Streptomycin

Usage

• Streptomycin is an aminoglycoside antibiotic primarily used to treat infections caused by susceptible gram-negative bacteria. It is particularly effective against Mycobacterium tuberculosis and is frequently used in combination therapy for tuberculosis. Other susceptible bacteria include Yersinia pestis (plague), Francisella tularensis (tularemia), and some strains of streptococci and enterococci.

• Pharmacological Classification: Aminoglycoside antibiotic.

• Mechanism of Action: Streptomycin inhibits bacterial protein synthesis by irreversibly binding to the 30S ribosomal subunit. This disrupts the reading of messenger RNA, leading to the production of non-functional proteins and ultimately bacterial cell death.

Alternate Names

• Streptomycin sulfate.

• Brand names vary depending on the manufacturer and region. Some examples might include Streptomycin Sulfate Injection. Please note that brand names may change over time and by location.

How It Works

• Pharmacodynamics: Streptomycin exerts its bactericidal effect by interfering with protein synthesis within bacterial cells, ultimately leading to cell death. Its action is concentration-dependent, meaning higher concentrations result in greater bacterial killing.

• Pharmacokinetics:

  • Absorption: Administered intramuscularly (IM) or intravenously (IV). Not absorbed orally. IM absorption can be affected by injection site and repeated injections at the same site.
  • Distribution: Distributes widely into extracellular fluids but has limited penetration into the cerebrospinal fluid (CSF), requiring higher doses for central nervous system infections like meningitis. Crosses the placental barrier and is present in breast milk.
  • Metabolism: Not significantly metabolized.
  • Elimination: Primarily excreted unchanged by the kidneys via glomerular filtration. Dosage adjustments are required for patients with renal impairment.

• Mode of Action: Binds irreversibly to the 30S ribosomal subunit of susceptible bacteria, interfering with the decoding of messenger RNA (mRNA). This leads to misreading of the genetic code, production of abnormal proteins, and disruption of the bacterial cell membrane, ultimately causing bacterial death.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Specifically targets the 30S ribosomal subunit. Does not interact with receptors, enzymes, or neurotransmitters in the same way as some other drug classes.

• Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Tuberculosis: 15 mg/kg IM once daily (maximum 1 g/day) or 25-30 mg/kg IM two to three times weekly (maximum 1.5 g/dose). Duration of therapy is typically at least 1 year in combination with other antituberculosis drugs.
• Other Infections: 1-2 g/day IM in divided doses every 6-12 hours, not exceeding 2 g/day. Dosage and duration depend on the specific infection and patient factors.

Children:

• 20-40 mg/kg/day IM, divided every 6-12 hours, not exceeding 1 g/day. Particular care should be taken to avoid excessive dosages in children.

Special Cases:

• Elderly Patients: Reduced dosage is recommended due to age-related decline in renal function and increased risk of toxicity. Consider 10 mg/kg/dose (maximum 750 mg) 5-7 times per week or 2-3 times per week after an initial period. Alternatively, 15 mg/kg/dose three times a week may be used. Closely monitor for toxicity.

• Patients with Renal Impairment: Dosage adjustment is crucial. 12-15 mg/kg/dose two to three times per week is recommended, avoiding daily dosing. Serum levels should be monitored to ensure appropriate drug concentrations while minimizing toxicity.

• Patients with Hepatic Dysfunction: While not extensively metabolized by the liver, caution is still warranted. Monitor for adverse events and adjust dosage if necessary.

• Patients with Comorbid Conditions: Evaluate for pre-existing hearing loss, vestibular dysfunction, or neuromuscular disorders, as these may be exacerbated by streptomycin. Consider the potential for drug interactions with other medications.

Clinical Use Cases

Dosage recommendations for specific clinical settings should be guided by published guidelines and tailored to individual patient needs. Factors such as infection severity, causative organism, and patient comorbidities should be considered.

Dosage Adjustments

Dose modifications may be necessary based on patient response, renal function, and other relevant factors. Therapeutic drug monitoring can be useful to optimize efficacy and minimize toxicity.

Side Effects

Common Side Effects:

• Nausea, vomiting
• Vertigo (spinning sensation)
• Loss of appetite
• Injection site reactions (pain, redness, irritation)
• Paresthesia (tingling or prickling sensation), particularly in the face
• Rash, fever, hives
• Edema (swelling)

Rare but Serious Side Effects:

• Ototoxicity (hearing loss, tinnitus, balance problems), which can be irreversible
• Nephrotoxicity (kidney damage)
• Neuromuscular blockade (muscle weakness or paralysis)
• Peripheral neuropathy (nerve damage)
• Anaphylaxis (severe allergic reaction)
• Blood dyscrasias (abnormalities in blood cell counts)

Long-Term Effects:

• Permanent hearing loss or balance problems can occur with prolonged use or high doses.
• Kidney damage can develop with prolonged exposure.

Adverse Drug Reactions (ADR):

• Any signs of ototoxicity, nephrotoxicity, or anaphylaxis require immediate medical attention and discontinuation of the drug.

