The Full Wiki

Aminoglycosides: Wikis


Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.


(Redirected to Aminoglycoside article)

From Wikipedia, the free encyclopedia

An aminoglycoside is a molecule composed of a sugar group and an amino group.[1]

Several aminoglycosides function as antibiotics that are effective against certain types of bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin[2], streptomycin, tobramycin, and apramycin.



Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the suffix -mycin, whereas those that are derived from Micromonospora are named with the suffix -micin.

This nomenclature system is not specific for aminoglycosides. For example, vancomycin is a glycopeptide antibiotic and erythromycin, which is produced from the species Saccharopolyspora erythraea (previously misclassified as Streptomyces) along with its synthetic derivatives clarithromycin and azithromycin, is a macrolide. All differ in their mechanisms of action, however.

Mechanisms of action

Aminoglycosides have several potential antibiotic mechanisms, some as protein synthesis inhibitors, although their exact mechanism of action is not fully known:

  • They interfere with the proofreading process, causing increased rate of error in synthesis with premature termination.[3]
  • Also, there is evidence of inhibition of ribosomal translocation where the peptidyl-tRNA moves from the A-site to the P-site.[3]
  • They can also disrupt the integrity of bacterial cell membrane.[4]

They bind to the bacterial 30S ribosomal subunit[5][6] (some work by binding to the 50S subunit[7])

There is a significant relationship between the dose administered and the resultant plasma level in blood. TDM, therapeutic drug monitoring, is necessary to obtain the correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug level detectable in blood, but there still seems to be inhibition of bacterial re-growth. This is due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels drop. This allows a prolonged dosage interval. Depending on their concentration they act as bacteriostatic or bactericidal agents.

The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli. Aminoglycosides competitively displace cell biofilm-associated Mg2+ and Ca2+ that link the polysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell membrane blebs, with formation of transient holes in the cell wall and disruption of the normal permeability of the cell wall. This action alone may be sufficient to kill most susceptible Gram-negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome[8]."

The antibacterial properties of aminoglycosides were believed to result from inhibition of bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This explanation, however, does not account for the potent bactericidal properties of these agents, since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not bactericidal. Recent experimental studies show that the initial site of action is the outer bacterial membrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer membrane probably accounts for most of the bactericidal activity. Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this uptake, so aminoglycosides are less active against anaerobes. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia, complicated intraabdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. Usually, once cultures of the causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.

Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.

Infections caused by gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. One of the most frequent combinations is ampicillin (a beta-lactam, or penicillin-related antibiotic) and gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent" for penicillin and gentamicin.

Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi, and viruses.

Experimentation with aminoglycosides as a treatment of cystic fibrosis (CF) has shown some promising results. CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In approximately 10% of CF cases, the mutation in this gene causes its early termination during translation, leading to the formation of is truncated and non-functional CFTR protein. It is believed that gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination codon, causing the ribosome to "skip" over the stop sequence and to continue with the normal elongation and production of the CFTR protein. The treatment is still experimental but showed improvement in cells from CF patients with susceptible mutations.[9]

Routes of administration

Since they are not absorbed from the gut, they are administered intravenously and intramuscularly. Some are used in topical preparations for wounds. Oral administration can be used for gut decontamination (e.g., in hepatic encephalopathy). Tobramycin may be administered in a nebulized form.

Clinical use

The recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reevaluate the use of these antibacterial agents.[10] This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Current evidence shows that aminoglycosides do retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world. Still, the relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment makes physicians reluctant to use these compounds in everyday practice. Recent advances in the understanding of the effect of various dosage schedules of aminoglycosides on toxicity have provided a partial solution to this problem, although more research still needs to be done in order to overcome this problem entirely.[11]


  1. ^ MeSH Aminoglycosides
  2. ^ Massachusetts Institute of Technology. "Bacterial 'Battle For Survival' Leads To New Antibiotic." ScienceDaily 27 February 2008. 28 February 2008 < /releases/2008/02/080226115618.htm>.
  3. ^ a b Pharmamotion --> Protein synthesis inhibitors: aminoglycosides mechanism of action animation. Classification of agents Posted by Flavio Guzmán on 12/08/08
  4. ^ Aminoglycosides versus bacteria--a description of the action, resistance mechanism, and nosocomial battleground. J Biomed Sci. 2008 Jan;15(1):5-14.
  5. ^ "Aminoglycosides: Bacteria and Antibacterial Drugs: Merck Manual Professional". 
  6. ^ "Aminoglycosides". 
  7. ^ Champney WS (May 2001). "Bacterial ribosomal subunit synthesis: a novel antibiotic target". Curr Drug Targets Infect Disord. 1 (1): 19–36. doi:10.2174/1568005013343281. PMID 12455231. 
  8. ^ Lorian, Victor. "Antibiotics in Laboratory Medicine". Williams & Wilkins Press, 1996 (pp.589-590)
  9. ^ Wilschanski M, Yahav Y, Yaacov Y, et al. (October 2003). "Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations". N. Engl. J. Med. 349 (15): 1433–41. doi:10.1056/NEJMoa022170. PMID 14534336. 
  10. ^ Falagas ME, Grammatikos AP, Michalopoulos A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti Infect Ther. 2008; 6(5):593-600 PMID:18847400
  11. ^ Durante-Mangoni E, Grammatikos A, Utili R, Falagas ME. Do we still need the aminoglycosides? Int J Antimicrob Agents. 2009; 33(3):201-5.PMID:18976888

External links



Got something to say? Make a comment.
Your name
Your email address