Gentamicin is an aminoglycoside antibiotic. Aminoglycosides are antibiotics that inhibit protein synthesis like the tetracyclines, and they also bind to the 30S ribosomal subunit of the bacterial ribosome. Other examples of aminoglycosides include kanamycin, tobramycin, netilmicin, spectinomycin, amikacin, neomycin and streptomycin. Streptomycin (which is naturally synthesized by the actinomycetes bacterium, Streptomyces griseus)is a unique aminoglycoside because it is used in combination with other anti-mycobacterial agents for the treatment of tuberculosis (TB) caused by Mycobacterium tuberculosis. Streptomycin is the first aminoglycoside antibiotic to be synthesized from actinomycetes and other related soil microbes; and it was discovered by Selman Abraham in 1943.
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SOURCE OF GENTAMICIN
Gentamicin is naturally produced by bacteria in the genus Micromonospora. However, members of the aminoglycosides can also be semi-synthesized through chemical processes especially by the chemical modification of the aminoglycoside nucleus. Aminoglycosides can also be produced by synthetic processes.
STRUCTURE OF GENTAMICIN
The structure of aminoglycosides (inclusive of gentamicin) is a 6-membered aminocyclitol nucleus (Figure 1). Aminoglycosides are mainly composed of amino sugars that are linked to each other by glycosidic bonds. The chemical modification of the aminoglycoside nucleus either by semi-synthetic or synthetic methods produces newer aminoglycosides such as kanamycin, tobramycin and amikacin.
CLINICAL APPLICATION OF GENTAMICIN
Gentamicin is generally used clinically to treat Gram-negative infections including those caused by Pseudomonas aeruginosa, a common nosocomial pathogen. But it is inactive against Neisseria species; and thus gentamicin is not used to treat infections caused by these pathogens. Aminoglycosides are used to treat bacterial infections caused by a wide variety of Gram-positive and Gram-negative bacteria. Some aminoglycosides such as streptomycin are also used to treat tuberculosis (TB) infection. Neomycin is only used for topical therapeutic applications because of its high toxicity.
SPECTRUM OF ACTIVITY OF GENTAMICIN
Gentamicin is a broad spectrum antibiotic and it is bactericidal in action. The aminoglycosides are bactericidal in action unlike the tetracyclines which are bacteriostatic in action. The binding of the aminoglycosides to the 30S ribosomal subunit of the bacterial ribosome during protein synthesis is irreversible; and this is why antibiotics in this category are bacteriocidal in action.
MECHANISM OR MODE OF ACTION OF GENTAMICIN
Gentamicin and other aminoglycosides bind to the 30S ribosomal subunit of the bacterial ribosomes; and their binding inhibit the synthesis of protein in the target pathogenic bacteria. The binding of the 30S ribosomal subunit leads to the misreading of the genetic information carried on the mRNA. This binding of the drug to the 30S ribosomal subunit of the target bacterium interrupts translation activities during protein synthesis in the bacteria.
BACTERIAL RESISTANCE TO GENTAMICIN
The absence of a binding site on the target pathogenic bacteria due to mutation as well as the production of antibiotic-degrading enzyme can make bacteria to be resistant to the antibacterial onslaught of gentamicin and other aminoglycosides.
PHARMACOKINETICS OF GENTAMICIN
Gentamicin is not systemically effective when orally administered. It is poorly absorbed by the body from the intestines or GIT. Aminoglycosides are usually administered parenterally to treat systemic infections. They do not penetrate the CNS. Aminoglycosides show a poor degree of oral absorption and hence intravenous administration is the route usually used in patients with severe infections. Aminoglycosides are not metabolized and are essentially eliminated by glomerular filtration.
SIDE EFFECT/TOXICITY OF GENTAMICIN
Gentamicin and other aminoglycosides have some untoward effects. The prolonged clinical use of the aminoglycosides affects the kidney by impairing its biological functions; and antibiotics in this group also affect the nerves responsible for hearing. Deafness may ensue when the auditory nerves are affected. Other side effects include aplastic anaemia (blood disorder in which the bone marrow and haematopoietic stem cells fails to produce enough blood), ataxia (lack of muscle coordination which may affect speech, eye movements, the ability to swallow, walking, and other voluntary movements), allergy (hypersensitivity) and nausea (the sensation of an urge to vomit) and mild disturbances of the normal bacterial flora of the body.
Ashutosh Kar (2008). Pharmaceutical Microbiology, 1st edition. New Age International Publishers: New Delhi, India.
Block S.S (2001). Disinfection, sterilization and preservation. 5th edition. Lippincott Williams & Wilkins, Philadelphia and London.
Courvalin P, Leclercq R and Rice L.B (2010). Antibiogram. ESKA Publishing, ASM Press, Canada.
Denyer S.P., Hodges N.A and Gorman S.P (2004). Hugo & Russell’s Pharmaceutical Microbiology. 7th ed. Blackwell Publishing Company, USA. Pp.152-172.
Ejikeugwu Chika, Iroha Ifeanyichukwu, Adikwu Michael and Esimone Charles (2013). Susceptibility and Detection of Extended Spectrum β-Lactamase Enzymes from Otitis Media Pathogens. American Journal of Infectious Diseases. 9(1):24-29.
Finch R.G, Greenwood D, Norrby R and Whitley R (2002). Antibiotic and chemotherapy, 8th edition. Churchill Livingstone, London and Edinburg.
Russell A.D and Chopra I (1996). Understanding antibacterial action and resistance. 2nd edition. Ellis Horwood Publishers, New York, USA.