Contraindications

• History of hypersensitivity to streptomycin or other aminoglycosides.
• Myasthenia gravis or other neuromuscular disorders.
• Pre-existing hearing or vestibular dysfunction.

Drug Interactions

• Other ototoxic drugs (e.g., other aminoglycosides, loop diuretics like furosemide and ethacrynic acid) increase the risk of hearing loss.

• Nephrotoxic drugs (e.g., amphotericin B, vancomycin, cisplatin) increase the risk of kidney damage.

• Neuromuscular blocking agents (e.g., atracurium, vecuronium) can enhance neuromuscular blockade.

• Numerous other potential drug interactions exist. Consult a comprehensive drug interaction resource for detailed information.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category D (evidence of human fetal risk, but potential benefits may outweigh risks in certain life-threatening situations). Avoid use during pregnancy unless absolutely necessary due to the risk of fetal ototoxicity (hearing loss or deafness).

• Breastfeeding: Streptomycin passes into breast milk. While the American Academy of Pediatrics considers streptomycin compatible with breastfeeding, monitor the infant for thrush, diarrhea, and other potential adverse effects. A decision to discontinue breastfeeding or the drug should be made based on the importance of the drug to the mother.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
• Side Effects: Nausea, vomiting, vertigo, ototoxicity, nephrotoxicity, neuromuscular blockade, hypersensitivity reactions.
• Contraindications: Hypersensitivity to aminoglycosides, myasthenia gravis, pre-existing hearing or vestibular dysfunction.
• Drug Interactions: Other ototoxic or nephrotoxic drugs, neuromuscular blocking agents.
• Pregnancy & Breastfeeding: Category D; use with caution during breastfeeding.
• Dosage: Varies depending on indication, age, and renal function.
• Monitoring Parameters: Renal function tests, audiometry, vestibular function tests.

Popular Combinations

• Streptomycin is often used in combination with other antituberculosis drugs, such as isoniazid, rifampin, pyrazinamide, and ethambutol, for the treatment of tuberculosis. This combination therapy helps prevent the development of drug resistance and enhances treatment efficacy.

Precautions

• Assess renal function, hearing, and vestibular function before and during treatment.
• Avoid concomitant use of other ototoxic or nephrotoxic drugs.
• Monitor for signs of hypersensitivity reactions.
• Use with caution in elderly patients and those with pre-existing renal impairment.
• Ensure adequate hydration to minimize nephrotoxicity.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Streptomycin?

A: The dosage varies depending on the indication, patient age, and renal function. For tuberculosis in adults, the standard dose is 15 mg/kg IM daily (maximum 1 g) or 25-30 mg/kg IM two to three times weekly (maximum 1.5 g/dose). For other infections, 1-2 g/day IM in divided doses every 6-12 hours, not to exceed 2 g/day. Pediatric dosages and adjustments for renal impairment are outlined above.

Q2: What are the major side effects of Streptomycin?

A: Ototoxicity (hearing loss and balance problems) and nephrotoxicity (kidney damage) are the most serious side effects. Other common side effects include nausea, vomiting, vertigo, paresthesia (especially of the face), rash, fever, and injection site reactions.

Q3: Can Streptomycin be used during pregnancy?

A: Streptomycin is a Category D drug and should be avoided during pregnancy unless absolutely necessary due to the risk of fetal ototoxicity.

Q4: How is Streptomycin administered?

A: Streptomycin is usually administered intramuscularly (IM). In certain circumstances, intravenous (IV) administration may be appropriate. It is not effective orally.

Q5: What are the contraindications for Streptomycin?

A: Contraindications include hypersensitivity to streptomycin or other aminoglycosides, myasthenia gravis or other neuromuscular disorders, and pre-existing hearing or vestibular dysfunction.

Q6: How does renal impairment affect Streptomycin dosing?

A: Patients with renal impairment require dose reduction and less frequent administration (e.g., two to three times per week) to avoid drug accumulation and toxicity. Serum drug level monitoring is essential.

Q7: What should be monitored during Streptomycin therapy?

A: Monitor renal function, hearing (audiometry), and balance (vestibular testing) regularly. Observe for signs of ototoxicity, nephrotoxicity, and hypersensitivity.

Q8: What other drugs interact with Streptomycin?

A: Numerous drug interactions are possible. Concomitant use of other ototoxic or nephrotoxic drugs should be avoided or carefully managed. Neuromuscular blocking agents may have their effects enhanced by streptomycin. Consult a drug interaction resource for detailed information.

Q9: Is Streptomycin effective against all types of bacteria?

A: No, Streptomycin primarily targets aerobic gram-negative bacteria, including Mycobacterium tuberculosis. It is not effective against anaerobic bacteria, fungi, or viruses. Susceptibility testing is crucial to ensure appropriate use.

Q10: What is the role of Streptomycin in tuberculosis treatment?

A: Streptomycin is an important component of combination therapy for tuberculosis, especially in cases of drug resistance to other first-line agents. It is effective against actively dividing Mycobacterium tuberculosis.