Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum β-lactamase-producing Escherichia coli with canine ex vivo modelling: a pilot study

• Published in: Access microbiology 2019-03, Vol.1 (1), p.e000004-e000004
• Main Authors: Harada, Kazuki, Shimizu, Takae, Miyashita, Naoki, Hikasa, Yoshiaki
• Format: Article
• Language: English
• Subjects: Short Communication
• ISSN: 2516-8290; 2516-8290
• DOI: 10.1099/acmi.0.000004

This study was carried out to investigate the urinary pharmacokinetics and pharmacodynamics of faropenem administered orally at 5 mg kg −1 in six healthy dogs to assess the efficacy of the drug for canine urinary tract infections (UTIs) with extended-spectrum β -lactamase (ESBL)-producing bacteria. Six strains of ESBL-producing Escherichia coli (ESBL-EC) with the following faropenem minimum inhibitory concentrations (MICs) were used: 1 µg ml −1 ( n =2), 2 µg ml −1 ( n =2), 4 µg ml −1 ( n =1) and 16 µg ml −1 ( n =1). Urine samples were obtained every 4 h for the first 12 h after administration to measure urinary drug concentration and urinary bactericidal titres (UBTs). Both the urine concentration of faropenem and the UBTs for all tested strains peaked at 0–4 h after administration, and decreased markedly at 8–12 h. The mean urinary concentration of faropenem at 8–12 h (23±5.2 µg ml −1 ) exceeded the MIC of 1 µg ml −1 by fourfold, which is required to inhibit the growth of 90  % of ESBL-EC. These findings indicate that faropenem administered twice daily at a dose of 5 mg kg −1 is acceptable for the treatment of most dogs with ESBL-EC-related UTIs.