47: Augmented renal clearance, endocarditis treatment, and tPA risk vs benefit

In this episode I’ll:

1. Review an article about augmented renal clearance of antibiotics in critically ill patients
2. Answer the drug information question “For a patient with rash to penicillin that is 5 months s/p TAVR and has 4/4 bottles positive for gram positive cocci resembling staph, what antibiotic regimen should be used?”
3. Share a resource I use to visually show the risks and benefits of tPA use in acute ischemic stroke
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Thank you to Pharmacy Monique for sharing this article!

Article

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

Authors: Athena L V Hobbs, Katherine M Shea, Kirtsen M Roberts, and Mitchell J Daley
Published in: Pharmacotherapy November 2015

Background

Augmented renal clearance (ARC) of medications has been reported in 30–85% of patients in the intensive care unit, depending on patient specific factors.

Purpose

This review article characterizes ARC in the critically ill, describes risk factors, reviews screening methods and assessment strategies, and illustrates its effect on in vivo drug concentrations and clinical outcomes.

Methods

The authors conducted a PubMed search that included all pertinent articles from January 1990 through April 2015.

Discussion

The authors state:

There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure.

Discussed in the article is a weighted scoring system previously published for ARC.  Patients get 6 points if they are 50 years or younger, 3 points if they are admitted for trauma, and 1 point if their SOFA score is 4 or less upon ICU admission.

An ARC score >7 is associated with 100% sensitivity and 71.4% specificity for detecting ARC.  This correlates with a 75% positive predictive value and a 100% negative predictive value.  For more on sensitivity, specificity, and predictive values of medical tests check out episode 23.

Using the ARC score, the authors of this review developed an algorithm for identification and assessment of ARC.

In critically ill patients with a serum creatinine less than 1.3 mg/dL and either an ARC score >7 or traumatic brain injury/subarachnoid hemorrhage, the authors recommend obtaining an 8 hour urine collection for creatinine clearance calculation. If the measured creatinine clearance is >130ml/min, the authors recommend using higher doses of antibiotics to account for the augmented renal clearance.

Antibiotic dose recommendations are based on pharmacodynamic dose-finding studies in patients with ARC and generally involve using higher doses and extended infusions such as:

– Piperacillin-tazobactam 4.5 g over 4 hours every 6 hours
– Meropenem 2 g over 3 hours every 8 hours
– Cefepime 2 g over 3 hours every 6 hours

For antibiotics that allow therapeutic drug monitoring such as vancomycin and aminoglycosides, the authors recommend dosing at the high end of usual dose ranges (vanco 25–30mg/kg loading dose, then 15–20 mg/kg every 8–12 hrs or gentamicin 7mg/kg/day) and adjusting as drug levels require.

Drug information question

Shout out to Nurse Practitioner Meagan for asking this excellent drug information question:

Q: For a patient with rash to penicillin that is 5 months s/p TAVR and has 4/4 bottles positive for gram positive cocci resembling staph, what antibiotic regimen should be used?

A: Vancomycin + rifampin + gentamicin

This patient met 2 of the major Duke Criteria for endocarditis:

1. Two sets of blood cultures positive with typical organisms (staph) and no other source.
2. A majority of 4 cultures positive.

A TAVR is a Transcatheter Aortic Valve Replacement.  This means we will need to cover our patient for prosthetic valve endocarditis.

As Nurse Practitioner Meagan astutely pointed out on rounds, the fact the patient had a TAVR tells us quite a bit about the patient’s baseline state of health.  Patients who undergo the TAVR procedure are considered either high-risk or too sick for open heart surgery.  This meant that treatment of endocarditis for this patient would likely be medical, not surgical.

There are AHA guidelines that can be used to help answer this question.  For prosthetic valve endocarditis due to staph, the recommended regimen is vancomycin + rifampin + 2 weeks of gentamicin.

As Meagan & I were discussing treatment options for this patient, Infectious Disease Doctor Phil came to see the patient.  He decided to delay giving rifampin/gentamicin until results of the trans-esophageal echocardiogram were available.

Resource

The resource I’m sharing for this episode is a position statement on tPA for acute ischemic stroke from the American Academy of Emergency Medicine.

On page 2 of the position statement there is a visual representation comparing usual care of acute ischemic stroke vs giving tPA within the first 3 hours per the NINDS protocol.

The colors green, red, and black are used to visually represent patients with a good outcome, poor outcome, and intracranial hemorrhage. I always use this visual aid when teaching pharmacy students and residents how to evaluate the risk vs benefit of tPA.

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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.

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