Effects Of Levofloxacin Combined With Amikacin On Mutant Selection Window Against Klebsiella Pneumoniae

Objective:To determine the minimal inhabitory concentration(MIC) and the mutant prevention concentration (MPC) of levofloxacin and amikacin alone and levofloxacin combined with amikacin against the clinic isolated strains of Klebsiella Pneumoniae. To calculate and compare MPC/MIC(selective index, SI) of levofloxacin alone and levofloxacin combined with amikacin against the clinic isolated strains of Klebsiella Pneumoniae. To evaluate the influence of levofloxacin combine with amikacin on the mutant selection window (MSW) against Klebsiella Pneumoniae in vitro, to guide clinicians using antibiotics rationally, and provide the theoretical evidence on preventing antibactics resistance.Methods:(1) the MICs of levofloxacin, amikacin alone and levoflo-xacin combined with amikacin against Klebsiella Pneumoniae were determined by agar plates dilution method:2μl1.5×107CFU/ml bacterial liquid of Klebsiella Pneumoniae were plated in agar plates containing various concentrations of levofloxacin or amikacin alone or levofloxacin combined with amikacin. incubation at 35℃for 24 hours. The concentrations that no clonies grow on drug-containing agar plates were MICs. (2) the MPCs of levofloxacin, amikacin alone and levofloxacin combined with amikacin againsting Klebsiella Pneumoniae were determined by agar plates dilution method:the cells of 3×1010 colony forming units per milliliter Klebsiella Pneumoniae were enriched in MH broth. 100μl bacterial liquid of Klebsiella Pneumoniae were plated in agar plates containing various concentrations of levofloxacin or amikacin alone or levofloxacin combined with amikacin.1.2×1010 CFU bacterial liquid of Klebsiella Pneumoniae were plated in each drug concentration, incubation at 35℃for 72 hours. The concentrations that no clonies grow on drug-containing agar plates were MPCs. (3) To calculate and compare MPC50, MPC90, MPC/MIC(selective index SI) of levofloxacin alone and levofloxacin combined with amikacin against the clinic isolated strains of Klebsiella Pneumoniae. Using the SPSS statistics software to analyze the data, To evaluate the influence of levofloxacin combined with amikacin on the mutant selection window (MSW) against Klebsiella Pneumoniae. Results:(1)MPC rages of levofloxacin alone were 2-16mg/l, MPC50=2mg/l, MPC90=8mg/l, MPC50/MIC50=16, MPC90/MIC90=16, MPCG=3.17; MPC rages of levofloxacin combined with amikacin were 1-8mg/l, MPC50=lmg/l, MPC90=2mg/l, MPC50/MIC50=8, MPC90/MIC90=8, MPCG=1.55; Compared with levofloxacin alone, the MPCmax, MPCmin, geometric mean, MPC50, MPC90, MPC50/MIC50 and MPC/MIC90 of levofloxacin combined with amikacin decreased. the diference of MPC was significant, p<0.05. (2) SI(MPC/MIC) rages of levofloxacin alone and levofloxacin combined with amikacin were 2-64, SI50=16, SI90=32. the diference of SI was non-significant, p>0.05. (3) Compared with levofloxacin alone, there were 15 SI decreased of levofloxacin combined with amikacin in against 30 strains of Klebsiella Pneumoniae,11 SI non-changed, and 4 SI increased.Conclusions: (1) levofloxacin combined with Ceftriaxone could decrease the MPC of levofloxacin against Klebsiella Pneumonia, It is helpful for the concentration of levofloxacin beyond the MPC, and it is in advantage to improve the ability of reducing the selective enrichment of resistant mutants, preventing drug resistant development further. (2) The influence of levofloxacin combined with amikacin on MSW of levofloxacin against Klebsiella Pneumonia included:narrowed, enlarged, and non-changed. The MSW narrowed was major. The narrow MSW is in advantage to improve the ability of reducing the selective enrichment of resistant mutants, the enlarged MSW raise the risk of the selective enrichment of resistant mutants.