Disclosures Consultant: Genentech Skin and soft tissue infections - PDF document

Disclosures § Consultant: Genentech Skin and soft tissue infections Sarah Doernberg, MD, MAS Associate Professor Medical Director of Antimicrobial Stewardship Outline Case #1: 63 y/o M with DMII, 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 § Cellulitis would you like to prescribe ? § Necrotizing infections § Special populations and exposures Cephalexin + tmp/smx PO A. § Abscess Clindamycin PO B. Linezolid PO C. Cephalexin PO D. Vancomycin IV E. 1 | [footer text here]

What happened? Is MRSA coverage for non-purulent cellulitis needed #1? 30-day cure Abscess Adverse event § Rx 7-14 dd Failure: 6.8% LEX vs. 6.8% +SXT LEX + PBO • Hospitalization 0% (-8.2 to 8.2%) 1 ○ endpoint: • Δ in Abx (N = 73) < 24h CFZ • Rx success • Drainage of abscess or NAF • Recurrence (~25%) • >12 y/o 2 ○ endpoints: • Cellulitis d/c home 53% LEX vs. 49% +SXT • Abscess • No abscess −4.1 (−20% to 12%) LEX + SXT • Adverse events • 3 EDs 82% LEX vs. 85% +SXT (N = 73) (mITT, N = 146) 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. Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. What happened? Is MRSA coverage for non-purulent cellulitis needed #2? Cure Hospitalization Adverse event § Rx 7 dd Cure (superiority) (per protocol) 5.2% LEX vs. 7.8% +SXT LEX + PBO 2.6% (-2.6 to 7.8) Absence of: (N = 248) ultrasound to Per protocol: • D3-4: fever, >25% ↑ exclude erythema, swelling, 86% LEX vs. 84% +SXT abscess • >12 y/o tenderness -2.0% (-9.7 to 5.7%) • Cellulitis 73.4% LEX vs. 75% +SXT • D8-10: No ↓ erythema, • Median 10x13 cm swelling, tenderness LEX + SXT mITT-1 • Included DM (11%) • D14-21: More than 69% LEX vs. 76% +SXT (N = 248) minimal erythema, • No abscess/pus/wound GI effects most common 7.3% (-1.0 to 15.5%) swelling, tenderness • 5 EDs Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. 2 | [footer text here]

Who was left out? How long should you treat? Randomized, double blind RCT § DM § Face, perianal, periungual 10 days 5 days § Peripheral vascular disease § Bite (n = 44) (n = 43) § Renal insufficiency § Immersion Could get 24h of another drug § Requires admission § IVDU Inpatient or outpatient Sickest excluded § Purulent discharge § Multifocal infection Resolution @ 14 days without 98% 98% § Cellulitis associated with § Underlying skin disease relapse @ 28 days hardware or device § Pregnant/lactating Most subjects still had mild residual signs of cellulitis § Immunocompromised at day 5 that resolved without further antibiotics Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. Hepburn MJ et al. Arch Intern Med. 2004 Aug 9-23;164(15):1669-74. Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. Bottom line Case, con’t: Your patient returns to clinic two days later for a scheduled wound check. He reports excellent adherence with the § Cephalexin is first-line for uncomplicated outpt cellulitis antibiotics, but states that his leg is not improved. On exam, temp is 38, other vitals stable; well-appearing, erythema now extends 2 inches § 5 days unless slow resolution or complicated course above the knee. No purulence noted. What is your next step? § In those patients, even if failure, invasive infection rare A. Switch to linezolid and schedule a follow-up in 2 days - Often failure due to unrecognized abscess B. Switch to linezolid, obtain an ultrasound, and schedule a § May need to consider MRSA or other coverage if: follow-up in 2 days - Immunocompromised - IVDU C. Admit, obtain an ultrasound, switch to vancomycin - Associated with ulceration or hardware D. Admit, obtain an ultrasound, switch to vancomycin and - Animal exposure - Immersion piperacillin/tazobactam 3 | [footer text here]

