Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro.
Presently, the two most commonly used drugs for treating microsporidiosis in persons with AIDS are albendazole and fumagillin. Albendazole is effective for treating disseminated infections due to Encephalitozoon spp. but is variably effective against Enterocytozoon bieneusi infections. Fumagillin is highly effective when used topically to treat ocular infections with Encephalitozoon hellem or Encephalitozoon intestinalis but is too toxic for systemic use. In this study, the fumagillin analog TNP-470 was assayed for antimicrosporidial activity in vitro. The MICs of TNP-470 at which 50% of isolates were killed (MIC50s) were 0.35 +/- 0.21 and 0.38 +/- 0.11 ng/ml for E. intestinalis and Vittaforma corneae, respectively, and were similar to the MIC50s of fumagillin for these organisms, which were 0.515 +/- 0.002 and 0.81 +/- 0.014 ng/ml, respectively. The MIC50 of albendazole for E. intestinalis was 8.0 +/- 4.23 ng/ml, significantly less (P < 0.01) than its MIC50 for V. corneae, which was 55.0 +/- 7.07 ng/ml. TNP-470 inhibited replication of E. intestinalis in RK-13 cells if it was given at the same time as infection or if treatment was initiated 7 days later. In addition, treatment of the infected cultures with TNP-470 at a dose of 10 ng/ml for 2 weeks, followed by discontinuation of the drug treatment, resulted in no significant increase in E. intestinalis shedding during the following 3 weeks in culture. Because TNP-470 acts against both E. intestinalis and V. corneae, and because TNP-470 was found by others to be less toxic in vivo, TNP-470 may be a promising new drug for the treatment of microsporidiosis.
Didier
E S
ES
Department of Microbiology, Tulane Regional Primate Research Center, Covington, Louisiana 70433, USA. esdid@tpc.tulane.edu
D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003510:Cyclohexanes; D004353:Drug Evaluation, Preclinical; D016819:Encephalitozoon / Q000187:drug effects* / Q000254:growth & development; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology
D000981:Antiprotozoal Agents; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin; D015766:Albendazole; D000077609:O-(Chloroacetylcarbamoyl)fumagillol