Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease

Abstract To design an antimicrobial treatment regimen for a bacterial disease, data on the drug pharmacodynamics (PD) against selected drug-susceptible strains of the pathogen are used. The regimen is applied across such strains in the field, assuming the PD parameter values remain the same. We used...

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Autores principales:	Xuesong Wen, Ronette Gehring, Jim E. Riviere, Brian V. Lubbers, Tara Nath Gaire, Bre’Anna Wyche, Breanna Fox, Victoria Quichocho, Victoriya V. Volkova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7175942a7a9345c482060723f665c418
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spelling	oai:doaj.org-article:7175942a7a9345c482060723f665c4182021-12-02T15:08:29ZVariation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease10.1038/s41598-018-28602-82045-2322https://doaj.org/article/7175942a7a9345c482060723f665c4182018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28602-8https://doaj.org/toc/2045-2322Abstract To design an antimicrobial treatment regimen for a bacterial disease, data on the drug pharmacodynamics (PD) against selected drug-susceptible strains of the pathogen are used. The regimen is applied across such strains in the field, assuming the PD parameter values remain the same. We used time-kill experiments and PD modeling to investigate the fluoroquinolone enrofloxacin PD against different isolates of two bovine respiratory disease pathogens: four Mannheimia haemolytica and three Pasteurella multocida isolates. The models were fitted as mixed-effects non-linear regression; the fixed-effects PD parameter values were estimated after accounting for random variation among experimental replicates. There was both inter- and intra- bacterial species variability in the PD parameters Hill-coefficient and E max (maximal decline of bacterial growth rate), with more variable PD responses among M. haemolytica than among P. multocida isolates. Moreover, the Hill-coefficient was correlated to the isolate’s maximal population growth rate in the absence of antimicrobial exposure (a.k.a. specific growth rate; Spearman’s ρ = 0.98, p-value = 0.003, n = 6 isolates excluding one outlier). Thus, the strain’s properties such as growth potential may impact its PD responses. This variability can have clinical implications. Modifying the treatment regimen depending on phenotypic properties of the pathogen strain causing disease may be a precision medicine approach.Xuesong WenRonette GehringJim E. RiviereBrian V. LubbersTara Nath GaireBre’Anna WycheBreanna FoxVictoria QuichochoVictoriya V. VolkovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xuesong Wen Ronette Gehring Jim E. Riviere Brian V. Lubbers Tara Nath Gaire Bre’Anna Wyche Breanna Fox Victoria Quichocho Victoriya V. Volkova Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
description	Abstract To design an antimicrobial treatment regimen for a bacterial disease, data on the drug pharmacodynamics (PD) against selected drug-susceptible strains of the pathogen are used. The regimen is applied across such strains in the field, assuming the PD parameter values remain the same. We used time-kill experiments and PD modeling to investigate the fluoroquinolone enrofloxacin PD against different isolates of two bovine respiratory disease pathogens: four Mannheimia haemolytica and three Pasteurella multocida isolates. The models were fitted as mixed-effects non-linear regression; the fixed-effects PD parameter values were estimated after accounting for random variation among experimental replicates. There was both inter- and intra- bacterial species variability in the PD parameters Hill-coefficient and E max (maximal decline of bacterial growth rate), with more variable PD responses among M. haemolytica than among P. multocida isolates. Moreover, the Hill-coefficient was correlated to the isolate’s maximal population growth rate in the absence of antimicrobial exposure (a.k.a. specific growth rate; Spearman’s ρ = 0.98, p-value = 0.003, n = 6 isolates excluding one outlier). Thus, the strain’s properties such as growth potential may impact its PD responses. This variability can have clinical implications. Modifying the treatment regimen depending on phenotypic properties of the pathogen strain causing disease may be a precision medicine approach.
format	article
author	Xuesong Wen Ronette Gehring Jim E. Riviere Brian V. Lubbers Tara Nath Gaire Bre’Anna Wyche Breanna Fox Victoria Quichocho Victoriya V. Volkova
author_facet	Xuesong Wen Ronette Gehring Jim E. Riviere Brian V. Lubbers Tara Nath Gaire Bre’Anna Wyche Breanna Fox Victoria Quichocho Victoriya V. Volkova
author_sort	Xuesong Wen
title	Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
title_short	Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
title_full	Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
title_fullStr	Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
title_full_unstemmed	Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
title_sort	variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7175942a7a9345c482060723f665c418
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Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease

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