Top tips for gentamicin prescribing
1. Know when to use
Gentamicin is an aminoglycoside antibiotic active against many gram negative organisms which has rapid bactericidal properties and is life-saving in acutely septic patients.
· Some antibiotic regimes, for example treating intra-abdominal infection and sepsis of unknown origin, depend on gentamicin for gram-negative coverage.
· Due to increasing antibiotic resistance and the need to preserve broad-spectrum antibiotics such as piperacillin/tazobactam and carbapenems, gentamicin is recommended in the Trust for a variety of severe infections.
· Gentamicin prescriptions should be reviewed within 24-48 hours and stopped or replaced with another agent in most cases.
2. Dosing gentamicin on body weight
Aminoglycosides have a low volume of distribution therefore accumulation can occur in obese patients.
· Gentamicin doesn't enter adipose tissue therefore there is a risk of over-dosing obese patients when dosing on actual body weight.
· The maximum dose of gentamicin is 450mg in a 24 hour period. The Trust gentamicin calculator will automatically adjust the dose for obese patients.
3. Once daily or multiple daily dosing?
Once daily dosing is the preferred regime.
· Aminoglycosides exhibit a peak dose killing profile (the higher the peak, the more cidal the drug), followed by a post antibiotic period of suppressed bacterial growth.
· Once daily dosing allows higher peak levels to be achieved, improving efficacy, and the gentamicin-free period between doses also helps to minimise oto- and nephro-toxicity.
· Once daily dosing is preferred in all patients except for the management of infective endocarditis as outlined in the antibiotic formulary.
4. Aminoglycosides in renal failure
In renal impairment, clearance of gentamicin is reduced and toxicity can occur.
· It is safe to give a STAT dose of gentamicin in septic patients with known CKD 4/5 (or an AKI on CKD). After a STAT dose please risk assess patient and discuss an alternative with senior clinician or microbiology.
· Close monitoring and extended dose intervals are advised in this group of patients.
· Monitor trough levels closely in renal patients and ensure no further doses given until level is <1mg/L.
· Renal function should be monitored daily whilst on gentamicin.
5. Aminoglycosides in myasthenia gravis (MG)
Gentamicin is contraindicated in myasthenia gravis as it can reduce the effectiveness of neuromuscular transmission and exacerbate symptoms of the disease. For more information please read the guidance on antibiotics in myasthenia gravis.
6. Avoid duplicate dosing
There have been numerous reports of patients receiving two doses within 24 hours.
· This typically occurs following a patient transfer from A&E or AMU or a critical care ward and transcription from paper chart to EPMA.
· Always check to see if your patient has had a dose of gentamicin in the last 24 hours before prescribing or administering a repeat dose.
· The discontinued section on EPMA can be used to check the timing of previous or STAT doses of gentamicin.
7. Minimising nephrotoxicity
Accumulation of gentamicin in the kidneys leads to nephrotoxicity.
· Single doses and shorter courses of therapy are associated with a lower risk.
· Prolonged duration of therapy, concurrent nephrotoxins and dehydration are risk factors for nephrotoxicity.
· Therapeutic drug monitoring is required to ensure safe dosing.
· Renal function should be monitored daily whilst on gentamicin.
· Gentamicin should be stopped or switched to another agent with gram negative activity as soon as clinically stable.
8. Minimising ototoxicity
Gentamicin can cause irreversible ototoxicity and vestibular toxicity.
· Loss of hearing usually occurs first and is detected by regular audiometric testing.
· Vertigo, loss of balance and auditory disturbances are also signs of ototoxicity.
· Ototoxicity and vestibular toxicity are not predicted by plasma concentrations, and prolonged therapy increases the risk.
· Courses >7 days should only be continued with regular audiometric testing.
9. Therapeutic drug monitoring
Levels are required to monitor for toxicity.
· Collect a serum gentamicin level 8 – 12 hours after the start of the first dose.
· Document on the request how many hours post dose the sample was taken.
· Use the nomogram below to determine whether the calculated dosing interval needs to be extended based on the individual patient’s serum concentrations. The frequency obtained from the nomogram will supersede that estimated by the calculator.
· Post-dose level 8-12 hours after gentamicin are only required after the first dose of gentamicin, then trough levels are required for ongoing monitoring.
Monitor for gentamicin toxicity by repeating trough levels twice per week if renal function is stable or more often as indicated. Aiming for a trough level <1mg/L. Doses should not be omitted whilst awaiting pre-dose levels, unless advised by a pharmacist.
If pre dose level is >1mg/L, please discuss further dosing with a pharmacist. Patient may need to be switched to an alternative regime.
Any advice regarding dosing provided by a pharmacist, will be recorded in a TDM pharmaceutical care note or PENs.
Renal function should be monitored daily whilst on gentamicin. If renal function worsens during therapy, seek immediate advice from Pharmacy or Medical Microbiology/Infectious Diseases before giving further doses.
Target Levels
For once-daily regimes: consult the nomogram as outlined above to interpret the level.
Trough level <1mg/L.
For multiple-daily dosing regimes:
Levels should be taken at the third dose, and repeated 2-3 times per week if renal function is stable or more often as indicated.
Both pre-dose and 1 hour post-dose levels are required:
Target pre-dose (trough) level <1mg/L, to avoid toxicity
Target post-dose (1 hour peak) 3-5mg/L, for therapeutic efficacy
1. Baxter, K, director. British National Formulary No71. London: British Medical Association and The Royal Pharmaceutical Society of Great Britain; March-September 2016. [Accessed 9/8/16] via www.bnf.org.uk.