gemifloxacin and trovafloxacin

Twenty-eight (11.6%) out of 241 Spanish patients enrolled in an international phase III clinical trial of mild to moderate community-acquired pneumonia (CAP) comparing gemifloxacin vs. trovafloxacin were diagnosed of Legionnaires' disease. A definite diagnosis was established by seroconversion in 13 patients of whom only 2 had a positive Legionella urinary antigen. The remaining 15 patients were possible Legionella infections based on a single elevated IgG titer (> or = 1:512). All patients had a radiologically confirmed diagnosis of pneumonia, 5 (19%) patients were older than 65, comorbidity was present in 9 (33%), and 10 (36%) had to be hospitalized. Fifteen patients were treated with oral gemifloxacin (320 mg/day) and 13 with oral trovafloxacin (200 mg/day). Overall, clinical success occurred in 25 (89.3%) patients after 7 days of treatment and only 1 patient needed a 14-day treatment. There were only one adverse event withdrawal and one clinical failure, and no patients died. In light of the favorable clinical outcome, the use of newer fluoroquinolones seems adequate for the treatment of suspected or proven Legionella pneumonia.

Topics: Community-Acquired Infections; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Immunoglobulin G; Legionella; Legionellosis; Naphthyridines; Pneumonia; Treatment Outcome

Topics: Anti-Infective Agents; Ciprofloxacin; Cross-Over Studies; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Male; Microbial Sensitivity Tests; Naphthyridines; Serum Bactericidal Test; Streptococcus pneumoniae

Topics: Adult; Anti-Infective Agents; Cross-Over Studies; Escherichia coli; Fluoroquinolones; Gemifloxacin; Humans; Male; Microbial Sensitivity Tests; Naphthyridines; Staphylococcus; Time Factors

Gemifloxacin and trovafloxacin were administered to 12 volunteers in a randomized crossover trial with a 2-week washout period. Stool samples were collected predose and 1, 2, and 3 days postdose. Both quinolones reduced the number of organisms of the family Enterobacteriaceae and aerobic gram-positive organisms. Escherichia coli reduction was greater with gemifloxacin than with trovafloxacin, with postdose isolation of quinolone-resistant strains for which MICs of trovafloxacin were higher than those of gemifloxacin.

Topics: Anti-Infective Agents; Bacteroides fragilis; Colony Count, Microbial; Cross-Over Studies; Escherichia coli; Feces; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines

Urine bactericidal titers (UBTs) against Escherichia coli ATCC 25922 and Staphylococcus saprophyticus ATCC 1970 were determined after the administration of single oral doses of gemifloxacin at 320 mg and trovafloxacin at 200 mg to healthy volunteers. Gemifloxacin presented significantly lower experimental versus mathematically predicted UBTs over 72 h, due to the effect of urine on the susceptibility of the E. coli strain. Experimental UBTs were significantly higher for gemifloxacin than trovafloxacin against both strains over 72 h.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Area Under Curve; Chromatography, High Pressure Liquid; Escherichia coli; Fluoroquinolones; Gemifloxacin; Humans; Male; Microbial Sensitivity Tests; Naphthyridines; Staphylococcus

This randomised, double-blind, double-dummy, multinational study compared the efficacy and safety of gemifloxacin with trovafloxacin in the treatment of acute exacerbations of chronic bronchitis. There were 617 patients randomised: 303 to gemifloxacin and 314 to trovafloxacin. Clinical success rates at follow-up (clinical per-protocol population) were 91.5% for gemifloxacin and 87.6% for trovafloxacin. For the intent-to-treat population, the clinical efficacy of gemifloxacin was statistically significantly superior to that of trovafloxacin. In general, the in vitro activity of gemifloxacin against the major respiratory bacterial pathogens was superior to that of other antibiotics tested. Per-patient bacteriological success rates at follow-up (bacteriology per-protocol population) were 86.8% for gemifloxacin and 82.4% for trovafloxacin. Both agents were well tolerated. The clinical and bacteriological efficacy of a once-daily 5-day course of gemifloxacin is at least as good as that of a similar regimen of trovafloxacin in the treatment of acute exacerbations of chronic bronchitis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Bronchitis, Chronic; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Follow-Up Studies; Gemifloxacin; Humans; Lung; Male; Middle Aged; Naphthyridines; Time Factors; Treatment Outcome

