Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Short course of antibiotics | Patients assigned to a 48-hour course of antibiotics. As the current standard of care, the antibiotics used in this treatment are Clindamycin, Vancomycin, Piperacillin-Tazobactam; these antibiotics may be administered combined or individually, based on individualized patient treatment. The specific choice of antibiotic therapy will not be dictated by the study protocol but by the attending surgeon taking care of the patient |
| |
| Long course of antibiotics | Patients assigned to a 7 day course of antibiotics. As the current standard of care, the antibiotics used in this treatment are Clindamycin, Vancomycin, Piperacillin-Tazobactam; these antibiotics may be administered combined or individually, based on individualized patient treatment. The specific choice of antibiotic therapy will not be dictated by the study protocol but by the attending surgeon taking care of the patient |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antibiotic duration (short course) | Other | The patient will be enrolled in a 48-hour course of antibiotics. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety of the antibiotic course duration | In-hospital complications | Through study completion, an average of 1 year |
| Mortality rate | In-hospital mortality | Through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Age | Age in years | Baseline, pre-intervention/procedure/surgery |
| Sex | Sex (male/female) | Baseline, pre-intervention/procedure/surgery |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Adult patients with a diagnosis of Necortizing Soft Tissue Infection who undergo consultation by the Emergency General Surgery service.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Areg Grigorian, MD | Contact | 8184389093 | agrigori@hs.uci.edu | |
| Jeffry Nahmias, MD | Contact | 9493073035 | jnahmias@hs.uci.edu |
| Name | Affiliation | Role |
|---|---|---|
| Areg Grigorian, MD | University of California, Irvine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Irvine Medical Center | Recruiting | Orange | California | 92868 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17610007 | Background | Yilmazlar T, Ozturk E, Alsoy A, Ozguc H. Necrotizing soft tissue infections: APACHE II score, dissemination, and survival. World J Surg. 2007 Sep;31(9):1858-1862. doi: 10.1007/s00268-007-9132-1. | |
| 11842952 | Background | Childers BJ, Potyondy LD, Nachreiner R, Rogers FR, Childers ER, Oberg KC, Hendricks DL, Hardesty RA. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Am Surg. 2002 Feb;68(2):109-16. |
Not provided
Not provided
The overall study results will be listed on Clinicaltrials.gov
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Biochemical procalcitonin on admission and daily for up to 7 days or after source control has been achieved.
| Antibiotic duration (extended course) | Other | The patient will be enrolled in a 7 day course of antibiotics. |
|
| BMI (body mass index) | Body mass index (weight and height will be combined to report BMI in kg/m^2) | Baseline, pre-intervention/procedure/surgery |
| Blood Pressure | Blood Pressure (mmHg) | Baseline, pre-intervention/procedure/surgery |
| Heart Rate | Heart rate (beats/minute) | Baseline, pre-intervention/procedure/surgery |
| Respiratory rate | Respiratory rate (breaths/minute) | Baseline, pre-intervention/procedure/surgery |
| Temperature | Temperature (Fahrenheit) | Baseline, pre-intervention/procedure/surgery |
| Comorbidities | Comorbidities (e.g., diabetes, hypertension, cirrhosis, chronic kidney disease, etc.) | Baseline, pre-intervention/procedure/surgery |
| Transfusion requirements | Number of Packed Red Blood Cells transfused measured in milliliters | Baseline, pre-intervention/procedure/surgery |
| NSTI location | Anatomical location of soft tissue infection | Baseline, pre-intervention/procedure/surgery |
| Operations | Number of surgical procedures | Through study completion, an average of 1 year |
| Serum concentration of procalcitonin | Procalcitonin ng/mL | Upon admission and daily blood sample for 7 days |
| Serum concentration of white blood cell | White blood cell count cells per microliter (cells/μL) | Through study completion, an average of 1 year |
| Serum concentration of hemoglobin | Hemoglobin grams/deciliter | Through study completion, an average of 1 year |
| Serum concentration of sodium | Sodium millimoles per liter (mmol/L) | Through study completion, an average of 1 year |
| Serum concentration of C-reactive protein | C-reactive protein milligrams/liter | Through study completion, an average of 1 year |
| Serum concentration of glucose | Glucose milligrams/deciliter | Through study completion, an average of 1 year |
| Serum concentration of creatinine | Creatinine milligram/deciliter | Through study completion, an average of 1 year |
| Total hospital length of stay | Total days of hospital stay | Through study completion, an average of 1 year |
| Total intensive care unit (ICU) | Total days of ICU stay | Through study completion, an average of 1 year |
| Total ventilator days | Total days of ventilation support for the patient | Through study completion, an average of 1 year |
| 17198329 | Background | Hefny AF, Eid HO, Al-Hussona M, Idris KM, Abu-Zidan FM. Necrotizing fasciitis: a challenging diagnosis. Eur J Emerg Med. 2007 Feb;14(1):50-2. doi: 10.1097/01.mej.0000228447.48276.7b. |
| 24973422 | Background | Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15;59(2):e10-52. doi: 10.1093/cid/ciu444. |
| 21936959 | Background | Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011 Sep 22;9:107. doi: 10.1186/1741-7015-9-107. |
| 15070906 | Background | Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr. Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab. 2004 Apr;89(4):1512-25. doi: 10.1210/jc.2002-021444. No abstract available. |
| 27834617 | Background | Faraklas I, Yang D, Eggerstedt M, Zhai Y, Liebel P, Graves G, Dissanaike S, Mosier M, Cochran A. A Multi-Center Review of Care Patterns and Outcomes in Necrotizing Soft Tissue Infections. Surg Infect (Larchmt). 2016 Dec;17(6):773-778. doi: 10.1089/sur.2015.238. Epub 2016 Nov 11. |
| 35451883 | Background | Terzian WTH, Nunn AM, Call EB, Bliss SE, Swinarska JT, Rigdon J, Avery MD, Hoth JJ, Miller PR 3rd. Duration of Antibiotic Therapy in Necrotizing Soft Tissue Infections: Shorter is Safe. Surg Infect (Larchmt). 2022 Jun;23(5):430-435. doi: 10.1089/sur.2022.011. Epub 2022 Apr 22. |
| 32833599 | Background | May AK, Talisa VB, Wilfret DA, Bulger E, Dankner W, Bernard A, Yende S. Estimating the Impact of Necrotizing Soft Tissue Infections in the United States: Incidence and Re-Admissions. Surg Infect (Larchmt). 2021 Jun;22(5):509-515. doi: 10.1089/sur.2020.099. Epub 2020 Aug 21. |