AUTHOR=Lei Zhixin , Liu Qianying , Yang Bing , Khaliq Haseeb , Cao Jiyue , He Qigai 

TITLE=PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00856

DOI=10.3389/fphar.2017.00856

ISSN=1663-9812

ABSTRACT=<p>Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the <italic>ex vivo</italic> activity of marbofloxacin against <italic>Streptococcus suis</italic> in pig serum, as well as the optimal dosages scheme for avoiding the fluoroquinolone resistance development. A single dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and serum samples were collected during the next 72 h. Serum marbofloxacin content was determined by high-performance liquid chromatography. We estimated the C<sub>max</sub> (6.28 μg/ml), AUC<sub>0-24 h</sub> (60.30 μg.h/ml), AUC<sub>0-∞</sub> (88.94 μg.h/ml), T<sub>1/2ke,</sub> (12.48 h), T<sub>max</sub> (0.75 h) and Cl<sub>b</sub> (0.104 L/h) of marbofloxacin in pigs, as well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral administration. We also determined the pharmacodynamic of marbofloxacin against 134 <italic>Streptococcus suis</italic> strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC<sub>90</sub> of 1 μg/ml. HB2, a virulent, serotype 2 isolate of <italic>SS</italic>, was selected for having antibacterial activity in TSB and serum to marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 μg/ml in TSB, 2 μg/ml in serum), minimum bactericidal concentration (MBC, 4 μg/ml in TSB, 4 μg/ml in serum), and mutant prevention concentration (2.56 μg/ml in TSB) for marbofloxacin against <italic>Streptococcus suis</italic> (HB2). In serum, by inhibitory sigmoid E<sub>max</sub> modeling, the AUC<sub>0-24h</sub>/MIC values for marbofloxacin against HB2 were 25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing <italic>Streptococcus suis</italic> were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36 (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16 (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a 90% target attainment ratio. The data presented here provides optimized dosage information for clinical use; however, these predicted dosages should also be validated in clinical practice.</p>