期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 178, 期 11, 页码 1180-1185出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200806-892OC
关键词
tuberculosis; oxazolidinones; linezolid; pharmacokinetics; antituberculosis agents
资金
- Tuberculosis Research Unit (TBRU)
- United States National Institutes of Allergy and Infectious Diseases
- National Institutes of Health and Human Services [NO1-A195383, HHSN266200700022C/NO1-Al-70022]
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).
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