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Tulathromycin is a semi-synthetic macrolide antimicrobial that has an important role in veterinary medicine for respiratory disease. The objective of the study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to examine the efficacy and determine an optimal dosage of tulathromycin intramuscular (IM) treatment against Haemophilus parasuis infection induced after intraperitoneal inoculation in neutropenic guinea pigs. The PKs of tulathromycin in serum and lung tissue after intramuscular administration at doses of 1, 10, and 20 mg/kg in H. parasuis-infected neutropenic guinea pigs were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The tulathromycin minimum inhibitory concentration (MIC) against H. parasuis was ~16 times lower in guinea pig serum (0.03 μg/mL) than in cation-adjusted Mueller-Hinton broth (CAMHB) (0.5 μg/mL). The ratio of the 168-h area under the concentration-time curve (AUC) to MIC (AUC168h/MIC) positively correlated with the in vivo antibacterial effectiveness of tulathromycin (R2 = 0.9878 in serum and R2 = 0.9911 in lung tissue). The computed doses to achieve a reduction of 2-log10 CFU/lung from the ratios of AUC72h/MIC were 5.7 mg/kg for serum and 2.5 mg/kg for lung tissue, which lower than the values of 13.2 mg/kg for serum and 8.9 mg/kg for lung tissue with AUC168h/MIC. In addition, using as objective a 2-log10 reduction and an AUC0−72h as the value of the PK/PD index could be more realistic. The results of this study could provide a solid foundation for the application of PK/PD models in research on macrolide antibiotics used to treat respiratory diseases.

Pseudomonas aeruginosa strains are potential pathogens that cause respiratory diseases in minks, and caused serious economic loss to mink breeding industry. In this study, we identified antimicrobial resistance and virulence genes in 125 P. aeruginosa isolates from mink in China from 2011 to 2020. The results showed at least one mutation in the gyrA (Thr83Val or Asp87Gly) and parC (Ser87 Leu) genes as well as single mutations in 56 isolates. At least 4-fold reductions in the fluoroquinolone minimum inhibitory concentration values were found when tested in the presence of PAβN in 23 isolates, while 44 isolates were positive for the extended spectrum β-lactamases and 15 antibiotic resistance genes were identified in this population with a prevalence between 1-32%, including qnrA, CTX-M-1G, ermB and C, cmlA, flor, catl, intl1, tetA, B, C, and D as well as sul1, 2, and 3 genes. Interestingly, one isolate carried ten resistance genes. Five virulence genes were detected, where exoS and algD were the most frequently detected (76.8%), which were followed by plcH (76%), lasB (73.6%), and pilB (31.2%). The isolates carrying the antibiotic resistance or virulence genes were genetically variable, suggesting a horizontal spread through the population. Hence, this study provides novel and important data on the resistance and pathogenicity of P. aeruginosa in farmed mink infections. These data provide important insights into the mechanism of fluoroquinolone resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in minks.