum conversion and increase treatment success.