SCCM Resource Library-51-Efficacy of Vancomycin Loading Doses in Methicillin-Resistant Staphylococcus aureus Bacteremia

Video Transcription

Hi, everyone. My name is Narelli Kalaria, and I'm a Critical Care Clinical Pharmacist at Christiana Care in Wilmington, Delaware. And I'll be presenting my research titled  Efficacy of Vancomycin Loading Doses in Methicillin-Resistant Staphylococcus aureus Bacteremia. I have nothing to disclose in relation to this presentation. For background, we know  vancomycin is routinely used to treat infections caused by methicillin-resistant staphylococcus  aureus, which I'll refer to as MRSAE going forward. In 2011, the vancomycin guidelines recommended a utilization of loading doses of 25 to 30 milligrams per kilogram in critically  ill patients to rapidly attain target serum concentrations of 15 to 20. This recommendation was rated a grade C level 3 due to minimal available evidence. I do want to acknowledge  that in March of 2020, the guidelines were updated after the initiation of this project with adjustment in the dose of the initial dose as well as monitoring parameters. The  reason for utilizing the loading dose is that higher initial doses have resulted in positive pharmacokinetic results with attainment of gold trough levels sooner. Theoretically,  the rapid achievement of therapeutic vancomycin levels should result in improved clinical outcomes. However, the clinical implication of this pharmacokinetic response has not been  extensively studied, which led to the grade C level 3 recommendation within the 2011 guidelines.  In 2018, Veselik et al. conducted a retrospective cohort study in patients with MRSA bacteremia.  They found that patients who received an initial vancomycin dose of 20 milligrams per kilogram  or greater had faster resolution of their systemic inflammatory response syndrome. However, they had no difference in mortality, time to negative blood culture, or hospital length  of stay. Due to the minimal available evidence, we conducted a retrospective cohort study to compare clinical outcomes in patients with MRSA bacteremia who did and did not receive  a vancomycin loading dose. And a loading dose was defined as an initial vancomycin dose of greater than 20 milligrams per kilogram. And our study period was from January 2014  to June 2019. Patients who were aged 18 or older, hospitalized with at least one positive blood culture, and received vancomycin for at least 72 hours were included in our study.  And our pertinent exclusion criteria includes patients weighing greater than 125 kilograms,  the maximum recommended loading dose per our institutional policy is 2,500 milligrams.  The primary outcome was rate of clinical failure, which was a composite of day seven microbiologic  failure, switching of vancomycin to another anti-MRSA antibiotic prior to blood culture clearance, as well as in-hospital mortality prior to blood culture clearance. Secondary  efficacy outcomes included day four microbiologic failure in addition to in-hospital mortality, and secondary safety outcome was the rate of nephrotoxicity. And this was defined as  an increase in serine creatinine by 0.5 or 50%, whichever was greater, on at least two  consecutive occasions or new onset dialysis within 120 hours from the initial dose of vancomycin.  For our patient population, there were 626 patients who had MRSA bacteremia within our time frame, and of those 359 patients met our inclusion and exclusion criteria.  And about a third of those patients did not receive a loading dose and the remainder at 239 did receive a loading dose. For baseline characteristics, there were significant  differences between the two groups going from top to bottom. The patients who did not receive  a loading dose were slightly older and weighed a little bit more than those who did receive a loading dose. Those without a loading dose also had a higher baseline serine creatinine  and more patients were chronically on hemodialysis. They also had a higher median Alexhauser comorbidity score. And overall, there is no difference in patients who received an  infectious disease consult or those with complicated bacteremia.  Majority of the patient population had an MIC of one or less  for vancomycin and majority of the patients had their vancomycin dose by pharmacy.  As expected, the median initial vancomycin dose was significantly higher in those who received a loading dose at 26 milligrams per kilogram compared to 16 milligrams per kilogram.  And interestingly, the median time to first therapeutic trough  was a lot longer in the loading dose group at 86 hours compared to 59 hours.  For our primary outcome of clinical failure, there was no significant difference found between those who did and did not receive a loading dose group with both groups at about 20%.  And when breaking down each component within the composite, there also was no significant difference between groups for day seven microbiologic failure, switching of vancomycin  into another anti MRSA antibiotic prior to blood culture clearance or in-hospital mortality prior  to blood culture clearance. When looking at the probability of treatment failure upon a continuum  of the initial dose or the unadjusted probability, there was slightly higher probability of failure  with doses less than 20 milligrams per kilogram and doses greater than 24 milligrams per kilogram.  And when this probability was adjusted for median ACM creatinine and Alex Hauser score,  the trend did skew more towards doses greater than 24 milligrams per kilogram.  For secondary outcomes of day four microbiologic failure, in-hospital mortality, and nephrotoxicity, there also was no significant difference between the two groups.  I do want to mention some important limitations. This study was a single center retrospective chart review. It was underpowered, and the maintenance vancomycin regimens were not  evaluated, which may have compounded in some of the outcomes. And there were differences in baseline characteristics between the two groups, which we did try to adjust for.  For conclusions, a significant difference in clinical outcomes was not observed with the use  of loading doses greater than 20 milligrams per kilogram. And when the composite treatment  failure was evaluated on a continuum of initial vancomycin doses, the risk of failure was higher  with initial doses greater than 24 milligrams per kilogram. Future studies are needed to determine  the safety and efficacy of vancomycin loading doses in MRSA bacteremia, and if utilized,  the optimal weight-based dosing range. I would like to acknowledge the individuals on this slide for their major contributions to this research project.  And with that, that concludes my presentation, and I'd like to thank everyone for joining me.

