Acquisition of cross- #resistance to #Bedaquiline and #Clofazimine following #treatment for #Tuberculosis in #Pakistan (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Acquisition of cross-resistance to Bedaquiline and Clofazimine following treatment for Tuberculosis in Pakistan

Arash Ghodousi, Alamdar Hussain Rizvi, Aurangzaib Quadir Baloch, Abdul Ghafoor, Faisal Masood Khanzada, Mehmood Qadir, Emanuele Borroni, Alberto Trovato, Sabira Tahseen,Daniela Maria Cirillo

DOI: 10.1128/AAC.00915-19

 

ABSTRACT

We report on the first six cases of acquired-resistance to bedaquiline in Pakistan. Seventy sequential isolates from 30 drug-resistant tuberculosis patients on bedaquiline-containing regimens were retrospectively tested for bedaquiline resistance by MIC test and by detection of mutations in relevant genes. We documented cases failing therapy developed specific mutations in Rv0678 and increased MICs associated with cross-resistance to clofazimine during treatment. This study underlines the relevance of surveillance programs following the introduction of new drugs.

Copyright © 2019 Ghodousi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; Tuberculosis; Pakistan; Bedaquiline; Clofazimine.

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#Outcomes of #Bedaquiline #Treatment in Patients with #MDR #Tuberculosis (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 5—May 2019 / Research

Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis

Lawrence Mbuagbaw  , Lorenzo Guglielmetti, Catherine Hewison, Nyasha Bakare, Mathieu Bastard, Eric Caumes, Mathilde Fréchet-Jachym, Jérôme Robert, Nicolas Veziris, Naira Khachatryan, Tinatin Kotrikadze, Armen Hayrapetyan, Zaza Avaliani, Holger J. Schünemann, and Christian Lienhardt

Author affiliations: St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada (L. Mbuagbaw); Centre for the Development of Best Practices in Health, Yaoundé, Cameroon (L. Mbuagbaw); McMaster University, Hamilton (L. Mbuagbaw, H.J. Schünnemann); Centre d’Immunologie et des Maladies Infectieuses, INSERM, Paris (L. Guglielmetti, E. Caumes, J. Robert, N. Veziris); Centre Hospitalier de Bligny, Bris-sous-Forges, France (L. Guglielmetti, M. Frechet-Jachym); Sorbonne Université, Paris, France (L. Guglielmetti, J. Robert, N. Veziris); Médecins Sans Frontières, Paris (C. Hewison); Janssen Research & Development, LLC, Titusville, New Jersey, USA (N. Bakere); Epicentre, Paris (M. Bastard); Hôpitaux Universitaires de l’Est Parisien, Paris (N. Veziris); Médecins Sans Frontières, Yerevan, Armenia (N. Khachatryan); Médecins Sans Frontières, Tbilisi, Georgia (T. Kotrikadze); National Tuberculosis Control Centre, Yerevan (A. Hayrapetyan); National Centre for Tuberculosis and Lung Disease, Tbilisi (Z. Avaliani); World Health Organization, Geneva, Switzerland (C. Lienhardt); Université de Montpellier, Montpellier, France (C. Lienhardt)

 

Abstract

Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%–81.9%), and the treatment success rate was 65.8% (95% CI 59.9%–71.3%). Death rate was 11.7% (95% CI 7.0%–19.1%). Up to 91.1% (95% CI 82.2%–95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%–23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.

Keywords: Antibiotics; Drugs Resistance; Tuberculosis; MDR-TB; XDR-TB; Bedaquiline.

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