TDK conference 2024

Potentiated sulfonamides (PSA) are antibacterial agents belonging to the AMEG D category. In our study, we investigated the susceptibility of bacteria involved in Porcine Respiratory Disease Complex (PRDC) to three potentiated sulfonamides and the degree of synergism between the two active substances in the combinations.

As the first step of our study, we determined the minimum inhibitory concentrations (MIC) of 12 Pasteurella multocida, 14 Streptococcus suis, 13 Actinobacillus pleuropneumoniae, and 10 Glaesserella parasuis strains, isolated from pigs under the VetPath program, against the combinations of trimethoprim-sulfamethoxazole (TRP-SX), trimethoprim-sulfaclorpyridazine (TRP-SCP), and trimethoprim-sulfadiazine (TRP-SD) in four different broth media (ratio of 1:19). Subsequently, we reassessed the MIC values of the potentiated sulfonamides in cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with NAD, this time in 1:5, 1:10, 1:19, and 1:40 ratios. Finally, we examined the strains' sensitivity to the three sulfonamide components and trimethoprim individually, enabling the calculation of the fractional inhibitory concentration (FIC) index, which provides insight into the synergy between the sulfonamide and trimethoprim agents.

In the case of P. multocida, the MIC values for the TRP-SX and TRP-SD combinations were consistently ≥128 µg/ml, regardless of the ratio between the two agents. The MIC50 for the TRP-SCP combination was 32 µg/ml across all examined ratios. For S. suis strains, the MIC50 value for TRP-SX decreased from 32 µg/ml to 8 µg/ml, and for TRP-SCP from 16 µg/ml to 2 µg/ml as the ratio of sulfonamide increased, while the MIC50 for the TRP-SD combination remained at 32 µg/ml across all ratios. For A. pleuropneumoniae, the MIC50 values for TRP-SX and TRP-SD decreased from 2 µg/ml to 1 µg/ml, and for TRP-SCP from 2 µg/ml to 0.5 µg/ml as the sulfonamide ratio increased. In G. parasuis strains, the MIC50 value for TRP-SX and TRP-SKP was 2 µg/ml, regardless of the trimethoprim-to-sulfonamide ratio, while for TRP-SD, the MIC50 decreased from 4 µg/ml to 2 µg/ml with an increase in the sulfonamide ratio.

Regarding the FIC values, as the ratio between trimethoprim and sulfonamide increased, the FIC value for all bacteria tested increased. For half of the S. suis, A. pleuropneumoniae and G. parasuis strains tested, a clear synergistic effect (FIC ≤ 0.5) was determined for all three PSAs, whereas for P. multocida strains, only the TRP-SKP active substance showed a clear synergistic effect.