sitafloxacin and garenoxacin

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Female; Fluoroquinolones; Humans; Japan; Male; Pneumonia; Quinolones

We investigated the degree of expression of Streptococcus pneumoniae genes associated with bacteriolysis and cell death in relation to the rapid bactericidal activity of sitafloxacin. S. pneumoniae ATCC 49619 was added to brain heart infusion containing sitafloxacin and garenoxacin concentrations equivalent to the Cmax achieved with the usual single dose and 4 h post-Cmax concentration. RNA was extracted and cDNA was prepared using reverse transcriptase. Following RNA extraction and cDNA synthesis, quantitative PCR was performed to determine the amount of gene expression for 13 genes associated with cell death. Of the 13 genes analyzed, S. pneumoniae exposed for 10 min to a sitafloxacin concentration of 4 h post-Cmax showed 3.9 times increased expression of lytA compared to the control strain. Furthermore, we observed a slightly increased expression for cibA encoding a competence induced bacteriocin. Our study suggests that the induction of a lytic enzyme and bacteriocin may reflect gene expression in response to sitafloxacin accounting for part of its rapid bactericidal activity against S. pneumoniae.

Topics: Anti-Bacterial Agents; Bacteriocins; Drug Resistance, Bacterial; Fluoroquinolones; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Microbial Sensitivity Tests; Streptococcus pneumoniae

Topics: Anti-Infective Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Gatifloxacin; Helicobacter pylori; Mutation

Sitafloxacin showed MICs of less than or equal to 0.5 microg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.

Topics: Anti-Bacterial Agents; DNA Gyrase; Fluoroquinolones; Helicobacter pylori; Levofloxacin; Microbial Sensitivity Tests; Mutation; Ofloxacin

DC-159a and sitafloxacin show greater bactericidal activity against Streptococcus pneumoniae than garenoxacin and other quinolones. We investigated whether the autolysis induced by these quinolones contributes to their rapid bactericidal activity.. Time-kill studies were conducted against a S. pneumoniae clinical isolate in broth with choline chloride, which is known to inhibit autolytic amidases, and lytA mutants. Western blot analysis was performed to examine LytA production. Scanning electron microscopy (SEM) was used to investigate morphological differences after exposure to quinolone.. Bactericidal activity of DC-159a and sitafloxacin against S. pneumoniae at 2 h of exposure to twice the minimum inhibitory concentration (MIC) was found to decrease by approximately 1 log CFU/ml when autolytic amidases were blocked. Time-kill studies using lytA mutants showed that DC-159a exhibited slower killing than that against the lytA-positive strains. On exposure to the MIC and twice the MIC of DC-159a and sitafloxacin, R6 and a clinical isolate overexpressed LytA, while garenoxacin caused a less significant increase in LytA than DC-159a and sitafloxacin. Scanning electron microscopy images revealed that R6 treated with DC-159a underwent distinct morphological changes, while the lytA mutant did not.. The present study demonstrated that quinolone-induced autolysis may provide quinolones more powerful bactericidal activity against S. pneumoniae.

Topics: Aminopyridines; Anti-Bacterial Agents; Bacteriolysis; Fluoroquinolones; Microbial Sensitivity Tests; N-Acetylmuramoyl-L-alanine Amidase; Streptococcus pneumoniae

The activities of BMS-284576, clinafloxacin, moxifloxacin, sitafloxacin, trovafloxacin, imipenem, cefoxitin, and clindamycin against 589 Bacteroides fragilis group isolates were determined. The activity of BMS-284576 was comparable to that of trovafloxacin. Sitafloxacin and clinafloxacin were the most active quinolones, and moxifloxacin was the least active. B. fragilis was the most susceptible of the species, and Bacteroides vulgatus was the most resistant. Association of specific antibiotic resistance with Bacteroides species was noted for all quinolones.

Topics: Anti-Infective Agents; Aza Compounds; Bacteroides; Bacteroides fragilis; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Indoles; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Quinolines; Quinolones