tiamulin and Swine-Diseases

Pleuromutilins (tiamulin and valnemulin) are antimicrobial agents that are used mainly in veterinary medicine, especially for swine and to a lesser extent for poultry and rabbits. In pigs, tiamulin and valnemulin are used to treat swine dysentery, spirochaete-associated diarrhoea, porcine proliferative enteropathy, enzootic pneumonia and other infections where Mycoplasma is involved. There are concerns about the reported increases in the MICs of tiamulin and valnemulin for porcine Brachyspira hyodysenteriae isolates from different European countries, as only a limited number of antimicrobials are available for the treatment of swine dysentery where resistance to these antimicrobials is already common and widespread. The loss of pleuromutilins as effective tools to treat swine dysentery because of further increases in resistance or as a consequence of restrictions would present a considerable threat to pig health, welfare and productivity. In humans, only one product containing pleuromutilins (retapamulin) is authorized currently for topical use; however, products for oral and intravenous administration to humans with serious multidrug-resistant skin infections and respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), are being developed. The objective of this review is to summarize the current knowledge on the usage of pleuromutilins, resistance development and the potential impact of this resistance on animal and human health.

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Diterpenes; Drug Resistance, Bacterial; European Union; Humans; Microbial Sensitivity Tests; Mycoplasma Infections; Pleuromutilins; Polycyclic Compounds; Poultry; Poultry Diseases; Rabbits; Swine; Swine Diseases

Phytogenic feed additives have become attractive alternatives for use in animal diets. The objective of the present study was to evaluate the effect of a phytogenic-based feed additive on growth performance, nutrient digestibility, blood profiles, fecal noxious gas emission, and intestinal morphology of weaning pigs after dietary challenge with E. coli K88. A total of 120 crossbred pigs [(Yorkshire×Landrace)×Duroc)] with an initial body weight (BW) of 6.09±0.96 kg (21 d of age) were assigned randomly to 1 of the 4 dietary treatments. Each pen housed 5 pigs, and there were 6 pens/treatment. Treatments included: T1, negative control (without antibiotics); T2, T1+antibiotic; T3, T1+0.05% phytogenics; and T4, T1+0.2% commercial mix of organic acids. Overall, the average daily gain (ADG) with the T3 treatment was higher (P<0.05). At wk 1, the apparent total tract digestibility (ATTD) of dry matter (DM) was increased (P<0.05) with T4 treatment. The ATTD of ash with T3 and T4 treatments was greater (P<0.05). At wk 3, pigs fed with the T4 diet had a significantly higher (P<0.05) ATTD of DM. The ATTD of ash and calcium (Ca) was significantly increased (P<0.05) with the T4 treatment. Pigs fed with the T3 diet had a higher (P<0.05) ATTD of phosphorus (P). At wk 6, the ATTD of ash was significantly increased (P<0.05) with the T1 and T3 treatments. The data indicate that phytogenics positively affect growth performance of weaning pigs, indicating that their use as an alternative in the diets of weaning pigs can significantly improve ADG, under challenge with E.coli K88.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Diet; Dietary Supplements; Digestion; Diterpenes; Escherichia coli; Escherichia coli Infections; Feces; Gases; Gastrointestinal Diseases; Intestines; Swine; Swine Diseases

The clinical efficacy of tulathromycin in the treatment of natural outbreaks of swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to 6 months of age) exhibiting clinical signs of SRD were treated intramuscularly with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n = 102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France). Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae infections were the most frequently diagnosed pathogens. For both tulathromycin-treated animals and those treated with tiamulin or florfenicol, there were significant (P = .0001) reductions in mean rectal temperature and the severity of abnormal clinical signs on days 2 and 10 compared with day 0. There were no significant differences (P > .05) between treatments in average daily weight gain. Tulathromycin was found to be safe and highly effective in the treatment of natural outbreaks of SRD.

Topics: Animals; Anti-Bacterial Agents; Disaccharides; Disease Outbreaks; Diterpenes; Europe; Heterocyclic Compounds; Injections, Intramuscular; Pasteurellosis, Pneumonic; Severity of Illness Index; Swine; Swine Diseases; Thiamphenicol; Treatment Outcome

The possibilities and economic benefits of controlling mycoplasmal pneumonia of pigs caused by Mycoplasma hyopneumoniae by immunisation with Respisure and by Tiamutin treatment were studied. The experiment was carried out in a herd comprising 1000 sows which was free of PRRS, Aujeszky's disease, swine dysentery and leptospirosis, and the prevalence of mycoplasmal pneumonia was low because the farm had recently been restocked. Groups C1 and C2 served as untreated controls, while Groups R1 and R2 received a prestarter diet containing 100 ppm Tiamutin from the time of weaning. Piglets of Group R1 were vaccinated with Respisure vaccine once on day 69, while those of Group R2 twice, on days 65 and 80. Piglets of Groups ST1 and ST2 were fed 100 ppm Tiamutin in the diet for 7 days at the time of weaning and then at 4 months of age, while pigs of Group ST2 received such treatment also in the 6th month of life. The efficacy of treatment was analysed on the basis of the number of animals that died, were emergency slaughtered or were retarded in growth in the different groups, the body weight of animals at weaning, at 94 and 148 days of age and at the time of slaughter, their daily body weight gain, the lung lesions found in animals slaughtered from the different groups, the costs of medication and vaccination, and the cost-benefit calculations of the results. The mortality and emergency slaughter rate was 2.88% and 4.62% in Groups ST2 and ST1, respectively, 4.23% and 4.62% in Groups R2 and R1, respectively, and 8.39% and 9.44% in the control groups (C2 and C1, respectively). The rate of growth retardation was 0.48% and 2.12% in Groups R1 and R2, respectively, 1.59% and 3.46% in Groups ST1 and ST2, respectively, as compared to 8.03% and 6.55% in the control groups (C1 and C2, respectively). The severity score of lung lesions was 1.82 and 1.46 in Groups R1 and R2, 2.18 and 2.93 in Groups ST1 and ST2, and 3.83 and 4.02 in the control groups C1 and C2, respectively. The mean finishing weight of pigs was 102.4-107.8 kg and 95.2-106.6 kg in the treated groups and 94.5-98.6 kg in the control groups. The classification of pigs according to the EUROP categories showed a shift to the E and U categories in the treated groups. The average feed cost per one kg of liveweight was 77.89-82.64 Forints in the treated groups and 85.66 Forints in the control groups.

Topics: Animals; Anti-Bacterial Agents; Bacterial Vaccines; Diet; Diterpenes; Drug Administration Schedule; Female; Mycoplasma pneumoniae; Pneumonia of Swine, Mycoplasmal; Pregnancy; Swine; Swine Diseases; Treatment Outcome; Vaccination

The purpose of this study was to compare the efficacy of Mycoplasma hyopneumoniae vaccination with pulse medication in a pig herd chronically infected with Mycoplasma hyopneumoniae. Control groups of pigs were compared to vaccinated or treated groups. Medication and vaccination induced a significant reduction of pneumonia score (46.37% and 29.8% respectively, compared to 53.85% for control groups, p < 0.05). The treatment did not induce a significant reduction of the mean range of lung lesions (3.75) compared to the control groups (4.25). The mean range of lung lesions was significantly reduced by vaccine (3.06, p < 0.005) but not by treatment. Neither the medication nor the vaccination were able to clear M hyopneumoniae or Pasteurella multocida from lung tissue. In this herd, the vaccination had a beneficial effect on daily weight gain of pigs (695.9 g/day compared to 683.1 g/day for the control groups). The improvement of the age at slaughtering was 1.3 days for treated groups and 2.4 days for vaccinated groups compared to control groups. The vaccination induced a significant improvement in muscle rate (57.05%) compared to control groups (56.41%, p < 0.05) and to treated groups (56.21%, p < 0.001). In this herd infected with M hyopneumoniae, after allowing for treatment cost, manpower excepted, the increase in value was from -3 FF to -11 FF for the antibiotic treatment and +10.4 FF for the vaccination. From economical and medical points of view, the vaccination was preferable to the treatment under the conditions described in this study.

