Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population

Kishk, Omayma A.; Lardieri, Allison; Heil, Emily L.; Morgan, Jill A.

doi:10.5863/1551-6776-22.1.41

Cited by 33 publications

(45 citation statements)

References 14 publications

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“…In children, trough vancomycin concentrations are routinely measured and, therefore, understanding the relationship between trough concentrations and AUC 24 is important to guide therapy for S. aureus infection. In children aged >2 months–18 years, a trough concentration of 11 mg/L was shown to correlate with an AUC 24 > 400 for 6‐hourly vancomycin dosing . Also, a population pharmacokinetic modelling study of children aged ≥3 months showed that doses of 60–70 mg/kg/day would be required to achieve an AUC 24 /MIC ≥ 400 in three‐quarters of children .…”

Section: Discussionmentioning

confidence: 98%

“…In children aged >2 months-18 years, a trough concentration of 11 mg/L was shown to correlate with an AUC 24 > 400 for 6-hourly vancomycin dosing. 26 Also, a population pharmacokinetic modelling study of children aged ≥3 months showed that doses of 60-70 mg/kg/day would be required to achieve an AUC 24 /MIC ≥ 400 in three-quarters of children. 27 In young infants aged 0-90 days, trough concentrations >20 mg/L and >15 mg/L for 6-and 12-hourly dosing, respectively, were required to achieve an AUC 24 ≥ 400 for a S. aureus infection with an MIC of 1 mg/L.…”

Section: Discussionmentioning

confidence: 99%

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Vancomycin is commonly under‐dosed in critically ill children and neonates

Sosnin

Curtis

Cranswick

et al. 2019

Brit J Clinical Pharma

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Aims Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. Methods We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10‐month period. Demographic, vancomycin dosing, TDM and drug‐related adverse effects data were collected. Results In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10–20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin‐attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome. Conclusion In critically ill children, individualised dosing is needed. In the absence of Bayesian model‐based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Vancomycin is commonly under‐dosed in critically ill children and neonates

Sosnin

Curtis

Cranswick

et al. 2019

Brit J Clinical Pharma

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“…The probability of achieving an AUC/MIC >400 using only one trough serum concentration and one minimum inhibitory concentration (MIC) in patients receiving 15 mg/kg every 6 hours is variable according to the method used to calculate AUC. In children, an AUC/MIC of 400 correlates with a Ctrough of 11 mg/L using a trapezoidal method to calculate AUC …”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…In children, an AUC/MIC of 400 correlates with a Ctrough of 11 mg/ L using a trapezoidal method to calculate AUC. 35 For pediatric patients, monitoring of vancomycin Ctroughs is a recommendation stated in the summary of product characteristics and by several professional societies. 3 During a study where vancomycin TDM was performed and 7935 vancomycin concentrations were obtained, the median Ctrough increased from 10.9 to 13.7 mg/L, 36 which agrees with the recommendations published by the Infectious Disease Society of America.…”

Section: Pediatric Patientsmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

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Vancomycin is a fundamental antibiotic in the management of severe Gram‐positive infections. Inappropriate vancomycin dosing is associated with therapeutic failure, bacterial resistance and toxicity. Therapeutic drug monitoring (TDM) is acknowledged as an important part of the vancomycin therapy management, at least in specific patient subpopulations, but implementation in clinical practice has been difficult because there are no consensus and agglutinator documents. The aims of the present work are to present an overview of the current knowledge on vancomycin TDM and population pharmacokinetic (PPK) models relevant to specific patient subpopulations. Based on three published international guidelines (American, Japanese and Chinese) on vancomycin TDM and a bibliographic review on available PPK models for vancomycin in distinct subpopulations, an analysis of evidence was carried out and the current knowledge on this topic was summarized. The results of this work can be useful to redirect research efforts to address the detected knowledge gaps. Currently, TDM of vancomycin presents a moderate level of evidence and practical recommendations with great robustness in neonates, pediatric and patients with renal impairment. However, it is important to investigate in other subpopulations known to present altered vancomycin pharmacokinetics (eg neurosurgical, oncological and cystic fibrosis patients), where evidence is still unsufficient.

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“…Several different methods have been used to calculate vancomycin AUC. [18][19][20][21] Most of them rely on calculated AUCs, which are the quotient of the total daily vancomycin dose and vancomycin clearance. However, each method defines vancomycin clearance differently.…”

mentioning

confidence: 99%

Optimizing Vancomycin Use Through 2‐Point AUC‐Based Therapeutic Drug Monitoring in Pediatric Patients

Suchartlikitwong

Anugulruengkitt

Wacharachaisurapol

et al. 2019

The Journal of Clinical Pharma

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The 24‐hour vancomycin area under the serum concentration‐time curve (AUC24) divided by the minimum inhibitory concentration (MIC) (AUC24/MIC) is more closely related to patient outcomes than serum trough concentrations (Ctrough). Two‐point simplified equations for calculating AUC based on serum peak concentrations (Cpeak) and Ctrough, named equation A (EqA) and equation B (EqB), have recently been adopted into clinical use for adult pediatric patients. We aimed to find the agreement between predicted AUC24 using the reference method (ref) relative to EqA and EqB and the correlation between Ctrough and AUC24. From June to December 2018, 43 pediatric patients with normal renal function, receiving 15 mg/kg of vancomycin intravenously every 6 hours, were enrolled. The pediatric patients’ median age was 2.2 years (range 0.1‐15.3). At steady state, vancomycin Cpeak and Ctrough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC24 was estimated using ref, EqA, and EqB. From Bland‐Altman analysis, the 2 AUC24s estimated by ref and EqA showed less bias than those estimated by ref and EqB (bias 1.3 and –72.1 mg⋅h/L, respectively). Ctrough and AUC24 using either ref or EqA were correlated more closely (r2 = 0.94) than with EqB (r2 = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC24 ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC24 ≥400 mg⋅h/L was never seen with Ctrough <8 mg/L but was always seen with Ctrough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC24 estimation. Ctrough >10 mg/L correlated highly to AUC24 ≥400 mg⋅h/L.

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Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population

Cited by 33 publications

References 14 publications

Vancomycin is commonly under‐dosed in critically ill children and neonates

Vancomycin is commonly under‐dosed in critically ill children and neonates

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Optimizing Vancomycin Use Through 2‐Point AUC‐Based Therapeutic Drug Monitoring in Pediatric Patients

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