TABLE 1.
Drug(s) | References | Mechanism of action | In vitro IC50 | Murine lethal challenge(s) and outcome (reference[s]) |
---|---|---|---|---|
Pyrimethamine | 15–20 | Antifolate | 0.4 μM | 10 mg/kg/day, 20–90% survival, depending on parasite strain (18) |
Dapsone, sulfadiazine, sulfadoxine, sulfamethoxazole | 17, 19, 21–27 | Antifolate | Dapsone, 1.2 μM; sulfadiazine, 1.6 μM; sulfamethoxazole, 395 μM | Dapsone, 100 mg/kg/day, 100% survival (24); sulfadiazine, 375 mg/kg/day, 100% survival (17); sulfamethoxazole, 600 mg/kg/day, 100% survival (26) |
Clindamycin | 17, 27–30 | Protein synthesis inhibitor | 0.005 μM | 300 mg/kg/day, increased survival by 11 days (17) |
Trimethoprim (typically combined with sulfamethoxazole) | 21, 25, 26, 31 | Antifolate | 17.2 μM | 70 mg/kg/day, 20% survival (26) |
Atovaquone | 27, 32, 33 | Mitochondrial electron transfer chain inhibitor | 0.82 μM | 5 mg/kg/day, 20% survival (19) |
Doxycycline, minocycline | 34, 35 | Apicoplast division inhibitor | Doxycycline, 14.4 μM | Doxycycline, 300 mg/kg/day, 100% survival (34) |
Acetylspiramycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, telithromycin, tylosin | 18, 29, 36–41 | Protein synthesis inhibitor | Azithromycin, 11.5 μM; clarithromycin, 401 μM; erythromycin, 19.6 μM; roxithromycin, 32.3 μM; spiramycin, 17.8 μM; telithromycin, 0.20 μM | Azithromycin, 200 mg/kg/day, 40–100% survival, depending on parasite strain (38); clarithromycin, 200 mg/kg/day, 80% survival (40); clarithromycin, 300 mg/kg/day, 100% survival (18); roxithromycin, 10 mg/day, 80–100% survival (36, 37); spiramycin, 400 mg/kg/day, no survival (38) |
The lowest observed IC50 values are reported in cases in which multiple values were found in the literature. Moreover, wide variations exist in the method of murine lethal challenge between studies: differences include infectious dose, parasite strain, drug delivery route, time postinfection before treatment initiation, treatment length, and time of observed survival.