Streptomycin

Streptomycin belongs to the pharmacological class of Aminoglycoside antibiotics.

Streptomycin has been approved to relieve symptoms and also for the treatment of Brucellosis, Endocarditis, Mycobacterial infection, Plague, treatment, Tuberculosis, Tularemia.

Streptomycin, an aminoglycoside antibiotic, is not effectively absorbed when taken orally, leading to its parenteral administration through intramuscular injection or intravenous infusion. Following intramuscular administration of 1 gram of streptomycin, a peak serum concentration of 25-50 mcg/mL is achieved within 1 hour. The specific volume of distribution and extent of protein binding for streptomycin are not available. Streptomycin undergoes minimal metabolism in the body and is primarily eliminated in the urine, with approximately 50% of the administered dose excreted within 24 hours after intravenous or intramuscular administration. Monitoring and adherence to recommended administration guidelines are important due to individual variations in pharmacokinetics and patient-specific factors.

The common side effects involved in using Streptomycin are Nausea, Painful or difficult urination, Sensation of spinning, Shortness of breath, Sore throat, Sores, ulcers, or the white spots on the lips or in the mouth, Swollen glands, Unsteadiness, Unusual bleeding or bruising, Unusual tiredness or weakness, Vomiting.

Streptomycin is available in the form of Powder for injection.

Streptomycin is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.

Streptomycin belongs to the pharmacological class of Aminoglycoside antibiotics.

Streptomycin is an antibiotic that exerts its therapeutic effect by inhibiting bacterial protein synthesis. It specifically targets the bacterial ribosomes, which are responsible for the production of proteins essential for bacterial growth and survival.

The mechanism of action of streptomycin involves binding to the 30S subunit of the bacterial ribosome, which interferes with the initiation complex formation and causes misreading of the genetic code during protein synthesis. This leads to the production of faulty or nonfunctional proteins, ultimately inhibiting bacterial growth.

Streptomycin has been approved to relieve symptoms and also for the treatment of Brucellosis, Endocarditis, Mycobacterial infection, Plague, treatment, Tuberculosis, Tularemia.

The peak concentration of streptomycin in the blood is typically achieved within 1 to 2 hours after intramuscular (IM) administration. Streptomycin reaches its peak concentration in the blood within 1 to 2 hours after IM administration. The onset of action of streptomycin varies depending on the condition being treated. In the case of bacterial infections such as tuberculosis or brucellosis, it may take several days to a few weeks to observe a significant therapeutic effect. Streptomycin is usually given in combination with other antibiotics, and the onset of action may be influenced by the overall treatment regimen. The duration of action of streptomycin also varies depending on the specific condition being treated. In some cases, streptomycin is administered for a limited duration, such as the first 14 to 21 days of therapy for brucellosis. For other conditions like tuberculosis, the duration of treatment may extend over several months. The therapeutic effect of streptomycin may persist for a period after the discontinuation of treatment due to its slow elimination from the body.

Streptomycin is found to be available in the form of Powder for injection.

Streptomycin can be used in the following treatment:

• Brucellosis
• Endocarditis
• Mycobacterial infection
• Plague, treatment
• Tuberculosis
• Tularemia

Streptomycin can help to relieve symptoms and also for the treatment of Brucellosis, Endocarditis, Mycobacterial infection, Plague, treatment, Tuberculosis, Tularemia.

Streptomycin is approved for use in the following clinical indications:

• Brucellosis
• Endocarditis
• Mycobacterial infection
• Plague, treatment
• Tuberculosis
• Tularemia

• Brucellosis:

Brucellosis treatment typically involves a combination therapy approach with streptomycin and doxycycline. The duration of treatment depends on the extent of the disease, with streptomycin usually administered for the first 14 to 21 days, followed by doxycycline monotherapy. It's important to note that different agents or regimens are preferred for neurobrucellosis, endocarditis, and pregnant women with brucellosis.