Topics: Animals; Anti-Bacterial Agents; Bacterial Vaccines; Chlortetracycline; Diterpenes; Lung; Mycoplasma; Mycoplasma Infections; Pasteurella Infections; Pasteurella multocida; Swine; Swine Diseases; Vaccination

Four field trials were carried out to evaluate the effect of feeding tiamulin hydrogen fumarate at 20 and 30 ppm to fattening pigs over an eight week period, on farms with histories of severe, complicated, enzootic pneumonia problems. These farms had a prevalence of pigs with pneumonic lesions from 81 to 94 per cent and a range between individual batches of 69 to 96 per cent. The results of the first three trials showed that tiamulin at 30 ppm significantly improved the weight gains and feed conversion efficiency of pigs, in comparison with controls and was superior to the groups fed 20 ppm tiamulin. A further trial with tiamulin at 30 ppm and controls only, confirmed the original findings. The overall average results showed that tiamulin improved average daily gain by 33 g (4.7 per cent) and feed conversion efficiency by 0.138 (4.7 per cent). This effect did not appear to result from a reduction in the total extent of pneumonic lesions and the possible reasons for this are discussed, but in the fourth trial the number of pigs requiring parenteral treatment was noticeably reduced.

Topics: Animal Feed; Animals; Body Weight; Clinical Trials as Topic; Diterpenes; Female; Male; Mycoplasma Infections; Pneumonia; Swine; Swine Diseases

Three field trials were carried out to evaluate the efficacy of tiamulin hydrogen fumarate at levels of 20 and 30 ppm in the feed for the prevention and control of swine dysentery. Tiamulin at 30 ppm was shown to be highly effective in preventing the clinical signs of dysentery. Treponema hyodysenteriae was not isolated from these pigs. Tiamulin at 20 ppm was effective in two out of three trials. The trials were performed on pigs either on or from farms with swine dysentery problems which had proven resistant to medication with other products.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Diterpenes; Dysentery; Female; Leucomycins; Male; Swine; Swine Diseases; Treponemal Infections

Treatment can be used as an indirect measure of morbidity, and treatment records can be used to describe disease patterns in a population. The aim of this study was to describe the rates of treatments with tiamulin and lincomycin by the intramuscular route in cohorts of pigs affected by swine dysentery. Data from treatment records from 19 cohorts of a 1500-head grower-finisher barn were analyzed using Poisson regression to determine factors associated with rates of treatment. Serial interval and reproductive numbers were extracted. Treatment rates displayed marked seasonality. The mean serial interval was estimated at 17 d with variability among batches. In the early period of most cohorts, the effective reproductive number did not exceed 1, and the highest estimate was 2.15 (95% CI: 1.46, 3.20). The average days-to-first treatment was 4.8 which suggests that pigs could have been infected at time of entry. The information about possible sources of infection and likely seasonality should be considered when developing disease and infection control measures in affected barns.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Lincomycin; Swine; Swine Diseases; Treatment Outcome

Production-limiting diseases in swine caused by Brachyspira are characterized by mucohemorrhagic diarrhea (B. hyodysenteriae and "B. hampsonii") or mild colitis (B. pilosicoli), while B. murdochii is often isolated from healthy pigs. Emergence of novel pathogenic Brachyspira species and strains with reduced susceptibility to commonly used antimicrobials has reinforced the need for standardized susceptibility testing. Two methods are currently used for Brachyspira susceptibility testing: agar dilution (AD) and broth microdilution (BMD). However, these tests have primarily been used for B. hyodysenteriae and rarely for B. pilosicoli. Information on the use of commercial susceptibility testing products such as antibiotic gradient strips is lacking. Our main objective was to validate and compare the susceptibility results, measured as the minimum inhibitory concentration (MIC), of 6 antimicrobials for 4 Brachyspira species (B. hyodysenteriae, "B. hampsonii", B. pilosicoli, and B. murdochii) by BMD and AD (tiamulin, valnemulin, lincomycin, tylosin, and carbadox) or antibiotic gradient strip (doxycycline) methods. In general, the results of a high percentage of all 4 Brachyspira species differed by ±1 log2 dilution or less by BMD and AD for tiamulin, valnemulin, lincomycin, and tylosin, and by BMD and antibiotic gradient strip for doxycycline. The carbadox MICs obtained by BMD were 1-5 doubling dilutions different than those obtained by AD. BMD for Brachyspira was quicker to perform with less ambiguous interpretation of results when compared with AD and antibiotic gradient strip methods, and the results confirm the utility of BMD in routine diagnostics.

Topics: Agar; Animals; Anti-Bacterial Agents; Brachyspira; Diarrhea; Diterpenes; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Swine; Swine Diseases

With the emergence of "Brachyspira hampsonii" associated with swine dysentery in North America, identification of effective treatments and interventions is a pressing need. Denagard® (tiamulin hydrogen fumarate) Liquid Concentrate 12.5% is approved in the United States for treatment of dysentery caused by Brachyspira hyodysenteriae at 0.006% in the water. In this study, the effectiveness of tiamulin in resolving clinical disease, eliminating viable spirochete shedding, and reducing neutrophilic colitis following infection with either "B. hampsonii" or B. hyodysenteriae was evaluated. Seventy-eight 7-week-old crossbred pigs were divided into three groups [sham-inoculated (n = 18), "B. hampsonii"-inoculated (n = 30), and B. hyodysenteriae-inoculated (n = 30)]. Each inoculum group was divided into three subgroups which received either 0.006% tiamulin, 0.018% tiamulin, or no medication. Both levels of tiamulin resolved clinical disease within 24 h of treatment initiation, eliminated spirochete shedding within 72 h of treatment initiation, and resolved and/or prevented histologic lesions in pigs infected with either Brachyspira spp.

Topics: Animals; Anti-Bacterial Agents; Brachyspira; Brachyspira hyodysenteriae; Colitis; Diterpenes; Dose-Response Relationship, Drug; Dysentery; Feces; Gram-Negative Bacterial Infections; Spirochaetales; Sus scrofa; Swine; Swine Diseases; Treatment Outcome

The effect of short-term antimicrobial treatment on natural excretion of Chlamydia suis in rectal swabs and C. suis and Chlamydophila psittaci in nasal swabs was investigated in 47 clinically normal piglets by quantitative real-time PCR. Pigs were treated IM with 4 mg/kg enrofloxacin for 5 days (n = 22) or 2.5mg/kg enrofloxacin for 3 days followed by 100mg/mL tiamulin (n = 25). Antimicrobial treatment reduced the number of pigs positive for chlamydiae and the quantity of chlamydial DNA in positive swabs for a few days, but chlamydial excretion recurred in both groups. Short-term antimicrobial treatment at dosages recommended for treatment of other bacterial infections in pig herds was not effective in eliminating naturally occurring subclinical chlamydial infection in pigs.

