Streptomycin is an aminoglycoside antibiotic with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. The antibiotic is synthesized by soil-dwelling aerobic bacteria of the genus Streptomyces, which form a large family and belong to the actinobacteria. Because of its undesirable side effects and risk of developing resistance, streptomycin is mainly used to combat tuberculosis and endocarditis if the inflammation is caused by streptococci or enterococci.
What is streptomycin?
Streptomycin is an aminoglycoside antibiotic with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. Streptomycin is an aminoglycoside antibiotic synthesized by numerous bacteria in the Streptomyces family. Aerobic Streptomyces belong to the large group of actinobacteria. They also produce fragrances that give fresh forest soil its characteristic odor. The chemical formula of streptomycin is C21H39N7O12, and the antibiotic has a broad spectrum of activity against Gram-negative and Gram-positive bacteria, such as the tuberculosis pathogen and infections and inflammations caused by enterococci and streptococci. Streptomycin was first isolated in 1943 and was the first effective antibiotic against tuberculosis. The mechanism of action of the antibiotic is that it interferes with the process of protein synthesis. By interfering with the docking of transport RNA (tRNA) to ribosomes, the bacterium synthesizes defective amino acid sequences that are useless for further growth. Due to the observed development of resistance and harmful side effects with prolonged use, streptomycin is mainly used against the causative agent of tuberculosis and brucellosis, as well as against streptococci or enterococci. Streptomycin is also used as a combination preparation, together with other antibiotics such as penicillin.
Pharmacologic action
The antibiotic streptomycin consists of three sugars, streptidin, N-methylglucosamine, and streptose, which are glycosidically linked. It has the property of being able to dock to a specific protein in the ribosomes of many Gram-negative species of bacteria, in cocci and mycobacteria. This is a protein to which the tRNA normally docks, which is loaded with the amino acids needed to build the protein. This process is disturbed by streptomycin, so that either no proteins can be synthesized or proteins with an “incorrect” amino acid sequence can be synthesized. As a consequence, functionless nonsense proteins can then be formed, which prevent further growth of the bacterium. The bacteria against which streptomycin is effective belong to the prokaryotes, in which the genetic material floats in the cytoplasm and is more easily accessible than in eukaryotes, in which the genetic material (DNA) is located in the cell nucleus, which is separated from the cytoplasm by its own membrane. Since streptomycin resides exclusively in the extracellular space, it is only effective against germs that are also in the extracellular space. This also explains the selective effect of the antibiotic. Degradation of streptomycin occurs renally, i.e., via the kidneys; however, degradation substances accumulate in the body, especially in the inner ear in the cochlea and vestibular organs, and in the kidneys, which explains ototoxicity and nephrotoxicity.
Medical application and use
Streptomycin turned out to be beneficial in the control of tuberculosis after its introduction in the 1950s. However, the germs often developed resistance in relatively short order, which drastically reduced the antibiotic’s effectiveness. Side effects that suggested inner ear and kidney toxicity did the rest. With the development of alternative antibiotics, streptomycin was greatly reduced and regulated in medical use. Nevertheless, the antibiotic still plays an important role in use against certain pathogens and is usually administered in combination with other antibiotics. One of the most important areas of use is inflammation of the inner lining of the heart caused by streptococci and enterococci. Usually streptomycin is administered in combination with penicillin. Another important field of application is the control of pathogens of the genus Brucella.It is a series of infectious diseases such as porcine brucellosis or Mediterranean fever and others. For the treatment of brucellosis, streptomycin is usually used in combination with tetracyclines. Streptomycin also still plays an important role in the control of tuberculosis. In principle, streptomycin can be administered orally or in the form of intramuscular injections. Oral administration is effective only for infections in the gastrointestinal tract due to low absorption, where it can develop locally. When systemic action is necessary, streptomycin is injected intramuscularly to ensure rapid absorption. Although the antibiotic distributes rapidly in body fluids, it cannot cross the blood–brain barrier.
Risks and side effects
There are some risks associated with the use of streptomycin, and mild to significant side effects can be expected, depending on the duration of therapy. The risks associated with monotherapy with streptomycin are primarily the relatively rapid development of resistance in the germs, which can even reverse the effect of the antibiotic, since the bacteria can then metabolize streptomycin for energy gain and also use it as a carbon source. Another risk complex is associated with the following listed possible side effects, which can lead to irreversible damage to the inner ear and kidneys. Side effects that are frequently observed, especially with long-term use of streptomycin, are, in addition to headache and eye pain, nausea and eye tremor (nystagmus), an onset of inner ear hearing loss and dizziness caused by a damaged sense of balance (vestibular system). The cochlea in the inner ear is connected to the vestibular organs, the arcades (rotatory accelerations) and the otolith organs (translatory accelerations) via the endolymphatic system within the membranous labyrinth. Another risk is the occurrence of renal dysfunction.
