374 



DESCRIPTIONS OF ANTIBIOTICS 



5.71%; N = 14.56%; S = 5.76% (9). Reineckate: 

 Small needles (4). Sesquiphosphate: Hexagonal 

 prisms (59). Thiosemicarhazone 3HCI: Colorless 

 crystals; m.p. 205 °C (54). Reineckate -sulfate dou- 

 ble salt: Long, thin plates; m.p. 162-164 °C (cor- 

 rected) (1, 10), 160-163°C (corrected) (7), or 164- 

 165°C (corrected) (4). Sulfate-sulfite double salt: 

 Fiber-like colorless crystals. Decomposition be- 

 gins at about 138°C, resulting in loss of the H2SO4 

 with final decomposition at 170°C without melt- 

 ing (72). Streptomycin also forms a number of 

 double salts with pentachlorophenate (73), but at- 

 tempts to form other double salts with a number 

 of other anions failed (58). "Tergifate" (see IIIB 

 under "Methods of Extraction"): Crystals; m.p. 

 141-142°C (decomposition). Soluble in alcohols. 

 Insoluble or soluble with difficulty in other organic 

 solvents. Addition of 5 to 10 per cent water in- 

 creases solubility in such solvents (59) . Streptomy- 

 cin forms an oxime (25) and a salt with orange II 

 (2,40). 



Streptomycin Chelates 



Streptomycin forms chelates with metals. These 

 are soluble in acetic acid-water; slightly soluble 

 in water, ethanol, diethyl ether, and glacial acetic 

 acid; and insoluble in propylene glycol. They are 

 stable to boiling. All are less biologically active 

 than streptomycin. Streptomycin-copper: Pale blue 

 substance. Decomposes at 165-170°C. Streptomy- 

 cin-cobalt: Blue -green substance. Decompo.ses at 

 145-150°C (93). 



Streptomycin Derivatives 



Biologically active, but more toxic derivatives 

 of streptomycin (certain N-alkyl streptomycyl- 

 amines) have been reported (31). 



Biological activity: Active on gram-negative and 

 gram-positive bacteria, including mycobacteria, 

 A. bovis, Nocardia, and certain spirochetes. Not 

 active on fungi (25). Has antialgal activity (63). 

 Interferes with the killer action of Paramecium 

 aurelia (var. 4, stock 51 killer, mating type VII) 

 (44). Increases the rate of division and length of 

 Tetrahymena pyriformis. The effect on rate of 

 division is also produced by streptobiosamine, 

 streptamine, streptidine, and guanidine (76). In- 

 activates phages of E. coli and Staph, aureus. 

 Most active at a weakly alkaline pH (25) . Resist- 

 ance to streptomycin develops rapidly in vitro 

 and in vivo. In pathogens, resistance is not accom- 

 panied by decreased virulence. Cross-resistance 

 exists with dihydrostreptomycin, mannosidostrep- 

 tomycin, and others of this group, as well as with 

 streptothricin, neomycin, streptolin, and others 



(53). Microorganisms dependent on streptomycin 

 have been reported (25). Streptomycin derivatives 

 have been reported that can replace streptomycin 

 for a dependent strain of Staph, aureus. Certain of 

 these same derivatives do not support the growth 

 of a dependent strain of E. coli but actually in- 

 hibit it, and some inhibit a streptomycin-resistant 

 strain of Staph, aureus (22). An extract of the cells 

 of a streptomycin-sensitive E. coli can replace 

 streptomycin for a dependent strain of E. coli. 

 This extract also acts to promote the early growth 

 of the sensitive strain from which it is obtained 

 (126). 



Effects on Morphology 



Certain gram-negative bacteria, such as Shigella 

 and Salmonella, became elongated, swollen, and 

 more refractory to staining when exposed to 

 slightly bacteriostatic concentrations. Sal. typhi- 

 murium assumes a coccoid form. Gram-positive 

 bacteria show no change, although mycobacteria 

 were reported to show increased granulation, de- 

 creased length, and loss of acid-fastness (25). 



Reversal of Activity 



Activity on Aerobacter aerogenes can be reversed 

 by several purine and pyrimidine derivatives. A 

 variety of salts reduce the activity of streptomycin 

 in vitro, as do glucose, cysteine, and other sub- 

 stances (25, 57). 



Activity in Vivo 



Active on M. tuberculosis (mice, guinea pigs, 

 chick embryos), Pasteurella pestis (mice and 

 guinea pigs), P. tularensis (mice), P. mjdtocida 

 (turkeys), H. influenzae (mice), H. ducreyi (rab- 

 bits), A', pneumoniae (mice), Sal. schottmuelleri 

 (mice), Sal. enteritidis (mice), Sal. puUorum 

 (chicks), Sal. typhosa (mice). Shigella gallinarum 

 (chick embryo), Sh. moniliformis (mice), Leish- 

 mania donovani (chick embryos), Staph, aureus 

 (mice), Streptococcus pyogenes (mice), D. pneu- 

 moniae (mice), and B. anthracis (mice). Moderate 

 activity on H. pertussis, Brucella (mice and guinea 

 pigs), E. coli (rabbits), Proteus (chick embryo), 

 Pseudomonas (mice), Erysipelothrix rhusiopathiae 

 (turkeys), BorreHa novyi (mice), Leptospira ic- 

 terohaemorrhagiae (Syrian hamsters and rabbits) 

 and other spirochetes, Clostridium perfringens but 

 not other Clostridia (25). Active on pleuropneu- 

 monia-like organisms (rats, chick embryos). Very 

 slightly active on Rickettsia burneti, R. akari, R. 

 prowazekii, R. rickettsii, and R. mooseri, when 

 given before infection (25). Rickettsiostatic ac- 

 tivity in eggs is reversed by X-ray irradiation 



