Episode 60- Should we load vancomycin?

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.