b.  Aminoglycoside Dosing and Monitoring

 

Ideal/Adjusted Body Weight Calculator         Creatinine Clearance Calculator  

Aminoglycoside antibiotics have limited tissue distribution and are renally cleared.  For underweight patients, use total body weight to calculate dose. For patients whose weight is 1-1.2 times their ideal body weight, use ideal body weight. For patients weighing >1.2 times ideal body weight, use adjusted body weight.   Careful selection of empiric dosing regimens and serum level monitoring when warranted are needed to ensure safety and efficacy of these drugs.  Patients anticipated to receive aminoglycosides for >2 weeks should be considered for audiometry.  There are several approaches to dosing aminoglycosides (does not cover special populations such as cystic fibrosis, pregnancy, or post-partum):

 

HIGH-DOSE, EXTENDED-INTERVAL DOSING (“ONCE-DAILY”)

-This approach exploits the concentration-dependent killing and post-antibiotic effect of aminoglycosides, and is generally as efficacious as traditional dosing with possibly less toxicity.  However, this strategy has not been adequately studied in all populations.

 

Inclusion criteria:

Patients with suspected or documented Gram-negative infections

 

Exclusion criteria:

Creatinine clearance <60 ml/min

Abnormal body composition (e.g. morbid obesity, burns)

Meningitis, endocarditis, or osteomyelitis

 

Dosing:

CrCl

Dose (gentamicin, tobramycin)

>60 ml/min

7 mg/kg IV q24h

 

Monitoring:

·Patients with who are anticipated to receive aminoglycosides for 3 days should have levels monitored.

·For patients who require monitoring, draw a single random level between 6 and 14 hours. Use the nomogram below to determine whether continued once-daily dosing is appropriate.

 

 

MULTIPLE-DAILY DOSING (“TRADITIONAL”)

-This approach should be used for the treatment of Gram-negative infections when “once-daily” dosing is not appropriate.

 

Inclusion criteria:

Patients with suspected or documented Gram-negative infections not eligible for “once-daily” dosing.

Patients with documented serious Gram-negative infections (e.g. Pseudomonas) receiving aminoglycosides in combination with a b-lactam agent.

 

Exclusion criteria:

Patients using aminoglycosides for synergistic activity against Gram-positive organisms (see below).

 

Dosing:

CrCl

Dose (gentamicin, tobramycin)

>60 ml/min

1.5-1.7 mg/kg/dose IV q8h

40-60 ml/min

1.2 - 1.5 mg/kg/dose IV q12h

20-40 ml/min

1.2-1.5 mg/kg/dose IV q12-24h

<20 ml/min

2 mg/kg loading dose

·A 2mg/kg loading dose may be administered in patients with severe infections.

·Contact pharmacy for maintenance doses for patients with CrCl <20 ml/min or on hemodialysis.

 

Monitoring:

·Patients with who are anticipated to receive aminoglycosides for 7 days should have levels monitored.

·For patients who require monitoring, draw peak and trough level.

·Peak levels should be drawn 30 minutes after the end of the infusion.  Trough levels should be drawn immediately before the next dose.  Levels should be drawn around the 3rd or 4th dose to allow the drug to reach steady-state.

 

Desired level (gentamicin, tobramycin)

Trough

<2 mcg/ml (<1 mcg/ml optimal)

Peak

5-8 mcg/ml

 

 

GRAM-POSITIVE COMBINATION DOSING (“SYNERGY”)

-Patients with serious Gram-positive infections may receive aminoglycosides in combination to achieve synergistic killing.

 

Inclusion criteria:

Patients with serious Gram-positive infection (e.g. endocarditis) being treated with a b-lactam or vancomycin.

 

Exclusion criteria

Patients with documented serious Gram-negative infections (e.g. Pseudomonas) receiving aminoglycosides in combination with a b-lactam agent. (see above)

 

Dosing:

CrCl

Dose (gentamicin)

>60 ml/min

1 mg/kg/dose IV q8h

·Contact pharmacy for maintenance doses for patients with CrCl <60 ml/min or hemodialysis.

 

Monitoring:

·Patients with who are anticipated to receive aminoglycosides for 7 days should have levels monitored.

·For patients who require monitoring, draw peak and trough level.

·Peak levels should be drawn 30 minutes after the end of the infusion.  Trough levels should be drawn immediately before the next dose.  Levels should be drawn around the 3rd or 4th dose to allow the drug to reach steady-state.

 

Desired level (gentamicin)

Trough

1 mg/ml

Peak

3 mcg/ml