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What is streptomycin? A Guide to the Aminoglycoside Antibiotic

4 min read

Discovered in 1943 from the bacterium Streptomyces griseus, streptomycin was the first antibiotic effective against tuberculosis. So, what is streptomycin? It is an aminoglycoside antibiotic used for severe bacterial infections that may not respond to other drugs.

Quick Summary

Streptomycin is an injectable antibiotic for treating serious bacterial infections like tuberculosis, plague, and tularemia. It works by stopping bacteria from making proteins, but carries risks of serious side effects.

Key Points

  • Discovery: Streptomycin was the first antibiotic effective against tuberculosis, discovered in 1943 from Streptomyces griseus.

  • Mechanism: It is an aminoglycoside that kills bacteria by binding to their 30S ribosomal subunit and inhibiting protein synthesis.

  • Primary Use: Its main use today is as a second-line treatment for multi-drug-resistant tuberculosis and other serious infections like plague and tularemia.

  • Administration: It is not absorbed orally and must be given by intramuscular or intravenous injection.

  • Major Risks: The drug has a black box warning for serious side effects, primarily irreversible ear damage (ototoxicity) and kidney damage (nephrotoxicity).

  • Resistance: Bacteria can become resistant by mutating the drug's target site on the ribosome or by acquiring genes that inactivate the drug.

  • Pregnancy Warning: Streptomycin can cross the placenta and may cause deafness in the developing fetus.

In This Article

The Landmark Discovery of Streptomycin

Streptomycin's discovery in 1943 by Albert Schatz, a graduate student in Selman Waksman's lab at Rutgers University, marked a monumental turning point in medicine. It was the result of a systematic search for antimicrobial agents from soil microbes, specifically from the actinomycete Streptomyces griseus. Unlike penicillin, which was ineffective against many gram-negative bacteria, streptomycin was the first "broad-spectrum" antibiotic. Its most celebrated success was being the first effective treatment against Mycobacterium tuberculosis, the bacterium that causes tuberculosis, which was a leading cause of death at the time. This breakthrough earned Selman Waksman the Nobel Prize in Physiology or Medicine in 1952.

How Streptomycin Works: Mechanism of Action

Streptomycin belongs to the aminoglycoside class of antibiotics and is bactericidal, meaning it kills bacteria. Its primary mechanism of action involves inhibiting protein synthesis, which is essential for bacterial survival and replication.

  1. Binding to the Ribosome: The drug binds specifically to the 16S rRNA component of the small 30S ribosomal subunit in bacteria.
  2. Inhibiting Protein Synthesis: This binding action blocks the ribosome's ability to correctly read the genetic code from messenger RNA (mRNA), interfering with the initiation of protein synthesis and causing misreading of the mRNA. This leads to the production of nonfunctional or toxic proteins.
  3. Cell Death: The disruption of protein synthesis and creation of faulty proteins ultimately results in bacterial death.

Because its entry into bacterial cells requires an oxygen-dependent transport system, streptomycin is effective against aerobic bacteria (those that require oxygen) but not anaerobic bacteria.

Clinical Uses and Indications

While newer and less toxic antibiotics have replaced streptomycin for many conditions, it remains a critical drug for several serious infections, often as part of a combination therapy to prevent the development of resistance. Its use is generally reserved for moderate to severe infections where other antibiotics are ineffective.

Key indications include:

  • Tuberculosis (TB): It is primarily used as a second-line agent in multi-drug-resistant tuberculosis (MDR-TB) treatment regimens. Historically, it was a first-line agent, but resistance developed rapidly when used as monotherapy.
  • Tularemia: An infection caused by Francisella tularensis.
  • Plague: An infection caused by Yersinia pestis.
  • Brucellosis: Often used in combination with doxycycline.
  • Endocarditis: Used for enterococcal endocarditis in combination with penicillin or ampicillin if the strain is susceptible.

Administration

Streptomycin is poorly absorbed from the gastrointestinal tract and must be administered parenterally, typically via a deep intramuscular (IM) injection. It can also be given intravenously (IV).

  • Administration Route: IM injections are given deep into a large muscle, such as the gluteal or mid-lateral thigh muscles, with sites being alternated to prevent pain and irritation.
  • Considerations: The appropriate amount of streptomycin depends on the specific infection, the patient's condition, age, weight, and kidney function. Adjustments are often necessary for older patients and those with reduced kidney function to minimize the risk of toxicity.

