In this episode I’ll:

1. Discuss an article about 3 different dosing strategies for daptomycin in VRE bacteremia.

2. Answer the drug information question “Should sequential compression devices be combined with chemoprophylaxis for venous thromboembolism prevention in critically ill patients?”

3. Share a resource for QT prolonging medications.

If you have been wondering if my Hospital Pharmacy Academy is right for you, now is the time to check it out. To ring in the new year I am offering a $1 trial where you can get full access to the Academy for a limited time. (Please note: the trial offer has ended but you can still click here to join the Academy) The Academy is entirely self-paced and is designed to help pharmacists like you develop new clinical pharmacy skills and stay ahead of the medical literature.

Each month, a new Masterclass is published. Topics include:

1. ICU rounds

2. Airway pharmacology

3. Patient assessment

4. Pharmacist response to emergencies 101

5. ECG recognition for pharmacists

Every week, I review the literature and create a brief digest in video and audio formats of the most important articles. I include my opinion of where each article fits in clinical practice.

To learn more go to pharmacyjoe.com/academy.

Article

Comparative Effectiveness and Safety of Standard, Medium, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Lead author: Nicholas S. Britt

Published in Clinical Infectious Diseases online December 2016

Background

Daptomycin is effective against Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSI). The optimal dose seems to continually creep higher and higher, perhaps because of the chance that on-treatment resistance can develop. In this study the authors attempt to analyze how high can the daptomycin dose go before efficacy plateaus or the risk:benefit analysis changes.

Methods

The authors performed a retrospective cohort study of 911 hospitalized Veterans Affairs patients treated with standard (6 mg/kg), medium (8 mg/kg), and high-dose (≥ 10 mg/kg) daptomycin for VRE-BSI. All doses were based on total body weight. The primary outcome was overall survival, and secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation.

Results

78%, 16%, and 6% of patients received standard, medium, and high dose daptomycin respectively. Both standard and medium dose groups had a statistically significantly greater hazard ratio for poorer survival compared to the high-dose group. Thirty-day mortality was also significantly lower among high-dose daptomycin-treated patients compared to medium and standard dose treated patients. There was no difference in the risk of CPK elevation between groups.

Conclusion

The authors concluded:

High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.

Discussion

Short of a randomized trial addressing the same question, this data is compelling enough to justify using 10 mg/kg based on total body weight of daptomycin to treat VRE bacteremia. That is a lot of daptomycin, especially in overweight and obese patients. As I discussed in episode 91, linezolid is also FDA approved for VRE bacteremia, and at some point, it may make more sense to use linezolid from a cost:benefit point of view. Also linked in episode 91 is a resource for dosing critical care medications in obese patients – the authors of that resource also recommend using total body weight to dose daptomycin.

Drug information question

Q: Should sequential compression devices be combined with chemoprophylaxis for venous thromboembolism prevention in critically ill patients?

A: No, it is not necessary to use sequential compression devices for patients on chemoprophylaxis for venous thromboembolism.

Shout out to “Intensivist Anwar” for asking this question. The 2012 CHEST guidelines recommend using sequential compression devices for VTE prophylaxis in patients at high bleeding risk and switching back to chemoprophylaxis (ex: enoxaparin or heparin) once the bleeding risk subsides. They do not recommend combining SCDs with chemoprophylaxis. The 10th edition update to these guidelines do not recommend combination therapy. Likewise, a PubMed search and review of tertiary resources like UpToDate did not find any recommendations on combining SCDs with chemoprophylaxis.

Resource

Shout out to “Pharmacy Melissa” for sending in this resource!

The website crediblemeds.com maintains various lists of medications which have been associated with QT prolongation. Registration is required (it is free) to be able to download and review all lists of QT-related medications. Because the lists are extensive and even a single report of QT prolongation can cause a medication to be added, I find this website very useful for avoiding QT prolonging medications in patients with long QT syndrome. For evaluating QT related drug interactions I prefer a more focused reference such as the Top 100 Drug Interactions by Hansten & Horn.

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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