SKIN AND SOFT TISSUE INFECTIONS

Ben Appenheimer, MD Assistant Professor Division of Infectious Diseases 4/2/19

*No disclosures or conflicts of interest OBJECTIVES • Understand the difference between purulent and non- purulent skin and soft tissue infections (SSTIs) • Understand how this difference affects microbiology and treatment • Learn how to identify necrotizing fasciitis and understand the basics of initial treatment • Understand the evidence behind treatment of purulent skin and soft tissue infections POLL EVERYWHERE

• Text BenA860 to 22333 for interactive polling • When the questions come up, simply text the letter associated with your answer to that same number (22333) Skin and Soft Tissue Infections

Non-Purulent Purulent

Erysipelas Cellulitis Necrotizing Abscess Furuncle Carbuncle Fasciitis

Importance of distinction: • Affects likely microbiology, treatment, and follow up Public Health Image Library, CDC NON-PURULENT SSTI: Non-Purulent CELLULITIS/ERYSIPELAS

Erysipelas Cellulitis Necrotizing Erysipelas Fasciitis • Generally refers to infection limited to upper dermis • Some use it synonymously with cellulitis • Well-demarcated, rapid onset fevers, chills, erythema • Almost exclusively caused by beta-hemolytic Strep

http://healthh.com/wp-content/uploads/2014/05/erysipelas-pictures-2.jpg https://www.uptodate.com/contents/image?imageKey=ID%2F110605&topicKey=ID%2F110529&source=outline_link&search=cellulitis&selectedTitle=2~150 NON-PURULENT SSTI: Non-Purulent CELLULITIS/ERYSIPELAS

Erysipelas Cellulitis Necrotizing Cellulitis Fasciitis • Infection involving deeper dermis and subcutaneous fat • Border is less demarcated, onset is more indolent • Essentially evaluated and treated the same as erysipelas • Coverage for beta-hemolytic Strep is required • Whether MSSA coverage is needed is debated

https://www.uptodate.com/contents/image?imageKey=ID%2F110605&topicKey=ID%2F110529&source=outline_link&search=cellulitis&selectedTitle=2~150

NON-PURULENT SSTI: CELLULITIS/ERYSIPELAS

Microbiology • Predominantly beta-hemolytic Strep species • i.e. Group A Strep (aka Strep pyogenes) • Staph aureus is a much less common cause of non-purulent cellulitis • IDSA Guidelines: • ‘Combined data from specimen cultures, serologic studies, and other methods suggests that the vast majority of these infections arise from Streptococci’

Open Forum Infectious Diseases, Volume 3, Issue 1, 1 January 2016, ofv181 WHAT COVERAGE IS NEEDED FOR ERYSIPELAS AND CELLULITIS?

• Historically we have worried about beta-hemolytic Strep, MRSA, and MSSA for skin and soft tissue infections • Strep coverage is always required for non-purulent SSTIs • Therefore, when deciding on antibiotics for non- purulent skin and soft tissue infections, the questions are: • Do I need MRSA coverage? • Do I need MSSA coverage? WHAT COVERAGE IS NEEDED?

Is MRSA coverage needed? Cephalexin Cephalexin + 95% CI P value alone TMP/SMX Pallin et al 2013 60/73 (82%) 62/73 (85%) -9.3% to 15% 0.66 Moran et al 2017 165/193 (85.5%) 182/218 (83.5%) -9.7% to 5.7% 0.50 What about in the inpatient setting? • One hospital looked at response to oxacillin or cefazolin in treatment of ‘non-culturable’ cellulitis • 116/121 (95.8%) had clinical response without MRSA coverage CONSIDERING MRSA COVERAGE IN CELLULITIS

• Purulence noted • Penetrating trauma • Including IV drug use • Open wound or underlying hardware • Evidence of MRSA infection elsewhere • Lack of response to beta-lactam therapy • Not necessarily based on appearance • Severe systemic symptoms

Clinical Infectious Diseases, Volume 59, Issue 2, 15 July 2014, Pages e10–e52, WHAT COVERAGE IS NEEDED? What about MSSA? • Studies cited above have included Strep and MSSA coverage in the control groups • No much data for regimens only covering Strep • Per guidelines, ‘many clinicians could include coverage against MSSA (weak recommendation, low evidence)’ • Some first line regimens per IDSA guidelines only cover Strep My take: • For presentations that are classic for erysipelas (ie rapid onset, well-demarcated erythema, no signs of deep fluid collection, no trauma or wound), I often focus my coverage on Strep pyogenes with either penicillin or amoxicillin • For cellulitis, would not be faulted for including MSSA coverage

Clinical Infectious Diseases, Volume 59, Issue 2, 15 July 2014, Pages e10–e52, NON-PURULENT SSTI: CELLULITIS/ERYSIPELAS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis Guideline recommended oral treatment for mild infections

