In Vitro And In Vivo The Antibacterial Activity Of Sansanmycin A Against Pseudomonas Aeruginosa And The Initial Study Of Antipsudomonas Mechanism Of Sansanmycin A

Objective:To study the antipsudomonas effect of the newly antibiotics_SansanmycinA,discovered by Chinese Academy of Medical Sciences&Peking Union Medical.The antibacterial activity of Sansanmycin A against clinically isolated strains of Pseudomonas aeruginosa was compared with commonly used ten antimicrobials,according to CLSI guidelinel,in orde to get the antipsudomonas advantages and disadvantages of SansanmycinA.While trying combining treatment method to look for effective drug combination to improve the antibacterial effect.And to evalute the effect of the Sansanmycin A against strains of Pseudomonas aeruginosa taking intravenous dosing method.Based on the above study,go into the antipsudomonas mechanism of Sansanmycin A initially.Methods:150 clinical isolates Pseudomonas aeruginosa from June 2009 to March 2010 were collected from five hospitals in Tianjin.Broth microdilution method was used in in vitro experience to determine the MIC values of Sansanmycin A and other ten reference antibiotics against 150 clinical isolates of Pseudomonas aeruginosa.Minimum bactericidal concentration(MBC)was determinated by plate count technique.Time-kill curves were constructer by observation the bactericidal activity of Sansanmycin A at concentration ranging from 1 × MIC to 8×MIC.Fractional inhibitory concentration index(FICI)was used to assess the effect of these drug combinations.Microdilution method was applied in ex vivo experience to determine the serum bactericidal activity(SBA)and serum bacteriostatic activity(SBS)of Sansanmycin A.Real-time fluorescent quantitative PCR was used to measure the level of Pseudomonas aeruginosa gene of mraY.Results:In vitro activity of Sansanmycin A against Pseudomonas aeruginosa was similar to that of Piperacillin with MIC50 and MBC50 values of 8 and 16 ?g/ml,respectively.But MIC50 and MBC50 values of Ceftriaxone and Ticarcillin against Pseudomonas aeruginosa was higher than that of Sansanmycin A by 2 to 4 times.The bactericidal activity of Sansanmycin A was influenced by the quantity of bacterias,and antipsudomonas effect of Sansanmycin A was good with the number of Pseudomonas aeruginosa low 105CFU/ml.The MIC range and MBCrange of SansanmucinA were 2?>512 ?g/ml and 2?>512 ?g/ml,respectively.Sansanmycin A had a concentration-dependent bactericidal effect on Pseudomonas aeruginosa.In ex vivo experiment,the peak SBS and SBA median of Sansanmycin A against Pseudomonas aeruginosa were 1:256 and 1:128,respectively.According to experiment done,we preliminary concluded that minimal inhibitory concentration of Sansanmycin A against Pseudomonas aeruginosa were ?16 ?g/ml?32?g/ml and?64?g/m,which were susceptible?intermediate and resistant respectively.This break poin was used to judge the sensitivity of Sansanmycin A against Pseudomonaas aeruginosa.The result showed that the resistance of Sansanmycin A was only 17.3%,lower than Piperacilli,Tobramycin,Ticarcillin,Ceftriaxone and Gentamicin(p<0.05).The sensitivity of Sansanmycin A aginst meropenem-resistan Pseudomonas aeruginosa was 73.3%,higher than the other nine drugs.After combining treatment,we did not find that Sansanmycin A can have synergy effect with six reference antibiotics.With the method of real-time fluorescent quantitative PCR measuring the level of the gene of mraY,the result showed that Sansanmycin A was relatived to mraY gene coding MraY translocase.Conclusion:Sansanmycin A is an antimicrobial agent with high in vivo and in vitro activity against Pseudomonas aeruginosa,with low toxicity and narrow-spectrum.Compared with commonly used ten antipsudomonas antimicrobials,Sansanmycin A has some advantages.It is worth further researching and developing.