SSTIs Sarah Doernberg, MD, MAS Assistant Professor 2.20.2018 - PDF document

SSTIs Sarah Doernberg, MD, MAS Assistant Professor 2.20.2018  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730933/  https://www.journalofhospitalmedicine.com/jhospmed/article/12829 6/evidence-based-care-cellulitis  J Hosp Med. 2016 Aug;11(8):587-90. doi: 10.1002/jhm.2593.  Overtreatment of nonpurulent cellulitis.  https://acphospitalist.org/archives/2017/02/rethinking-cellulitis.htm  https://academic.oup.com/cid/article/51/8/895/331695 2/7/2018 1 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Disclosures  Grant/funding from: Antibacterial Research Leadership Group (NIH), Infectious Diseases Society of America  Consultant: Actelion, Genentech Outline  Cellulitis  Necrotizing infections  Special populations and exposures  Abscess 2 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Skin anatomy  Impetigo : Superficial infection of the skin with pustules/vesicles that crust or form bullae  Cellulitis : Deep dermis + fat  Erysipelas : Superficial infection involving lymphatics; tender, erythematous, well-demarcated plaque  Folliculitis : Superficial infection of hair follicle with purulence in epidermis  Furuncle : Infection of hair follicle with subcutaneous abscess  Carbuncle : Cluster of furuncles  Abscess : Pus within dermis and deeper skin  Pyomyositis : Purulent ifxn of muscle  Necrotizing fasciitis: Infection of subcutaneous tissue spreading along fascial planes  Gas gangrene: Necrotizing ifxn of muscle By Don Bliss (artist) [Public domain], via Wikimedia Commons https://upload.wikimedia.org/wikipedia/commons/5/5d/Anatomy_The_Skin_-_NCI_Visuals_Online.jpg 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 would you like to prescribe ? A. Cephalexin + tmp/smx PO B. Clindamycin PO C. Linezolid PO D. Cephalexin PO E. Vancomycin IV 3 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Cephalexin +/- TMP/SMX for cellulitis #1  Multicenter double-blind, placebo-controlled RCT in 3 EDs of patients > 12 y/o with cellulitis not being admitted  Failure = subsequent hospitalization for the same infection, change in antibiotics, drainage of an abscess, or recurrence w/i 30 days  Allowed < 24 hours IV cefazolin or nafcillin (~25%) Population Cephalexin Ceph + TMP/SMX 95% CI 30-day cure 82% 85% 2.7% ( − 9.3 to 15) abscess 6.8% 6.8% 0% ( − 8.2 to 8.2) AE 53% 49% − 4.1 ( − 20% to 12%) Pallin DJ et al. Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1. Cephalexin +/- TMP/SMX for cellulitis #2  Multicenter, double-blind, placebo-controlled superiority RCT at 5 US EDs  Outpatients > 12 yrs with cellulitis treated for 7 days • No wound, abscess, or purulence  1 ○ endpoint: clinical cure • significant difference: >10%  Populations well-matched on DM, fever, hx MRSA, site of ifxn  Median length of lesion: 13 cm (IQR 8-21)  Median width of lesion: 10 cm (IQR: 6-15)  257 (51.8%) were 100% adherent;122 (24.6%) took 76% to 99% of doses Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. 4 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Results Population Cephalexin Ceph + TMP/SMX 95% CI Per protocol 85.5% 83.5% -2.0% (-9.7 to 5.7) mITT1 69.0% 76.2% 7.3% (-1.0 to 15.5) mITT2 82.8% 83.8% 1.0% (-6.1 to 8.1) Hospitalization 5.2% 7.8% 2.6% (-2.6 to 7.8) AE 73.4% 75.0% mITT1 = took at least 1 dose and had f/u @ TOC mITT2 = took at least 1 dose and had f/u at some point • Failures were mostly abscess or purulent drainage • 68% MRSA (if cultures done), no difference by rx group • No invasive infection developed Moran GJ et al. JAMA. 2017 May 23;317(20):2088-2096. doi: 10.1001/jama.2017.5653. Who was left out  DM  Bite  Peripheral vascular disease  Immersion  Renal insufficiency  IVDU  Requires admission  Multifocal infection  Purulent discharge  Underlying skin disease  Cellulitis associated with  Pregnant/lactating hardware or device  Immunocompromised  Face, perianal, periungual 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. 5 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

How long to treat?  Randomized, double-blind RCT of 5 versus 10 days of levofloxacin for 77 patients with cellulitis • Could get up to 24 hours of another abx • Inpatient or outpatient, sickest excluded  Endpoint: Resolution @ 14 days without relapse @ 28 days  Result: 43/44 (98%) in the 5 day group versus 42/43 (98%) in the 10 day group met endpoint • 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 outpatient 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 6 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

Brief antibiotic review GAS MSSA MRSA Enterobacteriaceae Pseudomonas Penicillin +++ - - - - Amoxicillin +++ - - +/- - Cephalexin/ +++ +++ - + - cefazolin Clindamycin +++ ++ ++ - - Doxycycline ++ +++ ++ - - TMP/SMX + +++ +++ ++ - Linezolid +++ +++ +++ - - Ceftriaxone +++ + - +++ - Piperacillin/ +++ +++ - +++ +++ tazobactam Case, con’t: Your patient returns to clinic two 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 7 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

IDSA recommendations Patients who have failed oral antibiotic treatment = severe infection 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 8 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]

DDx to revisit in a stable patient  Drug reaction  Panniculitis  Contact dermatitis  Neoplasia (Paget’s dz of the breast, CTCL)  Venous stasis dermatitis  Insect bite reaction  DVT  Injection site reaction  Superficial thrombophlebitis  IV line infiltration  Hematoma  Erythema migrans  Gout  HSV, VZV  Vasculitis  Fungal infection  Erythema nodosum  Abscess, septic  Sarcoidosis arthritis/bursitis, osteomyelitis, mycotic aneurysm  Eosinophilic cellulitis 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 Derm 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%)  Non-blinded RCT of Dermatology consults for patients dx’d with cellulitis by PCP • All got Derm consults with Dx disclosed to those randomized to consult arm and not to the “placebo” arm • Only 3/29 (10%) diagnosed by PCP with cellulitis were confirmed by Dermatologist • 100% of patients in control arm versus 10% of those in consult arm given abx Strazzula L et al. J Am Acad Derm 2015; 73(1): 70-75 Arakaki RY et al. JAMA Dermatol. 2014;150(10):1056-1061. doi:10.1001/jamadermatol.2014.1085 9 2/7/2018 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS]