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Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort
Peter Thomas Scully1, Weng Man Lam2, Alvaro Jose Coronado Munoz1
1Division of Pediatric Critical Care, Department of Pediatrics, McGovern Medical School, Houston, TX.
Objectives:
To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL).
Design:
Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL.
Setting:
Tertiary children's hospital.
Patients:
Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis.
Interventions:
Retrospective measurement of VTL, eGFR, and clinical variables.
Measurements And Main Results:
Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis.
Conclusions:
Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.
Insights
Augmented renal clearance (ARC) in pediatric sepsis patients is linked to lower vancomycin levels, potentially increasing treatment failure risk. Further research is needed to optimize dosing for these children.
Area of Science:
- Pediatric pharmacology
- Infectious disease
- Pharmacokinetics
Background:
- Augmented renal clearance (ARC) is associated with decreased serum drug concentrations in both adult and pediatric populations.
- Vancomycin is a critical antibiotic for treating Gram-positive infections, including sepsis.
- Subtherapeutic drug levels can lead to treatment failure and prolonged recovery.
Purpose of the Study:
- To investigate the association between ARC and subtherapeutic initial vancomycin trough levels (VTL) in pediatric patients with suspected sepsis.
- To determine if higher estimated glomerular filtration rates (eGFR) correlate with inadequate initial vancomycin dosing.
Main Methods:
- A retrospective study was conducted at a tertiary children's hospital.
- Patients aged 0-18 years receiving empiric vancomycin for suspected sepsis were included.
- Data on VTL, eGFR, and clinical variables were collected and analyzed using multivariable logistic regression.
Main Results:
- Of 73 patients, 44% had ARC, and 55% had subtherapeutic first VTL.
- Higher eGFR was independently associated with subtherapeutic VTL.
- The presence of ARC was significantly linked to lower initial vancomycin trough levels.
Conclusions:
- Subtherapeutic VTL is associated with ARC in pediatric patients with suspected sepsis.
- This association may pose a risk for treatment failure or delayed clinical response.
- Prospective studies are recommended to confirm these findings and guide vancomycin dosing optimization in patients with ARC.
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