What Is Streptomycin Resistance?

Streptomycin is an aminoglycoside antibiotic. In 1943, Dr. Selman A. Waxman, a professor at the University of California, Berkeley and Rutgers University, was isolated from Streptomyces [1-2] . Waxman also won the Nobel Prize in Physiology or Medicine in 1952 [1] . Its special effects against tuberculosis have opened a new era of tuberculosis treatment. Since then, the thousands of years of human tuberculosis raging human life have hopes of containment.

Streptomycin is an aminoglycoside antibiotic. In 1943, Dr. Selman A. Waxman, a professor at the University of California, Berkeley and Rutgers University, was isolated from Streptomyces [1-2] . Waxman also won the Nobel Prize in Physiology or Medicine in 1952 [1] . Its special effects against tuberculosis have opened a new era of tuberculosis treatment. Since then, the thousands of years of human tuberculosis raging human life have hopes of containment.
Streptomycin is an antibiotic extracted from the culture medium of Streptomyces griseus. It is an aminoglycoside basic compound. It binds to the tubercle bacillus ribonucleic acid protein, and interferes with the protein synthesis of tuberculosis, thereby killing or inhibiting the growth of tuberculosis. Because the intramuscular injection of streptomycin is relatively small, it is suitable for clinical use. As long as the application subject is properly selected and the dosage is appropriate, most patients can be injected for a long time (usually about 2 months). Therefore, it is still the main drug in antituberculosis treatment for decades.
Chinese name
Streptomycin
Foreign name
streptomycin
EINECS
200-355-3
Molecular weight
581.57
CAS
57-92-1
Molecular formula
C21H39N7O12

Streptomycin Compound Encyclopedia

Streptomycin Basic Information

Chinese name Streptomycin
Chinese alias: streptomycin A; 2,4-diguanidino-3,5,6-trihydroxycyclohexyl 5-deoxy-2-deoxy-2-methylamino-2-L-pyranyl -3-C-formyl--L-lysurafuranoside
English name: streptomycin
English alias: Neodiestreptopab; STREPTOMYCIN A; Streptomycin; streptomicina; 8th edition
CAS number: 57-92-1
Streptomycin
Molecular formula: C 21 H 39 N 7 O 12
Molecular weight: 581.57400
Exact mass: 581.26600
PSA: 331.43000

Streptomycin physicochemical properties

Appearance and properties: crystalline powder
Density: 1.98g / cm 3
Boiling point: 948.2ºC at 760mmHg
Flash point: 527.3ºC
Storage conditions: storeroom is ventilated, low-temperature and dry, and stored separately from food materials
Stability: Streptomycin is a white amorphous powder with hygroscopicity. Easily soluble in water, insoluble in most organic solvents, unstable under strong acid and alkali conditions. The appearance of streptomycin sulfate preparation is yellow powder, density 0.38g / L, pH 1.5 3.5, easily soluble in water, slightly acidic, stable under neutral and acidic conditions, and easy to fail under alkaline conditions.

Streptomycin Safety Information

Customs code: 2941200000 [3]

Streptomycin use

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

Streptomycin production method

It is divided into two major steps: Fermentation of strains, inoculating Streptomyces spores stored in cold-dry tubes or sandy soil tubes onto slant medium, and culturing at 27 ° C for 7 days. After the slant surface is full of spores, make a suspension and insert it into a shake flask filled with culture medium. Incubate at 27 ° C for 45 to 48 hours. After the mycelium grows vigorously, take several shake flasks and combine the culture solutions in it. It is inoculated into the sterilized medium in the seed tank, agitated with sterile air, cultured at a tank temperature of 27 ° C for 62-63 hours, and then inserted into the sterilized medium in the fermentor. Bacterial air, stirring culture, fermentation at a tank temperature of 27 ° C for about 7 to 8 days. Extraction and purification. The fermentation broth is acidified and filtered to remove hyphae and solids, then neutralized, ion-exchanged through a weak acid cation exchange resin, and eluted with dilute sulfuric acid to collect a high-concentration eluate, streptomycin. Sulfate solution. The eluent was desalted by a sulfonic acid ion exchange resin. At this time, the solution was acidic. After neutralization with an anionic resin, it was decolorized with activated carbon to obtain a refined solution (see color chart). The refined solution is concentrated into a concentrated solution through a thin film, and then spray-dried to obtain a sterile powdery product, or the concentrated solution is directly made into a water injection.

