Staphylococcus spp., Streptococci spp., E Coli, Enterobacter, Serratia spp., Proteus spp., Pseudomonas aeruginosa, Citrobacter, Aeromonas hydrophilia, Klebsiella spp.
Mechanism of Action:
Inhibition of protein biosynthesis by irreversible binding of the aminoglycoside to the bacterial ribosome 30S subunit.
Aminoglycosides correlate most with peak/MIC ratio
Half-life: 1.8 ± 0.23 hours; Volume of distribution: 0.297 ± 0.64 L/kg; Table 1
Otic: Ototoxicity – Auditory and/or vestibular
Neuromuscular: Cause or exacerbate neuromuscular blockade, myasthenia gravis (both rarely)
Injection, solution: 10 mg/mL; 40 mg/mL
Ointment, ophthalmic: 0.3% (3.5 g)
Solution for nebulization (TOBI®): 60 mg/mL (5 mL)
Solution, ophthalmic: 0.3% (5 mL)
Dosing in adults:
Individualization is critical because of the low therapeutic index
I.V.: Traditional dosing in Gram negative infection: 1.7-2mg/kg IV q8h
Alternatively: 7mg/kg OR 5mg/kg frequency per nomogram (once daily/extended interval dosing in this agent Figure 6 for 7mg/kg nomogram) Note: nomogram for 5mg/kg dosing not shown
Traditional dosing for Gram positive synergy: 1mg/kg IV q8h (note: extended interval dosing not recommended in this situation) Note: Can NOT use tobramycin for Gram-positive synergy in Enterococcus spp. – in this situation use gentamicin
Topical: Eczematoid dermatitis or Impetigo: Apply small amount of cream/ointment to affected area q8h OR q6h
Opthalmic: Ointment: Apply a small ribbon to the affected eye q12h OR q8h
Solution: One to two drops into the affected eye every 4 hours.
Pulmonary infections: Inhalation:
Standard aerosolized tobramycin: 60-80 mg 3 times/day
High-dose regimen (TOBI™): 300 mg every 12 hours (do not administer doses <6 hours apart); administer in repeated cycles of 28 days on drug followed by 28 days off drug
Disease state based dosing:
Renal failures (note: These are general guidelines, but should not substitute for patient specific data – frequency data below based on traditional dosing only):
Clcr 60 mL/minute: Administer every 8 hours.
Clcr 40-60 mL/minute: Administer every 12 hours.
Clcr 20-40 mL/minute: Administer every 24 hours.
Clcr 10-20 mL/minute: Administer every 48 hours.
Clcr<10 mL/minute: Administer every 72 hours.
Hemodialysis effects: Dialyzable; removal by hemodialysis: 30% removal of aminoglycosides occurs during 4 hours of HD. Administer dose after dialysis and follow serum levels.
Warnings: Aminoglycosides penetrate poorly into non-lean muscle mass. Use an adjusted body weight for patients > 120% their ideal body weight
Precautions should be taken in patients with:
Preexisting renal, vestibular, or auditory impairment; Patients with depressed neuromuscular transmission (eg, myasthenia gravis); Risk factors for the development of aminoglycoside toxicity include the following: concomitant administration potentially neurotoxic or nephrotoxic drugs, age, and dehydration; Concomitant use with potent diuretics (eg, ethacrynic acid or furosemide); Local irrigation or application may lead to significant absorption
Cidofovir: Increased risk for nephrotoxicity
Colistin: Increased risk for nephrotoxicity, respiratory depression
Cyclosporine: Nephrotoxicity (decreased renal function, decreased fractional sodium excretion, and a decline in diuresis)
Tacrolimus: Increased risk for nephrotoxicity
Vancomycin: Increased risk of nephrotoxicity
Category D: Risk established, but benefits may outweigh risk.
Urinalysis, urine output, BUN, serum creatinine; hearing should be tested before, during, and after treatment; particularly in those at risk for ototoxicity or who will be receiving prolonged therapy (>2 weeks). Peak serum levels of tobramcyin in traditional dosing are:
Serious infections: 6-8 mcg/mL (SI: 12-17 mg/L)
Life-threatening infections: 8-10 mcg/mL (SI: 17-21 mg/L)
Urinary tract infections: 4-6 mcg/mL (SI: 7-12 mg/L)
Synergy against gram-positive organisms: 3-5 mcg/mL
Trough levels in traditional dosing are typically: < 2 mcg/mL
Pretreatment audiograms should be undertaken and repeated throughout therapy if the drug is administered for periods greater than 5 days. Particularly in patients with renal dysfunction.
Inhalation: Serum levels are ~1 mcg/mL one hour following a 300 mg dose in patients with normal renal function.
Brand names/Manufacturer: AKTob®/Akorn; TOBI®/Pathogenesis; Tobrex®/Alcon; Tobramycin (Various manufacturers worldwide)