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What is streptomycin used for?

Posed on  December 19, 2020, edited by Jason, category  

What is streptomycin?

1. Definition

Streptomycin is an aminoglycoside antibiotic. Aminoglycosides are glycoside antibiotics formed by connecting amino sugars and amino cyclic alcohols through oxygen bridges. Aminoglycoside antibiotics inhibit protein synthesis and are bactericidal antibiotics in the stationary phase. It is characterized by anti-aerobic gram-negative bacilli, Pseudomonas, tuberculosis, and staphylococcus. Since aminoglycoside antibiotics must be aerobic to exert antibacterial effects, they are ineffective against anaerobic bacteria. Aminoglycoside drugs have varying degrees of ototoxicity, nephrotoxicity and neuromuscular blockade.

In 1943, a Ph.D. in University of California, Berkeley, Salman A. Waxman isolated it from Streptomyces, and it was the second antibiotic produced and used in clinical practice after penicillin. Waxman also won the Nobel Prize in Physiology or Medicine in 1952. The special effect of streptomycin against tuberculosis bacillus opened a new era of tuberculosis treatment. Since then, the history of Mycobacterium tuberculosis that has ravaged human life for thousands of years can be contained for the first time.

Streptomycin is an antibiotic extracted from the culture broth of Streptomyces griseus. It belongs to the basic aminoglycoside compound, which binds to the protein of the ribonucleic acid protein body of Mycobacterium tuberculosis and acts to interfere with the protein synthesis of Mycobacterium tuberculosis, thereby killing or inhibiting the growth of Mycobacterium tuberculosis.

Since the pain response of intramuscular injection of streptomycin is relatively small, it is suitable for clinical use. As long as the target is selected properly and the dose is appropriate, most patients can be injected for a long time (usually about 2 months). Therefore, it is still the main drug in anti-tuberculosis treatment for decades.

2. Streptomycin Uses

Streptomycin is a microbial bactericide, which can effectively control plant bacterial diseases, such as apple, pear fire blight, tobacco wildfire, blue mold, cabbage soft rot, tomato bacterial spot rot, late blight, and potato seed Rot, black shank, cucumber angular spot, downy mildew, bean downy mildew, bacterial blight, celery bacterial blight, sesame bacterial leaf spot.

Streptomycin has a bacteriostatic effect at low concentrations, and a bactericidal effect at high concentrations. It has a strong antibacterial effect on Mycobacterium tuberculosis. It also has an antibacterial effect on Escherichia coli, Shigella, Pertussis, and Pneumoniae. Tuberculosis, urinary tract infection, bacillary dysentery, sepsis, etc. Taking this medicine can cause numbness around the lips and face, which will affect the eighth cranial nerve when used. Long-term use of this medicine may cause kidney damage.

3. History

In 1945, Fleming, Flory, and Chan shared the Nobel Prize for Medicine in recognition of their discovery of the first ever panacea for bacterial infections-penicillin. But penicillin does not work against many kinds of bacteria, including tuberculosis, the pathogen of tuberculosis. Tuberculosis is one of the most harmful infectious diseases to humans.

In the 20th century, about 100 million people still died from tuberculosis. Famous writers such as Chekhov, Lawrence, Lu Xun and Orwell all died prematurely due to tuberculosis. Doctors all over the world have tried a variety of methods to treat tuberculosis, but none of them are really effective. Suffering from tuberculosis means being sentenced to death. Even after Koch discovered Mycobacterium tuberculosis in 1882, this situation has not improved for a long time. The magical effect of penicillin has brought new hope to people. Can a similar antibiotic be found to effectively treat tuberculosis?

Sure enough, a few months after the Nobel Prize was awarded in 1945, on February 22, 1946, Rutgers University professor Selman A. Waksman announced that his laboratory had discovered the second antibiotic used in the clinic, streptomycin, has specific effects against tuberculosis bacilli, and a new era of humans overcoming tuberculosis has begun. Unlike penicillin, the discovery of streptomycin is by no means accidental, but the result of well-designed and systematic long-term research.

4. Pharmacological effects

Streptomycin is an aminoglycoside drug. Streptomycin mode of action is to act on ribosomes in bacteria, inhibit bacterial protein synthesis, and destroy the integrity of bacterial cell membranes. Sensitive bacteria have an oxygen-dependent antibiotic transmembrane transport system.

