Aminoglycosides

Aminoglycosides 

Definition

Aminoglycosides are a group of antibiotics that are used to treat certain bacterial infections. This group of antibiotics includes at least eight drugs: amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin. All of these drugs have the same basic chemical structure.

Purpose

Aminoglycosides are primarily used to combat infections due to aerobic, Gram-negative bacteria. These bacteria can be identified by their reaction to Gram's stain. In Gram's staining, a film of material containing the possible bacteria is placed on a glass slide and dried. The slide is stained with crystal violet for one minute, cleaned off with water and then placed into a solution of Gram's iodine solution for one minute. The iodine solution is rinsed off and the slide is immersed in 95% ethyl alcohol. The slide is then stained again with reddish carbolfuchsin or safranine for 30 seconds, rinsed in water, dried and examined. Gram-positive bacteria retain the violet purple stain. Gram-negative bacteria accept the red stain. Bacteria that can successfully be combated with aminoglycosides include Pseudomonas, Acinetobacter, and Enterobacter species, among others. Aminoglycosides are also effective against mycobacteria, the bacteria responsible for tuberculosis.

The aminoglycosides can be used against certain Gram-positive bacteria, but are not typically employed because other antibiotics are more effective and have fewer side effects. Aminoglycosides are ineffective against anaerobic bacteria (bacteria that cannot grow in the presence of oxygen), viruses, and fungi. And only one aminoglycoside, paromomycin, is used against parasitic infection.

Like all other antibiotics, aminoglycosides are not effective against influenza, the common cold, or other viral infections.

Precautions

Pre-existing medical conditions-such as kidney disease, eighth cranial nerve disease, myasthenia gravis, and Parkinson's disease-should be discussed prior to taking any aminoglycosides. Pregnant women are usually advised against taking aminoglycosides, because their infants may suffer damage to their hearing, kidneys, or sense of balance. However, those factors need to be considered alongside the threat to the mother's health and life in cases of serious infection. Aminoglycosides do not pass into breast milk to any great extent, so nursing mothers may be prescribed aminoglycosides without injuring their infants.

Key terms

Aerobic bacteria — Bacteria which require oxygen in order to grow and survive.

Anaerobic bacteria — Bacteria which cannot grow or reproduce in the presence of oxygen.

Eighth cranial nerve disease — A disorder affecting the eighth cranial nerve, characterized by a loss of hearing and/or balance.

Gram's stain — A stain used in microbiology to classify bacteria and help identify the species to which they belong. This identification aids in determining treatment.

Gram-negative — Referring to a bacteria that take on a pink color when exposed to Gram's stain.

Gram-positive — Referring to a bacteria that takes on a purplish-black color when exposed to Gram's stain.

Kidney disease — Any disorder which impairs the kidney's ability to remove waste and toxins from the body.

Myasthenis gravis — A neuromuscular disease characterized by muscle weakness in the limbs and face.

Parkinson's disease — A neurological disorder caused by deficiency of dopamine, a neurotransmitter, that is a chemical that assists in transmitting messages between the nerves within the brain. It is characterized by muscle tremor or palsy and rigid movements.

Description

Streptomycin, the first aminoglycoside, was isolated from Streptomyces griseus in the mid-1940s. This antibiotic was very effective against tuberculosis. One of the main drawbacks to streptomycin is its toxicity, especially to cells in the inner and middle ear and the kidney. Furthermore, some strains of tuberculosis are resistant to treatment with streptomycin. Therefore, medical researchers have put considerable effort into identifying other antibiotics with streptomycin's efficacy, but without its toxicity.

Aminoglycosides are absorbed very poorly from the gastrointestinal tract; in fact, aminoglycosides taken orally are excreted virtually unchanged and undiminished in quantity. The route of drug administration depends on the type and location of the infection being treated. The typical routes of administration are by intramuscular (injection into a muscle) or intravenous injection (injection into a vein), irrigation, topical skin application, or inhalation. If the infection being treated involves the central nervous system, the drug can be injected into the spinal canal.

The bactericidal ability of aminoglycosides has not been fully explained. It is known that the drug attaches to a bacterial cell wall and is drawn into the cell via channels made up of the protein, porin. Once inside the cell, the aminoglycoside attaches to the cell's ribosomes. Ribosomes are the intracellular structures responsible for manufacturing proteins. This attachment either shuts down protein production or causes the cell to produce abnormal, ineffective proteins. The bacterial cell cannot survive with this impediment.

Antibiotic treatment using aminoglycosides may pair the drug with a second type of antibiotic, usually a beta-lactam or vancomycin, administered separately. Beta-lactams disrupt the integrity of the bacteria cell wall, making it more porous. The increased porosity allows more of the aminoglycoside into the bacteria cell.

Traditionally, aminoglycosides were administered at even doses given throughout the day. It was thought that a steady plasma concentration was necessary to combat infection. However, this administration schedule is time and labor intensive. Furthermore, administering a single daily dose can be as effective, or more effective, than several doses throughout the day.

Dosage depends on the patient's age, weight, gender, and general health. Since the drug is cleared by the kidneys, it is important to assess any underlying problems with kidney function. Kidney function is assessed by measuring the blood levels of creatinine, a protein normally found in the body. If these levels are high, it is an indication that the kidneys may not be functioning at an optimal rate and dosage will be lowered accordingly.

Risks

Aminoglycosides have been shown to be toxic to certain cells in the ears and in the kidneys. Approximately 5-10% of the people who are treated with aminoglycosides experience some side effect, affecting their hearing, sense of balance, or kidneys. However, in most cases the damage is minor and reversible once medication is stopped.

If cells in the inner ear are damaged or destroyed, an individual may experience a loss of balance and feelings of dizziness. Damage to the middle ear may result in hearing loss or tinnitus. Neomycin, kanamycin, and amikacin are the most likely to cause problems with hearing, and streptomycin and gentamicin carry the greatest risk of causing vertigo and loss of balance. Kidney damage, apparent with changes in urination frequency or urine production, is most likely precipitated by neomycin, tobramycin, and gentamicin.

Young children and the elderly are at the greatest risk of suffering side effects. Excessive dosage or poor clearance of the drug from the body can be injurious at any age.

Less common side effects include skin rashes and itching. Very rarely, certain aminoglycosides may cause difficulty in breathing, weakness, or drowsiness. Gentamicin, when injected, may cause leg cramps, skin rash, fever, or seizures.

If side effects linger or become worse after medication is stopped, it is advisable to seek medical advice. Side effects that may be of concern include tinnitus or loss of hearing, dizziness or loss of balance, changes in urination frequency or urine production, increased thirst, appetite loss, and nausea or vomiting.

Normal results

At the proper dosage and in the presence of gramnegative enteric (intestinal) bacteria, aminoglycosides are very effective in treating an infection.

Abnormal results

In some cases, bacteria are resistant to antibiotics that would normally kill them. This resistance becomes apparent after repeated exposure to the antibiotic and arises from a mutation that alters the bacteria's susceptibility to the drug. Various degrees of resistance have been observed in bacteria that normally would be destroyed by aminoglycosides. In general, though, aminoglycoside effectiveness has held up well over time.

Resources

Books

Chambers, Henry F., W. Keith Hadley, and Ernest Jawetz. "Aminoglycosides & Spectinomycin." In Basic and Clinical Pharmacology, edited by Bertram G. Katzung, 7th ed. Stamford: Appleton & Lange, 1998.

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aminoglycosides (mē´nōglī´ksīdz´),

n.pl the bacteriocidal antibiotics obtained from
Streptomyces that inhibit protein synthesis in bacterial ribosomes and are effective against aerobic gram-negative bacilli.