The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review

• Published in: Paediatric drugs Vol. 20; no. 2; pp. 153 - 164
• Main Authors: Tkachuk, Stacey, Collins, Kyle, Ensom, Mary H. H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2018; Springer; Springer Nature B.V
• Subjects: Antibiotics; Antimicrobial agents; Clinical outcomes; Dosage and administration; Drug dosages; Forecasts and trends; Internal Medicine; Medicine; Medicine & Public Health; Pediatrics; Pharmacotherapy; Pneumonia; Qualitative research; Staphylococcus infections; Streptococcus infections; Studies; Systematic Review; Vancomycin; Canada
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-018-0282-4

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.