Streptomycin Aminoglycoside

Among the older aminoglycoside derivatives, kanamycin A and sisomicin were, at one time, a significant part of medical practice, but have now been largely replaced by the compounds Hsted in Table 1. Streptomycin is stiH used in a few restricted situations. 

The aminoglycosides include amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Mycifradin), netilmicin (Netromycin), streptomycin, and tobramycin (Nebcin). 

Fig. 5.10 Some aminoglycoside antibiotics A, streptomycin B, kanamycins C, gentamicins D, amikacin.

Because they are hepatically cleared, isoniazid and rifampin do not require dose modification in renal failure.31,36,39 Pyrazinamide and ethambutol typically are reduced to three times weekly to avoid accumulation of the parent drug (ethambutol) or metabolites (pyrazinamide).28,31 Renally cleared TB drugs include the aminoglycosides (e.g., amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and lev-ofloxacin.28,31,33,39 Dosing intervals need to be extended for... 

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

The answer is d. (Hardman, pp 1105-1108.) The bactericidal activity of streptomycin and other aminoglycosides involves a direct action on the 305 ribosomal subunit, the site at which these agents both inhibit protein... 

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

Other key classes of antibacterials include the tetracyclines (Aureomycin, Terramycin), macrolides (erythromycin, Zithromax, Biaxin), and aminoglycosides (streptomycin, amikacin, neomycin). These antibacterials are protein synthesis inhibitors. 

Aminoglycosides Gentamicin Streptomycin Spectinomycin Phosphorylation Acetylation Nucleotidylation Efflux Altered target... 

All aminoglycosides are associated with auditory or vestibular nerve damage, especially during the second and third trimesters. The risk is greatest with streptomycin and is lower with gentamicin and tobramycin. 

Streptomycin must be given i.v. (pp. 278ff) like other aminoglycoside antibiotics. It damages the inner ear and the labyrinth. Its nephrotoxicity is comparatively minor. 

Although streptomycin was not the first antibiotic (penicillin, a fungal product, had been isolated some years earlier), its discovery was a landmark in antibiotic history. It was the first effective therapeutic for tuberculosis, a disease that had terrorized humans for cenmries and a cause of human morbidity and mortality unmatched by wars or any other pestilence. Streptomycin was the first aminoglycoside to be identified and characterized and is noteworthy in being the first useful antibiotic isolated from a bacterial source. At the present time, the use... 

Following on the discovery of streptomycin and its streptamine-based relatives (Figure 1.2), a new generation of the aminoglycosides derived from 2-deoxy-streptamine (DOS) was not long in coming (Figure 1.3). For a variety of reasons, many of these compounds have not been employed as hnman therapeutics for... 

Many applications of the aminoglycosides have been of historical significance in genetics and microbiology. For example, mutations to streptomycin resistance were employed as counterselective genetic markers in the historic experiments of William Hayes that demonstrated the existence of bacterial conjugation and the requirement of donor (Hfr or F-b) and receptor (F—) species. ... 

The biochemical mode of action of the aminoglycosides as antibacterials has long been a topic of great interest. Early experiments carried out soon after the introduction of streptomycin suggested a variety of modes of action, but these conclusions were based largely on symptomatic analyses of antibiotic-treated bacterial cultures. One important experiment done in 1948 showed that streptomycin blocks enzyme indnction in susceptible bacteria this was the closest that anyone came to identifying the mechanism of action at the time. 

A variety of bacterial genera have been shown to produce aminoglycoside-aminocyclitol antibiotics. These include Streptomyces, Micromonospora, Bacillus, and so on. Only those compounds emanating from Streptomyces are named -mycins (e.g., tobramycin) while others are -micins (gentamicin), -osins, -asins, or -acins. The biosynthetic pathways for the aminoglycosides and the control of their expression are not well-studied. Streptomycin is the exception. 

Piepersberg, W. Streptomycin and related aminoglycosides. In Biochemistry and Genetics of Antibiotic Biosynthesis Vining, L. Stuttard, C., Eds. Boston Butterworth-Heinemann, 1995 pp. 531-570. 

Figure 3.1A. Interaction of aminoglycosides with the acceptor site of the 30S ribosome. Schematic representation of (A) paromomycin and (B) streptomycin interactions with the 16S rRNA and ribosomal protein SI2.

Ramakrishnan and co-workers 3-A crystal structures of two different aminoglycosides (paromomycin and streptomycin) bound to the 30S subunit laid to rest much of the debate concerning the binding mode of aminoglycoside antibiotics. Paromomycin was found bound to the major groove of helix 44 (H44), confirming mutagenesis studies that had been carried out previously. ... 

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