Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis.
Author(s): Dietze R, Hadad DJ, McGee B, Molino LP, Maciel EL, Peloquin CA, Johnson DF, Debanne SM, Eisenach K, Boom WH, Palaci M, Johnson JL
Affiliation(s): Nucleo de Doencas Infecciosas Centro de Ciencias da Saude, Universidade Federal do Espirito Santo, Av. Marechal Campos, 1468 Maruipe,Vitoria-ES Brazil, CEP 29040-091. rdietze@ndi.ufes.br
Publication date & source: 2008-12-01, Am J Respir Crit Care Med., 178(11):1180-5. Epub 2008 Sep 11.
Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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 log10 cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log10 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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