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Amikacin
Omeed Sizar; Sajedur Rahman; Vidya Sundareshan.

Author Information and Affiliations

Last Update: July 17, 2023.

Continuing Education Activity

Amikacin is an antimicrobial with activity against more resistant gram-negative bacilli such as
Acinetobacter baumanii and Pseudomonas aeruginosa. It also has excellent activity against most
aerobic gram-negative bacilli from the Enterobacteriaceae family, including Nocardia sp. and
some Mycobacterium spp. (M. avium-intracellulare, M. chelonae, and M. fortuitum). Unlike
gentamicin, amikacin does not provide synergistic activity against Enterococcus faecium when
combined with beta-lactam antibiotics. This activity covers amikacin, its mechanism, activity
spectrum, and its place in an infectious disease regimen. Members of the interprofessional team
need to review its indications, coverage, contraindications, and adverse event profile to optimally
manage patients with infectious disease.

Objectives:

Summarize the mechanism of action of amikacin.

Identify the bacterial coverage and indications for amikacin.

Review the adverse events of amikacin, including proper monitoring procedures.

Explain amikacin's place in infectious disease management as it pertains to improving care

coordination amongst the interprofessional team and in the context of antimicrobial
stewardship.

Access free multiple choice questions on this topic.

Indications
Amikacin's niche is because it also has activity against more resistant gram-negative bacilli such
as Acinetobacter baumanii and Pseudomonas aeruginosa. It also has excellent activity against
most aerobic gram-negative bacilli from the Enterobacteriaceae family, including Nocardia sp.
and some Mycobacterium spp. (M. avium-intracellulare, M. chelonae, and M. fortuitum). Unlike
gentamicin, amikacin does not provide synergistic activity against Enterococcus faecium when
combined with beta-lactam antibiotics.[1][2][3]

Amikacin is rarely used alone and often combined with other antimicrobials.

Indications Include

Hospital-acquired/ventilator-associated/healthcare-associated pneumonia

Endophthalmitis, bacterial (intravitreal injection, OFF LABEL)

Meningitis (IV) or (intrathecal/intraventricular, OFF LABEL)

Wound infections caused by susceptible organisms

Urinary tract infections (Generally only if caused by resistant organisms, OFF LABEL)

Gram-negative bacteremia/sepsis (OFF LABEL)

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Mechanism of Action
Amikacin binds to the 30 S bacterial ribosome subunit, resulting in interference with a reading of
the genetic code and inhibition of protein synthesis, e.g., elicits premature protein termination
and incorporation of incorrect amino acid. Amikacin, as well as the rest of the aminoglycosides,
are generally bacteriocidal and probably have an additional mechanism of action, which as yet
remains undetermined. Aminoglycosides demonstrate bacterial killing that is concentration-
dependent and also have a post-antibiotic effect.

Amikacin, when combined with penicillins, can have an additive effect on specific
microorganisms.

Amikacin, when combined with carbapenems, can have a synergistic effect against some gram-
positive organisms.

Amikacin may retain activity against tobramycin- and gentamicin-resistant strains because of
reduced inactivation by bacterial acetylase, adenylase, and phosphorylase. Thus, its routine
clinical use should be reserved for difficult to treat serious nosocomial infections.[4]

Administration
Amikacin can be administered parenterally or via nebulization. There is no oral formulation of
the drug available because the drug is not absorbed from the gastrointestinal tract. Amikacin can
be administered intramuscularly when intravenous access is not available. In some patients with
meningitis, it can be administered intrathecally and reaches high concentrations in the
cerebrospinal fluid immediately.[5][6][7]

Dosing based on weight (Kg):

Underweight or nonobese: dose on ACTUAL body weight (ABW)

Obese (ABW/IBW* > or = to 1.25): dose on DOSING body weight (DBW= IBW +
0.4(ABW - IBW)

Adult Dosing:

Conventional Dosing: 5mg/kg IV every 8 hours - the elderly often require only a 12 hr
dosing interval

Adjustment for renal impairment (assuming every 8-hr dosing)

Greater than 50 mL/min (CrCL): no adjustment

30 to 50 mL/min: every 12 to 18 hrs

10 to 29 mL/min: every 18 to 24 hr

Less than 10 mL/min: dose based on plasma concentrations or consult a pharmacist.

