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Lower vancomycin dosage inadequate in younger oncology patients
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Pediatric oncology patients younger than 12 years receiving a vancomycin dosage of 60 mg/kg/day may not be treated adequately, according to recent study results published in The Pediatric Infectious Disease Journal.
Ron A.A. Mathôt, PharmD, PhD, of the department of clinical pharmacy at Emma Children’s Hospital, Academic Medical Center in Amsterdam, and colleagues evaluated 124 pediatric oncology patients (68 boys, 56 girls) younger than 18 years (median age, 5.3 years) treated with vancomycin between 2005 and 2009 to determine whether a dosage of 60 mg/kg/day led to adequate trough concentrations in the patients. Vancomycin treatment lasted a median duration of 5 days; the median trough concentration was 7.1 mg/L.
In more than half of the patients (58.1%), trough concentrations were subtherapeutic (<8 mg/L). In 18.5% of the patients, vancomycin trough concentrations were lower than 5 mg/L.
Age (P<.05), weight (P<.05) and serum creatinine (P<.01) were significantly correlated with trough concentrations.
Patients younger than 6 years (P=.003; median value, 6.6 mg/L) and those aged 6 to 12 years (P=.013; median value, 7.8 mg/L) had significantly lower trough concentrations compared with patients older than 12 years (median value, 9.8 mg/L).
Subtherapeutic trough concentrations decreased from 68% to 27% in patients younger than 6 years and from 56% to 19% in patients aged 6 to 12 years. In patients younger than 6 years, therapeutic trough concentrations increased from 25% to 52% and from 36% to 56% in patients aged 6 to 12 years. Supratherapeutic trough concentrations increased from 7% to 21% in patients younger than 6 years and from 8% to 25% in patients aged 6 to 12 years. In patients younger than 6 years, simulated supratherapeutic trough concentrations ranged from 17 mg/L to 36.3 mg/L and from 16.7 mg/L to 42.2 mg/L in patients aged 6 to 12 years.
“In conclusion, our study demonstrated that vancomycin trough concentrations are inadequate for pediatric oncology patients receiving 60 mg/kg/day,” the researchers wrote. “For patients younger than 12 years, a dosage of 90 mg/kg/day may lead to more adequate vancomycin exposure.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Chad Knoderer, PharmD
Sanders and colleagues’ retrospective cohort study of pediatric oncology patients demonstrate that the common empiric vancomycin dose of 60 mg/kg/day may be inadequate in certain patients to achieve desired trough serum concentrations. Children younger than 12 years had significantly lower trough concentrations than older children. These important findings come at a time when emerging pediatric evidence questions the most appropriate empiric vancomycin dose needed to achieve desired pharmacodynamic targets in children. Sanders et al suggest that oncology patients younger than 12 years may need up to 90 mg/kg/day empirically, based on simulation, to achieve the desired trough serum concentration, which in this study was 8 mg/L to 15 mg/L as recommended within Dutch vancomycin guidelines for children.
These findings highlight the complexity of pediatric dosing, which not only encompass developmental pharmacology issues, but also disease-state considerations. Pediatric vancomycin data published in 2013 suggests a trough serum concentration of 7 mg/L to 10 mg/L more accurately correlates with the target area under the curve to minimum inhibitory concentration ratio in children, and further challenges practitioners to optimize empiric vancomycin dosing to most effectively and safely treat pediatric patients. Along with the association of elevated vancomycin trough serum concentrations with acute kidney injury in children and adults, practitioners should carefully deliberate the risks and benefits to further increasing empiric vancomycin doses. Sanders and colleagues’ study of vancomycin dosing and serum concentrations provides additional valuable evidence on empiric dosing and target attainment. Their findings underscore that more research focusing specifically on vancomycin efficacy and safety outcomes in children is warranted.
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