b.  Aminoglycoside Dosing and Monitoring

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Aminoglycoside antibiotics have limited tissue distribution and are renally cleared.  Dosing is based on a patient’s ideal or adjusted body weight and renal function.  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):

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:

·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 3^rd or 4^th dose to allow the drug to reach steady-state.

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:

Monitoring:

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

·For patients who require monitoring, draw a single trough level.  Peak levels are not useful.

·Trough level should be drawn <30 minutes before next dose.  It is not necessary to wait until before the third dose to draw this level.

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:

·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 3^rd or 4^th dose to allow the drug to reach steady-state.