Dosing Resistance rate of Notes Group A Strep Penicillin VK 500mg QID 0% Narrowest spectrum Amoxicillin 500mg TID 0% 3x daily dosing Cephalexin 500mg QID 0% Only needed if MSSA coverage desired Dicloxacillin 500mg QID 0% Only needed if MSSA coverage desired Clindamycin 300mg QID ~5% Some resistance, some Staph coverage NON-PURULENT SSTI: CELLULITIS/ERYSIPELAS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis Guideline recommended oral treatment for mild infections

Dosing Resistance rate of Notes Group A Strep Penicillin VK 500mg QID 0% Narrowest spectrum Amoxicillin 500mg TID 0% 3x daily dosing Cephalexin 500mg QID 0% Only needed if MSSA coverage desired Dicloxacillin 500mg QID 0% Only needed if MSSA coverage desired Clindamycin 300mg QID ~5% Some resistance, some Staph coverage What about TMP/SMX or doxycycline? • Efficacy against beta-hemolytic Strep is not well established NON-PURULENT SSTI: CELLULITIS/ERYSIPELAS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis Guideline recommended IV treatment for moderate non-purulent SSTI

Resistance rate Notes of Group A Strep Penicillin G 0% Narrowest spectrum, continuous infusion Cefazolin 0% 3x daily dosing, covers MSSA Ceftriaxone 0% Once daily, broader than needed (ie GNR coverage) Clindamycin ~5% Occasionally covers Staph NON-PURULENT SSTI: CELLULITIS/ERYSIPELAS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis Guideline recommended IV treatment for moderate non-purulent SSTI

Resistance rate Notes of Group A Strep Penicillin G 0% Narrowest spectrum, continuous infusion Cefazolin 0% 3x daily dosing, covers MSSA Ceftriaxone 0% Once daily, broader than needed (ie GNR coverage) Clindamycin ~5% Occasionally covers Staph What about Vancomycin? • Relatively weak Strep drug. Technically covers it, but not well Medicine (Baltimore). 2010 Jul;89(4):217-26. doi: 10.1097/MD.0b013e3181e8d635. Non-Purulent DURATION OF THERAPY

Erysipelas Cellulitis Necrotizing • Uncomplicated cellulitis: Fasciitis • IDSA Guidelines: ‘Recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within this time period (strong recommendation, high quality evidence) • Evidence: RCT showed If symptoms have improved by 5 days, 5 day course is as effective as a 10 day course • Clinical manifestations did not need to be fully resolved • Caveat: this study used only levofloxacin

Arch Intern Med. 2004 Aug 9-23;164(15):1669-74. ADJUNCTIVE THERAPIES FOR CELLULITIS

• Limiting edema • Leg elevation • Look for portal of entry • Fissuring, scaling, or maceration between toes • Onychomycosis, psoriasis, etc • Prednisone • Per IDSA, ‘can consider 40mg PO x 7 days in non-diabetic patients’ • RCT with 108 patients showed more rapid clinical resolution without change in relapse or recurrence rates • Haven’t seen this done clinically very often

Scand J Infect Dis. 1997;29(4):377-82.

CELLULITIS MIMICS

• Stasis dermatitis • Erythema, hyperpigmentation, serous drainage, desquamation • Nontender, no systemic signs, usually bilateral • Contact dermatitis • Lymphedema

Cleveland Clinic Journal of Medicine. 2012 August;79(8):547-552 • 38 y/o with h/o untreated HCV who presents to the ED with left periorbital swelling, erythema, and pain. This started shortly after a fall where he hit his eye on a well pump. Over the next 24 hours he noticed progressive swelling, severe pain, and purplish discoloration. He was febrile up to 104.5, disoriented, and lethargic. His WBC was 20.1. Maxillofacial CT is seen below. What empiric regimen should be started? • Answers on following slide

Skin and Soft Tissue Infections

Non-Purulent Purulent

Erysipelas Cellulitis Necrotizing Abscess Furuncle Carbuncle Fasciitis

Importance of distinction: • Affects likely microbiology, treatment, and follow up NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Necrotizing fasciitis Fasciitis • Severe, rapidly progressing, life threatening soft tissue infection • Often starts with skin lesion from minor trauma • Exam may show blisters, purple discoloration, crepitus • Patients are usually ‘toxic’ • Surgical emergency

