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The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative
Stacey Tkachuk1,2, Kyle Collins1,2, Mary H H Ensom3,4
1Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Background:
In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC.
Objective:
This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients.
Methods:
We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC.
Results:
Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400.
Conclusions:
Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More research is needed to determine the relationships between vancomycin trough concentrations, AUC/MIC, and clinical outcomes.
Insights
For pediatric patients, vancomycin trough concentrations of 6-10 mg/l are generally sufficient to achieve the target AUC/MIC of 400, though higher levels may be needed for certain infections. Further research is required to confirm these findings.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Pediatric Infectious Diseases
- Antimicrobial Stewardship
Background:
- The area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is a key predictor of vancomycin efficacy in adults against methicillin-resistant Staphylococcus aureus.
- This AUC/MIC target (≥400) is often applied to pediatric patients without sufficient supporting evidence.
- Vancomycin trough concentrations are commonly used as a surrogate for AUC/MIC due to practical limitations in calculating AUC.
Purpose of the Study:
- To review the existing literature on the relationship between vancomycin trough concentrations and AUC/MIC in pediatric populations.
- To evaluate the adequacy of current vancomycin dosing strategies in children based on trough levels.
Main Methods:
- A systematic literature search was conducted in major databases (MEDLINE, Embase, Cochrane).
- Keywords included vancomycin, AUC, and pediatric/paediatric.
- Studies published in English reporting the relationship between vancomycin trough concentrations and AUC/MIC were included.
Main Results:
- Eleven studies met the inclusion criteria.
- For general pediatric patients, troughs of 6-10 mg/l were often sufficient for AUC/MIC > 400.
- Higher troughs (≥15 mg/l) were suggested for oncology patients, and specific targets varied in critical care and cardiothoracic surgery patients.
- One study indicated a trough of 9 mg/l was insufficient in critical care.
Conclusions:
- Vancomycin targets vary significantly across different pediatric populations.
- Trough concentrations of 6-10 mg/l appear adequate for general pediatric patients to reach an AUC/MIC ≥ 400.
- Higher troughs are likely necessary for infections with MIC ≥ 2 mg/l, and more research is needed to correlate troughs, AUC/MIC, and clinical outcomes in children.
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