• Endocarditis (alternate agent):

In the case of endocarditis caused by Enterococcus spp., particularly when they are susceptible to penicillin and streptomycin but resistant to gentamicin, streptomycin is used in combination with ampicillin or penicillin. The duration of therapy is typically 4 weeks for native valve endocarditis with symptoms present for less than 3 months, and at least 6 weeks for native valve endocarditis with symptoms present for 3 months or more, or for prosthetic valve endocarditis. However, for native valve endocarditis caused by ampicillin-susceptible E. faecalis, a combination regimen that does not include streptomycin is preferred.

• Mycobacterial infection (off-label use):

In the case of nontuberculous mycobacterial infections, such as Mycobacterium avium complex, streptomycin is used as an adjunctive agent. The dosage varies depending on the severity and type of pulmonary disease, with different guidelines suggesting daily or three times weekly dosing. Streptomycin is typically given as part of a combination regimen for the first 2 to 3 months of therapy. Specific considerations are given to older adults or patients requiring long-term parenteral therapy.

• Plague treatment:

For the treatment of plague caused by Yersinia pestis, streptomycin is administered intramuscularly or intravenously. The recommended dosage is 1 g every 12 hours for 7 to 14 days, with treatment continuing for a few days after clinical resolution.

• Tuberculosis (alternative agent):

In the case of tuberculosis, streptomycin can be used as an alternative agent. The recommended dosage is 15 mg/kg once daily or 25 mg/kg three times weekly.

• Tularemia (alternative agent):

In the treatment of tularemia, streptomycin is administered intramuscularly at a dosage of 1 g twice daily for a duration of at least 10 days, depending on the severity of the infection.

Powder for injection: 1g

Powder for injection

• Dosage Adjustments in Kidney Patients:

The manufacturer's labeling does not include specific dosage adjustments, so caution is advised along with a potential adjustment in dosage and/or time interval between doses.

• Dosage Adjustments in Pediatric Patients:

• Moderate to Severe Infections

The recommended dosage for streptomycin in moderate to severe infections is 20-40 mg/kg/day, given intramuscularly (IM), divided into doses every 6-12 hours.

• Tuberculosis

For daily therapy of tuberculosis, the recommended dosage is 20-40 mg/kg IM once a day, not exceeding 1 g per day.

For twice-weekly therapy of tuberculosis, the recommended dosage is 20-40 mg/kg IM two times a week, not exceeding 1.5 g per day.

• Plague

In the treatment of plague, the recommended dosage is 15 mg/kg IM every 12 hours for a minimum of 10 days, with a maximum daily dose of 2 g.

• Brucellosis

For patients older than 8 years with brucellosis, the recommended dosage is 20 mg/kg IM divided every 12 hours for 7-14 days, in combination with tetracycline or co-trimoxazole therapy. The maximum daily dose should not exceed 1 g.

There are no specific dietary restrictions associated with the use of streptomycin. However, it is always recommended to follow a balanced and healthy diet while undergoing any treatment.

Streptomycin may be contraindicated under the following conditions:

• Patients who have a known hypersensitivity to any component of Streptomycin or to other drugs in the same class.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

• Neurotoxicity and Impaired VIII Cranial Nerve Function:

Extreme caution is advised in individuals with impairment of the VIII cranial nerve. Patients with impaired kidney function or pre-renal azotemia are at a higher risk of severe neurotoxic reactions, including disturbances of the auditory nerve, optic nerve, peripheral neuritis, arachnoiditis, and encephalopathy. Renal function should be carefully assessed, and patients with renal damage and nitrogen retention should receive reduced dosage. Individuals with kidney damage should not exceed a peak serum concentration of 20 to 25 μg/mL.

• Concurrent Use of Neurotoxic and Nephrotoxic Drugs:

The simultaneous or sequential use of other neurotoxic and nephrotoxic drugs, such as neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, as well as tobramycin, should be avoided when using streptomycin sulfate.

• Neuromuscular Blockade and Anesthesia:

Streptomycin's neurotoxicity can result in respiratory paralysis through neuromuscular blockage, especially when the drug is administered shortly after anesthesia and the use of muscle relaxants.

• Administration and Laboratory Supervision:

The administration of streptomycin in parenteral form should be reserved for patients where adequate laboratory facilities are available, and the constant supervision of the patient is possible.

