Antimicrobial preparations / Aminoglycosides
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Aminoglycosides

Aminoglycosides is one of the first class of antibacterial preparations. The first aminoglycoside - streptomycin was synthesized in 1944 year. Currently aminoglycosides are divided into 3 generations:

Aminoglycosides classifications:

  1. generation
    • Streptomycin
    • Neomycin
    • Kanamycin
  2. generation
    • Gentamicin
    • Tobramycin
    • Netilmicin
  3. generation
    • Amikacin

The main clinical value of aminoglycosides consists in management of nosocomial infections caused by aerobic gram-negative pathogens, and also in the treatment of infective endocarditis. Streptomycin and kanamycin are used in the treatment of tuberculosis. Neomycin is the most toxic among the aminoglycosides and is used only locally. Aminoglycosides possess potential nephrotoxicity, ototoxicity and may cause neuromuscular block.

Action mechanism
Aminoglycosides exert bactericidal action, which is associated with interfering with protein synthesis on ribosomes. Aminoglycosides bind to 30S ribosomal subunits and disturbs protein synthesis. The level of antibacterial activity depends on their maximum (peak) concentration in the blood. Aminoglycosides possess synergism against some gram-negative and gram-positive aerobic microorganisms when used in combination with penicillin and cephalosporins.

Spectrum of aminoglycosides
II and III generation aminoglycosides are characterized by a dose-dependent bactericidal activity against Gram-negative microorganisms such as Enterobacteriaceae (E.coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp. Etc.), and nonfermentative gram-negative bacilli (P.aeruginosa , Acinetobacter spp.) Aminoglycosides are active against staphylococci for except of MRSA. Streptomycin and kanamycin act on M.tuberculosis, while amikacin is more active against M.avium and other atypical mycobacteria. Streptomycin and Gentamicin act on enterococci. Streptomycin is active against the causative agents of plague, tularemia, brucellosis. Aminoglycosides do not act on S.pneumoniae, S.maltophilia, B.cepacia, anaerobes (Bacteroides spp., Clostridium spp. Etc.). Moreover, resistance of S.pneumoniae, S.maltophilia and B.cepacia to aminoglycosides can be used for identification of these microorganisms. Despite the fact that aminoglycosides are active in vitro against shigella, salmonella, Legionella, clinical efficacy in the treatment of these infections caused by these pathogens has not been established.

Indications
Empiric therapy (in most cases they are prescribed in combination with ?-lactamase, glycopeptides anti-anaerobic drugs):

  • Sepsis of unknown etiology.
  • Infective endocarditis.
  • Post-traumatic and postoperative meningitis.
  • Fever in patients with neutropenia.
  • Nosocomial pneumonia (including ventilator).
  • Pyelonephritis.
  • Intra-abdominal infections.
  • Pelvic infections.
  • Diabetic foot.
  • Postoperative or post-traumatic osteomyelitis.
  • Septic arthritis.

Local therapy:
Eye infection - bacterial conjunctivitis and keratitis.

Specific therapy:

  • Plague (streptomycin).
  • Tularemia (streptomycin, gentamicin).
  • Brucellosis (streptomycin).
  • Tuberculosis (streptomycin, kanamycin).

Antibiotic prophylaxis:
Decontamination bowel before surgery on the colon (neomycin or kanamycin in combination with erythromycin).

Aminoglycosides should not be used for the treatment of community-acquired pneumonia in ambulatory and stationary conditions because of lack of activity against causative agent - pneumococcus. Aminoglycosides are indicated parenterally in the treatment of nosocomial infections. Aminoglycosides should not be used for therapy of shigellosis and salmonellosis (both inside and parenteral), because they are clinically ineffective against pathogens, which are localized intracellularly. Aminoglycosides are not recommended for monotherapy of staphylococcal infections. And should not be used for the treatment of uncomplicated infections of urinary system, except when the parasites are resistant to other less toxic antibiotics. Aminoglycosides must not be used for local application in the treatment of skin infections because of rapid development of resistance in microorganisms.

Contraindications
Aminoglycosides are contraindicated for use in:

  • Occlusive disease
  • Myasthenia gravis
  • Disease associated with inflammation of the VIII pair cranial nerves
  • Severe cardiovascular and renal disease
  • Uremia
  • Disorders of cerebral circulation,
  • Increased sensitivity to streptomycin
  • Pregnancy
  • Lactation (breastfeeding)

Aminoglycosides side effects

  • Urinary system: nephrotoxic effect may be manifested in increased thirst, significant increase or decrease of urine production, decrease in glomerular filtration and increased levels of creatinine in serum. This is especially common for patients with baseline renal dysfunction, elderly age, prolonged courses of treatment with high doses, simultaneous use with other nephrotoxic drugs (amphotericin B, polymyxin B, vancomycin, loop diuretics, cyclosporine).
  • Vestibular toxicity: disorder of motor coordination, dizziness. Vestibular toxicity is common for elderly patients, patients with initial vestibular disorders, prolonged course of treatment with high doses.
  • Nervous System: headache, general weakness, drowsiness, muscle twitching, paresthesia, convulsions. Streptomycin may cause burning sensation, numbness or paresthesia on the face and mouth.
  • Allergic reactions: skin rash, itching, hives, urticaria.
  • Local reactions: phlebitis at the place of injections

Drug interactions
Aminoglycosides should not be mixed in one vial with beta-lactam antibiotics or heparin. Toxic effects of aminoglycosides are increased in simultaneous application with drugs that cause nephrotoxicity and ototoxicity: polymixin B, amphoterecin B, ethacrinic acid, furosemide, vancomycin. Neuromuscular blockade is increased when aminoglycosides are used with medicines for inhalation narcosis. Indomethacin, phenylbutazone and other NSAID's disturbs renal circulation and may slow down the elimination of aminoglycosides.

Information for patients
During the therapy with aminoglycosides it is necessary to control the functions of auditory, vestibular and renal function. In case of occurrence of tinnitus, drowsiness, motor coordination disorders, decreased hearing, increasing or decreasing urine production seek immediate medication attention.