Routine Doses of Enrofloxacin Achieve Pharmacodynamic Target Likely to Treat Susceptible and Susceptible Dose-Dependent Bacterial Infections in Critically Ill Dogs.

Abstract

The fluoroquinolones, particularly enrofloxacin, are frequently used to treat life-threatening bacterial infections in small animal emergency and critical care practice. Achieving therapeutic plasma concentrations is essential for effective treatment, whereas inadequate concentrations select for resistance among Enterobacterales and Pseudomonas aeruginosa. We conducted a prospective observational study in 19 critically ill dogs to evaluate the pharmacokinetics (PK) of enrofloxacin and its active metabolite ciprofloxacin after administration of a standardized dosage (10 mg/kg IV q24 h). Plasma concentrations were measured at multiple time points using liquid chromatography-mass spectrometry, and PK modeling was performed to determine best-fit compartmental models. A 2-compartment model best described enrofloxacin PK. There was considerable between-dog variation in PK parameters, likely due to known challenges of drug dosing in critical illness. The percentage conversion of enrofloxacin to ciprofloxacin was lower than has previously been reported in healthy dogs. Pharmacodynamic analyses suggest that enrofloxacin administered at 10 mg/kg IV q24 h to critically ill dogs will likely result in effective treatment of infections by susceptible and susceptible dose-dependent bacteria, and achieved concentrations may be sufficient to reduce the risk of AMR development.