Introduction Potentiated sulfonamides are widely used in the treatment of porcine respiratory disease complex, but their synergistic activity depends on pathogen-related and pharmacodynamic factors, including the trimethoprim-to-sulfonamide ratio. This study aimed to systematically evaluate the effect of different ratios on in vitro antibacterial interactions against major porcine respiratory pathogens. Methods Trimethoprim was combined with sulfamethoxazole, sulfachloropyridazine, or sulfadiazine at four mass ratios (1:5, 1:10, 1:19, 1:40). Minimum inhibitory concentrations were determined using broth microdilution according to CLSI guidelines. Drug interactions were quantified using the fractional inhibitory concentration index, and a linear mixed-effects model was applied to assess the effects of bacterial species, compound combination, and ratio. Results The strongest and most consistent synergistic activity was observed at the 1:5 ratio across most pathogen–drug combinations. Increasing the proportion of the sulfonamide generally reduced synergism and occasionally resulted in antagonistic interactions, particularly in Glaesserella parasuis. Differences between sulfonamides were limited, although sulfachloropyridazine showed higher intrinsic activity against Actinobacillus pleuropneumoniae and G. parasuis, and greater efficacy in combination with trimethoprim against Pasteurella multocida. Statistical analysis confirmed significant effects of both drug ratio and combination on interaction outcomes. Discussion These findings demonstrate that synergism between trimethoprim and sulfonamides is strongly ratio-dependent and cannot be reliably characterized using a single fixed ratio. Ratio-specific evaluation may therefore support more rational antimicrobial use in veterinary medicine.
Mag et al. (Fri,) studied this question.