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Vancomycin Area Under the Curve to Minimum Inhibitory Concentration Ratio for Treatment Effectiveness in Pediatric
Rou-Yee Chenhsu1, Brent A Hall1, Heidi Tran1
1Department of Pharmacy (R-YC, BAH, HT, MAD), Department of Pediatrics, Division of Infectious Diseases (RC, NAN), UC Davis Children's Hospital, Sacramento, CA.
Objective:
To review pediatric data on vancomycin exposure threshold against methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS).
Methods:
A systematic review was conducted through July 2023. Publications in English that explored vancomycin effectiveness threshold against MRSA, CoNS, or S aureus in pediatrics were eligible. Effectiveness examined included clinical improvement, microbiologic sterilization, recurrence, and mortality, as defined by each individual study.
Results:
Twelve studies were eligible. One on MRSA bacteremia (MRSA-B) identified an area under the curve to minimum inhibitory concentration ratio (AUC:MIC) of 300 mg × hr/L associated with rapid bacteremia clearance. Two on CoNS bacteremia (percentage of MR-CoNS unreported) demonstrated an AUC of 300 mg x hr/L regardless of MIC and an AUC:MIC of 280 mg × hr/L for bacteriologic cure, respectively; and one on S aureus bacteremia (25.5% MRSA) found an AUC:MIC of 400 mg × hr/L for clinical improvement.
Conclusions:
There is overall limited pediatric data, and the observed AUC:MIC thresholds should be interpreted as hypothesis generating only. Further, the effectiveness outcome could be refined in future research by using time to bacteremia clearance only, as odds of complications increase with each additional day of MRSA-B, whereas the definition of recurrence is not standardized, and mortality is low. Additionally, extrapolating AUC:MIC for MRSA to CoNS is beyond the stated usage of current guidelines. To achieve an AUC:MIC ratio against CoNS with a MIC of >1 mg/L would require higher AUC with potential nephrotoxicity. More data on AUC (regardless of MIC) for MR-CoNS bacteremia are needed.
Insights
Pediatric vancomycin exposure data for MRSA and MR-CoNS is limited. Observed thresholds like AUC:MIC of 300 mg x hr/L are hypothesis-generating, requiring further research for clinical application.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacokinetics and Pharmacodynamics
- Antimicrobial Stewardship
Background:
- Vancomycin is a critical antibiotic for treating serious Gram-positive bacterial infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS).
- Establishing optimal vancomycin exposure thresholds in pediatric populations is crucial for maximizing efficacy and minimizing resistance development.
- Limited pediatric-specific data exists regarding vancomycin exposure targets against key pathogens.
Purpose of the Study:
- To systematically review existing pediatric data on vancomycin exposure thresholds.
- To evaluate effectiveness outcomes (clinical improvement, microbiologic sterilization, recurrence, mortality) in relation to vancomycin exposure against MRSA and MR-CoNS in children.
- To identify gaps in current knowledge and guide future research directions.
Main Methods:
- A systematic review of English-language publications was conducted up to July 2023.
- Studies focusing on vancomycin effectiveness thresholds against MRSA, CoNS, or S. aureus in pediatric patients were included.
- Effectiveness outcomes were assessed as defined within each individual study.
Main Results:
- Twelve studies met the eligibility criteria.
- For MRSA bacteremia, an area under the curve to minimum inhibitory concentration ratio (AUC:MIC) of 300 mg × hr/L was associated with rapid bacteremia clearance.
- For CoNS bacteremia, an AUC of 300 mg x hr/L (regardless of MIC) and an AUC:MIC of 280 mg × hr/L were linked to bacteriologic cure.
- One study on S. aureus bacteremia (with 25.5% MRSA) found an AUC:MIC of 400 mg × hr/L for clinical improvement.
Conclusions:
- Pediatric data on vancomycin exposure thresholds against MRSA and MR-CoNS remains limited.
- Observed AUC:MIC thresholds should be considered hypothesis-generating due to data scarcity.
- Future research should refine effectiveness outcomes, standardize definitions (e.g., recurrence), and investigate AUC targets for MR-CoNS, considering potential nephrotoxicity with higher AUCs.
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