Early and Extended Early Bactericidal Activity of Linezolid in Pulmonary Tuberculosis
Early and Extended Early Bactericidal Activity of Linezolid in Pulmonary Tuberculosis
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DOI：
10.1164/rccm.200806-892oc
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发表时间：
2008-12-01
影响因子：
24.7
通讯作者：
Johnson, John L.
中科院分区：
文献类型：
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作者：
Dietze, Reynaldo;Hadad, David Jamil;Johnson, John L.
基本原理：利奈唑胺，第一个恶唑烷酮批准用于临床使用，具有有效的在体外和有前途的在体内活动对结核分枝杆菌tuberculosis.Objectives：评价利奈唑胺的早期和延长的早期杀菌活性在肺tuberculosis.Methods：随机开放标签试验。30例新诊断的涂阳肺结核患者（每组10例）被分配接受异烟肼（300 mg每日一次）和利奈唑胺（600 mg每日两次或600 mg每日一次）治疗7天。在研究药物给药前2天采集用于定量培养的痰液，然后在7天研究药物给药期间每天采集。通过测量前2天内杆菌的下降来估计杀菌活性（早期杀菌活性）和研究药物给药的最后5天（延长的早期杀菌活性）。异烟肼的平均早期杀菌活性（0.67 log（10）cfu/ml/d）大于利奈唑胺每日两次和每日一次（分别为0.26和0.18 log（10）cfu/ml/d）。利奈唑胺在第2天和第7天之间的延长早期杀菌活性是minimal.Conclusions：利奈唑胺对空洞型肺结核患者在给药的前2天内快速分裂的结核杆菌具有适度的早期杀菌活性，但几乎没有延长早期杀菌活性。在www.clinicaltrials.gov注册的临床试验（NCT 00396084）。
Rationale: Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis.Objectives: To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis.Methods: Randomized open label trial. Thirty patients with newly diagnosed smear-positive pulmonary tuberculosis (10 per arm) were assigned to receive isoniazid (300 mg daily) and linezolid (600 mg twice daily or 600 mg once daily) for 7 days. Sputum for quantitative culture was collected for 2 days before and then daily during 7 days of study drug administration. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (early bactericidal activity) and the last 5 days of study drug administration (extended early bactericidal activity).Measurements and Main Results: The mean early bactericidal activity of isoniazid (0.67 log(10) cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log(10) cfu/ml/d, respectively). The extended early bactericidal activity of linezolid between Days 2 and 7 was minimal.Conclusions: Linezolid has modest early bactericidal activity against rapidly dividing tubercle bacilli in patients with cavitary pulmonary tuberculosis during the first 2 days of administration, but little extended early bactericidal activity. Clinical trial registered with www.clinicaltrials.gov (NCT00396084).