Streptomycin found

In 1945, Fleming, Flory and Chann shared the Nobel Prize in Medicine in recognition of their discovery of the first ever anti-bacterial
Streptomycin
A panacea for infectious diseases-penicillin. But penicillin does not work against many types of pathogens, including the tuberculosis pathogen Mycobacterium tuberculosis. Tuberculosis is one of the most harmful infectious diseases to human beings. After entering the 20th century, about 100 million people still died of tuberculosis. Famous writers such as Chekhov, Lawrence, Lu Xun and Orwell died prematurely due to tuberculosis . Doctors around the world have tried many ways to treat tuberculosis, but none of them is really effective. Being infected with tuberculosis means being sentenced to death. Even after Koch discovered Mycobacterium tuberculosis in 1882, this situation has not changed for a long time. The magical effect of penicillin has brought new hope to people. Can you find a similar antibiotic to effectively treat tuberculosis?
Sure enough, a few months after the 1945 Nobel Prize was awarded, on February 22, 1946, Professor Selman A. Waksman of Rutgers University announced that his laboratory had discovered Streptomycin, the second clinically used antibiotic, has special effects against tuberculosis, and a new era of human victory over tuberculosis has begun [1] . Unlike penicillin, the discovery of streptomycin was by no means accidental, but the result of well-designed and systematic long-term research. Like penicillin, this Nobel Prize-winning discovery is also full of controversy.
Waxman, a soil microbiologist, has been interested in actinomycetes in the soil since he was a university student. In 1915, he and his colleagues discovered streptomyces, streptomyces, at Rutgers University. It was later isolated from this actinomycete. It has long been noticed that Mycobacterium tuberculosis is quickly killed in the soil. In 1932, Waxman was commissioned by the American Association Against Tuberculosis to study this problem and found that it was probably due to the action of a certain microorganism in the soil. In 1939, funded by the pharmaceutical giant Merck, Waxman led his students to systematically study whether antibacterial substances could be isolated from soil microorganisms, which he later named antibiotics.
Waxman's students reached a maximum of 50 students, and they screened more than 10,000 strains in a division of labor. In 1940, Waxman and his colleague HB Woodruff isolated his first antibiotic, actinomycin. Unfortunately, it is too toxic and of little value. In 1942, Waxman isolated a second antibiotic, streptomycin. Streptomycin is very resistant to many types of bacteria, including tubercle bacilli, but it is too toxic to the human body. In the course of studying streptomycin, Waxman and colleagues developed a series of test methods that will be crucial for the future discovery of streptomycin.
Streptomycin was isolated by Waxman's student Albert Schatz. In 1942, Saz became a PhD student in Waxman. Soon, Saz was drafted into the army to work in a military hospital. In June 1943, Saz retired due to illness and returned to Waxman's laboratory to continue his PhD. Saz was assigned the task of discovering new species of Streptomyces. After working day and night in the converted laboratory in the basement for more than three months, Saz isolated two Streptomyces strains: one from the soil and one from the chicken's throat. These two strains are the same type of Streptomyces found by Waxman in 1915, but the difference is that they can inhibit the growth of several bacteria such as tuberculosis. According to Saz, he was aware of the discovery of a new antibiotic, streptomycin, on October 19, 1943. A few weeks later, after confirming that streptomycin was not very toxic, two doctors at the Mayo Clinic began to try it for patients with tuberculosis and it worked surprisingly well. In 1944, the United States and the United Kingdom began large-scale clinical trials, which proved that streptomycin is very effective in treating tuberculosis. It has also been shown to be effective against many infectious diseases such as plague, cholera, and typhoid. At the same time, Waxman and his students continued to study different strains of streptomyces, and found that different strains have different ability to produce streptomycin. Only four strains can be used for large-scale production of streptomycin. In 1946, Dr. Saz graduated and left Rutgers University. Before leaving Rutgers University, Saz, at Waksman's request, handed over the patent for streptomycin to Rutgers University for free. Saz thought that no one would profit from the streptomycin patent. But Waxman had other ideas. Waxman realized as early as 1945 that streptomycin would become an important medicine, and thus would generate huge patent revenue. But according to the agreement he signed with Merck in 1939, Merck will own all the patents for streptomycin. Waxman was worried that Merck did not have enough strength to meet the production needs of streptomycin, and felt that if other pharmaceutical companies could also produce streptomycin, the price of streptomycin would fall. So he asked Merck to cancel the 1939 agreement. Strangely enough, Merck even generously agreed to transfer the streptomycin patent to Rutgers University in 1946, only to obtain a license to produce streptomycin. Rutgers University issues 20% of patent revenue to Waxman.
Three years later, Saz learned that Waxman received personal income from the streptomycin patent, and that it had reached a total of US $ 350,000. He was very dissatisfied and sued Rutgers University and Waxman in the court for a share of patent revenue. In December 1950, the case was settled out of court. Rutgers University issued a statement recognizing Saz as a co-discoverer of streptomycin. According to the settlement agreement, Saz received US $ 120,000 in foreign patent revenue and 3% in patent revenue (approximately US $ 15,000 per year), Waxman received 10% in patent revenue, and another 7% in patent revenue was contributed by participating streptomyces Su share with others in early R & D work. Waxman voluntarily donated half of his patent revenue to a foundation to fund microbiology research.
In popular terms, Saz s approach undermines the hidden rules of the industry. Although winning a lawsuit, it has been difficult to establish a foothold in the academic world. He applied for faculty in more than 50 universities, and none of them was willing to accept a "scepter", so he had to teach at a private small farming college. Although Saz was legally a co-discoverer of streptomycin, academics did not recognize it. In October 1952, the Swedish Karolina Medical College announced that the Nobel Prize in Physiology or Medicine should be awarded to Waxman in recognition of his discovery of streptomycin. Through his agricultural college, Saz asked the Nobel Committee to let Saz share the honor and asked many Nobel laureates and other scientists for help, but few people were willing to speak for him. On December 12, the Nobel Prize in Physiology or Medicine was awarded to Waxman as scheduled. When Waxman introduced the discovery of streptomycin in the speech, he did not mention Saz, but said how about "we". Only at the end, Saz was included in the credit list. Waxman published his memoir in 1958, not mentioning Saz, but calling it "the graduate student."
Waxman has continued to study antibiotics since then. With his students, he discovered more than 20 antibiotics. Streptomycin and neomycin were the most successful. Waxman died at the age of 85 in 1973, leaving behind more than 500 papers and more than 20 books.
Saz never went to a first-class laboratory to conduct research. In the early 1960s, he couldn't find a job. He had to leave the United States to teach at a Chilean university. He returned to the United States in 1969, taught at Temple University, retired in 1980, and died in 2005 at the age of 84.
Saz's contribution to streptomycin was almost forgotten. He was gradually remembered after his retirement. This is due to Milton Wainwright, a microbiologist at the University of Sheffield, UK. In the 1980s, in order to write a book on antibiotics, Wynn Wright went to Rutgers University to check the archives of the streptomycin discovery process. For the first time, he learned about Saz's contribution. Saz. Weinley wrote several articles on the matter, and told the story of Saz in a book published in 1990. Waxman had already died at this time, and some professors at Rutgers University did not have to worry about embarrassing him, but also called for Saz to restore his reputation. For this reason, at the 50th anniversary of the discovery of streptomycin in 1994, Rutgers University awarded the Saz Medal.
Streptomycin sample
While complaining about Saz's neglect, it was accompanied by accusations against Waxman. For example, a comment published by the British "Nature" in February 2002 cited the discovery of streptomycin as an example to explain the unfairness of the ownership of scientific research findings, and Saz was the true discoverer of streptomycin. In 2004, a writer who was saved by streptomycin and co-authored Saz published "Dr. Saz Discovered". Waxman was portrayed as a research achievement that invaded Saz and took away the right to discover streptomycin. All glorious people.
Has Waxman invaded Saz's scientific research? The best way to judge a person's scientific research is to look at the paper publication record. In 1944, Waxman's laboratory published a paper on the discovery of streptomycin. The first author was Saz, the second author was E. Bugie, and Waxman was the last author. Judging from the order of the authors of this paper, it is completely in line with the practice in the biological world: Saz is the main finisher of the experiment, so he is ranked first, and Waxman is the director of the experiment, so he is ranked last. It can be seen that Waxman did not bury Saaz's contribution in the dissertation. Their subsequent disputes and mischiefs were caused by patent sharing and had nothing to do with the sharing of academic contributions.
Is it appropriate that the Nobel Prize be awarded to Waxman alone? Who are the main discoverers of streptomycin, Waksman and Saz? Streptomycin was not discovered by Saz alone for several months, but was the result of years of systematic research by Waxman's laboratory. It should be mainly attributed to the research plan designed by Waxman It's just part of the plan. According to this research plan and experimental procedure, the discovery of streptomycin is only a matter of time. Saz was just one of the laborers carrying out Waxman's research program. If you change to another graduate student, you can also find streptomycin. In fact, other students found streptomycin from other strains. Waxman's greatest contribution was to develop a systematic approach to discovering antibiotics, which has also been applied in other laboratories, and is therefore regarded by some as the father of antibiotics.
Therefore, the discovery right of streptomycin should mainly belong to the formulation and leader of the experimental project (ie, the mentor), and the specific performer (ie, the student) is secondary. This is actually the practice of awarding the Nobel Prize in Physiology or Medicine. It is not the discovery of streptomycin. Other Nobel Prize-winning biological results are usually awarded only to the leader of the experiment, and the students who perform the experiment rarely can share it. Saz obviously knew this too, so he later emphasized that he persuaded Waxman to study antibiotics against tuberculosis and tried to think of himself as the author of an experimental project. But this is not in line with historical facts, because before Saz joined Waxman's laboratory, Waxman's laboratory was testing the effect of antibiotics on Mycobacterium tuberculosis.

