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​Amikacin prescribing guidance

Introduction

Amikacin is an aminoglycoside antibiotic active against some Gram-positive organisms, principally Staphylococcus aureus (including some MRSA), and many Gram-negative organisms including Psuedomonas aeruginosa. It is primarily indicated for the treatment of serious infections caused by gentamicin-resistant Gram-negative bacilli. Amikacin should only be initiated after consultation with a microbiologist.

 

Cautions and contraindications

Amikacin is contraindicated in myasthenia gravis and in patients with a known allergy to aminoglycosides. It should be used in caution where there is pre-existing renal insufficiency or hearing/vestibular damage – baseline audiometry can assist in identifying this. Patients should be well hydrated during treatment with amikacin. The maximum licensed cumulative dose per course is 15g; exceeding this increases the risk of ototoxicity and audiological monitoring is recommended.

 

Pharmacokinetics

The clearance, volume of distribution and half-life of all aminoglycosides are similar and the same pharmacokinetic model can be used for each agent. The pharmacy department’s ‘gentamicin calculator’ is therefore applicable to amikacin. As aminoglycosides distribute poorly into the adipose tissue, using true body weight in obese patients may result in an overdose:

  •        if underweight use actual body weight
  •        if <20% overweight use actual body weight
  • ​    if >20% overweight use adjusted body weight


Adjusted body weight = ideal body weight + 0.4(actual body weight – ideal body weight)

[ideal body weight = (height in inches over 5 foot x 2.3) + 50 for males/45 for females]


  if Extended interval (ONCE daily) dosing regime

Most patients are suitable for ONCE daily amikacin dosing

  • If eCrCl >30mL/min and <65 years old, prescribe 15mg/Kg ONCE daily (maximum dose 1.5g). Trough level before second dose.
  • If eCrCl <30mL/min or >65 years old, prescribe 15mg/Kg STAT. Dosing interval may need to be increased; please refer to pharmacy for advice.
Traditional multiple daily dose regimes

This should not be recommended as once daily dosing has a greater safety profile

 

Method of administration

Infuse intravenously in 100mL 0.9% sodium chloride or 5% glucose over 20- 30 minutes.

Therapeutic drug monitoring

Amikacin exhibits concentration-dependent killing followed by a post-antibiotic period of supressed bacterial growth. Peak level monitoring is NOT routinely necessary in patients receiving once daily amikacin although it may be desirable in certain population groups (e.g. critical care patients). In these cases microbiology will advise on a target level as there is no universally agreed target peak. Maximum bactericidal effect is seen when serum amikacin levels exceed 10 times the minimum inhibitory concentration (MIC). As a general guide, the MIC breakpoint for the more problematic bacteria (including Pseudomonas and Enterobacteriaceae) is 8mg/L. The Bristol Centre for Antimicrobial Research and Evaluation recommends a target peak of >50mg/L. However for ongoing prescriptions of amikacin, microbiology should provide advice on MIC of organism and target peak.

 

For extended interval (ONCE daily) regimes

  • Take a trough level prior to the second dose; aim for <5mg/L
  • ‘Two-timed levels’ can also be used following pharmacy advice. The levels will need to be followed up within 24 hours to help determine ongoing dose/if appropriate to continue.
  • Patients with CrCl <30ml/min should have their levels reviewed before second dose is administered.
  • Routine peak level monitoring is NOT normally necessary (but see above)
  • Ensure patient receives daily U&Es whilst on amikacin

Levels should be taken in a red topped plain serum tube and for Aintree samples the laboratory informed that an amikacin level (s) is urgently required.

Amikacin levels can now be ordered on ICE and on EPMA in the same way as gentamicin. Levels should be monitored every 3 - 5 days.

 

Biochemistry can be contacted on extension Aintree site  3241, Royal site 4253