Topics: Animals; Anti-Bacterial Agents; Chlamydia Infections; Chlamydophila psittaci; Diterpenes; Enrofloxacin; Female; Fluoroquinolones; Male; Polymerase Chain Reaction; Recurrence; Swine; Swine Diseases; Treatment Outcome

Limited data regarding the susceptibility of Actinobacillus pleuropneumoniae to antimicrobials has been published during recent years. Accordingly, the aim of the present study was to investigate the distribution of MICs for the isolates of A. pleuropneumoniae from diseased pigs in the Czech Republic between 2007 and 2009. A total of 242 isolates were tested for susceptibility to 16 antimicrobial agents by a broth microdilution method. A low degree of resistance was observed for florfenicol (0.8%), amoxicillin and clavulanic acid (0.8%), tilmicosin (1.2%), tiamulin (1.7%) and ampicillin (3.3%), whereas resistance to tetracycline was detected more frequently, 23.9% of isolates. Interestingly, resistance to florfenicol has not yet been reported in any study investigating antimicrobial resistance of A. pleuropneumoniae. By PCR the presence of the floR gene was confirmed in all florfenicol resistant isolates.

Topics: Actinobacillus pleuropneumoniae; Amoxicillin; Ampicillin; Animals; Anti-Bacterial Agents; Clavulanic Acid; Czech Republic; Diterpenes; Genes, Bacterial; Microbial Sensitivity Tests; Swine; Swine Diseases; Tetracycline; Thiamphenicol; Tylosin

Tiamulin activity was measured against 19 UK field isolates of Actinobacillus pleuropneumoniae collected between 2003 and 2009 and the type strain ATCC 27090 as a control, with the intention of comparing broth with serum as growth media. Broth microdilution MIC/MBC tests were performed in accordance with the Clinical and Laboratory Standards Institute (CLSI) guideline M31-A3, in 'Veterinary Fastidious Medium' (VFM) (supplemented Mueller-Hinton broth at pH 7.3) and in 100% swine serum. For improved precision, a modified, overlapping doubling-dilution series was used (tiamulin concentration range 0.3-72 μg/ml). The MBC was reported as the lowest concentration producing a 99.9% reduction in bacterial density in the sub-cultured well contents, relative to the starting inoculum. The mean MBC/MIC ratio for tiamulin against A. pleuropneumoniae in VFM was low (1.74:1), even though tiamulin is classed as a bacteriostatic drug. Only three of the 19 isolates and the reference strain grew in 100% serum and their MICs were higher than those determined in VFM. It is postulated that this difference was due to differences in pH of the matrices or binding of tiamulin to serum proteins or a combination of both factors.

Topics: Actinobacillus pleuropneumoniae; Animals; Anti-Bacterial Agents; Culture Media; Diterpenes; Microbial Sensitivity Tests; Pleuropneumonia; Swine; Swine Diseases

A novel ABC transporter gene, vga(C), was identified on the 14,365-bp multiresistance plasmid pKKS825 in a porcine methicillin (meticillin)-resistant Staphylococcus aureus isolate of sequence type 398. The vga(C) gene encodes a 523-amino-acid protein which confers resistance not only to streptogramin A antibiotics but also to lincosamides and pleuromutilins. Plasmid pKKS825 also carries the resistance genes aadD, tet(L), and dfrK, which may enable the coselection of vga(C) under selective pressure by kanamycin/neomycin, tetracyclines, and trimethoprim.

Topics: Animals; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Diterpenes; Drug Resistance, Multiple, Bacterial; Kanamycin; Lincosamides; Methicillin-Resistant Staphylococcus aureus; Molecular Sequence Data; Neomycin; Plasmids; Pleuromutilins; Polycyclic Compounds; Staphylococcal Infections; Streptogramin A; Swine; Swine Diseases; Tetracyclines; Trimethoprim

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Diterpenes; Female; Gram-Negative Bacterial Infections; Male; Swine; Swine Diseases; Treatment Outcome

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

Brachyspira hyodysenteriae is the causative agent of swine dysentery, a severe diarrhoeal disease in pigs. Few drugs are available to treat the disease, owing to both antimicrobial resistance and withdrawal of drugs authorized for use in pigs. Tiamulin is the drug of choice in many countries, but isolates with decreased susceptibility have recently been reported. The mechanism of tiamulin resistance in B. hyodysenteriae is not known and this facet is essential to understand the dissemination of the trait. To study the resistance epidemiology of B. hyodysenteriae, further characterization of a set of isolates from Germany (n = 16) and the UK (n = 6) with decreased susceptibility to tiamulin was performed. The relatedness between the isolates was studied by comparing PFGE patterns, and the in vitro susceptibility to five other antimicrobials (aivlosin, doxycycline, salinomycin, chloramphenicol and avilamycin) was also determined. For comparison of the antimicrobial-susceptibility pattern, Swedish (n = 20) and British (n = 4) tiamulin-susceptible isolates were tested. The German isolates represented several different PFGE patterns, indicating that tiamulin usage has been sufficient to select clones with decreased tiamulin susceptibility at different farms in Germany. The PFGE pattern for the six British isolates with decreased tiamulin susceptibility was identical to that of the German isolates, and they had a similar antimicrobial-susceptibility pattern, except for resistance to aivlosin, which was only found in a few German isolates. No other co-resistance with tiamulin was found.

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Diterpenes; Drug Resistance, Bacterial; Dysentery; Electrophoresis, Gel, Pulsed-Field; England; Germany; Microbial Sensitivity Tests; Spirochaetales Infections; Sweden; Swine; Swine Diseases; Tylosin

The agar dilution method was used to investigate the sensitivity to pleuromutilins of 100 isolates of Brachyspira hyodysenteriae isolated from 63 pig farms between 1997 and 2001. In the period under investigation, MICs to both tiamulin and valnemulin increased, with differences between the periods 1997-98 and 1999-2001 being statistically significant (P < 0.001 for tiamulin and P < 0.0001 for valnemulin). Between 1997 and 2001, the MIC50 and MIC90 of tiamulin increased from 0.062 and 0.25 microg ml, respectively, to 1.0 and 4.0 microg ml. Valnemulin MIC50 and MIC90 were < or = 0.031 microg ml in 1997 and by 2001 were respectively, 2.0 and 8.0 microg ml. The increase in MICs of tiamulin and valnemulin demonstrated in this study reflect the intensity of pleuromutilin use in the treatment of swine dysentery in the Czech Republic.

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Czech Republic; Diterpenes; Drug Resistance, Bacterial; Dysentery; Microbial Sensitivity Tests; Spirochaetales Infections; Swine; Swine Diseases

In Germany treatment of swine dysentery is hampered by Brachyspira hyodysenteriae strains showing elevated MIC values to the few antibiotics licensed. Therefore, susceptibility testing of clinical isolates is an important service to the swine practitioner. This study compares the established agar dilution procedure for antimicrobial susceptibility testing of this fastidious anaerobe to the broth microdilution test newly developed [Anim. Health Res. 2 (2001) 59; Vet. Microbiol. 84 (2002) 123; J. Clin. Microbiol. 41 (2003) 2596]. A total of 221 isolates were examined twice with either test procedure using tiamulin and valnemulin as antibiotics. Both methods gave reproducible results, and the MIC values for the reference strains B. hyodysenteriae B204 and Staphylococcus aureus ATCC 29213 corresponded to previously published data. However, the results for individual strains differed significantly for both tests (P < 0.001) with MIC values being on average one dilution step lower in the broth dilution method. The 221 strains used for comparing test procedures were isolated between 1989 and 2001. An additional 102 strains isolated in 2002 were tested only with the broth dilution procedure. A significant rise in the average MIC value for both pleuromutilins could be demonstrated when comparing earlier isolates to those from 2000 to 2001 (P < 0.05), while in 2002 the average MIC significantly decreased when compared to the value in 2000 (P < 0.05). However, strains with MIC values for tiamulin as high as 8 microg/ml (broth dilution) could still be isolated.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Germany; Microbial Sensitivity Tests; Retrospective Studies; Spirochaetales; Spirochaetales Infections; 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

