Sitafloxacin (Trade name: Gracevit in Japan) belongs to a new generation, broad-spectrum oral fluoroquinolone antibiotics. It is highly active against various kinds of gram-negative, gram-positive and anaerobic clinical isolates, even including strains that are resistant to other kinds of fluoroquinolone antibiotics. It has been listed in Japan for the treatment of respiratory and urinary tract infections. It also shows potential for the treatment of Buruli ulcer. Its mechanism of action is through inhibiting the Topoisomerase II ligase domain of bacteria, causing DNA fragmentation to inhibit the DNA synthesis of bacteria.
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https://en.wikipedia.org/wiki/Sitafloxacin
Sitafloxacin hydrate is the newest member (fourth generation) of the fluoroquinolone family of antibiotics that exhibits broad spectrum activity against many Gram-positive, Gramnegative, and anaerobic clinical isolates, including strains resistant to other fluoroquinolones. Since the launch of the first fluoroquinolone norfloxacin (patented in 1978), 20 other versions have made it to market with ciprofloxacin and levofloxacin experiencing the most prevalent usage. The mechanism of action involves inhibition of bacterial type II topoisomerases, both DNA gyrase and topoisomerase IV. By inhibiting these enzymes and preventing DNA supercoiling, cell division is disrupted leading to cell death. In Gram-negative bacteria, the primary target appears to be gyrase, whereas topoisomerase IV is involved in Gram-positive bacteria. Dual inhibition is attractive for widespread activity and avoidance of resistance as both encoding genes would have to acquire mutations.
Antibacterial (DNA-gyrase inhibitor).
ChEBI: Sitafloxacin is a member of quinolines, a quinolone antibiotic and a fluoroquinolone antibiotic.
Pharmaceutical Applications
A group 4 quinolone formulated for oral or intravenous use. In-vitro activity is similar to or better than that of moxifloxacin. The antibacterial spectrum covers Gram-positive and Gram-negative bacteria including anaerobes. It has a chlorine atom at the C-8 position, and therefore has potential for phototoxicity. Early interest in this compound has not been maintained, but it is available in Japan.
As a class, the major adverse events for fluoroquinolones are cardiac arrhythmia (due to QT interval 622 Shridhar Hegde and Michelle Schmidt prolongation), major phototoxicity, CNS disturbances (seizures, dizziness, and headaches), and tendonitis. The GI side effects, common to most antimicrobials, include Clostridium difficile-associated diarrhea (CDAD) and alterations in glucose homeostasis. From the clinical safety profile of sitafloxacin (1,059 patients receiving either 50 mg b.i.d. or 100 mg b.i.d.), about a third of patients experienced an adverse event with the most common being diarrhea, liver enzyme elevations, and headaches; however, the risk of QT prolongation, hypoglycemia, and hepatotoxicity were all considered to be low. Phototoxicity appears to be the limiting toxicity, particularly in non-Asian patients.
