Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy

Abstract The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to cl...

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Autores principales:	Nayara Helisandra Fedrigo, Danielle Rosani Shinohara, Josmar Mazucheli, Sheila Alexandra Belini Nishiyama, Floristher Elaine Carrara-Marroni, Frederico Severino Martins, Peijuan Zhu, Mingming Yu, Sherwin Kenneth B. Sy, Maria Cristina Bronharo Tognim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1982216eca7d4de6a53da43ee6b273c2
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spelling	oai:doaj.org-article:1982216eca7d4de6a53da43ee6b273c22021-12-02T15:56:41ZPharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy10.1038/s41598-021-90709-22045-2322https://doaj.org/article/1982216eca7d4de6a53da43ee6b273c22021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90709-2https://doaj.org/toc/2045-2322Abstract The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.Nayara Helisandra FedrigoDanielle Rosani ShinoharaJosmar MazucheliSheila Alexandra Belini NishiyamaFloristher Elaine Carrara-MarroniFrederico Severino MartinsPeijuan ZhuMingming YuSherwin Kenneth B. SyMaria Cristina Bronharo TognimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nayara Helisandra Fedrigo Danielle Rosani Shinohara Josmar Mazucheli Sheila Alexandra Belini Nishiyama Floristher Elaine Carrara-Marroni Frederico Severino Martins Peijuan Zhu Mingming Yu Sherwin Kenneth B. Sy Maria Cristina Bronharo Tognim Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
description	Abstract The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.
format	article
author	Nayara Helisandra Fedrigo Danielle Rosani Shinohara Josmar Mazucheli Sheila Alexandra Belini Nishiyama Floristher Elaine Carrara-Marroni Frederico Severino Martins Peijuan Zhu Mingming Yu Sherwin Kenneth B. Sy Maria Cristina Bronharo Tognim
author_facet	Nayara Helisandra Fedrigo Danielle Rosani Shinohara Josmar Mazucheli Sheila Alexandra Belini Nishiyama Floristher Elaine Carrara-Marroni Frederico Severino Martins Peijuan Zhu Mingming Yu Sherwin Kenneth B. Sy Maria Cristina Bronharo Tognim
author_sort	Nayara Helisandra Fedrigo
title	Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
title_short	Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
title_full	Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
title_fullStr	Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
title_full_unstemmed	Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
title_sort	pharmacodynamic evaluation of suppression of in vitro resistance in acinetobacter baumannii strains using polymyxin b-based combination therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1982216eca7d4de6a53da43ee6b273c2
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Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy

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