Sarah Tierney, Pharm.D. and Jonathan Klein, MD
Peer Review Status: Internally Peer Reviewed 12/20/12

Gentamicin peak and trough guidelines1
  Goals When to draw level
Initial trough 0.3-1.0 Just prior to 2nd dose
Late troughs 0.3-1.0 Obtain on day 7 if continuing therapy >7 days and then weekly thereafter. Draw earlier and/or more frequent if there is decreased urine output or other changes in renal function.
Peaks 5-12 IV: 30 minutes after the end of the infusion

Gentamicin is a concentration-dependent, bactericidal antibiotic used for the treatment of gram-negative organisms including Pseudomonas, Escherichia coli, Proteus, and Serratia.  It is also used in combination with ampicillin for treatment of gram-positive group B Streptococcus species and Listeria monocytogenes.  The rationale for using the extended-interval dosing protocol for gentamicin is based on the concentration-dependent bactericidal activity of aminoglycosides, the extended post-antibiotic effect, and the possibility of reduced nephrotoxicity and ototoxicity.1,2 

Bactericidal Effects

The current gentamicin dosing protocol (Neofax) achieves an early and high peak gentamicin plasma concentration for optimal bactericidal effect about 94% of the time.3,4  In vitro, aminoglycosides eradicate bacteria at a rate proportional to the peak concentration attained.  Therefore, a high peak level results in a more rapid and efficient bactericidal effect against susceptible organisms.  In addition, aminoglycosides have an extended post-antibiotic effect (PAE) which is defined as the time period that surviving bacteria, following exposure to an antibiotic, cannot metabolize or multiply even though extracellular antibiotic is no longer present.  The duration of PAE is approximately 8-12 hours in the immunocompromised patient.1

Potential Toxicity

The uptake of aminoglycosides occurs in the renal tubular cells and is a saturable process; therefore, larger doses would not be expected to be any more nephrotoxic than smaller doses.  Both animal and human studies have shown that the concentration in the renal cortex is significantly lower when administered as a single daily dose than when divided and administered more frequently.  Animal data supports an accumulation threshold in the organ of Corti as well, so there is the potential for less ototoxicity.1,5  Although neonates are believed to experience a lower risk for ototoxicity and nephrotoxicity than adults;5 sustained elevated peak (>12 mg/L) or trough (>2 mg/L) concentrations may cause these toxicities in neonates.3

References

  1. Behm-Dillon, DM.  Appropriate Use of Antibiotics: The Antibiotic Advisory Subcommittee and You.  UIHC P&T News; Jan/Feb 2000.  Online www.healthcare.uiowa.edu/pharmacy/PTNews/2000/0102PTNews.html.  Accessed 10/28/2009. 
  2. Gentamicin.  Pediatric Dosage Handbook.  15 Edition. 2008: 819-823.
  3. Hoff DS, et al.  Pharmacokinetic Outcomes of a Simplified, Weight-Based, Extended-Interval Gentamicin Dosing Protocol in Critically Ill Neonates.  Pharmacotherapy 2009; 29 (11): 1297-1305.
  4. Gentamicin.  Neofax.  2008: 42-43.
  5. Haughey DB, et al.  Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates.  J Pediatr 1980; 96:325-30.