IN-VITRO SUSCEPTIBILITY OF EQUINE SALMONELLA STRAINS TO TRIMETHOPRIM AND SULFONAMIDE ALONE OR IN COMBINATION

The in vitro activity of trimethoprim (TMP) and 9 sulfonamides and the ir combinations in 6 concentration ratios was tested against 62 Salmon ella strains isolated from horses over a 3-year period in the Netherla nds, using the agar-dilution method. Most of the isolates were S typhi murium strains (n = 52); the others were S heidelberg (n = 3), S hadar (n = 2), S thompson (n = 2), S enteritidis (n = 1), S infantis (n = 1 ), and S derby (n = 1). The minimal TMP concentration at which 50% of the Salmonella strains were inhibited (MIC(50)) was 0.12 mu g/ml. Sulf achlorpyridazine (SCP; MIC(50) 16 mu g/ml), sulfamethoxazole (SMX; MIC (50), 32 mu g/ml), and sulfadiazine (SDZ; MIC(50); 32 mu g/ml) were th e most potent of the sulfonamides tested. The antimicrobial effect of the sulfonamides, in cbomination with TMP (additive, synergistic, or a ntagonistic), was expressed by the fractional inhibitory concentration (FIC) index. Concentrations of SDZ and SCP with TMP had marked synerg ism at all tested TMP-to-sulfonamide concentration ratios (1:1 to 1:16 0; FIC index, 0.10 to 0.50); SMX had synergy with TMP at all ratios, e xcept 1:1 (FIC index, 0.10 to 0.27). Sulfamethazine, sulfamerazine, su lfadoxine (SDX), sulfatroxazole, sulfadimethoxine, and sulfacetamide h ad MIC(50) greater than their breakpoint MIC value and are, therefore, less potent drugs. However, synergy with TMP was found for these less potent sulfonamides at certain concentration ratios, depending on the sulfonamide used. Sixteen Salmonella strains were resistant to TMP, a ll sulfonamides, and TMP-sulfonamide combinations; 14 of these strains were S typhimurium phage type 200, 1 was S typhimurium phage type 61, and 1 was S typhimurium phage type 10. Four additional Salmonella str ains were resistant to the sulfonamides alone (1 S typhimurium phage t ype 171 and 3 S typhimurium strains that could not be biotyped). Resul ts of this study indicate that SDZ, SCP, and SMX are the best sulfonam ides to combine with TMP for treatment of salmonellosis in equids, bec ause they are the most potent sulfonamides and have strong synergism w ith TMP at a wide range of TMP-to-sulfonamide concentration ratios.