Adult outpatient parenteral antimicrobial therapy (OPAT) good practice prescribing guide

Amikacin - management of Mycobacterial (tuberculosis and non-tuberculosis) infections

Amikacin is an aminoglycoside antibacterial with activity against a range of Gram-negative organisms including Pseudomonas, some Gram-positive organisms and also mycobacteria.  It is licensed for the treatment of serious infections where amikacin susceptible organisms have been identified.

This guide shares practical experience of the use of amikacin in an OPAT setting. We took an evidence based approach to create the guidance. We also used expert consensus and practical experience from across NHS Scotland.

This drug summary does not provide specific treatment guidance. Individual patient treatment should take into account the core principles of antimicrobial stewardship. This includes selection of the appropriate antimicrobial for the shortest duration with oral therapy being preferred, whenever possible.

For information on Route and method of administration, Contraindications, Cautions and adverse effects and Drug interactions please refer to the following approved resources:

These resources also have more information on licensed indication, use in pregnancy and use in breast feeding. When using unlicensed medicines, and/or off-label doses or indications, follow local health board governance processes.    

It is strongly recommended that OPAT services in Scotland adhere to the Key performance indicators for the management of patients in an outpatient parenteral antimicrobial therapy (OPAT) setting.

1.  Indication and dose

Off-label indications

It is recommended that off-label use is agreed with local OPAT infection specialist. Scottish experience of use in practice for off-label indications are below.

In the management of Mycobacterial infections, amikacin should be used in combination with other active antimicrobial therapies.

Off-label indications in the OPAT setting Dose
Mycobacterial (tuberculosis and non-tuberculosis) infections Initial intensive phase
(duration may vary depending on mycobacterium isolated)
Once daily dosing; see dosage table below
Continuous phase
Thrice/twice weekly dosing; see dosage table below
Monitor peak concentrations as per table below


Route and method of administration
Refer to Summary of Product Characteristics (SPC) or NHS Injectable Medicines Guide (Medusa) for further information

Intravenous infusion is the preferred route of administration:

  • Further dilute the required dose to 100ml with sodium chloride (NaCl) 0.9% or glucose 5% and give over 30 minutes.

2. Dose adjustments and monitoring
Dosage adjustments may be required under the following circumstances

Patient characteristic Dosage advice
Renal impairment See dosage table below
Hepatic impairment No dose adjustment necessary
Obesity See dosage table below
  • Ideally started as an inpatient to enable initial therapeutic drug monitoring and any necessary dose adjustments
  • DO NOT use eGFR. Calculate creatinine clearance (CrCl) using Cockcroft Gault equation (see below)
  • *Use the patient’s total body weight (TBW) or adjusted body weight (AdjBW) if TBW is greater than ideal body weight (IBW) (see below):
Creatinine Clearance (CrCl)

CrCl = (((140 – age in years) x weight*(kg)) / serum creatinine in micromol/L) x 1.04 (female) or 1.23 (male)
Ideal body weight (IBW) IBW = (((Height in cm – 152.4 cm) / 2.54) x 2.3) + 45 kg (female) or 50 kg (male)
Adjusted body weight (AdjBW)

AdjBW = (0.4 x (total body weight – IBW)) + IBW


Amikacin dosing tables

2a. Initial intensive phase: Once daily dosing

Weight (kg) less than 40 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-89 90 or higher
Once daily dose regimen (mg) 550 650 700 800 850 950 1000 1100 1150 1250 1350
CrCl 50 ml/min or higher 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly 24 hourly
CrCl 30-50 ml/min 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly 48 hourly
CrCl less than 30 ml/min Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours Sample at 48 hours


2b. Continuous phase: Three times a week / twice weekly dosing regimen

Weight (kg) less than 40 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-89 90 or higher
Dose 900 1000 1200 1300 1400 1600 1700 1800 1900 2000 2200
CrCl 50 ml/min or higher three times a week three times a week three times a week three times a week three times a week three times a week three times a week three times a week three times a week three times a week three times a week
CrCl 30-50 ml/min twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly twice weekly
CrCl less than 30 ml/min Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours Sample at 72 hours


3. Monitoring requirements

Frequency Recommended monitoring
Baseline

Urea and electrolytes (U&Es), liver function tests (LFTs), C-reactive protein (CRP), full blood count (FBC), magnesium, calcium

Baseline audiometry.

The mitochondrial DNA mutation m.1555A>G predisposes to severe hearing loss following aminoglycoside exposure.  Consider genetic testing, especially in patients requiring recurrent or long-term treatment with aminoglycosides (e.g. complex drug resistant infections including tuberculosis, cystic fibrosis or recurrent neutropenic sepsis) but DO NOT delay urgent treatment in order to test.
Routine monitoring
(Note this may be more frequent if clinically necessary)

WEEKLY U&Es*, LFTs, CRP and FBC.
(*Perform more frequently if clinically indicated).
MONTHLY magnesium, calcium
Therapeutic drug monitoring
(and see below)

Week 1; peak and trough concentration,

Week 2 – 5; if peak satisfactory repeat trough concentration weekly, 

Week 6 onwards; If trough satisfactory reduce frequency to fortnightly measurement

Perform both peak and trough monitoring more frequently if clinically indicated (e.g. if renal function deteriorates or improves significantly; a change in creatinine of more than 15–20% during amikacin therapy).
Audiology

Audiometry; baseline, monthly then 2 months after cessation therapy.
Follow-up

Ensure follow up is arranged with referring specialty


Therapeutic drug monitoring

Amikacin concentrations measurements are essential to guide ongoing therapy, clinical efficacy and possible toxicity.  See table below for target amikacin concentrations or seek advice from pharmacy if you are unsure how to interpret the results or if the concentrations are not within the target ranges below.

  • Take a peak amikacin concentration 1 hour after the end of the first amikacin infusion. Ensure 1 hour has elapsed, from the end of the infusion, as early concentrations will be invalid.
  • Take a trough amikacin concentration at the end of dosage interval (prior to the next dose).  Do not delay giving the second amikacin dose while waiting for the trough concentration to be reported, unless there are concerns over deteriorating renal function or CrCl less than 30 ml/min. 
  • If the amikacin trough concentration is higher than the target concentration (see table below) and a further dose has already been administered, repeat the trough concentration measurement and await the result before re-dosing. DO NOT give a further dose until the amikacin concentration is within target range.

 Target amikacin peak and trough concentrations

Dosage regimen

Target peak concentration
(1 hour post end of infusion)

 Target trough concentration
(end of dosage interval)
Once daily 25 – 40 mg/L less than 5 mg/L at 24 hrs
Three times weekly 45 – 65 mg/L less than 2 mg/L at 48 hrs
Twice weekly 45 – 65 mg/L less than 2 mg/L at 72 hrs


For the use of other antibiotics in an OPAT setting please refer to the SAPG website

 

 Scottish Antimicrobial Prescribing Group (SAPG) | April 2024 for review April 2027

Content updated: May 2024