International Journal of Molecular Sciences (Jan 2024)

Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs

  • Mizuki Kusumoto,
  • Makoto Jitsuiki,
  • Tomoki Motegi,
  • Kazuki Harada

DOI
https://doi.org/10.3390/ijms25021105
Journal volume & issue
Vol. 25, no. 2
p. 1105

Abstract

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Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales-producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs using a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs were intravenously administered at a bolus dose of FMX (40 mg/kg body weight). Serum concentrations of FMX were calculated with high-performance liquid chromatography-tandem mass spectrometry, and then applied to determine PK indices based on a non-compartmental model. The cumulative fraction of response (CFR) was estimated based on the dissemination of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. From the results, the dosage regimens of 40 mg/kg every 6 and 8 h were estimated to attain a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. By contrast, all regimens had a CFR of Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX every 6 and 8 h can be a non-carbapenem treatment for canine infections of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those of ESBL-producing Enterobacter cloacae.

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