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.

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Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa

European Respiratory Journal ◽

10.1183/13993003.00544-2018 ◽

2018 ◽

Vol 51 (5) ◽

pp. 1800544 ◽

Cited By ~ 30

Author(s):

Olatunde Olayanju ◽

Jason Limberis ◽

Aliasgar Esmail ◽

Suzette Oelofse ◽

Phindile Gina ◽

...

Keyword(s):

Outcome Data ◽

Favourable Outcome ◽

Cd4 Count ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Treatment Regimens ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

African Patients

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL−1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

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Long-term Follow-up Reveals High Posttreatment Mortality Rate Among Patients With Extensively Drug-Resistant Tuberculosis in the Country of Georgia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz152 ◽

2019 ◽

Vol 6 (4) ◽

Author(s):

Melanie Frank ◽

Natalia Adamashvili ◽

Nino Lomtadze ◽

Eka Kokhreidze ◽

Zaza Avaliani ◽

...

Keyword(s):

Mortality Rate ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

Long Term Follow Up ◽

Country Of Georgia

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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

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2021.1678 ◽

2021 ◽

Vol 91 (1) ◽

Author(s):

Anastasiia Russkikh ◽

Oleksandr Korotych ◽

Yuliia Sereda ◽

Anastasia Samoilova ◽

Jay Achar ◽

...

Keyword(s):

Russian Federation ◽

Sputum Culture ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Sputum Culture Conversion ◽

Treatment Regimens ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

The Russian Federation ◽

Culture Conversion

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.

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Faculty Opinions recommendation of Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1145225.602381 ◽

2009 ◽

Author(s):

Eliane Billaud

Keyword(s):

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant

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Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dku235 ◽

2014 ◽

Vol 69 (11) ◽

pp. 3103-3107 ◽

Cited By ~ 22

Author(s):

N. Padayatchi ◽

M. Gopal ◽

R. Naidoo ◽

L. Werner ◽

K. Naidoo ◽

...

Keyword(s):

South Africa ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

Hiv Coinfection

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Treatment of patients with multidrugresistant and extensively drug resistant tuberculosis depending on the composition of individualized regimens: immediate and longterm results

Tuberculosis Lung Diseases HIV Infection ◽

10.30978/tb2021-4-7 ◽

2021 ◽

pp. 7-15

Author(s):

Yu.I. Feshchenko ◽

N.A. Litvinenko ◽

N.V. Grankina ◽

M.V. Pogrebna ◽

Yu.O. Senko ◽

...

Keyword(s):

Effective Treatment ◽

Treatment Effectiveness ◽

Individualized Treatment ◽

Fluoroquinolone Resistance ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Treatment Regimens ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant

Objective — to study the effectiveness of treatment of MDR-TB (multidrug-resistant tuberculosis) and preXDR-TB/XDR-TB (pre-extensively and extensively drug resistant tuberculosis), depending on the composition of ITRs (individualized treatment regimens). Materials and methods. Тhe prospective observational study included 566 patients with MDR/preXDR-TB and XDR-TB during 2016—2020 on the scientific clinical bases of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine» and ME «Kryvyi Rih Anti-tuberculosis Dispensary» Dnipropetrovsk Regional Council Department. Patients were prescribed individualized treatment regimens in cases where short (standard or modified) regimens could not be prescribed. Patients were divided into comparison groups: 469 of them were treated with antimycobacterial therapy including bedaquiline and other effective antimycobacterial drugs groups A—C (without delamanid) — group 1. And 97 patients who were treated with the inclusion of both new antimycobacterial drugs (bedaquiline and delamanid) — group 2. Results and discussion. Regardless of whether the delamanid, in addition to bedaquiline and other drugs selected for the scheme according to WHO recommendations, «effective treatment» was found in 91.3 against 88.6 % of patients. In the remote period (6-month — 4-year follow-up period) there was no recurrence of the disease, regardless of the composition of the regime. The loss of treatment effectiveness was due to deaths from non-tuberculosis reasons and those lost for follow-up. Conclusions. For highly effective treatment, individualized regimens should include bedaquidine and linezolid from group A, and for previously ineffectively treated patients, clofazimine and carbapenems must be included (possibility to include 4 or more effective AMDs in ITR). For patients with fluoroquinolone resistance, treatment should include delamanid.

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