Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing.
Equine Vet J
; 53(5): 1047-1055, 2021 Sep.
Article
in En
| MEDLINE
| ID: mdl-33169427
ABSTRACT
BACKGROUND:
Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses.OBJECTIVES:
To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. STUDYDESIGN:
A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings.METHODS:
Horses (n = 131) received MBX intravenously at doses of either 2 or 10 mg/kg BW. They were richly sampled (five or six samples per horse). A population model was built to generate a virtual population of 5000 MBX disposition curves by Monte Carlo simulations (MCS) over 24 hours. The selected PK/PD index was the ratio of Area Under the free plasma concentration-time Curve divided by the MIC (fAUC/MIC). The PK/PDCO , which is the highest MIC for which 90% of horses can achieve an a priori selected critical value for the numerical value of the PK/PD index, was established for Gram-positive and Gram-negative bacteria for a dose of 2 mg/kg.RESULTS:
The PK/PDCO of MBX in horses was 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens. MBX MICs determined by broth microdilution for 54 Escherichia coli and 189 Streptococcus equi isolates are reported. MAINLIMITATION:
No clinical data are taken into account in the determination of a PK/PDco .CONCLUSION:
The computed PK/PDco predicts that MBX may be efficacious in horses to treat infections associated with Enterobacteriaceae but unlikely to those involving Staphylococcus aureus or Streptococcus equi.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anti-Infective Agents
/
Anti-Bacterial Agents
Type of study:
Prognostic_studies
/
Systematic_reviews
Limits:
Animals
Language:
En
Journal:
Equine Vet J
Year:
2021
Document type:
Article
Affiliation country:
France
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA