Amikacin Level

Peak serum levels correspond to efficacy of the drug. Trough serum levels correspond to toxicity.

Therapeutic levels

Amikacin, like other aminoglycosides, can be given in multiple daily doses (conventional) or once-daily dose (pulse).

Opinions on normal therapeutic levels vary among different authors and are summarized below.[1, 2, 3, 4]

Table 1. Normal Therapeutic levels (Open Table in a new window)

Peak level

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.[5]

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.[5] A peak-to-MIC ratio of more than 10 was associated with 90% fever resolution rate at 48 hours in gram-negative pneumonia.[6] 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.[7] Peak levels of more than 35-40 mcg/mL for prolonged periods correlate with incidence of nephrotoxicity.[1, 2, 8]

Trough level

Trough levels generally correspond to toxicity.

Amikacin trough levels of more than 10 mcg/mL have been associated with significant ototoxicity and nephrotoxicity.[2] Desired trough levels for conventional dosing are less than 8 mcg/mL.[8] In one study, pharmacokinetic dosing with maintenance of trough levels below 1 mcg/mL significantly reduced the incidence of nephropathy with amikacin.[9]

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.[2]

Collection and panel details are as follows:

• Specimen - Blood/serum

• Container - Red-top tube

  Red-top tube.

• 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.[2] Levels may be affected by concomitant administration of other aminoglycosides.[10]

Description

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.[11]

Indications/Applications

Measurement of serum amikacin levels is indicated in most cases in which amikacin is used for therapy, especially in patients in whom prolonged aminoglycoside therapy is expected and in those with compromised renal function, as well as in 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.[3]

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.[1]

Considerations

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.

A retrospective study by Goutelle et al found that in patients undergoing emergency surgery (including 74% with intra-abdominal infection), an amikacin dose of 21.5 mg/kg or less was associated with failure to reach the study’s target amikacin peak of over 64 mg/L. The investigators state, therefore, that the guideline-recommended amikacin dose of 15-20 mg/kg/24 h for intra-abdominal infections is not optimal in emergency surgery. The report found instead that either a dose of 30 mg/kg of total or corrected body weight or a fixed dose of 2500 mg is most likely to produce the desired peak.[12]