Due to the restrictive use of critical antibiotics in Europe, it is strongly recommended for veterinarians to use first-line antibiotics classified as category D by the EMA, such as the synergistic combination of sulfonamides (S) and trimethoprim (TMP). The optimal in vivo concentration ratio for synergism defined as 1:19 was determined 40 years ago for human medicine and using the TMP/sulfamethoxazole (SMX) combination. However, we have preliminary results showing that there are no universal “optimal” TMP:S ratios and range of synergism observed depends on the sulfonamide used in combination. Objectives : characterize the relationship between drug concentrations and effect of TMP/S combination against E. coli by developing a semi-mechanistic PK/PD model based on time-kill data.