Nebramycin complex

Apramycin is a broad-spectrum aminocyclitol antibiotic and component of the nebramycin complex, produced by a strain of Streptomyces tenebrarius. Use of this antibiotic is specifically aimed at mass therapy of colibacillosis and salmonellosis in veal calves and swine. It is administered to calves by intramuscular or oral route at a dose of 20-40 mg/kg body weight/day for 5 days, and to swine via the drinking water at a dosage of 7.5-12.5 mg/kg bw/day for 7 days, or via the feed at a rate of 100 mg/kg feed for 28 days. It is further used for treatment of colibacillosis in lambs given orally at a dosage of 10 mg/kg bw/day for 3-5 days, and for treatment of E. coli septicemia in poultry administered in the drinking water at a concentration of 250-500 mg/L for 7 days. In contrast to other aminoglycosides, apramycin is not used in human medicine. 

Reviews have appeared on the synthesis of aminoglycoside antibiotics, and on the formation of new aminocyclitol antibiotics by mutants of amino-cyclitol-producing organisms fed with aminocyclohexanol or related subunits. The structures of eight minor components of the nebramycin complex elaborated by Streptomyces tenebrarius have been elucidated besides neamine and related pseudo-disaccharides, the new components are pseudo-trisaccharides related to kanamycin B, and the 3 -hydroxy analogue of the principal component of the complex, apramycin (see Vol. 10, p. 130). ... 

The n.m.r. spectra of some of the components of the nebramycin complex have been reported. Resonances of the individual nitrogen nuclei were assigned by comparison of the spectra with those of structurally similar compounds. Substituent effects and the effects of pH on the N chemical shifts were also examined. 

The elucidation of the structures of the members of the nebramycin complex has continued. Factor 2 (now called apramycln) has the unique structure (6)1 8, factor 4 (7a) is 6"-0-carbamoyl kanamycin B, factor 5 is kanamycin B (7b). factor 5 is 6"-0-carbamoyl tobramycin (7c) and factor 6 (7d) is tobramycin. Factor 5 and tobranycin are not normally detected in fermentation broths but arise from the acid- or base-catalyzed hydrolysis of their carbamoyl derivatives.139... 

Resistance to tobramycin. A complex of anti-bacterial compounds known as nebramycin was first isolated from a strain of streptomyces [215,216]. Of these, factor 6, afterwards known as tobramycin, was the most active [217]. The compound is extremely effective as an anti-bacterial agent against Ps. aeruginosa. Neu [110] reported that 80% of strains tested were sensitive to 1.56 g/ml. 

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