Early bactericidal activity of sitafloxacin against pulmonary tuberculosis

Abstract Backgrounds: 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. Objective to evaluate the early bactericidal activity of sitafloxacin in patients with primary sensitive tuberculosis. Methods 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 early bactericidal activity (EBA), defined as log₁₀ CFU/ml sputum/day. The bactericidal activity was measured by measuring the first 2 days (early bactericidal activity) and the last 5 days (prolonged early bactericidal properties) of study drug administration. Results The early bactericidal activity of isoniazid (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). Isoniazid prolonged early bactericidal activity (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). Early bactericidal activity (0–2 days) and extended early bactericidal activity (2–7 days) were similar for the three drugs; however, the extended early bactericidal activity of sitafloxacin showed higher activity than isoniazid and levofloxacin. Conclusion In conclusion, sitafloxacin exhibits comparable early bactericidal activity, and higher extended early bactericidal activity relative to levofloxacin. In addition, this novel fluoroquinolone has good safety profile. Thus, our data highlights the potential of sitafloxacin in clinical management of drug-susceptible tuberculosis, as well as drug-resistant tuberculosis.