MRSA - Methicillin Resistant Staphylococcus Aureus Infection
Conditions
Brief summary
Vancomycin is an essential antimicrobial which is frequently used in the ICU for suspected methicillin-resistant Staphylococcus aureus (MRSA) infection. Therefore, it is vital to optimize the dosing of vancomycin for this critically ill population. The most efficacious method of administering vancomycin is debated in the literature. Since vancomycin is associated with slow bactericidal activity, it is important to closely monitor serum concentrations so as to achieve early target serum concentration, particularly when treating aggressive S. aureus infections. One study has shown that vancomycin infused continuously may enable faster and more consistent achievement of a therapeutic serum concentration when compared to intermittent infusion. A faster achievement in the goal serum vancomycin concentration would be a protective factor for intensive care unit mortality in patients with MRSA infection. Currently in the surgical ICU (SICU) of our institute, vancomycin is administered based on a vancomycin dosing nomogram. Less than fifty percent of the ICU patients following this nomogram achieved target vancomycin concentration of 15 after 24 hours. To better achieve target vancomycin concentration in 24 hours, we developed a new vancomycin dosing nomogram with a continuous infusion. The aim is to determine which of the two dosing nomogram is more efficient and safer for SICU patients.
Detailed description
Early administration of effective antibiotics is the cornerstone of management in septic patients; however, altered pharmacokinetics in critically ill patients has lead to subtherapeutic antibiotic exposure with standard antibiotic dosing and administration. This is further evidenced by low therapeutic target achievement with our intermittent vancomycin dosing nomogram. Administering vancomycin by continuous infusions may lead to achieving a therapeutic concentration and AUC24 more quickly than the administration by intermittent infusions as well as provide a more consistent concentration throughout the dosing period. Therefore, a new vancomycin continuous infusion nomogram was developed to increase the achievement of a goal vancomycin concentration within 24 hours. We hypothesized that vancomycin administered as continuous infusion would achieve the therapeutic target sooner and more consistently than when administered as an intermittent infusion in critically ill surgical patients. The aims of this study were to determine the dosing differences between continuous (CIV) and intermittent (IIV) dosing in critically ill surgical intensive care unit (SICU) patients with preserved renal function and whether calculated Cockcroft-Gault Creatinine Clearance (CG CrCL) or measured creatinine clearance (CrCL) is a better predictor of vancomycin clearance.
Interventions
Vancomycin 24 hour intravenous continuous infusion
DRUGVancomycin intermittent dosing interval
Vancomycin intravenous infusion at rate 1000mg/hr
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and non-pregnant female \> 18 years of age admitted to Surgical ICUs with suspected infection * Calculated creatinine clearance \> 60ml/min
Exclusion criteria
* Age \< 18 years * Allergic to vancomycin * Calculated creatinine clearance \< 60ml/min * Pregnant * Vancomycin administration more than 8 hour and less than 24 hour prior to study enrollment * Anticipated vancomycin treatment less than 2 days for surgical prophylaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved the Target Vancomycin Concentration | 24 hours | The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Required to Reach the Therapeutic Levels | as long as participants are receiving Vancomycin (mean (SD) 9 (3.8) days for continuous, 8.4 (4.1) days for intermittent) | The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV |
| Vancomycin Concentration at 24 Hours | 24 hours | The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vancomycin Continous Infusion Vancomycin continuous infusion: Vancomycin 24 hour intravenous continuous infusion infusion rate 1000mg/hr | 22 |
| Intermittent Infusion infusion rate 1000mg/hr
Vancomycin intermittent dosing interval: Vancomycin intravenous infusion at rate 1000mg/hr | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Vancomycin Continous Infusion | Intermittent Infusion | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 14.1 | 53.7 years STANDARD_DEVIATION 13.5 | 56.8 years STANDARD_DEVIATION 14.05 |
| Region of Enrollment United States | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 16 Participants |
| Sex: Female, Male Male | 16 Participants | 12 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 22 | 4 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Number of Participants Who Achieved the Target Vancomycin Concentration
The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV
Time frame: 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin With Continuous Infusion | Number of Participants Who Achieved the Target Vancomycin Concentration | 20 Participants |
| Vancomycin With Intermittent Dose Interval | Number of Participants Who Achieved the Target Vancomycin Concentration | 5 Participants |
Secondary
Time Required to Reach the Therapeutic Levels
The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV
Time frame: as long as participants are receiving Vancomycin (mean (SD) 9 (3.8) days for continuous, 8.4 (4.1) days for intermittent)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin With Continuous Infusion | Time Required to Reach the Therapeutic Levels | 26.1 hours | Standard Deviation 7 |
| Vancomycin With Intermittent Dose Interval | Time Required to Reach the Therapeutic Levels | 54.1 hours | Standard Deviation 25.8 |
Secondary
Vancomycin Concentration at 24 Hours
The therapeutic level was defined as 15-20 mcg/mL for IIV and 15-25 mcg/mL for CIV
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vancomycin With Continuous Infusion | Vancomycin Concentration at 24 Hours | 19.9 mcg/mL | Standard Deviation 3.7 |
| Vancomycin With Intermittent Dose Interval | Vancomycin Concentration at 24 Hours | 14.2 mcg/mL | Standard Deviation 6.6 |