sitafloxacin and clinafloxacin

The currently available fluoroquinolones have modest activity against anaerobes. Newer fluoroquinolones with increased in vitro activity against anaerobes are under development and include levofloxacin, clinafloxacin, sparfloxacin, trovafloxacin, grepafloxacin, and DU-6859a. Side effects of the quinolones have varied according to the specific compounds and include central nervous system stimulation, gastrointestinal disturbances, vasculitis, and photosensitization. Monitoring for toxicity is incompletely reliable in identifying all potential serious side effects such as the "temafloxacin syndrome." Other fluoroquinolones may produce this syndrome rarely or not at all. In this paper, I review limited published studies on the use of these agents for skin and skin-structure infections and gynecologic infections. Studies in progress are noted, and when available, in vitro data on the efficacy of these agents against bacterial isolates from specific sources are reviewed and evaluated in terms of potential clinical utility.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Fluoroquinolones; Humans; Levofloxacin; Naphthyridines; Ofloxacin; Piperazines; Quinolones; Safety; Syndrome

The number of Salmonella strains with reduced susceptibility to fluoroquinolones has increased during recent years in many countries, threatening the value of this antimicrobial group in the treatment of severe salmonella infections.. We analyzed the in vitro activities of ciprofloxacin and 10 additional fluoroquinolones against 816 Salmonella strains collected from Finnish patients between 1995 and 2003. Special attention was focused on the efficacy of newer fluoroquinolones against the Salmonella strains with reduced ciprofloxacin susceptibility.. The isolates represented 119 different serotypes. Of all 816 Salmonella strains, 3 (0.4%) were resistant to ciprofloxacin (MIC > or = 4 microg/ml), 232 (28.4%) showed reduced susceptibility to ciprofloxacin (MIC > or = 0.125-2 microg/ml), and 581 (71.2%) were ciprofloxacin-susceptible. The MIC50 and MIC90 values of ciprofloxacin for these strains were 0.032 and 0.25 microg/ml, respectively, being lower than those of the other fluoroquinolone compounds presently on market in Finland (ofloxacin, norfloxacin, levofloxacin, and moxifloxacin). For two newer quinolones, clinafloxacin and sitafloxacin, the MIC50 and MIC90 values were lowest, both 0.016 and 0.064 microg/ml, respectively. Moreover, clinafloxacin and sitafloxacin exhibited the lowest MIC50 and MIC90 values, 0.064 and 0.125 microg/ml, against the 235 Salmonella strains with reduced susceptibility and strains fully resistant to ciprofloxacin.. Among the registered fluoroquinolones in Finland, ciprofloxacin still appears to be the most effective drug for the treatment salmonella infections. Among the newer preparations, both clinafloxacin and sitafloxacin are promising based on in vitro studies, especially for strains showing reduced ciprofloxacin susceptibility. Their efficacy, however, has not been demonstrated in clinical investigations.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Salmonella enterica

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

The in vitro potency of three newer fluoroquinolones, moxifloxacin, clinafloxacin and sitafloxacin was tested against 248 genetically defined Staphylococcus aureus isolates, comprising 116 unrelated S. aureus, seven heterogeneous intermediate vancomycin-resistant S. aureus strains as well as 125 clonally related methicillin-resistant S. aureus. All strains were susceptible to clinafloxacin and sitafloxacin based on an investigational breakpoint of 1 mg/L and were less influenced by mutations within the grl and gyr gene loci. In one-quarter to one-third of the strains tested, reserpine decreased slightly the MICs of moxifloxacin, clinafloxacin and sitafloxacin. Compared with moxifloxacin, clinafloxacin and sitafloxacin showed a significantly increased anti-staphylococcal potency.

Topics: Anti-Infective Agents; Aza Compounds; Electrophoresis, Gel, Pulsed-Field; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Moxifloxacin; Quinolines; Staphylococcus aureus

The in vitro activity of early fluoroquinolone antibodies--including ciprofloxacin, ofloxacin, fleroxacin, pefloxacin, enoxacin, and lomefloxacin--against most anaerobes has been limited, a characteristic making them poor choices as antianaerobic agents. Newer fluoroquinolones, including levofloxacin, sparfloxacin, and grepafloxacin, have moderate activity against anaerobes, including the Bacteroides fragilis group as well as Clostridium, Peptostreptococcus, Prevotella, and Fusobacterium species. Fluoroquinolones that demonstrate the greatest activity against the B. fragilis group and other anaerobes include DU-6859a, clinafloxacin, and the related naphthyridone, trovafloxacin. There has been wide variation in the susceptibility results among different studies testing the same antibiotic; such variation may be due in part to the use of different methodologies, inoculum sizes, and testing media. In a direct comparison of susceptibility findings for ciprofloxacin, ofloxacin, and levofloxacin in three different media, we have determined that twofold dilution differences in minimum inhibitory concentration (MIC) values (MIC90, mode MIC, and geometric mean MIC) may occur in association with the choice of testing media. Thus, testing media should be considered when comparing results of different studies on the susceptibility of anaerobes to fluoroquinolones.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Culture Media; Drug Resistance, Microbial; Evaluation Studies as Topic; Fluoroquinolones; Humans; In Vitro Techniques; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Piperazines; Quinolones; United States

Between 1 January 1992 and 31 December 1993, our laboratory, as part of the Gonococcal Isolate Surveillance Project, found that 39 of 673 isolates of Neisseria gonorrhoeae from one local sexually transmitted diseases clinic demonstrated decreased susceptibilities to both ciprofloxacin and ofloxacin. The MICs of BAY y 3118, DU-6859a, and clinafloxacin at which 90% of the gonococci with decreased susceptibility to ciprofloxacin and ofloxacin were inhibited were all 0.016 microgram/ml, which was eightfold higher than those for ciprofloxacin-susceptible gonococci. Our report substantiates prior observations that diminished susceptibility to one quinolone is often associated with diminished susceptibility to other quinolones.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Ofloxacin; Quinolones; Spiro Compounds

Emerging resistance to the current fluoroquinolones has encouraged synthesis of new compounds in this class. We have evaluated the activity of DU-6859a, a novel halogenated quinolone, against a panel of 300 bacteria, relative to the activity of ciprofloxacin, clinafloxacin, fleroxacin, levofloxacin, ofloxacin, and sparfloxacin. DU-6859a was the most active of the fluoroquinolones studied and retains potentially useful activity against 80% of isolates resistant (minimum inhibitory concentration, > or = 4 micrograms/ml) to ciprofloxacin. Continued clinical investigation of DU-6859a and similar new quinolones is urged.

Topics: Anti-Infective Agents; Bacteria, Aerobic; Ciprofloxacin; Drug Resistance, Microbial; Drug Resistance, Multiple; Fleroxacin; Fluoroquinolones; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Quinolones; Spiro Compounds

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. Both quinolones produced a decrease in the log10 CFU per milliliter of > or = 3 within 3 h at 2 and 8 times the MIC for the ciprofloxacin-susceptible isolates and at 8 times the MIC for the ciprofloxacin-resistant isolates; however, only 8 times the MIC of DU-6859a consistently prevented regrowth of all isolates after 24 h of incubation.

Topics: Anti-Infective Agents; Drug Resistance, Microbial; Fluoroquinolones; Microbial Sensitivity Tests; Quinolones; Spiro Compounds; Staphylococcus aureus