Streptomycin drug description

Streptomycin pharmacological action

Streptomycin is an aminoglycoside. Its mechanism 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. Streptomycin can first pass through the outer membrane porin through passive diffusion, and then enter the cell through the cell membrane through this transport system. It does not reversibly bind to the isolated ribosomal 30S subunit. , Leading to the destruction of the A site, and further:
1. Prevent the correct localization of aminoacyl tRNA at the A position, interfere with the assembly of functional ribosomes, and inhibit the formation of 70S initiation complex;
2. Induced mismatch of tRNA and mRNA code triplet, causing the 30S subunit of the complete ribosome to misread the genetic code, resulting in abnormal, nonfunctional protein synthesis;
3. Blocking the termination factor from binding to the A site, preventing the release of the synthesized peptide chain, and preventing the dissociation of the 70S complete ribosome;
4. Impede the depolymerization and assembly process of polyribosomes, resulting in depletion of ribosomes in 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 against many Gram-negative bacteria such as E. coli, Klebsiella pneumoniae, Enterobacter, Salmonella, Shigella, Brucella, Pasteurella, Meningococcus and Neisseria Has a certain antibacterial activity. Streptomycin has poor antibacterial activity against most Gram-positive cocci such as Staphylococcus aureus. Streptomycin has no antibacterial effect on Enterococcus at commonly used doses. Streptococcus, Pseudomonas aeruginosa and anaerobic bacteria were resistant to streptomycin in each group [4] .

Streptomycin pharmacokinetics

Streptomycin streptomycin is not easily absorbed orally, and is well absorbed after intramuscular injection. After intramuscular injection of 0.5 g or 1 g, the blood concentration reached a peak after 30 min, which were 15 to 20 g / ml or 30 to 40 g / ml, respectively. The effective blood concentration can be maintained for about 12 hours. The streptomycin distribution volume (Vd) was 0.26 L / kg. The drug is mainly distributed in extracellular fluid after absorption, and can be distributed in all organs and tissues except the brain. Streptomycin can penetrate into bile, pleural effusion, peritoneal effusion, tuberculous abscess, and casein-like tissue. It has a higher concentration in urine and a lower concentration in cerebrospinal fluid and bronchial secretions. Streptomycin can penetrate the placental tissue, and the concentration in umbilical cord blood is similar to that in maternal blood. Streptomycin protein binding rate is 20% to 30%. The half-life is 2.4 to 2.7 h, and the half-life increases with age (2 to 3 h in young people, 9 h or more at the age of 40); the half-life can reach 50 to 110 h in renal failure. The drug is not metabolized in the body, and about 80% to 90% is filtered by the glomerulus and excreted in 24 hours with urine; another about 1% is excreted from bile, and there is also a very small amount excreted from milk, saliva and sweat. Hemodialysis can clear equivalent doses of the drug [4] .

