Background

Amikacins are a semisynthetic derivative of kanamycin. It shows high efficacy to the gram-negative bacteria like Mycobacteria and Nocardia. It binds to the 30s subunit of ribosome of the organism and inhibits the synthesis of protein. It has high and consistent serum concentrations like various aminoglycosides. But it has a limited therapeutic range. 99 % is eliminated unaltered from the kidneys where the glomerular filtration occurs. Nephrotoxicity and ototoxicity are the serious concern. Serum amikacin level is used to determine therapy to make sure adequate dose not the excessive doses.

Indications/Applications

Serum amikacin level is measured in the cases who are taking the amikacin-based therapy. It is indicated in the patients who are taking the aminoglycoside therapy for the long time, who has damaged renal function, and elder patients. It is important to check the peak level to make sure that a normal serum amikacin level is obtained to avoid underdosing in patients in critical conditions, and particularly in patients with high distribution volumes.

Seum amikacin level is measured in patients when the renal function changes and the dosage of drug is changed when patients develop the toxicity symptoms. It is also indicated when patients are taking other medication that are known to increase the toxicity or has other conditions that are known to affect the excretion of aminoglycosides.

Serum amikacin level is not measured when patients are taking aminoglycosides for less than 5 to 7 days or has a moderate illness or has no indication of risk for drug toxicity.

Clinical Significance:

To prevent falsely low or high results, it is necessary to note down the particular time at which the aminoglycosides dosage was given and the time the samples are taken.

As per the study of Goutelle et al, patients who are going for the emergency surgery about 74 % who have intra-abdominal infection have 21.5 mg/kg amikacin dose or less were linked to the failure to attain the amikacin peak level of 64 mg/L to reach the study goal. As per the research and guidelines, amikacin dosage of 15 to 20 mg/kg/24 hour for intra-abdominal infections are not ideal for emergency surgery. The study found that to achieve the expected peak level of amikacin, a fixed dosage of 2500 mg is given, or a dosage of 30 mg/kg of corrected or total body weight is given.

Reference Range

Peak serum levels indicate the effectiveness of the drug. Serum trough levels indicates the toxicity.

Therapeutic levels

Like any other aminoglycosides, amikacin can be administrated as a single daily dosage (pulse) or as many daily dosages (conventional).

Normal therapeutic levels:

Interpretation

Peak serum level

Peak serum level is correlated with the bactericidal effect or effectiveness of the drug. This is associated with the concentration dependent death of aminoglycosides and post antibiotic effects.

When the aminoglycosides concentration is on peak and greater than the minimum inhibitory concentration (MIC), they work more effectively. It is more effective if the peak level ratio to MIC is 10 or more than that.

It has been found that for gram-negative infections, a peak-to-MIC ratio of 8 to 10 and greater than 10 associated to relative chances of clinical response of 6.49% and 8.41%, respectively. In gram-negative pneumonia, a peak-to MIC ratio is more than 10 and linked to 90 % fever remission rate after 48 hours. High dosage and closer evaluation are necessary in critical patients with severe gram-negative infections to achieve the peak-to-MIC ratio of more than 8 to 10. Peak level greater than 35 to 40 mcg/mL ratio for the longer period of time lead to the nephrotoxicity.

Trough serum level

Trough serum level correlates to the toxicity.

Trough level of amikacin which is greater than 10 mcg/mL is associated with the symptoms of nephrotoxicity and ototoxicity. The ideal trough level for standard dosing is below 8 mcg/mL. Adjustment of the dosage based pharmacokinetic of drugs and maintain the trough level less than 1 mcg/mL reduced the chances of kidney damage associated with the amikacin.

Trough serum level of amikacin is more sensitive than the serum creatinine to indicate the nephrotoxicity. Trough serum levels increase before the serum creatinine level increase.

Collection And Panels

Sample type: Blood or serum

Sample collection container: Red top tube

Sample collection method: Venipuncture

Sample collection instructions: Spin down the samples within 2 hours of the blood drawn.

Unacceptable samples: Samples which are hemolyzed or lipemia are not acceptable.

Sample stability instructions: Samples are stable for up to 2 hour at normal room temperature and 14 days in refrigerator or in frozen condition.

Assay used: Enzyme multiplied immunoassay technique (EMIT)

Sample collection time: Samples for serum trough level are collected before the third dose, and for serum peak level, they are collected after the third dose. Samples for peak levels are collected after 1 hour of the start of the intravenous infusion and after 60 to 90 minutes of intramuscular infusion. The samples for serum peak levels are collected after the first dose in critical patients with severe gram-negative infection. Samples for serum trough levels are collected within 30 minutes of the next dosage. Serum trough level must be checked before the next dialysis in the hemodialysis patient.

Immunoassay technique is preferable method to assess the serum amikacin level. It produces more comparative results with other techniques like microbiological assay and gas chromatography. The normal level is affected by the other aminoglycosides administration.

References

https://www.ncbi.nlm.nih.gov/books/NBK430908/