tobramycin

Tobramycin is a broad-spectrum antibiotic belonging to the aminoglycosides class used to treat serious bacterial infections. Tobramycin is administered as intravenous or intramuscular injections for systemic infections. Tobramycin is also used in topical ophthalmic formulations and as inhalation solutions for lung infections in patients with cystic fibrosis.

Tobramycin is effective against most gram-negative bacteria and Staphylococcus aureus species of gram-positive bacteria. Gram-negative and gram-positive bacteria are structurally different, and the types are identified by whether the bacteria get dyed or not in the Gram stain lab test. Gram-negative bacteria have an additional membrane outside the cell wall that gram-positive bacteria lack.

Tobramycin works by inhibiting the synthesis of proteins that bacteria require to survive and grow. Tobramycin binds to 30S and 50S subunits in the bacterial ribosomes (cellular particles that synthesize proteins) and prevents the formation of peptide chains, which results in bacterial cell membrane damage and cell death.

Tobramycin is usually administered after performing bacterial culture and susceptibility tests. In serious life-threatening infections suspected to be from gram-negative bacteria, tobramycin may be initiated before obtaining test results, however, the decision to continue is made depending on the test results. Tobramycin is approved by the FDA for the treatment of the following infections from susceptible bacterial strains:

• Bloodstream infections (septicemia)
• Lower respiratory tract infections (pneumonia)
• Serious central nervous system infections (meningitis)
• Intra-abdominal infections including peritonitis
• Skin and skin structure infections
• Bone infections
• Complicated and recurrent urinary tract infections

Off-label uses include:

• Peritonitis treatment in peritoneal dialysis patients
• Plague (Yersinia pestis) treatment

Organisms susceptible to tobramycin include:

Gram-positive bacteria:

• Staphylococcus aureus

Gram-negative bacteria:

• Citrobacter species
• Enterobacter species
• Escherichia coli
• Klebsiella species
• Morganella morganii
• Pseudomonas aeruginosa
• Proteus mirabilis
• Proteus vulgaris
• Providencia species
• Serratia species

• Do not use tobramycin to treat patients with a history of hypersensitivity or toxic reactions to any aminoglycoside antibiotic.
• Tobramycin is neurotoxic, particularly to the ear and vestibular system (ototoxicity) and may affect hearing and balance. Patients with preexisting kidney damage or normal patients on high and/or prolonged therapy are at higher risk. Monitor patients for symptoms of ototoxicity and adjust dosage or discontinue drug accordingly.
• Tobramycin is potentially toxic to kidneys (nephrotoxic). The risk of nephrotoxicity is higher in patients undergoing high dosage prolonged therapy and in patients with impaired renal function, including elderly patients. Monitor renal function closely.
• Increased incidence of nephrotoxicity is reported with concomitant use of cephalosporin class of antibiotics with aminoglycosides.
• Aminoglycosides including tobramycin may be inactivated by beta-lactam antibiotics such as penicillin and cephalosporins in patients with severe renal impairment.
• Use with caution in premature infants and newborn babies because the kidneys are not fully developed, which can prolong the serum half-life of the drug.
• Neuromuscular blockade and respiratory paralysis have been reported following the use of aminoglycosides, especially when given soon after anesthesia or muscle relaxants. If blockage occurs, calcium salts may reverse these effects, but mechanical respiratory assistance may be necessary.
• Avoid concurrent use with other neurotoxic or nephrotoxic drugs including other aminoglycosides.
• Cumulative listing of drugs to avoid from all aminoglycosides include amphotericin B, bacitracin, cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin.
• Avoid use of potent diuretics such as ethacrynic acid and furosemide because they increase the risk of ototoxicity. When administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
• Monitor serum calcium, sodium and magnesium levels during tobramycin therapy.
• Discontinue tobramycin and initiate appropriate therapy if the patient develops allergic reactions. Although rare, serious, sometimes fatal, allergic reactions have been reported, including anaphylaxis, and severe skin reactions such as exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome.
• Tobramycin can cause Clostridium difficile associated diarrhea (CDAD) that may range from mild diarrhea to fatal colon inflammation (colitis).
• Consider possibility of clostridium difficile in all patients who present with diarrhea following antibiotic use; in case of suspected or confirmed CDAD:
  • All antibiotics excluding those directed against C. difficile must be stopped
  • Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted
• Patients with extensive burns or cystic fibrosis may have reduced concentration of tobramycin. Adjust dosage accordingly.
• Aminoglycosides including tobramycin should be used with caution in patients with muscular disorders, such as myasthenia gravis or parkinsonism, since these drugs may aggravate muscle weakness.
• Aminoglycosides can cause fetal harm if administered during pregnancy. If pregnancy takes place during therapy, patient should be apprised of potential hazard to the fetus.
• Aminoglycosides have not been approved for intraocular and/or subconjunctival use, may damage the macula in the retina.
• Tobramycin therapy may result in overgrowth of nonsusceptible organisms which should be treated appropriately.

