10/19/17 Disclosures I have no disclosures. Skin and Soft Tissue - PDF document

10/19/17 Disclosures § I have no disclosures. Skin and Soft Tissue Infections Management of the Hospitalized Patient October 19, 2017 Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases University of California, San Francisco Learning Objectives Roadmap At the end of this lecture, you will be able to: 1. Uncomplicated abscess 2. Purulent cellulitis 1. Describe the new data on adjunctive antibiotic use after I+D 3. Nonpurulent cellulitis of an uncomplicated abscess. 4. Necrotizing infections 2. Name the most common organisms that cause purulent vs. 5. Human and animal bites nonpurulent SSTI and choose empiric antibiotics based on this. 1. Identify the key elements of diagnosis and management of necrotizing SSTIs. 2. List the indications for and drug of choice for prophylaxis of human and animal bites. 1

10/19/17 Overview of Skin and Soft Tissue Infections Overview of Skin and Soft Tissue Infections SSTI SSTI Nonpurulent Nonpurulent Purulent SSTI Purulent SSTI SSTI SSTI Necrotizing Nonpurulent Purulent Uncomplicated Necrotizing Nonpurulent Purulent Uncomplicated SSTI cellultiis cellulitis Abscess SSTI cellultiis cellulitis Abscess Case #1 What is the Most Evidenced-Based Option? 1. No antibiotics needed 40 year old man with a history of injection drug 2. TMP/SMX use presents with a right hand abscess but is otherwise clinically stable. 3. Doxycycline He gets an I+D in the 4. Amoxicillin/clavulanate emergency room. 2

10/19/17 2 Studies That Changed Practice Antibiotics Are Better Than I+D Alone 85 83 82 80 Clindamycin 80 TMP-SMX TMP-SMX Clinical Cure (%) 75 73 Placebo § 2 RCT’s of 800-1200 patients 69 70 § Small abscesses (most <3cm) + surrounding erythema Placebo 65 § All got I+D plus (oral antibiotics vs placebo for 7-10 d) p<0.001 p=0.005 NNT=14 NNT=7 § ~50% MRSA, 17% MSSA 60 Talan 2016 Daum 2017 Talan et al, NEJM 2016, 374:823. Daum et al, NEJM 2017;376:2545. Talan et al, NEJM 2016, 374:823. Daum et al, NEJM 2017;376:2545. Microbiology of Skin Abscesses (Purulent SSTI) Empiric Oral Antibiotics for Abscess/Purulent SSTI Dose Strep Side Local S. aureus (5-10 days) Activity effects/Comments susceptibility Other (know yours!) 21% GNRs TMP-SMX 1 DS bid +/- • Hyperkalemia, AKI >95% sensitive 4% • Hypersensitivity MRSA 55% Beta- Doxycycline 100mg bid +/- • GI, photosensitivity >90% sensitive • Less data hemolytic Strep MSSA Clindamycin 300mg tid ++ • GI, risk C. difficile 45-65% MRSA 3% • Can have resistance 80-85% MSSA 17% Linezolid 600mg bid ++ • $$$ ~100% sensitive • Marrow suppression • Serotonin Syn w/SSRI Talan et al, NEJM 2016, 374:823. Daum et al, NEJM 2017;376:2545. Moran et al, NEJM 2006, 355:666. 3

10/19/17 Preferred Oral ABx for Known MRSA or MSSA Case #1 Conclusion § No abscess culture was done MRSA MSSA § Given TMP-SMX 1 DS PO bid x 1 week • TMP-SMX • Cephalexin • Doxycycline • Dicloxacillin • Clindamycin • Any MRSA options • Linezolid Stevens et al, Clin Infect Dis 2014, 59:e10. Overview of Skin and Soft Tissue Infections Case #2 35 year old man with Behcet’s on high dose prednisone is admitted with fever, tachycardia, and the skin lesions shown, now s/p I+D in the ER. He is SSTI allergic to vancomycin. Nonpurulent Purulent SSTI SSTI Necrotizing Nonpurulent Purulent Uncomplicated SSTI cellultiis cellulitis Abscess 4

10/19/17 Which Antibiotics Would You Start? Empiric IV Antibiotics for Purulent SSTI 1. Clindamycin IV MRSA MRSA MRSA SSTI Bacteremia Pneumonia Vancomycin ✓ ✓ ✓ 2. TMP-SMX IV Daptomycin ✓ ✓ ✕ Linezolid +/- ✓ ✓ 3. Daptomycin § Other MRSA-active agents: telavancin, ceftaroline, 4. Daptomycin + pip/tazo dalbavancin, oritavancin, delafloxacin § If MSSA confirmed à use nafcillin or cefazolin § Step down to oral antibiotics against MRSA/MSSA Case #2 Conclusion Purulent SSTI: Take-Home Points § Abscess cultures grew MSSA 1. For uncomplicated abscesses, give oral antibiotics in § Blood cultures negative addition to I+D (but weigh risks and benefits) § Daptomycin à Cefazolin à cephalexin (total 10 days) 2. Empiric oral or IV antibiotics should include coverage for MRSA and MSSA (>70% of abscesses) 3. For oral agents, TMP-SMX, doxycycline, and clindamycin are all good empiric options but know your local susceptibility patterns 4. For IV agents, consider if you also need coverage for bacteremia or pneumonia 5

