- Kanamycin is a broad-spectrum aminoglycoside antibiotic effective against a wide range of gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Proteus species, and Enterobacter species. It also exhibits activity against some gram-positive bacteria, such as Staphylococcus aureus, though generally less robust than its effect on gram-negative organisms. However, its use is limited due to widespread resistance caused by aminoglycoside-modifying enzymes.
- It is naturally produced by the actinomycete Streptomyces kanamyceticus during fermentation.
- The antibiotic exerts its bactericidal action by inhibiting bacterial protein synthesis. It specifically binds to the 30S ribosomal subunit, interfering with the initiation complex and causing misreading of the mRNA template. This results in the incorporation of incorrect amino acids into the growing peptide chain, leading to the production of nonfunctional proteins and ultimately bacterial cell death. Kanamycin’s ability to disrupt the bacterial cell membrane further enhances its bactericidal effects.
- Like other aminoglycosides, kanamycin is especially effective against aerobic bacteria and is typically reserved for infections resistant to other antibiotics.
- Structurally, kanamycin belongs to the aminoglycoside family, characterized by the presence of a central 2-deoxystreptamine (2-DOS) ring. In kanamycin, this central ring is glycosidically linked to two amino sugars: kanosamine and 3-glucosamine. This specific arrangement is critical for the molecule’s ability to bind bacterial ribosomes and accounts for its broad-spectrum antibacterial activity.
- Kanamycin is not a single compound but a natural mixture composed of three closely related components: kanamycin A, kanamycin B, and kanamycin C.
- Among these, kanamycin A is the major and most pharmacologically active form. It has a molecular formula of C₁₈H₃₆N₄O₁₁ and a molecular mass of 484.50 g/mol. Due to its potent antibacterial properties, kanamycin A is the form used in clinical medicine. It constitutes approximately 80–90% of the total kanamycin mixture produced during fermentation.
- Kanamycin B is a minor component, typically accounting for about 5–10% of the natural mixture. Its molecular formula is C₁₈H₃₆N₄O₁₀, with a slightly lower molecular mass of 468.49 g/mol. Structurally similar to kanamycin A, it lacks one hydroxyl group, which contributes to its reduced antibacterial potency. Kanamycin B is not used therapeutically but may appear as a trace impurity in commercial kanamycin preparations.
- Kanamycin C, the least abundant of the three, generally comprises only 1–3% of the natural mixture. It has the molecular formula C₁₈H₃₆N₄O₁₂ and a molecular mass of 500.49 g/mol. It contains one additional hydroxyl group compared to kanamycin A. Although structurally close, its biological activity is less significant, and it does not play a role in clinical use.
- The overall composition of kanamycin obtained from S. kanamyceticus can vary based on the specific strain and fermentation conditions. Nevertheless, industrial production is designed to maximize kanamycin A content, which is selectively purified due to its favorable efficacy and safety profile. Kanamycin B and C are generally treated as by-products or impurities in the manufacturing process.
- The pharmacokinetic profile of kanamycin includes poor oral bioavailability, necessitating administration via intramuscular or intravenous routes for systemic infections. It achieves widespread tissue distribution, with particularly high concentrations in the kidneys and inner ear, contributing to its nephrotoxic and ototoxic potential. Kanamycin is not metabolized significantly and is excreted almost entirely unchanged in the urine, with a half-life of 2 to 3 hours in patients with normal renal function. Dosage adjustments are required in patients with impaired kidney function to avoid toxicity.
- Despite its efficacy, kanamycin is associated with significant adverse effects, including nephrotoxicity, ototoxicity (both auditory and vestibular), and neuromuscular blockade. These side effects limit its use to severe infections where other less toxic antibiotics are ineffective or contraindicated.
