Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against Staphylococcus aureus Isolated from Caprine Clinical Mastitis

Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies de...

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Autores principales:	Augusto Matías Lorenzutti, Manuel Ignacio San Andrés-Larrea, Emilio Fernández-Varón, María del Pilar Zarazaga, Ana María Molina-López, Juan Manuel Serrano-Rodríguez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	marbofloxacin <i>S. aureus</i> inoculum size lactating goats clinical mastitis non-linear mixed effect modeling Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ea2ae575b35f4df2bc20960962fbbefc
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spelling	oai:doaj.org-article:ea2ae575b35f4df2bc20960962fbbefc2021-11-25T16:22:09ZEffects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis10.3390/antibiotics101112902079-6382https://doaj.org/article/ea2ae575b35f4df2bc20960962fbbefc2021-10-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1290https://doaj.org/toc/2079-6382<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against <i>S. aureus</i>. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on <i>S. aureus</i> isolated from mastitis goats’ milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller–Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 10<sup>5</sup> and 10<sup>8</sup> CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC<sub>50</sub> values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC<sub>24</sub>/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60–180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating <i>S. aureus</i> in lactating goats.Augusto Matías LorenzuttiManuel Ignacio San Andrés-LarreaEmilio Fernández-VarónMaría del Pilar ZarazagaAna María Molina-LópezJuan Manuel Serrano-RodríguezMDPI AGarticlemarbofloxacin<i>S. aureus</i>inoculum sizelactating goatsclinical mastitisnon-linear mixed effect modelingTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1290, p 1290 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	marbofloxacin <i>S. aureus</i> inoculum size lactating goats clinical mastitis non-linear mixed effect modeling Therapeutics. Pharmacology RM1-950
spellingShingle	marbofloxacin <i>S. aureus</i> inoculum size lactating goats clinical mastitis non-linear mixed effect modeling Therapeutics. Pharmacology RM1-950 Augusto Matías Lorenzutti Manuel Ignacio San Andrés-Larrea Emilio Fernández-Varón María del Pilar Zarazaga Ana María Molina-López Juan Manuel Serrano-Rodríguez Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
description	<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against <i>S. aureus</i>. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on <i>S. aureus</i> isolated from mastitis goats’ milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller–Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 10<sup>5</sup> and 10<sup>8</sup> CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC<sub>50</sub> values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC<sub>24</sub>/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60–180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating <i>S. aureus</i> in lactating goats.
format	article
author	Augusto Matías Lorenzutti Manuel Ignacio San Andrés-Larrea Emilio Fernández-Varón María del Pilar Zarazaga Ana María Molina-López Juan Manuel Serrano-Rodríguez
author_facet	Augusto Matías Lorenzutti Manuel Ignacio San Andrés-Larrea Emilio Fernández-Varón María del Pilar Zarazaga Ana María Molina-López Juan Manuel Serrano-Rodríguez
author_sort	Augusto Matías Lorenzutti
title	Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
title_short	Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
title_full	Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
title_fullStr	Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
title_full_unstemmed	Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis
title_sort	effects of growth medium and inoculum size on pharmacodynamics activity of marbofloxacin against <i>staphylococcus aureus</i> isolated from caprine clinical mastitis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ea2ae575b35f4df2bc20960962fbbefc
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Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against <i>Staphylococcus aureus</i> Isolated from Caprine Clinical Mastitis

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