Aminoglycosides

Aminoglycosides are a class of antibiotics produced by soil actinomycetes, including Streptomyces and Micromonospora. They are bactericidal agents that bind irreversibly to the 30S ribosomal subunit, causing misreading of mRNA and disruption of protein synthesis. Uptake requires oxygen, and they are poorly absorbed from the gut, so systemic infections are treated with parenteral administration. They are often used in combination with beta-lactams to achieve synergistic activity against certain organisms.

Spectrum and clinical use: They are active primarily against aerobic gram-negative bacteria, such as Enterobacteriaceae and Pseudomonas aeruginosa. They have limited activity against most gram-positive bacteria and are ineffective against anaerobes. Indications include severe nosocomial infections, septicemia, complicated urinary or intra-abdominal infections, and pneumonia caused by gram-negative rods; they are frequently used in synergy for Enterococcus or Staphylococcus endocarditis and in cystic fibrosis inhaled tobramycin for chronic Pseudomonas infection.

Pharmacokinetics and administration: Most aminoglycosides are given intravenously or intramuscularly. They distribute mainly into extracellular fluid, with limited intracellular penetration and poor CNS entry. They are predominantly renally excreted, requiring dose adjustment in renal impairment. Dosing can be traditional multiple daily or once-daily in selected settings, and drug levels are monitored to minimize toxicity.

Adverse effects and resistance: The principal toxicities are nephrotoxicity and ototoxicity, with risk increasing with duration of therapy and high trough levels. Neuromuscular blockade and respiratory depression may occur in susceptible patients. Mechanisms of resistance include aminoglycoside-modifying enzymes and 16S rRNA mutations that reduce binding. Because of toxicity and resistance, use is guided by susceptibility data and typically limited to specific indications.