An investigation into a mild diarrhea in a group of grower/finisher pigs was carried out in order to determine the etiology. A tiamulin injection and a carbadox-medicated ration were given to pens of pigs in a 2 x 2 factorial experimental design. Pens of pigs were assessed a score, based on the consistency of the feces in the pen, each week. The clinical investigation looked for the intestinal pathogens Brachyspira pilosicoli, B. hyodysenteriae, Lawsonia intracellularis, Salmonella spp., Yersinia spp., transmissible gastroenteritis virus, and rotavirus. Despite a rigorous investigation, the diarrhea was not attributed to any pathogen. A mild colitis was noted among pigs necropsied while affected with diarrhea. Improved diagnostic tools may allow a more effective response to an outbreak of mild disease, while at the same time reducing the amount of antimicrobials used in swine production.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Carbadox; Colon; Diarrhea; Diterpenes; Feces; Ileum; Male; Swine; Swine Diseases; Time Factors

The pleuromutilins are the only antimicrobial agents with sufficient minimum inhibitory concentration (MIC) values left to treat swine dysentery in Sweden. Other antimicrobials are either not approved for use against swine dysentery or only partly active against Brachyspira hyodysenteriae. To date, in Sweden two pleuromutilins, tiamulin and valnemulin, are authorized for use in pigs. This study includes a comparison between MICs of tiamulin and valnemulin for Swedish field isolates of B. hyodysenteriae, as determined by broth dilution. For different isolates the MIC of tiamulin was between 0 and 8 times higher than that of valnemulin. No resistance to pleuromutilins was recorded (tiamulin MIC range 0.031-2 microg/ml, valnemulin MIC range < or =0.016-1 microg/ml). In vitro development of tiamulin resistance was also studied. Two B. hyodysenteriae and two B. pilosicoli strains became resistant to tiamulin following reiterated passages on agar containing tiamulin in increasing concentrations. The resistance emerged slowly and three of the strains that went through more than 60 passages increased their tiamulin MICs from 0.031-0.25 to more than 128 microg/ml. The tiamulin MIC for one B. hyodysenteriae strain that went through 29 passages increased from 0.0125 to 4 microg/ml. One B. pilosicoli strain developed cross-resistance to valnemulin; the MIC increased from 0.25 to more than 64 microg/ml. The valnemulin MIC for one B. hyodysenteriae strain increased from 0.031 microg/ml to 32 microg/ml. Valnemulin MIC was not determined for the B. hyodysenteriae strain that only went through 29 passages. The valnemulin MIC of the other B. pilosicoli strain increased from 0.031 to 4 microg/ml.

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Diterpenes; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Dysentery; Microbial Sensitivity Tests; Pleuromutilins; Polycyclic Compounds; Spirochaetales Infections; Sweden; Swine; Swine Diseases

Brachyspira pilosicoli and B. innocens were isolated repeatedly from a herd of 60 sows which mostly produced feeder pigs but also raised some fattening pigs. Postweaning diarrhea had been a severe problem in this herd for years. The B. pilosicoli eradication plan was based on the general guidelines for elimination of B. hyodysenteriae, with some modifications. The eradication measures were run in August 1997. In-feed medication with 200 p.p.m. tiamulin lasted for 18-30 days, depending on the age group. The piggery unit was emptied, cleaned, disinfected and dried, and all worn surfaces were repaired. The animals were removed to temporary sheds situated 0-100 m from the piggery unit. Only the sows and the boar returned to the piggery unit. All other pigs were sold from the sheds within 3 months after the eradication. Immediately after the eradication, the clinical postweaning diarrhea disappeared. The success of the program was monitored four times bacteriologically, and the last control sampling was in December 1999, 7 months after the total withdrawal of antimicrobial feed additives. The primary cultures from the last three samplings were also analysed with B. pilosicoli-specific PCR. All the samples were negative for B. pilosicoli. However, B. innocens could be isolated from each batch of samples. The analysis of B. innocens isolates by pulsed-field gel electrophoresis indicated that at least one genotype persisted in the herd. The clinical and laboratory findings suggest that the eradication of B. pilosicoli had succeeded in this herd.

Topics: Age Factors; Animal Husbandry; Animals; Anti-Bacterial Agents; Brachyspira; Diarrhea; Diterpenes; Female; Male; Spirochaetales Infections; Swine; Swine Diseases; Weaning

Seventy-six, crossbred, porcine reproductive and respiratory syndrome virus (PRRSV)-free pigs were weaned at 12 days of age and randomly assigned to seven groups of 10 to 11 pigs each. Pigs in group 1 served as unchallenged controls. Pigs in groups 2 to 7 were challenged intranasally with 2 ml of high-virulence PRRSV isolate VR-2385 (10(4.47) 50% tissue culture infective doses per 2 ml) on day 0 of the study (30 days of age). Seven days after PRRSV challenge, pigs in groups 2 to 7 were challenged intranasally with 2 ml of Streptococcus suis serotype 2 (10(8.30) CFU/2 ml). Group 2 pigs served as untreated positive controls. Antimicrobial treatments included daily intramuscular injection with 66,000 IU of procaine penicillin G per kg of body weight on days 8 to 10 (group 3), drinking water medication with 23.1 mg of tiamulin per kg during days 8 to 10 (group 4), and daily intramuscular injection of 5.0 mg of ceftiofur hydrochloride per kg on days 8 to 10 (group 5). Vaccination regimens included two intramuscular doses of an autogenous killed S. suis vaccine (group 6) prior to S. suis challenge or a single 2-ml intramuscular dose of an attenuated live PRRSV vaccine (group 7) 2 weeks prior to PRRSV challenge. Mortality was 0, 63, 45, 54, 9, 40, and 81% in groups 1 to 7, respectively. Ceftiofur treatment was the only regimen that significantly (P < 0. 05) reduced mortality associated with PRRSV and S. suis coinfection. The other treatments and vaccinations were less effective. We conclude that ceftiofur administered by injection for three consecutive days following S. suis challenge was the most effective regimen for minimizing disease associated with PRRSV and S. suis coinfection.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cephalosporins; Diterpenes; Injections, Intramuscular; Penicillin G Procaine; Porcine Reproductive and Respiratory Syndrome; Porcine respiratory and reproductive syndrome virus; Streptococcal Infections; Streptococcus suis; Swine; Swine Diseases; Viral Vaccines; Virulence; Water Supply

Tiamulin is a diterpenic veterinary drug widely used in swine for the control of infectious diseases, including swine dysentery and enzootic pneumonia. Tiamulin is well tolerated and only a few drug interactions have been reported with some ionophore antibiotics. A case of tiamulin adverse drug interaction with nitrovin, a nitrofuranic growth promoter, in fattening pigs from a commercial farm is described. To confirm the diagnosis, experimental reproduction was conducted using 20 healthy female pigs. The animals were randomly divided into 4 groups: 1 of them receiving feed medicated with 100 mg tiamulin hydrogen fumarate/kg, another received 20 mg nitrovin/kg to establish the harmlessness of the drugs alone. The other 2 groups received feeds containing both drugs at the previous concentrations, one of which came from the farm. In the last 2 groups clinical signs appeared 72-96 h after initially feeding pigs the tiamulin hydrogen fumarate + nitrovin-containing feed. The animals had uneasiness, anxiety, skin erythema, and rash on snout, vulva and abdomen, and increased body temperatures. No mortality occurred, and there were no characteristic findings during pathological examination. The signs disappeared after 96 h of consuming the medicated feed, leaving a slight skin thickening of the affected regions. All signs disappeared spontaneously 4-5 d after ceasing medication.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Disease Outbreaks; Diterpenes; Drug Interactions; Female; Nitrovin; Reproducibility of Results; Swine; Swine Diseases

