Assessment of Initial Vancomycin Dosing in Pediatric Oncology Patients

Orr, Hillary; Trone, Deni; Elder, Joshua J.; Raj, Ashok

doi:10.3390/children4090079

Cited by 5 publications

(7 citation statements)

References 7 publications

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“…Logistic regression analyses for predicting the recommended vancomycin trough levels CI confidence interval, Crcl creatinine clearance, OR odds ratio 60 mg/kg/day). Studies from other parts of the world have similar conclusions[17,[28][29][30][31][32][33]. Chang et al predicted a mean dose of 75…”

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confidence: 75%

Vancomycin Use in a Paediatric Intensive Care Unit of a Tertiary Care Hospital

et al. 2019

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Background Vancomycin is one of the commonly used anti-microbial drugs in intensive care units (ICUs). Guidelines recommend maintaining therapeutic trough levels of vancomycin (10-20 mg/L). The success of achieving the recommended therapeutic concentration of vancomycin is influenced by several factors, and this is even more complex in children, particularly those admitted in the ICU. Hence, we carried out the present study in children admitted in the ICU who were administered vancomycin. Methods We carried out a chart review of children admitted in the paediatric ICU unit of a tertiary care hospital over a period of 3 years. Information on their demographic factors, diagnoses, duration of hospital stay, vancomycin treatment (dose, frequency and time of administration) and concomitant drugs, and vancomycin trough levels were retrieved. Descriptive statistics were used for representing the demographic factors, and multivariable logistic regression analyses were carried out to assess the determining factors. Results One-hundred and two children were identified, of whom 13 had renal dysfunction. Two-hundred and fifty-two vancomycin trough levels were available, of which only 25% were observed in the recommended range (10-20 mg/L) amongst patients without any renal dysfunction and 22% amongst patients with renal dysfunction. Vancomycin was administered intravenously at an average [standard deviation (SD)] dose (mg/dose) of 13 (3.9) mostly either thrice or four times daily. Even in patients receiving vancomycin as a definitive therapy, only 40.9% achieved the recommended trough levels. Lower trough levels were associated with an increased risk of mortality. Nearly 4% of the levels were above 20 mg/L (toxic range). Seven children were suspected to have acute kidney injury (AKI) during the course of therapy where the cumulative vancomycin dose and mortality rate was higher. Only one serum vancomycin level during augmented renal clearance was observed in the recommended range. All the patients received at least one concomitant drug that either had nephrotoxic potential or predominant renal elimination, and use of a greater number of such drugs was associated with an increased risk of AKI. Conclusion The current vancomycin dosing strategy is ineffective in achieving therapeutic trough levels in children admitted to the ICU. Sub-therapeutic vancomycin trough levels significantly increase the risk of mortality.

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confidence: 75%

Vancomycin Use in a Paediatric Intensive Care Unit of a Tertiary Care Hospital

et al. 2019

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“…This is of particular importance given that younger patients may be less likely to achieve target trough concentrations with standard dosing. 15,40 However, after controlling for age in our regression model, the use of a loading dose was still significantly associated with attainment of an initial target trough concentration. The difference in body weights between the 2 groups was likely related to the aforementioned age differences.…”

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confidence: 78%

“…For power calculations, we estimated a 20.8% target trough attainment without a loading dose from previously published work in children, 15 with an estimated 50.0% target trough attainment with the use of loading doses (based upon previous adult and pediatric data). 22,26 Using an alpha of 0.05 and 90% desired power, we estimated we would require 108 subjects (54 in each group) in order to detect a statistically significant difference in our primary outcome (initial target trough attainment), should one exist.…”

Section: Methodsmentioning

confidence: 99%

“…Despite standard dosing based upon accepted references, 14 initial vancomycin trough values in children are often subtherapeutic or below target goals. 15 Orr et al 15 reported that 79.2% of appropriately dosed pediatric oncology patients had subtherapeutic initial vancomycin trough concentrations, while Hsu et al 16 detailed a cohort of children with MRSA bacteremia, 73.0% of whom had a median vancomycin trough concentration of <10 mg/dL. Hoang et al 17 described a cohort of 188 children, 61.0% of whom failed to achieve target trough concentrations following vancomycin dosing, while Durham et al 18 reported that only 6.8% of 74 children receiving vancomycin at 60 mg/kg/day divided every 6 hours achieved a trough concentration of 15 to 20 mg/dL.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Vancomycin Loading Doses on the Attainment of Target Trough Concentrations in Hospitalized Children

Dolan¹,

Hellinga²,

London³

et al. 2020

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE Subtherapeutic vancomycin trough concentrations are common in children and may be associated with suboptimal therapeutic response. Our objective was to determine if vancomycin loading doses safely increase the frequency of target trough attainment in hospitalized children. METHODS Patients (≥6 months and <18-years-old) who received a vancomycin loading dose between February 1, 2018, and January 30, 2019, were retrospectively enrolled. These patients were compared to a convenience cohort of patients hospitalized between January 1, 2015, and December 31, 2015, who received vancomycin without a loading dose. Target trough concentrations were defined as >15 mg/dL for invasive infections and >10 mg/dL for non-invasive infections. RESULTS A total of 151 patients were enrolled, with 77 in the control arm and 74 in the loading dose arm. There was no significant difference in the frequency of comorbidities or need for intensive care unit admission between the two arms. Those receiving a vancomycin loading dose were older (mean age 9.1 vs 5.2 years, p < 0.0001). Patients given a loading dose achieved higher mean initial trough values (13.0 mg/dL vs 9.2 mg/dL, p < 0.0001), were more likely to have an initial trough at or above target (37.0% vs 10.4%, p = 0.0001), were more likely to reach target trough values at any point during therapy (52.1% vs 32.9%, p = 0.0081), and attained a target trough concentration more quickly (mean 41.1 hours vs 58.8 hours, p = 0.0118). There were no significant differences in the frequency of serum creatinine elevation or oliguria at the end of therapy. CONCLUSIONS Vancomycin loading doses may improve the ability to safely obtain target trough values in hospitalized children.

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“…In paediatric malignancy particularly, studies have shown frequent failure to achieve adequate trough levels despite using the current recommended doses of 45–60 mg/kg/day 20,21 . Even higher initial daily doses of 60 mg/kg may be insufficient to provide adequate trough levels in most patients in this group and doses of at least 80mg/kg/day have been suggested 22,23 24 and at the beginning of treatment the actual MIC for the pathogen is not known, resulting in use of estimates for the ratio.…”

Section: Discussionmentioning

confidence: 99%

Children may need higher vancomycin doses to achieve therapeutic levels

et al. 2021

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Aim Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10–20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used. Methods All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012 and 2016 were included. Vancomycin trough levels were registered. Student t test, Wilcoxon test and regression models were used for statistical analysis. Results A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p = 0.09). Conclusions In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.

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Assessment of Initial Vancomycin Dosing in Pediatric Oncology Patients

Cited by 5 publications

References 7 publications

Vancomycin Use in a Paediatric Intensive Care Unit of a Tertiary Care Hospital

Vancomycin Use in a Paediatric Intensive Care Unit of a Tertiary Care Hospital

Effect of Vancomycin Loading Doses on the Attainment of Target Trough Concentrations in Hospitalized Children

Children may need higher vancomycin doses to achieve therapeutic levels

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