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gentamicin

gentamicin

introduction

  • belongs to the aminoglycoside antibiotics which were originally obtained from Streptomyces species
  • ototoxic & nephrotoxic if high dose or prolonged use
  • active mainly against enteric Gram -ve bacteria
  • ATG recommend high dose “once daily” dosing for all indications EXCEPT infective endocarditis (including SBE) in which case “low dose 8 hourly dosing” schedule should be used
  • iv gentamicin is infused over 30min

relative contraindications

  • chronic renal failure or worsening renal function, particularly if the creatinine clearance is less than 30 ml/min, unless there is consultation with the Infectious Diseases or Renal units
  • pre-existing hearing problems
  • pre-existing vestibular problems, including dizziness, vertigo or tinnitus
  • age greater than 70 years old, other than for stat dose surgical prophylaxis or initial treatment of severe infection for 48 hours, unless no safer, appropriate alternative antibiotic is available
STOP gentamicin if there is new onset or worsening of vertigo, dizziness, balance disturbance, blurred vision, hearing difficulty or tinnitus.

indications

initial empirical iv gentamicin dose in ED where "once daily" regime is applicable

  • usual adult dose iv gentamicin 4-5mg/kg calculated to give closest dose to ampoule size (most ED's stock 80mg in 2ml ampoules, thus a common adult once daily dose is 320mg iv)
  • patients with severe sepsis have higher volumes of distribution and therefore require a higher mg/kg dose.

dosing according to Australian Therapeutic Guidelines 2011

age high dose once daily dose of iv gentamicin
neonates < 34wks post-conceptional age 3mg/kg
neonates >= 34wks post-conceptional age 3.5mg/kg
infants and children < 10 yrs age 7.5mg/kg up to max. 320mg
10 - 29 years age 4-6mg/kg up to max. 560mg
30 - 60 years age 4-5mg/kg up to max. 480mg
> 60 years age 4mg/kg up to max. 400mg
> 10 yrs age with severe sepsis 7mg/kg up to max. 640mg

administration

  • usually should be given in 100ml of comptible fluid and infused over 1 hour
  • however, prophylactic adult doses up to 120mg can be given over 3-5 minutes as a slow iv bolus

gentamicin CAN be given without requiring 1 hr delay following 1st dose penicillin

  • most written product information advise iv gentamicin must be given after at least 1 hour delay following iv penicillin dose if penicillin is being used.
  • the rationale is that gentamicin is inactivated by penicillin in vivo
  • unfortunately this advice if heeded may result in unnecessary delays incommencement of antiobiotic Rx in the critically ill patient, and delays in transferring patients from ED to the ward
  • gentamicin dose does NOT need to be delayed following the FIRST dose of iv penicillin but the line should be flushed with normal saline between the two medications.
  • the gentamicin dose should be delayed by at least 1 hour if there is a possibility of accumulation of penicillin such as with subsequent penicillin dosing, particularly in the those with renal impairment.

subsequent dosing

  • for subsequent dosing in patients on dialysis or in children with renal impairment, seek expert advice
  • monitoring of aminoglycosides in patients undergoing haemodialysis is difficult. Computerised AUC methods should be used and expert advice is needed. Alternative drugs should be considered.
  • if the duration of treatment extends beyond 48 hours, the treating doctor should, where possible:
    • inform the patient or next of kin/guardian of the rare chance of hearing or balance problems with gentamicin use, while simultaneously explaining the value that gentamicin has as an antibiotic in treating infection
    • tell the patient to report any hearing, balance or visual problems immediately.
    • document that the above have been done

high dose "once daily" or "interval adjustment" regime

  • “high dose once daily dosing” schedule is once daily dosing for patients with normal renal function, but may be less frequent if there is renal impairment with creatinine clearance < 60ml/min.
    • in patients with creatinine clearance > 60ml/min, 3 doses may be given at intervals of 24 hours
    • in patients with creatinine clearance 40 - 60ml/min, 2 doses may be given at interval of 36 hours
    • in patients with creatinine clearance 30 - 40ml/min, 2 doses may be given at interval of 48 hours
    • in patients with creatinine clearance < 30ml/min, the 1st empirical dose of gentamicin may be given but then changed to a non-aminoglycoside thereafter.
  • further dosing may require area under curve (AUC) computations of serial levels:
  • trough levels cannot be used for monitoring once daily dosing because they are often below lab. detectable threshold, but still high enough to increase risk of toxicity.

calculating creatinine clearance

adults
  • creatinine clearance can be approximated in adults using the modified Cockcroft-Gault formula:
    • adult males CrCl (mL/min) = [(140-age) x ideal weight in kg] / [0.814 x serum creatinine in micromol/L]
    • adult females = adult male calculation x 0.85
    • Ideal weight for adult male = 50 kg + 0.9 kg/each cm over 152 cm
    • Ideal weight for adult female = 45.5 kg + 0.9 kg/each cm over 152 cm
paediatric
  • 1 month to 2 years age: CrCl = 40 x height in cm / serum creatinine in micromol/L
  • 2 years to 12 years age: CrCl = 49 x height in cm / serum creatinine in micromol/L
  • 12 years to 21 years age females: CrCl = 49 x height in cm / serum creatinine in micromol/L
  • 12 years to 21 years age males: CrCl = 62 x height in cm / serum creatinine in micromol/L

rationale for "once daily" dosing:

  • Recent studies seem to indicate benefit in single daily doses for following reasons:
    1. higher concentration results in more rapid & extensive killing
    2. selection of resistant mutants during Rx less likely with higher concentration
    3. produce significant post-antibiotic growth suppression effects even after brief exposure
    4. efficacy determined by area-under-curve of drug exposure, not time concentration exceeds MIC
    5. nephrotoxicity & renal accumulation reduced with higher doses administered daily.
  • However, few studies using gentamicin & limited experience with pts with severe renal impairment (CRN > 300umol/L), febrile neutropenic sepsis, endocarditis or in paediatric pts. In addition, insufficient evidence for risks of ototoxicity.

low dose 8 hourly regime

  • “low dose 8 hourly dosing” requires close monitoring of TROUGH serum gentamicin levels AND clinical assessment for vestibular and auditory ototoxicity as this may be irreversible.
    • in this dosing regime, trough levels should be below 1mg/L to prevent ototoxicity
gentamicin.txt · Last modified: 2014/08/19 18:28 (external edit)