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

The effect of control programmes on proliferative enteropathy and its causative agent (Lawsonia intracellularis) was investigated on four farrow-to-finish pig farms in Britain. Faeces samples from groups of boars and gilts in breeding programmes, and from preweaning and postweaning pigs were monitored prospectively every month for six months by a L intracellularis-specific polymerase chain reaction (PCR). On one farm with 150 sows, an outbreak of acute proliferative enteropathy in boars and gilts was controlled clinically by the use of tiamulin and chlortetracycline. The percentage of detectable PCR-positive pigs decreased from between 50 to 70 per cent to zero in the treated pigs and their progeny less than 14 weeks old, but clinical signs of the disease and PCR-positive pigs were detected in some 14-week-old pigs derived from the treated groups. On another farm with 160 sows, an outbreak of chronic proliferative enteropathy in six-week-old pigs (23 to 26 per cent PCR-positive) was controlled by the use of oral tylosin phosphate. Faeces samples from the medicated pigs on this farm remained PCR-negative during the study period, whereas samples from unmedicated control pigs showed that the infection persisted in some pigs for at least six weeks. The two other monitored farms remained PCR-negative and clinically negative for the disease during the study period. These farms treated the pigs regularly with oral chlortetracycline.

Topics: Animals; Anti-Bacterial Agents; Disease Outbreaks; Diterpenes; Feces; Female; Gastroenteritis; Male; Polymerase Chain Reaction; Prevalence; Swine; Swine Diseases; United Kingdom

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

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Resistance, Microbial; Finland; Hemolysis; Microbial Sensitivity Tests; Spirochaetaceae; Spirochaetales Infections; Swine; Swine Diseases

This study was conducted to compare the Minimal Inhibitory Concentrations (MICs) for enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, of Mycoplasma hyosynoviae, isolated from pigs at notably different intervals (1968-71 and 1995-96). Each group comprised 21 low passage isolates and a Danish reference strain (M60) and the type strain (S16). MICs were determined in liquid medium with both initial and final readings. Enrofloxacin, lincomycin, tetracycline and tiamulin were active against all isolates, and tiamulin showed the highest activity. For tylosin all the isolates from 1968-71 were highly susceptible, whereas the isolates from 1995-96 could be divided into a highly susceptible (nine isolates) and relatively resistant (12 isolates) group. This difference between old and new strains was statistically significant (p = 0.0000415). The remaining agents, enrofloxacin, lincomycin, tiamulin and tetracycline, showed an unaltered good activity against M. hyosynoviae. The resistance to tylosin seems now to occur so often that this antibiotic cannot be recommended for therapeutic use any more. The most probable explanation for the emergence of resistance is the intensive use of tylosin during many years for therapy and growth promotion.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Diterpenes; Enrofloxacin; Fluoroquinolones; Lincomycin; Microbial Sensitivity Tests; Mycoplasma; Mycoplasma Infections; Quinolones; Swine; Swine Diseases; Tetracycline; Tylosin

The toxicity of the combination of salinomycin (sal.) and tiamulin (tia.) was investigated in dependence upon dosage and feeding method. In addition the efficacy of a safe dose for prophylactic treatment of dysentery was controlled. Following feed medications were tested for toxic effects in pigs: a) 3 mg sal. + 5 mg tia./kg BW, b) 3 mg sal. + 3 mg tia./kg BW, c) 3 mg sal. + 1 mg tia./kg BW, d) 3 mg sal./kg BW, e) 10 mg tia./kg BW, f) 30 mg tia./kg BW. The daily dose was given for 2 weeks by restricted feeding (twice a day) either as bolus or mixed in the whole ration or by feeding ad libitum. Animals were controlled for clinical symptoms and activities of creatine phosphokinase (CK) and aspartate aminotransferase (ASAT) were evaluated daily. Main clinical signs of poisoning were loss of appetite and locomotor disturbances and could be noticed for dosages of 8, 6 and 4 mg sal. + tia./kg BW. Activities of CK and ASAT were increased dose-related, the feeding method also had an influence on the degree of intoxication. Some animals showed locomotor disturbances without any corresponding changes of CK and ASAT levels. Single pigs remaining without any symptoms even at high dosage pointed to differences in individual susceptibility. Toxicity was not found to be age dependent. Feed medication with 60 ppm sal. + 20 ppm tia. (feeding ad libitum) did not result in any signs of toxicity, however, the transmission of Serpulina hyodysenteriae from infected pigs to healthy, treated control animals could not be inhibited efficiently. Therefore the simultaneous application of salinomycin and tiamulin should be avoided generally, because the risk of intoxication is high and subtherapeutical dosage has an insufficient effectiveness against Serpulina hyodysenteriae.

Topics: Animals; Anorexia; Anti-Bacterial Agents; Aspartate Aminotransferases; Brachyspira hyodysenteriae; Creatine Kinase; Diterpenes; Drug Interactions; Motor Activity; Pyrans; Spirochaetales Infections; Swine; Swine Diseases

The sensitivity of 332 strains of Serpulina hyodysenteriae isolated in Hungary between 1978 and 1992 was tested against seven chemotherapeutic drugs frequently used for the treatment of swine dysentery, and the changes in the patterns of resistance were also monitored. All the strains remained sensitive to carbadox, with minimum inhibitory concentrations (MIC) of only 0.05 to 0.40 microgram/ml at present. The susceptibility of the strains to dimetridazole has gradually decreased, but about half of the strains are still sensitive, with large numbers of "moderately sensitive' strains; the MIC values varied within wide limits (0.1 to 50 micrograms/ml). Most of the strains were resistant to tylosin, with MIC values from 0.1 to 100 micrograms/ml. The number of strains resistant to lincomycin has gradually increased, but about half of the strains remain sensitive; the MIC values ranged from 0.2 to 100 micrograms/ml. Recently, tiamulin has proved the most effective antibiotic, but some resistant strains have already emerged (MIC values 0.05 to 50 micrograms/ml). Monensin was good for the prevention of swine dysentery, but resistance may evolve quickly; the MIC values ranged from 0.4 to 25 micrograms/ml. For sedecamycin, the MIC values (6.25 to 100 micrograms/ml) were much higher than expected.

