Early outcome and safety of bedaquiline-containing regimens for treatment of MDR- and XDR-TB in China: a multicentre study

Gao, Mengqiu; Gao, Jingtao; Xie, Li; Wu, Guihui; Chen, Wei; Chen, Yu; Pei, Yi; Li, Guobao; Liu, Yuhong; Shu, Wei; Fan, Lin; Wu, Qianhong; Du, Juan; Chen, Xiaohong; Tang, Peijun; Xiong, Yu; Li, Mingwu; Cai, Qingshan; Jin, Long; Mei, Zaoxian; Pang, Yu; Li, Liang

doi:10.1016/j.cmi.2020.06.004

Cited by 55 publications

(57 citation statements)

References 18 publications

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“…A retrospective study was conducted in 13 TB specialized hospitals across China of MDR-TB patients receiving BDQ-containing regimens, of whom 91% had prior LZD treatment histories. Sputum specimens were collected from patients at baseline, 2, 4, 8, 12, 16, 20, and 24 weeks after treatment initiation, as previously reported ( Gao et al, 2020 ). MTB isolates collected at baseline and at final follow-up for each patient were recovered by culturing specimens on Löwenstein-Jensen medium for 4 weeks at 37°C prior to in vitro drug susceptibility testing.…”

Section: Methodsmentioning

confidence: 99%

Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination

Gao

Yu³

et al. 2021

Front. Microbiol.

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In this retrospective study in China, we aimed to: (1) determine the prevalence of linezolid (LZD) resistance among multidrug-resistant tuberculosis (MDR-TB)-infected patients; (2) monitor for dynamic LZD susceptibility changes during anti-TB treatment; and (3) explore molecular mechanisms conferring LZD resistance. A total of 277 MDR-TB patients receiving bedaquiline (BDQ)-containing regimens in 13 TB specialized hospitals across China were enrolled in the study. LZD and BDQ susceptibility rates were determined using the minimum inhibitory concentration (MIC) method, then DNA sequences of patient isolates were analyzed using Sanger sequencing to detect mutations conferring LZD resistance. Of 277 patients in our cohort, 115 (115/277, 41.5%) with prior LZD exposure yielded 19 (19/277, 6.9%) isolates exhibiting LZD resistance. The LZD resistance rate of LZD-exposed group isolates significantly exceeded the corresponding rate for non-exposed group isolates (P = 0.047). Genetic mutations were observed in 10 (52.6%, 10/19) LZD-resistant isolates, of which a Cys154Arg (36.8%, 7/19) substitution within ribosomal protein L3 was most prevalent. Analysis of sequential positive cultures obtained from 81 LZD-treated patients indicated that cultured organisms obtained from most patients (85.2%, 69/81) retained original LZD MIC values; however, organisms cultured later from two patients exhibited significantly increased MIC values that were attributed to the rplC substitution T460C. Overall, LZD resistance was detected in 6.9% of patients of an MDR-TB cohort in China. Low rate of acquired LZD resistance was noted in MDR-TB treated with BDQ-LZD combination.

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Section: Methodsmentioning

confidence: 99%

Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination

Gao

Yu³

et al. 2021

Front. Microbiol.

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“…Despite limited data, we observed that a patient with resistance to both LZD and BDQ but susceptible to FQ experienced treatment failure. In a recent BDQ clinical trial, the administration of BDQ-containing regimens provides particular benefit for pre-XDRand XDR-TB patients [15]. On one hand, the existing evidence from studies confirmed BDQ as a cornerstone in the treatment of MDR-TB patients.…”

Section: Discussionmentioning

confidence: 99%

“…Our data demonstrate that the rate of XDR-TB was noted in 6.8% of patients afflicted to MDR-TB, which was significantly decreased from 33.6% on the basis of previous definition. This low rate of XDR-TB was majorly attributed to relatively late introduction of BDQ and LZD for clinical management of MDR-TB in China, thereby preventing accumulation of drug resistant mutations [15]. Consequently, this holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Extensively Drug-resistant Tuberculosis in a Chinese Multidrug-resistant TB Cohort after Redefinition

Yao

guo

et al. 2021

Preprint

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Objectives: Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort. Methods: Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing. Results: A total of 411 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistant to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin. Conclusion: our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention.

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“…During the last year, several reports have shown the potential of combining BDQ other highly bactericidal drugs in order to shorten treatments, showing added cost-effectiveness [42][43][44][45][46][47]. Such evidence has moved the WHO to recommend shorter regimens based on a drug combination that takes into account different characteristics, especially oral administration and bactericidal/sterilizing activity (Table 1) [5].…”

Section: Clinical Efficacymentioning

confidence: 99%

Evaluating bedaquiline as a treatment option for multidrug-resistant tuberculosis

Martín-García

Esteban

2021

Expert Opinion on Pharmacotherapy

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Early outcome and safety of bedaquiline-containing regimens for treatment of MDR- and XDR-TB in China: a multicentre study

Abstract: Conclusion: Bedaquiline, when included in background regimens for treatment of MDR-TB and XDR-TB patients in China, was safe and associated with a high rate of culture conversion.

Cited by 55 publications

References 18 publications

Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination

Low Rate of Acquired Linezolid Resistance in Multidrug-Resistant Tuberculosis Treated With Bedaquiline-Linezolid Combination

Prevalence of Extensively Drug-resistant Tuberculosis in a Chinese Multidrug-resistant TB Cohort after Redefinition

Evaluating bedaquiline as a treatment option for multidrug-resistant tuberculosis

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