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DESCRIPTIONS OF ANTIBIOTICS 



Search for Salts of Lower Toxicity 



Streptomycin and streptidine are toxic to the 

 eighth cranial nerve, giving rise to vestibular dys- 

 function. Large or prolonged doses produce deaf- 

 ness. Interference with renal function is common, 

 but serious disability is rare except when there is 

 pre-existing kidney disease. Allergy to strepto- 

 mycin (dermatitis, etc.) occurs in certain patients, 

 and in persons such as nurses and agricultural 

 workers who are in rather constant contact with 

 the drug (25). Calcium was the first substance re- 

 ported to have a detoxifying effect on streptomy- 

 cin (26). German workers (83, 95) reported that 

 use of streptomycin pantothenate, instead of the 

 sulfate, reduced acute and vestibular toxicity in 

 animals. Subsequently, they found that this re- 

 duction of toxicity was partly caused by the pres- 

 ence of calcium in their preparations (from the 

 calcium pantothenate that was used). Neverthe- 

 less, they maintained that streptomycin panto- 

 thenate containing less than 1 per cent calcium was 

 still considerably less toxic than streptomycin 

 sulfate (96, 114). Sulfate: LDso (mice) 640 mg (as 

 base) per kg subcutaneously. Pantothenate: LD50 

 (mice) 1050 mg (as base) per kg, subcutaneously 

 (96). Certain workers subsequently confirmed 

 these findings (115, 116); others differed (117). In 

 some reports (115, 116), the tripantothenate was 

 found to be somewhat less toxic than the sulfate, 

 but not to the degree reported by the German 

 workers. Furthermore, the tripantothenate was 

 more toxic than the CaCl-i complex. No reduction 

 in vestibular toxicity was reported by either 

 group but a reduced ototoxicity to rats was re- 

 ported (116). LDso values reported are as follows 

 (115): Sulfate: LD50 (mice) 103.5 mg per kg intra- 

 venously. Tripantothenate: LDoo (mice) 140 mg per 

 kg intravenously. CaCh complex: LD.50 (mice) 169 

 mg per kg intravenously. The pantothenates are 

 not used clinically in the United States. 



Fish, Mollusks, Nematodes 



Streptomycin produces neurological symptoms 

 in goldfish, when it is dissolved in tank water (112) . 

 Toxic to the snail, Australorbis glabratus, inducing 

 behavioral abnormalities and inhibition of growth 

 and reproduction. This action is reversed by Ca+"'", 

 but not Mn++ (134). Slightly inhibitory to the 

 nematode Rhabditis briggsae (77). 



Plants, Algae, Protozoa, Fungi 



Exposure to certain concentrations of strepto- 

 mycin may obliterate chloroplasts in seed plants 

 (16) and in certain algal flagellates (38). In plants, 



chlorosis, or lack of chlorophyll, is not always 

 permanent (102), but sensitive plants may remain 

 chlorotic and stunted after exposure to sufficiently 

 high concentrations (103). In certain algae, such 

 as Euglena gracilis, bleached strains produced by 

 exposure to streptomycin may be maintained in- 

 definitely on simple synthetic media (38). Carote- 

 noid sjmthesis is reduced also, but not as much as 

 chlorophyll synthesis (110). These bleached cells 

 can survive 5 mg per ml of streptomycin, whereas 

 other genera are susceptible to 1 to 5 Mg per ml. 

 On the other hand, Chlorogonium euchlorum is 

 bleached by streptomycin, but no colorless strain 

 can be propagated. Resistance to bleaching and 

 killing can be induced in certain algae; however, 

 chloroplasts may be abnormal, and the pyrenoid 

 much reduced. Leucoplasts are unaffected. Re- 

 sistance to killing can also be induced in certain 

 normally colorless protozoa. In bleached stains, 

 the stigma is reduced in size and the effect on the 

 eye spot is variable (38). Dihydrostreptomycin is 

 also active, but streptobiosamine, streptamine, 

 and N-acetylglucosamine are inactive (42) . Plants 

 such as barley, germinating on a streptomycin- 

 containing medium, produce white coleoptiles and 

 first leaves containing neither chlorophyll nor 

 carotenoids, but normal amounts of anthocyanins. 

 Catalase activity is depressed (16). In cabbage 

 seedlings, a purple discoloration and death fol- 

 low seed treatment with 25 ppm. At 480 ppm, 

 applied as a spray, transient chlorosis in tobacco 

 plants has been noted (80). Na-K chlorophyllin 

 added to a 1000-ppm spray of streptomycin was 

 reported to have prevented achlorosis in bean and 

 cucumber plants (129). In the fungus Phycomyces 

 blakesleeanus , carotenoid synthesis, but not 

 growth, is inhibited by 0.1 to 0.2 per cent (weight 

 per volume) streptomycin or streptobiosamine in 

 an asparagine-glucose medium. Replacement of 

 the asparagine in whole or in part with an ammo- 

 nium salt permits carotenoid synthesis to occur. 

 If acetate replaces the glucose, both growth and 

 carotenogenesis are inhibited (110). 



Effect on Growth 



Inhibition: Stem and root growth are inhibited 

 when tomato seedlings are grown in a nutrient so- 

 lution containing 25 ppm of streptomycin sulfate. 

 Mn++ and, to a lesser extent, Ca++, reverse this 

 effect. As a spray, 10,000 ppm causes temporary 

 stunting and spotty apochlorosis of the stems, 

 followed by growth greater than the control; 

 root growth is also stimulated. Streptidine and 

 streptobiosamine show no effect (94) . Root growth 

 (percentage of control) is inhibited at 100 ppm in 