Topics: Animals; Anti-Bacterial Agents; Brachyspira hyodysenteriae; Carbadox; Dimetridazole; Diterpenes; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Dysentery; Hungary; Lincomycin; Macrolides; Microbial Sensitivity Tests; Monensin; Spirochaetales Infections; Swine; Swine Diseases; Tylosin

Fifty-four Japanese strains of Mycoplasma hyosynoviae isolated from porkers during 1980 to 1995, and 107 Japanese strains of M. hyorhinis isolated from piglets with respiratory disease during 1991 to 1994 were investigated for the in vitro activities of 13 antimicrobial agents [josamycin, tylosin, spiramycin, kitasamycin, erythromycin, lincomycin (LCM), kanamycin (KM), chloramphenicol (CP), thiamphenicol (TP), tiamulin (TML), oxytetracycline (OTC), chlortetracycline (CTC), and enrofloxacin (ERFX)] by the agar dilution method. Of the drugs tested TML showed the highest activity with minimum inhibitory concentration (MIC) of 0.013 to 0.1 microgram/ m/ (MIC90; 0.05 microgram/ml) against strains of M. hyosynoviae, and 0.2 to 0.78 microgram/ml (MIC90; 0.39 microgram/ml) against strains of M. hyorhinis. ERFX, LCM, most of the 16-membered macrolide antibiotics and tetracyclines also showed low MICs against both mycoplasma species. The susceptibility of KM, CP and TP to the mycoplasmas was considered to be of a secondary grade. Two of 54 strains of M. hyosynoviae, and 11 of 107 strains of M. hyorhinis showed resistance to all 14- and 16-membered macrolide antibiotics tested. Tetracyclines (OTC and CTC) showed a relatively broad MIC distribution from 0.1 to 6.25 micrograms/ml against the M. hyosynoviae strains tested. All of the strains isolated during 1980 to 1984 were susceptible at the concentration of 0.78 microgram/ml or less (MIC90; 0.78 microgram/ml) to OTC and 1.56 micrograms/ml or less (MIC90; 1.56 micrograms/ml) to CTC, while the susceptibility of strains isolated recently, during 1994 to 1995, was more than 0.78 microgram/ml (MIC90; 3.13 micrograms/ml) to OTC, and more than 1.56 micrograms/ml (MIC90; 6.25 micrograms/ml) to CTC.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Chloramphenicol; Diterpenes; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Enrofloxacin; Erythromycin; Fluoroquinolones; In Vitro Techniques; Josamycin; Kanamycin; Kitasamycin; Lincomycin; Mycoplasma; Mycoplasma Infections; Quinolones; Spiramycin; Swine; Swine Diseases; Tetracycline; Thiamphenicol; Tylosin

A program with the aim to eliminate infections with Mycoplasma hyopneumoniae was applied in 4 herds selling breeding pigs. A "fast" (1 month) variant of the program was applied in one herd selling young gilts (30 kg body weight) and in one herd selling adult breeding stock, and a "slow" (> or = 3.5 months) variant was applied in two corresponding herds. In both variants, the spread of infections was prevented by isolating the breeding stock. These animals were treated with tiamulin before being reintroduced to the original, but emptied and disinfected units. Further, the rearing of pigs born before and after initiating the program was separated. In both herds selling young gilts, no antibodies to Mycoplasma hyopneumoniae were detected in sera collected for at least 40 months after finishing the program. In the herds selling adult breeding pigs, elimination of infections with Mycoplasma hyopneumoniae was only achieved by the "fast" variant, while the infections still were present in the breeding herd using the "slow" variant of the program. The failure of the program in the latter herd was probably due to turbulent air flows between ventilation systems of units situated close to each other and simultaneously housing uninfected and infected pigs.

Topics: Animals; Anti-Bacterial Agents; Disinfection; Diterpenes; Female; Housing, Animal; Male; Mycoplasma Infections; Quarantine; Swine; Swine Diseases

Topics: Animal Feed; Animals; Diagnosis, Differential; Diterpenes; Poisoning; Pyrans; Swine; Swine Diseases

Topics: Animals; Anti-Bacterial Agents; Australia; Dimetridazole; Diterpenes; Dysentery; Lincomycin; Microbial Sensitivity Tests; Spectinomycin; Swine; Swine Diseases; Tetracycline; Treponema; Treponemal Infections; Tylosin

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Combinations; Poisoning; Pyrans; Swine; Swine Diseases

The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method. The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T. hyodysenteriae, followed by carbadox. Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T. hyodysenteriae isolates. Isolates of T. innocens were more sensitive to the various antimicrobials. Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin.

Topics: Animals; Anti-Bacterial Agents; Carbadox; Dimetridazole; Diterpenes; Dysentery; Lincomycin; Ronidazole; Swine; Swine Diseases; Treponema; Treponemal Infections

Eighteen 4-week-old pigs were used in a study to evaluate tiamulin in drinking water for control of experimentally induced Streptococcus suis type-2 infection. Pigs in groups A and B (n = 6 pigs/group) were aerosolized with a logarithmic-growth phase culture of S suis type 2, whereas pigs in group C (n = 6 pigs) served as noninfected and nonmedicated controls. After exposure to S suis, pigs in group B were given 180 mg of tiamulin/L of drinking water for 5 days. Pigs in group B consumed more feed (P = 0.009) and gained body weight faster (P = 0.02) than did pigs in group A. Pigs in group A had higher rectal temperature (P = 0.05) for up to 7 days after S suis exposure, higher clinical sign scores (P = 0.008), higher serum cortisol concentration on days 7 and 14, higher gross lesion scores (P = 0.03), and higher microscopic lesion scores (P = 0.01) than did pigs in groups B and C. Gross and microscopic lesions in pigs of groups A and B included meningitis, pneumonia, pleuritis, pericarditis, peritonitis, and synovitis of variable severity. Streptococcus suis type 2 was recovered from tissue specimens of 2 group-A pigs and 1 group-B pig. Data indicated that tiamulin administered via drinking water significantly reduced the effects of S suis type-2 infection.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Body Temperature; Diterpenes; Drinking; Eating; Streptococcal Infections; Swine; Swine Diseases; Weight Gain

The in vitro activities of 12 quinolones and four antibiotics were determined against 15 veterinary mycoplasmal species and four species of bacteria commonly involved in respiratory infections in pigs. The newer quinolones were markedly more active in vitro against a wide range of mycoplasmas than nalidixic acid and the earlier quinolones. Against Mycoplasma hyopneumoniae ciprofloxacin was the most active quinolone with a geometric mean minimal inhibitory concentration (MIC) against 16 strains of 0.01 microgram ml-1 compared with 0.04 microgram ml-1 for tiamulin, 0.06 microgram ml-1 for tylosin, 0.17 microgram ml-1 for oxytetracycline and 0.23 microgram ml-1 for gentamicin. M hyosynoviae was less sensitive to the quinolones with mean MICs of 0.6 microgram ml-1 for ofloxacin and 0.7 microgram ml-1 for ciprofloxacin compared with 0.034 microgram ml-1, or less, for tiamulin. Norfloxacin and its 6-chloro analogue were both mycoplasmacidal in vitro at five or 10 times their MICs against M hyopneumoniae UCD4. Tiamulin was mycoplasmastatic. The quinolones were also active against porcine Bordetella bronchiseptica and Pasteurella multocida strains and Haemophilus species. Ciprofloxacin was the most active quinolone with mean MICs of 0.58 microgram ml-1 against B bronchiseptica (nine strains), 0.026 microgram ml-1 against P multocida (five strains) and 0.01 microgram ml-1, or less, against Haemophilus pleuropneumoniae (nine strains) and H parasuis (two strains) compared with mean MICs of from 0.5 microgram ml-1 to 64 micrograms ml-1, or more, for the antibiotics. This combination of excellent mycoplasmacidal activity against M hyopneumoniae and good antibacterial activity, suggests that the quinolones have great potential for treating respiratory infections in pigs, including enzootic pneumonia.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bordetella; Diterpenes; Gentamicins; Haemophilus; Microbial Sensitivity Tests; Mycoplasma; Norfloxacin; Pasteurella; Respiratory Tract Infections; Swine; Swine Diseases; Time Factors

