Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study

Sun, Feng; Li, Yang; Chen, Yú; Guan, Wen‐Long; Jiang, Xieyuan; Ren, Pengfei; Li, Junlian; Shi, Jichan; He, Guiqing; M, Wu; Tang, Peijun; Wang, Fei; Sheng, Yunfeng; Huang, Feng; Zhou, Zumo; Huang, Heqing; Hong, Lei; Liu, Qihui; Zhang, Ying; Zhang, Wenhong

doi:10.1183/13993003.01770-2018

Cited by 26 publications

(24 citation statements)

References 47 publications

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“…[22][23][24][25][26] It has been reported that patients with early available molecular DST results had a more rapid culture conversion and higher rate of treatment success. 27,28 The RDBH assay we built took only 7 h from multiplex PCRs to provide results and allowed the simultaneous analysis of 42 clinical DNA samples for FQs and SLID susceptibility, which was comparable to that needed by the MTBDRsl v2.0 based on isolates and were obviously less than the time (6 weeks) needed for L-J slants based DST. 29 The present study also provides detailed performance of the RDBH assay on predicting KN, AMK and CPM resistance and XDR by comparing to the phenotypic DST and sequencing.…”

Section: Discussionmentioning

confidence: 99%

Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs Among Mycobacterium tuberculosis by a Reverse Dot Blot Hybridization Assay

Li¹,

Guo²,

Liu³

et al. 2020

IDR

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Background Reliable and timely determination of second-line drug resistance is essential for early initiation effective anti-tubercular treatment among multi-drug resistant (MDR) patients and blocking the spread of MDR and extensively drug-resistant tuberculosis. Molecular methods have the potency to provide accurate and rapid drug susceptibility results. We aimed to establish and evaluate the accuracy of a reverse dot blot hybridization (RDBH) assay to simultaneously detect the resistance of fluoroquinolones (FQs), kanamycin (KN), amikacin (AMK), capreomycin (CPM) and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis . Methods We established and evaluated the accuracy of the RDBH assay by comparing to the phenotypic drug susceptibility testing (DST) and sequencing in 170 M. tuberculosis , of which 94 and 27 were respectively resistant to ofloxacin (OFX) and SLIDs. Results The results show that, compared to phenotypic DST, the sensitivity and specificity of the RDBH assay for resistance detection were 63.8% and 100.0% for OFX, 60.0% and 100.0% for KN, 61.5% and 98.1% for AMK, 50.0% and 99.3% for CPM, and 55.6% and 100% for SLIDs, respectively; compared to sequencing, the sensitivity and specificity of the RDBH assay were 95.2% and 100.0% for OFX, 93.8% and 100.0% for SLIDs or KN (both based on mutations in rrs 1400 region and eis promoter), and 91.6% and 100.0% for AMK or CPM (both based on mutations in rrs 1400 region), respectively. The turnaround time of the RDBH assay was 7 h for testing 42 samples. Conclusion Our data suggested that compared to sequencing, the RDBH assay could serve as a rapid and reliable method for testing the resistance of M. tuberculosis against OFX and SLIDs, enabling early administration of appropriate treatment regimens among MDR tuberculosis patients.

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Section: Discussionmentioning

confidence: 99%

Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs Among Mycobacterium tuberculosis by a Reverse Dot Blot Hybridization Assay

Li¹,

Guo²,

Liu³

et al. 2020

IDR

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“…This cohort study was performed at two hospitals located in Zhejiang Province, China, and initiated by the Zhejiang Disease Control and Prevention Center (CDC) which has set up routine drug resistance monitoring for TB since 1999 10. The two clinical studies were completed in both the hospitals: one singer-arm study was supported by the Global Fund MDR-TB Project,11 and another cohort study entitled “Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide” was registered on ClinicalTrial.gov with number NCT02120638 12. To acquire complete follow-up information, we screened the patients in the two studies regarding eligibility consecutively.…”

Section: Methodsmentioning

confidence: 99%

Cycloserine for treatment of multidrug-resistant tuberculosis: a retrospective cohort study in China

Yang

Wang

et al. 2019

IDR

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Purpose Cycloserine has been used in multidrug-resistant tuberculosis (MDR-TB) treatment since the 1950s. We evaluated the efficacy and safety of cycloserine and sought to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB). Materials and methods A retrospective observational study was performed in Zhejiang Province, China. We enrolled 144 cycloserine-treated and 181 cycloserine-nontreated patients consecutively and determined the treatment outcome as the primary outcome. The proportion of patients with sputum culture conversion and the frequency of adverse drug reactions were also assessed. Results One-hundred (69.4%) out of 144 patients in the cycloserine group successfully completed treatment. The HR of any unfavorable treatment outcome after the introduction of cycloserine was 0.58 (95% CI: 0.38–0.86, P =0.008). Subgroup analysis showed that cycloser-ine could benefit simple MDR-TB cases reducing the risk of unfavorable treatment outcomes (HR: 0.43, 95% CI: 0.24–0.76, P =0.004), but not pre-XDR-TB (HR: 0.65, 95% CI: 0.30–1.38, P =0.263) or XDR-TB (HR: 0.73, 95% CI: 0.22–2.37, P =0.589). The culture conversion rate at the intensive phase was similar whether cycloserine was administered or not ( P =0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side effects attributed to cycloserine. Conclusion Cycloserine is an attractive agent for the treatment of MDR-TB, and its safety profile warrants its use in most MDR-TB cases. Cycloserine significantly improved the chance of a favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. Thus, more aggressive regimens might be required for pre-XDR-TB or XDR-TB patients.

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“…In a recent study, SUN et al [21] present interesting data from China in a prospective cohort of MDR-TB cases where pyrazinamide resistance was or was not tested. The study results show that optimisation of treatment regimens based on pyrazinamide DST significantly improves treatment outcomes [21].…”

Section: Dots-plusmentioning

confidence: 99%

“…The potential wide use of the regimen will, as for BPaL, be conditional to minimisation of creation of resistance to its new components. Concerningly, the presence of resistance to the fluoroquinolones and pyrazinamide among rifampicin-resistant cases, although frequently low, is already well documented in certain settings [20,21,37].…”

Section: While This Historical Account Summarises the Past And Presenmentioning

confidence: 99%

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

2019

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Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20–24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9–10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.

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Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study

Abstract: ERSpublications Early availability of reliable PZA drug-susceptible testing is a prerequisite for successful MDR-TB treatment. The optimised regimen achieved a treatment success rate of 82.4% and shortened the course to 12 months for PZA-susceptible patients http://ow.ly/ObdI30n3GF7

Cited by 26 publications

References 47 publications

<p>Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs Among <em>Mycobacterium tuberculosis</em> by a Reverse Dot Blot Hybridization Assay</p>

<p>Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs Among <em>Mycobacterium tuberculosis</em> by a Reverse Dot Blot Hybridization Assay</p>

<p>Cycloserine for treatment of multidrug-resistant tuberculosis: a retrospective cohort study in China</p>

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

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