Synergistic Gentamicin for Infective Endocarditis in Adults

These guidelines aim to produce a 1 hour post dose “peak” concentration of 3-5 mg/L, and an end of dosage interval “trough” concentration of  <1 mg/L.  Doses should be administered by IV bolus injection over 3-5 minutes.

Gentamicin: Synergistic Dosage Guidelines

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

Do NOT use eGFR: creatinine clearance must be calculated using Adjusted Body Weight or, if actual body weight ≤ideal body weight use actual body weight.

If the patient is already receiving full treatment dose gentamicin and is to switch to synergistic dosing

• If renal function is stable AND a gentamicin concentration taken in the past 48 hours is within the range expected for the current full treatment dose regimen then switch to synergistic dosing when the next dose of gentamicin is due.
• If renal function is not stable OR there are no gentamicin concentration results in the past 48 hours OR the concentration result suggests that an altered dose interval is required then confirm that the patient’s gentamicin concentration is <1mg/L before switching to synergistic dosing.

On the medicine chart prescribe as GENTAMICIN SYNERGISTIC (ENDOCARDITIS) with the dose, dosage frequency and intended duration (if known).

Do NOT use the (maroon) standard ‘Adult Parenteral Gentamicin (GGC): Prescribing, Administration & Monitoring Chart’ to prescribe synergistic gentamicin. The ‘Adult Parenteral Synergistic Gentamicin (GGC): Administration & Monitoring Chart’ should be printed out and used on the ward for accurate recording of administration and sample times; this is ESSENTIAL for the correct interpretation of gentamicin concentration results. This chart must NOT be used as a prescription chart; doses and dose times must be prescribed on the Medicine chart and amended on the medicine chart if the dose regimen is altered.

• Take a blood sample for gentamicin analysis one hour after the first gentamicin bolus injection has been administered (a “peak” sample).
• Take a second blood sample for gentamicin analysis at the end of the first dosage interval (a “trough” sample, just before the next dose is due) then give the next dose. Do NOT delay giving the second gentamicin dose while waiting for the trough concentration to be reported, unless there are concerns over deteriorating renal function.
• Record the exact time of all gentamicin samples on the Synergistic Gentamicin Administration and Monitoring Chart. Ensure all TrakCare sample request forms are printed at the time of sample collection (so that accurate sample times are recorded on TrakCare/Clinical Portal).
• See the table below for advice on interpreting gentamicin concentration results.
• Monitor the patient’s creatinine daily and record this on the Synergistic Gentamicin Administration and Monitoring Chart.
• If the prescribed dose amount/dose frequency is altered ensure this is updated and prescribed on the medicine chart.

Consultant Microbiologist should be consulted to advise on the duration of synergistic gentamicin at the following times:

• Within 72 hours of starting antibiotic therapy
• At 1 week of therapy, if continuation of gentamicin is being considered at that point
• If the patient is causing concern (e.g. failure to respond, evidence of toxicity; see below)
• If discharge/OPAT is being considered (N.B. there are alternatives to synergistic gentamicin if patients are being discharged via OPAT)

In general, synergistic gentamicin therapy should continue for up to 2 weeks, except in the case of enterococcal IE when it may be given for 2-6 weeks on microbiology/ID advice. The addition of synergistic gentamicin in staphylococcal native valve IE is no longer routinely recommended as it increases renal toxicity without evidence of additional benefit.

If a patient is switched from full treatment dose gentamicin to synergistic dosing (without a significant break in therapy) then the days of full dose gentamicin therapy WOULD count towards the intended synergistic course duration.

Gentamicin can cause nephrotoxicity and ototoxicity (cochlear and vestibular). The risk of gentamicin toxicity increases with increasing duration of therapy.

Nephrotoxicity

• Monitor creatinine daily. Seek advice from pharmacy if renal function is unstable (e.g. a change in creatinine of >15-20%).
• Be alert for and react to any signs of renal toxicity e.g. increasing creatinine, decreased urine output/oliguria.
• Discuss the ongoing need for gentamicin with microbiology/ID if the patient has signs of worsening renal function.

Ototoxicity

• Gentamicin-induced ototoxicity occurs independently of drug concentration.
• Toxicity is usually associated with prolonged gentamicin use (usually >7 days, however it may occur sooner) and is secondary to accumulation of drug within the inner ear.
• Ototoxicity is suggested by any of the following: new tinnitus, dizziness, poor balance, hearing loss, oscillating vision.
• Patients prescribed gentamicin should be advised to report signs of ototoxicity (see below regarding the Patient Information Leaflet which should be issued to the patient). Patients should be asked regularly about any signs and symptoms of ototoxicity and this should be documented in the case notes.
• If gentamicin continues for >7 days the patient should be referred to audiology for ongoing audiometry testing and the case re-discussed with microbiology or ID. Contact the local audiology department directly to confirm their referral method/requirements.
• If ototoxicity is suspected STOP gentamicin treatment and refer to microbiology/ID for advice on ongoing therapy.

All patients prescribed synergistic gentamicin should be given a copy of the NHSB Gentamicin Patient Information Leaflet ‘Information for adult patients about intravenous gentamicin’ at the earliest opportunity. This should be documented in the relevant section of the Synergistic Gentamicin Administration and Monitoring Chart. If this is not possible the reasons for non-issue of the leaflet should be recorded on the chart.