In this episode, I’ll discuss a recent survey of intensive care professionals about clinically relevant pharmacokinetic knowledge on antibiotic dosing.
Lead author: Lucas M. Fleuren
Published May 2019 in the journal Critical Care
This study was of a survey that was sent out to over 20,000 intensive care professionals in May of 2018. There were over 1400 responses, mostly from clinicians in European countries. Respondents in descending order of frequency were intensivists, residents, fellows, and nurses.
The survey was a set of 12 questions designed to cover clinically relevant topics related to antibiotic pharmacokinetics in the setting of intensive care medicine.
The core competencies which the questions were drawn from were defined by the Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) collaboration.
The questionnaire pass rates were 42.5% for intensivists, 36.1% for fellows, 24.8% for residents, and 5.8% for nurses.
The authors concluded that
Clinically relevant pharmacokinetic knowledge on antibiotic dosing among intensive care professionals is insufficient. This should be addressed given the importance of adequate antibiotic exposure in critically ill patients with sepsis. Solutions include improved education, intensified pharmacy support, therapeutic drug monitoring, or the use of real-time bedside dosing software. Questions may provide useful for teaching purposes.
In this and the upcoming episodes of this podcast, I will review the answers to the survey questions asked and the clinical relevance of each question.
The first question listed 4 antibiotics: vancomycin, ceftriaxone, meropenem, and ciprofloxacin. Respondents were asked to categorize each antibiotic as lipophilic or hydrophilic.
Ciprofloxacin is lipophilic, while vancomycin, ceftriaxone, and meropenem are hydrophilic.
This is clinically relevant because the degree of hydro- or lipophilicity heavily influences the apparent volume of distribution (Vd) of antibiotics. While the hydrophilic antibiotics listed have a volume of distribution ranging from 7 to 69 L, ciprofloxacin has a Vd of 150 L or greater. Changes in critically ill patients may increase the Vd – such as fluid overload from resuscitation or leaking capillary beds from sepsis.
With this knowledge of hydro- or lipophilicity, the clinician can predict that the lipophilic/high Vd drug ciprofloxacin is much less likely to be affected by changes in Vd due to critical illness than vancomycin, ceftriaxone, or meropenem.
Questions 2 and 3 were open-ended and asked “Which antibiotic is barely protein-bound?” and “For which antibiotic, using continuous infusion, is a loading dose least (!) important?” The answer to both of these questions is meropenem. Meropenem’s hydrophilicity and lack of protein binding make it have a very low Vd. It also has a very short half-life of 1 hour. For these reasons, meropenem reaches steady state very quickly compared with other antibiotics, and a loading dose is less important than with, for example, vancomycin.
Questions 4 and 5 addressed the effects of severe renal dysfunction on the dosing schedules for vancomycin, ceftriaxone, meropenem, and ciprofloxacin. Question 4 asked “In case of severe renal dysfunction, how should the maintenance dose be adapted for these antibiotics?” and question 5 asked “In case of severe renal dysfunction, how should the initial dose be adapted for these antibiotics?” For all antibiotics listed in these questions, the initial dose is unchanged and the maintenance doses should be decreased. The authors of the survey also accepted increasing the dosing interval for question 4, not just lowering the dose.
Pharmacists that practice in intensive care settings can play a key role in ensuring clinicians have adequate pharmacokinetic knowledge on antibiotic dosing. You can do so by designing education material for your colleagues based on the questions highlighted in this study or by sharing this podcast with them.
To download a copy of my free visual critical care antibiotic coverage guide, go to pharmacyjoe.com/abx.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.