Streptomycin

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Streptomycin
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Clinical data
AHFS/Drugs.com Monograph
Pregnancy
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  • US: D (Evidence of risk)
    Routes of
    administration
    intramuscular, intravenous
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 84% to 88% IM (est.) [1] 0% by mouth
    Elimination half-life 5 to 6 hours
    Excretion kidney
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    PDB ligand
    ECHA InfoCard 100.000.323 Blue pencil.svg
    Chemical and physical data
    Formula C21H39N7O12
    Molar mass 581.574 g/mol g·mol−1
    3D model (JSmol)
    Melting point 12 °C (54 °F)
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    Streptomycin is an antibiotic used to treat a number of bacterial infections. [2] This includes tuberculosis, Mycobacterium avium complex, endocarditis, brucellosis, Burkholderia infection, plague, tularemia, and rat bite fever. [2] For active tuberculosis it is often given together with isoniazid, rifampicin, and pyrazinamide. [3] It is given by injection into a vein or muscle. [2]

    Antibiotic drug used in the treatment and prevention of bacterial infections

    An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. 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.

    Tuberculosis Infectious disease caused by the bacterium Mycobacterium tuberculosis

    Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. The classic symptoms of active TB are a chronic cough with blood-containing sputum, fever, night sweats, and weight loss. It was historically called "consumption" due to the weight loss. Infection of other organs can cause a wide range of symptoms.

    Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium that are commonly grouped together because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause disease in humans called Mycobacterium avium-intracellulare infection or Mycobacterium avium complex infection.

    Contents

    Common side effects include feeling like the world is spinning, vomiting, numbness of the face, fever, and rash. [2] Use during pregnancy may result in permanent deafness in the developing baby. [2] Use appears to be safe while breastfeeding. [3] It is not recommended in people with myasthenia gravis or other neuromuscular disorders. [3] Streptomycin is an aminoglycoside. [2] It works by blocking the ability of 30S ribosomal subunits to make proteins, which results in bacterial death. [2]

    Vertigo Type of dizziness where a person feels as if they or the objects around them are moving

    Vertigo is a symptom where a person feels as if they or the objects around them are moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties walking. It is typically worse when the head is moved. Vertigo is the most common type of dizziness.

    Pregnancy time when children develop inside the mothers body before birth

    Pregnancy, also known as gestation, is the time during which one or more offspring develops inside a woman. A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy can occur by sexual intercourse or assisted reproductive technology. Childbirth typically occurs around 40 weeks from the last menstrual period (LMP). This is just over nine months, where each month averages 31 days. When measured from fertilization it is about 38 weeks. An embryo is the developing offspring during the first eight weeks following fertilization, after which, the term fetus is used until birth. Symptoms of early pregnancy may include missed periods, tender breasts, nausea and vomiting, hunger, and frequent urination. Pregnancy may be confirmed with a pregnancy test.

    Breastfeeding Known as nursing, is the feeding of babies and young children with milk from a womans breast

    Breastfeeding, also known as nursing, is the feeding of babies and young children with milk from a woman's breast. Health professionals recommend that breastfeeding begin within the first hour of a baby's life and continue as often and as much as the baby wants. During the first few weeks of life babies may nurse roughly every two to three hours, and the duration of a feeding is usually ten to fifteen minutes on each breast. Older children feed less often. Mothers may pump milk so that it can be used later when breastfeeding is not possible. Breastfeeding has a number of benefits to both mother and baby, which infant formula lacks.

    Streptomycin was discovered in 1943 from Streptomyces griseus . [4] [5] It is on the World Health Organization's List of Essential Medicines, which lists the most effective and safe medicines needed in a health system. [6] The wholesale cost in the developing world is between US$0.38 and $4.39 per day. [7] In the United States, a course of treatment costs more than $200. [8]

    <i>Streptomyces griseus</i> species of bacterium

    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.

    A health system, also sometimes referred to as health care system or as healthcare system, is the organization of people, institutions, and resources that deliver health care services to meet the health needs of target populations.

    Uses

    Medication

    Infective endocarditis endocarditis that is characterized by inflammation of the endocardium caused by infectious agents.

    Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cell count. Complications may include valvular insufficiency, heart failure, stroke, and kidney failure.

    Gentamicin chemical compound

    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.

    Isoniazid chemical compound

    Isoniazid, also known as isonicotinylhydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For latent tuberculosis it is often used by itself. It may also be used for atypical types of mycobacteria, such as M. avium, M. kansasii, and M. xenopi. It is usually taken by mouth but may be used by injection into muscle.

    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. [1]

    Intramuscular injection injection of a substance directly into a muscle

    Intramuscular injection, often abbreviated IM, is the injection of a substance directly into muscle. In medicine, it is one of several alternative methods for the administration of medications. Muscles have larger and more blood vessels than subcutaneous tissue and injections here usually have faster rates of absorption than subcutaneous injections or intradermal injections. Depending on the injection site, an administration is limited to between 2 and 5 milliliters of fluid.

