Second Line Injectable Drug Resistance and Associated Genetic Mutations in Newly Diagnosed Cases of Multidrug-Resistant Tuberculosis

Ramakrishna, Vangala; Singh, Pravin Kumar; Prakash, Shantanu; Jain, Amita

doi:10.1089/mdr.2019.0215

Cited by 9 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, among 27 SLID resistant isolates, the most frequent mutation detected was rrs A1401G (40.7%), which was consistent with the reports from China, 4,6,49 Georgia America, 50 eSwatini, Uganda and Somalia 48 and Northwest Pakistan, 51 while different from the report from India which showed that the most prevalent mutation was eis C (−12)T (46.1%). 52 As for the SLID resistance, the RDBH assay showed 51.9% sensitivity and 100% specificity compared to the phenotypic DST. The inclusion of probes targeted at mutations in the eis promoter in the RDBH assay obtained an increased sensitivity with 11.1% than that based on probes targeted only in rrs 1400 region, which was comparable to the reported sensitivity differences between MTBDRsl v2.0, which added probes targeted at eis promoter, and MTBDRsl v1.0.…”

Section: Discussionmentioning

confidence: 94%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 94%

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

View full text Add to dashboard Cite

show abstract

“…According to Yadav et al [ 24 ], levofloxacin and kanamycin resistance using phenotypic DST was respectively, 176/415 (42.4%) and 40/415 (9.6%). A study from India showed phenotypic resistance to ofloxacin (59.1%), SLIDs (11.8%,) and to both antibiotics (10.0%) by phenotypic drug susceptibility testing using the MGIT 960 system [ 26 ]. According to Singh et al [ 27 ], who used phenotypic drug susceptibility testing (DST) assess baseline resistance to second-line drugs DST, RR-TB positive patients also showed a high resistance to fluoroquinolones (FQs; levofloxacin 56%; moxifloxacin 44%) followed by kanamycin (8%) and capreomycin (6%).…”

Section: Discussionmentioning

confidence: 99%

Direct detection of resistance to fluoroquinolones/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India

Singh

Kumari

Gupta

et al. 2021

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

Background According to World Health Organization (WHO), drug-resistant tuberculosis (DR-TB) is a major contributor to antimicrobial resistance globally and continues to be a public health threat. Annually, about half a million people fall ill with DR-TB globally. The gradual increase in resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs), poses a serious threat to effective TB control and adequate patient management. Therefore, WHO suggests the use of GenoType MTBDRsl v.2.0 assay for detection of multiple mutations associated with FQs and SLIDs. Hence, the study was conducted to determine the prevalence of resistance to FQs and SLIDs by comparing direct GenoType MTBDRsl v.2.0 assay with phenotypic drug susceptibility testing (DST). Methods The study was conducted on 1320 smear positive sputum samples from a total of 2536 RR-TB, confirmed by GeneXpert MTB/RIF. The smear positive specimens were decontaminated, and DNA extraction was performed. Furthermore, the extracted DNA was used for GenoType MTBDRsl v.2.0 assay. While 20% of the decontaminated specimens were inoculated in Mycobacterium growth indicator tube (MGIT) for drug susceptibility testing (DST). Results Out of 1320 smear positive sputum samples, 1178 were identified as Mycobacterium tuberculosis complex (MTBC) and remaining were negative by GenoType MTBDRsl v.2.0 assay. Of the 1178 MTBC positive, 26.6% were sensitive to both FQs and SLIDs, whereas 57.3% were only FQs resistant and 15.9% were resistant to both FQs and SLIDs. Further DST of 225 isolates by liquid culture showed that 17% were sensitive to both FQs and SLIDs, 61.3% were only FQs resistant and 21.3% were resistant to both. The specificity for FQs and SLIDs was 92.31% and 100% whereas sensitivity was 100% respectively by GenoType MTBDRsl v.2.0 assay in direct sputum samples. Conclusions Our study clearly suggests that GenoType MTBDRsl v.2.0 assay is a reliable test for the rapid detection of resistance to second-line drugs after confirmation by GeneXpert MTB/RIF assay for RR-TB. Though, high rate FQ (ofloxacin) resistance was seen in our setting, moxifloxacin could be used as treatment option owing to very low resistance.

show abstract

“…At the same time the un expected occurrence of amikacin resistant isolates at high frequency (26.5%) in this group is an alarming situation that further limits the spectrum of already limited number of second line drugs. The prevalence of amikacin resistance in M. tuberculosis usually falls below 10% [23][24][25]. Most likely, amikacin resistance in these isolates is not the consequence of the prior exposure to amikacin as infected patients were not on amikacin treatment.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Mycobacterium tuberculosis associated with treatment failure for intrinsic and efflux pump mediated resistance: a comparative retro perspective cohort study

Mushtaq

Raza

Ahmad

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: To treat tuberculosis is very complicated and difficult procedure that involves the administration of a panel of five antimicrobial drugs for the period of 6 months. The purpose of this study was to determine antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure and to determine efficacy of the second line drugs and the efflux pump inhibitor verapamil against M. tuberculosis associated with treatment failure.Methods: The identity of isolates was confirmed by ZN staining and multiplex PCR through detection of Mycobacterium species specific loci rv0577, mtbk_20680, 16S rRNA, RD9, IS 1311, mass_3210 and mkan_rs12360. Drug susceptibly testing (DST) and efficacy of the efflux pump inhibitor verapamil were performed through MGIT 960. Mutations associated with drug resistance were determined through DNA sequencing of ropB, katG, pncA, rrs and eis loci. The transcription of efflux pump gene rv1258 was assessed by real time quantitative PCR. Results: Upon monitoring 1200 tuberculosis patients, 64 were found not-cured after six months of treatment course. From M. tuberculosis isolates recovered from sputum of these 64 patients, 3.1% isolates were detected resistant to four anti M. tuberculosis drugs (extreme drug resistant) 48.4% were resistant to three anti M. tuberculosis drugs (extensive drug resistant), 26.5% were resistant to two anti M. tuberculosis drugs (multi drug resistant). High frequency of resistance to the second line drug amikacin was detected in 26,5% isolates whereas moxifloxacin and linezolid resistance was detected in only 3.1% isolates. The Serine 315 in katG was the most frequent amino acid mutated in treatment failure group. Three novel mutations were detected at codons 99, 149 and 154 in pncA associated with pyrazinamide resistance. Rifampicin and isoniazid enhanced the transcription of the efflux pump gene rv1258 in drug susceptible isolates collected from the treatment failure patients whereas verapamil reduced minimum inhibitory concentrations of antimicrobial drugs in these isolates.Conclusion: The use of Amikacin as a second line drug is not appropriate as compare to moxifloxacin and linezolid. Verapamil enhanced anti-bacterial activity of rifampicin and isoniazid in drug susceptible M. tuberculosis isolates cured from treatment failure patients but not in drug resistant isolates.

show abstract

Second Line Injectable Drug Resistance and Associated Genetic Mutations in Newly Diagnosed Cases of Multidrug-Resistant Tuberculosis

Cited by 9 publications

References 17 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>

Direct detection of resistance to fluoroquinolones/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India

Evaluation of Mycobacterium tuberculosis associated with treatment failure for intrinsic and efflux pump mediated resistance: a comparative retro perspective cohort study

Contact Info

Product

Resources

About