Chemotherapy of Experimental Chagas' Disease with Thirty Antibiotics

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Abstract
Summary The following antibiotics were tested against Trypanosoma cruzi both in vitro and in vivo, 23 for the first time: 1. acti-dione; 2. antibiotic S; 3. aureomycin hydrochloride; 4. bacillin culture filtrate; 5. bacitracin—topical; 6. borrelidin sodium; 7. Bristol A6786-52; 8. chloramphenicol (chloromycetin); 9. circulin (antibiotic Q-19); 10. dihydrostreptomycin sulfate; 11. endomycin; 12. fradicin; 13. fumagillin; 14. gliotoxin; 15. gramicidin; 16. neomycin sulfate; 17. penicillin G sodium; 18. penicillin O potassium (allymercaptomethyl); 19. 1,2-diphenyl-2-methylamine ethanol penicillin; 20. pleocidin; 21. polymyxin B sulfate; 22. rimocidin; 23. streptomycin sulfate; 24. subtilin; 25. terramycin hydrochloride; 26. thiolutin; 27. tyrocidine hydrochloride; 28. tyrothricin; 29. viomycin sulfate; 30. viridin. In vitro tests were performed by a newly developed method with the 30 antibiotics against two strains of Tr. cruzi (Pack-Brazil-46 and WBHT). Out of the 30 antibiotics, 18 showed immobilizing or trypanocidal effects at the end of 5, 10, 15, and 60 minutes or at the end of 24 hours. The trypanostatic or trypanocidal effects ranged from dilutions of 1:10 to as high as dilutions 1:400,000, depending upon the antibiotics and time of contact periods. The remaining 12 antibiotics (Nos. 4, 5, 6, 7, 10, 13, 15, 16, 18, 19, 23, 29), used in highest concentrations practical, were innocuous to Tr. cruzi in vitro at the end of 24 hours' exposure period. In vivo tests, in spite of the above findings, were all essentially negative. None of the above 30 antibiotics, when administered intraperitoneally in maximum tolerated doses into mice infected with the virulent WBHT strain of Tr. cruzi, produced an absolute cure. All of the experimental animals, with the exception of a few which developed chronic infections, died of acute trypanosomiasis within two weeks. A few instances of suppressive action were obtained with the following antibiotics: endomycin, gramicidin, rimocidin, antibiotic S, thiolutin, tyrocidine hydrochloride, tyrothricin, and viridin. Although there were definite reductions in the number of trypanosomes present in the blood of these mice as compared with the number in the untreated mice, many died earlier than did the controls because of the toxicity of the drugs. The most marked suppression was produced by antibiotic S. However, no curative effects were obtained.