Objectives: The emergence of carbapenem-resistant Enterobacteriaceae, especially\nKlebsiella pneumoniae, has become a major concern in clinic settings. Combination\ntherapy is gaining momentum to counter the secondary resistance and potential\nsuboptimal efficacy of monotherapy. The aim of this study was to evaluate the bactericidal\neffect of fosfomycin (FM), amikacin (AMK), or colistin (COL) alone and combinations\nagainst KPC2-producing K. pneumoniae using dynamic model by simulating human\npharmacokinetics in vitro.\nMethods: The Pharmacokinetics Auto Simulation System 400 system was employed\nto simulate different dosing regimens of FM, AMK, and COL alone and combination.\nBacterial growth recovery time (RT) and the area between the control growth and\nantibacterial killing curves (IE) were used as unbiased and comprehensive means for\ndetermining the antimicrobial effect.\nResults: We observed that COL alone was much pronounced than FM or AMK against\nKPC-Kp. IE of FM (8 g every 8 h) plus AMK (15 mg/kg once-daily) and FM (8 g every\n8 h) plus COL (75,000 IU/kg every 12 h) were higher (>170 and >200 LogCFU/mLÃ?·hâË?â??1,\nrespectively) than that of monotherapies against sensitive strains. Of note, the rate of\nresistance was lower when using the combination of FM (8 g every 8 h) plus COL (75,000\nIU/kg every 12 h) than using COL (75,000 IU/kg every 12 h) alone.\nConclusions: The combination of FM (8 g every 8 h) plus AMK (15 mg/kg once-daily)\nand FM (8 g every 8 h) plus COL (75,000 IU/kg every 12 h) were effective at maximizing\nbacterial killing and suppressing emergence of resistance.
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