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.

Introduction. Wild animals are one of the putative reservoirs of antimicrobial-resistant bacteria, but the significance of raccoon dogs remains to be investigated. Hypothesis. Raccoon dogs can be a reservoir of antimicrobial-resistant bacteria. Aim. This study aimed to explore the prevalence of antimicrobial resistance, mainly extended-spectrum cephalosporins resistance, in Escherichia coli isolates from faeces of 80 Japanese raccoon dogs in Kanagawa Prefecture, Japan. Methodology. All of the 80 faecal samples were streaked onto deoxycholate-hydrogen sulfate-lactose (DHL) and cefotaxime (CTX)-supplemented DHL (DHL-CTX) agars. Susceptibilities to ten antimicrobials were determined using the agar dilution method. Additionally, extended-spectrum β-lactamases (ESBLs) and AmpC-type β-lactamases (ABLs) were identified in addition to sequence types (STs), in ESC-resistant isolates by a polymerase chain reaction and sequencing. Results. Out of all the samples, 75 (93.8 %) and 20 (25.0 %) E. coli isolates were isolated by DHL and DHL-CTX agars, respectively. Significantly higher resistance rates to most of the drugs were found in DHL-CTX-derived isolates than DHL-derived isolates (P<0.01). Genetic analysis identified CTX-M-14 (n=6), CTX-M-2 (n=2), CTX-M-1 (n=1) and CTX-M-55 (n=1) as ESBLs, and CMY-2 (n=8) and DHA-1 (n=1) as ABLs in 20 DHL-CTX-derived isolates. Most of the detected STs were related to Japanese humans (i.e. ST10, ST58, ST69, ST131, ST357, ST648 and ST4038). Notably, this is the first report on ST69, ST131, ST155 and ST648, which are well-known international high-risk clones in Japanese raccoon dogs. Conclusion. Our findings underscore the need to understand the significance of raccoon dogs as an antimicrobial-resistant bacteria reservoir using one health approach.

20Extended-spectrum β-lactamase (ESBL)-producing bacteria are of great concern in companion 21 animals with urinary tract infections (UTIs). Because of its high safety and stability in the 22 presence of ESBLs, faropenem is assumed to be a candidate antimicrobial agent for canine UTIs 23 with ESBL-producing bacteria. This study was performed to investigate the urinary 24 pharmacokinetics and pharmacodynamics of faropenem administered at 5 mg/kg body weight in 25 six healthy dogs using an ex vivo model. Six UTI pathogenic strains of ESBL-producing 26 Escherichia coli (ESBL-EC) with the following faropenem minimum inhibitory concentrations 27 (MICs) were used: 1 µg/mL (n = 2), 2 µg/mL (n = 2), 4 µg/mL (n = 1), and 16 µg/mL (n = 1). 28Urine samples were obtained every 4 h for the first 12 h after faropenem administration for 29 measurement of the urine drug concentration and urinary bactericidal titers (UBTs). The urine 30 concentration of faropenem peaked at 0 to 4 h after administration, with a mean maximum 31 concentration of 584 μg/mL, and markedly decreased at 8 to 12 h (23 μg/mL). The median 32 UBTs for all tested ESBL-EC strains were highest at 0 to 4 h and then significantly decreased at 33 8 to 12 h. These findings indicate that administration of faropenem more than once daily is 34 recommended for the treatment of ESBL-EC-related UTIs in dogs. In addition, the median areas 35 under the UBT-time curves (AUBTs) were significantly inversely correlated with the 36 corresponding MICs for faropenem in the tested strains (P < 0.05). Notably, the median AUBTs 37 were significantly higher in ESBL-EC strains with an MIC of 1 µg/mL than in those with an 38 MIC of ≥4 µg/mL (P < 0.05). The present study serves as the basis of clinical application of 39 faropenem for ESBL-producing bacteria-related UTIs in dogs.3 41