Common side effects of tobramycin include:

• Nephrotoxicity with signs and symptoms including:
  • Elevated blood urea nitrogen (BUN) levels
  • Increase in serum creatinine
  • Casts in urine (cylindruria)
  • Reduced urination (oliguria)
  • Excessive protein in urine (proteinuria)
• Neurotoxicity with symptoms that may include:
  • Hearing loss
  • Ringing in the ears (tinnitus)
  • Vertigo
  • Dizziness
  • Headache
  • Lethargy
  • Confusion
  • Disorientation
• Nausea
• Vomiting
• Diarrhea
• Skin reactions such as:
  • Rash
  • Hives (urticaria)
  • Itching (pruritus)
• Pain at injection site
• Fever
• Elevation of liver enzymes AST and ALT
• Increase in serum bilirubin
• Decrease in electrolytes, calcium, magnesium, sodium and potassium
• Increase in lactate dehydrogenase (LDH) enzyme
• Increase in non-protein nitrogen (NPN) compounds in blood
• Blood disorders including:
  • Low red blood cell count (anemia)
  • Low count of granulocyte immune cells (granulocytopenia)
  • Increase/decrease in leukocyte immune cells (leukocytosis/leukopenia)
  • High levels of eosinophil immune cells (eosinophilia)
  • Low platelet levels (thrombocytopenia)
• Clostridium difficile associated diarrhea (CDAD)

Rare and severe side effects of tobramycin include:

• Serious allergic reaction (anaphylaxis)
• Severe skin reactions such as:
  • Erythema multiforme
  • Exfoliative dermatitis
  • Toxic epidermal necrolysis
  • Stevens-Johnson syndrome

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 10 mg/ml
• 40 mg/ml

Solution reconstituted

• 1.2 g

Adult:

Bacterial infections

• 3-6 mg/kg/day intravenously/intramuscularly (IV/IM) divided every 8 hours OR
• 4-7 mg/kg/dose IV/IM each day

Renal Impairment

• Creatinine Clearance over 60 mL/min: every 8 hours
• Creatinine Clearance 40-60 mL/min: every 12 hours
• Creatinine Clearance 20-40 mL/min: every 24 hours
• Creatinine Clearance 10-20 mL/min: every 48 hours
• Creatinine Clearance under 10 mL/min: every 72 hours
• Following dialysis in end stage renal disease (ESRD)

Pediatric

Cystic Fibrosis

• IV/IM: 2.5-3.3 mg/kg every 6-8 hours

Neonates

Less than 30 weeks gestation

• Infants less than 28 days old: 2.5 mg/kg IV/IM every day
• Infants 28 days or older: 3 mg/kg IV/IM every day

30-36 week gestation

• Infants less than 14 days old: 3 mg/kg IV/IM every day
• Infants 14 days or older: 5 mg/kg/day IV/IM divided every 12 hours

Over 37 week gestation

• Infants less than 7 days old: 5 mg/kg/day IV/IM divided every 12 hours
• Infants 7 days or older: 7.5 mg/kg/day IV/IM divided every 8 hours

Bacterial infections

• Children under 5 years old: 2.5 mg/kg/dose IV/IM every 8 hours
• Children 5 years and older: 2-2.5 mg/kg/dose IV/IM every 8 hours
• Hemodialysis: 1.25-1.75 mg/kg/dose post dialysis

Monitor

Adult and pediatric:

• Peak and trough concentrations, renal and auditory function
• Life-threatening infection: 8-10 mcg/mL
• Serious infection: 6-8 mcg/mL
• Urinary Tract Infections: 4-6 mcg/mL
• Synergy for infections caused by gram-positive organisms: 3-5 mcg/mL

• Oral ingestion of tobramycin is unlikely to cause any serious effects because aminoglycosides are poorly absorbed in the gastrointestinal tract.
• Tobramycin injections are administered in a clinical setting and overdose may result with prolonged treatment and/or high dosages, particularly in patients with impaired renal function.
• Tobramycin overdose can result in nephrotoxicity and ototoxicity. Symptoms include kidney injury, dizziness, vertigo, tinnitus, and hearing loss. The severity of symptoms depends on the patient’s age, renal function, hydration state, and concurrent administration of other drugs with similar toxicities.
• Neurotoxicity from tobramycin can lead to neuromuscular blockade and respiratory paralysis/failure, especially when given soon after anesthesia or muscle relaxants.
• Overdose in patients with normal renal function may require only adequate hydration and monitoring. Hemodialysis may be beneficial for patients with renal impairment.
• Treatment of patients with respiratory paralysis or failure will require immediate establishment and maintenance of open airway with ventilation, oxygenation and resuscitative measures if necessary.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Tobramycin has no known severe interactions with other drugs.
• Tobramycin has serious interactions with at least 25 different drugs.
• Tobramycin has moderate interactions with at least 66 different drugs.
• Tobramycin has mild interactions with at least 72 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Tobramycin can cause fetal harm if administered during pregnancy. There are reports of irreversible bilateral congenital deafness with maternal use of streptomycin, another aminoglycoside. Although serious side effects are not reported with other aminoglycosides, use tobramycin with caution during pregnancy only if maternal benefits outweigh potential risks to the fetus.
• Tobramycin is excreted in breast milk. Aminoglycosides have poor oral bioavailability and may be used with caution in nursing mothers after considering the mother’s clinical need and the potential risks to the breastfed infant. All antibiotics alter gut flora and the breastfed infant should be monitored for loose or bloody stools, thrush and diaper rash.

• Diarrhea is a common problem with antibiotic treatments which should resolve with the completion of the therapy. Symptoms can develop even up to two months after the last dose of antibiotic.
• Contact your physician as soon as possible if you have watery or bloody stools, with or without stomach cramps and fever.