Pharmacodynamics And Drug Interactions Of Gatifloxacin: An In Vitro Study

OBJECTIVE: Gatifloxacin is a novel extended-spectrum fluorquinolone , which is developed by Japan.Clinical trials of gatifloxacin is recently studed in China. The aim of this study was to investigate the phamacodynamics of Gatifloxacin on escherichea coli by studying the in vitro activity ,the activity of antimicrobial combinations,time-kill curves, Postantibiotic effect and the mechanisms. The other aim of this study was to assess the potential drug interactions betweem gatifloxacin and various other drugs by studying the effects of gatifloxacin on mice hepatic microsomal enzymes(CYP450).These study offer to theorial data for clinical reasonable medcation.METHODS: We compared the in vitro activity of four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin) to seven of beta-lactams on 78 strains of E.coli from clinical with the agar dilution method.;To evaluate the antibacterial effects of gatifloxacin and ciprofloxacin respectively combined with cefmetazole on 26 strains of E.coli. by checkerboard method. The minimum inhibited concentration(MIC) of cefathiamidine alone and combine with 6 antimicrobial agents against the 26 strains of E.coli was determined by broth dilution method , the FIC(Fraction Inhibited Concentration) index was calculated according to MICs results; To investigate the killing curves of gatifloxacin and cefmetazole.We employed viable counts to follow time-kill curves for E.coli ATCC 25922 with exposure to the two antimicrobials at concentrations from one-fourth to 128 times the MIC. To evaluate the antibacterial effects of gatifloxacin combined with cefmetazole at concentrations one-fourth to one-second times the MIC on E.coli ATCC 25922. by checkerboard method; We have investigate gatifloxacin has long postantibiotic effect(PAE) with traditional viable-counting techniques. The combination of flow cytometry with fluorescent probes allows several physiological parameters to be measured on individual cells within a bacterial culture. We have used flow cytometry to investigate changes in filament formation, membrane potential, and barrier function in cells exposed to gatifloxacin. the morphology changes were observed with Atomic ForceMicroscope(AFM); The effects of gatifloxacin on mice hepatic microsomal enzymes(CYP450) were study by spectrophotometer; In vitro studies with wistar mice liver microsomes found that gatifloxacin did not inhibit a number of hepatic enzymes (cytochrome b5, NADPH- cytochrome C reductase, aminopyrine-N-demethylase, erytheomycin- N-demethylase, 7-ethoxycoumarin-o-deethylase), which suggests a low potential for interaction with agents that are biotransformed by these enzymes.RESULTS: The in vitro activity of four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin) to seven of beta-lactams on 78 strains of escherichea coli from clinical showed four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin) and seven of beta-lactams on escherichea coli from clinical have high resistance. The sensilivily result in combition showed synergism and additivity of gatifloxacin combined with cefmetazole, there are no indifferent and antagonism. The conclusion showed the killing curves of Gatifloxacin mehanesulfanae is characterized by concentration-dependent killing over a range of concentrations, yet the killing curves of cefmetazole is characterized by minimal concentration-dependent killing, As well as additivity of Gatifloxacin combined with cefmetazole. The PAE phase characterized by filament formation after exposure to gatifloxacin as seen through atomic force microscope. The flow cytometry showed similar results: a profound increase on Escherichia coli ATCC25922 size and nucleic acid after exposure to gatifloxacin , this morphological alteration was characterized by an apparently dose-dependent manner yet smaller changes were observed in membrane potential, and barrier function in cells. Gatifloxacin did not inhibit activity of a number of hepatic enzymes (cytochrome b5, NADPH-cytochrome C reduc...