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Concentration-dependent enrichment of resistant Enterococcus faecium exposed to linezolid in an in vitro dynamic model.
Alieva, Kamilla N; Golikova, Maria V; Portnoy, Yury A; Dovzhenko, Svetlana A; Kobrin, Mikhail B; Zinner, Stephen H; Firsov, Alexander A.
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  • Alieva KN; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Golikova MV; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Portnoy YA; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Dovzhenko SA; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Kobrin MB; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Zinner SH; b Department of Medicine, Mount Auburn Hospital, Harvard Medical School , Cambridge , Massachusetts , USA.
  • Firsov AA; a Department of Pharmacokinetics and Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
J Chemother ; 30(6-8): 364-370, 2018.
Article en En | MEDLINE | ID: mdl-30663551
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enterococcus faecium / Linezolid Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Chemother Asunto de la revista: ANTINEOPLASICOS / TERAPIA POR MEDICAMENTOS Año: 2018 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enterococcus faecium / Linezolid Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Chemother Asunto de la revista: ANTINEOPLASICOS / TERAPIA POR MEDICAMENTOS Año: 2018 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Reino Unido