ORIGINAL ARTICLE AUC- vs. Trough-Guided Monitoring of Vancomycin in Infants Abdullah Alsultan 1,2 & Manal Abouelkheir 3 & Ahmad Albassam 4 & Emad Alharbi 3 & Ahmed Assiri 3 & Saeed Alqahtani 1,2 Received: 18 March 2019 /Accepted: 17 December 2019 # Dr. K C Chaudhuri Foundation 2020 Abstract Objective Improving vancomycin therapy with therapeutic drug monitoring is recommended. Over the past few years, a few studies have demonstrated that trough concentrations may not be the optimal parameter for monitoring vancomycin concentra- tion and Area under the curve (AUC) should be used instead. In this study authors evaluate two methods to estimate the AUC. The first method is based on linear regression using only a trough concentration. The second method uses a simplified two- sample equation-based strategy to estimate the AUC. Methods Data from 70 infant patients were collected retrospectively from their medical records at King Saud University Medical City. The prediction accuracy for vancomycin therapy monitoring was optimized by comparing the two methods for the AUC calculation, the simple linear regression and simplified two-sample equation-based strategy. Results The target AUC > 400 μg × h/ml was achieved in 10%, 71%, and 100% of patients with trough concentration ranges of 5–10, 10–15, and > 15 μg/ml, respectively. There was a strong correlation between the predicted and observed AUC calculated using the simplified two-sample equation-based strategy (R 2 = 0.91, bias = -3.9%, precision =12%). Conclusions The target AUC > 400 μg × h/ml can be achieved at trough concentrations <15 μg/ml in most patients. Targeting trough concentrations >15 can lead to overdoing and increase risk of nephrotoxicity. The authors recommend estimating the AUC using the simplified two-sample equation strategy for more precise dosing of vancomycin. Using AUC-guided dosing instead of the trough-guided approach can prevent over dosing and reduce the risk of nephrotoxicity. Keywords Dosing . Infants . Pharmacokinetics . Vancomycin Introduction Vancomycin is a glycopeptide antibiotic commonly used in pediatrics for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin effi- cacy in MRSA infections has been linked to an Area under the curve (AUC) / Minimum inhibitory concentration (MIC) > 400 [1–3]. Developing dosing regimens that can rapidly reach this target are important. Several studies have determined the optimal vancomycin starting dose in infants. However, only a few studies have discussed the optimal method to monitor vancomycin dosing [4–8]. In clinical practice, trough concentrations are typically used to guide vancomycin monitoring and dosing. The ASHP/IDSA/ SIDP treatment guidelines recommend targeting trough values in the range of 15–20 μg/ml in adults for serious infections like infective endocarditis, meningitis, and hospital-acquired pneu- monia [9]. Because no such guideline has been published for pediatrics, many pediatric institutions extrapolate this recommen- dation for infants and children. However, to reach these troughs in children is difficult. In addition, vancomycin efficacy is mainly linked to the AUC/MIC and not trough values. Importantly, a recent meta-analysis showed that there is no correlation between trough values and clinical efficacy [10]. The rationale for targeting trough values is to use it as a surrogate for the AUC. Trough values >15 μg/ml typically ensure an AUC > 400 μg× h/ml. However, recent studies showed that we can achieve an AUC > 400 μg × h/ml at even lower trough values, specifically in pediatrics [11]. Therefore, targeting elevated trough * Abdullah Alsultan absultan@ksu.edu.sa 1 Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia 2 Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia 3 Pediatric Clinical Pharmacy Services, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia 4 Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia The Indian Journal of Pediatrics https://doi.org/10.1007/s12098-019-03162-5