Necrotizing Soft Tissue Infection
Conditions
Brief summary
Necrotizing soft tissue infection (NSTI) is a devastating disease that results in a high rate of in-hospital complications and despite advances in critical care, wound care, and early intervention, NSTI continues to be associated with a mortality rate of nearly 30%. The antibiotics used in this treatment are Clindamycin, Vancomycin, Piperacillin Tazobactam; these antibiotics may be administered combined or individually, based on individualized patient treatment. Although one of the tenets of management for NSTI is early broad-spectrum intravenous antibiotics (listed above), the duration of antibiotics needed is not well defined. Currently, there exists wide variation in the duration of antibiotics for NSTI ranging between 2-16 days. The objective of this study is to evaluate the safety of a shorter course of antibiotics hypothesizing that a short duration of antibiotics for 48-hours after source-control is achieved will have similar risk of morbidity and mortality compared to a 7-day course of antibiotics post source control. A second aim of this study will be to identify if serum procalcitonin levels/ratio correspond to resolution of systemic infection in patients with NSTI.
Detailed description
The objective of this study is to evaluate the safety of a shorter course of antibiotics hypothesizing that a short duration of antibiotics for 48-hours after source-control is achieved will have similar risk of morbidity and mortality compared to a 7-day course of antibiotics post source control. The proposed shortened duration is considered within standard of care as the IDSA suggests 48-72 hours of antibiotics after source control, however this was due mostly to expert opinion until a recent single-center study using historical controls demonstrated a 48-hour duration of antibiotics to be safe. A second aim of this study will be to identify if serum procalcitonin levels/ratio correspond to resolution of systemic infection in patients with NSTI. This pilot study may help limit use of antibiotics which are associated with both cost and significant adverse events including antimicrobial resistance and clostridium difficile infections. In addition, the data would support grant submission of a larger, multi-center study with sufficient power to demonstrate the safety profile and potential benefits of a shorter duration of antibiotics, which has been shown to be beneficial in previous large surgical infection studies. Specific Aims: Aim#1: Establish the safety of an abbreviated course (48 hours after source control) compared to a prolonged (7 days after source control) course of antibiotics in terms of in-hospital mortality. Aim#2: Compare the incidence of hospital length of stay and in-hospital complications including unplanned return to the operating room, ventilator days, and antibiotic associated complications (e.g., clostridium difficile infection) in the two comparison groups: abbreviated (48-hours) and prolonged antibiotics (7-days) after source control. Aim#3: Identify a critical threshold of biochemical procalcitonin or a % decrease in procalcitonin from the initial procalcitonin obtained upon admission that suggests resolution of systemic infection in patients with NSTI. This will be done by obtaining a serum procalcitonin upon admission and daily for up to 7 days from admission or once source control has been achieved.
Interventions
OTHERAntibiotic duration (short course)
The patient will be enrolled in a 48-hour course of antibiotics.
OTHERAntibiotic duration (extended course)
The patient will be enrolled in a 7 day course of antibiotics.
Sponsors
University of California, Irvine
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients 18 years of age or older with all following criteria: * Presenting to the Emergency Department with history, exam and/or imaging concerning NSTI, AND * Patients who undergo consultation by the Emergency General Surgery service, AND * Patients included must have skin or soft tissue findings consistent with NSTI (erythema, crepitus, or pain out of proportion to exam), AND * Systemic signs of infection including fever (temperature \>38.0°C) or leukocytosis (≥11,000 peripheral white cells per cubic millimeter), AND * Patients who undergo excisional debridement and/or amputation to achieve source control.
Exclusion criteria
* Pregnant patients * Prisoners * Patients with bacteremia upon admission * Patients unable to provide consent (including no legally authorized representative)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality rate | Through study completion, an average of 1 year | In-hospital mortality |
| Safety of the antibiotic course duration | Through study completion, an average of 1 year | In-hospital complications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory rate | Baseline, pre-intervention/procedure/surgery | Respiratory rate (breaths/minute) |
| Temperature | Baseline, pre-intervention/procedure/surgery | Temperature (Fahrenheit) |
| Age | Baseline, pre-intervention/procedure/surgery | Age in years |
| Sex | Baseline, pre-intervention/procedure/surgery | Sex (male/female) |
| BMI (body mass index) | Baseline, pre-intervention/procedure/surgery | Body mass index (weight and height will be combined to report BMI in kg/m\^2) |
| Comorbidities | Baseline, pre-intervention/procedure/surgery | Comorbidities (e.g., diabetes, hypertension, cirrhosis, chronic kidney disease, etc.) |
| Transfusion requirements | Baseline, pre-intervention/procedure/surgery | Number of Packed Red Blood Cells transfused measured in milliliters |
| NSTI location | Baseline, pre-intervention/procedure/surgery | Anatomical location of soft tissue infection |
| Operations | Through study completion, an average of 1 year | Number of surgical procedures |
| Serum concentration of procalcitonin | Upon admission and daily blood sample for 7 days | Procalcitonin ng/mL |
| Serum concentration of white blood cell | Through study completion, an average of 1 year | White blood cell count cells per microliter (cells/μL) |
| Serum concentration of hemoglobin | Through study completion, an average of 1 year | Hemoglobin grams/deciliter |
| Serum concentration of sodium | Through study completion, an average of 1 year | Sodium millimoles per liter (mmol/L) |
| Serum concentration of C-reactive protein | Through study completion, an average of 1 year | C-reactive protein milligrams/liter |
| Serum concentration of glucose | Through study completion, an average of 1 year | Glucose milligrams/deciliter |
| Serum concentration of creatinine | Through study completion, an average of 1 year | Creatinine milligram/deciliter |
| Total hospital length of stay | Through study completion, an average of 1 year | Total days of hospital stay |
| Total intensive care unit (ICU) | Through study completion, an average of 1 year | Total days of ICU stay |
| Blood Pressure | Baseline, pre-intervention/procedure/surgery | Blood Pressure (mmHg) |
| Total ventilator days | Through study completion, an average of 1 year | Total days of ventilation support for the patient |
| Heart Rate | Baseline, pre-intervention/procedure/surgery | Heart rate (beats/minute) |
Countries
United States
Contacts
CONTACTAreg Grigorian, MD
CONTACTJeffry Nahmias, MD
PRINCIPAL_INVESTIGATORAreg Grigorian, MD
University of California, Irvine
Outcome results
None listed