Episode 60- Should we load vancomycin?


 

Episode Summary:

Does loading vancomycin lead to achieving target levels within the first 24 hours? Does it increase the risk of nephrotoxicity?

Show Notes:

Key Points:

“Should we load vancomycin?:”
– Guidelines recommend giving a loading dose of vancomycin to critically-ill adult patients with severe infections. They also recommend an AUC (area under the curve) / MIC (minimum inhibitory concentration) target of 400-600 mg x h/L as a predictor of vancomycin activity against MRSA strains with an MIC of </= 1
– Trough levels are used as a surrogate measure of the AUC. A trough level between 15-20 mg/L has been shown to achieve an AUC/MIC >/= 400
– In one study, the authors wanted to see if using a vancomycin loading dose of 25 mg/kg (max 2,500 mg) improved AUC/MIC target attainment and if this loading dose increased the risk of acute kidney injury (AKI) or mortality
– This prospective observational before/after study looked at two groups of patients; those that were treated per their old protocol with a fixed 1,000 mg loading dose (CD group) and those who received a loading dose of 25 mg/kg (LD group ). All patients were then continued on 1,000 mg Q12 H followed by dose adjustments based on vancomycin levels
-A total of 89 vancomycin courses were included (39 in the CD group and 50 in the LD group). Baseline characteristics were similar; 60% were male, the average age was 60 years, the average weight was 75 kg, and APACHE II scores were ~ 19 in each group. Patients also had similar rates of obesity, similar renal function, and cumulative treatment durations (~90 hours). Sources of infection were mostly intra-abdominal or catheter-related bloodstream infections
– The LD group had a higher chance of achieving an AUC >/= 400 compared to the CD group (88% vs 54%, P= 0.0006). New-onset AKI was not different between the groups (38% in LD vs. 29% in CD group, P= 0.48). There was also no difference in mean AKI duration (37 h vs 75 h), percentage of patients needing dialysis at discharge (32% vs 21%), or mortality (27% vs 33%)
ER-Rx Episode 60

Please click HERE to leave a review of the podcast!

Transcript:

Hello and welcome to Episode 60 of ER-Rx. In this “Fresh Fruit” series, we discuss an article published in the Journal of Antimicrobial Chemotherapy in August 2021. This one is entitled “Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients.”

First, a little bit of history on how we monitor vancomycin. The first monitoring guidelines were published in 2009, and they were just recently updated in 2020. Of importance to us in the ER and ICU, both of the guidelines recommend using actual body weight (ABW) for vancomycin dosing and using a loading dose (LD) in critically-ill patients with severe infections- despite the fact that neither of these recommendations are supported by great evidence from large, randomized trials. They also recommend an AUC (area under the curve) / MIC (minimum inhibitory concentration) target of 400-600 mg x h/L as a predictor of vancomycin activity against MRSA strains with an MIC of Still, most centers, like mine, only monitor vancomycin trough levels, and not the AUC. That’s because in the past, calculating an AUC required multiple vancomycin levels and pharmacokinetic software and it just wasn’t possible for most centers to carry out. That’s why we’re all much more familiar with vancomycin trough monitoring. Trough levels are used as a rough surrogate measure of the AUC. A trough level between 15-20 mg/L has been shown to achieve an AUC/MIC >/= 400 (when the MIC of vancomycin is In patients with MRSA bacteremia, the achievement of an adequate AUC/ MIC in the first 24 hours is associated with a significant decrease in treatment failure and mortality. On the flip side, as we get higher trough and AUC levels, the risk of acute kidney injury (AKI) increases.

To add to the literature regarding the use of vancomycin loading doses in critically ill adults, the authors of this study wanted to see if using a vancomycin loading dose of 25 mg/kg (based on ABW; max of 2,500 mg) improved AUC/MIC target attainment and if this loading dose increased the risk of AKI or mortality during an ICU stay. This is the largest study on the effect of a loading dose on AUC target attainment that we have.

This was a prospective observational before/after study that looked at two groups of patients; those that were treated per their old protocol with a fixed 1,000 mg loading dose (CD group) and those who received a loading dose of 25 mg/kg (LD group). All patients were then continued on 1,000 mg Q12 H followed by dose adjustments based on vancomycin levels.

