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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Antibiotic duration (short course)
  The patient will be enrolled in a 48-hour course of antibiotics.
• Другое Antibiotic duration (extended course)
  The patient will be enrolled in a 7 day course of antibiotics.

Первичные конечные точки

• Safety of the antibiotic course duration [Срок оценки: Through study completion, an average of 1 year]
• Mortality rate [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (12)

• Age [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Sex [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• BMI (body mass index) [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Blood Pressure [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Heart Rate [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Respiratory rate [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Temperature [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Comorbidities [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Transfusion requirements [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• NSTI location [Срок оценки: Baseline, pre-intervention/procedure/surgery]
• Operations [Срок оценки: Through study completion, an average of 1 year]
• Serum concentration of procalcitonin [Срок оценки: Upon admission and daily blood sample for 7 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Pregnant patients
• Prisoners
• Patients with bacteremia upon admission
• Patients unable to provide consent (including no legally authorized representative)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• University of California Irvine Medical Center — Orange

Публикации

• 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. PMID 17610007
• 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. PMID 11842952
• 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. PMID 17198329
• 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. PMID 24973422
• 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. PMID 21936959
• 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. PMID 15070906
• 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. PMID 27834617
• 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. PMID 35451883

Идентификаторы

NCT: NCT06002607 · 2826

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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