Elimination kinetics of ceftiofur hydrochloride in milk after an 8-day extended intramammary administration in healthy and infected cows.

Rongwei Han,Nan Zheng,Zhongna Yu,Jiaqi Wang,Songli Li,Jun Wang

doi:10.1371/journal.pone.0187261

Rongwei Han, Nan Zheng + Show 4 more

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https://doi.org/10.1371/journal.pone.0187261

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Abstract

Ceftiofur hydrochloride (CEF) is occasionally used for the intramammary (IMM) treatment of mastitis. This extralabel manner could result in a drug-residue violation of the milk. The objective of this study was to determine the elimination kinetics of IMM CEF in lactating dairy cattle. The pharmacokinetic profile of CEF after repeated IMM administration in nine healthy cows and nine Staphylococcus aureus infected cows was investigated, alongside determining the MICs of Staph. aureus field strains. The MIC 90 value for CEF in Staph. aureus field strains (n = 31) was 0.25 μg/mL. The t >MIC CEF values for low- production quarters were longer than those for high- and mid- production quarters. The results showed that ceftiofur was detected in milk up to 108 h after the last infusion in both healthy and infected cows. Cows with low milk production eliminate IMM drugs more slowly than cows with higher production. Our findings suggest that this extralabel use is not encouraged and a prudent use is recommended for mastitis therapy. The use of CEF should be reserved for infections where susceptibility tests indicate its efficacy and when alternatives are not available.

Highlights

Bovine mastitis remains a serious challenge to the worldwide dairy industry due to the high incidence rate, for example, of approximately 17% in the United States and 33% in China [1,2]
The use of 3rd and 4th generation cephalosporins has been revised in food producing species in Europe and USA and the advice of a prudent use has been reported to limit the spread of microbial resistance
The elimination kinetics of Ceftiofur hydrochloride (CEF) product administered every 24 h via IMM in every quarter at a dose of 125 mg for cow mastitis therapy use was demonstrated in this work

Summary

Introduction

Bovine mastitis remains a serious challenge to the worldwide dairy industry due to the high incidence rate, for example, of approximately 17% in the United States and 33% in China [1,2]. For bovine mastitis episodes caused by highly contagious staphylococci or streptococci, an intramammary infusion (IMM) of antimicrobial agents is usually used to treat clinical mastitis[4,5]. This treatment has been confirmed as having a good therapeutic effect as an antimicrobial agent, and it can attain and maintain an adequate and effective drug concentration at the site of infection in mammary tissue [6,7]. Ceftiofur hydrochloride (CEF) is approved only for intramuscular injection and for subcutaneous injection to treat respiratory infections and necrobacillosis in cows, and when administered according to the instructions, it does not result in drug concentrations in milk greater than the tolerance

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