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Aminoglycosides are bactericidal antibiotics that inhibit protein synthesis by binding to the 30s ribosomal subunit and disrupting the formation of the initiation complex. This leads to the misreading of mRNA, which ultimately causes cell death.

The most common clinical application of the aminoglycosides is in the treatment of serious infections caused by aerobic gram-negative bacilli, usually in combination with a beta-lactam antibiotic or vancomycin, which are cell wall active drugs. These drugs enhance the ability of aminoglycosides to penetrate cells.

There are different types of aminoglycosides: neomycin (useful in bowel preparation before colorectal surgery), streptomycin (effective against tularemia and plague), gentamicin and tobramycin (used for severe infections by gram-negative bacteria), and amikacin (for resistant gram-negative bacteria).

Two major adverse effects of aminoglycosides are ototoxicity and nephrotoxicity, and as such, it is important to monitor serum concentrations to prevent toxicity. Contraindications to aminoglycoside use include pregnancy (can cause deafness in newborn) and myasthenia gravis (due to the risk of neuromuscular blockade).

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How do aminoglycosides work as antibacterial agents?

Aminoglycosides exert their antibacterial effect by binding irreversibly to the 30S ribosomal subunit within the bacteria. This binding disrupts the formation of the initiation complex, which leads to the misreading of mRNA and impedes the process of protein synthesis, eventually leading to apoptosis. Since these processes are critical for bacterial growth and survival, aminoglycosides are considered bactericidal, meaning they can kill bacteria rather than just inhibiting their growth.

What types of bacteria are aminoglycosides active against?

Aminoglycosides are primarily effective against aerobic gram-negative bacilli. This includes bacteria like Enterobacter, Serratia, Klebsiella, and Pseudomonas. However, while less common, aminoglycosides are also useful against certain gram-positive and parasite organisms, especially when paired with cell wall active agents such as penicillins or vancomycin. For example, aminoglycosides show activity against enterococcus when combined with a cell wall active agent.

How are aminoglycosides typically administered?

Most aminoglycosides are administered intravenously (IV) to guarantee systemic delivery. There are exceptions, like neomycin and paromomycin which are often used for their local effect in the gastrointestinal (GI) tract. Neomycin is used in bowel preparation prior to colorectal surgery, and paromomycin is used as a luminal agent against GI parasites like Entamoeba histolytica.

What are the potential side effects and risks associated with aminoglycosides?

Aminoglycosides have several associated toxicities, most notably nephrotoxicity and ototoxicity. Nephrotoxicity manifests as injury to the kidney cells, and can lead to acute tubular necrosis. Ototoxicity can cause damage to both the vestibular and cochlear parts of the ear, leading to balance disorders or hearing loss. These antibiotics are also known to cross the placenta during pregnancy, with the potential to cause deafness in the newborn. Another concern is the potential for neuromuscular blockade, particularly in patients with myasthenia gravis, for which aminoglycosides are contraindicated.

How is the effectiveness of aminoglycoside treatment monitored?

To ensure the optimal effectiveness and safety of aminoglycoside treatment, plasma levels of the drugs are frequently monitored. This is especially important due to their narrow therapeutic index and potential for toxicity. Monitoring these levels helps guide dosing adjustments and helps avoid potential toxic side effects such as ototoxicity and nephrotoxicity.