Tobramycin

Tobramycin
Systematic (IUPAC) name
(2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol
Clinical data
Trade names Tobrex
AHFS/Drugs.com monograph
MedlinePlus a682660
  • D (Injection, Inhalation); B (Ophthalmic) (US)
IV, IM, inhalation, ophthalmic
Pharmacokinetic data
Protein binding < 30%
Identifiers
32986-56-4 Yes
J01GB01 S01AA12
PubChem CID 36294
DrugBank DB00684 Yes
ChemSpider 33377 Yes
UNII VZ8RRZ51VK Yes
KEGG D00063 Yes
ChEBI CHEBI:28864 Yes
ChEMBL CHEMBL1747 Yes
Chemical data
Formula C18H37N5O9
467.515 g/mol
 Yes (what is this?)  (verify)

Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius and used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.[1]

Mechanism of action

Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing formation of the 70S complex. As a result, mRNA cannot be translated into protein, and cell death ensues. According to Kotra, Haddad and collaborators "aminoglycosides, including Tobramycin, are multifunctional hydrophilic sugars that possess several amino and hydroxy functionalities. The amine moieties are mostly protonated in biological media; hence, these antibiotics can be considered polycationic species for the purpose of understanding their biological interactions. Since they are polycationic, they show a binding affinity for nucleic acids. Specifically, aminoglycosides possess high affinities for certain portions of RNAs, especially the prokaryotic rRNA. In addition, aminoglycosides bind to the hammerhead ribozyme, tRNA(Phe), the Rev response element (RRE) transcriptional activation region in human immunodeficiency virus (HIV), the ribozyme from hepatitis delta virus, and group I self-splicing introns.[4]"

Administration and indications

Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract, so for systemic use it can only be given intravenously or intramuscularly. Ophthalmic (tobramycin only, Tobrex, or combined with dexamethasone, sold as TobraDex) and nebulised formulations both have low systemic absorption. The formulation for injection is branded Nebcin. The nebulised formulation (brand name Tobi) is indicated in the treatment of exacerbations of chronic infection with Pseudomonas aeruginosa in patients diagnosed with cystic fibrosis. A proprietary formulation of micronized, nebulized tobramycin has been tested as a treatment for bacterial sinusitis.[2] Tobrex is a 0.3% tobramycin sterile ophthalmic solution is produced by Bausch & Lomb Pharmaceuticals. Benzalkonium chloride 0.01% is added as a preservative. It is available by prescription only in the United States and Canada. In certain countries, such as Italy, it is available over the counter. Tobrex and TobraDex are indicated in the treatment of superficial infections of the eye, such as bacterial conjunctivitis. Tobramycin (injection) is also indicated for various severe or life-threatening gram-negative infections: meningitis in neonates, brucellosis, pelvic inflammatory disease, Yersinia pestis infection (plague). Tobramycin is preferred over gentamicin for Pseudomonas aeruginosa pneumonia due to better lung penetration..

Side effects

Like other aminoglycosides, tobramycin is ototoxic: it can cause hearing loss, or a loss of equilibrioception, or both in genetically susceptible individuals. These individuals carry a normally harmless genetic mutation that allows aminoglycosides such as tobramycin to affect cochlear cells. Aminoglycoside-induced ototoxicity is generally irreversible.

As with all amino glycosides, tobramycin is also nephrotoxic, it can damage or destroy the tissue of the kidneys [3]. This effect can be particularly worrisome when multiple doses accumulate over the course of a treatment or when the kidney concentrates urine by increasing tubular reabsorption during sleep. Adequate hydration may help prevent excess nephrotoxicity and subsequent loss of renal function. For these reasons parenteral tobramycin needs to be carefully dosed by body weight, and its serum concentration monitored. Tobramycin is thus said to be a drug with a narrow therapeutic index.

Spectrum of susceptibility

Tobramycin has a narrow spectrum of activity and is active against Gram-negative bacteria. Clinically, tobramycin is frequently used to eliminate Pseudomonas aeruginosa in cystic fibrosis patients. The following represents MIC susceptibility data for a few strains of Pseudomonas aeruginosa:

It's not active against gram positive Bacteria except for Staphylococcus aureus.

References

  1. ↑ "Tobramycin" (pdf). Toku-E. 2010-01-12. Retrieved 2012-06-11.
  2. ↑ "Nebulized Tobramycin in treating bacterial Sinusitis" (Press release). July 22, 2008. Retrieved 2009-12-06.
  3. ↑ http://www.toku-e.com/Assets/MIC/Tobramycin.pdf

3. Davis, Bernard D. "Mechanism of bactericidal action of aminoglycosides." Microbiological reviews 51.3 (1987): 341.


4. Kotra, Lakshmi P., Jalal Haddad, and Shahriar Mobashery. "Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance." Antimicrobial agents and chemotherapy 44.12 (2000): 3249-3256.

External links