Additional Drug Resistance of Multidrug-Resistant Tuberculosis in Patients in 9 Countries

Kurbatova, Ekaterina V.; Dalton, Tracy; Ershova, Julia; Tupasi, Thelma E.; Caoili, Janice Campos; Walt, Martie van der; Kvasnovsky, Charlotte; Yagui, Martín; Bayona, Jaime; Contreras, Carmen; Leimane, Vaira; Via, Laura E.; Kim, Hee Jin; Akksilp, Somsak; Kazennyy, Boris Y.; Volchenkov, Grigory; Jou, Ruwen; Kliiman, Kai; Demikhova, Olga V.; Cegielski, J. Peter

doi:10.3201/eid2106.141329

Cited by 14 publications

(8 citation statements)

References 11 publications

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“…XDR-TB comprised 12.4% of MDR-TB patients. Such a high level of additional drug resistance poses a challenge to building of an effective treatment regimen and comparable with findings from several countries ( 8 - 10 ).…”

Section: Discussionsupporting

confidence: 68%

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

et al. 2017

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Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea.

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Section: Discussionsupporting

confidence: 68%

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

et al. 2017

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“…Dalton et al and Kurbatova et al have reported data from the Preserving Effective TB Treatment Study (PETTS), a cohort of adults (including individuals from Estonia and Latvia) with pulmonary MDR-TB who started treatment with second-line drugs 2005–2008 [ 6 , 7 ]. Although both papers examined additional drug resistance in MDR-TB cases (although not reporting separately for new and retreatment cases), Kurbatova pooled data across continents.…”

Section: Discussionmentioning

confidence: 99%

Drug Susceptibility Patterns in MDR-TB Patients: Challenges for Future Regimen Design. A Cross-Sectional Study

et al. 2015

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Globally, there is substantial concern regarding the challenges of treating complex drug resistance patterns in multidrug resistant tuberculosis cases. Utilising data from three different settings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles for multidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen, and inform future regimen selection. Demographic and microbiological surveillance data for multidrug resistant tuberculosis cases from 2004–13 were analysed. High levels of additional resistance to currently recommended second line drugs were seen in all settings, with extensive variability between countries. Accurate drug susceptibility testing and drug susceptibility testing data are vital to inform the development of comprehensive, flexible, multidrug resistant tuberculosis guidance.

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“…28,91 In this setting, cessation of the 9-month short-course regimen and replacement with a bedaquilinecontaining regimen is recommended. 96 In addition to the ongoing West Africa study, the efficacy of the Bangladesh regimen is currently being evaluated in the STREAM trial, encompassing several countries including South Africa, Ethiopia, Mongolia and Vietnam, comparing its efficacy and safety with that of the WHO regimen as a necessary prerequisite prior to possible recommendation as a standard regimen for the treatment of MDR-TB patients. In this study, 424 patients, including those who are HIV-positive, have been enrolled during the period 2012 -2015, while patients infected with fluorquinoloneand injectable agent-resistant DR-TB isolates have been excluded.…”

Section: Clinical Efficacy Of Clofaziminementioning

confidence: 99%

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

Cholo

Mothiba

Fourie

et al. 2016

J. Antimicrob. Chemother.

113

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Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F/F-ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.

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Additional Drug Resistance of Multidrug-Resistant Tuberculosis in Patients in 9 Countries

Abstract: Less toxic and less expensive drugs and shorter treatment regimens are needed.

Cited by 14 publications

References 11 publications

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

Drug Susceptibility Patterns in MDR-TB Patients: Challenges for Future Regimen Design. A Cross-Sectional Study

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

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