Necrotizing Soft Tissue Infections Addison K. May, MD, FACS, FCCM Professor of Surgery and Anesthesiology Division of Trauma and Surgical Critical Care Vanderbilt University Medical Center SIS 35th Annual Meeting Four Seasons Westlake Village, CA

60 yo female with DM and HTN Presents to ED ~36 hrs after repair of contaminated LE laceration –10/10 pain –LE swelling, erythema, ecchymosis –Vitals: temp 98, HR 110, BP 107/76 1 hr after presentation –Labs: WBC 13.8, HCT 50, Na 131, CO2 18, Glucose 348, Creat 2.05 –Plain X-ray: gas in tissue –IV antibiotics given 3 hrs after presentation - admit to OBSERVATION –Admission diagnosis: CELLULITIS –Bullous lesions documented 7.5 hrs after presentation – transferred to higher level of care –9.5 hrs after presentation – AKA –Died after several weeks in the hospital

Disclosures Research funding: Fresenius Kabi Bayer HealthCare Pharmaceuticals Inc Cubist Pharmaceuticals, Inc BHR Pharma, LLC Consultant: Atox Bio, Ltd.

What’s New in NSTI? Ovid: 2005 – 2015 for NSTI, NF, Fournier’s, Gas Gangrene –English language, human: 1508 –English, human, review articles: 215 –Prospective studies:36 –25 NSTI/NF/Fournier’s (2 hyperbaric) –7 Streptococcal/Vibrio epidemiology –4 total hyperbaric –Randomized trials: 0 1 RTC in NSTI: Bulger, EM. JAMA Surg. 2014;149:

Overall mortality remains high: 74 retrospective reports patients Overall mortality – 22.6% – : mortality – 27.8% – : mortality – 21.2% (~ 24% RR reduction) May AK. Surg Clin N Am. 2009; 89:403–420 May AK. Surg Infect. 2009; 10: Unpublished data NSTI: still - may be lethal

Today’s focus 1.Importance of nomenclature and implications of pathophysiology 2.Establishing the diagnosis 3.Important components of therapy

Necrotizing Soft Tissue Infections Is this name important? Literature commonly misuses the term NECROTIZING FASCIITIS for all necrotizing soft tissue infections So what?... –Incorrectly consolidates three tissue layers –Confounds the understanding of inherent resistance of each tissue layer and the pathophysiology of bacterial infection –Limits an in-depth understanding of both antibiotic and surgical approach

NSTI: Tissue layers and infection Dermis and subcutaneous fat –Good resistance to bacterial invasion, proliferation –Infection: NECROTIZING CELLULITIS Fascia (deep or muscle) –Tentative blood supply, poor lymphatic drainage, and low resistance to bacterial invasion, growth, and spread –Infection: NECROTIZING FASCIITIS Muscle –Very good blood supply and good resistance to bacterial invasion and proliferation –Infection: MYOSITIS and MYONECROSIS

Determinants of Infection Pathogen Host vs HOST TISSUE RESISTANCE BACTERIAL VIRULENCE GROWTH CHARACTERISTICS … Presentation and severity of infection determined by a balance between these factors …

NSTI: bacterial pathogenesis Type 1: polymicrobial typically arise from a chronic, indolent source spread along fascial planes most common ~ 50-75% of NSTIs Type 2: monomicrobial virulent Gm +, aerobic cocci pathophysiology related to toxin production +/- growth rate Streptococcus species CA-MRSA Type 3: monomicrobial virulent Gm + or Gm – bacilli pathophysiology related to toxin production +/- growth rate Clostridia species Bacillus species Vibrio species Aeromonas species Eikenella species Rapidly progressive

NSTI with CA-MRSA Tissue Resistance vs Bacterial Virulence

NSTI - CA-MRSA Tissue Resistance vs Bacterial Virulence 1 week S/P STSG to area of soft tissue loss

Necrotizing Soft Tissue Infection: Diagnosis Difficult to distinguish from cellulitis and complex abscesses Diagnosis is frequently delayed Cellulitis and abscess – most common admitting diagnoses –~65-80% of patients Wong CH. J Bone Joint Surg. 2003; 85A: Hsiao CT. Am J Ethics Med. 2008;26:170–5 Wong CH. Crit Care Med. 2004;32:1535–41

Delays in diagnosis associated with increased morbidity and mortality Predictors of mortality in NSTI : –Time to first debridement –Extent of tissue involvement –# Failed organs on admission –Inadequate first debridement –Age > 60 years –Bacteremia –Elevated lactate Why is early diagnosis important? McHenry CR. Ann Surg. 1995; 221: Bosshardt TL. Arch Surg. 1996;131: Elliott DC. Ann Surg. 1996; 224: Bilton BD. Am Surg. 1998; 64: Childers BJ. Am Surg. 2002; 68: Wong CH. J Bone Joint Surg. 2003; 85A:

Clinical features: (1C) 1.pain disproportionate to the findings on physical examination 2.tense edema 3.bullae 4.skin ecchymosis/necrosis 5.cutaneous anesthesia 6.systemic toxicity 7.progression despite antibiotic therapy Laboratory values: (1C) 1.white blood cell count >14 x 10 9 /L 2.serum sodium concentration <135 mmol/L 3.BUN >15 mg/dL 4.CRP > 150 mg/L Radiographic findings: (1C) 1.Presence of gas on imaging May AK. Surg Infect. 2011; 12: May AK. Surg Infect. 2009; 10: Symptoms and findings predictive of NSTI

Laboratory parameters aid in diagnosis 21 consecutive patients who proved to have NSTI Chan, T. Am. J. Surg. 2008; 196:

Questionnaire of Chief Resident during evaluation Chan, T. Am. J. Surg. 2008; 196: Mean time to OR: 10 hours (1 - 46) Mortality 25% Laboratory parameters add to diagnosis

Treatment of NSTI – What really matters? Early appropriate antibiotic therapy of pathogens (1C) Timely surgical debridement (1C) Adequate surgical debridement (1C) Re-evaluation and/or return to OR within 24 h (1C) May AK. Surg Infect. 2011; 12: May AK. Surg Infect. 2009; 10:

NSTI: AB therapy based upon presentation Non-rapidly progressive NSTI – Polymicrobial or less virulent pathogens Possible MRSA Rapidly progressive NSTI – highly virulent pathogens due to toxin production Gram positive –Gram positive cocci – (Type 2) Grp A strep, Ca-MRSA –Gram positive bacilli – (Type 3) clostridia, bacillus Gram negative (Type 3) –Vibrio species –Aeromonas species –Eikenella species Rapidly progressive Dual coverage with antiribosomal agents may improve outcome Gm +: Clindamycin / Linezolid Gm -: Tetracycline class Single or combination broad spectrum AB +/- anti MRSA

Aeromonas hydrophila in a trauma patient

NSTI: Approach to Surgical Debridement OR as soon as the diagnosis is suspected Approach based upon tissues involved –Fasciitis: “ladder” incisions with drainage, irrigation, and debridement –Necrotizing cellulitis: excision of non-viable tissues –Myositis, myonecrosis: excision of non-viable tissues Ensure adequate tissue perfusion and viability Prevent fluid pooling or collections Re-evaluate/return to OR in 24 hours

Does time to re-debridement matter? 64 patients with NSTI at USC-LAC over 6 years Practice algorithms by 2 different services –Short duration (24-48 hrs) vs Extended duration (> 48 hrs) until second debridement Short duration associated with lower AKI and mortality Okoye O. Amer Surg. 2013; 79:

Necrotizing Soft Tissue Infections SIS 35th Annual Meeting Four Seasons Westlake Village, CA Thank you for your attention