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- W4306923367 abstract "Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window ( f T MSW ) and the fraction of time that the free drug concentration was above the MPC ( f T >MPC ) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize f T MSW and f T >MPC from drug exposures in the blood. Mean f T >MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean f T MSW was reduced to <30% and <15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting." @default.
- W4306923367 created "2022-10-21" @default.
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- W4306923367 date "2022-10-20" @default.
- W4306923367 modified "2023-10-18" @default.
- W4306923367 title "Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii" @default.
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- W4306923367 doi "https://doi.org/10.3389/fmicb.2022.1013939" @default.
- W4306923367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36338049" @default.
- W4306923367 hasPublicationYear "2022" @default.
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