    Pesticide

    Streptomycin also is used as a pesticide, 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. [9] 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. [10]

    Cyanobacteria phylum of prokaryotes

    Cyanobacteria, also known as Cyanophyta, are a phylum of bacteria that obtain their energy through photosynthesis and are the only photosynthetic prokaryotes able to produce oxygen. The name cyanobacteria comes from the color of the bacteria. Cyanobacteria, which are prokaryotes, are also called "blue-green algae", though the term algae in modern usage is restricted to eukaryotes.

    Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, and profit. Fungicides are used both in agriculture and to fight fungal infections in animals. Chemicals used to control oomycetes, which are not fungi, are also referred to as fungicides, as oomycetes use the same mechanisms as fungi to infect plants.

    Cell culture

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

    Spectrum of activity

    Streptomycin can be used clinically to treat tuberculosis in combination with other medications and susceptible strains which cause bacterial endocarditis.[ citation needed ]

    Side effects

    The most concerning side effects, as with other aminoglycosides, are kidney toxicity and ototoxicity. [11] 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. [12]

    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. [2] Congenital deafness has been reported in children whose mothers received streptomycin during pregnancy. [2] Use appears to be okay while breastfeeding. [3]

    It is not recommended in people with myasthenia gravis. [3]

    Mechanism of action

    Streptomycin is a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. [13] 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. [14] 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. [15] Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria, [16] 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. [17] [18] 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". [19] Waksman was later accused of playing down the role of Schatz who did the work under his supervision. [20] [21] [22] [23]

    The Rutgers team reported streptomycin in the medical literature in January 1944. [24] 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. [25] :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. [25] :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. [25] :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 patient treated did not survive; the second patient survived but became blind as a side effect of the treatment. In March 1946, the third patient Robert J. Dole, later Majority Leader of the United States Senate and Presidential nomineeexperienced a rapid and robust recovery. [26]

    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. [27] It is widely accepted to have been the first randomised curative trial. [28]

    Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug. [27]

    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. [29] [30]

    See also

    Related Research Articles

    Macrolide A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone

    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.

    Neomycin antibiotic, mixture of chemical

    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.

    Broad-spectrum antibiotic type of antibiotic

    The term broad-spectrum antibiotic can refer to 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 molecule or a portion of a molecule composed of amino-modified sugars

    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.

    Selman Waksman American scientist, biochemist, microbiologist who discovered Streptomycin and many antibiotics

    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 Rutgers University's 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 was later sued by Albert Schatz, one of his PhD students, for minimizing Schatz's role in the discovery of streptomycin.

    Albert Schatz (scientist) American microbiologist

    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 chemical compound

    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.

    Carbapenem group of β-lactam antibiotics

    Carbapenems are a class of highly effective antibiotic agents commonly used for the treatment of severe or high-risk bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

    Tobramycin chemical compound

    Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.

    Lincosamides group of chemical compounds

    Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.

    Spectinomycin chemical compound

    Spectinomycin, sold under the tradename Trobicin among others, is an antibiotic useful for the treatment of gonorrhea infections. It is given by injection into a muscle.

    β-Lactamase inhibitor Endogenous substances and drugs that inhibit or block the activity of beta-lactamases

    Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. They act by breaking the beta-lactam ring that allows penicillin-like antibiotics to work. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

    Dihydrostreptomycin chemical compound

    Dihydrostreptomycin is a derivative of streptomycin that has a bactericidal property. It's a semisynthetic aminoglycoside antibiotic used in the treatment of tuberculosis.

    Arbekacin chemical compound

    Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin was originally synthesized from dibekacin in 1973. It has been registered and marketed in Japan since 1990 under the trade name Habekacin. Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.

    Antibiotic resistance in gonorrhea

    The Gonorrhea bacterium Neisseria gonorrhoeae has developed antibiotic resistance to many antibiotics.

    Pen-Strep is a mixture of penicillin and streptomycin widely used in mammalian cell culture media to prevent bacterial contamination. The solution contains 5,000 Units of Penicillin G which acts as the active base, and 5,000 micrograms of Streptomycin (sulfate), formulated in 0.85% saline. In general, 50-100 Units of Pen-Strep per milliliter of media is used to avoid contamination in cell culture. Thus, the retail product is generally 100 X more concentrated. It is recommended for use in cell culture applications at a concentration of 10 ml per Liter. It is the most common antibiotic solution for the culture of mammalian cells and it does not have any adverse effects on the cells themselves. It is first introduced in 1955 in cell culture.

    Elizabeth Bugie Gregory was an American biochemist who identified Streptomycin, an antibiotic that was active against Mycobacterium tuberculosis.

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    Further reading