Streptomycin dosage

adult
Commonly used amount Antibacterial, intramuscular injection, 0.5g (calculated as streptomycin, the same below), once every 12 hours, combined with other antibacterial drugs; endocarditis (bacterial), intramuscular injection, and penicillin G Combined, 1g at a time, once every 12 hours, for a continuous week, followed by 0.5
Streptomycin
g, once every 12 hours for a week; patients over 60 years old should be reduced to 0.5g, once every 12 hours for two consecutive weeks. Endocarditis (enterococcal), intramuscular injection, combined with penicillin G, 1g at a time, once every 12 hours; two consecutive weeks, followed by 0.5g, once every 12 hours for four consecutive weeks. Plague, intramuscular injection of 0.5 ~ 1.0g, once every 12 hours, the course of treatment for 10 days. Tularemia, intramuscular injection, 0.5 to 1.0 g, once every 12 hours for 7 to 10 consecutive days. Tuberculosis, combined with other anti-tuberculosis drugs, intramuscular injection, 1.0g a day, two times a day, or 0.75g once a day; if clinical conditions permit, switch to intermittent administration, which is reduced to weekly administration 2 to 3 times, 1 g each time; intramuscular injection in elderly patients, once 0.5 to 0.75 g, once daily.
Children
Commonly used intramuscular injection, other infections are administered in divided doses of 15 to 25 mg / kg daily for body weight; tuberculosis, combined with other anti-tuberculosis drugs, 20 mg / kg once daily for a maximum daily dose of no more than 1g.
Summary
The usage of streptomycin is as follows. It is used for intramuscular injection. At present, it is believed that a single injection of 750 mg per day for adults can achieve the therapeutic purpose.
Streptomyces spore chain
G twice daily intramuscular injection, its effect is exactly the same as a single intramuscular injection. Therefore, a 750 mg intramuscular injection is 250 mg less a day, and side effects are reduced due to a decrease in the dose. The dosage can be increased or even doubled for individual patients with severe illness, but the continuous application time should not be too long, generally should not exceed 1 week, and must be applied under close observation. The dose for the elderly is appropriately reduced, and children should be around 25 milligrams per kilogram of body weight per day. It must also be closely observed. A side reaction should be promptly taken. Now we are using streptomycin sulfate. In the past, dihydrostreptomycin was used. Because more patients have permanent deafness (deafness), dihydrostreptomycin has been eliminated by the State Medical Administration and no longer produced and use.
After intramuscular injection of streptomycin, the peak blood absorption concentration can appear in half an hour to two hours, and the concentration that effectively inhibits bacterial growth can be maintained for 12 hours. Older patients may take longer. Excretion of streptomycin is mainly performed by the kidneys. After injection of streptomycin, it easily penetrates into the thoracic cavity and abdominal cavity, and can also enter the fetal amniotic fluid through the placenta, and the drug concentration is also high. Because of the high concentration in the amniotic fluid, it cannot be used in pregnant women. Because it cannot pass (or pass in a small amount) the blood-brain barrier, it cannot be used to treat tuberculous meningitis.

Streptomycin considerations

Patients should pay attention to monitoring: electrocardiogram, elderly patients need to perform electrocardiogram to detect high-frequency hearing damage before, during and after long-term medication; temperature stimulation test, regular before and during medication It is used to detect vestibular toxicity after long-term medication; Renal function measurement. Renal function is regularly measured before and during medication to prevent serious renal toxicity.
(1) The blood drug concentration and peak blood drug concentration should be monitored to increase the possibility of causing toxic reactions when the blood drug concentration exceeds 50 g / ml. For patients with renal insufficiency, the blood drug peak concentration should be monitored frequently, preferably not more than 20 to 25 g / ml .
(2) When the blood concentration cannot be measured, the dose should be adjusted according to the creatinine clearance rate, and the creatinine clearance
Streptomycin chemical formula
The rate can be calculated from the formula attached to aminoglycosides in this chapter.
(3) After the first saturation dose is given, patients with renal insufficiency, vestibular or hearing loss should be reduced or discontinued. Streptomycin is not metabolized in the body and is mainly excreted by urine. Patients with renal insufficiency may Accumulate to reach toxic concentration.
(4) Patients should be given sufficient water to reduce the degree of tubular damage.
(5) When the patient feels better after taking the medicine for several days or weeks (tuberculosis), he still needs to complete the prescribed course of treatment. This is extremely important, especially during TB treatment. The treatment of tuberculosis must be continued for 1-2 years, sometimes even for several years or long-term continuous application. However, streptomycin should be discontinued when symptoms of poisoning have appeared or are about to occur, or when bacteria have developed resistance.
(6) Intramuscular injection should often change the injection site, the concentration of the drug solution is generally 200 ~ 250mg / ml, should not exceed 500mg / ml.
(7) Long-term medication may cause excessive growth of insensitive bacteria.

