Kanamycin

Usage

Kanamycin is an aminoglycoside antibiotic indicated for the short-term treatment of serious bacterial infections caused by susceptible Gram-negative bacteria, including E. coli, Proteus species, Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, and Acinetobacter species. It is also used in the treatment of multi-drug resistant tuberculosis (MDR-TB) as part of a combination therapy when first-line agents are ineffective or not tolerated. It is not effective against viral infections.

Pharmacological Classification: Aminoglycoside antibiotic.

Mechanism of Action: Kanamycin irreversibly binds to the 30S ribosomal subunit, inhibiting protein synthesis in susceptible bacteria. This leads to bacterial cell death.

Alternate Names

Generic Name: Kanamycin sulfate

Brand Name: Kantrex (discontinued)

How It Works

Pharmacodynamics: Kanamycin exhibits concentration-dependent bactericidal activity. Its efficacy is related to the peak concentration achieved and the duration for which the concentration exceeds the minimum inhibitory concentration (MIC) of the target organism.

Pharmacokinetics:

• Absorption: Rapidly absorbed after intramuscular (IM) injection, reaching peak serum levels in about one hour. Oral absorption is poor and primarily used for suppression of intestinal bacteria.
• Distribution: Widely distributed in extracellular fluids, crosses the placenta, and small amounts enter breast milk. Limited penetration into the cerebrospinal fluid (CSF), even with inflamed meninges.
• Metabolism: Not significantly metabolized.
• Elimination: Primarily excreted unchanged by the kidneys, with a half-life of 2-4 hours (prolonged in renal impairment).

Mode of Action: Kanamycin exerts its bactericidal effect by interfering with bacterial protein synthesis. It irreversibly binds to the 30S ribosomal subunit, leading to misreading of mRNA codons, premature termination of polypeptide chains, and inhibition of translocation.

Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Kanamycin binds to specific sites on the 30S ribosomal subunit.

Elimination Pathways: Renal excretion.

Dosage

Standard Dosage

Adults:

• Intramuscular/Intravenous: 15 mg/kg/day divided every 8-12 hours, not to exceed 1.5 g/day. For IV administration, infuse over 30-60 minutes (adults) or 1-2 hours (children).

Children:

• Intramuscular/Intravenous: 15-30 mg/kg/day (maximum 1 g) in divided doses every 8-12 hours.
• Pediatric Safety Considerations: Monitor renal function closely in neonates and premature infants due to immature renal function.

Special Cases:

• Elderly Patients: Reduce dosage and monitor renal function closely. Single daily dosing of 0.5-0.75 g may be appropriate.
• Patients with Renal Impairment: Dosage adjustment is necessary. Reduce dose or increase dosing interval based on creatinine clearance.
• Patients with Hepatic Dysfunction: Use with caution, as severe liver disease may progress to hepatorenal syndrome.
• Patients with Comorbid Conditions: Use with caution in patients with pre-existing hearing loss, myasthenia gravis, or other neuromuscular disorders.

Clinical Use Cases

Dosage recommendations should be individualized based on the specific infection and patient factors. The dosage mentioned below are general recommendations and should be adjusted as clinically indicated:

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Follow standard adult or pediatric dosing guidelines.
• Emergency Situations: Initial dose may be higher but should be adjusted based on patient response and renal function.

Dosage Adjustments: Refer to special cases above. Monitor serum drug levels (peak and trough) for optimal dosing and to minimize toxicity.

Side Effects

Common Side Effects:

• Pain at injection site
• Skin rash or itching
• Nausea or vomiting
• Headache
• Fever

Rare but Serious Side Effects:

• Ototoxicity (hearing loss, tinnitus, vertigo)
• Nephrotoxicity (decreased urine output, fluid retention)
• Neuromuscular blockade (muscle weakness, respiratory paralysis)
• Allergic reactions (anaphylaxis)

Long-Term Effects:

• Permanent hearing loss
• Kidney damage

Adverse Drug Reactions (ADR): Anaphylaxis, ototoxicity, nephrotoxicity, neuromuscular blockade.

