Next Article in Journal
Oxytocin Receptor Gene Polymorphism in Lactating Dogs
Next Article in Special Issue
Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep
Previous Article in Journal
Chitosan Treatment of E-11 Cells Modulates Transcription of Nonspecific Immune Genes and Reduces Nodavirus Capsid Protein Gene Expression
Previous Article in Special Issue
Comparison of Short- versus Long-Course Antimicrobial Therapy of Uncomplicated Bacterial Pneumonia in Dogs: A Double-Blinded, Placebo-Controlled Pilot Study
 
 
Article

PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci

1
Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Córdoba X5016DHK, Argentina
2
Department of Nursing, Pharmacology and Physiotherapy, Pharmacology Area, Faculty of Veterinary Medicine, Universidad de Córdoba, 14071 Córdoba, Spain
3
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editors: Ana M. Sahagun and Raquel Diez
Animals 2021, 11(11), 3098; https://doi.org/10.3390/ani11113098
Received: 5 August 2021 / Revised: 24 October 2021 / Accepted: 25 October 2021 / Published: 29 October 2021
Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved to treat mastitis in animals. Since the efficacy of an antimicrobial is related with its concentration in the site of infection, and the latter depends of dose and biological processes that determine the distribution of the antimicrobial in different tissues and secretions, the objectives of this study were to evaluate the efficacy of a dose regimen of marbofloxacin (10 mg/kg/24 h) administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci, by an evaluation of the concentrations of marbofloxacin achieved in blood and milk over time (called pharmacokinetics), and characterizing the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk, by time kill assays, in order to determine the concentrations of marbofloxacin related with an adequate bacterial count reduction (measured by efficacy index AUC/MIC). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in a microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that marbofloxacin concentrations needed for antimicrobial efficacy were higher in goat milk compared with Mueller Hinton broth. Bacterial resistance to antimicrobials is a serious problem, since marbofloxacin is considered a critically important antimicrobial, and its rational and prudent use could extend its utility over time.
Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth. View Full-Text
Keywords: marbofloxacin; pharmacokinetic; pharmacodynamic; mastitis; goats; coagulase negative staphylococci marbofloxacin; pharmacokinetic; pharmacodynamic; mastitis; goats; coagulase negative staphylococci
Show Figures

Figure 1

MDPI and ACS Style

Lorenzutti, A.M.; Vico, J.P.; Serrano-Rodríguez, J.M.; Himelfarb, M.A.; Andrés-Larrea, M.I.S.; Lucas-Burneo, J.J.d.; Litterio, N.J. PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci. Animals 2021, 11, 3098. https://doi.org/10.3390/ani11113098

AMA Style

Lorenzutti AM, Vico JP, Serrano-Rodríguez JM, Himelfarb MA, Andrés-Larrea MIS, Lucas-Burneo JJd, Litterio NJ. PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci. Animals. 2021; 11(11):3098. https://doi.org/10.3390/ani11113098

Chicago/Turabian Style

Lorenzutti, Augusto Matías, Juan Pablo Vico, Juan Manuel Serrano-Rodríguez, Martín Alejandro Himelfarb, Manuel Ignacio San Andrés-Larrea, José Julio de Lucas-Burneo, and Nicolás Javier Litterio. 2021. "PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci" Animals 11, no. 11: 3098. https://doi.org/10.3390/ani11113098

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop