Aminoglycoside antibiotics
Aminoglycoside antibiotics are a class of antibacterial agents that are primarily effective against aerobic, gram-negative bacteria. Derived from soil bacteria such as Streptomyces and Micromonospora, these antibiotics are known for their ability to disrupt bacterial ribosomal functions, thereby inhibiting protein synthesis. The first aminoglycoside, streptomycin, was discovered in 1943 and has been used to treat tuberculosis. Common aminoglycosides include neomycin, gentamicin, and tobramycin, which are employed for various infections, including those caused by Neisseria gonorrhoeae and Pseudomonas aeruginosa.
While aminoglycosides can be administered topically for minor infections, serious infections often require parenteral administration to achieve effective drug levels. Despite their efficacy, aminoglycosides pose risks of nephrotoxicity and ototoxicity, which necessitate careful monitoring, especially in prolonged treatments. Though their use has diminished due to resistance and toxicity concerns, aminoglycosides remain vital for treating serious infections, particularly in areas where other antibiotics may be less effective. As antibiotic resistance evolves, the role of aminoglycosides may again become crucial in medical treatments.
Aminoglycoside antibiotics
Definition
Aminoglycoside is an antibacterial drug class that consists of six-membered rings with amino (NH2) and glycoside groups, derived from or related to the soil bacteria Streptomyces, which block bacterial ribosomal functions.
Diseases Treated
Aminoglycosides, such as neomycin, gentamicin, and tobramycin, are active primarily against aerobic, gram-negative bacilli. The first aminoglycoside, named streptomycin for its origin in Streptomyces soil bacteria, was discovered in 1943 and was used to treat tuberculosis caused by Mycobacterium tuberculosis. All aminoglycoside antibiotics are naturally or synthetically derived from either Streptomyces or Micromonospora soil bacteria and treat similar types of bacterial infections. Aminoglycosides are active against Neisseria gonorrhoeae,Pseudomonas aeruginosa, and more common gram-negative pathogens. They are used topically for eye and ear infections and skin infections resulting from burns or ulcers. These antibiotics also may successfully treat serious infections such as sepsis, meningitis, and enterococcal endocarditis.
Administration
Drugs in the aminoglycoside class generally have a short half-life of two to three hours and have poor oral absorption. Neomycin, in particular, is used frequently in topical creams or ointments for minor infections and in topical liquid preparations for eye and ear infections. Aminoglycosides are administered parenterally (by injection into a muscle or vein) in cases of complicated infection to achieve high enough drug levels for antibacterial action. Aminoglycosides are also given by oral inhalation to treat lung infections, such as pneumonia, and topically as a wound irrigation to treat local skin infections.
Mechanism of Action
Aminoglycosides disrupt bacterial cell wall permeability to a degree proportional to the antibiotic concentration in bacterial cells. Specifically, aminoglycosides reversibly bind to mRNA (messenger ribonucleic acid) nucleotides at the 30S subunits of prokaryotic ribosomes. This binding causes conformational changes in the bacterial cell adenines, which blocks the translation of mRNA in the cell. The ribosomal binding reduces protein synthesis in the cell wall. Resistance to aminoglycosides is rare but focuses on A-to-G mutations and changes in the subunit that decrease binding of the drugs.
Side Effects
The primary side effects of aminoglycosides are nephrotoxicity, ototoxicity, and increased neuromuscular block. Nephrotoxicity may be reversible and proportional to dose, whereas ototoxicity is possibly irreversible. Persons who receive aminoglycosides, especially for more than two weeks, should be observed carefully for any early signs of ear and hearing damage. Neuromuscular block alone is infrequent but is more likely when aminoglycosides are given concomitantly with drugs that inhibit acetylcholine, such as pancuronium. Side effects of aminoglycosides are more likely to occur in older persons, and they can be reduced by using shorter treatment courses and dosing regimens designed to minimize toxicity.
Impact
Aminoglycosides were developed from natural sources in the 1940s, leading to increased resistance and high toxicity and contributing to its reduced use. In the early twenty-first century, medical treatments often combine beta-lactams with cephalosporins instead of aminoglycosides for these reasons. However, aminoglycosides are still used for serious infections, and they retain their usefulness in remote areas of the world. As resistance develops to agents in the beta-lactam class, aminoglycosides may again prove necessary in more populated areas of the world.
Bibliography
"Aminoglycosides." Drugs.com, www.drugs.com/drug-class/aminoglycosides.html. Accessed 30 Oct. 2024.
Durante-Mangoni, E., et al. "Do We Still Need the Aminoglycosides?" International Journal of Antimicrobial Agents, vol. 33, no. 3, 2009, pp. 201-205.
Germovsek, Eva, et al. "What Do I Need to Know about Aminoglycoside Antibiotics?" Archives of Disease in Childhood: Education and Practice Edition, vol. 102, no. 2, 2017, pp. 89-93, doi:10.1136/archdischild-2015-309069. Accessed 30 Oct. 2024.
Gilbert, David N., and James E. Leggett. "Aminoglycosides." Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Gerald L. Mandell, John F. Bennett, and Raphael Dolin. 7th ed., Churchill Livingstone/Elsevier, 2010.
Leibovici, L., L. Vidal, and M. Paul. "Aminoglycoside Drugs in Clinical Practice: An Evidence-Based Approach." Journal of Antimicrobial Chemotherapy, vol. 62, no. 2, 2009, pp. 246-251.
Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. "Antibacterial Agents." Medical Microbiology. 6th ed., Mosby/Elsevier, 2009.
Sanford, Jay P., et al. The Sanford Guide to Antimicrobial Therapy. 18th ed., Antimicrobial Therapy, 2010.
Werth, Brian J. "Aminoglycosides - Merck Manual Consumer Version." Merck Manuals, May 2024, www.merckmanuals.com/home/infections/antibiotics/aminoglycosides. Accessed 30 Oct. 2024.
Wilson, Michael, Brian Henderson, and Rod McNab. Bacterial Disease Mechanisms: An Introduction to Cellular Microbiology. Cambridge University Press, 2002.