AUTHOR=Zhou Yu-Feng , Peng Hui-Min , Bu Ming-Xiao , Liu Ya-Hong , Sun Jian , Liao Xiao-Ping 

TITLE=Pharmacodynamic Evaluation and PK/PD-Based Dose Prediction of Tulathromycin: A Potential New Indication for Streptococcus suis Infection

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00684

DOI=10.3389/fphar.2017.00684

ISSN=1663-9812

ABSTRACT=Tulathromycin is the first member of the triamilide antimicrobial drugs that has been registered in more than 30 countries. The goal of this study is to provide a potential new indication of tulathromycin for Streptococcus suis infections. We investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin against experimental S. suis infection in piglets. Tulathromycin demonstrated a relatively long elimination half-life (74.1 h) and a mean residence time of 97.6 h after a single intramuscular administration. The minimal inhibitory (MIC) and bactericidal (MBC) concentrations in serum were markedly lower than those in broth culture, with MHB/serum ratios of 40.3 and 11.4, respectively. The post-antibiotic effects (PAE) were at 1.27 h (1×MIC) and 2.03 h (4×MIC) and the post-antibiotic effect sub-MIC (PA-SME) values ranged from 2.47 to 3.10 h. The ratio of the area under the concentration-time curve divided by the MIC (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of tulathromycin (R2=0.9711). The calculated AUC12h/MIC ratios in serum required to produce the net bacterial stasis, 1-log10 and 2-log10 killing activities were 9.62, 18.9 and 32.7, respectively. Based on the results of Monte Carlo simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be effective, achieving for a bacteriostatic activity against S. suis infection over 5 days period. Tulathromycin may become a potential option for the treatment of S. suis infections.