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

• Main Authors: Augusto Matías Lorenzutti (Author), Manuel Ignacio San Andrés-Larrea (Author), Emilio Fernández-Varón (Author), María del Pilar Zarazaga (Author), Ana María Molina-López (Author), Juan Manuel Serrano-Rodríguez (Author)
• Format: Book
• Published: MDPI AG, 2021-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics10111290; 2079-6382
• Keywords: marbofloxacin; <i>S. aureus</i>; inoculum size; lactating goats; clinical mastitis; non-linear mixed effect modeling; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 10, Iss 11, p 1290 (2021)

<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 10⁵ and 10⁸ 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 EC₅₀ values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC₂₄/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.