In the end, a total of 89 vancomycin courses were included (39 in the CD group and 50 in the LD group). Baseline characteristics were similar; 60% were male, the average age was 60 years, the average weight was 75 kg, and APACHE II scores were about 19 in each group. Patients also had similar rates of obesity, similar renal function, and cumulative treatment durations (~90 hours). Sources of infection were mostly intra-abdominal or catheter-related bloodstream infections. However, there were no MRSA or VRE strains isolated in any patient.

In terms of results, the LD group had a higher chance of achieving an AUC >/= 400 compared to the CD group (88% vs 54%, P= 0.0006). And better yet, new-onset AKI was not different between the groups (38% in LD vs. 29% in CD group, P= 0.48). There was also no difference in mean AKI duration (37 h vs 75 h), percentage of patients needing dialysis at discharge (32% vs 21%), or mortality (27% vs 33%).

As a side note, as previously reported, achieving an AUC >/= 400 (39% vs 15%, P=0.031) or >/= 600 (49% vs 25%, P=0.017) as compared to not reaching those thresholds was associated with a higher incidence of new-onset AKI. This shows that higher vancomycin exposure overall is associated with an increased risk of AKI, but it’s unclear whether a loading dose increases this risk. The authors stress getting levels within 24-48 hours and adjusting vancomycin maintenance doses as needed to reduce the risk of AKI.

In conclusion, the results of this study aren’t too surprising and match up well with the guideline recommendations. There are some limits to this study, of course. It was a small, single-center study out of the Netherlands (with their lower average weights, lower rates of obesity, and with their nomograms showing that only 1% of staph aureus isolates are MRSA). The study also didn’t actually have any patients with MRSA infections, which may skew mortality rates just a bit. But despite all of this, we can still be just a bit more confident that loading patients with vancomycin in the ER is the right thing to do. In my ER, we load all adult patients with serious infections with 25 mg/kg (with a max of 2,500 mg) and use a nomogram for subsequent maintenance doses. We do still monitor trough levels only at this point in time, despite the new guidelines recommending monitoring AUCs instead of troughs—but we are hoping to implement this change in the future. >p> As always, thank you so much for your time. Are you guys loading your vancomycin? What dose do you use, and what do you cap it at? Please reach out to us on errxpodcast.com or on the @ERRxPodcast Instagram page. I’d love to hear about your practice and will share all answers as they come in.

References:


Leave a Reply

Your email address will not be published. Required fields are marked *

Recent Reviews/ Comments

“Perfect amount of knowledge in a great length to refresh ICU and ED topics. Explains concepts in an easy to understand fashion”

–  RxLaura, Apple Podcasts review

“I love listening to this podcast because I can listen to 1 or 2 on my way to work and it provides great info! As a paramedic, this podcast has really helped me understand the “why” we give certain meds.”

cresjr, Apple Podcasts review

“Ideal podcast to listen on the way to my shift. Learning points throughout!”

andmatjos, Apple Podcasts review

“I’m currently in my last year of pharmacy school […] I just happen to come across your podcast on YouTube as I was trying to find a good explanation regarding the misleading sulfa allergy in non-antibiotic sulfonamides. Your explanation was great. I can’t believe I’m only now finding out about your podcasts but please continue to make them for as long as you can. Prospective pharmacists, such as myself, really appreciate you taking the time to put such great educational content out there.”

– S.P., Pharmacy Student

“Adis does a wonderful job of gathering the evidence-based answers to the hard questions that we all get as pharmacists and putting them into a nice, neat package.”

– rebroush1, Apple Podcasts review

“This is a great podcast to listen to at work and is not too overwhelming and well put together. Highly recommended for anyone in healthcare, even outside of emergency medicine.”

Peelage, Apple Podcasts review

“Great reviews on drug-related topics with useful details on drug mechanisms, pharmacodynamics and administration considerations as well as data to support recommendations. Great for pharmacists, providers and learners!”

-JaayyZzee, Apple Podcasts review

“I found the topics very helpful. I have been recommending this show to pharmacy students and residents, who are also enjoying it.”

hvgjnfd, Apple Podcasts review

“As a PA, I found this very informative. I like that the episodes are short, making them easy to listen to on my way to and from work. Would love to hear more pediatric topics!”

-Pediatric PA, Apple Podcasts review

“Good podcast thats very informative for all healthcare providers. Very easy to listen to and enjoy.”

-Bradlley88, Apple Podcasts review