Streptomycin and Dihydrostreptomycin

Side effects of streptomycin and dihydrostreptomycin treatment are mainly toxic in nature. Toxicity to the auditory vestibular organs, nephrotoxicity, hepatotoxicity, and toxicity to the bone marrow have all been observed (Rasmussen 1972 Hoigne 1975). There are also reports of peripheral neuritis and neuromuscular blockade, occurring presumably as a result of the potentiation of non-depolarizing anesthetics (Hoigne 1975). Because of its strong ototoxicity, dihydrostreptomycin is no longer in use in the Western hemisphere. 

Streptomycin, and to a much lesser extent dihydrostreptomycin, have been reported to be sensitizers in humans and also in guinea pigs (John 1960 Smith 1960 Epstein and Wenzel 1962 Chung and Carson 1976). There are a few reports in the literature dealing with anaphylactic shock, urticaria, and serum-sickness-like reactions in patients with tuberculosis who are receiving streptomycin therapy, or in connection with skin tests using streptomycin (Rossen 1948 Grudzinski 1960  

---

Streptomycin and dihydrostreptomycin are aminoglycoside antibiotics closely related in structure, which are active against mainly gram-negative bacteria. Streptomycin is produced by certain strains of Streptomyces griseus dihydrostreptomycin can be prepared by reduction of streptomycin. 

They are active against many gram-negative bacteria but resistance develops rapidly and limits their use. Streptomycin and dihydrostreptomycin are less nephrotoxic than other aminoglycosides. They may cause neurological distur-... 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

In traditional electrophoresis, separation efficiency is limited by thermal diffusion and convection. Owing to long analysis times and low efficiencies, these procedures never enjoyed wide usage. Problems have arisen when trying to differentiate between structurally related drug residues such as streptomycin and dihydrostreptomycin, tetracyclines, lincomycin and clindamycin, and erythromycin and oleandomycin (83, 84). To overcome these problems, anticonvective media, such as polyacrylamide or agarose gels, have also been used. 

An indirect competitive ELISA has been also developed for the determination of streptomycin and dihydrosticptomyciri in milk (24). Prior to the analysis, the milk sample was skimmed and treated with oxalic acid. The antiserum was raised in rabbits using streptomycin linked to a bacterial protein as the antigen. To perform the test, microtiter plates were coated with streptomycin, and antiserum and milk samples were mixed to be added in the wells where they were incubated for 1 h. Depending on the amount of residues in the sample, more or less antibody remained available for binding to the streptomycin coat. A pig antirabbit antibody-enzyme conjugate was subsequently added and incubated for 90 min. Using a suitable substrate, streptomycin and dihydrostreptomycin could be detected down to 1.6 ppb, whereas quantification could be made possible up to 100 ppb when samples were used undiluted. 

GC Gerhardt, CDC Salisbury, JD MacNeil. Determination of streptomycin and dihydrostreptomycin in animal tissue by on-line sample enrichment liquid chromatography. J AOAC Int 77 334-337, 1994. 

Osterberg, A. C., J. J. Olsen, N. N. Yuda, C. E. Rauh, H. G Parr, and L. W. Will. 1957. Cochlear, vestibular, and acute toxicity studies of streptomycin and dihydrostreptomycin pantothenate salts, In Antibiotics Annual, 1956-1957, edited by H. VNfelch and F. Marti-lban ez, 564-573. New York Medical Encyclopedia. 

Vinas, R, Balsalobre, N., and Hemdndez-Cdrdoba, M. Liquid chromatography on an amide stationary phase with post-column derivatization and flnorimetric detection for the determination of streptomycin and dihydrostreptomycin in foods. Talanta 2007, 72, 808-812. 

The lack of suitable chromophores for UV-Vis detection can be circumvented by derivatization, and the same strategy can be nsed to obtain the required fluorescence of an analyte if it does not naturally fluoresce. Many flnorophores were investigated and nsed. Determination of leukocyte DNA 6-thioguanine nucleotide levels relied on derivatization with chloroacetaldehyde [25]. A post-column derivatization with )8-naphthoqninone-4-sulfonate allowed the detection of streptomycin and dihydrostreptomycin in foods [26], A post-colnmn derivatization with 0-phthalaldehyde was used for the detection of biogenic amines and polyamines in vegetable products... 

Moskowitz M, Kelker N, Sensitivity of cultured mammalian cells to streptomycin and dihydrostreptomycin, Science, 1963,141 647-48. 

Aminoglycoside antibiotics contain amino sugars in their structure. Deoxystreptamine-containing members are neomycin, framycetin, gentamicin, kanamycin, tobramycin, amikacin, netilmicin and sisomicin. Both streptomycin and dihydrostreptomycin contain streptidine, whereas the aminocycli-... 

