Tobramycin

Tobramycin belongs to the aminoglycoside family, antibiotics with a bactericidal action. Once inside the bacterium, it binds to the 16S ribosomal RNA of the 30S subunit of the ribosome, precisely at the A site, known as the aminoacyl site. The ribosome is the machine that builds proteins by reading the messenger RNA codon by codon. By attaching to this key location, tobramycin disrupts this reading.

This binding causes a misreading of the codons and blocks the initiation step of translation. The bacterium then assembles faulty proteins and can no longer produce the ones it needs to survive. These mistranslated proteins disturb the bacterial membrane, which explains the bactericidal effect of the molecule, unusual for an inhibitor of protein synthesis.

Tobramycin targets Gram-negative bacteria, in particular Pseudomonas aeruginosa. It is used to treat serious or deep infections: sepsis, respiratory, urinary, intra-abdominal and bone infections such as osteomyelitis, and meningitis. Its bactericidal action and its spectrum make it a resort against these difficult germs.

It comes in several forms depending on the target. The inhaled form is indicated in patients with cystic fibrosis aged 6 years and over when they are colonised by Pseudomonas aeruginosa. An ophthalmic form, as eye drops, treats eye infections.

Tobramycin is given intravenously, intramuscularly, by inhalation or topically, but never orally. The reason is the P-glycoprotein efflux pump on the brush border of the intestine, which pushes the molecule back out and makes its oral bioavailability too low to be useful. The route of administration therefore depends on the infection being targeted and on the patient’s condition.

Its half-life is about 2 hours in adults, and lengthens to 4.5 to 8.7 hours in the newborn, whose kidneys are still immature. To adjust the dose, serum concentrations are measured, at peaks and troughs. Prolonged concentrations above 12 mcg/mL are avoided, and a trough above 2 mcg/mL may signal accumulation in the tissues. Regular dosing and adherence to the prescribed schedule determine the efficacy and safety of the treatment.

Two effects dominate monitoring. Nephrotoxicity, damage to the kidney, occurs in 10 to 25 % of patients treated with aminoglycosides; it is generally reversible, and its risk factors include dehydration, pregnancy, liver failure and the concurrent use of NSAIDs or diuretics. Ototoxicity, damage to the inner ear, is reported in 2 to 45 % of adults; it is dose-dependent and can affect the vestibular or cochlear apparatus. Cochlear damage, which concerns hearing, is irreversible, whereas vestibular damage can recover; tobramycin mainly causes the latter.

The FDA boxed warnings concern these two risks, ototoxicity and nephrotoxicity, as well as a third, neuromuscular blockade. The eye drop form mainly exposes the patient to local effects: watering, itching, tingling or burning, swelling of the eye, and briefly blurred vision with the ointment. Knowing these signs helps to raise them early with the doctor.

Beyond its antibacterial action, tobramycin affects the balance of minerals. Aminoglycoside antibiotics are among the drugs that can cause hypomagnesemia, that is, a loss of magnesium. During treatment, serum magnesium can therefore fall, which is why it is measured regularly.

Laboratory monitoring is not limited to magnesium: serum sodium, calcium and magnesium are checked during treatment. Magnesium and calcium are thus the two minerals for which food offers the simplest lever to rebuild reserves, in support of medical monitoring.

Some combinations increase the risks and should be avoided. Powerful loop diuretics, such as furosemide and ethacrynic acid, increase the risk of ototoxicity. Other nephrotoxic and neurotoxic drugs must likewise be set aside: other aminoglycosides, vancomycin, colistin, polymyxin B and cisplatin. Tobramycin is also contraindicated in case of hypersensitivity to itself or to another aminoglycoside.

Particular caution is required in case of kidney failure, neuromuscular disease such as myasthenia, Parkinson’s disease, and dehydration. Since the molecule is excreted mainly by the kidneys, monitoring of renal function is a pillar of follow-up, alongside regular serum measurements. Treatment is always carried out with the doctor, and is not stopped on one’s own initiative.