Gentamicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria. Gentamicin works by preventing bacterial organisms from manufacturing the vital proteins they require for growth and function. Gentamicin binds to components in the bacterial cell which result in the production of abnormal proteins. These proteins are necessary for the bacteria's survival. Therefore the production of these abnormal proteins is ultimately fatal to the bacteria. Aminoglycosides are antibiotics which are highly effective against many gram-negative bacteria and to a lesser degree against gram-positive bacteria.
Gentamicin is effective against Pseudomonas aeruginosa, whereas aminoglycosides such as Streptomycin and Kanamycin are not. Aminoglycosides are ineffective against fungi and yeast.
Gentamicin consists of a mixture of Gentamicin C1, C1a and C2. These compounds differ in the two side chains attached to an amino sugar. The antimicrobial effect of the three compounds is practically the same. Aminoglycosides consist of a central hexose or diaminohexose molecule to which two or more amino sugars are attached by a glycosidic bond. The bactericidal effect of these antibiotics is based on the inhibition of protein synthesis. Gentamicin binds to both ribosomal subunits. Attachment to the 30S subunit results in stagnation of the initiation phase during translation. Because of this stagnation elongation can no longer take place and protein synthesis stops.
The antibiotic inhibits protein synthesis mitochondria and chloroplasts. Plant cells are therefore generally intolerant to aminoglycosides. The inhibition is based on the similarity between protein synthesis in these cell organelles and that of bacteria, making Gentamicin a toxic agent for eukaryotic cells. Resistance to Gentamicin is obtained relatively slower than resistance for example to Kanamycin, Streptomycin and Neomycin.
The mechanism through which resistance is built up is attributable mainly to chemical modification of the antibiotic, resulting in the loss of antimicrobial activity. There is complete cross resistance with Streptomycin, Kanamycin and Neomycin. The antimicrobial effect of the antibiotic depends on the extracellular pH. Antimicrobial activity decreases significantly at pH levels of 6.5 or lower. The presence of divalent cations (Ca2+ and Mg2+ ) in the medium also decreases the antimicrobial activity.
Gentamicin is active against Enterobacteriaceae organisms including Escherichia coli, Proteus, Klebsiella, Serratia, Enterobacter, and Citrobacter. In general, Pseudomonas aeruginosa is usually sensitive to gentamicin, although considerable variability in its susceptibility exists. Other pseudomonal species also may be susceptible but are usually less so than Pseudomonas aeruginosa. Staphylococcus aureus is sensitive, while Neisseria and Haemophilus genera are not. Many strains of Streptococcus are sensitive, although gentamicin is usually used in combination with another antibiotic to treat these organisms. Against Enterococcus faecalis, aminoglycosides are used only in combination with a cell-wall active antibiotic such as a penicillin or vancomycin.