Tiamulin Activity against Fastidious and Nonfastidious Veterinary and Human Bacterial Isolates: Initial Development of In Vitro Susceptibility Test Methods

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Abstract
Tiamulin is a pleuromutilin derivative used in veterinary practice for the control and specific therapy of infections in swine. This report summarizes studies to establish standardized susceptibility testing methods, interpretive criteria, and reagent details for use in veterinary methods recently developed by the National Committee for Clinical Laboratory Standards (NCCLS) (standards M31-A and M37-A, NCCLS, Wayne, Pa., 1999). A total of 636 fastidious and nonfastidious animal and human pathogens were processed by using media and procedures described by the NCCLS. Tiamulin disk diffusion tests used a 30-μg disk concentration, and the proposed MIC breakpoints corresponding to levels achievable in animal target tissues (lung) were ≤4 μg/ml for susceptibility and ≥32 μg/ml for resistance. Correlate zone diameters for specific nonfastidious species were as follows: for Pasteurella multocida and staphylococci tested on Mueller-Hinton agar, susceptibility at ≥19 mm and resistance at ≤11 mm, and for Actinobacillus suis , Erysipelothrix rhusiopathiae , and Streptococcus suis tested on enriched chocolate Mueller-Hinton agar, susceptibility at ≥16 mm and resistance at ≤8 mm. When Actinobacillus pleuropneumoniae was tested, a susceptibility breakpoint of ≤16 μg/ml (≥9 mm) was suggested for veterinary fastidious medium broth and enriched chocolate Mueller-Hinton agar. Absolute categorical agreement between NCCLS dilution and disk diffusion test results with these criteria ranged from 90.5 to 96.2%. Tiamulin susceptibility testing methods appear to be accurate in their categorical classification for indicated species, and their availability will allow immediate testing of animal isolates to guide therapy via appropriate levels of dosing and to monitor the development of resistance for agents in this unique class.