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Streptomycin

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Streptomycin
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Clinical data
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • US:D (Evidence of risk) [1]
    Routes of
    administration
    Intramuscular, intravenous
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only)
    • US: ℞-only
    Pharmacokinetic data
    Bioavailability 84% to 88% IM (est.) [2] 0% by mouth
    Elimination half-life 5 to 6 hours
    Excretion Kidney
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    PDB ligand
    CompTox Dashboard (EPA)
    ECHA InfoCard 100.000.323 OOjs UI icon edit-ltr-progressive.svg
    Chemical and physical data
    Formula C21H39N7O12
    Molar mass 581.580 g·mol−1
    3D model (JSmol)
    Melting point 12 °C (54 °F)
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    Streptomycin is an antibiotic medication used to treat a number of bacterial infections. [3] This includes tuberculosis, Mycobacterium avium complex, endocarditis, brucellosis, Burkholderia infection, plague, tularemia, and rat bite fever. [3] For active tuberculosis it is often given together with isoniazid, rifampicin, and pyrazinamide. [4] It is given by injection into a vein or muscle. [3]

    Contents

    Common side effects include vertigo, vomiting, numbness of the face, fever, and rash. [3] Use during pregnancy may result in permanent deafness in the developing baby. [3] Use appears to be safe while breastfeeding. [4] It is not recommended in people with myasthenia gravis or other neuromuscular disorders. [4] Streptomycin is an aminoglycoside. [3] It works by blocking the ability of 30S ribosomal subunits to make proteins, which results in bacterial death. [3]

    Streptomycin was discovered in 1943 from Streptomyces griseus . [5] [6] It is on the World Health Organization's List of Essential Medicines. [7] The World Health Organization classifies it as critically important for human medicine. [8]

    Uses

    Medication

    Streptomycin is traditionally given intramuscularly, and in many nations is only licensed to be administered intramuscularly, though in some regions the drug may also be administered intravenously. [2]

    Fungicide

    Streptomycin also is used as a fungicide, to combat the growth of bacteria beyond human applications. Streptomycin controls bacterial diseases of certain fruit, vegetables, seed, and ornamental crops. A major use is in the control of fireblight on apple and pear trees. As in medical applications, extensive use can be associated with the development of resistant strains. Streptomycin could potentially be used to control cyanobacterial blooms in ornamental ponds and aquaria. [10] While some antibacterial antibiotics are inhibitory to certain eukaryotes, this seems not to be the case for streptomycin, especially in the case of anti-fungal activity. [11]

    Cell culture

    Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.[ medical citation needed ]

    Protein purification

    When purifying protein from a biological extract, streptomycin sulfate is sometimes added as a means of removing nucleic acids. Since it binds to ribosomes and precipitates out of solution, it serves as a method for removing rRNA, mRNA, and even DNA if the extract is from a prokaryote.[ medical citation needed ]

    Side effects

    The most concerning side effects, as with other aminoglycosides, are kidney toxicity and ear toxicity. [12] Transient or permanent deafness may result. The vestibular portion of cranial nerve VIII (the vestibulocochlear nerve) can be affected, resulting in tinnitus, vertigo, ataxia, kidney toxicity, and can potentially interfere with diagnosis of kidney malfunction. [13]

    Common side effects include vertigo, vomiting, numbness of the face, fever, and rash. Fever and rashes may result from persistent use.[ citation needed ]

    Use is not recommended during pregnancy. [3] Congenital deafness has been reported in children whose mothers received streptomycin during pregnancy. [3] Use appears to be okay while breastfeeding. [4]

    It is not recommended in people with myasthenia gravis. [4]

    Mechanism of action

    Streptomycin is a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome irreversibly, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. [14] This leads to codon misreading, eventual inhibition of protein synthesis and ultimately death of microbial cells through mechanisms that are still not understood. Speculation on this mechanism indicates that the binding of the molecule to the 30S subunit interferes with 50S subunit association with the mRNA strand. This results in an unstable ribosomal-mRNA complex, leading to a frameshift mutation and defective protein synthesis; leading to cell death. [15] Humans have ribosomes which are structurally different from those in bacteria, so the drug does not have this effect in human cells. At low concentrations, however, streptomycin only inhibits growth of the bacteria by inducing prokaryotic ribosomes to misread mRNA. [16] Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria, [17] and is therefore a useful broad-spectrum antibiotic.

    History

    Streptomycin was first isolated on October 19, 1943, by Albert Schatz, a PhD student in the laboratory of Selman Abraham Waksman at Rutgers University in a research project funded by Merck and Co. [18] [19] Waksman and his laboratory staff discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein, neomycin, fradicin, candicidin, and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first antibiotic cure for tuberculosis (TB). In 1952 Waksman was the recipient of the Nobel Prize in Physiology or Medicine in recognition "for his discovery of streptomycin, the first antibiotic active against tuberculosis". [20] Waksman was later accused of playing down the role of Schatz who did the work under his supervision, claiming that Elizabeth Bugie had a more important role in its development. [21] [22] [23] [24]

    The Rutgers team reported streptomycin in the medical literature in January 1944. [25] Within months they began working with William Feldman and H. Corwin Hinshaw of the Mayo Clinic with hopes of starting a human clinical trial of streptomycin in tuberculosis. [26] :209–241 The difficulty at first was even producing enough streptomycin to do a trial, because the research laboratory methods of creating small batches had not yet been translated to commercial large-batch production. They managed to do an animal study in a few guinea pigs with just 10 grams of the scarce drug, demonstrating survival. [26] :209–241 This was just enough evidence to get Merck & Co. to divert some resources from the young penicillin production program to start work toward streptomycin production. [26] :209–241

