Vancomyin Dosing and Serum Trough Levels in Hospitalized Children

Background: Guidelines from the Infectious Disease Society of America (IDSA) recommend vancomycin serum trough concentrations > 10 mg/L to avoid development of resistance. Previous studies in pediatrics have not assessed the impact of initial dosing regimens on time to effective trough concentration. Further, delayed attainment of adequate trough concentrations may result in increased morbidity and mortality.

Methods: A retrospective cohort study of vancomycin courses was performed at a tertiary care children’s hospital between January 1, 2010 and December 31, 2010. Eligible subjects were hospitalized children ≤ 18 years old who received ≥1 intravenous vancomycin course. A vancomycin courses were defined as continuous administration for ≥ 72 hours. Initial daily dose was defined as mg/kg of vancomycin in the first 24 hours, and categorized as < 40, ≥ 40 and < 50, ≥ 50 and < 60, and ≥ 60 mg/kg/day. The primary outcome was time in hours between initial vancomycin dose and first attainment of trough level of 10 mg/L. Hazard ratios were calculated using Cox proportional hazards regression.

Results: Overall, 315 patients received 432 courses. The most common reasons for prescribing vancomycin were suspected sepsis or blood stream infection (n=138, 32.7%), isolated fever (n=100, 23.7%), and skin or soft tissue infection (n=51, 12.1%). Seventy-one courses (16.4%) were prescribed to neonates, and 114 courses (26.3%) were prescribed to infants 1-12 months in age. The median course duration was 145.8 hours (IQR: 100.3-228.1 hours), and the median time to trough attainment ≥10 mg/L was 58.6 hours (IQR: 31.5-91.0 hours).  Approximately 83% of all courses attained a trough level of 10 mg/L. Initial dose was a significant predictor of timely trough attainment (p=0.0087).

Conclusion: While high initial dosing leads to modest increases in proportion of courses with eventual trough attainment of 10 mg/L, hazard ratios markedly increased. Higher initial dosing can potentially reduce antibiotic selective pressure associated with trough levels <10 mg/L. 

 

Initial daily dose (mg/kg/day)	Number of courses	% with trough attainment >10 mg/L	Hazard Ratio
<40	193	80.8	Ref
≥40 and <50	165	83.0	1.213
≥50 and <60	49	89.7	1.488
≥60	25	92.0	1.874

Serra Akyar, BA, Epidemiology, Columbia University Mailman School of Public Health, New York, NY, Jennifer Duchon, MDCM, MPH , Pediatrics, Columbia University Medical Center, New York, NY and Sameer Patel, MD, MPH, Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL

Disclosures:

S. Akyar, None

J. Duchon, None

S. Patel, None

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