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Gentamicin pharmacokinetic assessment

A 45 year old female hemodialysis patient I had been following was febrile during her nocturnal dialysis session. That night an order for gentamicin 80mg IV post-HD had been ordered. She has polycystic kidney disease and the concern was infection from a ruptured cyst could quickly turn fatal. I completed an assessment of the order the following day and the empiric dosing had not taken into consideration the patient’s dry weight of 110kg at a height of 5’4. She did recover quickly following a gentamicin dose of ~1mg/kg and the cause was likely not bacterial. After speaking with the nephrologist, I documented the assessment in her chart including her adjusted body weight (ABW), calculations to reassess if her weight changes significantly and suggestions to consider for dosing. She is considered at high risk of a cyst rupture requiring timely and effective antibiotic dosing. Given a long list of drug allergies which include antibiotics, gentamicin would likely be employed if this occurred. Her antibiotic allergies are cephalexin (hives/vomiting), ciprofloxacin (hives/anaphylaxis), sulfa drugs (anaphylaxis), vancomycin (hives/anaphylaxis). So I wanted to share this if only to solidify it in my own head. Just to be clear, I am not in anyway implying that the nephrologist need the equations written in the chart. It’s just that as long as she remains on nocturnal dialysis, there is the possibility of a 2 am call and no matter how brilliant you are, EVERYONE deserves an equation sheet at 2 am.

Given her weight and height, an adjusted weight of 76.8kg was calculated. Firstly a loading dose (LD) of 2-3mg/kg for an infection of this etiology was recommended. A LD would more quickly approach steady state concentrations (not steady state!). Gentamicin exhibits concentration dependent killing whereas adverse drug reactions are generally time dependent. Gentamicin 160mg IV post-HD as a LD was suggested rather than 200mg IV on the higher end of the spectrum. This was in part in an effort to protect any residual kidney function and in part because it seems like a very high dose (very scientific, I know). When determining an appropriate maintenance dose, the most likely pathogens from a burst cyst are reportedly E. coli (75%) or another gram negative rod (UptoDate). The suggested dosing for this was gentamicin 1.5-2mg/kg. This gives a maintenance dose of 120mg IV post-HD or alternately 100mg IV post-HD (1.3mg/kg) which is a safer dose in the absence of gentamicin level and close to the reference range. Optimally, the maintenance dose is guided by a pre-HD trough (target 2.5-5mg/L in HD patients).

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