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

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-g disk concentration, and the proposed MIC breakpoints corresponding to levels achievable in animal target tissues (lung) were <4 g/ml for susceptibility and >32 g/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 g/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.Tiamulin is a pleuromutilin derivative antimicrobial used in the control and treatment of veterinary gram-positive and gram-negative pathogens, with a particular emphasis on infections in swine (11). It has exceptional activity (MIC, Յ1 g/ml) against anaerobic bacterial species, intestinal spirochetes, and Mycoplasma spp. (3,12,13). The present study was initiated in order to document the sustained antimicrobial activity of tiamulin against indicated bacterial species and rapidly growing and fastidious animal pathogens and to establish choices of diagnostic reagents. MIC and disk diffusion zone diameter correlates were determined in order to ensure the precision and accuracy of the susceptibility testing procedures performed according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines for susceptibility testing of veterinary antimicrobial agents (5, 6). MATERIALS AND METHODSOrganisms tested. The organisms tested were isolates from various types of infections and included both human and veterinary pathogens. A total of 636 strains were processed, each identified by routine methods at the institution of initial isolation and confirmed by reference testing at a referral location (CAST Laboratories, Iow...

Assessment of antibiotic susceptibility in Lactobacillus isolates from chickens

“…Callens et al [ 22 ] showed that the MIC for Streptococcus suis (332 isolates tested) from pigs ranged from 0.03 to 128 μg/ml, and MIC = 4 μg/ml was established as an epidemiological cut-off value. Jones et al [ 23 ] showed that MIC90 was >32 μg/ml for enterococci (71 isolates tested), and 2 μg/ml for S. aureus (150 isolates).…”

Activity of Retapamulin (SB-275833), a Novel Pleuromutilin, against Selected Resistant Gram-Positive Cocci

“…Compared to tiamulin, retapamulin appears to be uniformly eightfold more potent. While this antimicrobial class has not been developed previously for human application, the use of related antimicrobial agents in veterinary medicine has been well established (6,9). Given the declining efficacy of contemporary approved topical agents (mupirocin), the development of novel agents lacking cross-resistance to other antimicrobial classes appears warranted.…”

“…In veterinary practice, tiamulin and valnemulin (two semisynthetic pleuromutilin analogs) are used for the control and treatment of serious infections in swine (1,5). Tiamulin has exceptional activity (MIC, Յ1 g/ml) against anaerobic bacteria, Mycoplasma spp., and intestinal spirochetes (1,5,6). Tiamulin has also shown potent activity against some staphylococci from human sources (MIC 50 , Յ0.5 g/ml) (5).…”

Evaluation of antibacterial activity of Australian basidiomycetous macrofungi using a high-throughput 96-well plate assay

“…and Pleurotus passeckerianus Pilat (Pleurotaceae) (Kavanagh et al, 1951). A number of pleuromutilin derivatives have since been developed for veterinary use in the treatment of Mycoplasma infections (Drews et al, 1975;Werner et al, 1978;Hannan et al, 1997;Hunt, 2000;Jones et al, 2002;Xu et al, 2009). Furthermore, retapamulin (Altabax) has emerged as an antibiotic for human use for the topical treatment of Gram+ve bacterial skin infections including methicillin-resistant Staphylococcus aureus (Jones et al, 2006;Novak & Shlaes, 2010).…”