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Published on: September 8, 2021
Efficacy and safety of vancomycin loading doses in critically ill patients with methicillin-resistant Staphylococcus
Alexander H Flannery1, Katie L Wallace2, Christian N Rhudy3
1Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone Street, TODD 251, Lexington, KY 40536, USA Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA.
Background:
While vancomycin loading doses may facilitate earlier pharmacokinetic-pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults.
Methods:
Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent.
Results:
There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences.
Conclusion:
Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection.
Insights
Vancomycin loading doses did not improve clinical outcomes for critically ill patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. This study found no significant differences in clinical failure rates between groups receiving a loading dose or not.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pharmacology
Background:
- Critically ill patients with MRSA infections face high mortality risks.
- Vancomycin loading doses may improve early drug concentration targets.
- The clinical benefit of vancomycin loading doses in this population is not well-established.
Purpose of the Study:
- To investigate the association between vancomycin loading doses and clinical outcomes in critically ill adults with MRSA infections.
Main Methods:
- A cohort study of 449 critically ill patients with MRSA bloodstream or respiratory infections.
- Patients were grouped based on receipt of a vancomycin loading dose (≥20 mg/kg actual body weight).
- Primary outcome was clinical failure, a composite of mortality, persistent bacteremia, and other clinical markers.
Main Results:
- No significant difference in clinical failure rates between the loading dose and no loading dose groups (74.8% vs. 72.8%).
- Secondary outcomes, including mortality and acute kidney injury, were similar between groups.
- Subgroup and multivariable analyses also showed no benefit from loading doses.
Conclusions:
- Vancomycin loading doses were not associated with improved clinical outcomes in critically ill patients with MRSA infections.
- The findings suggest that standard dosing may be sufficient for this patient population.
- Further research could explore specific subgroups or alternative dosing strategies.
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