Streptomycin adverse reaction

Allergic reaction
Both streptomycin and dihydrostreptomycin can be combined with serum proteins to form a full antigen, but the antibodies produced are different, so there is no cross-reaction, and those who are allergic to streptomycin can use dihydrostreptomycin. However, there is a history of allergies to both, which requires considerable attention. Allergic reactions include: rash (0.3% to 11%), which can manifest as skin such as maculopapular rash, urticaria, erythema, measles-like rash, scarlet fever-like rash, pemphigoid-like rash, eczema-like rash, purpura, and angioedema which performed. Severe allergic shock can occur, and severe allergic reactions can be complicated by acute hemolytic anemia, hemoglobinuria, shock, acute renal failure, and so on.
This product can cause allergic reactions, more common are rash, fever, and eosinophilia. The incidence of rashes ranges from 0.3% to 10% (average 5%).
Streptomycin
It usually occurs 7 to 9 days after starting treatment, but patients who have previously received streptomycin treatment can appear quickly within a few hours. The most common are maculopapular rash, accompanied by itching, which usually subsides after 5 to 10 days; a few can develop exfoliative dermatitis, which quickly subsides within 1 to 3 days after stopping the drug. Rare rashes include urticaria, erythema, measles-like rash, scarlet fever-like rash, pemphigoid-like rash, eczema-like rash, etc., and may also be associated with angioedema or purpura. Contact dermatitis often occurs in medical workers who often come in contact with streptomycin, repackaging workers in pharmaceutical factories, and those who use the product topically, which usually occurs 3 to 12 months after exposure; rashes often occur on both hands, back of the hand, eyelid, The neck and other areas show skin redness, pruritus, pimples, eyelid swelling, eyelid eczema, etc., which can resolve after stopping contact. Therefore, the topical application of this product has been ignored. This product can also cause anaphylactic shock, and some patients may develop similar symptoms based on specific constitution. Patients often do not take large doses, and most of them have sudden onset of dyspnea, pale, bruising, coma, convulsions, foaming in the mouth, and incontinence, etc. within 1 to 2 minutes after injection. Children with respiratory infections are more common. Although the incidence of anaphylactic shock caused by this product is lower than that caused by penicillin, there have been no fewer than 100 domestic reporters, and deaths due to shock are not a minority, which has caused people to be highly vigilant. Nervous system: The initial preparation of streptomycin is not pure, which often causes headache, numbness, dizziness, tinnitus, vomiting and dilated peripheral blood vessels, redness of the skin, and sharp drop in blood pressure. Refined streptomycin can still cause headaches, dizziness, and numbness, but the incidence is obviously lower. The clinical toxicity of streptomycin is related to the daily dose and duration of treatment. Ototoxicity is directly proportional to the daily dose. If the dose is higher than 1g / day, the incidence of ototoxicity will increase. Vestibular damage can occur if the total amount is 1g and the total amount is within the range of 5-30g. The most common and serious toxic reaction is damage to the 8th nerve to the brain. Ototoxicity caused by it accounts for 14.8% of sensorineural deafness; children or elderly patients, those with impaired renal function, those whose blood concentration is continuously above 25 g / ml, and those with otitis media are more likely to develop ototoxic symptoms. The main symptoms of vestibular disorders are dizziness and sudden movements that can cause nausea and vomiting. The severe patients still feel that they continue to continue after each movement is stopped. Streptomycin mainly causes vestibular ganglion lesions of the vestibular system. In addition, the ampullary ridges and sensory epithelial cells of the vestibular plaques of the peripheral organs of the inner ear also have different degrees of lesions. Cochlear damage generally occurs relatively late, often after several months of medication or after discontinuation. High-frequency hearing is often affected first, and its damage is also severe. The main symptoms of cochlear damage are tinnitus and deafness. Persistent tinnitus and fullness of the ears are sometimes a precursor to hearing loss. Deafness can be prevented if the medication is stopped immediately. It has been reported that people with familial susceptible constitutions can cause significant hearing damage by using a small amount of streptomycin; some particularly sensitive people can have hearing loss with only 0.2 ~ 3g. This familial streptomycin ear poisoning is inherited only through the maternal line, and has no cross-susceptibility to other aminoglycosides such as gentamicin, neomycin, and kanamycin. Therefore, streptomycin should be used with caution in relatives or family members who have experienced hearing loss with streptomycin. Most of the toxic reactions of streptomycin to the inner ear appear after a certain period (January to June), and they are rarely found during the administration, so it is not easy to attract people's attention. When a large amount of streptomycin is applied in the chest or abdominal cavity, respiratory failure and cardiac arrest may occur due to neuromuscular blockade, but it is rare. Peripheral neuritis is rare and can cause optic neuritis and vision loss.
Urinary system: Streptomycin can cause mild damage to the kidney, and patients may have proteinuria, cast urine, etc. Generally, it does not affect continued medication. A small number of patients may have renal dysfunction, but can recover after stopping the drug. Taking sodium bicarbonate and other drugs to make urine urine alkaline can reduce the chance of proteinuria production. [Blood system] Leukopenia is more common. In addition, granulocytopenia, thrombocytopenia, and aplastic anemia can occur. [Special organs] Long-term use of streptomycin can cause complete or partial loss of olfactory function. It has been reported to use this product to treat Meniere's syndrome in 95% of patients, and dizziness disappeared while hearing remained.
Others: There may be pain and swelling at the intramuscular injection site, which is usually mild and does not last long. After intramuscular injection, it can often cause transient numbness and dizziness around the mouth. Heavier patients can be accompanied by numbness of the frontal face, scalp and limbs, which can disappear automatically after several hours, and sometimes last longer. There are also hirsutism, conjunctivitis, paresthesia, joint pain, mental disorders, toxic encephalopathy, dark spots in the center of the eyes, visual impairment, myocarditis, and hypertension. Others include stomatitis, scrotal dermatitis, and diarrhea due to vitamin deficiency; secondary infections such as staphylococcal enteritis and fungal endocarditis are also occasionally seen.
Streptomycin
Toxic reaction
1) Acute toxic reactions: numbness, dizziness, deafness, etc. are more common, and most often occur within 10 days after administration. The shortest person appears numbness within 20 minutes after injection, which lasts for 1 to 6 hours. In severe cases, it can continue for 24 hours. . Peripheral numbness, dizziness, dyskinesia, headache, fatigue, vomiting, facial flushing also occur in severe cases, and severe sweating, dyspnea, spasms are not easy to distinguish from anaphylactic shock. However, acute reactions are more common or gradually aggravated, and some cases only respond when the injection is started, and then disappear. The acute response of streptomycin is generally thought to be related to the impurities it contains.
2) Chronic toxicity: The eighth pair of cranial nerve damage; a) the vestibular damage of the ear, which mainly manifests dizziness, headache, and often finger errors. Later on, ataxia of exercise ataxia, etc .; b) Cochlear damage: generally occurs later, often after a few months of medication or after discontinuation. Its main symptoms are tinnitus and deafness. Local stimulation: intramuscular injection of local pain, swelling, sterile abscess, etc. Intrathecal injection can cause fever, paleness, agitation, decreased appetite, convulsions, shock, and severe cases can lead to death. Damage to the kidney: Streptomycin has less damage to the kidney, which is manifested by proteinuria and cast urine. Some of them have temporarily decreased renal function and can be recovered after stopping the drug. Serious permanent kidney damage is rare. Bone marrow suppression: Leukocytes, thrombocytopenia, aplastic anemia, and oligocytosis. Leukopenia is common, and aplastic anemia and pancytopenia are rare. There are hirsutism, conjunctivitis, arthralgia, myocarditis, toxic encephalopathy and so on.
other
Intestinal flora imbalance, secondary infection, multivitamin deficiency, angular cheilitis, dermatitis, diarrhea, etc.
Prevention
1) Reasonable use of streptomycin and strict control of indications. Streptomycin is currently mainly used for tuberculosis and plague.
2) It is necessary to strictly control the dosage and course of treatment. 0.75 g / day is enough for adults with tuberculosis. Do not use 1 g. It can reduce the occurrence of side effects. The elderly, children, and people with renal insufficiency should be used with caution. The dosage should be small and the course of treatment should be short.
3) Strictly observe the symptoms and signs of various toxic and side effects. Once found, they should be dealt with in a timely manner and immediately discontinued if necessary.
4) It should not be administered by intravenous or subcutaneous injection.
5) Rescue should be organized immediately when anaphylactic shock occurs.
6) Banned for pregnant women, infants and young children should be avoided as much as possible.