During 3 trials, using affected pigs of various ages, tiamulin was evaluated for treatment of experimentally induced mycoplasmal pneumonia. Pneumonia was induced in respiratory tract disease-free swine by intratracheal inoculation of a lung homogenate containing Mycoplasma hyopneumoniae. Eleven days after inoculation, when more than 20% of pigs were coughing, pigs were allotted to 3 or 4 groups (n = 8 pigs each) and were given regimens of no medication or 60 mg, 120 mg, or 180 mg of tiamulin/L of drinking water for 10 days. Twenty-one days after cessation of medication, pigs were euthanatized and then were necropsied. Results obtained from the 3 trials did not indicate significant difference among treatment groups in severity of macroscopic or microscopic lesions induced by M hyopneumoniae or in detection of M hyopneumoniae by use of immunofluorescent technique. Clinical evaluations, daily gain, and feed efficiency did not differ significantly among treatment groups. In this study, tiamulin administration did not have beneficial effects in swine with mycoplasmal pneumonia.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Evaluation; Female; Male; Pneumonia of Swine, Mycoplasmal; Swine; Swine Diseases; Water Supply

In 1977 swine dysentery was made a notifiable disease in the German Democratic Republic, with the intention of eradicating it by the systematic treatment of clinically affected herds using intensive medication and hygiene control programmes. On individual farms the scheme appeared to be successful, but the national incidence of the disease did not decline, owing to the continuous presence of latently infected herds and the movement of carrier pigs to uninfected farms. In 1981 the scheme was re-appraised and a new scheme was introduced in one region where all the breeding herds were screened for the presence of Treponema hyodysenteriae; all positive herds were treated with either metronidazole or tylosin, and the movement of pigs into the region was controlled. This programme effectively eradicated the disease from the region and is being introduced to the rest of the country. Owing to concern about the safety of metronidazole and the development of resistance to tylosin, alternative antimicrobials were examined and tiamulin was selected to assess its suitability for inclusion in the programme. A 560 sow breeding herd and progeny were treated for five days with tiamulin at 10 mg/kg bodyweight. This was coupled with extensive cleaning, disinfection and rodent control programmes. The results of the trial showed that the clinical disease stopped in two days and that no further clinical signs were seen in the subsequent two-and-a-half years. Bacterial monitoring of faeces samples and colonic scrapings from dead pigs failed to identify viable T hyodysenteriae. There was a significant increase of 0.6 piglets weaned per litter and improvements in weaning weights and growth rates. It was concluded that tiamulin was suitable for inclusion in the swine dysentery eradication programme in the GDR.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Female; Follow-Up Studies; Germany, East; Leucomycins; Male; Metronidazole; Swine; Swine Diseases; Treponemal Infections; Tylosin

Modulation of acute monensin toxicosis in swine was evaluated in 2 studies. In study 1, 56 weanling male pigs were allotted to 14 groups of 4 each. Pigs in 7 groups were given tiamulin in the drinking water (to supply 7.7 mg/kg of body weight/day) for 3 days before and for 2 days after monensin administration. Monensin was given as a single oral dose (at 0, 7.5, 15, 25, 50, 75, or 100 mg/kg) to pigs in groups with or without tiamulin exposure. Prominent acute clinical signs of monensin toxicosis (hypermetria, hind limb ataxia, paresis, knuckling of hind limbs, and recumbency) developed by 2 to 6 hours after dosing in pigs given 15 or 25 mg of monensin/kg with tiamulin exposure, but not in pigs given the 15 or 25 mg of monensin/kg without tiamulin exposure. Also, the extent of monensin-induced skeletal muscle damage at 4 days after monensin dosing was enhanced in pigs given 7.5, 15, or 25 mg of monensin/kg and exposed to tiamulin. In study 2, 48 weanling male pigs were allotted to 8 groups of 6 each. Four groups of pigs were given 20 mg of monensin/kg orally, and 4 groups were given 100 mg of monensin/kg orally. For each monensin dose, a group was treated 24 hours before monensin administration with (i) selenium (Se)-vitamin E preparation, 0.25 mg of Se and 68 IU of d-alpha-tocopheryl acetate (vitamin E)/kg, IM; (ii) vitamin E only, 68 IU of d-alpha-tocopheryl acetate/kg; (iii) Se only, 0.25 mg of Se/kg; or (iv) vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Synergism; Male; Monensin; Selenium; Swine; Swine Diseases; Vitamin E

Topics: Animals; Diterpenes; Dysentery; Erythema; Swine; Swine Diseases

The diarrhea of swine dysentery receded in swine treated with 60 or 45 mg of tiamulin/L of drinking water (60 or 45 ppm). However, within 2 to 10 days (average 4.1 days) after drug withdrawal, diarrhea recurred. Tiamulin (22.5 mg/L in drinking water) did not markedly reduce the diarrhea during medication, and tylosin (66 mg/L in the drinking water) was not effective. In swine treated with 120 mg of dimetridazole/L of drinking water, there was no recurrence of diarrhea. After the recurrence of diarrhea in swine, repeated medication with tiamulin in drinking water reduced the severity of diarrhea and prevented deaths. After 1 to 3 retreatments, swine were immune to exposure with swine dysentery inoculum, and there was a significant (P less than 0.05) increase in their serum anti-Treponema hyodysenteriae antibodies. Seemingly, drug withdrawal permitted the occurrence and recurrence of diarrhea that was necessary to stimulate immunity.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Leucomycins; Recurrence; Swine; Swine Diseases; Treponemal Infections; Water Supply

The antibacterial effects of a combination of tiamulin and chlortetracycline in vitro against a number of field isolates of Pasteurella multocida, Haemophilus pleuropneumoniae and Bordetella bronchiseptica were examined. There was a marked synergism between the two antibiotics against all eight isolates of P multocida, against seven of nine isolates of H pleuropneumoniae and against the single strain of B bronchiseptica tested. Two field trials were carried out on a herd with a history of complicated enzootic pneumonia where the presence of Mycoplasma hyopneumoniae and P multocida had been established and subsequently the presence of H pleuropneumoniae was discovered. Feed containing tiamulin at 100 ppm combined with chlortetracycline at 300 ppm was given for seven days to pigs affected with pneumonia, and the results were compared with untreated controls and pigs receiving chlortetracycline at 300 ppm. There was a follow-up observation period of three weeks when all groups received unmedicated feed. During the medication period the combination treated groups showed a statistically significant increase in average daily weight gain of 156 g (20.4 per cent) and in feed conversion efficiency of 0.576 (20.8 per cent) and a numerical improvement in average disease score in comparison with the untreated controls. These improvements were approximately double those observed in the groups treated with 300 ppm chlortetracycline which showed improvements of 93 g (12.2 per cent) in average daily gain and 0.301 (10.9 per cent) in feed conversion efficiency. During the following three weeks most of the initial gains were lost, probably owing to the reinfection of the treated groups by the untreated controls.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Bacterial Infections; Chlortetracycline; Diterpenes; Drug Synergism; Drug Therapy, Combination; Microbial Sensitivity Tests; Pneumonia; Pneumonia of Swine, Mycoplasmal; Swine; Swine Diseases

Topics: Animals; Anti-Bacterial Agents; Dimetridazole; Diterpenes; Dysentery; Nitroimidazoles; Swine; Swine Diseases

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Mycoplasma Infections; Swine; Swine Diseases

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Pneumonia, Mycoplasma; Swine; Swine Diseases

