Amikacin

Amikacin is an aminoglycoside antibiotic used to treat various types of bacterial infections, especially those caused by Gram-negative bacteria. Amikacin is effective against a wide range of pathogens, including many types of microorganisms resistant to other antibiotics.

Amikacin binds to the 30S subunit of bacterial ribosomes, thereby disrupting protein synthesis, resulting in bacterial death. This mechanism of action makes amikacin effective against infections caused by many aerobic Gram-negative and some Gram-positive bacteria.

Indications Amikacin

1. Respiratory tract infections: Pneumonia, including gram-negative infections such as those caused by Pseudomonas aeruginosa, Klebsiella pneumoniae and other bacteria.
2. Skin and soft tissue infections: Including burns, purulent infections and other skin infections caused by Gram-negative bacteria.
3. Urinary tract infections: Including acute and chronic pyelonephritis, cystitis, and infections caused by Pseudomonas aeruginosa and other bacteria.
4. Bone and joint infections: Osteomyelitis, infectious arthritis and other gram-negative musculoskeletal infections.
5. Abdominal infections: Peritonitis and other abdominal infections caused by gram-negative bacteria.
6. Septic shock: Intensive care for sepsis caused by gram-negative bacteria.

Release form

1. Solution for injection

Amikacin is most often available as a solution for injection, which is used for intramuscular (IM) or intravenous (IV) administration. This form is fast acting, making it the preferred choice for treating serious infections.

• Concentrations:
  • 100 mg/2 ml
  • 250 mg/2 ml
  • 500 mg/2 ml

2. Powder for preparation of solution for injection

Amikacin may also be available as a lyophilized powder that must be diluted before use. This form allows long-term storage and precise dosing when diluted.

• The powder is generally available in vials with different amikacin contents, such as:
  • 500 mg
  • 1000 mg.

Pharmacodynamics

1. Mechanism of Action: Amikacin acts by binding to bacterial ribosomes (30S subunits), which interferes with protein synthesis in bacterial cells. This mechanism leads to disruption of protein synthesis and ultimately to the death of the bacterial cell.

2. Broad spectrum of activity: Amikacin has a broad spectrum of activity against many gram-positive and gram-negative bacteria, including pathogens such as:

Gram-positive bacteria:

1. Staphylococcus aureus (including methicillin-sensitive strains).
2. Staphylococcus epidermidis.
3. Streptococcus pneumoniae.
4. Streptococcus pyogenes (group A Streptococcus).
5. Streptococcus agalactiae (group B Streptococcus).
6. Streptococcus viridans group.

Gram-negative bacteria:

3. Escherichia coli.
4. Klebsiella pneumoniae.
5. Klebsiella oxytoca.
6. Enterobacter aerogenes.
7. Enterobacter cloacae.
8. Proteus mirabilis.
9. Proteus vulgaris.
10. Serratia marcescens.
11. Pseudomonas aeruginosa.
12. Acinetobacter spp.
13. Citrobacter spp.
14. Morganella morganii.
15. Providencia spp.

3. Cross-resistance and superinfections: It is important to note that resistance to amikacin can develop in some bacteria, especially with improper or frequent use. This can lead to superinfections or cross-resistance with other antibiotics.

Pharmacokinetics

1. Absorption: Amikacin is generally not absorbed from the gastrointestinal tract after oral administration and is usually administered by intravenous or muscle injection.
2. Distribution: It penetrates well into various tissues and body fluids, including plasma, lung, kidney, skin, bone, soft tissue, and cerebrospinal fluid (CSF). The volume of distribution is usually large.
3. Protein binding: Amikacin binds to blood plasma proteins to an insignificant extent (about 10-20%).
4. Metabolism: Amikacin is practically not metabolized in the body.
5. Excretion: Most amikacin is excreted by the kidneys by glomerular filtration. Its glomerular filtration is dependent on renal function and may be reduced in patients with impaired renal function.
6. Excretionhalf-life: The elimination half-life of amikacin from the body depends on the rate of glomerular filtration and is usually about 2-3 hours in adults with normal renal function.

Dosing and administration

Method of application

Amikacin is usually administered intramuscularly (IM) or intravenously (IV). Intravenous administration can be either a continuous infusion or a bolus.

1. Intramuscular injection (v/m):

   • Quickly injected into deep muscles (e.g., gluteal muscles) to minimize tissue irritation and improve absorption.

2. Intravenous administration (IV):

   • Bolus administration: Amikacin can be administered as a slow bolus over 2-3 minutes.
   • Infusion: Infusion solution is prepared by diluting amikacin in 100-200 mL of a compatible solvent (e.g., 0.9% sodium chloride solution or 5% dextrose solution) and administered over 30-60 minutes.