Estreptomicina can first diffuse through the outer cell membrane porin through passive diffusion, then enter the cell through the cell membrane by this transport system, and irreversibly bind to the isolated ribosomal 30S subunit, leading to the destruction of the A position, and then:

  • Prevent the correct positioning of aminoacyl tRNA at position A, interfere with the assembly of functional ribosomes, and inhibit the formation of 70S initiating complex;
  • Induce the mismatch of tRNA and mRNA code triplet, causing the 30S subunit of the intact ribosome to misread the genetic code, leading to abnormal and non-functional protein synthesis;
  • Prevent the termination factor from binding to the A site, so that the synthesized peptide chain cannot be released, and the dissociation of the 70S intact ribosome is prevented;
  • hinders the depolymerization and assembly process of polyribosomes, causing the depletion of ribosome in the bacteria. Streptomycin has a strong antibacterial effect on Mycobacterium tuberculosis, and its minimum inhibitory concentration (MIC) is generally 0.5mg/L. Atypical mycobacteria are mostly resistant to streptomycin.

Streptomycin is effective against many gram-negative bacilli such as Escherichia coli, Klebsiella pneumoniae, Enterobacter, Salmonella, Shigella, Brucella, Pasteurella, Meningococcus and Neisseria gonorrhoeae, etc. Streptomycin has poor antibacterial activity against most gram-positive cocci such as Staphylococcus aureus. Streptococcus, Pseudomonas aeruginosa and anaerobic bacteria are resistant to streptomycin.

What is streptomycin used for?

1. Indications

  • Estreptomicina is suitable for tularemia, or combined with other antibacterial drugs for plague, venereal granulomatosis, brucellosis, rodent bite fever, and can also be combined with penicillin to treat or prevent Streptococcus viridans or Enterococcus caused by endocarditis.
  • Estreptomicina can also be used in combination with other anti-tuberculosis drugs for various tuberculosis or other mycobacterial infections caused by Mycobacterium tuberculosis.
  • Estreptomicina is mainly used in combination with other anti-tuberculosis drugs for initial cases of tuberculosis caused by Mycobacterium tuberculosis, or other sensitive Mycobacterium infections.
  • The product can be used for the treatment of tularemia alone or in combination with other antibacterial drugs for the treatment of plague, granuloma inguinal, brucellosis, rodent bite fever, etc.
  • It can also be combined with penicillin or ampicillin to treat endocarditis caused by Streptococcus viridans or Enterococcus faecalis.

2. Streptomycin Dosage

At present, it is believed that one injection of 750 mg a day for adults can achieve the purpose of treatment. In the past, 500 mg was injected intramuscularly twice a day, and its curative effect was exactly the same as an intramuscular injection. Therefore, a 750 mg intramuscular injection dose is 250 mg less a day, so side effects are also reduced.

The dose can be increased or even doubled for individual patients with severe illness, but the continuous application time should not be too long, generally not more than 1 week, and must be applied under close observation. The dose for the elderly should be appropriately reduced. Children’s dose is about 25 mg per kilogram of body weight per day. They must also be closely observed.

We use streptomycin sulfate now. There was dihydrostreptomycin in the past. Because many patients had permanent hearing loss (deafness), now dihydrostreptomycin has been eliminated by the State Medical Administration and is no longer produced.

Streptomycin-test
Streptomycin-test

Streptomycin Side Effects

1. Adverse Reaction

A. Allergic reactions

Both Estreptomicina and dihydrostreptomycin can be combined with serum proteins to form a complete antigen, but the antibodies produced are different, so there is no cross-reaction. Dihydrostreptomycin can be used for those allergic to streptomycin.

Allergic reactions include: skin rash (0.3%-11%), which can be manifested as maculopapular rash, urticaria, erythema, measles-like rash, scarlet fever-like rash, pemphigus-like rash, eczema-like rash, purpura, and angioedema. In severe cases, anaphylactic shock can occur, and severe allergic reactions can have acute hemolytic anemia, hemoglobinuria, shock, and acute renal failure.

Streptomycin can cause mild damage to the kidneys, and patients may develop proteinuria, tubular urine, etc., which generally do not affect continuous medication. A few patients may have decreased renal function, but they can recover after stopping the drug. Taking drugs such as sodium bicarbonate can reduce the chance of proteinuria. Leukopenia is more common, in addition to occasional neutropenia, thrombocytopenia, aplastic anemia, etc. Long-term use of streptomycin can cause complete or partial loss of olfactory function. It has been reported that the intratympanic injection of the product was used to treat Meniere's syndrome, and 95% of patients had dizziness disappeared but hearing remained.