• Ototoxicity and Vestibular Symptoms:

Streptomycin frequently affects the vestibular branch of the auditory nerve, leading to severe nausea, vomiting, and vertigo. The incidence of ototoxicity is directly proportional to the duration and dosage of the drug. Advanced age and renal impairment increase the risk of ototoxicity. Discontinuation of the drug usually results in the subsiding of symptoms and complete recovery. Although long-term therapy may cause hearing loss, ototoxic effects on the auditory branch of the eighth nerve are infrequent and usually preceded by vestibular symptoms. Extensive hearing loss, when it occurs, is usually permanent.

• Usage in Pregnancy and Fetal Risk:

Streptomycin should only be used during pregnancy if the potential benefit outweighs the risk to the mother and fetus. The drug readily crosses the placental barrier, and caution is necessary to prevent ototoxicity in the fetus.

• Susceptibility/Resistance and Development of Drug-Resistant Bacteria:

Prescribing streptomycin in the absence of a proven or strongly suspected bacterial infection is unlikely to benefit the patient and increases the risk of developing resistant organisms.

• Potential for Microbial Overgrowth:

The use of streptomycin may promote the selection of non-susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.

• Precautions and Audiometric Testing:

Baseline and periodic caloric stimulation tests and the audiometric tests are advisable during extended streptomycin therapy. Tinnitus, roaring noises, or a sense of fullness in the ears indicates the need for audiometric examination or discontinuation of streptomycin therapy or both. Care should be taken by the individuals handling or preparing streptomycin for injection to avoid skin sensitivity reactions.

• Injection Site and Techniques:

Streptomycin for injection should be administered well within the body of a relatively large muscle. The preferred sites for adults are the upper outer quadrant of the buttock (gluteus maximus) or the mid-lateral thigh. In infants and small children, the periphery of the upper outer quadrant of the gluteal region should only be used when necessary, such as in burn patients, to minimize the risk of sciatic nerve damage. The deltoid area should only be used in well-developed individuals.

Streptomycin is primarily metabolized and eliminated by the kidneys, and alcohol can potentially have negative effects on kidney function. Additionally, alcohol can also have toxic effects on the liver, just like streptomycin. Therefore, it is generally advisable to avoid consuming alcohol while taking streptomycin to minimize the risk of any additional strain on the kidneys and liver.

Moreover, alcohol can potentially worsen the side effects of streptomycin, such as dizziness, lightheadedness, and impaired coordination. These side effects can be more pronounced when alcohol is consumed, increasing the risk of accidents or injuries.

When considering the use of streptomycin in breastfeeding mothers, it is important to assess the potential for significant adverse reactions in nursing infants. A careful decision should be made, weighing the importance of the drug to the mother against the potential risks to the nursing infant. This decision may involve either discontinuing nursing or discontinuing the use of streptomycin, based on an individualized evaluation of the situation. It is crucial to prioritize the well-being and safety of both the mother and the infant when making this determination.

Pregnancy Category D:

The administration of streptomycin to pregnant women can result in harm to the fetus. Due to the ability of streptomycin to easily cross the placental barrier, caution must be exercised to avoid ototoxicity in the developing fetus. In cases where streptomycin is used during pregnancy or if a patient becomes pregnant while taking the drug, it is essential to inform the patient about the potential risks to the fetus. Ensuring the patient is aware of the potential hazard to the fetus is crucial for making informed decisions regarding the use of streptomycin during pregnancy.

There are no specific food warnings associated with the use of streptomycin. However, it is generally recommended to take streptomycin on an empty stomach, at least one hour before or two hours after meals, as food can interfere with its absorption.

