Disease relevance of Gatiflo

• Pharmacodynamic profiling of levofloxacin and gatifloxacin using Monte Carlo simulation for community-acquired isolates of Streptococcus pneumoniae [1].
• Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents [2].
• The fluoroquinolones were highly active against these cultured isolates from community-acquired respiratory tract infection patients, with >99% of all S pneumoniae, H influenzae, and M catarrhalis strains susceptible to gatifloxacin (MIC(90), 0.5 microg/mL) and levofloxacin (MIC(90), 2 microg/mL) [3].
• Myoclonus and generalized seizures associated with gatifloxacin treatment [4].
• AM-1155 strongly inhibited the supercoiling activities of DNA gyrases purified from E. coli and S. aureus [5].

Psychiatry related information on Gatiflo

• Gatifloxacin-induced hallucinations in a 19-year-old man [6].
• A 48-year-old man participating in a residential treatment program was treated with gatifloxacin for a urinary tract infection [7].
• Single-dose gatifloxacin may offer advantages over 3-day fluoroquinolone therapy for uncomplicated UTI by decreasing secondary use of medical resources and improving patient compliance [8].

High impact information on Gatiflo

• Evidence from clinical trials indicates clinical success rates of > 90% for moxifloxacin, gatifloxacin, and levofloxacin in the treatment of CAP due to S pneumoniae [9].
• Among the fluoroquinolones, levofloxacin and gatifloxacin offer coverage for the gram-negative and gram-positive pathogens, which may make them preferable in treating urinary tract infections empirically in such patient groups [10].
• There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin [11].
• In this report Monte Carlo simulation was used to estimate the probability of attaining various target AUC:MIC ratios using AUC values from patients treated with either gatifloxacin or levofloxacin and the in vitro potency of the compounds as assessed in 881 clinical isolates of Streptococcus pneumoniae isolated from outpatients [1].
• Other IC50 values were as follows: grepafloxacin, 50 microM; moxifloxacin, 129 microM; gatifloxacin, 130 microM; levofloxacin, 915 microM; and ciprofloxacin, 966 microM [12].

Chemical compound and disease context of Gatiflo

• Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause Clostridium difficile-associated disease than levofloxacin [13].
• Against experimental pneumonia with Klebsiella pneumoniae and P. aeruginosa, AM-1155 was two- to fourfold more active than ciprofloxacin and ofloxacin [14].
• Fluoroquinolone Resistance in Streptococcus pneumoniae: Area Under the Concentration-Time Curve/MIC Ratio and Resistance Development with Gatifloxacin, Gemifloxacin, Levofloxacin, and Moxifloxacin [15].
• Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin [16].
• Clostridium difficile isolates from a 2004 outbreak in Qu??bec, Canada, were all found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and moxifloxacin [17].

Biological context of Gatiflo

• A population pharmacokinetic model was developed to describe the pharmacokinetics of gatifloxacin in children [18].
• Gatifloxacin is absorbed well from the gastrointestinal tract (oral bioavailability is almost 100%) [19].
• To demonstrate the impact of the pharmacokinetics of gatifloxacin (GA) relative to those of ciprofloxacin (CI) on the antimicrobial effect (AME), the killing and regrowth kinetics of two differentially susceptible clinical isolates each of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae were studied [20].
• Ten S. pneumoniae strains were studied; seven exhibited penicillin resistance, six demonstrated macrolide resistance, and two exhibited gatifloxacin resistance [21].
• The broad spectrum of antimicrobial activity, oral bioavailability, extensive tissue distribution, and once-daily intravenous or oral dosing of gatifloxacin, an expanded-spectrum 8-methoxy fluoroquinolone, make it a potentially useful agent for the treatment of pediatric infections [18].

Anatomical context of Gatiflo

• The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated [22].
• The 6-Fluoro-8-Methoxy Quinolone Gatifloxacin Down-Regulates Interleukin-8 Production in Prostate Cell Line PC-3 [23].
• The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration [22].
• At 10 h, seven of eight animals treated with gatifloxacin had <10 CFU/ml in their cerebrospinal fluid, compared with one of seven treated with cefotaxime therapy (P = 0.01) [24].
• The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase [25].

Associations of Gatiflo with other chemical compounds

• Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed [26].
• On the other hand, gyrA mutants were isolated by selection with gatifloxacin and sparfloxacin [27].
• We conducted a multicenter, randomized, open-label study comparing gatifloxacin monotherapy to clarithromycin alone or combined with ceftriaxone for patients with multiple risk factors [28].
• Aluminum magnesium hydroxide given 4 h after gatifloxacin (treatment F) showed no influence on the gatifloxacin pharmacokinetics [29].
• In this work, we studied the in vitro sensitivity of 24 strains of Actinomadura madurae to a new oxazolidinone (DA-7867), gatifloxacin, moxifloxacin, and garenoxacin by using a broth microdilution method [30].

Gene context of Gatiflo

• Moxifloxacin and gatifloxacin produced a significant decrease in IL-8 in C. pneumoniae-infected and TNF-alpha-stimulated HUVEC; however, moxifloxacin was the only fluoroquinolone that produced a significant decrease in MCP-1 levels under both conditions [31].
• Selection of a gyrA Mutation and Treatment Failure with Gatifloxacin in a Patient with Streptococcus pneumoniae with a Preexisting parC Mutation [32].
• Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate [33].
• STUDY OBJECTIVE: To confirm findings from an in vitro study that showed gatifloxacin did not substantially inhibit cytochrome P450 (CYP) 3A4 model substrate metabolism [34].
• CONCLUSION: Data from this in vivo trial support in vitro experience with gatifloxacin and suggest that interactions are unlikely between gatifloxacin and drugs that are metabolized by CYP3A [34].

Analytical, diagnostic and therapeutic context of Gatiflo

• Low levels of resistance were seen to the newer fluoroquinolones levofloxacin (minimum inhibitory concentration [MIC](90) = 2 microg/mL) and gatifloxacin (MIC(90) = 0.5 microg/mL), with the 4 major bacterial isolates having a 95% to 100% rate of susceptibility to these medications [35].
• Gatifloxacin concentrations were measured by a validated bioassay and high-performance liquid chromatography [29].
• Concentrations of gatifloxacin in plasma and urine and penetration into prostatic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers [36].
• This was a double-blind, multicenter study in which 410 adults (> or =18 years of age) with uncomplicated skin and soft tissue infections (SSTIs) were randomized to receive either 400 mg of gatifloxacin orally once daily or 500 mg of levofloxacin orally once daily for 7 to 10 days [37].
• In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of C. difficile-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin [13].

References