tiamulin and Actinobacillus-Infections

Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were tested using selected bacteria with previously defined minimal inhibitory concentrations (MIC). The TIA metabolites tested were: N-deethyl-tiamulin (DTIA), 2beta-hydroxy-tiamulin (2beta-HTIA) and 8alpha-hydroxy-tiamulin (8alpha-HTIA), and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR-N). Bacteria, all of porcine origin, were selected as representatives of bacterial infections (Staphylococcus hyicus and Actinobacillus pleuropneumoniae), zoonotic bacteria (Campylobacter coli) and indicator bacteria (Escherichia coli and enterococci). Furthermore the effects of these compounds were tested on the microbial community of active sludge to test any negative effect on colony forming units (CFU). DTIA had a potency of 12.5-50% of the potency of TIA. 2beta-HTIA and 8alpha-HTIA had potencies less than 1% of the potency of TIA. ENR-N had a potency of 0.75-1.5% of the potency of ENR, while CIP and ENR had similar potencies. Results obtained here indicate that CIP and DTIA could contribute to the selective pressure for upholding antimicrobial resistant bacteria in animals under ENR or TIA treatment. The most potent metabolites CIP and DTIA showed considerable potencies against activated sludge bacteria compared to the parent compounds. EC(50) (microg/ml) for ENR, CIP, TIA and DTIA were 0.018 [95% CI: 0.028-0.149], 0.064 [95% CI: 0.007-0.046], 6.0 [95% CI: 3.6-9.8], and 9.7 [95% CI: 5.8-16.3], respectively. This indicates that the compounds can change the bacterial population in the sludge, and hereby alter the properties of the sludge.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Diterpenes; Drug Resistance, Bacterial; Enrofloxacin; Fluoroquinolones; Microbial Sensitivity Tests; Sewage; Staphylococcal Infections; Staphylococcus aureus; Swine; Swine Diseases

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

This study was conducted to compare the applicability of three different media in sensitivity testing of Actinobacillus pleuropneumoniae by means of MIC and tablet diffusion tests. The media used were: modified PPLO agar, chocolatized Mueller-Hinton-II and Columbia agar supplemented with NAD. Seven antimicrobial agents were tested: ceftiofur, enrofloxacin, penicillin, spectinomycin, tiamulin, trimethoprim + sulfadiazine and tylosin, against 40 randomly selected A. pleuropneumoniae isolates. In general, good agreement was found between results obtained with all combinations of media, most antimicrobials tested and the two-test systems. Some variations between media were observed for spectinomycin, tiamulin and tylosin. For ceftiofur and trimethoprim + sulfadiazine some isolates with low MIC-values were classified as resistant using tablet diffusion, indicating that the break points of resistance for these antimicrobials using the tablet diffusion tests need adjustment. Using current break points for resistance with MIC-determinations, all isolates tested susceptible to ceftiofur, enrofloxacin, penicillin, tiamulin and trimethoprim + sulfadiazine. A larger number of isolates tested resistant to spectinomycin and tylosin on all three media using both MIC determinations and tablet diffusion.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Cephalosporins; Colony Count, Microbial; Culture Media; Diterpenes; Drug Combinations; Drug Resistance, Microbial; Enrofloxacin; Fluoroquinolones; Latex Fixation Tests; Microbial Sensitivity Tests; Penicillins; Quinolones; Spectinomycin; Sulfadiazine; Swine; Swine Diseases; Trimethoprim; Tylosin

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

The present study was aimed at scrutinizing the efficacy of oral antimicrobial treatments at experimental challenge using a strain of Actinobacillus pleuropneumoniae serotype 2 known to cause severe disease. SPF pigs aged 10 weeks were infected intranasally and the antimicrobial treatments were initiated 5 h prior to that exposure. Several antimicrobial drugs, as well as the length of the treatment period, were elucidated. The outcome of the challenge was monitored by registration of clinical symptoms, weight gains and the development of serum antibodies to A. pleuropneumoniae. At necropsy, the magnitude of pathological lesions in the respiratory tract and the rate of reisolation of the infective strain were recorded. Animals that became diseased displayed a decreased growth rate caused, to a large extent, by a reduced feed intake. The performance with respect to daily weight gain and feed conversion corresponded well with the clinical signs developed and serologic reactions, as well as with the findings made at necropsy. The results obtained among pigs treated with enrofloxacin, but also with florfenicol or chlortetracycline, were superior to those of pigs treated with penicillin, tiamulin or tilmicosin. A positive effect was obtained using a strategic in-feed medication against infection with A. pleuropneumoniae. Provided that the drug used is effective against the target microbe, initiating treatment prior to infection appeared to be more important than the length of the treatment. It should, however, be remembered that A. pleuropneumoniae was reisolated from all but one medicated group following an experimental challenge given after initiating the medication. Consequently medical treatment as described did not eradicate the microbe.

Topics: Actinobacillus Infections; Actinobacillus pleuropneumoniae; Administration, Oral; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Chlortetracycline; Diterpenes; Enrofloxacin; Fluoroquinolones; Macrolides; Penicillin V; Quinolones; Swine; Swine Diseases; Thiamphenicol; Tylosin