Once Daily Dosing:

Not to be used in patients with ascites, over 20% BSA burns, pregnant patients, or patients on
dialysis. (Use conventional dosing or consult a pharmacist.)

15 mg/kg per dose once daily

Adjustment for renal impairment:

60 mL/min (CrCL) and above: every 24 hours

40 to 59 mL/min: every 36 hours

30 to 39 mL/min: every 48 hours

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Less than 30mL/min: Use conventional dosing method

Intravitreal: 0.4 mg/0.1 mL of normal saline (preservative-free formulation, OFF LABEL)

Intrathecal/intraventricular: 5 to 50 mg/day, usual dose is 30 mg (preservative-free

formulation, OFF LABEL)

*IBW: Ideal body weight, ABW: Actual body weight, DBW: Dosing body weight, CrCL:
creatinine clearance (not eGFR)

There is also liposomal amikacin undergoing clinical trials to treat respiratory infections in
patients with cystic fibrosis and bronchiectasis. In the trials, the liposomal dosage form is being
used to treat nontuberculous bacteria and Pseudomonas aeruginosa. Liposomal amikacin is FDA
indicated for the treatment of Mycobacterium avium complex (MAC), which is inhaled using a
nebulizer for 14 to 20 minutes.

Special Populations

Amikacin use requires great caution in the elderly population who tend to have decreased renal
function. Also, young children do not have a fully developed renal system, and hence smaller
doses are necessary.

Adverse Effects
Major Adverse Effects

Nephrotoxicity is the most common, occurring in 1% to 10% of patients. The nephrotoxicity is

reversible if detected early and the drug discontinued. Renal damage is more likely to occur in
dehydrated patients, have a low glomerular filtration rate, have diabetes, sepsis, fever, or are on
NSAIDs.[8]

Ototoxicity, vestibular, and auditory (4% to 6%) can occur when using high doses. The patient
may complain of loss of balance and hearing loss, which can be permanent if drug therapy
continues for prolonged periods. The ototoxicity is believed to be due to oxidative free radicals,
which damage the hair cells in the cochlea. Many hospitals now routinely monitor hearing
before, during, and after therapy in infants.

Neuromuscular blockade is less common.

Minor Effects

Increase in BUN/Cr (5% to 25%), drug fever, and rash (less common).

Neurotoxicity may present in some patients with paresthesias, tingling, and numbness.

Contraindications
Patients may demonstrate hypersensitivity to amikacin, other aminoglycosides, or any
component of the drug formulation.

Amikacin can pass through breast milk and the placenta. Hence it is not recommended in
pregnant women as the drug may cause congenital deafness in the infant. Even though only small
amounts pass into breast milk, experts do not recommend breastfeeding while on amikacin.

In general, amikacin is not used in infants. Further, since infants and small children tend to have
a large volume of distribution, the drug remains in the systemic circulation for prolonged periods.

Clinicians should not use amikacin in combination with other drugs that have the potential to
cause renal and auditory toxicity. The list of medications that should be avoided includes
amphotericin B, acyclovir, capreomycin, bacitracin, vancomycin, and cisplatin. Also, amikacin

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should not be used in patients receiving neuromuscular blockers because it can prolong muscle
paralysis and weakness.[4]

Monitoring
Monitor renal function (BUN/Cr every 1 to 2 days based on the stability of renal function), Ins
and Outs (daily), hearing parameters (baseline and weekly audiograms), symptoms of
vertigo/dizziness (daily), peak concentrations (conventional dosing, no need in once-daily
dosing) and trough concentrations (both conventional and once-daily dosing, repeat every 2 to 3
days and prolong if plasma concentrations are stable.[9]

Conventional Dosing Concentrations

Obtain peak concentrations (1 hr after the start of a 30 min infusion) after 24 hrs or four
half-lives

Obtain trough concentrations (30 min before the next scheduled dose) again after

Goal Concentrations

Peak:

Serious infection: 20 to 25 mg/dL

Life-Threatening infection: 25 to 30 mg/dL

Trough:

Serious infection: 1 to 4 mg/dL

Life-Threatening infection: 4 to 8 mg/dL

Once Daily Dosing Concentrations:

Monitor after the initial dose, no need to wait for four half-lives

Clinicians can use the Hartford nomogram (multiply drug concentration scale by a factor
of 2 to use) to estimate the appropriateness of the once-daily dosing (ODD) regimen.

