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Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort.
Clin Infect Dis 2015; 60(2):188-94CI

Abstract

BACKGROUND

Bedaquiline is a new antibiotic that was approved for the treatment of multidrug-resistant (MDR) tuberculosis. We aimed to evaluate the short-term microbiological efficacy and the tolerability profile of bedaquiline.

METHODS

We performed a retrospective cohort study among patients with MDR tuberculosis receiving bedaquiline for compassionate use between January 2010 and July 2013 and evaluated at 6 months of bedaquiline treatment.

RESULTS

A total of 35 patients with MDR tuberculosis were included in the study. Nineteen (54%) had extensively drug-resistant (XDR) tuberculosis, and 14 (40%) had isolates resistant to fluoroquinolones (Fqs) or second-line injectables. Bedaquiline was associated with a median of 4 (range, 2-5) other drugs, including linezolid in 33 (94%) cases. At 6 months of bedaquiline treatment, culture conversion was achieved in 28 of 29 (97%) cases with culture-positive pulmonary tuberculosis at bedaquiline initiation. Median time to culture conversion was 85 days (range, 8-235 days). Variables independently associated with culture conversion were treatment with a Fq (P = .01), absence of lung cavities (P < .001), and absence of hepatitis C virus infection (P = .001). A total of 7 patients (20%) experienced a ≥60-ms increase in QT interval, leading to bedaquiline discontinuation in 2 (6%) cases. Severe liver enzyme elevation occurred in 2 patients (6%). During the study period, 1 death (3%) occurred and was reported as unrelated to tuberculosis or antituberculosis treatment.

CONCLUSIONS

The use of bedaquiline combined with other active drugs has the potential to achieve high culture conversion rates in complicated MDR and XDR tuberculosis cases, with a reassuring safety profile at 6 months of treatment.

Authors+Show Affiliations

Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie).Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges Assistance publique-Hôpitaux de Paris (AP-HP), CHU Raymond Poincaré, Garches.Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges.AP-HP, Service des Maladies Infectieuses et Tropicales.Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie).AP-HP, Service des Maladies Infectieuses et Tropicales.Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie) AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges.Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie) AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25320286

Citation

Guglielmetti, Lorenzo, et al. "Compassionate Use of Bedaquiline for the Treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis: Interim Analysis of a French Cohort." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 60, no. 2, 2015, pp. 188-94.
Guglielmetti L, Le D슩 D, Jachym M, et al. Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort. Clin Infect Dis. 2015;60(2):188-94.
Guglielmetti, L., Le D슩, D., Jachym, M., Henry, B., Martin, D., Caumes, E., ... Robert, J. (2015). Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 60(2), pp. 188-94. doi:10.1093/cid/ciu786.
Guglielmetti L, et al. Compassionate Use of Bedaquiline for the Treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis: Interim Analysis of a French Cohort. Clin Infect Dis. 2015 Jan 15;60(2):188-94. PubMed PMID: 25320286.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort. AU - Guglielmetti,Lorenzo, AU - Le D슩,Damien, AU - Jachym,Mathilde, AU - Henry,Benoît, AU - Martin,Diane, AU - Caumes,Eric, AU - Veziris,Nicolas, AU - Métivier,Nathalie, AU - Robert,Jérôme, AU - ,, Y1 - 2014/10/15/ PY - 2014/10/17/entrez PY - 2014/10/17/pubmed PY - 2015/9/4/medline KW - TMC207 KW - bedaquiline KW - extensively drug-resistant tuberculosis KW - multidrug-resistant tuberculosis KW - safety SP - 188 EP - 94 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 60 IS - 2 N2 - BACKGROUND: Bedaquiline is a new antibiotic that was approved for the treatment of multidrug-resistant (MDR) tuberculosis. We aimed to evaluate the short-term microbiological efficacy and the tolerability profile of bedaquiline. METHODS: We performed a retrospective cohort study among patients with MDR tuberculosis receiving bedaquiline for compassionate use between January 2010 and July 2013 and evaluated at 6 months of bedaquiline treatment. RESULTS: A total of 35 patients with MDR tuberculosis were included in the study. Nineteen (54%) had extensively drug-resistant (XDR) tuberculosis, and 14 (40%) had isolates resistant to fluoroquinolones (Fqs) or second-line injectables. Bedaquiline was associated with a median of 4 (range, 2-5) other drugs, including linezolid in 33 (94%) cases. At 6 months of bedaquiline treatment, culture conversion was achieved in 28 of 29 (97%) cases with culture-positive pulmonary tuberculosis at bedaquiline initiation. Median time to culture conversion was 85 days (range, 8-235 days). Variables independently associated with culture conversion were treatment with a Fq (P = .01), absence of lung cavities (P < .001), and absence of hepatitis C virus infection (P = .001). A total of 7 patients (20%) experienced a ≥60-ms increase in QT interval, leading to bedaquiline discontinuation in 2 (6%) cases. Severe liver enzyme elevation occurred in 2 patients (6%). During the study period, 1 death (3%) occurred and was reported as unrelated to tuberculosis or antituberculosis treatment. CONCLUSIONS: The use of bedaquiline combined with other active drugs has the potential to achieve high culture conversion rates in complicated MDR and XDR tuberculosis cases, with a reassuring safety profile at 6 months of treatment. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/25320286/Compassionate_use_of_bedaquiline_for_the_treatment_of_multidrug_resistant_and_extensively_drug_resistant_tuberculosis:_interim_analysis_of_a_French_cohort_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciu786 DB - PRIME DP - Unbound Medicine ER -