Methods and compositions for reducing Shiga toxin induced toxicity in mammals
Manganese compositions effective in reducing Shiga toxin-induced toxicity in mammals infected with Shiga toxin-producing bacteria such as E. coli O157:H7 are described. Manganese compositions described herein can be combined with antibiotic therapy as manganese can block the toxic effects of Shiga toxin released from dying bacteria.
1. A method of reducing Shiga toxin (STx)-induced toxicity in a mammal infected with STx-producing bacteria, said method comprising administering to said infected mammal a manganese composition comprising from about 0.002 mg/kg of body weight to about 50 mg/kg of body weight of manganese.
2. The method of claim 1 , wherein reducing STx-induced toxicity comprises reducing occurrence or severity of one or more enteric symptoms selected from the group consisting of diarrhea, hemorrhagic diarrhea, abdominal cramps, nausea, and vomiting.
3. The method of claim 1 , wherein reducing STx-induced toxicity comprises reducing risk of developing hemolytic uremic syndrome (HUS) or hemorrhagic colitis.
4. The method of claim 1 , wherein said manganese composition comprises a manganese salt or a manganese amino acid chelate.
5. The method of claim 4 , wherein said manganese salt is manganese carbonate, manganese acetate, manganese citrate, manganese oleate, manganese oxalate, manganese chloride, manganese borate, manganese nitrate, manganese phosphate, or manganese sulfate, or wherein said manganese amino acid chelate comprises manganese ions bound to one or more of arginine, asparagine, cysteine, glutamine, histidine, lysine, ornithine, and tryptophan.
6. The method of claim 1 , where said STx-producing bacteria are STx-producing E. coli or Shigella dysenteriae .
7. The method of claim 6 , wherein said STx-producing E. coli are E. coli strain O26, O45, O103, O104, O111, or O157.
8. The method of claim 7 , wherein said E. coli strain O157 is O157:H7 or wherein said E. coli strain O104 is O104:H4.
9. The method of claim 1 , said method further comprising administering an antibiotic to said infected mammal.
10. The method of claim 9 , wherein said antibiotic is selected from the group consisting of a cephalosporin, an aminoglycoside, a macrolide, a quinolone, a monobactam, a sulfonamide, or a carbapenem.
11. The method of claim 10 , wherein said quinolone is nalidixic acid or a fluoroquinolone or wherein said fluorquinolone is norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, lomefloxacin, fleroxacin, perfloxacin, or amifloxacin.
12. The method of claim 1 , said method further comprising administering an antidiarrheal agent to said infected mammal.
13. The method of claim 12 , wherein said antidiarrheal agent is an agonist of the μ opioid receptor.
14. The method of claim 1 , wherein said manganese composition is administered intravenously or orally.
15. The method of claim 1 , wherein said mammal is a human.
16. The method of claim 1 , wherein said mammal is diagnosed as being infected with said STx-producing bacteria before administering said manganese composition.
17. A method of reducing risk of a mammal developing STx-induced toxicity from STx-producing bacteria, said method comprising administering to said mammal a manganese composition comprising from about 0.002 mg/kg of body weight to about 50 mg/kg of body weight of manganese.
18. The method of claim 17 , wherein said manganese composition comprises a manganese salt or a manganese amino acid chelate.
19. A method of treating a mammal infected with STx-producing bacteria, said method comprising administering to said infected mammal (i) a manganese composition comprising from about 0.002 mg/kg of body weight to about 50 mg/kg of body weight of manganese and (ii) an amount of an antibiotic effective to at least inhibit growth of said STx-producing bacteria.
20. A method of treating a mammal, said method comprising determining whether said mammal is infected with STx-producing bacteria, and based on the determination that the mammal is infected with STx-producing bacteria, treating the mammal with a manganese composition comprising from about 0.002 mg/kg of body weight to about 50 mg/kg of body weight of a manganese.
21. The method of claim 20 , said method further comprising selecting an antibiotic based on the sensitivity of said STx-producing bacteria that has infected said mammal to said antibiotic and administering said selected antibiotic to said mammal.
22. A method of reducing Shiga toxin (STx)-induced toxicity in a human infected with STx-producing bacteria, said method comprising administering to said infected human a manganese composition comprising from about 0.002 mg/kg of body weight to about 50 mg/kg of body weight of manganese.
23. The method of claim 1 , wherein the method avoids adverse side effects.
24. The method of claim 22 , wherein the method avoids adverse side effects.
25. The method of claim 23 or 24 , wherein the adverse side effects are selected from the group consisting of lethality, paralysis, reduced body weight, and reduced locomotion.
26. A method of reducing Shiga toxin (STx)-induced toxicity in a mammal infected with STx-producing bacteria, said method comprising administering to said infected mammal a manganese composition comprising from 20-30 mg/kg of body weight of manganese.
27. A method of reducing Shiga toxin (STx)-induced toxicity in a human infected with STx-producing bacteria, said method comprising administering to said infected human a manganese composition comprising from 20-30 mg/kg of body weight of manganese.
28. The method of claim 1 wherein the amount of the manganese composition administered is selected from the group consisting of from 0.002 to 0.01 mg/kg of body weight, 0.1 to 1 mg/kg of body weight, 0.15 to 0.8 mg/kg of body weight, 0.5 to 1.0 mg/kg of body weight, 1 to 10 mg/kg of body weight, 5 to 15 mg/kg of body weight, 10 to 20 mg/kg of body weight, 15 to 25 mg/kg of body weight, 20 to 30 mg/kg of body weight, 25 to 35 mg/kg of body weight, 30 to 40 mg/kg of body weight, 35 to 45 mg/kg of body weight, and 40 to 50 mg/kg of body weight.
29. The method of claim 22 wherein the amount of manganese administered is selected from the group consisting of from 0.002 to 0.01 mg/kg of body weight, 0.1 to 1 mg/kg of body weight, 0.15 to 0.8 mg/kg of body weight, 0.5 to 1.0 mg/kg of body weight, 1 to 10 mg/kg of body weight, 5 to 15 mg/kg of body weight, 10 to 20 mg/kg of body weight, 15 to 25 mg/kg of body weight, 20 to 30 mg/kg of body weight, 25 to 35 mg/kg of body weight, 30 to 40 mg/kg of body weight, 35 to 45 mg/kg of body weight, and 40 to 50 mg/kg of body weight.
30. The method of claim 1 wherein manganese is administered at about 25 mg/kg of body weight.
31. The method of claim 1 wherein manganese is administered at about 50 mg/kg of body weight.