IDSA recommendations Reasons for failing outpatient therapy § Medication nonadherence or malabsorption Patients who have failed oral antibiotic treatment § Wrong diagnosis § Resistant bacteria § Nonbacterial infection § Abscess/deep infection § Anatomic issues (e.g. lymphedema, venous stasis) slowing Treat as a severe infection (i.e. vancomycin + piptazo) response § Is this really needed? § Organism is eradicated but inflammation persists Stevens DL et al. CID 2014; 59(2), e10–e52 DDx to revisit in a stable patient Cellulitis can be challenging to diagnose Drug reaction Vasculitis Pyoderma § § § § Retrospective study of 74 Dermatology consults for cellulitis at gangrenosum Contact dermatitis Erythema nodosum § § 4 academic medical centers IV line infiltration § Venous stasis Sarcoidosis § § - 55 (74%) diagnosed with pseudocellulitis dermatitis Erythema migrans § Eosinophilic cellulitis § - Common final diagnoses: DVT HSV, VZV § § Panniculitis § § stasis dermatitis (31%) Superficial Fungal infection § § Neoplasia (Paget’s dz § thrombophlebitis § contact dermatitis (15%) of the breast, CTCL) Abscess, septic § Hematoma arthritis/bursitis, § § inflammatory tinea (9%) Insect bite reaction § osteomyelitis, mycotic Gout § Injection site reaction § aneurysm Strazzula L et al. J Am Acad Derm 2015; 73(1): 70-75 Raff AB and Korshinsky D. JAMA. 2016;316(3):325-337. doi:10.1001/jama.2016.8825 4 | [footer text here]

ID consults can help, too Dermatology consults for cellulitis in the office setting § Outpatients with cellulitis deemed to need IV abx 2 (10%) dx’d with cellulitis - Pre period: ED-staffed clinic Derm consult • 2 (10%) à abx - Post period: ID-staffed clinic (N = 20) • All better @ 1 wk ED (149) ID (136) P value f/u • Cellulitis dx’d by PCP Cellulitis confirmed 133 (89%) 82 (60%) < 0.0001 • Stable 3 (33%) dx’d with • No immunocompromise Antibiotics stopped 0 16 (11%) <0.0001 Blinded derm eval cellulitis Admission 11 (7%) 2 (1.5%) 0.01 (N = 9) • 9 (100%) à abx Jain SR et al. Diag Micro and ID 2017; 87(4): 371-375 Arakaki RY et al. JAMA Dermatol. 2014;150(10):1056-1061. doi:10.1001/jamadermatol.2014.1085 Oral antibiotic failure risk factors Microbiology of oral antibiotic failure N = 497 pts discharged from ED with cellulitis § 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 Failure = hospitalization or Δ of antibiotics for worsening ifxn Organism No PO abx (354) PO abx (179) P value Any 139 (39) 63 (35) 0.4 Risk factors for failure (OR, 95% CI) 102 (21%) failed • Fever @ initial triage: 4.3 (1.6-11.7) MRSA 38 (27) 26 (41) 0.05 • 78% for Δ abx • Leg ulcers: 2.5 (1.1-5.2) • 22% for hospitalization GNR 18 (13) 2 (3) 0.03 • Lymphedema: OR 2.5 (1.5-4.2) § 100% of those failing outpatient PO rx survived to discharge • 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. 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. 5 | [footer text here]

Key interventions if outpatient rx fails When is MRSA coverage indicated for cellulitis? § Revisit the diagnosis § Hemodynamic instability § Overlying/associated with an indwelling medical device § Ensure adequate drainage § Known MRSA colonization § Address underlying anatomical issues § Recent prior MRSA infection - Edema, tinea § Heavy hospital exposure (including dialysis, longterm care) § Coverage of MRSA § Injection drug use - GNR coverage probably not needed unless unstable § Lack of response to a regimen not covering MRSA Case, con’t: You switch your patient to IV vancomycin, and he What about these new long-acting abx? 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? § Dalbavancin and oritavancin = long-acting lipoglycopeptides A. Cephalexin; 5 days from admission Study Drug Comparator Outcome DISCOVER I and II Dalbavancin VAN à LZD x 10-14 Noninferior B. Cephalexin; 10 days from admission day 1 and 8 days C. TMP/SMX plus amoxicillin; 5 days from admission SOLO I and II Oritavancin x 1 VAN x 7-10 days Noninferior D. TMP/SMX plus amoxicillin; 10 days from admission Dalba dosing trial Dalbavancin Dalba 1000 mg day Noninferior E. Oritavancin x 1 dose 1500 mg x 1 1 and 500 mg day 8 F. Place a PICC and administer vancomycin x 10 days 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. 6 | [footer text here]