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Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized
Abdulwhab Shremo Msdi1,2, Jacinda C Abdul-Mutakabbir3,4, Karen K Tan5,6
1Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA, 92354, USA.
Introduction:
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC0-24). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC0-24 following a VAN LD of 20 mg/kg.
Methods:
This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC0-24. Therapeutic AUC0-24 was defined as 400-600 mg/l*h.
Results:
Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m2 and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC0-24, patients with subtherapeutic AUC0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m2 (67 vs. 52%). In contrast, patients with supratherapeutic AUC0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.
Insights
Only half of patients reach the target vancomycin (VAN) exposure with a 20 mg/kg loading dose (LD). Younger, heavier patients are often underexposed, while older patients with kidney issues risk overexposure.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections necessitate effective vancomycin (VAN) treatment.
- Achieving target vancomycin area under the curve (AUC) is crucial for favorable clinical outcomes.
- Current guidelines suggest a VAN loading dose (LD) of 20-35 mg/kg, but data on day 1 AUC (AUC0-24) impact is limited.
Purpose of the Study:
- To calculate and describe the AUC0-24 following a 20 mg/kg VAN LD using pharmacokinetic equations.
- To evaluate the proportion of patients achieving therapeutic VAN AUC0-24 targets.
- To identify patient factors associated with subtherapeutic or supratherapeutic VAN exposures.
Main Methods:
- Retrospective study of adult patients receiving VAN 20 mg/kg LD.
- Inclusion criteria: ≥48 hours of treatment, two consecutive serum VAN levels within 24 hours.
- Calculation of AUC0-24 using linear, non-trapezoidal PK equations and two post-infusion VAN levels.
Main Results:
- 50% of 123 patients achieved the therapeutic AUC0-24 (400-600 mg*h/L).
- 22% were subtherapeutic, and 28% were supratherapeutic.
- Subtherapeutic levels were associated with younger age and higher BMI (≥30 kg/m²); supratherapeutic levels with older age and chronic kidney disease.
Conclusions:
- A 20 mg/kg VAN LD results in suboptimal AUC0-24 achievement in 50% of patients.
- Dosing adjustments are needed: younger, heavier patients may require higher doses, while older patients with renal impairment may need lower doses.
- Individualized dosing strategies are essential for optimizing VAN therapy and improving patient outcomes.
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