Streptomycin indication

1. This product is suitable for tularemia, or combined with other antibacterial drugs for plague, venereal disease granuloma, brucellosis, rat bite fever, and can be used in combination with penicillin to treat or prevent Streptococcus aureus or Enterococcus Endocarditis.
2. This product can also be used in combination with other anti-tuberculosis drugs for various tuberculosis or other mycobacterial infections caused by Mycobacterium tuberculosis.
3 This product is mainly used in combination with other antituberculosis drugs for newly treated cases of various tuberculosis caused by Mycobacterium tuberculosis, or other sensitive mycobacterial infections.
4 The product can be used alone for the treatment of tularemia or in combination with other antibacterial drugs for the treatment of plague, groin granuloma, brucellosis, and rat fever.
5. It can also be combined with penicillin or ampicillin to treat endocarditis caused by Streptococcus lividans or Enterococcus faecalis.

Streptomycin contraindications

(1) Cross-allergies. Patients who are allergic to one aminoglycoside may also be allergic to other aminoglycosides. Those with a history of streptomycin allergy are contraindicated.
(2) Streptomycin can pass through the placenta, and its concentration in umbilical cord blood is about the same as that in maternal blood. It has been reported that streptomycin has caused hearing loss in human fetuses. Pregnant women must weigh the pros and cons fully.
(3) Elderly patients can produce various toxic reactions after application of aminoglycosides, so it is extremely important to monitor renal function (preferably to measure creatinine clearance) during aminoglycoside treatment. Hearing loss may also occur in patients with normal renal function. In addition, older patients should take smaller doses to suit their age, renal function, and function of the 8th pair of brain nerves.
(4) The following situations should be used with caution:
Dehydration, as the blood concentration increases, the possibility of toxic reactions increases;
The 8th pair of brain nerve damage, streptomycin can cause damage to the auditory nerve and vestibular function;
Myasthenia gravis or Parkinson's disease, streptomycin can cause neuromuscular blockade, resulting in skeletal muscle weakness;
Renal function damage, streptomycin can cause renal toxicity. This product can also cause fetal hearing loss, so pregnant women should avoid or use it with caution.
The side effects of a few patients are serious. Therefore, the use of streptomycin must be applied under the guidance of a doctor.

Streptomycin considerations

1. Patients who are allergic to one aminoglycoside may be allergic to other aminoglycosides.
2. Streptomycin should be used with caution in the following situations:
(1) Dehydration can increase blood drug concentration and cause toxic reactions.
(2) The eighth pair of brain nerve damage, because this product can cause damage to the vestibular nerve and the auditory nerve.
(3) Myasthenia gravis or Parkinson's disease, because this product can cause neuromuscular blockade, resulting in skeletal muscle weakness.
(4) Impaired renal function due to its nephrotoxicity.
3 During the course of treatment, the following inspections should be carried out regularly:
(1) Urine routine and renal function tests to prevent severe renal toxicity.
(2) Hearing test or electrogram (especially high-frequency hearing) measurement, which is particularly important for elderly patients.
4 When possible, monitor blood concentration and adjust the dose accordingly, especially for newborns, elderly and patients with impaired renal function. Those who administer 7.5 mg / kg every 12 hours should maintain the peak plasma concentration at 15-30 g / ml and trough concentration 5-10 g / ml; those who administer 15 mg / kg once a day should maintain the peak plasma concentration at 56-64 g / ml, trough concentration <1 g / ml.
5. Interference to diagnosis: This product can increase the measured values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin concentration and lactate dehydrogenase concentration; blood calcium, magnesium The measured values of potassium, potassium, and sodium may decrease. This product belongs to the class of aminoglycosides, which belongs to Class D for pregnant women, which is harmful to humans, but the benefits may outweigh the disadvantages. The product can enter the fetal tissue through the placenta. It has been reported that pregnant women have caused fetal hearing loss after using this product. Therefore, pregnant women must fully weigh the advantages and disadvantages before using this product. Breastfeeding should be suspended during medication. Patients are prone to various toxic reactions after application of aminoglycosides.

Streptomycin drug interactions

(1) The use of streptomycin with other aminoglycosides or continuous local or systemic application can increase the possibility of ototoxicity, renal toxicity, and neuromuscular blockade. Hearing loss may occur and deafness may progress after stopping the drug; hearing damage may recover or be permanent. Neuromuscular blockade can lead to skeletal muscle weakness, respiratory depression or paralysis (apnea). Anticholinergic drugs or calcium salts can help block recovery.
(2) The combination of streptomycin and neuromuscular blockers can aggravate neuromuscular blockade, resulting in muscle weakness, respiratory depression or paralysis (apnea). The combination of streptomycin with capreomycin, cisplatin, uric acid, furosemide, or vancomycin, or continuous local or systemic application may increase ototoxicity and renal toxicity, hearing damage may occur, and it may still occur after stopping the drug May develop deafness, hearing damage may recover or be permanent.
(3) Local or systemic application of streptomycin and ceftiophen may increase renal toxicity.
(4) The combination of streptomycin and polymyxins, or continuous local or systemic application, can increase renal toxicity and neuromuscular blockade, which can cause skeletal muscle weakness, respiratory depression or paralysis (apnea) .

