Shorter Versus Extended Course of Antibiotic Therapy for Necrotizing Soft Tissue Infections

Necrotizing Soft Tissue Infection Clinical Trial

Official title:

Pilot Randomized Controlled Trial of Shorter Versus Extended Course of Antibiotic Therapy for Necrotizing Soft Tissue Infections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06002607
• Other study ID #: 2826
• Status: Recruiting
• Start date: December 28, 2023
• Est. completion date: September 1, 2025

Study information

• Verified date: December 2023
• Source: University of California, Irvine
• Contact: Areg Grigorian, MD
• Phone: 8184389093
• Email: agrigori[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Necrotizing Soft Tissue Infection
• Soft Tissue Infections

Intervention

Other:
• Antibiotic duration
The patient will be enrolled in a 48-hour course of antibiotics.
• Antibiotic duration
The patient will be enrolled in a 7 day course of antibiotics.

Locations

Country	Name	City	State
United States	University of California Irvine Medical Center	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Irvine

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Clin Infect Dis. 2015 May 1;60(9):1448. Dosage error in article text. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of the antibiotic course duration	In-hospital complications	Through study completion, an average of 1 year
Primary	Mortality rate	In-hospital mortality	Through study completion, an average of 1 year
Secondary	Age	Age in years	Baseline, pre-intervention/procedure/surgery
Secondary	Sex	Sex (male/female)	Baseline, pre-intervention/procedure/surgery
Secondary	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
Secondary	Blood Pressure	Blood Pressure (mmHg)	Baseline, pre-intervention/procedure/surgery
Secondary	Heart Rate	Heart rate (beats/minute)	Baseline, pre-intervention/procedure/surgery
Secondary	Respiratory rate	Respiratory rate (breaths/minute)	Baseline, pre-intervention/procedure/surgery
Secondary	Temperature	Temperature (Fahrenheit)	Baseline, pre-intervention/procedure/surgery
Secondary	Comorbidities	Comorbidities (e.g., diabetes, hypertension, cirrhosis, chronic kidney disease, etc.)	Baseline, pre-intervention/procedure/surgery
Secondary	Transfusion requirements	Number of Packed Red Blood Cells transfused measured in milliliters	Baseline, pre-intervention/procedure/surgery
Secondary	NSTI location	Anatomical location of soft tissue infection	Baseline, pre-intervention/procedure/surgery
Secondary	Operations	Number of surgical procedures	Through study completion, an average of 1 year
Secondary	Serum concentration of procalcitonin	Procalcitonin ng/mL	Upon admission and daily blood sample for 7 days
Secondary	Serum concentration of white blood cell	White blood cell count cells per microliter (cells/µL)	Through study completion, an average of 1 year
Secondary	Serum concentration of hemoglobin	Hemoglobin grams/deciliter	Through study completion, an average of 1 year
Secondary	Serum concentration of sodium	Sodium millimoles per liter (mmol/L)	Through study completion, an average of 1 year
Secondary	Serum concentration of C-reactive protein	C-reactive protein milligrams/liter	Through study completion, an average of 1 year
Secondary	Serum concentration of glucose	Glucose milligrams/deciliter	Through study completion, an average of 1 year
Secondary	Serum concentration of creatinine	Creatinine milligram/deciliter	Through study completion, an average of 1 year
Secondary	Total hospital length of stay	Total days of hospital stay	Through study completion, an average of 1 year
Secondary	Total intensive care unit (ICU)	Total days of ICU stay	Through study completion, an average of 1 year
Secondary	Total ventilator days	Total days of ventilation support for the patient	Through study completion, an average of 1 year