Clinical data | |
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Trade names | Nebcin, Tobrex, Tobi, others |
Other names | 47663, SPRC-AB01 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682660 |
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Pregnancy category | |
Routes of administration | Intravenous, intramuscular, inhalation, ophthalmic |
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Pharmacokinetic data | |
Protein binding | Not bound [7] |
Metabolism | Not metabolized |
Elimination half-life | 2–3 hrs |
Excretion | Exclusively via kidneys |
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ChEBI | |
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PDB ligand | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.046.642 |
Chemical and physical data | |
Formula | C18H37N5O9 |
Molar mass | 467.520 g·mol−1 |
3D model (JSmol) | |
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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 . [8]
It was patented in 1965, and approved for medical use in 1974. [9] It is on the World Health Organization's List of Essential Medicines. [10] In 2021, it was the 299th most commonly prescribed medication in the United States, with more than 500,000 prescriptions. [11] [12]
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. 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. [13] [14]
Tobramycin eye drops (with or without dexamethasone) are indicated in the treatment of superficial infections of the eye, such as bacterial conjunctivitis. [15] [16] [17] [18]
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. [19] [5]
Tobramycin has a narrow spectrum of activity and is active against Gram-positive Staphylococcus aureus and various Gram-negative bacteria. [19] Clinically, tobramycin is frequently used to eliminate Pseudomonas aeruginosa in cystic fibrosis patients. [ citation needed ]The following represents the minimum inhibitory concentration (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 [unpublished][ clarification needed ].[ medical citation needed ]
Tobramycin is contraindicated in people with hypersensitivity against aminoglycoside antibiotics. [21] The Infusion is also contraindicated in people with myasthenia gravis. [7]
Like other aminoglycosides, a major side effect for tobramycin is ototoxicity or a loss of equilibrioception, or both in genetically susceptible individuals. [22] Other side effects include nephrotoxicity, neuromuscular toxicity, and hypersensitivity reactions. [23] Nephrotoxicity can be particularly worrisome when multiple doses accumulate over the course of a treatment [24] 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. [25] 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.[ citation needed ]
Muscle relaxants and diethylether can add to the neuromuscular blocking effects of tobramycin. [7]
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. [7]
Combining tobramycin with betalactam 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. [7]
Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing formation of the 70S complex. [26] As a result, mRNA cannot be translated into protein, and cell death ensues. [27] Tobramycin also binds to RNA-aptamers, [28] 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.[ 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. [29]
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. [7]
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. [7]
Tobramycin was patented in 1965, and approved for medical use in 1974. [9]
Tobramycin in the form of eye drops is available in Bulgaria, Hungary, the United States, and Canada by prescription only, whereas in the other countries it may be available over the counter.[ citation needed ]
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.[ citation needed ]
In Egypt, tobramycin (in the form of eye drops) is sold under the brand Tobrin, produced by EIPICo.[ citation needed ]
Tobramycin is on the World Health Organization's List of Essential Medicines. [10]
In 2021, tobramycin was the 299th most commonly prescribed medication in the United States, with more than 500,000 prescriptions. [11]
Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever. Its use by mouth or by injection is only recommended when safer antibiotics cannot be used. Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.
Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.
Carbenicillin is a bactericidal antibiotic belonging to the carboxypenicillin subgroup of the penicillins. It was discovered by scientists at Beecham and marketed as Pyopen. It has Gram-negative coverage which includes Pseudomonas aeruginosa but limited Gram-positive coverage. The carboxypenicillins are susceptible to degradation by beta-lactamase enzymes, although they are more resistant than ampicillin to degradation. Carbenicillin is also more stable at lower pH than ampicillin.
Neomycin/polymyxin B/bacitracin, also known as triple antibiotic ointment, is an antibiotic medication used to reduce the risk of infections following minor skin injuries. It contains the three antibiotics neomycin, polymyxin B, and bacitracin. It is for topical use.
Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein, muscle, or eye.
Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents. A 2007 meta-analysis suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics. In response, the U.S. Food and Drug Administration (FDA) performed their own meta-analysis which found no mortality difference.
Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.
Ciprofloxacin/dexamethasone (Ciprodex) is an antibiotic/steroid combination medication. It contains the synthetic broad-spectrum antibacterial agent, ciprofloxacin hydrochloride (0.3%), combined with the anti-inflammatory corticosteroid, dexamethasone (0.1%), in a sterile, preserved suspension for otic use.
Capreomycin is an antibiotic which is given in combination with other antibiotics for the treatment of tuberculosis. Specifically it is a second line treatment used for active drug resistant tuberculosis. It is given by injection into a vein or muscle.
Apramycin is an aminoglycoside antibiotic used in veterinary medicine. It is produced by Streptomyces tenebrarius.
Polymyxin B, sold under the brand name Poly-Rx among others, is an antibiotic used to treat meningitis, pneumonia, sepsis, and urinary tract infections. While it is useful for many Gram negative infections, it is not useful for Gram positive infections. It can be given by injection into a vein, muscle, or cerebrospinal fluid or inhaled. The injectable form is generally only used if other options are not available. It is also available as the combinations bacitracin/polymyxin B and neomycin/polymyxin B/bacitracin for use on the skin.
Cefotiam is a parenteral third-generation cephalosporin antibiotic. It has broad-spectrum activity against Gram-positive and Gram-negative bacteria. As a beta-lactam, its bactericidal activity results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins.
Netilmicin (1-N-ethylsisomicin) is a semisynthetic aminoglycoside antibiotic, and a derivative of sisomicin, produced by Micromonospora inyoensis. Aminoglycoside antibiotics have the ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore only given by injection or infusion. It is only used in the treatment of serious infections particularly those resistant to gentamicin.
Tobramycin/dexamethasone, sold under the brand name Tobradex, is a fixed-dose combination medication in the form of eye drops and eye ointment, marketed by Alcon. The active ingredients are tobramycin and dexamethasone. It is prescribed for the treatment of pink eye in combination with bacterial infections.
Sisomicin, is an aminoglycoside antibiotic, isolated from the fermentation broth of Micromonospora inositola. It is a newer broad-spectrum aminoglycoside most structurally related to gentamicin.
Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic which was derived from kanamycin. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Arbekacin was originally synthesized from dibekacin in 1973 by Hamao Umezawa and collaborators. It has been registered and marketed in Japan since 1990 under the trade name Habekacin. Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.
Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections. As of 2019 it is recommended only for those in whom alternatives are not an option. It is given by injection into a vein.
Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.