Sitafloxacin (Synonyms: DU6859a, DU-6859)

Sitafloxacin is a new fluoroquinolone offering a broader spectrum , as a broad-spectrum antimicrobial agent^[2],has more potent activity against Gram-positive, Gramnegative and atypical pathogens than other quinolones such as ofloxacin, CPFX and sparfloxacin^[7,8].

Sitafloxacin suppressed TNFα production more strongly than the other quinolone antibiotics. It did not suppress the signaling pathways that produced TNFα but increased phosphorylated ERK. Sitafloxacin inhibited the extracellular release of TNFα^[5,6].TACE specifically cleaves pro-TNFα to release TNFα from cell. Sitafloxacin reduced the phosphorylation and activity of TACE^[1]. Sitafloxacin is effective against pneumococcal infections, and incidence of drug-resistant mutants is low in vitro conditions^[3].

Sitafloxacin was effective against Haemophilus influenzae pneumonia in a murine model. In Sitafloxacin-treated mice, H. influenzae was decreased by 3 days after starting oral administration of Sitafloxacin, total cell counts and neutrophil counts in BALF were considerably decreased, and histopathologically inflammatory changes were greatly improved with Sitafloxacin treatment ^[4]. Sitafloxacin can achieve a higher tissue concentration than CPFX^[9]. Besides, Sitafloxacin monotherapy might be effective against low-risk FN in lung cancer patients^[10].

References:
[1]: Sakamaki I, Fukushi M, 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. Sci Rep. 2021 Dec 17;11(1):24154. doi: 10.1038/s41598-021-03511-5. PMID: 34921186; PMCID: PMC8683466.
[2]: Sato K, Hoshino K, et,al. Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates. Antimicrob Agents Chemother. 1992 Jul;36(7):1491-8. doi: 10.1128/AAC.36.7.1491. PMID: 1324647; PMCID: PMC191610.
[3]: Onodera Y, Uchida Y, et,al. Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae. J Antimicrob Chemother. 1999 Oct;44(4):533-6. doi: 10.1093/jac/44.4.533. PMID: 10588315.
[4]: Nakamura S, Yanagihara K, et,al. In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube. Int J Antimicrob Agents. 2009 Sep;34(3):210-4. doi: 10.1016/j.ijantimicag.2009.03.011. Epub 2009 Apr 24. PMID: 19394203.
[5]: Black RA, Rauch CT, et,al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997 Feb 20;385(6618):729-33. doi: 10.1038/385729a0. PMID: 9034190.
[6]: Moss ML, Jin SL, et,al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6. doi: 10.1038/385733a0. Erratum in: Nature 1997 Apr 17;386(6626):738. PMID: 9034191.
[7]: Milatovic D, Schmitz FJ, et,al. In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates. Antimicrob Agents Chemother. 2000 Apr;44(4):1102-7. doi: 10.1128/AAC.44.4.1102-1107.2000. PMID: 10722524; PMCID: PMC89825.
[8]: Miyashita N, Niki Y, et,al. In vitro and in vivo activities of sitafloxacin against Chlamydia spp. Antimicrob Agents Chemother. 2001 Nov;45(11):3270-2. doi: 10.1128/AAC.45.11.3270-3272.2001. PMID: 11600398; PMCID: PMC90824.
[9]: Fukuda Y, Yanagihara K, et,al. In vivo efficacies and pharmacokinetics of DX-619, a novel des-fluoro(6) quinolone, against Streptococcus pneumoniae in a mouse lung infection model. Antimicrob Agents Chemother. 2006 Jan;50(1):121-5. doi: 10.1128/AAC.50.1.121-125.2006. PMID: 16377676; PMCID: PMC1346772.
[10]: On R, Matsumoto T, et,al. Lung Oncology Group in Kyushu (LOGIK). Efficacy and Safety of Sitafloxacin in Treating Low-risk Febrile Neutropenia in Patients with Lung Cancer. JMA J. 2022 Jul 15;5(3):334-340. doi: 10.31662/jmaj.2021-0227. Epub 2022 May 23. PMID: 35992295; PMCID: PMC9358298.