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

NCT ID: NCT06002607

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-12-28
• Study Completion Date: 2025-12-01

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.

Conditions

Necrotizing Soft Tissue Infection

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Antibiotic duration

Intervention Type: OTHER

The patient will be enrolled in a 48-hour course of antibiotics.

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

Antibiotic duration

Intervention Type: OTHER

The patient will be enrolled in a 7 day course of antibiotics.

Interventions

Antibiotic duration

The patient will be enrolled in a 48-hour course of antibiotics.

Intervention Type: OTHER

Antibiotic duration

The patient will be enrolled in a 7 day course of antibiotics.

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Areg Grigorian

Assistant Clinical Professor, Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Areg Grigorian, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Irvine

Locations

University of California Irvine Medical Center

Orange, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Areg Grigorian, MD

Role: CONTACT

agrigori@hs.uci.edu

8184389093

Jeffry Nahmias, MD

Role: CONTACT

jnahmias@hs.uci.edu

9493073035

Facility Contacts

Areg Grigorian, MD

Role: primary

agrigori@hs.uci.edu

8184389093

Jeffry Nahmias, MD

Role: backup

jnahmias@hs.uci.edu

9493073035

References

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Reference Type: BACKGROUND

PMID: 17610007 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11842952 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17198329 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 24973422 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21936959 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15070906 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 27834617 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35451883 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32833599 (View on PubMed)

Other Identifiers

2826

Identifier Type: -

Identifier Source: org_study_id