This multicentre, randomized, double blind, parallel group study compared the efficacy and safety of gemifloxacin (320 mg once daily) with trovafloxacin (200 mg once daily) in 571 patients with community-acquired pneumonia (CAP). Although treatment was given routinely for 7 days it could be extended to 14 days; two-thirds of patients were treated for 7 days. High clinical success rates were noted at follow-up in the per-protocol population in both the gemifloxacin group (95.8%) and the trovafloxacin group (93.6%), non-inferiority with 95% CI. In the intent-to-treat population, the clinical success rate at follow-up was significantly superior for gemifloxacin (87.6%) compared with trovafloxacin (81.1%; 95% CI 0.5, 12.4). The pathogens identified most commonly at presentation were Mycoplasma pneumoniae and Streptococcus pneumoniae. Gemifloxacin eradicated 100% of S. pneumoniae. One bacteraemic isolate of S. pneumoniae was associated with clinical failure in the trovafloxacin group (MIC of trovafloxacin 8 mg/L). Gemifloxacin was well tolerated and the incidence of transient liver function abnormalities was very low. Gemifloxacin is an effective and well-tolerated treatment for patients with CAP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Community-Acquired Infections; Double-Blind Method; Drug Resistance, Microbial; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumonia, Bacterial

The serum bactericidal activity against 2 Streptococcus pneumoniae strains (ciprofloxacin MIC 1 and 4 mg/l) was measured in 12 volunteers who received oral single doses of gemifloxacin 320 mg and trovafloxacin 200 mg in a crossover fashion. The 4-fold increase in ciprofloxacin MIC from the susceptible to the resistant strain resulted in a 2-fold increase in MIC (from 0.015 to 0.03 mg/l), a 2-fold decrease in C(max)/MIC (104 vs 52) and in AUC(0-24 h)/MIC (532 vs 266), but a 5.6-fold decrease in area under the bactericidal curve (AUBC: 168 vs 30) for gemifloxacin. Trovafloxacin showed a 4-fold higher MIC (0.25 vs 0.06 mg/l), a 4-fold lower C(max)/MIC (8.6 vs 36), a 4-fold lower AUC(0-24 h)/MIC (85 vs 356) and a 11-fold lower AUBCs (2 vs 22) against the resistant isolate compared with the susceptible one. Trovafloxacin serum bactericidal titres against the ciprofloxacin-resistant strain were measurable generally only at 1 h after dosing (median titre=2). Gemifloxacin showed similar ex vivo bactericidal activity against the ciprofloxacin-resistant strain to that of trovafloxacin against the ciprofloxacin-susceptible strain.

Topics: Adult; Anti-Infective Agents; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Male; Microbial Sensitivity Tests; Naphthyridines; Serum Bactericidal Test; Streptococcus pneumoniae

Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients.. Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2 x 2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper.. NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Cardiovascular Diseases; Drug-Related Side Effects and Adverse Reactions; Fluoroquinolones; Gemifloxacin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Theoretical; Naphthyridines; Pneumonia; Preventive Medicine; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.

Topics: Aza Compounds; Ciprofloxacin; DNA Gyrase; DNA Topoisomerase IV; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Levofloxacin; Moxifloxacin; Mutagenicity Tests; Naphthyridines; Ofloxacin; Quinolines; Selection, Genetic; Staphylococcus aureus; Streptococcus pneumoniae

The MIC of gemifloxacin and five other quinolones was tested against 31 clinical isolates of Neisseria gonorrhoeae; strains were analyzed for the presence of mutations in both the gyrA and parC genes. Only seven strains were resistant to nalidixic acid due to a mutation in the gyrA gene but not in the parC gene, with six and two considered intermediate to ciprofloxacin and levofloxacin, respectively. The activity of gemifloxacin was similar to that of trovafloxacin and moxifloxacin, but was more active than nalidixic acid, ciprofloxacin or levofloxacin against the gyrA mutant strains. Gemifloxacin is a valid therapeutic alternative to treat infections with N. gonorrhoeae, retaining its activity against strains already presenting a mutation in gyrA.