Contraindications

• Hypersensitivity to kanamycin or other aminoglycosides
• Pregnancy (Category D)
• Pre-existing hearing loss or vestibular dysfunction
• Myasthenia gravis or other neuromuscular disorders
• Intestinal obstruction (for oral administration)

Drug Interactions

Kanamycin interacts with a large number of medications, including:

• Other nephrotoxic or ototoxic drugs: (e.g., other aminoglycosides, amphotericin B, cisplatin, vancomycin, loop diuretics) - increased risk of kidney and hearing damage.
• Neuromuscular blocking agents: Increased risk of respiratory paralysis.
• Certain antibiotics: (e.g., penicillins) - may reduce kanamycin effectiveness.

Pregnancy and Breastfeeding

Pregnancy Safety Category: D

Fetal Risks: Ototoxicity (hearing loss) and nephrotoxicity.

Drug Excretion in Breast Milk: Small amounts are excreted in breast milk. Monitor infant for diarrhea, thrush, and other signs of altered gut flora.

Alternative Safer Options: Consult with an infectious disease specialist for alternative antibiotic choices during pregnancy and breastfeeding.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
• Side Effects: Ototoxicity, nephrotoxicity, neuromuscular blockade, allergic reactions.
• Contraindications: Hypersensitivity, pregnancy, pre-existing hearing/vestibular dysfunction, myasthenia gravis, intestinal obstruction.
• Drug Interactions: Other nephrotoxic/ototoxic drugs, neuromuscular blocking agents, certain antibiotics.
• Pregnancy & Breastfeeding: Category D; excreted in breast milk – monitor infant.
• Dosage: Adults: 15 mg/kg/day divided every 8-12 hours (max 1.5g/day). Children: 15-30 mg/kg/day divided every 8-12 hours (max 1g/day).
• Monitoring Parameters: Renal function (creatinine, BUN), hearing tests, serum drug levels (peak and trough).

Popular Combinations

Kanamycin is often used in combination with other antibiotics in the treatment of MDR-TB, as per WHO guidelines.

Precautions

• Assess renal function, hearing, and vestibular function prior to and during therapy.
• Ensure adequate hydration to minimize nephrotoxicity.
• Avoid concurrent use with other ototoxic or nephrotoxic drugs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Kanamycin?

A: Adults: 15 mg/kg/day IM/IV divided every 8-12 hours, not to exceed 1.5 g/day. Children: 15-30 mg/kg/day IM/IV divided every 8-12 hours, not to exceed 1 g/day. Dose adjustments are necessary for patients with renal impairment.

Q2: What are the most serious side effects of Kanamycin?

A: Ototoxicity (hearing loss, tinnitus, vertigo) and nephrotoxicity are the most serious side effects. Neuromuscular blockade and allergic reactions can also occur.

Q3: Can Kanamycin be used during pregnancy?

A: Kanamycin is contraindicated during pregnancy (Category D) due to the risk of fetal ototoxicity.

Q4: How is Kanamycin administered?

A: Kanamycin can be administered intramuscularly (IM) or intravenously (IV). It can also be given orally, but this route is primarily for suppression of intestinal bacteria. For IV administration, infuse over 30-60 minutes for adults and 1-2 hours for children.

Q5: What are the indications for Kanamycin use?

A: Kanamycin is indicated for serious bacterial infections caused by susceptible Gram-negative bacteria and for the treatment of MDR-TB in combination with other anti-TB drugs.

Q6: What monitoring parameters are important for patients receiving Kanamycin?

A: Monitor renal function (serum creatinine, BUN), hearing (audiometry), and serum kanamycin levels (peak and trough) during therapy.

Q7: What are the drug interactions of Kanamycin?

A: Kanamycin interacts with other nephrotoxic or ototoxic drugs, neuromuscular blocking agents, and certain antibiotics. Concurrent use should be avoided or carefully monitored.

Q8: Can Kanamycin be used in patients with renal impairment?

A: Yes, but dosage adjustments are necessary. Reduce dose or increase dosing interval based on creatinine clearance. Close monitoring of renal function and serum drug levels is crucial.

Q9: What are the symptoms of Kanamycin overdose?

A: Symptoms of overdose may include increased severity of side effects, such as hearing loss, kidney damage, and neuromuscular blockade. Supportive care and hemodialysis may be required.

Q10: How should Kanamycin be stored?

A: Store Kanamycin vials in the refrigerator. Reconstituted solutions should be used promptly or stored as per manufacturer’s instructions.