Peak serum levels correspond to efficacy of the drug. Trough serum levels correspond to toxicity.
Amikacin, like other aminoglycosides, can be given in multiple daily doses (conventional) or once-daily dose (pulse).
Table 1. Normal Therapeutic levels (Open Table in a new window)
|Indication||Peak Serum Levels/Efficacy||Trough Serum Levels/Toxicity|
|Multiple daily dose regimen|
|Nonbacteremic gram-negative infection (UTI, synergism with beta-lactams)||15-30 mcg/mL||1-4 mcg/mL|
|Serious gram-negative infection (bacteremia, pneumonia, sepsis)||25-40 mcg/mL||4-8 mcg/mL|
|Once daily dosing|
|Critically ill patients with gram-negative infection||55-64 mcg/mL||< 1 mcg/mL|
Peak serum levels correspond to the efficacy or bactericidal effect of the drug. This is due to the concentration-dependent killing and postantibiotic effect exhibited by aminoglycosides.
Aminoglycosides work more effectively when the peak concentration exceeds the minimum inhibitory concentration (MIC) of the target organism. It is best achieved if the ratio of peak level to MIC is 10 or more. 
A peak-to-MIC ratio of 8-10 and more than 10 have been shown to provide a 6.49% and 8.41% relative odds of clinical response in gram-negative infections, respectively.  A peak-to-MIC ratio of more than 10 was associated with 90% fever resolution rate at 48 hours in gram-negative pneumonia.  In critically ill patients with serious gram-negative infections, higher loading doses and closer monitoring of amikacin levels are required to achieve a peak-to-MIC ratio of greater than 8-10.  Peak levels of more than 35-40 mcg/mL for prolonged periods correlate with incidence of nephrotoxicity. [1, 2, 8]
Trough levels generally correspond to toxicity.
Amikacin trough levels of more than 10 mcg/mL have been associated with significant ototoxicity and nephrotoxicity.  Desired trough levels for conventional dosing are less than 8 mcg/mL.  In one study, pharmacokinetic dosing with maintenance of trough levels below 1 mcg/mL significantly reduced the incidence of nephropathy with amikacin. 
Trough serum levels are more sensitive indicators of nephrotoxicity that serum creatinine. Increase in serum trough levels can precede an increased serum creatinine by several days. 
Collection and Panels
Collection and panel details are as follows:
Specimen - Blood/serum
Collection method - Routine venipuncture
Collection time - Serum trough and peak levels are collected before and after the third dose, respectively. Serum samples for peak concentrations are collected 60 minutes after the start of intravenous infusion and 60–90 minutes after intramuscular injection. In critically-ill patients, the peak serum levels are drawn after the first dose. Samples for trough concentrations are collected within 30 min of the next dose. [5, 9] In hemodialysis patients, trough levels should be checked prior to the next scheduled dialysis.
Collection Instruction - Spin down within 2 hours of blood draw.
Specimen rejection - Gross hemolysis, lipemia
Specimen stability information - Stable for 2 hours at room temperature and for 14 days when refrigerated or frozen
Commercial assay - Enzyme multiplied immunoassay technique (EMIT)
Immunoassay techniques are the preferred methods of measurement of serum amikacin levels and produce comparable results with other testing techniques such as gas chromatography and microbiological assays.  Levels may be affected by concomitant administration of other aminoglycosides. 
Amikacin is a semisynthetic analogue of kanamycin and is highly active against most gram-negative bacteria, Nocardia, and Mycobacteria. It acts by binding to the 30S ribosomal subunit of the organism, thereby inhibiting protein synthesis. It achieves high, sustained serum concentrations but, like other aminoglycosides, has a narrow therapeutic index. Ninety-nine percent is excreted unchanged in the kidneys, where the drug undergoes glomerular filtration. Ototoxicity and nephrotoxicity are of significant concern. Serum amikacin levels are used to guide therapy to ensure adequate but not excessive levels. 
Measurement of serum amikacin levels is indicated in most cases in which amikacin is used for therapy, especially in patients whom prolonged aminoglycoside therapy is expected and those with compromised renal function and the elderly. It is particularly important to monitor the peak level in the critically-ill patients to ensure adequate serum levels are achieved and to prevent underdosing, especially in patients who have large volume of distribution. 
Monitoring of serum levels is indicated when changes in renal function occur and the drug dose is changed if the patient exhibits symptoms of toxicity, has co-existing processes known to alter aminoglycoside excretion, or is concomitantly receiving drugs known to potentiate toxicity. [1, 2]
Monitoring is not recommended for aminoglycoside use for less than 5-7 days or for treatment of mild infections in patients with no risk factors for drug toxicity. 
It is important to document the exact time at which aminoglycoside dose was administered and the time at which samples were obtained to avoid falsely high or low values.