Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis

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).

Figure 1.

Change in colony-forming units (cfu) in sputum before and during 7 days of study drug administration with isoniazid (INH, 300 mg once daily) and linezolid (600 mg, once or twice daily). Sputum was collected for 12 hours for 2 days before and daily during 7 days of drug administration. Data represent the mean change in log₁₀ cfu/ml of sputum ± SD for each of the 7 days of study drug administration. Mean baseline colony-forming unit counts for each treatment group are listed in the text.