|Trade names||Tobrex, Tobi, others|
|Other names||47663, SPRC-AB01|
|Main uses||Sepsis, meningitis, urinary tract infections, bone infections, lung infections|
|Side effects||Hearing problems, balance problems, kidney problems|
|IV, IM, inhalation, eye drop|
|Protein binding||< 30%|
|Chemical and physical data|
|Molar mass||467.515 g·mol−1|
|3D model (JSmol)|
Tobramycin is an antibiotic used to treat a variety of infections including sepsis, meningitis, urinary tract infections, bone infections, and lung infections. This includes infections due to Pseudomonas. It may be given by injection into a vein or muscle, or inhaled into the lungs.
Common side effects include hearing problems, balance problems, and kidney problems. Other side effects may include paralysis and anaphylaxis. The dose needs to be lowered in those with kidney problems. Use in pregnancy may harm the baby. It is an aminoglycoside.
Tobramycin was patented in 1965, and approved for medical use in 1974. It is available as a generic medication. In the United Kingdom 80 mg for injection costs the NHS about £5 while a month of inhaled medication is about £780. This amount of inhaled solution in the United States costs about 4,900 USD as of 2021. It is made from Streptomyces tenebrarius.
Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract, so for systemic use it can only be given intravenously or by injection into a muscle. 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 people diagnosed with cystic fibrosis.
Tobrex is a 0.3% tobramycin sterile ophthalmic solution produced by Bausch & Lomb Pharmaceuticals. Benzalkonium chloride 0.01% is added as a preservative. It is available by prescription only in Bulgaria, Hungary, 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 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.
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 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
The MIC for Klebsiella pneumoniae, KP-1, is 2.3±0.2 µg/mL at 25 °C [unpublished].
For lung infections due to Pseudomonas in people with cystic fibrosis it may be inhaled at a dose of 112 mg to 300 mg twice a day for 4 weeks.
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 aminoglycosides, tobramycin is also nephrotoxic, it can damage or destroy the tissue of the kidneys. 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. 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.
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.
Society and culture
The cost of this medication in the U.S. is $28 (USD) for 30 ml injectable solution 40 mg/mL
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