Topics: Anti-Infective Agents; Aza Compounds; Ciprofloxacin; DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Genes, Bacterial; Gonorrhea; Humans; In Vitro Techniques; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mutation; Nalidixic Acid; Naphthyridines; Neisseria gonorrhoeae; Ofloxacin; Quinolines

Intra-abdominal infections are biphasic, synergistic processes with early peritonitis and bacteremia due to aerobes and a later abscess component due to anaerobes. Although Bacteroides fragilis is the most commonly recognized pathogen, other anaerobes, including other members of the B. fragilis-group species, are major components of infection. Anaerobic bacteremia is often associated with an intra-abdominal source. New antimicrobial agents with anaerobic activity are in various stages of development for the therapy of intra-abdominal infections. The in vitro activity and the currently available sparse clinical data are reviewed for a new carbapenem (ertapenem), several fluoroquinolones (trovafloxacin, moxifloxacin, and gemifloxacin), and a desfluoroquinolone (BMS-284756).

Topics: Abdominal Abscess; Anti-Bacterial Agents; Aza Compounds; Bacteremia; Bacteria, Anaerobic; Bacteroides fragilis; Bacteroides Infections; beta-Lactams; Carbapenems; Clinical Trials as Topic; Ertapenem; Fluoroquinolones; Gemifloxacin; Humans; Indoles; Lactams; Moxifloxacin; Naphthyridines; Quinolines; Quinolones

The ability of sequential subcultures in subinhibitory concentrations of gemifloxacin, trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to select resistant mutants was studied in 16 pneumococci [eight with ciprofloxacin MICs (mg/L) 0.25-1; four with 8-16; four with 16-32]. Subculturing was done 50 times, or until mutants with elevated MICs (> or = 4 x) to the selecting drug emerged. Subculturing in gemifloxacin selected six resistant mutants (gemifloxacin MICs 2 mg/L); trovafloxacin selected nine (trovafloxacin MICs 2-4 mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8-128 mg/L); gatifloxacin selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2-16 mg/L). DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE or GyrB. Some new mutations were found in ParE or GyrB that have not yet been reported; GyrB mutation might be associated with moxifloxacin resistance. Both DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin; gemifloxacin also selected mutants with single modifications in gyrA, parC or parE alone among derived mutants by repeated exposure to subinhibitory concentrations of fluoroquinolones. In the presence of reserpine, most mutants had lower MICs of ciprofloxacin and gemifloxacin (4-32 x), and gatifloxacin (4-8 x), suggesting an efflux mechanism; none had lower trovafloxacin and moxifloxacin MICs. All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones.

Topics: Anti-Infective Agents; Aza Compounds; Biological Transport; Ciprofloxacin; DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Humans; Microbial Sensitivity Tests; Moxifloxacin; Mutation; Naphthyridines; Quinolines; Selection, Genetic; Serotyping; Streptococcus pneumoniae

To compare the antimicrobial effects of gemifloxacin and trovafloxacin on Staphylococcus aureus, their pharmacodynamics were studied in an in vitro dynamic model. A series of pharmacokinetic profiles of gemifloxacin and trovafloxacin with half-lives of 7.4 and 9.2 h, respectively, were simulated in vitro over an eightfold range of area under the curve (AUC)-to-MIC ratio, from 58 to 466 h. The relationships observed between the intensity of antimicrobial effect (I(E)) and log AUC/MIC were linear, species- and strain-independent and were distinct (not superimposed) for both gemifloxacin and trovafloxacin (r(2) = 0.99 in both cases). At AUC/MICs > 100 h, trovafloxacin had greater effects than gemifloxacin. For example, at an AUC/MIC of 250 h, the antimicrobial effect of trovafloxacin was 17% higher than gemifloxacin. However, due to its higher intrinsic activity, gemifloxacin may be as efficient as trovafloxacin at their clinical doses (320 and 200 mg, respectively): the I(E)s on a hypothetical strain of S. aureus with gemifloxacin's and trovafloxacin's MICs corresponding to the MIC(50)s were similar-290 and 310 (log CFU/mL)x h, respectively. This analysis suggests that both AUC/MIC and dose relationships of the antimicrobial effect are needed for comprehensive comparisons of fluoroquinolone pharmacodynamics.

