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Am J Respir Crit Care Med. 2008 Dec 1;178(11):1180-5. doi: 10.1164/rccm.200806-892OC. Epub 2008 Sep 11.

Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis.

Author information

1
Núcleo de Doenças Infecciosas Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468 Maruípe,Vitória-ES Brazil, CEP 29040-091. rdietze@ndi.ufes.br

Abstract

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).

PMID:
18787216
PMCID:
PMC2588492
DOI:
10.1164/rccm.200806-892OC
[Indexed for MEDLINE]
Free PMC Article

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