The Study On Mutant Prevention Concentration Of Nemonoxacin Against Staphylococcus Aureus And Streptococcus Pneumonia

Objective:To compare the antibacterial activities and the abilities of restricting selection of resistant mutants of a novel des-F(6)-quinolone(NFQ),nemonoxacin,and fluoroquinolone,levofloxacin and moxifloxacin,against Streptococcus pneumonia and Staphylococcus aureus,including Staphylococcus aureus,methicillin resistant Staphylococcus aureus,fluoroquinolone resistant-MRSA andcommunity acquired-MRSA;To compare the bacterial recovery and growth of MRSA with different gene site mutations at different concentrations of drugs.Based on this,three quinolones' target preferences to gyrA gene,gyr B gene,parC gene and parE gene for Staphylococcus aureus are assessed.Methods:The minimal inhibit concentrations of three quinolones against 50 MRSAs,33 FR-MRSAs,43 CA-MRSAs and 10 streptococcus pneumonia were determined by agar dilution method;Determine the mutant prevention concentration of 5 FR-MRSAs and 5 streptococcus pneumonias at random,while the whole 43 CA-MRSAs.Calculate their selection indexes.Determine the mutant gene sites of RN450 and RN450A1,and their induced mutant strains in plate containing levofloxacin,RN450A2 and RN450A3.Their minimal inhibit concentrations and mutant prevention concentrations were determined by agar dilution method.Explore the bacterial growth and draw the bacterial recovery growth curve by colony-counting method.Results:The MIC90 of nenomofloxacin,levofloxacin and moxifloxacin against 50 MRSAs were 0.5?g/m L,16?g/m L and 2?g/mL respectively;The MIC90 of nenomofloxacin,levofloxacin and moxifloxacin against 33 FR-MRSAs were 4?g/mL,> 32?g/mL and 8?g/m L respectively;The MIC90 of nenomofloxacin,levofloxacin and moxifloxacin against 43 CA-MRSAs were 0.5?g/m L,8?g/m L and 2?g/m L respectively.The selection indexes of nemonofloxacin,levofloxacin and moxifloxacin against 5 FR-MRSAs were 4,2~8 and 4~8 respectively;and against 5 streptococcus pneumonias were all 4~16;and 43 CA-MRSAs were all 4~8.RN450 is wild strain,and RN450A1 is gyrA gene(ser84?leu)mutant.RN450A2,parC gene(ser80?phe)single site mutant,is derived from RN450 mutant induced by levofloxacin 0.8?g/m L;RN450A3,which contains gyrA gene(Ser84?Leu and Gly106?Asp)and parC gene(Ser80?Phe)mutant,is derived from RN450A1 mutant induced by levofloxacin 7.0?g/m L.The MICs of nemonofloxacin against RN450,RN450A1,RN450A2 and RN450A3 are 0.031?g/m L,0.062?g/mL,0.031?g/m L and 0.5?g/m L;and the MICs of levofloxacin are 0.125?g/m L,0.25?g/m L,0.25?g/mL and 8?g/m L;and the MICs of moxifloxacin are 0.031?g/m L,0.062?g/m L,0.062?g/m L and 1?g/m L.The mutant prevention concentrations of nemonoxacin against four experimental strains are 0.125?g/mL,1?g/m L,1?g/mL and 2?g/m L;and the mutant prevention concentrations of levofloxacin are 1?g/m L,8?g/m L,8?g/m L and 32?g/m L;and the mutant prevention concentrations of moxifloxacin are 0.25?g/mL,1?g/mL,4?g/m L and 16?g/m L.Under the circumstances of same drug concentrations and different strains,the proportion of bacterial recovery growth of nemonoxacin is minimum,while the levofloxacin is maximum;RN450 recovery growth proportion is minimum and RN450A3 is maximum for different mutant sites bacterial strain.Conclusions:The antibacterial activities of nemonoxacin against MRSA?FR-MRSA?CA-MRSA and Streptococcus pneumoniain vitro is slightly higher thanmoxifloxacin and remarkably higher than levofloxacin;The abilities of nemonoxacin for restricting the selection of next-step resistant mutants may be stronger than those of levofloxacin and moxifloxacin.For Staphylococcus aureus,compared with levofloxacin and moxifloxacin,nemonoxacin inhibites bacteria at lower concentrations,and nemonoxacin is highly efficacious against different genes mutant strains.Nenomoxacinandmoxifloxacin may act on the gyrA and parC almost at the same time,or both of their target preferences may be the gyr A gene of DNA gyrase,while the target preference of levofloxacin may be the parC gene of topoisomerase IV.