Topics: Anti-Infective Agents; Area Under Curve; Dose-Response Relationship, Drug; Escherichia coli; Fluoroquinolones; Gemifloxacin; Microbial Sensitivity Tests; Models, Biological; Naphthyridines; Predictive Value of Tests; Staphylococcus aureus

Topics: Anti-Infective Agents; Community-Acquired Infections; Double-Blind Method; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Pneumonia; Randomized Controlled Trials as Topic

Ciprofloxacin resistance influences the in vitro effect of new quinolones on Streptococcus pneumoniae.. The early (over 3 h) in vitro bactericidal activity of gemifloxacin, trovafloxacin and ciprofloxacin was explored by time-kill tests against two ciprofloxacin-susceptible (MIC = 0.5 and 1 microg/ml) and two ciprofloxacin-resistant (MIC = 16 microg/ml) S. pneumoniae strains.. At subinhibitory concentrations (0.5 x MIC) and inhibitory concentrations (1 x MIC), only gemifloxacin exhibited significant bactericidal activity with, respectively, approximately 85 and approximately 95% decrease in the initial inoculum of the two ciprofloxacin-resistant strains. At concentrations similar to peak serum concentrations (1.5, 3 and 2.5 microg/ml for gemifloxacin, trovafloxacin and ciprofloxacin, respectively) after standard doses, only gemifloxacin exhibited an approximately 99.9% (3 log(10)) reduction in the initial inoculum for the four strains tested, regardless of their susceptibility to ciprofloxacin. No bactericidal activity was exhibited for the other two quinolones against the ciprofloxacin-resistant strains.. Gemifloxacin offers high early bactericidal activity at concentrations similar to peak and trough levels, theoretically preventing regrowth over the dosing interval, and thus dealing with the problem of ciprofloxacin resistance in S. pneumoniae.

Topics: Anti-Infective Agents; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Microbial Sensitivity Tests; Naphthyridines; Streptococcus pneumoniae

Newer fluoroquinolones have good activity against Streptococcus pneunoniae and may be useful clinically for the treatment of pneumonia. Although resistance among Streptococcus pneumoniae has been reported, it is rare. The frequency of single-step resistance and the emergence of resistance were compared in serial transfer of 49 clinical isolates of penicillin-sensitive and -resistant Streptococcus pneumoniae to ciprofloxacin, levofloxacin, trovafloxacin, grepafloxacin, and gemifloxacin. Single-step resistance frequencies to four times the minimum inhibitory concentration were 2.73 x 10(-6) (+/- 8.46 x 10(-6)) for ciprofloxacin, 1.78 x 10(-7) (+/- 4.62 x 10(-7)) for trovafloxacin, 5.45 x 10(-7) (+/- 1.24 x 10(-6)) for grepafloxacin, 6.78 x 10(-7) (+/- 1.38 x 10(-6)) for gemifloxacin, and 9.23 x 10(-8) (+/- 4.47 x 10(-7)) for levofloxacin. In serial transfer experiments, all isolates became resistant to clinically relevant levels of all fluoroquinolones after eight passages. The resistance occurred most rapidly with ciprofloxacin followed by grepafloxacin, gemifloxacin, trovafloxacin, and levofloxacin. These results show that strains with decreased susceptibility to fluoroquinolones occur frequently in cultures of Streptococcus pneumoniae, and this organism can readily become resistant to clinically relevant concentrations of fluoroquinolones in vitro.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Piperazines; Streptococcus pneumoniae

