264 



DESCRIPTIONS OF ANTIBIOTICS 



erythomyciii B by a variety of systems with paper 

 chromatography has been reported (18). Other 

 information on Rf values given in reference 13. 

 pK;/ = 8.6 to 8.8 (1, 15j. Cry.stallographic data 

 given in references 1, 13, and 16. Moderately stable 

 at pH 5.0 to 8.5; 75 per cent activity lost on boil- 

 ing for 1 hour; 50% lost after heating at 60°C for 

 5 minutes (3). C = 61.05%; H = 9.43%; N = 

 1.91%; C— CH, = 17.98% (13). After dra.stio acid 

 degradation, products include dimethylamine and 

 desosamine. Desosamine (3-dimethylamino-4-des- 

 oxy-5-methylaldopentose) (I): CsHnNO^HCl; 

 m.p. 183-184°C or 191-193°C. [a]f = +54.5° (c = 

 2 per cent in ethanol) (9, 15). Treatment with 0.3 

 A' HCl at 25°C yields a nitrogen-free sugar, cladi- 

 nose (II), a neutral oil, CsHif04 , and erythralos- 

 amine (III). Cladinose: Soluble in water, alcohols, 

 acetone, ether, and benzene; slightly soluble in 

 petroleum ether. Positive Tollen and iodoform 

 tests. Acid-labile (10, 25). Erythralosaniinc: Elon- 

 gated prisms; m.p. 206-207°C. Soluble in dilute 

 HCl, alcohols, acetone, ether, chloroform, and 

 benzene. Insoluble in water and dilute alkali. 

 Hydrolysis products include I (10, 15). Reduction 

 of erythromycin gives dihi/droerythroniycin, m.p. 

 133-135°C, C;nH69NOu (IV). Treatment with 

 HCl -methanol removed II, to give a substituted 

 polyhydroxylactone, C29H.55N()io (V), differing 

 from III. Acid hydrolysis of V gave dihydroeryth- 

 ronolide (VI) , C21H40O8 , in which the ketone group 

 of the aglycone of erythromycin (erythronolide) 

 has been reduced to a hydroxyl (24, 26). Structural 

 formula (C^HgtOisN) given in Chapter 6. Solvates: 

 Very stable to heating. Solvent easily removed on 

 addition of water (39). Hydrochloride: White 

 needles; m.p. 170-173°C. Very solul)le in lower 

 alcohols. Soluble to 40 mg per ml in water. Slightly 

 soluble in ethyl acetate, ether, amyl acetate, and 

 chloroform (5, 13). Infrared spectrum given in 

 reference 13. Acid addition salt (with unidentified 

 organic acid, see II under "Methods of Extrac- 

 tion"): White hexagonal needles; m.p. 82-83. 5°C 

 (13). A number of derivatives, none of which had 

 'activity greater than erythromycin, are reported 

 in references 31 and 32. 



Biological activity: In vitro: Active on gram- 

 positive bacteria, mycol)actoria, corynebacteria, 

 Actinomyces israelii, Clostridia, and certain gram- 

 negative bacteria of the Heniophilns-Brucella 

 group (1-3, 0, 8). Not active on A', asteroides or 

 pathogenic fungi (8). Active on Endamoeba histo- 

 lytica only in the presence of bacteria, and Tricho- 

 monas vaginalis (1, 12). Active on pleuropneu- 

 monia-like organisms isolated from arthritic 

 goats (27). Most active at alkaline pH (3). Bac- 



teriostatic or l)actericidal depending on concen- 

 tration of 1 he antibiotic and on the organism used. 

 Active only on multiplying bacteria (4). Cross- 

 resistance with carbomycin, spiramycin, oleando- 

 mycin, and streptogramin (22). In vivo: Active 

 (mice) on Streptococcus pyogenes, D. pneumoniae, 

 Hemophilus pertussis (only when organism was 

 injected intranasally, not intracerebrally), Co- 

 rynehacteriuni diphtheriae, Clostridium tetani, 

 Borrelia novyi, Leptospira icterohaemorrhayiae 

 (hamsters), and moderatel}' active on M. tubercu- 

 losis (1, 6, 7, 14, 29, 30). Active on Endamoeba 

 histolytica (rats) (12), Trichomonas vaginalis (1), 

 Trypanosoma equipcrdum (but not T. cruzi), and 

 toxoplasmosis in mice (1, 12). Active (chick em- 

 bryos) on Rickettsia proioazekii and R. typhi; mod- 

 erately active on R. rickettsii and R. akari; and 

 slightly active on Coxiella burnetii (7, 20). Active 

 (chick embryos) on psittacosis, meningopneumo- 

 nitis, lymphogranuloma venereum, and feline and 

 mouse pneumonitis agents (1, 6, 7, 21, 28), but 

 not on MM, Semiliki Forest, poliomyelitis (Lan- 

 sing type 2), influenza A (PR 8), or Ij'mphocytic 

 choriomeningitis viruses (7). Active (mice) on 

 oxyurids, Syphacia obvelata, and Aspicularis 

 let rapt era (12). Increases growth rate of swine, 

 chicks (11), and turkey poults (36). 



Toxicity: Base: LD.,o (mice) 1800 to >2500 mg 

 per kg sul)cutaneously, 3112 ± 211 mg per kg 

 orally, and >700 mg per kg intraperitoneally 

 (1,5). LDou (rat) >3000 mg per kg orally, >2C00 

 mg per kg subcutaneously (5). LD50 (guinea pig) 

 413.4 ± 51.7 mg per kg intraperitoneally (5). A 

 delayed toxicity for guinea pigs was reported 

 (17). Pigs exhibiting toxic symptoms at as low a 

 dose as 1.5 mg per pig have no gross morphological 

 findings excejjt paleness and spleen shrinkage 

 (35). LDoo (hamster) 3018 ± 190 mg per kg orally 

 (5). Increasing toxicity to hamsters was noted 

 over a period following introduction ot the drug 

 into the laboratory- (30). Hydrochloride: LDso 

 (mice) 425.6 ± 15.7 mg per kg intravenously, 

 490.0 ± 30.4 mg per kg intraperitoneally, 1849 ± 

 89 mg per kg sul)cutaneously, and 2927 ± 162 mg 

 per kg orally (5). Nontoxic to carnation cuttings 

 at 120 ppm (23). Least injurious doses for human 

 skin and chick embryo spleen cells in tissue cid- 

 ture are 85 to 170 and 30 to 60 jug per ml, resjjcc- 

 tively (19). Highest concentration permitting 

 migration of epithelial cells in tissue culture is 

 2.5 mg per ml (40). Minimal dose inhibiting mitosis 

 ot HeLa cells is 1 to 2 mg per ml (33). 



Utilization: Infections caused by gram-positive 

 bacteria, especially those in which penicillin can- 



