PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Zhixin Lei; Qianying Liu; Bing Yang; Haseeb Khaliq; Jiyue Cao; Qigai He

doi:10.3389/fphar.2017.00856

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Front Pharmacol. 2017 Nov 20:8:856. doi: 10.3389/fphar.2017.00856. eCollection 2017.

Authors

Zhixin Lei^{1

2}, Qianying Liu^{1

2}, Bing Yang^{1

2}, Haseeb Khaliq¹, Jiyue Cao^{1

2}, Qigai He³

Affiliations

¹ Department of Veterinary Pharmacology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
² National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
³ State Key Laboratory of Agriculture Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Abstract

Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the ex vivo activity of marbofloxacin against Streptococcus suis 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_max (6.28 μg/ml), AUC_{0-24 h} (60.30 μg.h/ml), AUC_0-∞ (88.94 μg.h/ml), T_1/2ke, (12.48 h), T_max (0.75 h) and Cl_b (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 Streptococcus suis strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC₉₀ of 1 μg/ml. HB2, a virulent, serotype 2 isolate of SS, 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 Streptococcus suis (HB2). In serum, by inhibitory sigmoid E_max modeling, the AUC_0-24h/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 Streptococcus suis 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.

Keywords: Streptococcus suis; fluoroquinolone; marbofloxacin; optimal dosage; pharmacodynamic; pharmacokinetic.