Skin and soft tissue infections Sarah Doernberg, MD, MAS Associate - PDF document

Skin and soft tissue infections Sarah Doernberg, MD, MAS Associate Professor Medical Director of Antimicrobial Stewardship Disclosures  Consultant: Genentech, Basilea Pharmaceutica

Outline  Cellulitis  Necrotizing infections  Special populations and exposures  Abscess Case #1: 63 y/o M with chronic venous stasis and CHF presents to your clinic with 1 day of LLE erythema and warmth. He lives at home, has no recent hospitalizations, and denies prior history of skin infections. NKDA. Exam: Afebrile, well-appearing, cellulitis of LLE to knee without purulence. What antibiotic would you like to prescribe ? Cephalexin + tmp/smx PO A. Clindamycin PO B. Linezolid PO C. Cephalexin PO D. Vancomycin IV E.

Is MRSA coverage for non-purulent cellulitis needed #1?  Rx 7-14 dd LEX + PBO 1 ○ endpoint: (N = 73) < 24h CFZ • Rx success or NAF (~25%) • >12 y/o 2 ○ endpoints: • Cellulitis d/c home • Abscess • No abscess LEX + SXT • Adverse events • 3 EDs (N = 73) (mITT, N = 146) Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. What happened? 30-day cure Abscess Adverse event Failure: 6.8% LEX vs. 6.8% +SXT • Hospitalization 0% (-8.2 to 8.2%) • Δ in Abx • Drainage of abscess • Recurrence 53% LEX vs. 49% +SXT − 4.1 ( − 20% to 12%) 82% LEX vs. 85% +SXT GI effects most common 2.7% (-9.3 to 15%) Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1.

Is MRSA coverage for non-purulent cellulitis needed #2? Cure (superiority)  Rx 7 dd (per protocol) LEX + PBO Absence of: (N = 248) ultrasound to • D3-4: fever, >25% ↑ exclude erythema, swelling, abscess • >12 y/o tenderness • Cellulitis • D8-10: No ↓ erythema, • Median 10x13 cm swelling, tenderness LEX + SXT • Included DM (11%) • D14-21: More than (N = 248) • No abscess/pus/wound minimal erythema, swelling, tenderness • 5 EDs Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. What happened? Cure Hospitalization Adverse event 5.2% LEX vs. 7.8% +SXT 2.6% (-2.6 to 7.8) Per protocol: 86% LEX vs. 84% +SXT -2.0% (-9.7 to 5.7%) 73.4% LEX vs. 75% +SXT mITT-1 69% LEX vs. 76% +SXT GI effects most common 7.3% (-1.0 to 15.5%) Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653.

Who was left out?  DM  Face, perianal, periungual  Peripheral vascular disease  Bite  Renal insufficiency  Immersion  Requires admission  IVDU  Purulent discharge  Multifocal infection  Cellulitis associated with  Underlying skin disease hardware or device  Pregnant/lactating  Immunocompromised Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. How long should you treat? Randomized, double blind RCT 10 days 5 days (n = 44) (n = 43) Could get 24h of another drug Inpatient or outpatient Sickest excluded Resolution @ 14 days without 98% 98% relapse @ 28 days Most subjects still had mild residual signs of cellulitis at day 5 that resolved without further antibiotics Hepburn MJ et al. Arch Intern Med. 2004 Aug 9-23;164(15):1669-74.

Bottom line  Cephalexin is first-line for uncomplicated outpt cellulitis  5 days unless slow resolution or complicated course  In those patients, even if failure, invasive infection rare - Often failure due to unrecognized abscess  May need to consider MRSA or other coverage if: - Immunocompromised - IVDU - Associated with ulceration or hardware - Animal exposure - Immersion Case, con’t: Your patient returns to clinic four days later for a scheduled wound check. He reports excellent adherence with the antibiotics, but states that his leg is not improved. On exam, temp is 38, other vitals stable; well-appearing, erythema now extends 2 inches above the knee. No purulence noted. What is your next step? A. Switch to linezolid and schedule a follow-up in 2 days B. Switch to linezolid, obtain an ultrasound, and schedule a follow-up in 2 days C. Admit, obtain an ultrasound, switch to vancomycin D. Admit, obtain an ultrasound, switch to vancomycin and piperacillin/tazobactam

IDSA recommendations Patients who have failed oral antibiotic treatment Treat as a severe infection (i.e. vancomycin + piptazo)  Is this really needed? Stevens DL et al. CID 2014; 59(2), e10–e52 Reasons for failing outpatient therapy  Medication nonadherence or malabsorption  Wrong diagnosis  Resistant bacteria  Nonbacterial infection  Abscess/deep infection  Anatomic issues (e.g. lymphedema, venous stasis) slowing response  Organism is eradicated but inflammation persists

