Tobramycin

Overview

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

It was patented in 1965, and approved for medical use in 1974. It is on the World Health Organization's List of Essential Medicines. In 2023, it was the 298th most commonly prescribed medication in the United States, with more than 400,000 prescriptions.[2–5] WP

Uses, dosage and effects

Medical uses

Tobramycin does not pass the gastro-intestinal tract, so for systemic use it can only be given intravenously or by injection into a muscle. Eye drops and ointments (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 people diagnosed with cystic fibrosis.[6][7] WP

Tobramycin eye drops (with or without dexamethasone) are indicated in the treatment of superficial infections of the eye, such as bacterial conjunctivitis.[8–11] WP

Tobramycin, in its injectable form, is also indicated for various severe or life-threatening infections caused by susceptible strains: sepsis, meningitis, lower respiratory tract infections, intra-abdominal infections, skin infections, bone infections, and skin structure infections, complicated and recurrent urinary tract infections.[12][13] WP

Spectrum of susceptibility

Tobramycin has a narrow spectrum of activity and is active against Gram-positive Staphylococcus aureus and various Gram-negative bacteria. Clinically, tobramycin is frequently used to eliminate Pseudomonas aeruginosa in cystic fibrosis patients. The following represents the minimum inhibitory concentration (MIC) susceptibility data for a few strains of Pseudomonas aeruginosa:[12] WP⚠ Wikipedia itself has flagged this text: citation needed.

• Pseudomonas aeruginosa - <0.25 μg/mL – 92 μg/mL[12] WP⚠ Wikipedia itself has flagged this text: medical citation needed.
• Pseudomonas aeruginosa (non-mucoid) – 0.5 μg/mL - >512 μg/mL[12] WP⚠ Wikipedia itself has flagged this text: medical citation needed.
• Pseudomonas aeruginosa (ATCC 27853) – 0.5 μg/mL – 2 μg/mL[14] WP

The MIC for Klebsiella pneumoniae, KP-1, is 2.3±0.2 μg/mL at 25 °C [unpublished]. WP⚠ Wikipedia itself has flagged this text: clarification needed.⚠ Wikipedia itself has flagged this text: medical citation needed.

Risks and side effects

Contraindications

Tobramycin is contraindicated in people with hypersensitivity against aminoglycoside antibiotics. The Infusion is also contraindicated in people with myasthenia gravis.[15] WP

Side effects

Like other aminoglycosides, a major side effect for tobramycin is ototoxicity or a loss of equilibrioception, or both in genetically susceptible individuals. Other side effects include nephrotoxicity, neuromuscular toxicity, and hypersensitivity reactions. Nephrotoxicity 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.[16–19] WP⚠ Wikipedia itself has flagged this text: citation needed.

Interactions

Interactions

Muscle relaxants and diethylether can add to the neuromuscular blocking effects of tobramycin.[15] WP

Methoxyflurane, when used as an inhalational anesthetic, can aggravate the nephrotoxic effects of injected tobramycin. Likewise, combining injected tobramycin with other nephrotoxic or ototoxic drugs can lead to more adverse effects; examples include amphotericin B, ciclosporin, cisplatin, vancomycin, and the diuretic furosemide. Other diuretics can also increase the risk for side effects because they raise tobramycin concentrations in the body fluids.[15] WP

Combining tobramycin with beta-lactam antibiotics can be desirable because of their synergistic effects. However, when they are given through the same drip, as well as in people with reduced kidney function, they can react with each other to form antibiotically inactive amides.[15] WP

Pharmacology

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. Tobramycin also binds to RNA-aptamers, 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.[20][21][22] WP⚠ Wikipedia itself has flagged this text: citation needed.

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.[23] WP

Pharmacokinetics

Tobramycin is not absorbed in the gut. When given as infusion, it is distributed in the extracellular fluid. It can accumulate in the kidney's tubular cells and in the lymph of the inner ear. Only low concentrations reach the central nervous system and breast milk. Tobramycin passes the placenta: in the fetus, 20% of the mother's concentrations have been measured.[15] WP

The substance is neither bound to plasma proteins, nor is it metabolized. It is excreted in unchanged form via the kidneys with a biological half-life of about 2 to 3 hours. Elimination from deep compartments such as the renal cortex follows after 8 to 12 hours. In newborns the half-life is 4.6 hours on average; in those with a low birth weight it is as long as 8.7 hours on average. People with reduced kidney function also have a longer half-life for tobramycin, while in those with severe burns it can be shorter.[15] WP

