tiamulin and danofloxacin

Mycoplasma hyopneumoniae is the major pathogenic microorganism causing enzootic pneumonia in pigs. With increasing resistance of M. hyopneumoniae to conventional antibiotics, treatment is becoming complicated. Herein, we investigated the mutant selection window (MSW) of doxycycline, tylosin, danofloxacin, tiamulin, and valnemulin for treating the M. hyopneumoniae type strain (ATCC 25934) to determine the likelihood of promoting resistance with continued use of these antibiotics. Minimum inhibitory concentration (MIC) values against M. hyopneumoniae were determined for each antimicrobial agent based on microdilution broth and agar dilution methods (bacterial numbers ranged from 105 colony-forming units (CFU)/mL to 109 CFU/mL). The minimal concentration inhibiting colony formation by 99% (MIC99) and the mutant prevention concentration (MPC) were determined by the agar dilution method with three inoculum sizes. Antimicrobial killing was determined based on MIC99 and MPC values for all five agents. MIC values ranged from 0.001 to 0.25 μg/mL based on the microdilution broth method, and from 0.008 to 1.0 μg/mL based on the agar dilution method. MPC values ranged from 0.0016 to 10.24 μg/mL. MPC/MIC99 values were ordered tylosin > doxycycline > danofloxacin > tiamulin > valnemulin. MPC achieved better bactericidal action than MIC99. Based on pharmacodynamic analyses, danofloxacin, tylosin, and doxycycline are more likely to select resistant mutants than tiamulin and valnemulin.

Topics: Anti-Bacterial Agents; Diterpenes; Doxycycline; Fluoroquinolones; Kinetics; Microbial Sensitivity Tests; Microbial Viability; Mutation; Mycoplasma hyopneumoniae; Tylosin

Biomarkers of infection were screened for their possible role as evaluators of antibiotic treatment in an aerosol infection model of porcine pneumonia caused by Actinobacillus pleuropneumoniae (Ap). Following infection of 12 pigs, clinical signs of pneumonia developed within 20 h, whereafter the animals received a single dose of either danofloxacin (2.5mg/kg) or tiamulin (10 mg/kg). To test the discriminative properties of the biomarkers, the dosage regimens were designed with an expected difference in therapeutic efficacy in favour of danofloxacin. Accordingly, the danofloxacin-treated pigs recovered clinically within 24h after treatment, whereas tiamulin-treated animals remained clinically ill until the end of the study, 48 h after treatment. A similar picture was seen for the biomarkers of infection. During the infection period, plasma C-reactive protein (CRP), interleukin-6 and haptoglobin increased, whereas plasma zinc, ascorbic acid and alpha-tocopherol decreased. In the danofloxacin-treated animals, CRP, interleukin-6, zinc, ascorbic acid and alpha-tocopherol reverted significantly towards normalisation within 24h of treatment. In contrast, signs of normalisation were absent (CRP, zinc and ascorbic acid) or less marked (interleukin-6 and alpha-tocopherol) in the tiamulin-treated animals. Plasma haptoglobin remained elevated throughout the study in both groups. This indicates that CRP, zinc, ascorbic acid and to a lesser extent interleukin-6 and alpha-tocopherol might be used to evaluate antibiotic treatment of acute Ap-infection in pigs. The present model provides a valuable tool in the evaluation of antibiotic treatments, offering the advantage of clinical and pathological examinations combined with the use of biochemical infection markers.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; alpha-Tocopherol; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Ascorbic Acid; Biomarkers; C-Reactive Protein; Diterpenes; Fluoroquinolones; Haptoglobins; Interleukin-6; Leukocyte Count; Lung; Macrolides; Male; Pleuropneumonia; Random Allocation; Swine; Swine Diseases; Zinc

SPF pigs aged 10 weeks were infected intranasally with Actinobacillus pleuropneumoniae serotype 2. After the onset of clinical symptoms of respiratory disease, which occurred 20 h post-infection, parenteral treatment with ceftiofur, danofloxacin, enrofloxacin, penicillin or tiamulin was initiated (n = 8 per group). Untreated groups, of which one was infected, served as controls. The uninfected control group did not show any signs of disease, while the infected control group was severely affected by the infection and also expressed a decreased weight gain following the challenge. Based on clinical signs, the magnitude of pathological lesions in the respiratory tract found at necropsy performed 17 days post-infection and the number of reisolates of A. pleuropneumoniae made at necropsy, treatments with the quinolones (danofloxacin and enrofloxacin) and the cephalosporine (ceftiofur) were superior to those with penicillin and tiamulin. The latter groups also developed antibodies to A. pleuropneumoniae to a larger extent. Some of the pigs treated with ceftiofur and danofloxacin developed antibodies to A. pleuropneumoniae, and the microbe was reisolated from approximately 50% of these animals. In contrast, pigs treated with enrofloxacin did not develop antibodies to A. pleuropneumoniae, and the challenge strain was not found at necropsy. The performance with respect to daily weight gain and feed conversion corresponded well with the clinical signs developed and the findings made at necropsy. The decreased growth recorded during the acute phase of the disease was, to a large extent, caused by a reduced feed intake.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Body Weight; Cephalosporins; Diterpenes; Enrofloxacin; Fluoroquinolones; Lung; Lung Diseases; Penicillins; Quinolones; Swine; Swine Diseases; Weight Gain