Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii

© 2020 The Authors.

Detalles Bibliográficos
Autores: Aranzana-Climent, V., Buyck, J. M., Smani, Younes, Pachón, Jerónimo, Marchand, S., Couet, W., Grégoire, N.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/238083
Acceso en línea:http://hdl.handle.net/10261/238083
Access Level:acceso abierto
Palabra clave:Acinetobacter baumannii
Combinations
GPDI
Minocycline
PK/PD modelling
Polymyxin B
id ES_026e4cf63d5d996c5ecb2b4ce7ca3a5b
oai_identifier_str oai:digital.csic.es:10261/238083
network_acronym_str ES
network_name_str España
repository_id_str
spelling Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumanniiAranzana-Climent, V.Buyck, J. M.Smani, YounesPachón, JerónimoMarchand, S.Couet, W.Grégoire, N.Acinetobacter baumanniiCombinationsGPDIMinocyclinePK/PD modellingPolymyxin B© 2020 The Authors.[Objectives]: To expand on previous reports of synergy between polymyxin B (PMB) and minocycline (MIN) against Acinetobacter baumannii; and to gain insight into the qualitative and quantitative determinants of their synergy.[Methods]: A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed on the basis of data from in vitro time-kill experiments with determination of resistant bacterial count to describe the effects of PMB and MIN alone and in combination. The model was enriched by complementary experiments providing information on the characteristics of the resistant subpopulation.[Results]: The model successfully described the data and made possible quantification of the strength of interaction between the two drugs and formulation of hypotheses about the mechanisms of the observed interaction. The effect of the combination was driven by MIN, with PMB acting as an helper drug; simulations at clinically achievable concentrations showed that 1.5 mg/L MIN +0.2 mg/L PMB is expected to produce sustained killing over 30 hours, while 0.3 mg/L MIN +1 mg/L PMB is met by bacterial regrowth. Interaction equations showed that maximal synergy is reached for PMB concentrations ≥0.1 mg/L and MIN concentrations ≥1 mg/L.[Conclusions]: Semi-mechanistic PK/PD modelling was used to investigate the quantitative determinants of synergy between PMB and MIN on a PMB-resistant A. baumannii strain. The developed model, improving on usual study techniques, showed asymmetry in the drug interaction, as PMB acted mostly as a helper to MIN, and provided simulations as a tool for future studies.We thank L. Friberg (Uppsala University) for input related to model building and E. Marquizeau (Université de Poitiers) for technical support.ElsevierUppsala UniversityUniversité de PoitiersConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/238083reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.cmi.2020.01.017Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2380832026-05-22T06:33:51Z
dc.title.none.fl_str_mv Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
title Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
spellingShingle Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
Aranzana-Climent, V.
Acinetobacter baumannii
Combinations
GPDI
Minocycline
PK/PD modelling
Polymyxin B
title_short Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
title_full Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
title_fullStr Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
title_full_unstemmed Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
title_sort Semi-mechanistic PK/PD modelling of combined polymyxin B and minocycline against a polymyxin-resistant strain of Acinetobacter baumannii
dc.creator.none.fl_str_mv Aranzana-Climent, V.
Buyck, J. M.
Smani, Younes
Pachón, Jerónimo
Marchand, S.
Couet, W.
Grégoire, N.
author Aranzana-Climent, V.
author_facet Aranzana-Climent, V.
Buyck, J. M.
Smani, Younes
Pachón, Jerónimo
Marchand, S.
Couet, W.
Grégoire, N.
author_role author
author2 Buyck, J. M.
Smani, Younes
Pachón, Jerónimo
Marchand, S.
Couet, W.
Grégoire, N.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Uppsala University
Université de Poitiers
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Acinetobacter baumannii
Combinations
GPDI
Minocycline
PK/PD modelling
Polymyxin B
topic Acinetobacter baumannii
Combinations
GPDI
Minocycline
PK/PD modelling
Polymyxin B
description © 2020 The Authors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/238083
url http://hdl.handle.net/10261/238083
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.cmi.2020.01.017
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869402654539513856
score 15,811543

Similares en LA Referencia