Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled Trial

Gwee, Amanda; Cranswick, Noel; McMullan, Brendan; Perkins, Elizabeth; Bolisetty, Srinivas; Gardiner, Kaya; Daley, Andrew J; Ward, Meredith C.; Chiletti, Roberto; Donath, Susan; Hunt, Rod W.; Curtis, Nigel

doi:10.1542/peds.2018-2179

Cited by 48 publications

(56 citation statements)

References 29 publications

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“…These findings are also consistent with data for other drugs that are renally cleared, such as gentamicin, where increased doses are required in the intensive care setting secondary to an illness‐induced hyperdynamic state and consequent increased volume of distribution . Continuous infusions of vancomycin have been proposed as a solution to the poor attainment of therapeutic vancomycin concentrations with intermittent dosing . Overall, our data suggest that a more aggressive approach to vancomycin dosing in critically ill children and neonates is necessary.…”

Section: Discussionsupporting

confidence: 87%

“…36 Continuous infusions of vancomycin have been proposed as a solution to the poor attainment of therapeutic vancomycin concentrations with intermittent dosing. [37][38][39][40] Overall, our data suggest that a more aggressive approach to vancomycin dosing in critically ill children and neonates is necessary. Doses at the higher end of daily recommendations were required in older children, with 75% of children attaining therapeutic concentrations with doses >50 mg/kg/day.…”

Section: Discussionmentioning

confidence: 81%

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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: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 81%

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

Sosnin

Curtis

Cranswick

et al. 2019

Brit J Clinical Pharma

Self Cite

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“…Gwee et al 33 recently published the only randomized controlled trial of CIV versus IIV in children ( Table 1). This multicenter, non-blinded study included 104 infants aged 0 to 90 days, treated at 2 NICUs in Australia.…”

Section: Clinical Evidencementioning

confidence: 99%

Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence

Girand¹

2020

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE To evaluate the use of continuous infusion vancomycin in pediatric patients. DATA SOURCES AND STUDY SELECTION PubMed, Cochrane Library, International Pharmaceutical Abstracts, and Google Scholar were searched to identify relevant published articles (1977 to November 2019) using the following search terms: vancomycin, neonates, pediatrics, infusion, continuous, administration, children, nephrotoxicity, pharmacokinetics, and pharmacodynamics. All English-language primary references that evaluated continuous infusion vancomycin in pediatric patients were included in this review. DATA SYNTHESIS Vancomycin is typically administered with intermittent infusions, but continuous infusion is an alternative delivery method used to improve achievement of target serum concentrations. Fifteen articles were reviewed that evaluated continuous infusion vancomycin in pediatric patients. Study data were heterogeneous with limited evidence to support improved clinical or microbiologic outcomes as compared with intermittent dosing. Potential benefits and limitations of continuous infusions are discussed. CONCLUSIONS Currently available evidence is lacking to support routine implementation of continuous infusion vancomycin in pediatric patients. However, it is a therapeutic option in certain clinical conditions and could be beneficial for individuals with serious Gram-positive infections where rapid achievement of target serum concentrations is critical. Continuous infusions may also benefit individuals who do not achieve target concentrations or who experience significant red man syndrome with traditional dosing, particularly when high daily doses are required. Optimal dosing and ideal target serum concentrations have not been established and may vary for different populations. Future prospective randomized clinical trials should be performed to identify optimal dosing and monitoring regimens and determine comparative safety and efficacy with traditional intermittent dosing in various pediatric populations.

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“…Vancomycin is a commonly used antibiotic to treat neonatal sepsis, and therefore dose optimisation is vital to maximise therapeutic effectiveness while limiting toxicity and preventing bacterial resistance. Vancomycin is a time-dependent antibiotic, and activity is highly correlated with the duration of bacterial exposure to the antibiotic rather than being concentration-dependent 2. Targeting the ‘Area under the curve over 24 hours/Minimal Inhibitory Concentration’ (AUC24/MIC) increases the chance of maximum clinical efficacy with the least side effects.…”

Section: Commentarymentioning

confidence: 99%

“…This is an important consideration in the neonatal population as sampling can be timed with other blood tests. Some of the potential issues of continuous infusions include the requirement for secure intravenous access and certain drug incompatibilities 2. While most of these neonates with sepsis would require secure venous access anyway, the issue of drug incompatibilities remains.…”

Section: Commentarymentioning

confidence: 99%