Streptomycin preparation

Based on streptomycin. Streptomycin sulfate for injection (1) 0.75g (750,000 units) (2) 1g (1 million units) (3) 2g (2 million units) (4) 5g (5 million units). Because it is not absorbed in the gastrointestinal tract, it is only effective for intestinal infections and is now less commonly used. Intramuscular injection, 0.75 1g per day, divided into 1 or 2 times, 1 to 2 Monday course, 15-30mg / kg per day for children, divided into 2 times, 20mg / kg per day for tuberculosis, divided into 2 times, every other day , Newborns 10 to 20mg / kg a day.

Streptomycin Expert Reviews

Streptomycin has been in clinical use for more than half a century and is still the first-line antituberculosis drug. In recent years, due to the increase of resistant tuberculosis strains, it is mainly used in the initial stage of tuberculosis. Streptomycin can be used alone in rabbit fever, with good curative effect, and the course of treatment is 6 days. Combined with tetracycline for the treatment of plague is the drug of choice. Can also be used for brucellosis, the dosage is 1 to 2g per day, and 500mg once a day with tetracycline, 4 times a day, for 3 consecutive weeks or more. Streptomycin 1 to 2 g per day, combined with penicillin for the treatment of Streptococcus grass green endocarditis for 4 consecutive weeks, the two have a synergistic effect [4] .