Dosage

The dosage of amikacin depends on the severity of the infection, renal function, and patient weight. The following are general recommendations:

1. Adults and children over 1 month of age:

   • Usual dose: 15 mg/kg body weight per day, divided into 2-3 equal doses every 8-12 hours.
   • Severe infections: The dose may be increased to 500 mg every 8 hours, not to exceed 1.5 g per day.

2. Newborns (including premature infants):

   • First 7 days of life (if interval between delivery and mother's last menstrual period <40 weeks): 10 mg/kg every 12 hours.
   • After the first week of life: 7.5 mg/kg every 12 hours.

Use Amikacin during pregnancy

The use of amikacin (aminoglycoside antibiotic) during pregnancy should be based on strict medical indications and under the supervision of a doctor. The doctor may prescribe amikacin when the benefit to the mother outweighs the potential risk to the fetus.

It is important to consider that aminoglycoside antibiotics such as amikacin can pass through the placenta and affect the developing fetus. Animal studies have shown that aminoglycosides can cause congenital anomalies and other adverse effects on fetal development. However, in human patients, data on the safety of amikacin during pregnancy are limited.

If amikacin is needed to treat an infection in a pregnant woman, the doctor should carefully assess the potential benefits and risks. If amikacin is prescribed during pregnancy, careful fetal monitoring and monitoring of possible side effects are recommended.

Contraindications

1. Hypersensitivity: People with known hypersensitivity to aminoglycoside antibiotics, including amikacin, should use the drug with caution or avoid it completely.
2. Renal impairment: Patients with impaired renal function may experience accumulation of amikacin in the body, which may lead to toxic effects. Dosage should be adjusted depending on the degree of renal impairment.
3. Neuromuscular Diseases: The use of amikacin may be dangerous for people with myasthenia gravis (a disorder of neuromuscular transmission), as it may potentiate neuromuscular blockers.
4. Pregnancy and lactation: Information on the use of amikacin during pregnancy is limited. Therefore, the use of amikacin during this period should be performed only under strict indications and under medical supervision. It is also necessary to consult a physician regarding the possibility of using amikacin during breastfeeding.
5. Acousticneuritis: When using aminoglycosides, including amikacin, acoustic neuritis may develop, resulting in hearing impairment. This is especially important in patients with hearing impairment.
6. Myasthenia gravis: In myasthenia gravis, characterized by impaired neuromuscular transmission, the use of amikacin may potentiate neuromuscular blockers and worsen disease symptoms.

Side effects Amikacin

1. Renal damage: Amikacin may cause renal toxicity, especially in patients with a predisposition to renal failure. This may be manifested by worsening renal function, protein urinary syndrome or blood in the urine.
2. Hearingdamage: One of the most serious side effects of amikacin is hearing damage, including hearing loss or tinnitus. This is usually temporary, but in rare cases may be permanent.
3. Balance and coordination disorders: Some patients may experience dizziness or balance disorders as a result of amikacin.
4. Allergic reactions: Including urticaria, pruritus, skin rash, swelling of the lips or face, angioedema and anaphylaxis. In case of signs of an allergic reaction, seek immediate medical attention.
5. Other side effects: Nausea, vomiting may also occur

Overdose

1. Renal dysfunction: Amikacin overdose may cause toxic effects on the kidneys, which may manifest as deterioration of renal function, edema and electrolyte balance disorders.
2. Hearing complications: Amikacin may cause toxic effects on the vestibular apparatus and auditory nerve, which may result in hearing loss or dizziness.
3. Neurotoxicity: Some patients may develop symptoms of neurotoxicity such as muscle weakness, paresis, shaking, or pain in the extremities.
4. Anemia and other bleeding: Complications of hematopoiesis such as anemia, thrombocytopenia and leukopenia may occur.
5. Common symptoms of overdose: This may include nausea, vomiting, headache, seizures, and general weakness.

Interactions with other drugs

1. Other aminoglycoside antibiotics: Combined use of amikacin with other aminoglycoside antibiotics may increase their toxic effects on the kidneys and hearing.
2. Nephrotoxic drugs: Use of amikacin with other nephrotoxic drugs such as amphotericin B or cyclosporine may increase the risk of renal failure.
3. Neurotoxic drugs: Combined use of amikacin with drugs that have neurotoxic effects, such as bismuth, vincristine, or anesthetics, may increase neurotoxic effects.
4. Myorelaxants: Amikacin may increase the myorelaxant effects of myorelaxants such as pancuronium or vecuronium.
5. Drugs affecting renal function: The use of amikacin with drugs that affect renal function, such as diuretics, may increase the risk of renal failure.
6. Drugs that increase blood potassium levels: Combined use of amikacin with drugs that increase blood potassium levels, such as spironolactone or angiotensin-converting enzyme inhibitors (ACEIs), may result in hyperkalemia.