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

Vietnam has been using a levofloxacin-based shorter treatment regimen (STR) for rifampicin resistant/multidrug-resistant tuberculosis (RR/MDR-TB) patients since 2016 on a pilot basis. This regimen lasts for 9–11 months and is provided to RR/MDR-TB patients without second-line drug resistance. We report the treatment outcomes and factors associated with unsuccessful outcomes. We conducted a cohort study involving secondary analysis of data extracted from electronic patient records maintained by the national TB program (NTP). Of the 302 patients enrolled from April 2016 to June 2018, 259 (85.8%) patients were successfully treated (246 cured and 13 ‘treatment completed’). Unsuccessful outcomes included: treatment failure (16, 5.3%), loss to follow-up (14, 4.6%) and death (13, 4.3%). HIV-positive TB patients, those aged ≥65 years and patients culture-positive at baseline had a higher risk of unsuccessful outcomes. In a sub-group of patients enrolled in 2016 (n = 99) and assessed at 12 months after treatment completion, no cases of relapse were identified. These findings vindicate the decision of the Vietnam NTP to use a levofloxacin-based STR in RR/MDR-TB patients without second-line drug resistance. This regimen may be considered for nationwide scale-up after a detailed assessment of adverse drug events.

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Faculty Opinions recommendation of Pharmacokinetics and drug-drug interactions of lopinavir/ritonavir administered with first and second-line antituberculosis drugs in HIV-infected children treated for multidrug-resistant tuberculosis.

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

10.3410/f.732115250.793540735 ◽

2017 ◽

Author(s):

Brian Eley

Keyword(s):

Drug Interactions ◽

Multidrug Resistant ◽

Second Line ◽

Antituberculosis Drugs ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽

10.1186/s12916-021-01932-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chathika K Weerasuriya ◽

Rebecca C Harris ◽

C Finn McQuaid ◽

Fiammetta Bozzani ◽

Yunzhou Ruan ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Multidrug Resistant ◽

Second Line ◽

Second Line Therapy ◽

China And India ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Line Therapy ◽

Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

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Emergence of Extensive Drug Resistance during Treatment for Multidrug-Resistant Tuberculosis

New England Journal of Medicine ◽

10.1056/nejmc0805644 ◽

2008 ◽

Vol 359 (22) ◽

pp. 2398-2400 ◽

Cited By ~ 35

Author(s):

Helen S. Cox ◽

Caterina Sibilia ◽

Silke Feuerriegel ◽

Stobdan Kalon ◽

Jonny Polonsky ◽

...

Keyword(s):

Drug Resistance ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Extensive Drug Resistance

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Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait

Scientific Reports ◽

10.1038/s41598-021-87516-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Noura M. Al-Mutairi ◽

Suhail Ahmad ◽

Eiman Mokaddas

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Mutation Detection ◽

Susceptibility Testing ◽

Multidrug Resistant ◽

Genetic Mutations ◽

Second Line ◽

Injectable Drugs ◽

Mdr Tb ◽

Phenotypic Susceptibility

AbstractMolecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.

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