Early bactericidal activity of sitafloxacin against pulmonary tuberculosis

Sitafloxacin is a quinolone broad-spectrum antimicrobial agent, and its pharmacologic properties and in vitro data demonstrate that sitafloxacin has a potent killing effect against Mycobacterium tuberculosis, including drug-resistant strains, which is superior to that of other available quinolones. However, its efficacy in patients with primary-sensitive tuberculosis is unclear. This study aims to evaluate the early bacterici dal activity (EBA) of sitafloxacin in patients with primary drug-susceptible tuberculosis. In this early bactericidal activity study, 30 patients with primary smear-positive tuberculosis were randomized to the once-daily oral administration of 200 mg sitafloxacin, 500 mg levofloxacin, or 300 mg isoniazid (INH) for 7 days. Sputum for quantitative culture was collected 2 days before the study of drug administration, followed by 16 hours of overnight sputum collected daily for 7 days of monotherapy. Colony-forming units (CFU) of Mycobacterium tuberculosis were counted from the collected overnight sputum on agar plates to calculate the EBA, defined as log10 CFU/mL sputum/day. The bactericidal activity was measured by measuring the first 2 days (early bactericidal activity 0-2) and the last 5 days (prolonged early bactericidal properties 2-7) of study drug administration. The EBA 0-2 of INH (0.39 +/- 0.22 log10CFU/mL/day) was higher than that of levofloxacin (0.26 +/- 0.27 log10CFU/mL/day) and sitafloxacin (0.22 +/- 0.25 log10CFU/mL/day), with no statistically significant difference (P = 0.08). EBA 0-2 was similar for the three drugs. INH prolonged early bactericidal activity (2-7) (0.17 +/- 0.16 log10CFU/mL/day) was higher than levofloxacin (0.14 +/- 0.10 log10CFU/mL/day) and lower than sitafloxacin (0.26 +/- 0.31 log10CFU/mL/day), with no statistically significant difference (P = 0.59). The EBA 2-7 of sitafloxacin showed higher activity than INH and levofloxacin. Sitafloxacin exhibits comparable early bactericidal activity and higher extended early bactericidal activity relative to levofloxacin. In addition, this novel fluoroquinolone has a good safety profile . The study data highlights the potential of sitafloxacin in the clinical management of drug-susceptible tuberculosis, as well as drug-resistant tuberculosis.