Early and Extended Early Bactericidal Activity of Linezolid in Pulmonary Tuberculosis
- 1 December 2008
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 178 (11), 1180-1185
- https://doi.org/10.1164/rccm.200806-892oc
Abstract
Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis. To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis. 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). 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. 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).This publication has 31 references indexed in Scilit:
- In Vitro Activities of Linezolid against Clinical Isolates of Mycobacterium tuberculosis Complex Isolated in Taiwan over 10 YearsAntimicrobial Agents and Chemotherapy, 2008
- In Vitro Activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensisAntimicrobial Agents and Chemotherapy, 2006
- In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolatesInternational Journal of Antimicrobial Agents, 2006
- Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosisJournal of Antimicrobial Chemotherapy, 2006
- Pharmacokinetic and Pharmacodynamic Issues in the Treatment of Mycobacterial InfectionsEuropean Journal of Clinical Microbiology & Infectious Diseases, 2004
- Oxazolidinones: activity, mode of action, and mechanism of resistanceInternational Journal of Antimicrobial Agents, 2004
- Intrapulmonary penetration of linezolidJournal of Antimicrobial Chemotherapy, 2003
- Clinical Pharmacodynamics of Linezolid in Seriously Ill Patients Treated in a Compassionate Use ProgrammeClinical Pharmacokinetics, 2003
- In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosisInternational Journal of Antimicrobial Agents, 2002
- Intrapulmonary Pharmacokinetics of LinezolidAntimicrobial Agents and Chemotherapy, 2002