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A novel parameter to predict the effects of antibiotic combinations on the development of Staphylococcus aureus resistance: in vitro model studies at subtherapeutic daptomycin and rifampicin exposures.
Golikova, Maria V; Strukova, Elena N; Portnoy, Yury A; Dovzhenko, Svetlana A; Kobrin, Mikhail B; Zinner, Stephen H; Firsov, Alexander A.
Afiliación
  • Golikova MV; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Strukova EN; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Portnoy YA; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Dovzhenko SA; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Kobrin MB; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
  • Zinner SH; b Department of Medicine , Mount Auburn Hospital, Harvard Medical School , Cambridge , MA , USA.
  • Firsov AA; a Department of Pharmacokinetics & Pharmacodynamics , Gause Institute of New Antibiotics , Moscow , Russia.
J Chemother ; : 1-9, 2019 Jul 17.
Article en En | MEDLINE | ID: mdl-31314704
The search for optimal predictors of anti-mutant effects remains a pressing problem in studies of antibiotic-associated bacterial resistance. To relate the emergence of bacterial resistance with the antibiotic mutant prevention concentration (MPC), a novel integral parameter - the area around the resistance threshold, i.e. MPC level (AAMPC) is proposed. The AAMPC is the algebraic sum of the area under the antibiotic concentration-time curve that is above the MPC (positive area) and the area above the concentration-time curve that is under the MPC (negative area). To assess the predictive performance of AAMPC, the enrichment of resistant Staphylococcus aureus was studied by simulating treatment with daptomycin and rifampicin alone and in combination in an in vitro dynamic model. The enhanced anti-mutant effects of the antibiotic combinations were due to lowering the negative 24-h AAMPCs. These findings suggest that a novel MPC-related parameter is a reliable predictor of mutant enrichment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Chemother Asunto de la revista: ANTINEOPLASICOS / TERAPIA POR MEDICAMENTOS Año: 2019 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 Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Chemother Asunto de la revista: ANTINEOPLASICOS / TERAPIA POR MEDICAMENTOS Año: 2019 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Reino Unido