The adverse reactions related to Streptomycin can be categorized as follows:

Common 

• Black, tarry stools
• Sensations of burning, crawling, itching, numbness, prickling, "pins and needles," or tingling
• Chest pain
• Chills
• Clumsiness
• Cough
• Dizziness or feeling lightheaded
• Feeling of constant movement of self or surroundings
• Fever
• Large swelling resembling hives on the face, eyelids, lips, tongue, throat, hands, legs, feet, or the sex organs
• Nausea
• Painful or difficult urination
• Sensation of spinning
• Shortness of breath
• Sore throat
• Swollen glands
• Unsteadiness
• Unusual bleeding or bruising
• Unusual tiredness or weakness
• Vomiting

Less Common 

• Back, leg, or stomach pains
• Bleeding gums
• Bloody or cloudy urine
• Blurred vision
• Changes in vision
• Dark urine
• Deafness
• Difficulty breathing
• Difficulty swallowing
• Dry mouth
• Fast heartbeat
• General swelling of the body
• Headache
• Hives
• Impaired vision
• Itching
• Loss of appetite
• Muscle weakness
• Nosebleeds
• Pain in the lower back or side
• Pale skin
• Pinpoint red spots on the skin
• Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• Skin rash
• Thirst
• Tightness in the chest
• Wheezing
• Yellowing of the eyes or skin

Rare 

• Changes in frequency of urination or amount of urine
• Drowsiness
• Increased thirst
• Swelling of the feet or lower legs
• Weakness

The clinically relevant drug interactions of Streptomycin are briefly summarized here:

• Diuretics (e.g., furosemide): Concurrent use of streptomycin with diuretics may increase the risk of developing ototoxicity (hearing loss and balance problems).
• Neuromuscular blocking agents (e.g., succinylcholine): Streptomycin may enhance the neuromuscular blocking effects of these agents, leading to increased muscle weakness or paralysis.
• Other ototoxic drugs (e.g., vancomycin, cisplatin): Combining streptomycin with other drugs known to cause ototoxicity may increase the risk of hearing loss and balance disturbances.
• Nephrotoxic drugs (e.g., aminoglycosides, amphotericin B): Concurrent use of streptomycin with other nephrotoxic drugs may enhance the risk of kidney damage and impaired kidney function.
• Antacids containing aluminum, calcium, or magnesium: These antacids may decrease the absorption of streptomycin, potentially reducing its effectiveness.
• Neuromuscular blockers (e.g., vecuronium): Streptomycin can potentiate the effects of neuromuscular blockers, increasing the risk of respiratory muscle paralysis.
• Other drugs that affect hearing or balance: Concurrent use of streptomycin with drugs that affect hearing or balance may increase the risk of ototoxicity.

The following are the side effects involving Streptomycin:

• Black, tarry stools
• Sensations of burning, crawling, itching, numbness, prickling, "pins and needles," or tingling
• Chest pain
• Chills
• Clumsiness
• Cough
• Dizziness or feeling lightheaded
• Feeling of constant movement of self or surroundings
• Fever
• Large swelling resembling hives on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• Nausea
• Painful or difficult urination
• Sensation of spinning
• Shortness of breath
• Sore throat
• Swollen glands
• Unsteadiness
• Unusual bleeding or bruising
• Unusual tiredness or weakness
• Vomiting

Pregnancy

Pregnancy Category D:

The administration of streptomycin to pregnant women can result in harm to the fetus. Due to the ability of streptomycin to easily cross the placental barrier, caution must be exercised to avoid ototoxicity in the developing fetus. In cases where streptomycin is used during pregnancy or if a patient becomes pregnant while taking the drug, it is essential to inform the patient about the potential risks to the fetus. Ensuring the patient is aware of the potential hazard to the fetus is crucial for making informed decisions regarding the use of streptomycin during pregnancy.

Nursing Mothers

When considering the use of streptomycin in breastfeeding mothers, it is important to assess the potential for significant adverse reactions in nursing infants. A careful decision should be made, weighing the importance of the drug to the mother against the potential risks to the nursing infant. This decision may involve either discontinuing nursing or discontinuing the use of streptomycin, based on an individualized evaluation of the situation. It is crucial to prioritize the well-being and safety of both the mother and the infant when making this determination.

Pediatric Use

It is advisable to administer intramuscular injections in the mid-lateral muscles of the thigh whenever possible. In infants and small children, the periphery of the upper outer quadrant of the gluteal region should only be used when necessary, such as in burn patients, to minimize the potential damage to the sciatic nerve.

