358 



DESCRIPTIONS OF ANTIBIOTICS 



bacteria, including mycobacteria, and Actino- 

 myces bovis, l)ut not on gram-negative bacteria, 

 yeasts, filamentous fungi, or protozoa. A and B 

 show cross-resistance to each other, but no cross- 

 resistance to erythromycin, penicillin, strepto- 

 mycin, the tetracyclines, chloramphenicol, or 

 polymyxin B. Development of resistance is slow. 

 Bactericidal. B is about 3 to 4 times more active 

 than A against streptococci in vitro and in vivo. 

 Active in vivo on Streptococcus pyogenes, Staph. 

 (iKreiis, and D. pneumoniae, but not on Mycobac- 

 leriuiii in mice (1, 4, 5). 



Toxicity: LD50 (mice) intravenously: ristocetin 

 A sulfate: 1350 to 2000 mg per kg; ristocetin B 

 sulfate: 645 to 760 mg per kg; complex (predomi- 

 nantly A) : 888 to 1820 mg per kg. The lower figure 

 in each case represents rapid injection; the higher 

 figure, slow injection. Orally, 5 to 12.5 gm per 

 kg, and subcutaneously, 1 gm per kg of the com- 

 plex are tolerated by mice (3). Hematologic com- 

 plications noted during therapy in 8 out of 10 

 patients tested (4). 



Utilization: Enterococcal, staphylococcal, and 

 ])neumococcal infections resistant to other anti- 

 ))iotics. Used intravenously only (1, 4, 6, 7). 



References: 



1. Grundy, W. E. e/ o/. Antibiotics Ann. 1956- 



1957, pp. 687-715. 



2. British Patent 765,886, January 16, 1957. 



3. Hwang, K. et al. Antibiotics Ann. 1957- 



1958, pp. 163-179. 



4. Gangarosa, E. J. et al. New Engl. J. Med. 



259: 156-161, 1958. 



5. Helper, J. C. et al. Antibiotics Ann. 1958- 



1959, pp. 425-427. 



6. Kanner, I. F. Antibiotics Ann. 1958-1959, 



pp. 432-436. 



7. Miller, J. M. et al. Antibiotics Ann. 1958- 



1959, pp. 441-446. 



Ro.seocilriii B 



Produced by: Streptomyces roseocitrcus (4). This 

 culture also produces roseocitrin A, a substance 

 more closely related to streptothricin (see strepto- 

 thricins). 



Method of extraction: I. Isolation procedure 

 like that of streptomycin (1, 2). II. Broth-fil- 

 trate extracted with 1 per cent lauric acid-buta- 

 nol. Extract re-extracted into water (pH 2.0). 

 Aqueous extract concentrated, shaken with 80 

 per cent phenol, then with ether. Chromato- 

 graphed on AI2O.3 with 50 per cent acetone as 

 solvent and developer. Active fractions dried in 

 vacuo, dissolved in methanol, then precipitated 

 with acetone. Precipitated from a methanolic 



solution with acetone-ether. Purified by conver- 

 sion to the helianthate, then the hydrochloride 

 (3). 



Chemical and physical properties: Basic sub- 

 stance. Solul)Ie in 50 to 60 per cent acetone. In- 

 soluble in ether (2). Hydrochloride: Needles. 

 Helianthate: d.p. 305-306°C. Positive Molisch, 

 indole, and Eison-Morgan tests. Negative Feh- 

 ling, maltol, biuret, ninhydrin, xanthoproteic, 

 Adamkiewitz, Liebermann, Neubauer, and Saka- 

 guchi tests (3). Rf values in various systems given 

 in reference 2. Stable to acid (3). 



Biological activity: Moderately active (12.5 to 

 100.0 ixg per ml) on gram-positive and gram-nega- 

 tive bacteria and mycobacteria. No cross-resist- 

 ance with streptothricin or streptomycin. Most 

 active at alkaline pH (3). 



Toxicity: Mice tolerate 1 gm per kg intrave- 

 nously (3). 



References: 



1. Kato, H. J. Antibiotics (Japan) 3: 579- 



581, 1950. 



2. Kato, H. J. Antibiotics (Japan) 6B: 3-8; 



6A:42, 1953. 



3. Kato, H. J. Antibiotics (Japan) 6B: 141- 



149; 6A:108, 1953. 



4. Kato, H. J. Antibiotics (Japan) 6B: 205- 



209, 1953. 



Roseomycin 



Produced by: Streptomyces roseochromoyenes 

 strains (1, 2, 6, 10), and Streptoinyces sp. (6). 



Remarks: Roseomycin is classified as a "strepto- 

 thricin r"-t.ype antibiotic, according to the ter- 

 minology of certain Japanese workers. See strep- 

 tothricin-like antibiotics for an explanation. 



Synonym: Antibiotic 36 (4). 



Method of extraction: Same as that for strepto- 

 thricin (1, 2). 



Chemical and physical properties: Basic sub- 

 stance. Reineckate: Platelets; m.p. 114°C (decom- 

 position) (1, 7). Helianthate: Platelets; m.p. 211- 

 216°C (decomposition) (1, 7). Hydrochloride: 

 Positive Fehling, Molisch, glucosamine, and 

 Tollen tests (1, 10). Negative biuret, ninhydrin, 

 xanthoproteic, Adamkiewitz, Liebermann, Neu- 

 bauer, Tollen naphthoresorcinol, indole, maltol, 

 and Sakaguchi tests (7, 10). Boiling at pH 2.0 or 

 5.0 for 20 minutes causes a 90 per cent loss in ac- 

 tivity; at pH 9.0, a 50 per cent loss (10). 



Biological activity: See "Remarks" above. More 

 active in vitro than streptomj^cin on V. cholerae 

 (2). More active on streptomycin-resistant E. 

 coli than on the parent strain (5, 10). Equally ac- 

 tive as streptomycin against tularemia and 



