In vitro and ex vivo antibacterial activity of levofloxacin against Pasteurella multocida and Escherichia coli isolated from rabbits (Oryctolagus cuniculus) – A preliminary study

Funding Information: This study was funded from the Riga Stradins University doctoral grant. Funding Information: The authors sincerely thank Dr. Aneliya Milanova (Trakia University, Bulgaria) and Dr. Cristina Vercelli (University of Turin, Italy) for their scientific advice and help. Publisher Copyright: © 2023 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.Levofloxacin veterinary formulations are available in Argentina, China and India for the use in dogs, cattle, pig and sheep, but not currently in the rabbit. Only the extra-label use in rabbits is possible. Levofloxacin is not labelled for veterinary use in the EU or the USA. The activity of levofloxacin against rabbit pathogens Pasteurella multocida (P. multocida) and Escherichia coli (E. coli) was evaluated. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined in broth and serum for 10 P. multocida isolates and 5 E. coli isolates from rabbits. One isolate of each bacterial species was used for the time-killing curve study in vitro and ex vivo. In vitro AUC24/MIC ratios were used for building the inhibitory pharmacodynamic Imax model. The P. multocida MIC were 0.008–0.5 μg/mL, MBC – 0.015–0.5 μg/mL. Escherichia coli MIC was 0.008–0.03 μg/mL and MBC – 0.03–0.25 μg/mL. Bacterial counts were reduced to the limit of detection after 24 h with levofloxacin concentrations of 2 MIC and higher. All serum samples from rabbits treated with levofloxacin eliminated the bacteria within 24 h. AUC24/MIC ratios for bacteriostatic, bactericidal and bacterial elimination effects for P. multocida and E. coli isolates were 21, 29 and 75 h and 27, 32 and 60 h, respectively. Proposed daily doses against P. multocida (MIC = 0.015 μg/mL) and E. coli (MIC = 0.03 μg/mL) isolates were calculated as ≤0.91 and ≤1.43 mg/kg, respectively. Fluoroquinolones are categorized by WHO as ‘highest priority critically important antimicrobials’. Considering the increasing importance of antimicrobial stewardship, antimicrobials from a lower importance category that are active against the isolate of interest should be used in preference to fluoroquinolones. Fluoroquinolone use in veterinary medicine should be based on antimicrobial susceptibility testing in order to mitigate the risk to public health and prevent the spread of bacterial resistance.Peer reviewe

Doxycycline pharmacokinetics in geese

Funding Information: This work was supported by University of Pisa (ex 60%). The authors acknowledge ThothPro (Gdansk, Poland) for supplying the software used for the pharmacokinetic analysis. The authors are grateful to Mr. Zbigniew Kołodziej (Majątek Rutka, Puchaczow, Poland) for assistance conducting animal experiment and for supplying animals and facilities. The authors sincerely thank Dr. Victoria Llewelyn (Flinders University, Australia) for the scientific and English editing of the manuscript. Funding Information: This work was supported by University of Pisa (ex 60%). The authors acknowledge ThothPro (Gdansk, Poland) for supplying the software used for the pharmacokinetic analysis. The authors are grateful to Mr. Zbigniew Ko?odziej (Maj?tek Rutka, Puchaczow, Poland) for assistance conducting animal experiment and for supplying animals and facilities. The authors sincerely thank Dr. Victoria Llewelyn (Flinders University, Australia) for the scientific and English editing of the manuscript. Publisher Copyright: © 2021 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley &Sons Ltd.The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations have been performed to investigate the predicted plasma concentration after either a 10 or 20 mg/kg daily administration repeated consecutively for 5 days. Ten geese were enrolled in a two-phase cross-over study with a washout period of two weeks. All animals were treated intravenously and orally with doxycycline, and blood samples were collected up to 48 h after drug administration. Sample analysis was performed using a validated HPLC-UV method. A non-compartmental approach was used to evaluate the pharmacokinetic parameters of the drug. A long elimination half-life was observed (13 h). The area under the curve was statistically different between the two treatments, with the oral bioavailability being moderate (43%). The pharmacokinetic/pharmacodynamic index (%T>MIC) during the 48 h treatment period in the present study (71%) suggests that doxycycline appears to have therapeutic efficacy against some Mycoplasma species in the goose. The multiple-dose simulations showed a low accumulation index. A dosage of 10 mg/kg/day for 5 days seemed to be adequate for a good therapeutic efficacy without reaching unnecessarily high plasma concentrations.publishersversionPeer reviewe