From 10 days before the expected date of farrowing onwards, 97 sows infected by Mycoplasma hyopneumoniae and Treponema hyodysenteriae were given tiamulin daily at a dosage of 20 mg/kg bodyweight via the feed. Three days before farrowing the sows were washed with a disinfectant and transferred to an isolated farrowing house. The sucking piglets remained with their dams for five days, during which time the sows continued to receive the tiamulin-containing feed. The sucking piglets also received tiamulin daily at a dosage of 30 mg/kg bodyweight. At six days old the weaker piglets of the litter were returned to the original herd, together with their dams. A total of 574 piglets of about 1.5 kg bodyweight each were transferred to an isolated and previously disinfected pig farm and reared there. A total of 13.8 per cent of these pigs died by 50 days old. On the isolated farm, 10.9 per cent of the 829 second generation piglets born to the 101 first generation sows, died up to the age of 50 days. On the isolated farm about 2000 pigs were subjected to repeated clinical, pathological and laboratory examinations for M hyopneumoniae, T hyodysenteriae, Aujeszky's disease virus and Leptospira species during the three year period of study. No evidence of infection with any of these agents was found in the 2000 pigs of the isolation herd, although the original sow herd had been latently infected by these pathogens. No maternally derived antibodies against these pathogens were detectable in sera of three-day-old sucking piglets of the second and third generations.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Diterpenes; Female; Mycoplasma Infections; Pregnancy; Pregnancy Complications, Infectious; Swine; Swine Diseases; Time Factors; Treponemal Infections; Weaning

Simultaneous administration of monensin and tiamulin to pigs resulted in enhanced myotoxicity. Skeletal muscles of tongue, diaphragm and legs were preferentially affected, whereas the masseter, longissimus thoracis and cardiac muscles, including the left auricle, were spared. Histochemical examination revealed an involvement of both type I and II fibers of skeletal muscles.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Synergism; Food Additives; Furans; Histocytochemistry; Male; Monensin; Muscles; Muscular Diseases; Swine; Swine Diseases; Weaning

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Interactions; Food Additives; Foodborne Diseases; Pyrans; Swine; Swine Diseases; Switzerland

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Diterpenes; Female; Mycoplasma Infections; Swine; Swine Diseases

Tiamulin hydrogen fumarate has been shown to be highly active in vitro against Mycoplasma hyosynoviae, an organism that causes arthritis in pigs. A gilt-multiplier herd with a history of this condition was selected to evaluate the efficacy of tiamulin in vivo for the treatment of this disease. The presence of M hyosynoviae was confirmed by its isolation from two typically affected cases. A field trial was carried out on clinically affected pigs, using tiamulin at 10 mg and 15 mg/kg bodyweight given by injection for three consecutive days, by comparing their weight gains and reduction in lameness scores during a seven day trial period (days 0 to 7) with those of negative untreated controls and positive controls injected with lincomycin at 10 mg/kg bodyweight for three days. Both of the tiamulin treatment levels appeared to be effective, as there were marked improvements in weight gains and reduction in lameness scores in comparison with the negative controls. The improvements were similar to those achieved with the positive control, lincomycin.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Diterpenes; Lincomycin; Mycoplasma Infections; Swine; Swine Diseases

Topics: Animals; Diterpenes; Dysentery; Injections, Intramuscular; Swine; Swine Diseases; Treponemal Infections

Tiamulin, a semisynthetic antibiotic, was fed to growing pigs and its value in maintaining weight gain and feed efficiency in the face of mycoplasmal pneumonia was determined. Four treatments divided among 64 growing pigs from a conventional pig farm were used to test the effects of tiamulin administered in feed at levels of 10, 20 and 30 ppm. All pigs were artificially infected with Mycoplasma hyopneumoniae. Medication was started on the 14th day after infection (d 0) and continued for 28 d (d 0 to 28). Pigs were continued on test for an additional 14-d period for further observation (d 28 to 42) after the medicated feed was withdrawn. Tiamulin fed at 10, 20 and 30 ppm for 28 d did not cure the mycoplasmal pneumonia. The effect of tiamulin on growth performance was not the same for all periods. During the medication period (d 0 to 28), both daily gain and feed conversion were not significantly affected by dietary tiamulin concentrations. For the post-treatment period (d 28 to 42), tiamulin improved daily gain (P less than .05) and feed conversion (P less than .05) over those of nonmedicated controls, and the responses of both daily gain and feed efficiency increased linearly (P less than .05) as dietary tiamulin levels increased.

Topics: Animals; Anti-Bacterial Agents; Body Weight; Diterpenes; Food Additives; Lung; Male; Pneumonia of Swine, Mycoplasmal; Swine; Swine Diseases

The clinical efficacy of tiamulin given in the drinking water at levels of 0.0045 per cent for five days and 0.006 per cent for three days was evaluated for the treatment of swine dysentery in six clinical studies and compared with positive controls using tylosin at 0.02 per cent in the drinking water for five days and untreated controls. Efficacy was evaluated by assessment of the pigs' general appearance; the extent of diarrhoea and dehydration; performance, as measured by average daily gains and feed conversion efficiency; the presence or absence of Treponema hyodysenteriae in the faeces and mortality. As a result of statistical analysis of these parameters tiamulin medication was found to be an efficacious therapeutic regimen for naturally occurring swine dysentery when given at either level in the drinking water.

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Swine; Swine Diseases; Treponemal Infections; Water

The effects of tylosin tartrate and tiamutilin were examined in pneumonias induced experimentally in neonatal piglets with a homogenate of pneumonic pig lung, obtained from pigs with naturally acquired enzootic pneumonia. The homogenate contained mycoplasmas, including Mycoplasma hyopneumoniae (M suipneumoniae) and M hyorhinis, and certain bacteria and viruses. The experimental pneumonias generally resembled mycoplasmal pneumonia histologically but were complicated by aspiration pneumonia in some animals. both tylosin tartrate (50 mg/kg) and tiamutilin (10 mg/kg) administered orally twice daily for 10 days, beginning 14 days after intranasal infection, significantly reduced the incidence and severity of macroscopical pneumonic lung lesions. M hyopneumoniae could be isolated from the lungs of the unmedicated piglets, but not from drug-treated piglets. The numbers of M hyorhinis, Acholeplasma granularum, Haemophilus parasuis, Pasteurella multocida and P haemolytica in the lung tissue of the infected piglets were significantly reduced by drug therapy. The role of bacterial in the experimental infection appeared to be that of secondary invaders.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Diterpenes; Drug Therapy, Combination; Leucomycins; Pneumonia; Pneumonia of Swine, Mycoplasmal; Pneumonia, Aspiration; Pneumonia, Viral; Swine; Swine Diseases; Tylosin

Topics: Animal Feed; Animals; Diterpenes; Drug Interactions; Furans; Monensin; Swine; Swine Diseases

Topics: Animals; Diterpenes; Female; Furans; Male; Swine; Swine Diseases

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Drug Interactions; Female; Furans; Male; Monensin; Muscular Diseases; Swine; Swine Diseases

Tiamulin was found to be effective in the treatment of experimental swine dysentery when included in the drinking water at 22.5, 45 and 60 ppm for three and five days. Only medication of the drinking water with 60 ppm for three and five days resulted in complete prevention of relapse and the elimination of T hyodysenteriae. When tiamulin was given in the feed for 47 days at 25, 30, 35 and 40 g per ton it prevented the development of the clinical signs or post mortem lesions of experimental swine dysentery. The results obtained suggested that it may not have completely prevented the establishment of T hyodysenteriae in the intestines of some of the pigs. The possibility that tiamulin had some effect on the lesions of enzootic pneumonia when given in the drinking water at 60 ppm and in the feed at 40 g per ton is discussed.

Topics: Administration, Oral; Animal Feed; Animals; Anti-Bacterial Agents; Diterpenes; Dysentery; Swine; Swine Diseases; Treponemal Infections; Water

Topics: Animals; Anti-Bacterial Agents; Diterpenes; Leucomycins; Mycoplasma; Mycoplasma Infections; Oxytetracycline; Pneumonia; Swine; Swine Diseases

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Body Weight; Diterpenes; Dysentery; Food Additives; Swine; Swine Diseases; Treponemal Infections