Legal status

Society and culture

Tobramycin was patented in 1965, and approved for medical use in 1974. Tobramycin is on the World Health Organization's List of Essential Medicines. In 2023, tobramycin was the 298th most commonly prescribed medication in the United States, with more than 400,000 prescriptions.[2–5] WP

Tobrex eye drops are a 0.3% tobramycin sterile ophthalmic solution produced by Alcon Pharmaceuticals. Benzalkonium chloride 0.01% is added to Tobrex as a preservative. WP⚠ Wikipedia itself has flagged this text: citation needed.

Brand names

In Egypt, tobramycin (in the form of eye drops) is sold under the brand Tobrin, produced by EIPICo. WP⚠ Wikipedia itself has flagged this text: citation needed.

Chemistry

Formula

C18H37N5O9 PC

CAS number

32986-56-4 PC

Molar mass (g/mol)

467.5 PC

IUPAC name (computed by PubChem)

(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 PC

SMILES

C1[C@@H]([C@H]([C@@H]([C@H]([C@@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)N)O)O)O[C@@H]3[C@@H](C[C@@H]([C@H](O3)CN)O)N)N PC

InChIKey

NLVFBUXFDBBNBW-PBSUHMDJSA-N PC

PubChem CID

36294

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Tobramycin. 12 January 2010
2. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
3. Other World Health Organization. The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
4. Other The Top 300 of 2023
5. Other Tobramycin Drug Usage Statistics, United States, 2014 - 2023
6. Journal / agency Tobi- tobramycin solution. 5 October 2018
7. Journal / agency Tobi Podhaler. 17 September 2018
8. Journal / agency Tobrex- tobramycin ointment. 16 September 2019
9. Other Tobradex Eye Drops – Summary of Product Characteristics (SmPC). 21 January 2020
10. Journal / agency Tobradex- tobramycin and dexamethasone ointment. 11 September 2019
11. Journal / agency Tobradex- tobramycin and dexamethasone suspension/ drops. 9 September 2019
12. Journal / agency Tobramycin- tobramycin sulfate injection, powder, for solution. 11 October 2019
13. Other Tobramycin 40mg/mL Injection – Summary of Product Characteristics (SmPC). 9 October 2018
14. Other Tobramycin Susceptibility and Minimum Inhibitory Concentration (MIC) Data
15. Other Austria-Codex. 2021
16. Journal / agency Lerner AM, Reyes MP, Cone LA, Blair DC, Jansen W, Wright GE, Lorber RR. Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin. Lancet. May 1983. doi:10.1016/S0140-6736(83)92864-7 · PMID 6133153
17. Journal / agency Neu HC. Tobramycin: an overview. The Journal of Infectious Diseases. August 1976. doi:10.1093/infdis/134.supplement_1.s3 · PMID 787451
18. Journal / agency Pedersen SS, Jensen T, Osterhammel D, Osterhammel P. Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis. Antimicrobial Agents and Chemotherapy. April 1987. doi:10.1128/AAC.31.4.594 · PMID 3606063 · PMC174783
19. Journal / agency Reyhanoglu G, Reddivari AK. StatPearls. January 2022. PMID 31869159
20. Journal / agency Yang G, Trylska J, Tor Y, McCammon JA. 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. September 2006. doi:10.1021/jm060288o · PMID 16942021
21. Journal / agency Haddad J, Kotra LP, Llano-Sotelo B, Kim C, Azucena EF, Liu M, Vakulenko SB, Chow CS, Mobashery S. Design of novel antibiotics that bind to the ribosomal acyltransfer site. Journal of the American Chemical Society. April 2002. doi:10.1021/ja011695m · PMID 11916405
22. Journal / agency Kotra LP, Haddad J, Mobashery S. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrobial Agents and Chemotherapy. December 2000. doi:10.1128/aac.44.12.3249-3256.2000 · PMID 11083623 · PMC90188
23. Journal / agency Meylan S, Porter CB, Yang JH, Belenky P, Gutierrez A, Lobritz MA, Park J, Kim SH, Moskowitz SM, Collins JJ. Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control. Cell Chemical Biology. February 2017. doi:10.1016/j.chembiol.2016.12.015 · PMID 28111098 · PMC5426816

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.