The activity of the diaminopyrimidine dihydrofolate reducatase inhibitor, iclaprim, against Toxoplasma gondii in an in vitro model: a pilot study

The objective of this pilot study was to examine the activity of iclaprim, a diaminopyrimidine dihydrofolate reducatase inhibitor, in an in vitro infection model of infection with Toxoplasma gondii. Toxoplasma growth was assessed by enzyme linked immunoassay (ELISA) performed directly on the fixed cultures using a peroxidase labeled monoclonal antibody directed against the SAG-1 surface protein of T. gondii. For each well, the results were expressed as optical density (OD) values. Iclaprim inhibited T gondii growth at concentrations between 0.1 and 10 mg/L; the IC50 was estimated at 0.26 mg/L (95% confidence interval 0.22-0.33). Iclaprim was about 10 times more active than trimethoprim, which had an IC50 of 2.3 mg/L. Iclaprim demonstrated synergistic effects at concentrations of 0.02, 0.05 and 0.1 mg/L when combined with subinhibitory concentrations of sulfamethoxazole (0.1 or 0.02 mg/L). These results show that iclaprim is a potent inhibitor of T. gondii growth in vitro. In addition, iclaprim exhibited synergy in vitro when tested in the presence of sulfamethoxazole. Iclaprim should be further investigated as an agent for the treatment or prophylaxis of toxoplasmosis. (C) 2020 Elsevier Inc. All rights reserved.