Lorenzo Guglielmetti1, Damien Le Dû2, Mathilde Jachym3, Benoît Henry4, Diane Martin1, Eric Caumes4, Nicolas Veziris5, Nathalie Métivier3, Jérôme Robert5. 1. 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). 2. Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges Assistance publique-Hôpitaux de Paris (AP-HP), CHU Raymond Poincaré, Garches. 3. Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges. 4. AP-HP, Service des Maladies Infectieuses et Tropicales. 5. 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.
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.
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: David C Alexander; Ravikiran Vasireddy; Sruthi Vasireddy; Julie V Philley; Barbara A Brown-Elliott; Benjamin J Perry; David E Griffith; Jeana L Benwill; Andrew D S Cameron; Richard J Wallace Journal: J Clin Microbiol Date: 2016-12-07 Impact factor: 5.948
Authors: Rosemary V Swanson; Nicole C Ammerman; Bongani Ngcobo; John Adamson; Chivonne Moodley; Afton Dorasamy; Sashen Moodley; Zinhle Mgaga; Linda A Bester; Sanil D Singh; Deepak V Almeida; Jacques H Grosset Journal: Antimicrob Agents Chemother Date: 2016-04-22 Impact factor: 5.191
Authors: Barbara A Brown-Elliott; Julie V Philley; David E Griffith; Foram Thakkar; Richard J Wallace Journal: Antimicrob Agents Chemother Date: 2017-01-24 Impact factor: 5.191