Recommend confirmatory trough concentration 30 min before the next scheduled dose if
using the nomogram: less than 2.5 mg/dL (goal trough with ODD)

Toxicity
No antidote for toxicity is available, only 20% dialyzable; however, this is variable based on
hemodialysis filter. Avoid potentially toxic prolonged peak concentrations above 35 mcg/mL.

Drug Interactions

Clindamycin, chloramphenicol, and tetracycline can inactivate amikacin and other

aminoglycosides.

High-ceiling diuretics like furosemide increase ototoxicity and have the potential to increase the
concentration of amikacin, thereby worsening the ototoxicity.

Other medications that can increase amikacin concentrations in the blood include NSAIDs
(especially indomethacin) and quinidine.

Enhancing Healthcare Team Outcomes

Amikacin is a beneficial drug to treat aerobic gram-negative infections. Healthcare workers,
including the clinicians who prescribe it, should always check renal function regularly as the
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drug is nephrotoxic. In many inpatient facilities, the clinician or infectious disease specialist will
initiate amikacin as part of the antimicrobial regimen and then allow the clinical pharmacist to
handle dosing and subsequent dose adjustment. Nursing will perform drug administration and
should have open access to both the clinicians and the pharmacists. If problems arise, the nurse
or pharmacist must reach out to the clinician to adjust therapy. The interprofessional team,
including all clinicians, specialists, nurses, and pharmacists, should all be responsible for
assessing treatment effectiveness and monitoring for side effects. [Level 5]

Review Questions

Access free multiple choice questions on this topic.

Comment on this article.

References
1. Endo A, Nemoto A, Hanawa K, Maebayashi Y, Hasebe Y, Kobayashi M, Naito A, Kobayashi
Y, Yamamoto S, Isobe K. Relationship between amikacin blood concentration and ototoxicity
in low birth weight infants. J Infect Chemother. 2019 Jan;25(1):17-21. [PubMed: 30539740]
2. Nolt VD, Pijut KD, Autry EB, Williams WC, Burgess DS, Burgess DR, Arora V, Kuhn RJ.
Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo
simulation. Pediatr Pulmonol. 2019 Jan;54(1):33-39. [PubMed: 30507069]
3. Kulengowski B, Clark JA, Burgess DS. Killing activity of meropenem in combination with
amikacin against VIM- or KPC-producing Enterobacteriaceae that are susceptible,
intermediate, or resistant to amikacin. Diagn Microbiol Infect Dis. 2019 Apr;93(4):372-375.
[PubMed: 30514595]
4. Block M, Blanchard DL. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL):
Jul 17, 2023. Aminoglycosides. [PubMed: 31082149]
5. Sturkenboom MGG, Simbar N, Akkerman OW, Ghimire S, Bolhuis MS, Alffenaar JC.
Amikacin Dosing for MDR Tuberculosis: A Systematic Review to Establish or Revise the
Current Recommended Dose for Tuberculosis Treatment. Clin Infect Dis. 2018 Nov
28;67(suppl_3):S303-S307. [PubMed: 30496466]
6. Illamola SM, Huynh HQ, Liu X, Bhakta ZN, Sherwin CM, Liou TG, Carveth H, Young DC.
Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis. Antimicrob
Agents Chemother. 2018 Oct;62(10) [PMC free article: PMC6153835] [PubMed: 30061295]
7. Liu X, Smits A, Wang Y, Renard M, Wead S, Kagan RJ, Healy DP, De Cock P, Allegaert K,
Sherwin CMT. Impact of Disease on Amikacin Pharmacokinetics and Dosing in Children.
Ther Drug Monit. 2019 Feb;41(1):44-52. [PubMed: 30299427]
8. Arnold A, Cooke GS, Kon OM, Dedicoat M, Lipman M, Loyse A, Chis Ster I, Harrison TS.
Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in
Multidrug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2017 Sep;61(9) [PMC free
article: PMC5571306] [PubMed: 28696239]
9. Wrohan I, Redwood L, Ho J, Velen K, Fox GJ. Ototoxicity among multidrug-resistant TB
patients: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2021 Jan
01;25(1):23-30. [PubMed: 33384041]

Disclosure: Omeed Sizar declares no relevant financial relationships with ineligible companies.

Disclosure: Sajedur Rahman declares no relevant financial relationships with ineligible companies.

Disclosure: Vidya Sundareshan declares no relevant financial relationships with ineligible companies.

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