- Aminoglycosides are potent broad-spectrum antibiotics primarily effective against aerobic gram-negative bacteria. These drugs were first discovered with streptomycin in 1943, and since then, various compounds like gentamicin, tobramycin, amikacin, and neomycin have been developed.
- The mechanism of action of aminoglycosides is unique: they bind irreversibly to the 30S subunit of bacterial ribosomes, disrupting protein synthesis. This binding leads to misreading of the genetic code and production of defective proteins. Additionally, these drugs have a concentration-dependent killing effect and demonstrate post-antibiotic effect, meaning they continue to suppress bacterial growth even after drug levels fall below the minimum inhibitory concentration.
- These antibiotics are particularly useful in treating severe infections caused by gram-negative organisms such as Pseudomonas, Enterobacter, E. coli, and Klebsiella. They’re often used in combination with β-lactams for synergistic effects in serious infections like sepsis, endocarditis, and complicated urinary tract infections. The once-daily dosing regimen has become standard practice, as it maximizes the concentration-dependent killing while potentially reducing toxicity.
- However, aminoglycosides come with significant potential toxicities that require careful monitoring. The most serious adverse effects are nephrotoxicity and ototoxicity (both vestibular and auditory), which can be permanent. These toxicities are dose-dependent and more common in elderly patients, those with renal impairment, or with prolonged therapy. Regular monitoring of drug levels and renal function is essential during treatment.
- The pharmacokinetics of aminoglycosides are characterized by poor oral absorption, necessitating parenteral administration. They exhibit poor penetration into cerebrospinal fluid and respiratory secretions but achieve good concentrations in urine. Due to their potential toxicity and the emergence of bacterial resistance, their use is often reserved for serious infections where alternatives are limited or less effective.
