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Chapter 50 : Mutilins
Some mutilins, such as tiamulin and valnemulin, were introduced into veterinary medicine for the treatment of swine infections with Brachyspira hyodysenteriae (diarrhea) and Mycoplasma hyopneumoniae (pneumonia). Mutilins are semisynthetic derivatives having a tricyclic diterpenoid structure. They differ in their side chains. It was shown that the C-14 side chain is essential for antibacterial activity. The tricyclic diol mutilin did not inhibit protein synthesis. Pleuromutilins are mainly active against gram-positive bacteria and display moderate activity against fastidious gram-negative bacilli. Tiamulin MICs of >32, 4.0, and 0.06 to 0.5 µg/ml are observed for Bordetella bronchiseptica, Leptospira spp., and Mycoplasma spp., respectively. Tiamulin and valnemulin interact with adenines 2058 and 2059 and uracils 2506, 2584, and 2585. A new series of semisynthetic pleuromutilins was presented and one compound was selected for a preclinical investigation, SB264128. In pneumococcal infections, the burden reduction obtained with SB 264128 was significant (2.7 ± 1.0 log10 CFU/lung [mean plus/minus standard deviation]). In Haemophilus influenzae H 128 infection, bacterial counts in untreated rats were 5.3 plus/minus 0.7 log10 CFU/lung. SB 264128 exhibited a higher clearing activity (1.8 ± 0.2 log10 CFU/lung) than co-amoxiclav (3.5 ± 1.2 log10 CFU/lung).