Streptomycin

Instruction manual for streptomycin sulfate for injection
Drug Name
Common name: Streptomycin sulfate for injection
English name: Streptomycin Sulfate for Injection
Phonetic script: Zhusheyong Liusuan Lianmeisu
The main ingredient of this product is streptomycin sulfate, and its chemical name is O -2-methylamino-2-deoxy- a -L-glucopyranosyl- (1 2) -O -5-deoxy-3-C -Formyl- a -L-lysofuranosyl- (1 4) -N , N -diamidyl-D-streptomycin sulfate.
Its structural formula is:
Molecular formula: (C21H39N7O12) 2 · 3H2SO4
Molecular weight: 1457.40
[Character]
This product is white or off-white powder.
[Pharmacology and Toxicology]
Streptomycin sulfate is an aminoglycoside antibiotic. Streptomycin has a strong antibacterial effect on Mycobacterium tuberculosis, and its minimum inhibitory concentration is generally 0.5 mg / ml. Most non-tuberculous mycobacteria are resistant to this product. Streptomycin also affects many Gram-negative bacteria such as Escherichia coli, Klebsiella, Proteus, Enterobacter, Salmonella, Shigella, Brucella, Pasteurella, etc. Antibacterial effect; Neisseria meningitidis and Neisseria gonorrhoeae are also sensitive to this product. Streptomycin has a poor effect on Staphylococcus and other Gram-positive cocci. Streptococcus, Pseudomonas aeruginosa and anaerobic bacteria in each group were resistant to this product.
Streptomycin mainly binds to the bacterial ribosome 30S subunit and inhibits bacterial protein synthesis. Bacteria are prone to drug resistance after contact with streptomycin. The combination of streptomycin and other antibacterial or antituberculosis drugs can reduce or delay the development of resistance.
Pharmacokinetics
Good absorption after intramuscular injection. It is mainly distributed in extracellular fluid and can be distributed to systemic organs and tissues other than the brain. The amount of this product reaching the cerebrospinal fluid, brain tissue and bronchial secretion is small; but it can reach bile, pleural fluid, ascites, tuberculous abscess and cheese Like tissue and can enter fetal tissue through the placenta. Protein binding rate is 20% to 30%. The blood elimination half-life (t1 / 2b) is 2.4 to 2.7 hours, which can be significantly prolonged when renal function declines. This product is not metabolized in the body and is mainly excreted through glomerular filtration. 80% to 98% is excreted in urine 24 hours after administration, about 1% is excreted from bile, and a small amount is excreted from milk, saliva and sweat. This product can clear a considerable amount by hemodialysis.
[Indications]
1. This product is mainly used in combination with other antituberculosis drugs for newly treated cases of various tuberculosis caused by Mycobacterium tuberculosis, or other sensitive mycobacterial infections.
2. This product can be used alone for the treatment of Tularemia, or in combination with other antibacterial drugs for the treatment of plague, groin granuloma, brucellosis, and rat fever.
3 It can also be combined with penicillin or ampicillin to treat endocarditis caused by Streptococcus aureus or Enterococcus.
Dosage
1. Adult common dose
(1) Intramuscular injection, 0.5g (calculated as streptomycin, the same below), once every 12 hours, combined with other antibacterial drugs; bacterial (streptococcus grass) endocarditis, intramuscular injection, each 1 g at 12 hours, combined with penicillin for 1 week, followed by 0.5 g every 12 hours, for 1 week; patients over 60 years old should be reduced to 0.5 g every 12 hours for 2 weeks.
(2) Enterococcal endocarditis, intramuscular injection, combined with penicillin, 1 g every 12 hours for 2 weeks, followed by 0.5 g every 12 hours for 4 weeks.
(3) Plague, intramuscular injection, 0.5 ~ 1g once, once every 12 hours, combined with tetracycline, the course of treatment is 10 days.
(4) Tularemia, intramuscular injection, 0.5 to 1 g every 12 hours for 7 to 14 consecutive days.
(5) Tuberculosis, intramuscular injection, 0.5g every 12 hours, or 0.75g once a day, combined with other anti-tuberculosis drugs; if intermittent therapy is used, it is administered 2 to 3 times a week, each time 1g; intramuscular injection in elderly patients, once 0.5 ~ 0.75g, once a day.
(6) Brucellosis, 1 ~ 2g daily, divided into two intramuscular injections, combined with tetracycline, the course of treatment is 3 weeks or more.
2. Intramuscular injection is commonly used in children, and it is administered in divided doses of 15 to 25 mg / kg daily based on body weight. For tuberculosis, 20 mg / kg is administered once daily, and the maximum daily dose does not exceed 1 g. Combined.
3 Patients with renal insufficiency: The normal dose of streptomycin in normal renal function is once a day, 15mg / kg intramuscular injection. Creatinine clearance rate> 50 90ml / min, 50% of the normal dose given every 24 hours; Creatinine clearance rate of 10 50ml / min, 50% of the normal dose given every 24 72 hours; 50% of the normal dose is given every 72 to 96 hours. Creatinine clearance can be measured directly or calculated from the patient's serum creatinine value as follows:
(140-age) × standard weight (kg)
Adult male creatinine clearance =
72 × patient blood creatinine concentration (mg / dl)
(140-age) × standard weight (kg)
or
50 × patient's blood creatinine concentration (umol / L)
(140-age) × standard weight (kg)
Adult female creatinine clearance = × 0.85
72 × patient blood creatinine concentration (mg / dl)
(140-age) × standard weight (kg)
Or × 0.85
50 × patient's blood creatinine concentration (umol / L)
Adverse reactions
1. Renal toxicity symptoms such as hematuria, decreased urination or decreased urine output, decreased appetite, thirst, and a few can increase blood urea nitrogen and creatinine values.
2. When affecting vestibular function, there may be symptoms such as instability, dizziness, etc .; the hearing nerve, hearing loss, tinnitus, and ear fullness may be affected.
3 Some patients may experience symptoms of peripheral nerve inflammation such as facial or limb numbness, acupuncture.
4 Occasionally, vision loss (optic neuritis), drowsiness, weakness, dyspnea and other neuromuscular block symptoms can occur.
5. Occasionally rash, itching, and swelling may occur. Ototoxic symptoms such as hearing loss, tinnitus, and fullness in the ear can still occur after a few patients stop taking the drug, which should be paid attention to.
Contraindications
Patients who are allergic to streptomycin or other aminoglycosides are contraindicated.
Precautions
1. Patients who are allergic to one aminoglycoside may be allergic to other aminoglycosides.
2. Streptomycin should be used with caution in the following situations:
(1) Dehydration can increase blood drug concentration and cause toxic reactions.
(2) The 8th pair of brain nerve damage, because this product can cause damage to the vestibular nerve and the auditory nerve.
(3) Myasthenia gravis or Parkinson's disease, because this product can cause neuromuscular blockade, resulting in skeletal muscle weakness.
(4) Impaired renal function due to its nephrotoxicity.
3 During the course of treatment, the following inspections should be carried out regularly:
(1) Urine routine and renal function tests to prevent severe renal toxicity.
(2) Hearing test or electrogram (especially high-frequency hearing) measurement, which is particularly important for elderly patients.
4. When necessary, monitor the blood concentration and adjust the dose accordingly, especially for newborns, elderly and patients with impaired renal function. Those who administer 7.5 mg / kg every 12 hours should maintain the peak plasma concentration at 15-30 mg / ml and trough concentration 5-10 mg / ml; those who administer 15 mg / kg once a day should maintain the peak plasma concentration at 56 64mg / ml, trough concentration <1mg / ml.
5. Interference to diagnosis: This product can increase the measured values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin concentration and lactate dehydrogenase concentration; blood calcium, magnesium The measured values of potassium, potassium, and sodium may decrease.
[Medication for pregnant and lactating women]
This product belongs to Class D for pregnant women, which is harmful to humans, but the benefits may outweigh the disadvantages. This product can enter the fetal tissue through the placenta. It has been reported that pregnant women have caused fetal hearing loss after using this product. Therefore, pregnant women must fully weigh the advantages and disadvantages before using this product. Breastfeeding should be suspended during medication.
[Child medication]
This product belongs to aminoglycosides, and should be used with caution in pediatrics, especially the kidney tissues of premature babies and newborns are not fully developed, which prolongs the half-life of this class of drugs, and the drugs are easy to accumulate in the body and produce toxic reactions.
[Medication for elderly patients]
Elderly patients are prone to various toxic reactions after application of aminoglycosides, and blood concentrations should be monitored during the course of treatment as much as possible. There is a certain degree of physiological decline in renal function in elderly patients. Even if the measured renal function is within the normal range, a small amount of treatment should be used.
medicine interactions
1. This product combined with other aminoglycosides or successive local or systemic applications can increase the possibility of ototoxicity, nephrotoxicity and neuromuscular blockade.
2. This product combined with neuromuscular blocking drugs can aggravate neuromuscular blockade. This product is used in combination with capreomycin, cisplatin, itanilic acid, furosemide, or vancomycin (or norvancomycin), or successive local or systemic applications may increase ototoxicity and renal toxicity.
3 This product can be used locally or systemically with cefotaxime or cefazolin, which may increase renal toxicity.
4 This product is used in combination with polymyxin injections, or successively applied locally or systemically, which can increase renal toxicity and neuromuscular blockade.
5. Other nephrotoxic drugs and ototoxic drugs should not be combined with this product or applied in order to avoid aggravating nephrotoxicity or ototoxicity.
[Drug overdose]
Due to the lack of specific antagonists, when this product is excessive or causes toxic reactions, symptomatic therapy and supportive therapy are mainly used, and a large amount of water is added at the same time. Hemodialysis or peritoneal dialysis can help remove streptomycin from the blood.
specification
(1) 0.75g (750,000 units) (2) 1g (1 million units)
(3) 2g (2 million units) (4) 5g (5 million units)
Storage
Keep tightly closed and store in a dry place [5] .

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