Disease relevance of Sitafloxacin

• The 50% inhibitory concentrations of DU-6859a were 0.86 and 1.05 micrograms/ml for the supercoiling activities of DNA gyrases isolated from E. coli and P. aeruginosa, respectively [1].
• Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903, sitafloxacin (DU-6859a), gatifloxacin (AM-1155), and levofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex [2].
• The new 4-quinolones DU-6859a and DV-7751a show enhanced activity against Streptococcus pneumoniae [3].
• Time killing curves were calculated at concentrations of 2 and 8 times the MICs of DU-6859a and clinafloxacin against six isolates of Staphylococcus aureus [4].
• DU-6859a showed potent broad-spectrum activity against gram-positive, gram-negative, and anaerobic bacteria, and its activity was greater than those of the control quinolones [1].

High impact information on Sitafloxacin

• DQ-113 was compared in vitro to sitafloxacin, moxifloxacin, levofloxacin, and ciprofloxacin for potential to select mutational resistance in multiresistant staphylococci, pneumococci, and enterococci [5].
• The mean +/- standard error of the mean viable bacterial counts in murine lungs infected with PSSP and treated with DX-619, sitafloxacin, ciprofloxacin (10 mg/kg twice daily), and saline (twice daily) were 1.75 +/- 0.06, 1.92 +/- 0.23, 6.48 +/- 0.28, and 7.57 +/- 0.13 log10 CFU/ml, respectively [6].
• In murine lung infections caused by PSSP, the 50% effective doses (ED50s) of DX-619, sitafloxacin, and ciprofloxacin were 9.15, 11.1, and 127.6 mg/kg of body weight, respectively [6].
• Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA [7].
• These results indicated that, compared with other available quinolones, sitafloxacin maintained higher activity against recent clinical isolates with multiple mutations in gyrA and parC, which can be explained by the high inhibitory activities of sitafloxacin against both mutated enzymes [8].

Chemical compound and disease context of Sitafloxacin

• DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae [9].
• Gemifloxacin was equivalent to sitafloxacin (DU 6859a) against peptostreptococci, C. perfringens, and C. ramosum, and sitafloxacin was 2 to 3 dilutions more active against fusobacteria [10].
• We compared the in vitro antimycobacterial activity of a new fluoroquinolone, HSR-903, with strong activity against gram-positive cocci with those of levofloxacin (LVFX), sitafloxacin (STFX), and gatifloxacin (GFLX) [2].
• Against Bacteroides fragilis, CP 99,219 (MIC90 0.25 mg/L) and DU 6859 (MIC90 0.03 mg/L) were more active than the other quinolones [11].
• In-vitro activity of DU-6859a against methicillin-resistant Staphylococcus aureus isolates with reduced susceptibilities to vancomycin [12].

Biological context of Sitafloxacin

• Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers [13].
• Food intake did not affect the rate and extend of absorption of DU-6859a to a clinically significant extent [13].
• In vitro and in vivo studies were conducted to investigate the drug interaction between a new quinolone antimicrobial, DU-6859a, and theophylline (TP) [14].
• The viable cell counts of E. coli and B. fragilis in the DU-6859a- and levofloxacin-treated groups were significantly lower than those in the untreated group [15].
• In vitro activity of sitafloxacin against clinical strains of Streptococcus pneumoniae with defined amino acid substitutions in QRDRs of gyrase A and topoisomerase IV [16].

Anatomical context of Sitafloxacin

• The effect of DU-6859a on TP metabolism was evaluated in vitro by measuring the rate of TP metabolite formation by using human liver microsomes [14].
• We examined the effects of ten fluoroquinolone antibacterial agents, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin, tosufloxacin, gatifloxacin, grepafloxacin, moxifloxacin and sparfloxacin, on action potentials recorded from guinea pig ventricular myocardia [17].
• During the administration, DU-6859a was detected in feces at high concentrations which correlated well with the decrease of susceptible members of fecal flora as well as their detection rate [18].
• In bile duct-cannulated rats, 57.8 % of the orally administered radioactivity was excreted in the bile within 48 h, and at least 45 % of the sitafloxacin-related material secreted in the bile was re-absorbed from the gastrointestinal tract [19].

Associations of Sitafloxacin with other chemical compounds

• Quinolones with the greatest in vitro activity against anaerobes include clinafloxacin and sitafloxacin (DU-6859a) [20].
• DU-6859a inhibited the metabolism of TP, especially the formation of 1-methylxanthine, in vitro, but to a lesser extent than other drugs that are known to interact with TP [14].
• The in-vitro activity of a new fluoroquinolone, CP 99,219 was compared with that of ciprofloxacin, DU 6859, sparfloxacin and levofloxacin [11].
• The most active agents (mupirocin, sitafloxacin and clinafloxacin) were also tested for activity at pH 5.4 against the same strains [21].
• The apparent Km values for human liver microsomes ranged from 1.9 to 10.0 mM, and the intrinsic clearance values (calculated as Vmax/Km) had a rank order of MFLX > GPFX > STFX > > LVFX [22].

Gene context of Sitafloxacin

• In a bank of human liver microsomes (n = 14), the glucuronidation activities of LVFX, MFLX, and STFX correlated highly with UGT1A1-selective beta-estradiol 3-glucuronidation activity, whereas the glucuronidation activity of GPFX correlated highly with UGT1A9-selective propofol glucuronidation activity [22].
• Sitafloxacin was effective in VRE and some recalcitrant MRSA infections [23].
• Possible relationship between phototoxicity and photodegradation of sitafloxacin, a quinolone antibacterial agent, in the auricular skin of albino mice [24].
• Sitafloxacin concentrations in the auricle were markedly decreased under UVA irradiation, whereas those in sera were not affected [24].
• Mild transient increases in alanine aminotransferase and alkaline phosphatase occurred in the sitafloxacin treatment group, but there were no apparent trends in the other serum enzyme levels [25].

Analytical, diagnostic and therapeutic context of Sitafloxacin

• Sitafloxacin might be a candidate for clinical trials on campylobacteriosis [26].
• Here, we investigate the clonal diversity of the 155 P. aeruginosa and 145 Acinetobacter spp. sitafloxacin-resistant isolates from that study by automated ribotyping [27].
• Laboratory-derived fluoroquinolone-resistant mutants were obtained by serial passage of Streptococcus sanguis and Streptococcus anginosus isolates on agar containing increasing concentrations of old and new fluoroquinolones, ofloxacin and DU-6859a, respectively [28].
• Standardized methods recommended by the National Committee for Clinical Laboratory Standards were used for all minimum inhibitory concentration tests, and DU-6859a was additionally tested by the standardized disk diffusion procedure (5-mu g disks) [29].
• We then determined the time course change of sitafloxacin concentrations in serum and auricular tissue by high performance liquid chromatography [24].

References