https://www.jyi.org/2002-may/2002/5/23/when-bacteria-go-bad-the-case-of-necrotizing-fasciitis Guberman and Faroqi. Podiatry today, volume 24, issue 9, September 2011. NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Microbiology Fasciitis • Variable • Type I Necrotizing fasciitis • Polymicrobial (as in Fournier’s gangrene or odontogenic infections) • Mix of aerobic and anaerobic bacteria (including Clostridium perfringens) • Type II necrotizing fasciitis • Monomicrobial • Strep pyogenes infection • Staph aureus NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis Clinical manifestations • Initial presentation is similar to cellulitis • Progresses to include systemic toxicity • High fevers, disorientation, lethargy • Skin can become firm, necrotic (purple/black/gray), blister, and have crepitus • Pain out of proportion to exam • Very high mortality with Strep pyogenes • 30-70% • Those who survive often have significant morbidity NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Fasciitis NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Diagnosis Fasciitis • Definitive diagnosis is with surgery • ‘dishwater gray’ tissues • Radiographs (CT is best) showing subcutaneous air are suggestive of necrotizing SSTIs • If high suspicion, should not wait for imaging prior to surgical consult • This is a relatively late finding NON-PURULENT SSTI: NECROTIZING INFECTIONS Non-Purulent

Erysipelas Cellulitis Necrotizing Treatment Fasciitis • Immediate surgical consult for emergent operative debridement • Often require multiple re-explorations • Initially cover with broad spectrum antibiotics • As previously mentioned, microbiology can be variable • Need to cover Strep, Staph (including MRSA), resistant GNRs, and anaerobes • Once the organism is known, tailor therapy accordingly Skin and Soft Tissue Infections

Non-Purulent Purulent

Erysipelas Cellulitis Necrotizing Abscess Furuncle Carbuncle Fasciitis

Importance of distinction: • Affects likely microbiology, treatment, and follow up DEFINITIONS (PURULENT) Abscess • Collections of pus within the dermis and deeper skin tissues • Painful, tender, and fluctuant Furuncles • Infections of the hair follicle with pus down to the subcutaneous tissues • Aka ‘boils’ Carbuncles • Infection involving several adjacent follicles

https://www.uptodate.com/contents/image?imageKey=ID%2F110605&topicKey=ID%2F110529&source=outline_link&search=cellulitis&selectedTitle=2~150

PURULENT SSTI

Microbiology • Most common: Staph aureus (MSSA and MRSA) • Occasionally see Strep, GNRs but we don’t often empirically cover for these Antibiotics • Empiric therapy should target MRSA and MSSA with narrowing after susceptibilities • TMP/SMX or doxycycline • Vancomycin

CID 2014:59 (15 July) https://www.uptodate.com/contents/image?imageKey=ID%2F53261&topicKey=ID%2F110529&source=outline_link&search=abscess&selectedTitle=4~126 UIHC ANTIBIOGRAM TREATMENT OF UNCOMPLICATED ABSCESSES

Group Clindamycin TMP/SMX Placebo Cured/ % Cured/ % Cured/ % Total (95% CI) Total (95% CI) Total (95% CI) Intention to treat 221/266 83.1% 215/263 81.7% 177/257 68.9% (78.3-87.9) (76.8-86.7) (62.9-74.9) Population available 221/238 92.9% 215/232 92.7% 177/220 80.5% for evaluation (89.3-96.4) (89.0-96.3) (74.8-86.1)

N Engl J Med 2017; 376:2545-2555 TREATMENT OF ABSCESSES

Favors Antibiotics Favors Control

Treatment Failure in 1 month OR 0.58 (0.37,0.90)

Recurrence or new lesion within 1 month OR 0.48 (0.3, 0.77)

Recurrence or new lesion > 1 month OR 0.64 (0.48, 0.85)

BMJ Open. 2018 Feb 6;8(2) TO PACK OR NOT TO PACK

Abscesses < 5cm, immunocompetent Packing No packing RR, 95% CI P value N = 23 N= 25 Re-intervention at 48 hours 4 5 1.3, (0.4 – 4.2) 0.72 Use of ibuprofen in first 48 hrs (600mg pills) 2.29 1.97 0.12 Use of oxycodone/APAP (pills) 3.1 0.91 0.03

Acad Emerg Med. 2009 May;16(5):470-3. TAKE HOME POINTS

• Most non-purulent skin and soft tissue infections are due to beta-hemolytic Strep and empiric coverage should be targeted at these organisms • Use beta-lactam antibiotics • MRSA coverage is not necessary for non-purulent skin and soft tissue infections • Unless there is penetrating trauma or open wound • Relatively short course treatment can be considered for uncomplicated cases (ie 5 days) • Be wary of ‘bilateral cellulitis’ TAKE HOME POINTS

• If concerned for necrotizing fasciitis, call surgery and cover broadly • Imaging can show subcutaneous air but this is a late finding and is not sensitive for detecting nec fasc • There is increasing evidence that patients benefit from anti-MRSA antibiotics after I & D • TMP/SMX and doxycycline have highest susceptibility rates • There is some question whether packing small abscesses after I&D provides any significant benefit

QUESTIONS?