Aminoglycosides are a class of potent antibiotics derived from microorganisms such as Streptomyces bacteria. These compounds are reserved for treating serious bacterial infections when other antibiotics may not be effective. Their unique method of action makes them a specific tool for combating severe illnesses. This group of drugs is used under close medical supervision due to its powerful effects and potential for side effects.
How Aminoglycosides Work
The primary function of aminoglycoside antibiotics is to disrupt protein synthesis within bacterial cells. Proteins are fundamental to a bacterium’s ability to survive, maintain its structure, and replicate. These antibiotics enter the bacterial cell and bind to a component of its cellular machinery called the 30S ribosomal subunit. This ribosome reads genetic instructions from messenger RNA (mRNA) to build proteins.
The binding of the aminoglycoside to the ribosome causes a disruption in this assembly line. It leads to the misreading of the mRNA’s instructions, resulting in the creation of incorrect and nonfunctional proteins. The defective proteins cannot perform their intended jobs, compromising the structural integrity of the bacterial cell wall.
This disruption of protein production is bactericidal, meaning it leads to the death of the bacterium. The accumulation of abnormal proteins and the shutdown of protein manufacturing overwhelm the cell’s ability to function. This mechanism is specific to bacterial ribosomes, which differ from those in human cells, allowing the antibiotic to target bacteria without harming the patient’s cells.
Clinical Applications
Aminoglycosides are primarily employed to treat severe infections, many acquired in a hospital setting and caused by gram-negative bacteria. These infections can be life-threatening and include sepsis, complicated intra-abdominal infections, and severe urinary tract infections that do not respond to other treatments. They are also used for certain types of pneumonia, particularly in patients on mechanical ventilators.
In cases of endocarditis, an infection of the heart’s inner lining, aminoglycosides are often used in combination with other antibiotics like penicillins to create a more powerful effect. This synergistic approach helps to eradicate resilient bacteria causing the heart infection. The most commonly prescribed aminoglycosides for these systemic infections are gentamicin, tobramycin, and amikacin. Gentamicin is frequently chosen for its reliability, while tobramycin may be preferred for Pseudomonas aeruginosa infections. Amikacin is reserved for infections caused by bacteria resistant to other aminoglycosides.
Due to poor absorption from the digestive system, aminoglycosides are administered directly into the bloodstream through an intravenous (IV) infusion or into a muscle via an intramuscular (IM) injection. This ensures the drug reaches effective concentrations to fight the infection. An exception is the oral use of neomycin, which is not absorbed and acts locally within the intestines to reduce bacteria before certain surgery.
Toxicity and Monitoring
The potent nature of aminoglycosides means they carry a risk of significant side effects, requiring careful management. The two most documented risks are nephrotoxicity (damage to the kidneys) and ototoxicity (damage to the inner ear). These toxicities are a primary reason these antibiotics are closely supervised by healthcare professionals.
Nephrotoxicity involves kidney damage, as the drug can accumulate in the cells of the kidney tubules. This side effect is common, with incidence rates from about 9% to 14% in adult patients. The damage is often reversible if the antibiotic is stopped promptly once signs of kidney dysfunction appear.
Ototoxicity is damage to the inner ear, which can affect both hearing and balance. This can manifest as hearing loss, which can be permanent, or as vestibular issues like vertigo and dizziness. The risk of ototoxicity increases with longer treatment durations and higher doses of the medication.
To mitigate these risks, physicians perform therapeutic drug monitoring, taking regular blood samples to measure the drug’s concentration. The goal is to maintain a level high enough to kill bacteria but low enough to minimize harm to the kidneys and inner ear. Doctors also monitor kidney function with blood tests to detect early signs of nephrotoxicity.
Bacterial Resistance
Beyond side effects in patients, a separate challenge is the ability of bacteria to develop resistance. This occurs when bacteria evolve defense mechanisms that prevent the antibiotic from working effectively. Bacterial resistance is not a side effect on the patient, but a change in the bacteria that renders the treatment ineffective.
Bacteria have developed several strategies to counteract aminoglycosides. One common method is producing enzymes that chemically modify and inactivate the antibiotic molecule, preventing it from binding to the ribosome. Another mechanism involves altering the bacterial cell’s structure to block the antibiotic from entering in the first place. Bacteria can change their outer membrane or use efflux pumps, which are specialized proteins that actively pump the antibiotic out of the cell before it can reach its target.
The development of resistance is a natural evolutionary process, but it is accelerated by the overuse and misuse of antibiotics. When these drugs fail because of resistance, it can make treating serious infections more difficult. This underscores the importance of using antibiotics only when necessary to preserve their effectiveness.