10/19/17 Purulent SSTI: Therapy Review Overview of Skin and Soft Tissue Infections SSTI Nonpurulent Purulent SSTI SSTI SSTI Necrotizing Nonpurulent Purulent Uncomplicated SSTI cellultiis cellulitis Abscess Nonpurulent Purulent SSTI SSTI MSSA MRSA or Empiric • I+D if possible Necrotizing Nonpurulent Purulent Uncomplicated Oral IV Oral SSTI cellultiis cellulitis Abscess • Cephalexin • Oral or IV Abx against • TMP-SMX • Vancomycin • Dicloxacillin Doxycycline • Daptomycin • MRSA and MSSA (5- Linezolid • Clindamycin • IV 10 days) • Linezolid • Cefazolin • Nafcillin Case #3 Should You Get Blood Cultures? 45 year old man with no 1. Yes significant PMH is admitted with fever to 38.2˚C and a red 2. No painful leg. Other vitals stable. WBC is 12. 6

10/19/17 Nonpurulent SSTI: When to Get Blood Cultures? Nonpurulent SSTI: Skin Sampling for Culture § Yield of blood cultures in uncomplicated § Yield of needle aspiration: <5% - 40% nonpurulent cellulitis is <5% § Yield of skin biopsy: 20% § Rarely changes management When should you get blood cultures in cellulitis? When should you consider a skin biopsy? 1. Severe infection (high fever, hypotension, ññ WBC) 1. Failure of appropriate empiric Rx - especially if severe, 2. Immunocompromise (including malignancy) immunocompromised or at risk for unusual organisms 3. Risk for unusual organisms (immersion injury, bites) 2. Consider upfront in severe infections in immunocompromised 4. Risk of S. aureus bacteremia (IDU, severe purulent cellulitis) 3. Concern for a cellulitis mimicker Perl et al, Clin Infect Dis 1999, 29:1483. Bauer et al, Eur J Intern Med 2016, 36:50. Stevens et al, Clin Infect Stevens et al, Clin Infect Dis 2014, 59:e10. Hook et al Arch Intern Med 1986, 146:295. Duvanel et al, Arch Dis 2014, 59:e10. Intern Med 1989, 149:293. Case #3: What Antibiotics Would You Start? Nonpurulent SSTI: Microbiology None 1. Vancomycin • >95% response to beta-lactams identified 12% • So MRSA is not a major player S. aureus 2. Cefazolin 3% 3. Vancomycin + pip/tazo Beta-hemolytic 4. Cefazolin + clindamycin Strep 85% Bruun et al, Open Forum Infect Dis 2016. Jeng et al, Medicine 2010, 89:217. 7

10/19/17 No MRSA Coverage Needed: How Are We Doing? So Do You Need MRSA Coverage or Not? Bottom Line: MRSA coverage is NOT needed Regimens for nonpurulent cellulitis in ED visits that include in uncomplicated nonpurulent cellulitis 100 MRSA coverage: 86 85 90 84 82 80 Cephalexin + Placebo Cephalexin + Placebo 2007 Cephalexin + TMP-SMX Cephalexin + TMP-SMX 70 % Clinical Cure 60 50 56% 68% 40 30 2010 20 p=0.66 10 p=0.50 0 Pallin 2013 Moran 2017 Pallin et al, West J Emerg Med 2014, 15:282. Pallin et al, CID 2013, 56:1754. Moran et al, JAMA 2017, 317:2088. Empiric Abx for Nonpurulent SSTI When to Expand Coverage? Beta-hemolytic MSSA MRSA When to Cover for MRSA? When to Cover for GNRs? Strep IV options ••Severe infection ••Severe infection ••Severe immunocompromise ••Severe immunocompromise Penicillin ✓ ✕ ✕ ••Penetrating trauma (surgical ••Surgical site infections in Cefazolin ✓ ✓ ✕ site infection, IV drug use) abdomen or axilla Ceftriaxone +/- ✓ ✕ ••Concurrent MRSA ••Orbital cellulitis Clindamycin ✓ ✓ ✓ elsewhere ••Not getting better without it PO options ••Not getting better without it Penicillin ✓ ✕ ✕ Amoxicillin ✓ ✕ ✕ Cephalexin IV: Vanco, Daptomycin, Linezolid IV: pip/tazo, cefepime, ertapenem ✓ ✓ ✕ Dicloxacillin PO: Clinda alone or beta-lactam + PO: Amoxicillin/clavulanate, ✓ ✓ ✕ (doxycycline or TMP-SMX) fluroquinolone Clindamycin ✓ ✓ ✓ Stevens et al, Clin Infect Dis 2014, 59:e10. Stevens et al, Clin Infect Dis 2014, 59:e10. 8

10/19/17 Case #3 Continued When Would You Escalate Abx For Cellulitis? He is started on cefazolin. By the next day, there is no 1. After 1 day change in his exam, vitals signs, or WBC count. 2. After 2 days How many days would you wait for a clinical response before escalating therapy? 3. After 3 days 4. After 4 days When Should Cellulitis Get Better? Case #3 Continued § He was escalated to vancomycin and pip/tazo by the Day 1 Day 2 Day 3 overnight provider. Cessation of 50% § After another 36 hours he is doing much better and spread, improved 85% inflammation 98% is ready for discharge. Now what regimen should he be discharged on? Defervesce and 40% WBC ê 85% 65% Escalation of Abx within 2 days was common but not associated with ñ response à likely was premature Bruun et al, Clin Infect Dis 2016, 63:1034. 9