The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant Staphylococcus epidermidis isolates, and coagulase-negative staphylococci.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Bacteremia; Ciprofloxacin; Fluoroquinolones; Gemifloxacin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Piperazines; Quinolines

The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC > or =2 microg/ml; 30 strains with intermediate resistance [MIC 2 microg/ml] and 43 strains with complete resistance [MIC > or =4 microg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P< or =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs. 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 and > or =16 microg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (> or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

In vitro activities of seven fluoroquinolones against 140 clinical Acinetobacter baumannii isolates representing 138 different strain types were determined. The rank order of activity was clinafloxacin > gatifloxacin > levofloxacin > trovafloxacin > gemifloxacin = moxifloxacin > ciprofloxacin. The 31 outbreak-related A. baumannii strains were significantly more resistant than were 109 sporadic strains.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Infective Agents; Aza Compounds; Ciprofloxacin; Disease Outbreaks; Drug Resistance, Microbial; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Germany; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Quinolines

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

Antimicrobial activity of gemifloxacin (SB-265805), a newly developed fluoroquinolone, to Japanese isolates of Neisseria gonorrhoeae was compared with those of various fluoroquinolones, including norfloxacin, ciprofloxacin, tosufloxacin, levofloxacin, sparfloxacin, and trovafloxacin. Among the fluoroquinolones tested, gemifloxacin was most active against N. gonorrhoeae isolates. The MIC90 values of gemifloxacin for 94 N. gonorrhoeae isolated from 1992 through 1993 and 100 isolated from 1996 through 1997 were 0.03 and 0.125 microg/ml, respectively. On the other hand, MIC90 values of the other fluoroquinolone for the 1992-1993 isolates and the 1996-1997 isolates ranged from 0.125 to 2 microg/ml and from 0.5 to 8 microg/ml, respectively. Gemifloxacin was also the most potent fluoroquinolone against 31 ciprofloxacin-resistant isolates with the ciprofloxacin MIC of 1 to 16 microg/ml, for which the gemifloxacin MIC50 and MIC90 values were 0.25 and 2 microg/ml, respectively. Moreover, the activity of gemifloxacin against fluoroquinolone-resistant gonococcal isolates containing multiple amino acid substitutions in both GyrA and ParC proteins was superior to those of the other compounds.

Topics: Amoxicillin; Anti-Infective Agents; Ciprofloxacin; Clavulanic Acid; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Gonorrhea; Humans; Levofloxacin; Naphthyridines; Neisseria gonorrhoeae; Norfloxacin; Ofloxacin

The activities of two investigational fluoroquinolones and three fluoroquinolones that are currently marketed were determined for 182 clinical isolates of Streptococcus pneumoniae. The collection included 57 pneumococcal isolates resistant to levofloxacin (MIC >/= 8 microg/ml) recovered from patients in North America and Europe. All isolates were tested with clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, and trovafloxacin by the National Committee for Clinical Laboratory Standards broth microdilution and disk diffusion susceptibility test methods. Gemifloxacin demonstrated the greatest activity on a per gram basis, followed by clinafloxacin, trovafloxacin, gatifloxacin, and levofloxacin. Scatterplots of the MICs and disk diffusion zone sizes revealed a well-defined separation of levofloxacin-resistant and -susceptible strains when the isolates were tested against clinafloxacin and gatifloxacin. DNA sequence analyses of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE from 21 of the levofloxacin-resistant strains identified eight different patterns of amino acid changes. Mutations among the four loci had the least effect on the MICs of gemifloxacin and clinafloxacin, while the MICs of gatifloxacin and trovafloxacin increased by up to six doubling dilutions. These data indicate that the newer fluoroquinolones have greater activities than levofloxacin against pneumococci with mutations in the DNA gyrase or topoisomerase IV genes. Depending upon pharmacokinetics and safety, the greater potency of these agents could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains.

Topics: Anti-Bacterial Agents; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Humans; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Streptococcus pneumoniae

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.

Topics: Anti-Infective Agents; Aza Compounds; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Humans; Klebsiella; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Quinolines; Urinary Tract Infections