Tobramycin
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| Trade names | Tobrex, Tobi |
AHFS/Drugs.com | Monograph |
| MedlinePlus | a682660 |
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| Routes of administration | IV, IM, inhalation, ophthalmic |
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| Protein binding | < 30% |
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| ECHA InfoCard | 100.046.642  |
| Chemical and physical data | |
| Formula | C18H37N5O9 |
| Molar mass | 467.515 g/mol |
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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]
Contents
1 Medical uses
1.1 Spectrum of susceptibility
2 Side effects
3 Mechanism of action
4 References
5 External links
Medical uses
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, 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).[citation needed] Tobramycin is preferred over gentamicin for Pseudomonas aeruginosa pneumonia due to better lung penetration.[citation needed].
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:
Pseudomonas aeruginosa - <0.25 µg/mL - 92 µg/mL [ref?]
Pseudomonas aeruginosa (non-mucoid) - 0.5 µg/mL - >512 µg/mL [ref?]
Pseudomonas aeruginosa (ATCC 27853) - 0.5 µg/mL - 2 µg/mL[3]
The MIC for Klebsiella pneumoniae, KP-1, is 2.3±0.2 µg/mL at 25 °C [unpublished].
It's not active against gram positive Bacteria except for Staphylococcus aureus.
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.
Mechanism of action
Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing formation of the 70S complex.[4] As a result, mRNA cannot be translated into protein, and cell death ensues.[5] Tobramycin also binds to RNA-aptamers,[6] artificially created molecules to bind to certain targets. However, there seems to be no indication that Tobramycin binds to natural RNAs or other nucleic acids.
The effect of tobramycin can be inhibited by metabolites of the Krebs (TCA) cycle, such as glyoxylate. These metabolites protect against tobramycin lethality by diverting carbon flux away from the TCA cycle, collapsing cellular respiration, and thereby inhibiting Tobramycin uptake and thus lethality.[7]
References
^ "Tobramycin" (pdf). Toku-E. 2010-01-12. Retrieved 2012-06-11..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
^ "Nebulized Tobramycin in treating bacterial Sinusitis" (Press release). July 22, 2008. Retrieved 2009-12-06.
^ http://www.toku-e.com/Assets/MIC/Tobramycin.pdf
^ Yang, Grace; Trylska, Joanna; Tor, Yitzhak; McCammon, J. Andrew (2006-09-07). "Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies". Journal of Medicinal Chemistry. 49 (18): 5478–5490. doi:10.1021/jm060288o. ISSN 0022-2623. PMID 16942021.
^ Haddad, Jalal; Kotra, Lakshmi P.; Llano-Sotelo, Beatriz; Kim, Choonkeun; Azucena, Eduardo F.; Liu, Meizheng; Vakulenko, Sergei B.; Chow, Christine S.; Mobashery, Shahriar (2002-04-03). "Design of novel antibiotics that bind to the ribosomal acyltransfer site". Journal of the American Chemical Society. 124 (13): 3229–3237. ISSN 0002-7863. PMID 11916405.
^ Kotra, L. P.; Haddad, J.; Mobashery, S. (December 2000). "Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance". Antimicrobial Agents and Chemotherapy. 44 (12): 3249–3256. ISSN 0066-4804. PMID 11083623.
^ Meylan, Sylvain; Porter, Caroline B.M.; Yang, Jason H.; Belenky, Peter; Gutierrez, Arnaud; Lobritz, Michael A.; Park, Jihye; Kim, Sun H.; Moskowitz, Samuel M. "Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control". Cell Chemical Biology. 24 (2): 195–206. doi:10.1016/j.chembiol.2016.12.015.
- Davis, Bernard D. "Mechanism of bactericidal action of aminoglycosides." Microbiological Reviews 51.3 (1987): 341.
External links
Tobramycin bound to proteins in the Protein Data Bank
