Mutant Prevention Concentration Of Fluoroquinolones For Klebsiella Pneumoniae

PrefaceFollwing the use of broad-spectrum antimicrobial agents,imunosuppressed drugs,corticosteriod and invasiv procedures,Klebsiella pnumoniae has risen to prominence over the last decad as an important nosocomial pathogen,which mobidity is increasing every year.In our contury,the resistence of K.pnumoniae toβ-lactamases antimicrobials is increasing,so fluorquinolones are used in clinical treatment.Inorder to lenthen the useful lifspan of antimicrobials,especially the newer fluorquinolones,Drlica proposed thr concept of antimicrobials prevention concentration(MPC),which is thelowest concentration that inhibit firststep mutants growth.MPC can be used to evaluate antimicrobials not only the efficacy but also the potency of restricting resistant mutants and it provides a rationale for deciding whether acompound shuld be administered as part of acombination regimen rather than being used alone.In our study,we have determined MPC of four fluorquinolones to guide clinical antimicrobials choice.Methods1.Experiment Materials(1)Organisms sourceWe collected 23 clinical strains of K.pnumoniae in Sheng Jing hospital during January to December 2005.(2)ReagentMuller-Hinton broth,Muller-Hinton agar,gatifloxacin powder,levofloxacin powder,lomefloxacin powder,ciprofloxacin powder. 2.Experiment methods(1)Detection of minimal inhibitory concentrations(MIC)MICs were determined by standard agar dilution method on MH medium after a 24h incutation at 37℃.(2)Detection of MPCThe MPC was defined as the lowest drug concentration that prevented recovery of lolonies when more than 10¹⁰cells.High-desity cultrues were prepared from overnight cultrues grown in MH agar medium followed by 6h of incubation with shaking in MH broth at 37℃.Inculated for fluorquinolone-impregnated plates were incubated for 72h,at which time the MPC was recorded as the lowest fluorquinolone concentration completely inhibting baterial growth.Results1.MIC offluorquinolones for K.pnumoniaeThe susceptibility of gatifloxacin,levofloxacin,,lomefloxacin,ciprofloxacin were 91.3%,82.6%,and70%and 52%.2.MPC of fluorquinolones for K.pnumoniaeThe MPCs were determined increasingly by the order gatifloxacin=levofloxacin＜ciprofloxacin＜lomefloxacin.The MSW were determined increasingly by the order levofloxacin＜gatifloxacin＜ciprofloxacin＜lomefloxacin.ConclusionsGatifloxacin and levofloxacin have high activity against K.pnumoniae;combine with the pharmacokinetic parameters,the serum concentration of the four agents were all between MIC and MPC,which suggested the agents could not rsestrict the selective enrichment of resistsnt mutsnts while being used alone.