Vancomycin Area Under the Curve to Minimum Inhibitory Concentration Ratio for Treatment Effectiveness in Pediatric and Neonatal Staphylococcal Infections: A Systematic Review.

Abstract

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.