Aminoglycosides (Gentamicin, Tobramycin, Amikacin, Plazomicin)

Aminoglycosides: Overview

Aminoglycosides are a potent class of bactericidal antibiotics primarily used to treat serious Gram-negative infections. They are often reserved for hospital settings and severe infections, especially when there is a concern for drug resistance. These antibiotics are typically given intravenously or intramuscularly due to poor oral absorption and are used in combination with other antibiotics for synergy, particularly against Gram-positive bacteria.

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Common Aminoglycosides:

• Gentamicin
• Tobramycin
• Amikacin
• Streptomycin
• Neomycin
• Plazomicin (newest)

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Mechanism of Action:

Aminoglycosides bind to the 30S ribosomal subunit of bacteria, causing misreading of mRNA and inhibiting protein synthesis, which leads to bacterial cell death. These antibiotics exhibit concentration-dependent killing, meaning higher doses are associated with better bacterial killing.

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Spectrum:

1. Gram-negative bacteria:

   • Excellent coverage, especially against Enterobacteriaceae (E. coli, Klebsiella, Proteus, Enterobacter) and Pseudomonas aeruginosa.
   • Plazomicin, the newest aminoglycoside, is particularly effective against carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase (ESBL)-producing organisms.

2. Gram-positive bacteria:

   • Limited activity when used alone, but aminoglycosides are often used in synergy with beta-lactams or vancomycin to enhance efficacy against Gram-positive organisms like Enterococcus and Staphylococcus aureus in severe infections like endocarditis.

3. No anaerobic coverage:

   • Aminoglycosides are ineffective against anaerobes due to their oxygen-dependent uptake into bacterial cells.

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Key Uses:

1. Serious Gram-negative infections:

   • Aminoglycosides, such as Gentamicin, Tobramycin, and Amikacin, are often used for life-threatening infections like sepsis, hospital-acquired pneumonia, and bacteremia caused by multidrug-resistant Gram-negative bacteria.
   • Plazomicin is particularly useful for treating CRE and ESBL-producing Enterobacteriaceae in complicated urinary tract infections (cUTIs).

2. Synergy for Gram-positive infections:

   • Aminoglycosides are commonly used in low doses alongside other antibiotics for synergistic effects in endocarditis caused by Enterococcus or Staphylococcus aureus.

3. Urinary tract infections (UTIs):

   • Aminoglycosides, particularly gentamicin, are often used for complicated UTIs caused by resistant Gram-negative organisms.

4. Tuberculosis:

   • Streptomycin is used in combination with other agents for Mycobacterium tuberculosis, though it is used less frequently due to rising resistance.

5. Topical use:

   • Neomycin is used topically in ointments or creams for minor skin infections and wound care. It is also used orally for gut decontamination in hepatic encephalopathy.

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Plazomicin: The Newest Aminoglycoside:

• Plazomicin is a newly approved aminoglycoside that provides potent activity against carbapenem-resistant Enterobacteriaceae (CRE) and ESBL-producing Gram-negative bacteria.
• It is particularly used for complicated urinary tract infections (cUTIs) and hospital-acquired Gram-negative infections where other antibiotics fail.
• Plazomicin requires careful monitoring for nephrotoxicity and ototoxicity, similar to other aminoglycosides, though it offers hope in treating highly resistant infections.

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Key Side Effects:

1. Nephrotoxicity:

   • Aminoglycosides are known for their potential to cause kidney damage (nephrotoxicity), particularly with prolonged use or high doses. Regular monitoring of serum creatinine is crucial, especially in patients with pre-existing kidney issues.

2. Ototoxicity:

   • These antibiotics can cause irreversible hearing loss and vestibular toxicity (balance problems), making it essential to monitor for symptoms like tinnitus or dizziness during therapy.

3. Neuromuscular blockade:

   • Aminoglycosides can cause neuromuscular blockade, leading to muscle weakness and respiratory paralysis in rare cases, especially in patients with underlying neuromuscular disorders or when combined with anesthetics.

4. Therapeutic drug monitoring:

   • Due to the narrow therapeutic window, peak and trough levels of aminoglycosides should be monitored to optimize efficacy and minimize toxicity.

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Key Notes:

• Synergy: Aminoglycosides are used with beta-lactams or vancomycin to provide synergy against Gram-positive organisms like Enterococcus and Staphylococcus.
• Pseudomonas: Tobramycin is preferred for Pseudomonas aeruginosa infections, especially in respiratory diseases like cystic fibrosis.
• Plazomicin: This newer aminoglycoside is especially important for treating multidrug-resistant Gram-negative infections, particularly CRE and ESBL-producing bacteria.
• Toxicity: Careful monitoring for nephrotoxicity and ototoxicity is essential with all aminoglycosides.

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Summary:

• Aminoglycosides are a class of potent antibiotics used primarily for serious Gram-negative infections and as synergistic agents in Gram-positive infections.
• Gentamicin, Tobramycin, Amikacin, and the new Plazomicin provide broad coverage for multidrug-resistant Gram-negative bacteria, including Pseudomonas and CRE.
• Nephrotoxicity and ototoxicity are major concerns, necessitating regular monitoring of drug levels and kidney function.

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