DDx to revisit in a stable patient Drug reaction Vasculitis Pyoderma    gangrenosum Contact dermatitis Erythema nodosum   IV line infiltration  Venous stasis Sarcoidosis   dermatitis Erythema migrans  Eosinophilic cellulitis  DVT HSV, VZV   Panniculitis  Superficial Fungal infection   Neoplasia (Paget’s dz  thrombophlebitis of the breast, CTCL) Abscess, septic  Hematoma arthritis/bursitis,  Insect bite reaction  osteomyelitis, mycotic Gout  Injection site reaction aneurysm  Raff AB and Korshinsky D. JAMA. 2016;316(3):325-337. doi:10.1001/jama.2016.8825 Cellulitis can be challenging to diagnose  Retrospective study of 74 Dermatology consults for cellulitis at 4 academic medical centers - 55 (74%) diagnosed with pseudocellulitis - Common final diagnoses:  stasis dermatitis (31%)  contact dermatitis (15%)  inflammatory tinea (9%) Strazzula L et al. J Am Acad Derm 2015; 73(1): 70-75

Dermatology consults for cellulitis in the office setting 2 (10%) dx’d with cellulitis Derm consult • 2 (10%)  abx (N = 20) • All better @ 1 wk f/u • Cellulitis dx’d by PCP • Stable 3 (33%) dx’d with • No immunocompromise Blinded derm eval cellulitis (N = 9) • 9 (100%)  abx Arakaki RY et al. JAMA Dermatol. 2014;150(10):1056-1061. doi:10.1001/jamadermatol.2014.1085 ID consults can help, too  Outpatients with cellulitis deemed to need IV abx - Pre period: ED-staffed clinic - Post period: ID-staffed clinic ED (149) ID (136) P value Cellulitis confirmed 133 (89%) 82 (60%) < 0.0001 Antibiotics stopped 0 16 (11%) <0.0001 Admission 11 (7%) 2 (1.5%) 0.01 Jain SR et al. Diag Micro and ID 2017; 87(4): 371-375

Oral antibiotic failure risk factors N = 497 pts discharged from ED with cellulitis Failure = hospitalization or Δ of antibiotics for worsening ifxn Risk factors for failure (OR, 95% CI) 102 (21%) failed • Fever @ initial triage: 4.3 (1.6-11.7) • 78% for Δ abx • Leg ulcers: 2.5 (1.1-5.2) • 22% for hospitalization • Lymphedema: OR 2.5 (1.5-4.2) • Prior cellulitis: OR 2.1 (1.3-3.5) Quirke M et al. BMJ Open. 2015 Jun 25;5(6):e008150. doi: 10.1136/bmjopen-2015-008150. Microbiology of oral antibiotic failure  Multicenter retrospective cohort of inpatients with SSTIs (N = 533) - 179/533 (34%) got prior abx  Those failing outpatient abx had fewer comorbidities, less fever, and lower WBCs and CRP Organism No PO abx (354) PO abx (179) P value Any 139 (39) 63 (35) 0.4 MRSA 38 (27) 26 (41) 0.05 GNR 18 (13) 2 (3) 0.03  100% of those failing outpatient PO rx survived to discharge Jenkins TC et al. Am J Emerg Med. 2016 Jun;34(6):957-62. doi: 10.1016/j.ajem.2016.02.013. Epub 2016 Feb 12.

Key interventions if outpatient rx fails  Revisit the diagnosis  Ensure adequate drainage  Address underlying anatomical issues - Edema, tinea  Coverage of MRSA - GNR coverage probably not needed unless unstable When is MRSA coverage indicated for cellulitis?  Hemodynamic instability  Overlying/associated with an indwelling medical device  Known MRSA colonization  Recent prior MRSA infection  Heavy hospital exposure (including dialysis, longterm care)  Injection drug use  Lack of response to a regimen not covering MRSA

Case, con’t: You switch your patient to IV vancomycin, and he responds well to therapy with regression of the erythema and resolution of the fever. On day #3, he is ready to go home. What oral antibiotic will you give him and for what duration? A. Cephalexin; 5 days from admission B. Cephalexin; 10 days from admission C. TMP/SMX; 5 days from admission D. TMP/SMX; 10 days from admission E. Oritavancin x 1 dose F. Place a PICC and administer vancomycin x 10 days What about these new long-acting abx?  Dalbavancin and oritavancin = long-acting lipoglycopeptides Study Drug Comparator Outcome DISCOVER I and II Dalbavancin VAN  LZD x 10-14 Noninferior day 1 and 8 days SOLO I and II Oritavancin x 1 VAN x 7-10 days Noninferior Dalba dosing trial Dalbavancin Dalba 1000 mg day Noninferior 1500 mg x 1 1 and 500 mg day 8 Boucher HW et al. N Engl J Med. 2014 Jun 5;370(23):2169-79. doi: 10.1056/NEJMoa1310480. Corey GR et al. N Engl J Med. 2014 Jun 5;370(23):2180-90. doi: 10.1056/NEJMoa1310422. Corey GR et al. Clin Infect Dis. 2015 Jan 15;60(2):254-62. doi: 10.1093/cid/ciu778.