DESCRIPTIONS OF ANTIBIOTICS 



291 



the cell wall in E. coU . Resistance to E. coti de- 

 velops slowly, in stepwise fashion. Resistance of 

 mycobacteria develops rapidly (3, 4, 9, 18). Active 

 in mice on D. pnnnnoin'ae, Sal. typhosa. Staph. 

 o///T».s, and Pr. Dilcians infections. Not active on 

 Streplococcus heinoli/ticiis (I, 2, 11). Preventive 

 action on mouse leprosy, leptospira in guinea pigs, 

 and Treponema pallidum infections in rabbits (8, 

 9). Not active on sarcoma 180 or lOhrlich carci- 

 noma (16). 



Toxicity: Crystalline sulfate: LD50 (rats) 415 to 

 830 mg per kg intravenously; (rabbits) 225 to 300 

 mg per kg intravenously (3). LDsn (mice) 167.9 

 mg per kg intraperitoneally, 1648 mg per kg sub- 

 €Utaneously, and 316.3 mg per kg intravenously. 

 Doses greater than 10,000 mg per kg are tolerated 

 orally (poorly absorbed from the intestinal tract ). 

 Less vestibular toxicity to cats than streptomy- 

 cin; less auditory toxicity to rats than dihydro- 

 streptomycin. Much less nephrotoxicity to dogs 

 than neomycin (5). Nephrotoxic and ototoxic in 

 human beings, but does not have the delayed oto- 

 toxicity of neomycin (20). 



Utilization: Active on certain diseases caused 

 by gram-positive and gram-negative organisms. 

 Can be given orally, parenterally, or topically 

 (19). Not considered effective in infections caused 

 by enterococci, pneumococci, or anaerobes (20). 

 Somewhat active on tuberculosis (21). Relief of 

 typhoid and Endamoeba histolytica carrier states 

 (22, 23) and can be used safely in patients allergic 

 to streptomycin (12). Possibly beneficial in cirrho- 

 sis (13). Bowel sterilization (14). Bacterial infec- 

 tions resistant to commonly used antibiotics (15). 



References: 



1. Takeuchi, T. et al. J. Antibiotics (Japan) 



lOA: 107-114, 1957. 



2. Umezawa, H. et al. J. Antibiotics (Japan) 



lOA: 181-188, 1957. 



3. Maeda, K. et al. J. .\iitil)iotics (Japan) 



lOA: 228-231, 1957. 



4. Steenken, W., Jr. et al. Trans. 17th Veter- 



ans Admin. Conf. Chemotherapy Tuberc. 

 386-391, 1958. 



5. Dickison, H. L. and Tisch, D. E. Trans. 



17th Veterans Admin. Conf. Chemother- 

 apy Tuberc. 391-397, 1958. 



6. Cron, M. J. (7 at. J. Am. Chem. Soc. »0: 



752-753, 1958. 



7. Cron, M. J. et al. J. Am. Chem. Soc. HO: 



4741-4742, 1958. 



8. Kawaguchi, Y. ct al. Japan. J. Microbiol. 



2: 95-99, 1958. 



9. Umezawa, H. Ann. N. Y. Acad. Sci. 76: 



20-26, 1958. 



10. Cron, M. J. et al. Ann. N. Y. Acad. Sci. 



76: 27-30, 1958. 



11. Hunt, G. A. and Moses, A. J. Ann. N. Y. 



Acad. Sci. 76: 81-87, 1958. 



12. Donomae, I. Ann. N. Y. Acad. Sci. 76: 



166-187, 1958. 



13. Chalmers, T. C. et al. Ann. N. Y. Acad. 



Sci. 76: 188-195, 1958. 



14. Cohn, I., Jr. Ann. N. Y. Acad. Sci. 76: 



212-223, 1958. 



15. Yow, E. M. and Monzon, O. T. Ann. N. Y. 



Acad. Sci. 76: 372-390, 1958. 



16. Sugiura, K. Ann. N. Y. Acad. Sci. 76: 



575-585, 1958. 



17. Umezawa, S. et al. J. Antibiotics (Japan) 



llA: 162, 1958. 



18. Morikubo, Y. J. Antibiotics (Japan) llA: 



171-180, 1958. 



19. Russo, J. J. and Movmtain, C. Antibiotics 



Ann. 605, 1958-1959. 



20. Finegold, S. M. et al. Antil)iotics Ann. 



(506-622, 1958-1959. 



21. Shapiro, M. and Hyde, L. Antibiotics 



Ann. 708-710, 1958-1959. 



22. Bettag, O. L. et al. Antibiotics Ann. 721- 



724, 1958-1959. 



23. Ruiz Sanchez, F. R. et al. Antibiotics Ann. 



725-735, 1958-1959. 



24. Japanese Patent 3749, May 18, 1959. 



Kananiyciii B 



Produced by: Streptomyces kanainyceticus. This 

 culture also produces kanamycin A and another 

 antibiotic (see kanamycin A). 



Method of extraction: Isolated l)y countercurrent 

 distribution of salicylidene derivatives of the 

 mixture of kanamycins A and B (methanol-water- 

 chloroform-benzene, 5:4:2:1) and chromatog- 

 raphy on Amberlite XE-64 (NH/ form) with 0.08 

 A" NH4OH. Recrystallized from 90 i)er cent etha- 

 nol (1). 



Chemical and physical properties: Basic sub- 

 stance. Decomposes over a wide range above 

 170°C. Soluble in water; slightly soluble in lower 

 alcohols; insoluble in nonpolar organic solvents. 

 Infrared data given in reference 1; spectrum is 

 said to resemble kanamycin A. [ajl = +135° (c = 

 0.63 per cent in H2O). Positive Molisch, Elson- 

 Morgan, and ninhydrin tests. Negative Fehling 

 and Benedict tests. C = 44.75%; H = 7.50%; 

 N = 12.55%. Yields Schiff bases with aromatic 

 aldehydes. Unlike kanamycin A, yields no fur- 

 fural after sulfvu-ic acid treatment. Acid hydroly- 

 sates contain desoxystrept amine, kanosamine, 

 and one unidentified ninhydrin -positive spot. 



