Gentamicin

Pseudomonas aeruginosa, E. coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp., Providencia spp., Acinetobacter spp., and Citrobacter spp., Morganella spp., S. aureus., Staphylococcus spp., Viridans stertococci, Enterococcus spp., Mycobacterium spp.

Mechanism of Action:

Inhibition of protein biosynthesis by irreversible binding of the aminoglycoside to the bacterial ribosome 30S subunit.

Pharmacodynamics:

Aminoglycosides correlate most with peak/MIC ratio

Pharmacokinetics:

Half-life: 2.1 hours; Volume of distribution: 0.27 L/kg; Total Clearance: 1.35 mL/min/kg; Table 1

Adverse Effects:

Otic: Ototoxicity – Auditory and/or vestibular

Kidney: Nephrotoxicity

Neuromuscular: Cause or exacerbate neuromuscular blockade, myasthenia gravis (both rarely)

Dosage:

Cream, topical, as sulfate: 0.1% (15 g, 30 g)

Injection, solution: 10 mg/mL, 40 mg/mL

Injection, solution (preservative free – for intrathecal administration): 10 mg/mL

Ointment, ophthalmic, as sulfate: 0.3% (3.5 g)

Ointment, topical, as sulfate: 0.1% (15 g, 30 g)

Solution, ophthalmic, as sulfate: 0.3% (5 mL, 15 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)

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.

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.

Contraindications/Warnings/Precautions:

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

Drug Interactions

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

Pregnancy:

Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements:

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 gentamicin 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 (< 1mcg/mL per American Heart Association guidelines for synergy treatment in endocarditis)

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.

Brand names/Manufacturer:

Genoptic®/Allergan; Gentak®/Akorn; Garamycin®/Shering; Gentamicin (Various generic manufacturers worldwide)