sitafloxacin and trovafloxacin

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 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 bactericidal activity and mechanisms of action of the new fluoroquinolone gemifloxacin were investigated against the laboratory strains Escherichia coli KL16, Staphylococcus aureus E3T and Streptococcus pneumoniae C3LN4. Gemifloxacin was found to be highly bactericidal against these bacteria, producing a biphasic dose-response curve typical of the fluoroquinolones. This novel fluoroquinolone was more bactericidal than all other fluoroquinolones so far tested (ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, levofloxacin, clinafloxacin, trovafloxacin, DV-7751 and sitafloxacin) against S. aureus and was more bactericidal than most other fluoroquinolones against E. coli or Str. pneumoniae. These data show gemifloxacin to be an improved member of the fluoroquinolone class of antibacterial agents.

Topics: Anti-Infective Agents; Escherichia coli; Fluoroquinolones; Gemifloxacin; Naphthyridines; Staphylococcus aureus; Streptococcus pneumoniae

Sitafloxacin (DU-6859a) and trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug-resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1x, 4x, and 10x MIC and the killing effect after exposure to 1x and 4x MIC. Rifampin was applied for interactive studies at a concentration of 2 micrograms/mL, which is equal to its mean serum level. Median PAEs produced by 1x, 4x, and 10x MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1x, 4x, and 10x MIC of trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by trovafloxacin; PAEs achieved by a concentration of 10x MIC of each quinolone did not differ significantly from those achieved by a concentration of 4x MIC. Both the 4x and 10x MIC concentrations produced a more prolonged PAE than the 1x MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug-resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.

Topics: Anti-Infective Agents; Drug Interactions; Fluoroquinolones; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Naphthyridines; Rifampin; Staphylococcus aureus

In a study designed to obtain data on compounds active against enterococci, the minimum inhibitory concentrations (MICs) of quinupristin/dalfopristin (RP 59500) and the novel quinolones DU-6859a, trovafloxacin, levofloxacin, and sparfloxacin were determined for 122 Enterococcus faecalis and seven Enterococcus faecium isolates. In addition, 15 Enterococcus faecalis isolates resistant to gentamicin, DU-6859a, and trovafloxacin were exposed over time to combinations of DU-6859a plus gentamicin and trovafloxacin plus gentamicin. DU-6859a and trovafloxacin were found to be the most active compounds against Enterococcus faecalis and DU-6859a and RP 59500 against Enterococcus faecium. Synergy between either DU-6859a or trovafloxacin and gentamicin was observed with 27 to 35% of the isolates. It is concluded that DU-6859a and trovafloxacin are very potent against enterococci, especially when combined with gentamicin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Fluoroquinolones; Gentamicins; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Quinolones; Virginiamycin

A new method of assessing the bactericidal activity of quinolones and other antibacterial agents, known as the bactericidal index or BI, is introduced and discussed. The BI represents total bacterial kill over a drug concentration range limited to levels achievable in vivo. This method allows the bactericidal activity of drugs to be readily compared. Calculation of BI produces a single value per bacterial strain/antibacterial agent combination that represents overall bactericidal activity at clinically relevant concentrations. As an example, the bactericidal activities of quinolones against Enterococcus faecalis are compared.

Topics: Anti-Infective Agents; Ciprofloxacin; Enterococcus faecalis; Fluoroquinolones; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Quinolones

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