Sitafloxacin is a fluoroquinolone antibiotic, Sitafloxacin exerts bactericidal effects by inhibiting bacterial DNA gyrase and topoisomerase IV, thereby blocking DNA replication and transcription. Sitafloxacin maintains strong antibacterial activity against some multidrug-resistant bacteria. Sitafloxacin can be used in research on respiratory tract infections, urinary tract infections, Helicobacter pylori infections, and other bacterial infections[1-4].
In vitro, treatment of Mycobacterium tuberculosis-infected human macrophage Mono Mac 6 cells and human type II alveolar epithelial A-549 cells with Sitafloxacin (0.06-1μg/mL) for 0-7 days inhibited intracellular replication of Mycobacterium tuberculosis and exerted bactericidal effects[5]. Treatment of lipopolysaccharide-stimulated THP-1 cells with Sitafloxacin (1-50μg/mL) for 4h dose-dependently inhibited TNFα production, increased ERK phosphorylation, elevated the percentage of intracellular TNFα, and inhibited TACE phosphorylation and activity, thereby reducing TNFα release from cells[6]. Combination treatment of Mycobacterium tuberculosis-infected mouse macrophage RAW264.7 cells with Sitafloxacin (0.06μg/mL) and anti-tuberculosis drugs such as rifampin, rifalazil, isoniazid, pyrazinamide, ethambutol, streptomycin, or clofazimine enhanced killing activity against intracellular Mycobacterium tuberculosis[7].
In vivo, oral administration of Sitafloxacin at 10mg/kg twice daily for 3 days to ddY mice intratracheally inoculated with Haemophilus influenzae via sterile tube starting 24h post-infection eliminated viable bacteria from mouse lungs, reduced total cell counts and neutrophil counts in bronchoalveolar lavage fluid, and alleviated inflammatory changes in lung tissue[8]. A single intravenous administration of Sitafloxacin at 40mg/kg or 80mg/kg to BALB/c mice immediately followed by UVA irradiation for 4h induced retinal degeneration in mice[9]. Oral gavage of Sitafloxacin at 12.5mg/kg/day for 6 weeks to BALB/c mice inoculated with Mycobacterium ulcerans in footpads reduced the burden of Mycobacterium ulcerans and alleviated footpad swelling[10].
References:
[1] Nishizawa T, Munkjargal M, Ebinuma H, et al. Sitafloxacin for Third-Line Helicobacter pylori Eradication: A Systematic Review. J Clin Med. 2021 Jun 20;10(12):2722.
[2] Keating GM. Sitafloxacin: in bacterial infections. Drugs. 2011 Apr 16;71(6):731-44.
[3] Anderson DL. Sitafloxacin hydrate for bacterial infections. Drugs Today (Barc). 2008 Jul;44(7):489-501.
[4] Guo S, Li X, Li Y, et al. Sitafloxacin pharmacokinetics/pharmacodynamics against multidrug-resistant bacteria in a dynamic urinary tract infection in vitro model. J Antimicrob Chemother. 2022 Dec 23;78(1):141-149.
[5] Sato K, Tomioka H, Sano C, et al. Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines. Journal of Antimicrobial Chemotherapy. 2003;52(2):199-203.
[6] Sakamaki I, Fukushi M, Ohashi W, et al. Sitafloxacin reduces tumor necrosis factor alpha(TNFα) converting enzyme(TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells. Scientific Reports. 2021 Dec;11:24154.
[7] Tomioka H, Sato K, Shimizu T, et al. Anti-Mycobacterium tuberculosis activities of new fluoroquinolones in combination with other antituberculous drugs. Journal of Infection. 2002;44(2):160-165.
[8] Nakamura S, Yanagihara K, Araki N, et al. In vivo efficacy of sitafloxacin in a new murine model of nontypable Haemophilus influenzae pneumonia by sterile intratracheal tube. International Journal of Antimicrobial Agents. 2009 Sep;34(3):210-214.
[9] Shimoda K, Okawara S, Kato M, et al. Phototoxic retinal degeneration and toxicokinetics of sitafloxacin, a quinolone antibacterial agent, in mice. Arch Toxicol. 2001;75(7):395-399.
[10] Dhople AM, Namba K. Activities of Sitafloxacin(DU-6859a), Either Singly or in Combination with Rifampin, Against Mycobacterium ulcerans Infection in Mice. Journal of Chemotherapy. 2003;15(1):47-52.