gentamicin

see also;

• antibiotics
• aminoglycoside antibiotics
• WH guideline - Gentamicin - Interval Adjustment Dosing Method for Adults (pdf) - WH intranet only
• WH guideline - Gentamicin Administration in the Neonate and Child (pdf) - WH intranet only

• 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

• 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

• severe acute acute pyelonephritis with 2g iv ampicillin 6hrly
• peritonitis (eg. perforated viscus) with 1g ampicillin 6hrly and metronidazole 500g 12hrly
• cholecystitis or ascending cholangitis with 1g iv ampicillin 6hrly
• severe diverticulitis with 1g ampicillin 6hrly and metronidazole 500g 12hrly
• infective endocarditis (including SBE) - 8hrly dosing regime!!!
• other Gram negative infections

• 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.
• see elsewhere for infective endocarditis (including SBE) Rx

• 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

• 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.

• “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:
  • one serum level is near peak and the other is taken 6-14 hours after dosing
  • Aladdin AUC calculator
  • TCIWorks AUC calculator
• 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.

• 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

• 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

• 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 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