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

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.

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

2018 ◽  
Vol 51 (5) ◽  
pp. 1800544 ◽  
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.

scholarly journals What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Jan Heyckendorf ◽  
Sönke Andres ◽  
Claudio U. Köser ◽  
Ioana D. Olaru ◽  
Thomas Schön ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Resistance Testing ◽  
Drug Resistant ◽  
True Rate ◽  
Drug Resistant Tuberculosis ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Lowenstein Jensen

ABSTRACTRapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus2.0 and MTBDRsl2.0) and whole-genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.

scholarly journals 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

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.

scholarly journals In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Yu Pang ◽  
Zhaojing Zong ◽  
Fengmin Huo ◽  
Wei Jing ◽  
Yifeng Ma ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Genetic Characteristics ◽  
Acquired Drug Resistance ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACT Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent in vitro activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.

Sign in / Sign up

Export Citation Format

Share Document