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.
Clin Infect Dis. 2015 Jan 15;60(2):188-94. doi: 10.1093/cid/ciu786. Epub 2014 Oct 15.
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.
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.
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.
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.
贝达喹啉是一种新的抗生素，已被批准用于治疗耐多药（MDR）结核病。我们旨在评估贝达喹啉的短期微生物疗效和耐受性。
我们对 2010 年 1 月至 2013 年 7 月期间接受同情性贝达喹啉治疗的 MDR 结核病患者进行了回顾性队列研究，并在贝达喹啉治疗 6 个月时进行了评估。
共纳入 35 例 MDR 结核病患者。19 例（54%）患有广泛耐药性（XDR）结核病，14 例（40%）耐氟喹诺酮类药物（Fqs）或二线注射剂。贝达喹啉平均与 4（范围 2-5）种其他药物联合使用，包括 33 例（94%）患者使用利奈唑胺。在贝达喹啉治疗 6 个月时，29 例（97%）初始培养阳性肺结核患者中有 28 例培养转阴。中位培养转阴时间为 85 天（范围 8-235 天）。与培养转阴相关的独立变量包括使用 Fqs（P=0.01）、无肺空洞（P<0.001）和无丙型肝炎病毒感染（P=0.001）。共有 7 例（20%）患者出现 QT 间期延长≥60 ms，导致 2 例（6%）患者停用贝达喹啉。2 例（6%）患者出现严重肝酶升高。在研究期间，有 1 例（3%）死亡，报告与结核病或抗结核治疗无关。
贝达喹啉联合其他有效药物使用，有可能在复杂的 MDR 和 XDR 结核病病例中实现高培养转阴率，在 6 个月的治疗中具有可靠的安全性。