B. Toxic reaction

Numbness, dizziness, deafness, etc. are common, and they usually appear within 10 days after the medication. The shortest case occurs within 20 minutes after the injection, which lasts for 1 to 6 hours, and the severe case can continue for 24 hours. Perioral numbness, dizziness, dyskinesia, headache, fatigue, vomiting, and facial flushing may also occur. In severe cases, sweating, dyspnea, and cramps are not easily distinguished from anaphylactic shock. However, acute reactions are more common to accumulate or gradually aggravate. In some cases, the reaction only occurs at the beginning of the injection and disappears later. The acute reaction of streptomycin is generally believed to be related to its impurities.

Streptomycin damages the kidneys slightly, manifested as proteinuria and tubular urine, some of which temporarily decline in renal function, which can be restored after stopping the drug. Serious permanent renal damage is rare. Suppressive effect on bone marrow: manifested as leukopenia, thrombocytopenia, aplastic anemia and oligocytosis. Leukopenia is common, while aplastic anemia and pancytopenia are rare. It is also easy to cause hirsutism, conjunctivitis, arthralgia, myocarditis, toxic encephalopathy, etc.

2. Taboos

  • Cross allergy. Patients who are allergic to one aminoglycoside may also be allergic to other aminoglycosides. This drug is contraindicated in people with a history of streptomycin allergy.
  • Streptomycin can pass through the placenta, and its concentration in umbilical cord blood is approximately similar to that in maternal blood. It is reported that streptomycin has caused hearing damage in human fetuses. Pregnant women must fully weigh the pros and cons.
  • Elderly patients can produce various toxic reactions after using aminoglycosides, so it is extremely important to monitor renal function (it is best to measure creatinine clearance) during the course of aminoglycosides treatment. People with normal renal function may also experience hearing loss after medication. In addition, older patients should use a smaller dose to suit their age, renal function and the function of the eighth pair of cranial nerves.

3. Matters needing attention

  • Patients who are allergic to one aminoglycoside may also be allergic to other aminoglycosides.
  • This product can cause vestibular nerve and auditory nerve damage.
  • Because the product can cause neuromuscular blockade, resulting in skeletal muscle weakness.
  • The product is nephrotoxic.
  • During the course of treatment, attention should be paid to regular urinary tests and renal function tests to prevent severe nephrotoxic reactions and hearing tests (especially high-frequency hearing) tests, which is especially important for elderly patients.

4. Drugs Interactions

  • Streptomycin and other aminoglycosides used together or successively applied locally or systemically can increase the possibility of ototoxicity, nephrotoxicity and neuromuscular blockade. Hearing loss may occur, and it may progress to deafness after stopping the drug; the hearing loss may be restored or not. Neuromuscular blockade can cause skeletal muscle weakness, respiratory depression or respiratory paralysis (apnea). Anticholinerase drugs or calcium salts can help the blockage recovery.
  • Combination of streptomycin and neuromuscular blockers can aggravate neuromuscular blockade, resulting in muscle weakness, respiratory depression or respiratory paralysis (apnea). Combination of streptomycin with capreomycin, cisplatin, diuretic acid, furosemide, or vancomycin, or continuous topical or systemic application, may increase ototoxicity and nephrotoxicity, hearing damage, and even deafness.
  • The local or systemic application of streptomycin and cefalotin may increase nephrotoxicity.
  • Combination of streptomycin and polymyxins, or successive local or systemic applications, can aggravate nephrotoxicity and neuromuscular blockade. The latter can cause skeletal muscle weakness, respiratory depression or paralysis.
Streptomycin
Streptomycin

Conclusion

Streptomycin has been used clinically for more than half a century, and it is still the first-line anti-tuberculosis drug. In recent years. Due to the increase of drug-resistant tuberculosis strains, it is mainly used in the initial stage of tuberculosis.

Streptomycin can be used alone for tularemia, or can be combined with tetracycline to treat plague and brucellosis, and penicillin to treat Streptococcus viridans endocarditis.

BALLYA provides a betalactam-tetracycline-streptomycin-chloramphenicol-combo-test-kit to tell you if there are streptomycin, beta lactam, tetracycline and chloramphenicol residues in dairy products you eat every day.

References

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