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Updated: Jan 30, 2026

Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Concentration-dependent enrichment of resistant Enterococcus faecium exposed to linezolid in an in vitro dynamic
Kamilla N Alieva1, Maria V Golikova1, Yury A Portnoy1
1a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
Abstract:
To explore the relationship between pharmacokinetic variables and enterococcal resistance to linezolid, a vancomycin-resistant strain whose mutant prevention concentration (MPC) exceeded the MIC by two fold was selected among six clinical isolates of Enterococcus faecium. The selected strain was exposed to simulated pharmacokinetics of twice-daily linezolid for five days. Mutants resistant to 2 × MIC of the antibiotic were enriched at ratios of the 24-h area under the concentration-time curve (AUC24) to the MIC of 15 and 30 h but not at 60 and 120 h. These observations could be explained by the different times when antibiotic concentrations exceed the MPC (T>MPC): 0 to 14, 63 and 100% of the dosing interval. Using the area under the bacterial mutant concentration-time curve (AUBCM) determined in this study and in previous work with other E. faecium strains (MPC/MIC 4), a strain-independent T>MPC relationship with mutant enrichment was established.
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