Synergistic Dosing of Gentamicin in Adults

Antimicrobial prescribing: NHS Lothian
NHS Lothian

This guidance is for NHS Lothian staff wishing to use SYNERGISTIC DOSE GENTAMICIN.

For once-daily gentamicin see here.

Indications

  • Endocarditis
  • On advice from infectious diseases or microbiology

Exclusions and contraindicationsDo not use this guidance in the following groups:

  • Patient <16 years old
  • Pregnancy
  • Myasthenia gravis

Use in the these groups ONLY on advice from infection specialists & antimicrobial pharmacist

Cautions:

  • Acute or chronic renal impairment or unstable creatinine
  • Patients on medicines that increase risk of toxicity (consider stopping):
    • Nephrotoxicity: NSAID, ACE inhibitor
    • Ototoxicity: diuretics (particularly loop diuretics like furosemide)

Required monitoring

Check U+E daily; if renal function changes significantly (by >15%), recalculate creatinine clearance and adjust dosing.

  • Take a “peak” level 1 hour after the first gentamicin bolus dose
  • Take a “trough” level before the second gentamicin dose (i.e at the end of the dosage interval)
    • DO NOT await the trough result before re-dosing unless there are concerns about deteriorating renal function.
Creatinine Clearance (ml/min) Monitoring frequency
<45 Daily
≥45 Monitor peak/trough daily until target levels achieved; then move to 2-3 per week

Document peak/trough levels on TRAK, along with dose adjustments made if applicable (see below).

Audiometry:If therapy continues for >7d, obtain baseline audiometry then repeat monthly.

Gentamicin toxicity

Nephrotoxicity:

  • Dose-dependent: further rise in creatinine/oliguria will lead to gentamicin accumulation
  • Ensure good hydration, avoid co-prescription nephrotoxic medication (eg. furosemide)

Ototoxicity

  • Dose-independent; related to drug accumulation in the inner ear
  • Associated with prolonged use (usually >10 days but may be >72 hours).
  • Symptoms: new tinnitus, dizziness, poor balance, hearing loss or oscillating vision.

If therapy continues for >7d, obtain baseline audiometry then repeat monthly.

If ototoxicity/vestibulotoxicity is suspected, discontinue aminoglycoside therapy, refer to ENT for assessment and call microbiology to discuss alternative antimicrobials.

Calculate synergistic gentamicin dose

Document your calculations in TRAK. Ensure clinical pharmacist review at earliest opportunity.

1. Calculate the patient's creatinine clearance

  • Calculate using patient's age, height, weight & serum creatinine.
  • Calculator available here (NB: Intranet only)
  • Other online calculators can be used as long as they use the Cockcroft-Gault formula
  • As a last resort calculate manually. 

2. Calculate dosage

Dose depends on the patient’s weight

Actual body weight (kg) Dose
<45 40 mg
45-65 60 mg
66-85 80 mg
86-110 100 mg
>110 120 mg

Dosing interval depends on the creatinine clearance: 

Creatinine clearance (ml/min) Dosing interval
<25

Take sample after 24 hours

Do not give a further dose until the concentration is <1mg/l
25-44 24 hourly
>44 12 hourly

If creatinine is not known: give 1mg/kg gentamicin (maximum 120mg) and seek advice from pharmacy

3. Prescribing synergistic gentamicin

  • Prescribe on the medicine chart (Kardex) or HEPMA (electronically) the gentamicin dose/interval as calculated above
  • Gentamicin is administered as slow IV bolus over 5 minutes

Print out the synergistic gentamicin therapeutic drug monitoring chart.

4. Documenting calculations

 Use TRAK backslash code \syngent to document outcome.

SYNERGISTIC GENTAMICIN DOSING CALCULATIONS

Height (cm):

Weight (kg):

Creatinine (micromol/L):

 

Dosage:

Frequency:

Day of first trough level:

Day of first peak level:

SIGNED:

Checked with pharmacist [Y/N]:

Monitoring levels

Check U+E daily; if renal function changes significantly, recalculate creatinine clearance and adjust dosing.

Recommended target levels: 

Level

Timing

Target (mg/l)

Peak

1 hour post-dose

3-5

Trough

Immediately pre-dose

≤1

DOCUMENT TIMING ACCURATELY when levels were taken on the synergistic gentamicin therapeutic drug monitoring chart. 

Adjusting the dose based on levels

General advice: 

  • High trough – Increase dosage interval.

    • From 12 to 24 hourly

    • From 24 to 48 hourly

  • Low peak- Increase the dose. Doubling the dose will double the serum level (e.g. if peak level consistently 2mg/L, increasing the dose by 50% should bring the level up to 3mg/L.

See below table of common scenarios and suggestions of actions on how to adjust dose and monitoring

Trough

Peak

Action

<1

<3

Increase dose (up to 120mg)

Recheck peak/trough after dose increase

<1

3-5

Continue

<1

>5

Reduce dose but keep the same dose interval

Check trough & peak levels with next dose

>1

<3

Take trough before next dose

If <1, consider increase dose if renal function stable- check peak after increase dose and check trough before next dose- Then if trough >1 and peak ~3-5, withhold until trough <1 and consider if dosing was 12 hourly increase to daily dosage.

>1

3-5

Take trough before next dose

If <1, give next dose & monitor daily

If >1, withhold until trough below target, if dosing was 12 hourly consider to increase to daily dose

>1

>5

Withhold until trough below target

If dosing was 12 hourly, increase to daily dose and may consider to reduce dose

Check trough & peak levels with next dose

References

  • Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy J Antimicrob Chemother 2012; 67:269-289
  • NHS Greater Glasgow and Clyde Clinical Guideline: Synergistic Gentamicin for Endocarditis in Adults. Version 3 published 20/11/2019. Accessed online on 26/07/2021
  • NHS Highland: Guidelines for Gentamicin dosing in infective endocarditis in adults. Last reviewed 30 May 2019. Accessed online on 26/07/2021