Mycoplasma hyopneumoniae is the major pathogen causing enzootic pneumonia in\npigs. M. hyopneumoniae infection can lead to considerable economic losses in the pig-breeding\nindustry. Here, this study established a first-order absorption, one-compartment model to study\nthe relationship between the pharmacokinetics/pharmacodynamics (PK/PD) index of tilmicosin\nagainst M. hyopneumoniae in vitro. We simulated different drug concentrations of timicosin in the\nfluid lining the lung epithelia of pigs. The minimum inhibitory concentration (MIC) of tilmicosin\nagainst M. hyopneumoniae with an inoculum of 106 CFU/mL was 1.6 microg/mL using the microdilution\nmethod. Static timeâ??kill curves showed that if the drug concentration > 1 MIC, the antibacterial\neffect showed different degrees of inhibition. At 32 MIC, the amount of bacteria decreased by\n3.16 log10 CFU/mL, thereby achieving a mycoplasmacidal effect. The M. hyopneumoniae count was\nreduced from 3.61 to 5.11 log10 CFU/mL upon incubation for 96 h in a dynamic model with a dose\nof 40â??200 mg, thereby achieving mycoplasmacidal activity. The area under the concentration-time\ncurve over 96 h divided by the MIC (AUC0â??96 h/MIC) was the best-fit PK/PD parameters for\npredicting the antibacterial activity of tilmicosin against M. hyopneumoniae (R2 = 0.99), suggesting\nthat tilmicosin had concentration-dependent activity. The estimated value for AUC0â??96 h/MIC for\n2log10 (CFU/mL) reduction and 3log10 (CFU/mL) reduction from baseline was 70.55 h and 96.72 h.\nFour M. hyopneumoniae strains (M1â??M4) with reduced sensitivity to tilmicosin were isolated from the\nfour dose groups. The susceptibility of these strains to tylosin, erythromycin and lincomycin was also\nreduced significantly. For sequencing analyses of 23S rRNA, an acquired A2058G transition in region\nV was found only in resistant M. hyopneumoniae strains (M3, M4). In conclusion, in an in vitro model,\nthe effect of tilmicosin against M. hyopneumoniae was concentration-dependent and had a therapeutic\neffect. These results will help to design the optimal dosing regimen for tilmicosin in M. hyopneumoniae\ninfection, and minimize the emergence of resistant bacteria.
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