Video Summary

In this presentation, the speaker discusses the use of loading doses of vancomycin in the treatment of methicillin-resistant Staphylococcus aureus bacteremia. The speaker explains that although loading doses have been recommended to rapidly achieve target serum concentrations, there is limited evidence on the clinical implications of this approach. The speaker conducted a retrospective cohort study comparing clinical outcomes in patients who received a loading dose versus those who did not. The study found no significant difference in clinical outcomes between the two groups. The speaker suggests that future studies are needed to determine the safety and efficacy of vancomycin loading doses in MRSA bacteremia.

Asset Subtitle

Pharmacology, Infection, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Nirali Kalaria

Introduction/Hypothesis: Vancomycin is routinely used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In critically ill patients, vancomycin loading doses are utilized to rapidly attain target serum concentrations. The vancomycin guidelines cite the use of loading doses as a level II, grade B recommendation due to a lack of robust evidence. Using higher initial doses has resulted in positive pharmacokinetic results, with more patients reaching goal trough levels sooner. However, the clinical implication of this pharmacokinetic response has not been extensively studied. The purpose of this study was to compare clinical outcomes in patients with MRSA bacteremia who did and did not receive a vancomycin loading dose.

Methods: This retrospective, single-center, cohort study included patients who received vancomycin for at least 72 hours for MRSA bacteremia from January 2014 to June 2019. The cutoff of 20 mg/kg of vancomycin was used to identify patients who received a loading dose. The primary objective was to compare composite clinical failure. This endpoint included day seven microbiological failure, switching of vancomycin to another anti-MRSA antibiotic prior to blood culture clearance, and in-hospital mortality prior to blood culture clearance. Statistical analysis was performed using the chi-square test for categorical data and the Wilcoxon signed rank test for continuous data.

Results: A total of 359 patients were included in the study, with 239 patients receiving a loading dose. The median initial vancomycin dose administered in the control group was 16.1 mg/kg compared to 26 mg/kg in the loading dose group (p<0.001). Baseline characteristics were similar between groups except a higher median baseline serum creatinine (1.94 mg/dL vs 0.92 mg/dL, p<0.001) and Elixhauser comorbidity score (25 vs 17, p=0.001) in the control group. There was no significant difference in the composite primary outcome (20.8% vs 19.2%, p=0.45) or its individual components. There was also no significant difference in secondary outcomes between the two groups: Day four microbiological failure (26.7% vs 25.9%), in-hospital mortality (12.5% vs 9.2%), and nephrotoxicity (11.1% vs 6.6%).

Conclusions: The utilization of a vancomycin loading dose did not alter clinical outcomes in patients with MRSA bacteremia.

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Area Infection

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Antibiotics

Year 2021

Keywords

loading doses

vancomycin

treatment

methicillin-resistant Staphylococcus aureus bacteremia

clinical outcomes

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