Surgical Site Infection, Vancomycin
Conditions
Brief summary
A study of plasma and tissue vancomycin pharmacokinetics in pediatric surgical patients.
Detailed description
Background: Vancomycin is used for antibiotic prophylaxis in pediatric surgical patients without a complete understanding of plasma and soft tissue pharmacokinetics. Guidelines recommend incision within 60 minutes after administration; however, tissue concentrations of vancomycin at that early time may not be therapeutic. The Investigators conducted a study of plasma and tissue concentrations in pediatric neurosurgical and orthopedic patients to characterize intraoperative vancomycin pharmacokinetics. Patients, ages (0.1-18.8 years), undergoing posterior spinal fusion (n=30) or ventriculoperitoneal shunt placement (n=30), received intravenous vancomycin 15 mg/kg over one hour. Skin biopsies were taken at incision and skin closure. Blood samples were also collected at incision and closure; additional samples were drawn at 2- and 4-hours if patient was still in surgery. Population pharmacokinetic (PK) analysis was performed to characterize PK parameter estimates and to develop a model of intraoperative plasma and tissue vancomycin concentrations vs. time.
Interventions
DRUGAdministration of Vancomycin
Intravenous Vancomycin Administration
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
31 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Neurosurgery patients between the ages of 31 days up to 18 years 2. Receiving a single dose of vancomycin administered prior to surgery for cerebrospinal fluid (CSF) shunt placement or revision. 3. Orthopedic surgical patients between the ages of 31 days up to 18 years 4. Receiving a single dose of vancomycin administered prior to surgery for definitive spinal fusion.
Exclusion criteria
1. Patients already receiving vancomycin for treatment of an active infection, 2. Patients who have a Creatinine ≥1.2, 3. Patients who's creatinine clearance less than 50, 4. Known chronic renal failure and are on dialysis, 5. Patients with a known allergy to vancomycin, not including Red Man Syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Analysis: V˅c | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Volume of the central compartment. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: V˅2 | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Volume of the peripheral compartment Typical value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: Q | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Intercompartmental clearance between central compartment (Vc) and peripheral compartment (V2) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: Cle | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Elimination clearance. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: sf˅V2 | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Scaling Factor for Body weight covariate for V2 (Volume of the peripheral compartment) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: sf˅Cle | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed). | Scaling Factor for Body weight covariate for Cle (elimination clearance) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: K˅skin0 | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | Accounts for the equilibration rate between plasma and skin. Typical Value should be read as 3.6E-05. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: PC | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | Partition coefficient, models skin drug concentration between plasma and skin. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: δ ˅R-plasma | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | Proportional or relative intrasubject variability for plasma data Typical Value. There is no unit of measure for this measurement. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
| Pharmacokinetics Analysis: δ ˅A-skin | 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed) | Additive intrasubject variability for skin data Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available. |
Countries
United States
Participant flow
Recruitment details
30 patients scheduled to undergo posterior spinal fusion 30 patients scheduled to undergo ventriculo-peritoneal (VP) shunt placement
Participants by arm
| Arm | Count |
|---|---|
| Administration of Vancomycin Administration of Vancomycin 15 mg/kg over 1 hour prior to surgical incision
Administration of Vancomycin: Intravenous Vancomycin Administration | 59 |
| Total | 59 |
Baseline characteristics
| Characteristic | Administration of Vancomycin | — |
|---|---|---|
| Age, Categorical <=18 years | 57 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 2 Participants | — |
| Age, Continuous | 7.8 years STANDARD_DEVIATION 5.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 37 Participants | — |
| Sex: Female, Male Male | 22 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 0 / 59 |
| serious Total, serious adverse events | 0 / 59 |
Outcome results
Primary
Pharmacokinetics Analysis: Cle
Elimination clearance. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: Cle | Typical value | 0.09 L/min/1.73 m^2 |
| Administration of Vancomycin | Pharmacokinetics Analysis: Cle | ꙍ^2 (Intersubject variability) | 0.13 L/min/1.73 m^2 |
Primary
Pharmacokinetics Analysis: K˅skin0
Accounts for the equilibration rate between plasma and skin. Typical Value should be read as 3.6E-05. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: K˅skin0 | ꙍ^2 (Intersubject variability) | 2.0 min^-1 |
| Administration of Vancomycin | Pharmacokinetics Analysis: K˅skin0 | Typical value | 3.6 min^-1 |
Primary
Pharmacokinetics Analysis: PC
Partition coefficient, models skin drug concentration between plasma and skin. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: PC | Typical value | 32.0 Coefficient |
| Administration of Vancomycin | Pharmacokinetics Analysis: PC | ꙍ^2 (Intersubject variability) | 3.7 Coefficient |
Primary
Pharmacokinetics Analysis: Q
Intercompartmental clearance between central compartment (Vc) and peripheral compartment (V2) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: Q | 0.12 L/min |
Primary
Pharmacokinetics Analysis: sf˅Cle
Scaling Factor for Body weight covariate for Cle (elimination clearance) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: sf˅Cle | 1.69 L/min/1.73m^2 |
Primary
Pharmacokinetics Analysis: sf˅V2
Scaling Factor for Body weight covariate for V2 (Volume of the peripheral compartment) Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: sf˅V2 | 1.01 L/35kg |
Primary
Pharmacokinetics Analysis: V˅2
Volume of the peripheral compartment Typical value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: V˅2 | 5.30 L/35kg |
Primary
Pharmacokinetics Analysis: V˅c
Volume of the central compartment. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed).
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: V˅c | Typical value | 2.56 L |
| Administration of Vancomycin | Pharmacokinetics Analysis: V˅c | w^2 | 1.14 L |
Primary
Pharmacokinetics Analysis: δ ˅A-skin
Additive intrasubject variability for skin data Typical Value. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: δ ˅A-skin | 7.5 μg |
Primary
Pharmacokinetics Analysis: δ ˅R-plasma
Proportional or relative intrasubject variability for plasma data Typical Value. There is no unit of measure for this measurement. This outcome measure was pre-specified to utilize advanced mathematical modeling for this assessment. No measure of central tendency is available.
Time frame: 1 Day (measured and combined from the time of the incision, through 2 hours after the incision, 4 hours after the incision, until when the incision is closed)
Population: One participant was excluded because the sample was lost.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Administration of Vancomycin | Pharmacokinetics Analysis: δ ˅R-plasma | 0.23 No unit of measure |