Disease relevance of Gemifloxacin

• We investigated DNA cleavage by Streptococcus pneumoniae topo IV and gyrase stabilized by gemifloxacin and other antipneumococcal fluoroquinolones [1].
• Fluoroquinolones are recommended as first-line therapy for patients with chronic bronchitis who have risk factors; gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly encountered pathogens [2].
• The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections [3].
• The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents [4].
• Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus [5].

High impact information on Gemifloxacin

• The Food and Drug Administration has approved linezolid for clinical use, and new drug applications for gemifloxacin and telithromycin were filed [6].
• Fluoroquinolone Resistance in Streptococcus pneumoniae: Area Under the Concentration-Time Curve/MIC Ratio and Resistance Development with Gatifloxacin, Gemifloxacin, Levofloxacin, and Moxifloxacin [7].
• The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log(10) CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates [7].
• Gemifloxacin preferentially selected for parC mutants both in vitro and in vivo [8].
• We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia [8].

Chemical compound and disease context of Gemifloxacin

• Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin [9].
• 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 [10].
• Gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, was tested against 359 recent clinical anaerobic isolates by the National Committee for Clinical Laboratory Standards reference agar dilution method with supplemented brucella blood agar and an inoculum of 10(5) CFU/spot [11].
• The macrolides, particularly azithromycin, were more active than gemifloxacin against Mycoplasma pneumoniae (MIC range 0.001-0.0025 mg/L) and Mycoplasma genitalium (0.0005-0. 001 mg/L) isolates but were less active against Mycoplasma fermentans and U. urealyticum and inactive against Mycoplasma hominis [12].
• The comparative in vitro potency and post-antibiotic effect (PAE) of gemifloxacin (SB-265805), moxifloxacin, trovafloxacin, grepafloxacin, levofloxacin, ofloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin and rifampicin were evaluated against Legionella pneumophila serogroups 1-9 and 12 (n = 204) and other Legionella spp [13].

Biological context of Gemifloxacin

• These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose [14].
• We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin [15].
• These data indicate that gemifloxacin is an effective antipneumococcal agent and that AUC/MIC is the best predictor of antibacterial effect as measured by AUBKC(48) [16].
• Thus, gemifloxacin is active against clinical strains exhibiting altered topoisomerase and efflux phenotypes [17].
• Overexpression of the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a mutation in the promoter region of the gene for NorA was selected only in the sixth step of serial selection of mutants [5].

Anatomical context of Gemifloxacin

• In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections [14].
• Intracellular penetration and activity of gemifloxacin in human polymorphonuclear leukocytes [18].
• Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues [19].
• The ratios of the mean AUC(0-10) for tissue to the AUC(0-10) for free gemifloxacin in plasma were 1.7 +/- 0.7 (mean +/- standard deviation) for skeletal muscle and 2.4 +/- 1.0 for adipose tissue [19].
• Gemifloxacin is effective against L. pneumophila in infected macrophages and in a guinea pig model of Legionnaires' disease, even with an abbreviated course of therapy [20].

Associations of Gemifloxacin 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 [21].
• For gemifloxacin, the drug concentrations that caused 25% linearization of the input DNA by gyrase and topoisomerase IV were 2.5 and 0.1 to 0.3 microM, respectively; these values were 4-fold and 8- to 25-fold lower than those for moxifloxacin, respectively [22].
• In vitro activities of the newer quinolones garenoxacin, gatifloxacin, and gemifloxacin against human mycoplasmas [23].
• Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L. pneumophila pneumonia [20].
• With each quinolone resistance genotype, the order of activity, based on MIC90, against the ciprofloxacin-resistant isolates was PGE 9262932, gemifloxacin, moxifloxacin, gatifloxacin and levofloxacin [24].

Gene context of Gemifloxacin

• Staphylococcus aureus (MSSA) were highly susceptible (MIC(90) 0.06 mg/L) but MRSA less susceptible (MIC(90) 8 mg/L) to gemifloxacin [25].
• Whereas LPS induced a rapid increase in NF-kappa B activation, gemifloxacin alone did not [26].
• In addition, RNA from THP-1 cells was used in Northern blots to determine whether inhibition of secretion of IL-1 beta and TNF-alpha by gemifloxacin occurred at the transcription or translation level [26].
• (i) The gemifloxacin MICs for isogenic 7785 mutants bearing either parC or gyrA quinolone resistance mutations were marginally higher than wild type at 0.12 to 0.25 microgram/ml, whereas the presence of both mutations increased the MIC to 0.5 to 1 microgram/ml [27].
• The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin [5].

Analytical, diagnostic and therapeutic context of Gemifloxacin

• In a randomized crossover study, 16 volunteers (8 men, 8 women) received single oral doses of 320 mg of gemifloxacin and 400 mg of ofloxacin on two separate occasions in the fasting state to assess the urinary excretion and urinary bactericidal titers (UBTs) at intervals for up to 144 h [28].
• Although clinical trials have shown that gemifloxacin is effective for the treatment of uncomplicated urinary tract infections, whether an oral dosage of 320 mg of gemifloxacin once daily is also adequate for the treatment of complicated urinary tract infections has yet to be confirmed [28].
• Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2) [14].
• The successful chiral separation of gemifloxacin in a urinary solution was demonstrated for both capillary and microchip electrophoresis [29].
• Dose fractionation was used to simulate concentrations of gemifloxacin in human serum associated with 640 mg every 48 h (one dose), 320 mg every 24 h (two doses), and 160 mg every 12 h (four doses) [16].

References