The deltoid area should only be utilized if well developed, typically in certain adults and older children. Even then, caution should be exercised to prevent radial nerve injury. Injection into the lower and mid-third of the upper arm should be avoided for intramuscular injections. As with any intramuscular injection, aspiration is necessary to prevent unintended injection into a blood vessel.

To minimize the risk of complications, it is important to alternate injection sites. In cases of more severe or rapidly progressing infections (e.g., endocarditis, meningitis), higher doses or prolonged streptomycin therapy may be required. In such instances, the physician should remain vigilant for any signs or symptoms of toxicity arising from streptomycin treatment and take appropriate measures promptly.

Geriatric Use

The use of streptomycin in geriatric populations (elderly individuals) should be approached with caution and careful consideration of individual patient characteristics. Here are some key points to consider regarding the usage of streptomycin in the geriatric population:

Age-related changes: Elderly individuals may experience age-related changes in kidney function, which can affect the pharmacokinetics of streptomycin. It is important to monitor renal function and adjust the dosage accordingly to prevent drug accumulation and potential toxicity.

Renal function: Due to potential renal impairment in older adults, dose adjustment may be necessary to ensure appropriate drug levels and minimize the risk of adverse effects.

Ototoxicity: Streptomycin is known to have the potential to cause ototoxicity, particularly affecting the auditory system. Geriatric patients may be more susceptible to this side effect, and therefore, careful monitoring of hearing function is crucial during streptomycin therapy.

Comorbidities and polypharmacy: Geriatric patients often have multiple comorbidities and may be taking multiple medications. It is important to consider potential drug-drug interactions and evaluate the overall risk-benefit ratio of using streptomycin in such cases.

Individualized approach: Treatment decisions should be individualized, taking into account the patient's overall health status, renal function, potential drug interactions, and the severity of the infection being treated. Close monitoring for efficacy and adverse effects is recommended.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of over dosage of Streptomycin.

No data has been found in the manufacturer’s label.

Pharmacodynamics

Due to antibiotic resistance, the spectrum of activity for streptomycin, which initially covered a wide range of gram-negative and gram-positive bacteria, has significantly narrowed. Presently, streptomycin is effective against susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. However, streptomycin's activity against pseudomonas aeruginosa is not consistently reliable.

Like other aminoglycosides, streptomycin is known to have a narrow therapeutic index. It carries the risk of nephrotoxicity and ototoxicity as characteristic toxicities. Patients need careful monitoring for early signs of hearing loss and vestibular dysfunction to prevent permanent damage to sensorineural cells. Although rare, neuromuscular blockade has also been reported as a potential adverse effect.

Pharmacokinetics

Streptomycin, when administered orally, is not absorbed into the gastrointestinal tract, indicating the need for parenteral administration to achieve systemic effects. Upon intramuscular injection of 1 g of streptomycin, a peak concentration of 25 to 50 μg/mL is reached within an hour, gradually decreasing by approximately 50% after 5 to 6 hours. This drug is found in significant concentrations in various organ tissues except for the brain. Notably, notable amounts have been discovered in pleural fluid and tuberculous cavities. Streptomycin can cross the placenta, with cord blood exhibiting similar serum levels to the mother. Small quantities are excreted in breast milk, saliva, and sweat. Glomerular filtration facilitates rapid elimination of streptomycin through urine. In individuals with normal kidney function, approximately 29 to 89% of a single 600 mg dose is excreted within 24 hours. Reduced glomerular activity leads to decreased drug excretion and a corresponding increase in serum and tissue levels.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/064210s009lbl.pdf
• https://www.webmd.com/drugs/2/drug-11249/streptomycin-intramuscular/details
• https://go.drugbank.com/drugs/DB01082
• https://www.mayoclinic.org/drugs-supplements/streptomycin-intramuscular-route/description/drg-20074514
• https://www.healthlinkbc.ca/medications/streptomycin-injection
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• https://reference.medscape.com/drug/streptomycin-342682
• https://www.thermofisher.com/order/catalog/product/15140148