Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing <i>Escherichia coli</i> with Canine Ex Vivo Modeling: A Pilot Study

Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to ass...

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Bibliographic Details
Main Authors: Kazuki Harada, Takae Shimizu, Koji Kawaguchi, Takeshi Furuhashi, Genki Ishihara
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/9/5/230
Description
Summary:Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to assess its efficacy for canine urinary tract infections (UTIs) caused by ESBL-producing bacteria. Four strains of ESBL-producing <i>Escherichia coli</i> (ESBL-EC) characterized by fosfomycin minimum inhibitory concentrations (MICs) of 0.5, 1, 2, and 32 µg/mL were used. Urine samples for the measurement of urinary drug concentrations and urinary bactericidal titers (UBTs) were obtained after drug administration. The urinary concentrations (µg/mL, mean ± SE) were 1348.2 ± 163.5, 1191.6 ± 260.2, and 661.1 ± 190.4 at 0–4, 4–8, and 8–12 h, respectively, after drug administration. The mean urinary area under the curve during the test period (AUC<sub>0</sub><sub>–</sub><sub>12</sub>) of fosfomycin was estimated to be 12,803.8 µg·h/mL. The UBTs for all tested strains fluctuated closely with urine concentration during the test period (r = 0.944–1.000), and the area under the UBT-versus-time curve correlated with the urinary AUC/MIC of each strain (r = 0.991). According to the optimal urinary PK/PD target value, fosfomycin at 80 mg/kg twice daily may be suitable for the treatment of canine UTIs caused by ESBL-EC presenting MIC ≤ 128 µg/mL.
ISSN:2079-6382