tiamulin and Dysentery

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

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

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

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

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

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

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

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

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

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

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

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

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