Serious Warnings and Side Effects

Streptomycin carries a black box warning from the FDA due to the risk of severe neurotoxic reactions. These risks are sharply increased in patients with impaired renal function.

Major Toxicities:

  • Ototoxicity (Ear Damage): This is the most concerning side effect and can affect both hearing (cochlear toxicity) and balance (vestibular toxicity). The damage can be irreversible and is related to the dose and duration of therapy. Symptoms include vertigo, dizziness, nausea, ringing in the ears (tinnitus), and hearing loss.
  • Nephrotoxicity (Kidney Damage): While considered the least nephrotoxic of the aminoglycosides, it can still cause kidney damage, especially with prolonged use or in patients with pre-existing kidney problems. Renal function must be monitored during therapy.
  • Neuromuscular Blockade: High amounts can lead to muscle weakness and, in rare cases, respiratory paralysis. This risk is higher if given soon after anesthesia or muscle relaxants.
  • Fetal Harm: Streptomycin can cross the placenta and has been reported to cause deafness in babies whose mothers received the drug during pregnancy.

Comparison with Other Aminoglycosides

Streptomycin is structurally distinct from many other aminoglycosides like gentamicin and tobramycin because it lacks the 2-deoxystreptamine moiety.

Feature Streptomycin Gentamicin / Tobramycin Amikacin
Primary Use Tuberculosis, plague, tularemia Broad-spectrum for severe Gram-negative infections (e.g., Pseudomonas) Often reserved for gentamicin-resistant infections
Ototoxicity Higher risk of vestibular (balance) toxicity Higher risk of cochlear (hearing) toxicity Similar to other aminoglycosides
Nephrotoxicity Considered the least nephrotoxic aminoglycoside More nephrotoxic than streptomycin Similar to other aminoglycosides
Resistance Widespread resistance limits its use Resistance is a growing concern Often effective against bacteria resistant to gentamicin

The Challenge of Antibiotic Resistance

Soon after its introduction, bacteria began to develop resistance to streptomycin, particularly when it was used as a single agent. Resistance can emerge through several mechanisms:

  • Target Site Modification: Mutations in the bacterial genes rpsL (encoding ribosomal protein S12) or rrs (encoding 16S rRNA) can alter the drug's binding site on the ribosome, preventing it from working effectively.
  • Enzymatic Inactivation: Some bacteria acquire genes, often on plasmids, that produce enzymes (like phosphotransferases or adenylyltransferases) that chemically modify and inactivate the antibiotic.
  • Efflux Pumps: Some bacteria can actively pump the drug out of the cell before it can reach its target.

Conclusion

Streptomycin holds a significant place in medical history as the first effective chemotherapy for tuberculosis, saving countless lives and paving the way for the antibiotic era. While its modern use is limited by widespread resistance and the availability of safer alternatives, it remains a vital tool in the fight against multi-drug-resistant TB and other specific, serious bacterial infections. Its story serves as a powerful reminder of both the immense power of antibiotics and the persistent challenge of antimicrobial resistance. Careful, supervised use is essential to mitigate its serious risks of ototoxicity and nephrotoxicity.


For more information from an authoritative source, visit the CDC page on Tuberculosis Treatment.

Frequently Asked Questions

Yes, but its use is limited. It is now primarily used as part of a multi-drug regimen for treating drug-resistant tuberculosis and for other serious infections like plague and tularemia where other antibiotics may not be effective.

Streptomycin is not effective when taken by mouth, so it must be given as a deep intramuscular (IM) injection or, in some cases, intravenously (IV) by a healthcare professional.

The most serious side effects are ototoxicity (damage to the ears, which can cause permanent hearing loss and balance problems) and nephrotoxicity (kidney damage). It also carries a risk of causing fetal harm if taken during pregnancy.

Due to its potential for serious side effects and the widespread development of bacterial resistance, streptomycin is reserved for severe infections where safer antibiotics are not an option.

No, streptomycin is an antibiotic and is only effective against bacterial infections. It will not work for viral infections such as the common cold or flu.

A black box warning is the FDA's most serious warning for drugs. For streptomycin, it highlights the increased risk of severe neurotoxic reactions, including irreversible ear damage (vestibular and cochlear) and potential for respiratory paralysis, especially in patients with kidney problems.

Bacteria can develop resistance through mutations in the genes that form the antibiotic's target (the ribosome), preventing the drug from binding. They can also acquire genes that produce enzymes to inactivate the drug or use efflux pumps to pump it out of the cell.

References

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Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice.