Staphylococcus spp., Streptococci spp., E Coli, Enterobacter, Serratia spp., Proteus spp., Pseudomonas aeruginosa, Citrobacter, Aeromonas hydrophilia, Klebsiella spp.
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)
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.
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
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.
AKTob®/Akorn; TOBI®/Pathogenesis; Tobrex®/Alcon; Tobramycin (Various manufacturers worldwide)