Amikacin Level
No Results
No Results
processing….
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).
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)
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. [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 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
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]
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]
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. [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]
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.
McCormack J.P, Jewesson P.J. A critical reevaluation of the “Therapeutic range” of aminoglycosides. Clinical Infectious Diseases. 1992 Jan. 14:320-39. [Medline].
Hammett-Stabler CA, Johns T. Laboratory Guidelines for Monitoring of Antimicrobial Drugs. Clinical Chemistry. 1998 May. 44:1129-1140. [Medline].
Taccone FS, Laterre PF, Spapen H, Dugernier T, Delattre I, Layeux B, et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care. 2010 Apr. 14(2):R53. [Medline].
Gilbert DN, Moellering RC, Eliopoulos GM, Chambers HF, Saag MS. The Sanford Guide To Antimicrobial Therapy. 2010. 40.
Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987 Jan. 155(1):93-9. [Medline].
Kashuba AD, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother. 1999 Mar. 43(3):623-9. [Medline]. [Full Text].
Duszynska W, Taccone FS, Hurkacz M, Kowalska-Krochmal B, Wiela-Hojenska A, Kübler A. Therapeutic drug monitoring of amikacin in septic patients. Crit Care. 2013 Jul 25. 17(4):R165. [Medline].
Wilson JW, Estes LL. Mayo Clinic Antimicrobial Therapy Quick Guide. 2008.
Bartal C, Danon A, Schlaeffer F, Reisenberg K, Alkan M, Smoliakov R, et al. Pharmacokinetic dosing of aminoglycosides: a controlled trial. Am J Med. 2003 Feb 15. 114(3):194-8. [Medline].
Fukuchi H, Yoshida M, Tsukiai S, Kitaura T, Konishi T. Comparison of enzyme immunoassay, radioimmunoassay, and microbiologic assay for amikacin in plasma. Am J Hosp Pharm. 1984 Apr. 41(4):690-3. [Medline].
Ristuccia AM, Cunha BA. An overview of amikacin. Ther Drug Monit. 1985. 7(1):12-25. [Medline].
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
Pratibha Seshadri, MBBS, MD Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center
Disclosure: Nothing to disclose.
Antonette B Climaco, MD Attending Physician, Division of Infectious Diseases, Department of Medicine, Albert Einstein Medical Center
Antonette B Climaco, MD is a member of the following medical societies: Infectious Diseases Society of America, Philippine Medical Association, HIV Medicine Association, American Academy of HIV Medicine
Disclosure: Nothing to disclose.
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology
Disclosure: Nothing to disclose.
Amikacin Level
Research & References of Amikacin Level |A&C Accounting And Tax Services
Source
