| Objective:To investigate the antimicrobial activity of nemonoxacin,a novel non-fluorinated quinolone.Then to study the influence of two important chemical factors oof alveolar microenvironment on the activity of nemonoxacin in vitro.Methods:Broth microdilution was used to detect the minimal inhibitory concen-trations（MICs）of nemonoxacin against 38 Staphylococcus aureus,included 24methicillin-resistant Staphylococcus aureus（MRSA）and 14 methicillin-sensitive Staphylococcus aureus（MSSA）isolates,30 Streptococcus pneumoniae isolates,24Haemophilus influenzae isolates.Time-kill curve experiments were performed with nemonoxacin against quality control strains of the three kinds of isolates.MIC values of nemonoxacin and control antimicrobial agents were measured in different p H of broth.Antibiotic activity was determined by time-kill curve studies with nemonoxacin against three quality control strains in media with and without surfactant.Result:Nemonoxacin（MIC50,0.5μg/ml;MIC90,4μg/ml）displayed greater activity than levofloxacin and moxifloxacin against the MRSA.The antibacterial activity of nemonoxacin(MIC50,0.016μg/ml;MIC90,0.25μg/ml)was higher than that of levofloxacin against the MSSA,but was similar to moxifloxacin.The antibacterial activity of nemonoxacin(MIC50,0.125μg/ml;MIC90,0.125μg/ml)against S.pneumoniae was the greatest of the quinolones tested.The MIC values of nemonoxacin(MIC50,0.016μg/ml;MIC90,1μg/ml)against H.influenzae displayed slightly higher than moxifloxacin,but showed no significant difference to levofloxacin.The susceptible rates of nemonoxacin to MRSA was 83.33%,which was significantly higher than levofloxacin and moxifloxacin.The susceptible rates of nemonoxacin to MSSA and S.pneumoniae were all 100%,slightly greater than levofloxacin and moxifloxacin.The susceptible rates of nemonoxacin to H.influenzae was 92.00%,similar to levofloxacin but a little greater than moxifloxacin.The susceptible rates of nemonoxacin was less than linezolid（not against H.influenzae）against MRSA,equal to linezolid against MSSA and S.pneumoniae.In the same MIC conditions,nemonoxacin（1MIC,2MIC-4h）was faster than levofloxacin to achieve the bactericidal effect against S.aureus,faster than or similar to moxifloxacin.Linezolid displayed bacteriostatic to S.aureus.Nemonoxacin（1MIC-12h,2MIC-8h）is more effective than levofloxacin,moxifloxacin,and linezolid against S.pneumoniae.Nemonoxacin（bacteriostatic effect at 2MIC,bactericidal effect at 4MIC-2h）achieved bactericidal after or the same to levofloxacin against H.influenzae,but before moxifloxacin.For moxifloxacin,the MICs rose significantly against MRSA at p H6.0,whereas nemonoxacin and levofloxacin were not sensitive in acidic conditions.The activity of daptomycin（not against H.influenzae）against S.aureus and S.pneumoniae reduced after the addition of pulmonary surfactant.For nemonoxacin,the activity of S.aureus was significantly inhibited by PS when its concentration was lower than 16MIC.For levofloxacin,the activity decrease even at 16MIC.Killing rates were unchanged against S.pneumoniae and only increased at 2MIC against H.influenzae with nemonoxacin and levofloxacin.Conclusion:1.Nemonoxacin is a concentration-dependent bactericidal agent like other quinolones.It shows great activity against gram-positive and gram-negative organisms.The activity of nemonoxacin is greater than levofloxacin,slightly greater than moxifloxacin against gram-positive cocci,especially for MRSA.Therefore,during treatment of community-acquired pneumonia in adults caused by gram-positive pathogens,Nemonoxacin is more effective than levofloxacin and moxifloxacin theoretically.2.p H in lungs of patients underlying chronic pulmonary disease will decrease.When these people infected by MRSA,the effect of nemonoxacin may greater than levofloxacin and moxifloxacin.3.The effect of pulmonary surfactant on the bactericidal activity of nemonoxacin was less than that of levofloxacin against staphylococcus aureus.Nemonoxacin can overcome inhibition of pulmonary surfactant at 16MIC but levofloxacin can not.However,the concentration of these two quinolones in lung is higher than 16MIC,the highest tested concentration in this study.Consequently,pulmonary surfactant may not influence bactericidal activity of nemonoxacin and levofloxacin in clinical treatment.This should be investigated in future. |