Walker, J.B. Skorvaga, M. Phosphorylation of streptomycin and dihydrostreptomycin by Streptomyces. Enzymatic synthesis of different diphos-phorylated derivatives. J. Biol. Chem., 248, 2435-2440 (1973)... 

Streptomycin and dihydrostreptomycin are used only in special cases, e.g. in combination with isoniazid for the treatment of tuberculosis or in combination with tetracycline in the case of brucellosis... 

The most difficult total syntheses in this class of pseudotrisaccharides were those of streptomycin and dihydrostreptomycin. About 35 years after their discovery and the elucidation of their structure, S. Umezawa and colleaguessucceeded in synthesising these compounds. The glycosyl derivative (I), prepared through several steps from streptobiosaminide, was condensed with the protected streptidine (II), to yield dihydrostreptomycin, after deprotection. Subsequent oxidation with DMSO/dicyclo-hexylcarbodiimide (DCC) produced streptomycin... 

Streptomycin and dihydrostreptomycin are inactivated by R-factor-carrying E.coU or Pseudomonas strains through 0-phosphorylation or 0-adenylation in the 3"-position. 3 -Deoxystreptomycin is the first modified streptomycin in which this type of resistance does not develop ... 

Streptomycin and dihydrostreptomycin inhibit the initiation step of translation, and there are also slight misreading effects. 

Ferguson JP, Baxter GA, McEvoy JDG, Stead S, Rawlings E, Sharman M, Detection of streptomycin and dihydrostreptomycin residues in milk, honey and meat samples using an optical biosensor, Analyst 2002 127 951-956. 

Shin-ichi K, Analysis of impurities in streptomycin and dihydrostreptomycin hy hydrophilic interaction chromatog-raphy/electrospray ionization quadrupole ion trap/time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2009 23(6) 907-914. 

Streptomycin (333) is prepared by fermentation of Streptomyces griseus [427] although its total synthesis has been achieved [428]. It is a broad-spectrum antibiotic one of the first to be discovered. It has particular value against tuberculosis, but is used to treat several other infections as well [429]. Dihydrostreptomycin (334), also an antibiotic, can be obtained by hydrogenation of streptomycin or by fermentation [430-432]. The tot synthesis was achieved by a Japanese group [433-436]. The mechanism of action of streptomycin and dihydrostreptomycin has been reviewed [437, 438],... 

Intestinal mucus, which contains the polysaccharide mucin, can avidly bind streptomycin and dihydrostreptomycin (E. Nelson et al, unpublished data). This binding may contribute to the... 

Fig. 3. Aminoglycoside antibiotics chemical structures of streptomycin (/) and dihydrostreptomycin (//). Ring = streptidine ring 5=streptose ring C=iV-methyl-L-glucosa-mine ring D = streptobiosamine...

Wenzel FJ, Epstein S (1964) Cross-sensitivity between streptomycin and dihydrostreptomycin. J Invest Dermatol 43 99-101... 

Immediate allergic reactions including anaphylaxis also occur to other aminoglycoside antibiotics with cases recorded for neomycin, gentamycin, tobramycin, framycetin, streptomycin, and dihydrostreptomycin. In some of these cases where tests were undertaken, patch and/or skin tests proved positive to the culprit aminoglycoside, but cross-reactivity with bacitracin has not been reported or, it seems, looked for. 

For detection with ninhydrin the plates were sprayed with the reagent (Ig ninhydrin + 50 ml ethanol + 10 ml acetic acid) and heated for 15 min at 110°C (not for streptomycin and dihydrostreptomycin). For detection with naphthoresorcinol the plates were sprayed with 2% naphthoresorcinol in ethanol, followed by 9 N H2SO4 and heating for 5-10 min at 120 C. The arising colors were characteristic, depending on the temperature and duration of heating Table 10 shows the values. 

Amikacin can also be determined by reversed-phase h.p.Lc. following derivatization with 1-fluoro-2,4-dinitrobenzene. The aminoglycoside antibiotics spectinomycin, hygromycin, streptomycin and dihydrostreptomycin were determined in bovine tissues by ion-pair reversed-phase h.p.l.c. using volatile ion-pair reagents, and by HPAEC. ... 

There are two generally accepted methods for the assay of streptomycin and dihydrostreptomycin. The plate diffusion assay uses a spore suspension inoculum and a technique almost identical to the penicillin plate assay described above. It has been the authors experience that the turbidimetric assay described below is more precise. This method is also applicable to dihydrostreptomycin with appropriate substitution of the standard. 

---