Tobramycin


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.
It was patented in 1965 and approved for medical use in 1974.

Medical uses

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 and nebulised formulations both have low systemic absorption. The formulation for injection is branded Nebcin. The nebulised formulation 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 is produced by Bausch & Lomb Pharmaceuticals. Benzalkonium chloride 0.01% is added as a preservative. It is available by prescription only in Bulgaria, 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 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:
The MIC for Klebsiella pneumoniae, KP-1, is 2.3±0.2 µg/mL at 25 °C .

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 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 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 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.