ATCvet code: QJ01XQ01

Tiamulin is a bacteriostatic semi-synthetic antibiotic belonging to the pleuromutilin group of antibiotics and acts at the ribosomal level to inhibit bacterial protein synthesis.

Tiamulin has shown a high level of in vitro activity against porcine and avian Mycoplasma species as well as gram-negative anaerobes (Brachyspira hyodysenteriae, Brachyspira pilosicoli), and gram-negative aerobes (Actinobacillus pleuropneumoniae and Pasteurella multocida).

Tiamulin has been shown to act at the 70S ribosome level and the primary binding sites are on the 50S subunit. It appears to inhibit microbial protein production by producing biochemically inactive initiation complexes, which prevent elongation of the polypeptide chain.

Bactericidal concentrations can be reached but vary according to the bacterium. It can be as little as two times the MIC for Brachyspira hyodysenteriae and Actinobacillus pleuropneumoniae but as high as 50-100 times the bacteriostatic level for Staphylococcus aureus. The MIC distribution for tiamulin against Brachyspira hyodysenteriae is bimodal, suggesting reduced susceptibility of some strains to tiamulin. Due to technical constraints the susceptibility of Lawsonia intracellularis is difficult to test in vitro.

Resistance derives from chromosomal mutations in the 23 rRNA and rplC genes. These chromosomal mutations emerge relatively slowly and in a stepwise fashion and are not transferred horizontally. In addition, resistance genes can be located on plasmids or on transposons like the vga genes and the cfr gene. This type of resistance is transferable between bacteria and bacterial species. The mechanism of antimicrobial resistance varies according to the bacterial species. Mutations in the ribosomal protein L3 gene and 23S ribosomal RNA gene affecting the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira species. Mutations in the 23S ribosomal RNA gene are also associated with tiamulin resistance in Mycoplasma species.

Tiamulin hydrogen fumarate is well absorbed in the pig (over 90%) following oral administration and widely distributed through the body.

Following a single oral dose of 10 mg and 25 mg tiamulin hydrogen fumarate/kg body weight the Cmax was 1.03 μg/ml and 1.82 μg/ml in serum respectively by microbiological assay and the Tmax was 2 hours for both. It has been shown to concentrate in the lung, polymorphonuclear leucocytes and also in liver, where it is metabolised and excreted (70-85%) in the bile, the remainder is excreted via the kidney (15-30%). Serum protein binding is approximately 30%. Tiamulin, which has not been absorbed or metabolised, passes down the intestines to the colon. Colon contents concentrations of tiamulin have been estimated at 3.41 μg/ml following administration of tiamulin hydrogen fumarate at 8.8 mg/kg body weight.

Tiamulin hydrogen fumarate is well absorbed in chickens (70-95%) after oral administration and reaches peak concentrations in 2-4 hours (Tmax 2.85 hours). Following a 50 mg tiamulin hydrogen fumarate/kg body weight single dose the Cmax was 4.02 μg/ml in serum by microbiological assay and after a 25 mg/kg dose it was 1.86 μg/ml. In drinking water the 250 ppm (0.025%) tiamulin hydrogen fumarate concentration provided a rolling serum level over a 48 hour medication period of 0.78 μg/ml (range 0.45-1.4 μg/ml) and at 125 ppm (0.0125%), 0.38 μg/ml (range 0.2-0.65 μg/ml) in eight-week old chickens. Serum protein-binding was approximately 45%. It distributes widely through the body and has been shown to concentrate in the liver and kidney (sites of excretion) and in the lung (30 times serum level). Excretion is mainly via the bile (55-65%) and kidney (15-30%) as mainly microbiologically inactive metabolites and is quite rapid, 99% of the dose within 48 hours.

In turkeys serum levels of tiamulin hydrogen fumarate are lower with a 50 mg tiamulin hydrogen fumarate/kg body weight single dose giving a Cmax of 3.02 μg/ml in serum, and 25 mg/kg giving 1.46 μg/ml. These were achieved at about 2-4 hours after dosing. In breeders on 0.025% tiamulin hydrogen fumarate the average serum level was 0.36 μg/ml (range 0.22-0.5 μg/ml). Serum protein-binding was approximately 50%.

Tiamulin is very persistent in soils.