    At the end of World War II, the United States Army experimented with streptomycin to treat life-threatening infections at a military hospital in Battle Creek, Michigan. The first person who was treated with streptomycin did not survive; the second person survived but became blind as a side effect of the treatment. In March 1946, the third person Robert J. Dole, later Majority Leader of the United States Senate and presidential nomineeexperienced a rapid and robust recovery. [27]

    The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946 through 1948 by the MRC Tuberculosis Research Unit under the chairmanship of Geoffrey Marshall (1887–1982). The trial was neither double-blind nor placebo-controlled. [28] It is widely accepted to have been the first randomised curative trial. [29]

    Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug. [28]

    New Jersey

    Because streptomycin was isolated from a microbe discovered on New Jersey soil, and because of its activity against tuberculosis and Gram negative organisms, and in recognition of both the microbe and the antibiotic in the history of New Jersey, S. griseus was nominated as the Official New Jersey state microbe. The draft legislation was submitted by Senator Sam Thompson (R-12) in May 2017 as bill S3190 and Assemblywoman Annette Quijano (D-20) in June 2017 as bill A31900. [30] [31]

    See also

    Related Research Articles

    Antibiotic Antimicrobial substance active against bacteria

    An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.

    Antimicrobial resistance Ability of a microbe to resist the effects of medication


    Antimicrobial resistance occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. The term antibiotic resistance is a subset of AMR, as it applies to bacteria that become resistant to antibiotics. Resistant microbes are more difficult to treat, requiring higher doses, or alternative medications which may prove more toxic. These approaches may also be more expensive. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR).

    Macrolide

    The macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Macrolides are bacteriostatic in that they suppress or inhibit bacterial growth rather than killing bacteria completely.

    Clarithromycin

    Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.

    Neomycin

    Neomycin is an aminoglycoside antibiotic found in many topical medications such as creams, ointments, and eyedrops. Neomycin belongs to aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds.

    Gentamicin Antibiotic medication

    Gentamicin, sold under brand name Garamycin among others, is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not effective for gonorrhea or chlamydia infections. It can be given intravenously, by injection into a muscle, or topically. Topical formulations may be used in burns or for infections of the outside of the eye. In the developed world, it is often only used for two days until bacterial cultures determine what specific antibiotics the infection is sensitive to. The dose required should be monitored by blood testing.

    Broad-spectrum antibiotic

    A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial infection is suspected but the group of bacteria is unknown or when infection with multiple groups of bacteria is suspected. This is in contrast to a narrow-spectrum antibiotic, which is effective against only a specific group of bacteria. Although powerful, broad-spectrum antibiotics pose specific risks, particularly the disruption of native, normal bacteria and the development of antimicrobial resistance. An example of a commonly used broad-spectrum antibiotic is ampicillin.

    Aminoglycoside

    Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.

    Aztreonam

    Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by injection into a vein or muscle or breathed in as a mist.

    Selman Waksman

    Selman Abraham Waksman was a Ukrainian-born Jewish-American inventor, biochemist and microbiologist whose research into the decomposition of organisms that live in soil enabled the discovery of streptomycin and several other antibiotics. A professor of biochemistry and microbiology at Rutgers University for four decades, he discovered a number of antibiotics, and he introduced procedures that have led to the development of many others. The proceeds earned from the licensing of his patents funded a foundation for microbiological research, which established the Waksman Institute of Microbiology located on the Rutgers University Busch Campus in Piscataway, New Jersey (USA). In 1952, he was awarded the Nobel Prize in Physiology or Medicine for "ingenious, systematic and successful studies of the soil microbes that led to the discovery of streptomycin." Waksman and his foundation later were sued by Albert Schatz, one of his PhD students and first discoverer of streptomycin, for minimizing Schatz's role in the discovery of streptomycin.

    Ceftriaxone

    Ceftriaxone, sold under the brand name Rocephin, is an antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint infections, intra-abdominal infections, skin infections, urinary tract infections, gonorrhea, and pelvic inflammatory disease. It is also sometimes used before surgery and following a bite wound to try to prevent infection. Ceftriaxone can be given by injection into a vein or into a muscle.

    Albert Schatz (scientist)

    Albert Israel Schatz was an American microbiologist and science educator, best known as the discoverer of the antibiotic streptomycin. Schatz graduated from Rutgers University in 1942 with a bachelor's degree in soil microbiology, and received his doctorate from Rutgers in 1945.

    Kanamycin A

    Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. As with most antibiotics, it is ineffective in viral infections.

    Tigecycline

    Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

    Amikacin

    Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.

    Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States. And generic only in the United States, ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

    Dicloxacillin

    Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

    <i>Streptomyces griseus</i>

    Streptomyces griseus is a species of bacteria in the genus Streptomyces commonly found in soil. A few strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along with most other streptomycetes, S. griseus strains are well known producers of antibiotics and other such commercially significant secondary metabolites. These strains are known to be producers of 32 different structural types of bioactive compounds. Streptomycin, the first antibiotic ever reported from a bacterium, comes from strains of S. griseus. Recently, the whole genome sequence of one of its strains had been completed.

    Elizabeth Bugie American biochemist

    Elizabeth Bugie Gregory was an American biochemist who identified Streptomycin, an antibiotic that was active against Mycobacterium tuberculosis. Selman Waksman went on to win the Nobel Prize for Medicine in 1952 and took the credit for the discovery.

    References

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    Further reading