In this episode I’ll:
1. Discuss an article about high-dose daptomycin for patients with MRSA bacteremia.
2. Answer the drug information question “Which patients receiving once-daily gentamicin dosing should have a trough level checked?”
3. Share a resource for up to date antimicrobial sensitivity breakpoints.
Article
Lead author: Tristan T Timbrook
Published ahead of print in Pharmacotherapy December 2017
Background
Current IDSA guidelines give a class B-III recommendation to use higher daptomycin doses than the labeled dose of 6mg/kg for MRSA bacteremia or endocarditis. However, the evidence supporting this recommendation is weak, coming from in vitro and case series studies. The authors conducted this study to evaluate the comparative effectiveness of daptomycin 6 mg/kg versus higher daptomycin doses in patients with MRSA bacteremia.
Methods
The study was a retrospective cohort study which looked at 371 adult patients with MRSA bacteremia. To be included in the study patients had to be initially treated with vancomycin within 24 hours of initial culture collection, and then switched to daptomycin therapy within 7 days. 138 patients (37.2%) received daptomycin doses higher than 6 mg/kg, and 233 (62.8%) received daptomycin 6mg/kg.
Results
Propensity score–matched 30-day mortality was 8.6% among the higher dose group versus 18.6% among the 6 mg/kg dose group. A categorization and regression tree (CART) analysis suggested that higher doses of daptomycin provided benefit only among patients with a 51% or higher predicted probability of 30-day mortality.
Conclusion
The authors concluded:
To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (≥7 mg/kg) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia.
Discussion
Higher daptomycin doses were associated with improved survival. This information justifies the current guideline recommendations of using higher daptomycin doses in patients with MRSA bacteremia or endocarditis. This data fits with recent studies that have suggested that higher daptomycin doses improve outcomes in patients with vancomycin-resistant enterococcal (VRE) bacteremia. I discussed one of these studies in episode 153.
In this study, creatinine phosphokinase (CPK) elevations in the 6mg/kg dose group versus the higher daptomycin dose group were not significantly different. Nevertheless, when using daptomycin at doses higher than 6mg/kg, I prefer to check CPK levels several times weekly.
Drug information question
Q: Which patients receiving once-daily gentamicin dosing should have a trough level checked?
A: I check a trough at least once for my once-daily gentamicin patients if they are in the ICU, elderly, receiving a concomitant nephrotoxin, or receiving gentamicin for longer than 3 days. My target trough for these patients is less than 1 mcg/mL.
Some good references for gentamicin monitoring are the University of San Francisco guidelines and Johns Hopkins Antibiotic Guide.
Resource
The resource for this episode is the new FDA webpage promoting FDA-recognized antimicrobial susceptibility test interpretive criteria. The previous system of updating sensitivity breakpoints was inefficient and slow to reach practicing clinicians. This new webpage allows the FDA to expedite the recognition of antimicrobial susceptibility test interpretive criteria and provide up-to-date information to the healthcare community in a more streamlined manner. The page will be updated by the FDA at least once every 6 months.
I have over 15 free downloadable resources for critical care and hospital pharmacists in my free download area. For immediate access to the complete list, go to pharmacyjoe.com/free.
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.
Hi Pharmacy Joe, thanks so much for the great episode!! I was curious if the daptomycin study stated what body weight equation was used for all the patients and if there was any information regarding whether obese patients were included.
Hi Matt! Actual body weight was used. The authors reported more patients receiving the label dose were obese compared with those receiving the higher dose (39.9% vs 29.0%, p=0.03).