Skin and Soft Tissue Infections: MRSA and Beyond

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1 Skin and Soft Tissue Infections: MRSA and Beyond Catherine Liu, M.D. Assistant Clinical Professor Division of Infectious Diseases University of California, San Francisco Abscesses Cellulitis Recurrent SSTI Animal Bites Necrotizing fasciitis Other SSTI Overview 1

2 Case 1 20 y/o Mpresents with 3 days of an enlarging, painful lesion on his L arm that he attributes to a spider bite T 36.9 BP 118/70 P 82 What is the appropriate management of this patient? A. Incision and drainage alone B. Incision and drainage plus oral anti MRSA antimicrobial agent C. Oral anti MRSA antimicrobial agent 2

3 Abscesses Incision and drainage is the primary treatment (AII). For simple abscesses or boils, I&D alone likely adequate Do antibiotics provide additional benefit? 100% 80% Clinical cure 60% 40% 20% 0% p=.25 p=.12 p=.52 cephalexin TMP-SMX TMP-SMX Rajendran'07 Duong'09 Schmitz'10 Antibiotic Placebo 1 Rajendran AAC 2007; 2 Duong Ann Emerg Med 2009; 3 Schmitz G Ann Emerg Med 2010; Liu CID 2011; 52: Antibiotic therapy is recommended for abscesses associated with: Severe, extensive disease, rapidly progressive with associated cellulitis or septic phlebitis Signs & sx of systemic illness Associated comorbidities, immunosuppressed Extremes of age Difficult to drain area (e.g. face, hand, genitalia) Failure of prior I&D (AIII) Liu CID 2011; 52:

4 Microbiology of Purulent SSTIs: ER Patients non B hemolytic strep 4% other 8% unknown 9% viridans strep, 2% other/ unknown, 15% B hemolytic strep 3% MSSA 17% MRSA 59% B hemolytic strep, 2% coag neg staph, 6% MSSA 16% MRSA 59% Moran NEJM 2006; Talan CID 2011 Purulent Cellulitis Cellulitis associated with purulent drainage or exudate without a drainable abscess Empiric Rx for CA MRSA is recommended (AII). Empiric Rx for hemolytic strep unlikely needed (AII). Duration of therapy: 5 10 days, individualize based on clinical response Liu CID 2011; 52:

5 Outpatient purulent cellulitis: Empiric Rx for CA MRSA MRSA MSSA hemolytic strep Comments TMP/ SMX 1 2 DS tab BID Doxycycline, Minocycline 100 mg BID Clindamycin TID Linezolid 600 mg BID + + Low rates of resistance + + Low rates of resistance +/ ( resistance) + + C. diff risk Most expensive option Case 2 28 year old woman with erythema of her left foot x 48 hours. No purulent drainage, exudate or abscess. T 37.0 BP 132/70 P 78 Eells SJ et al Epidemiology and Infection

6 What is the appropriate management of this patient? A. Clindamycin 300 mg PO tid B. Cephalexin 500 mg QID C. Cephalexin 500 mg QID and TMP/ SMX 2 DS tab PO bid Nonpurulent Cellulitis: hemolytic strep vs. staph? Empiric Rx for hemolytic strep recommended (AII) Prospective study 1, 248 hospitalized pts 73% due to hemolytic strep 27% with no identified cause. Overall 96% response rate to lactam antibiotic (cefazolin, oxacillin, cephalexin, dicloxacillin). Retrospective study 2 treatment failures with TMP SMX vs. lactam or clindamycin * Consider coverage for MRSA if: History/evidence of MRSA infection elsewhere, failure to respond to lactam 1 Jeng et al Medicine 2010; 2 Elliott et al Pediatrics 2009; Liu CID 2011; 52:

7 Cephalexin vs. Cephalexin + TMP SMX in patients with Uncomplicated Cellulitis N=146 Pallin CID 2013; 56: Outpatient nonpurulent cellulitis: Empiric Rx for hemolytic streptococci, +/ MRSA MRSA MSSA hemolytic strep Penicillin V K 500 mg QID/ Amoxicillin 500 mg TID Dicloxacillin 500 mg QID Cephalexin 500 mg QID Clindamycin mg TID Linezolid 600 mg BID Rare +/ / ( resistance)

8 322 hospitalized patients with cellulitis, abscess, complicated SSTI 97% of cases had S. aureus or Streptococcus spp. 74% S. aureus or Streptococcus ONLY Microbiology of SSTI: Hospitalized Patients Enterococci 3% Jenkins CID 2010; 51: Antibiotic Utilization Following Implementation of a QI Project on Management of Inpatient SSTI * *Recommended empiric vanco *Discouraged gram neg/ anaerobic *Suggested Rx for 7 days * * * *p<.05 Jenkins Arch Intern Med 2011; 171:

9 Other Outcomes Median duration of Rx (13 vs. 10d, p<.001) No differences in clinical outcomes Clinical failure (7.7% vs. 7.4%, p=ns) Recurrent infection Rehospitalization due to SSTI Length of hospital stay Jenkins Arch Intern Med 2011; 171: Complicated SSTI Surgical debridement & empiric Rx for MRSA pending cx Antibiotic Adult Vancomycin mg/kg IV Q8 12 Linezolid 600 mg PO/ IV BID Daptomycin 4 mg/kg IV QD Telavancin 10 mg/kg IV QD Ceftaroline 600 mg IV Q12 Tigecycline 100 mg IV x 1, then 50 IV Q12 9

10 Summary: empiric management of SSTIs Purulent (MRSA) Non purulent (β hemolytic strep) Uncomplicated Complicated I&D Consider addition of anti MRSA antibiotic in select situations 1 I&D plus vancomycin (or alternative),no gram neg in most cases 3 Cephalexin 500 QID Dicloxacillin 500 QID Consider MRSA active agent in select situations 2 Vancomycin (or alternative), no gram neg in most cases 3 1. Systemic illness, purulent cellulitis/wound infection, comorbidities, extremes of age, abscess difficult to drain or face/hand, septic phlebitis, lack of response of to I&D alone. PO antibiotic : TMP SMX 1 2 DS BID, Clindamycin 300 mg TID, Doxycycline 100 PO BID 2. History/ evidence of MRSA elsewhere, failure to respond to lactams 3. Except: critically ill pts with serious SSTI (nec fasc), perirectal/ periorbital infections, decubitus ulcer infections, severe diabetic foot infections, animal bites, water exposure Recurrent SSTI Recurrent abscess, furunculosis: Staphylococcus aureus (MRSA and MSSA) Recurrent cellulitis: hemolytic streptococci 10

11 Recurrent Staphylococcal SSTI Decolonization strategies: do they work? Mupirocin based regimens appear to be effective in reducing S. aureus colonization BUT no data shows decolonization prevents recurrent SSTI Hygiene education: keep draining wounds covered, wash hands after touching infected wound, avoid sharing personal items, clean high touch surfaces Regimens to consider: Mupirocin +/ chlorhexidine or bleach x 5 10 days Dilute bleach baths: ¼ cup per ¼ tub (13 gallons) of water for 15 min, 2x/week for 3 mths Liu CID 2011; 52: ; Fritz ICHE 2011; 32: Household vs. Individual Decolonization? Open label RCT children with community onset SSTI and S. aureus colonization (nares, axilla, inguinal) 2 Index case vs. household decolonization (mupirocin + CHG baths x 5d) All received hygiene education: Avoid sharing personal hygiene items Use liquid pump or pour soaps and lotions (vs. bar soaps and lotion jars) Launder towels and washcloths after each use Launder bed linens once weekly No difference in rate of eradication of S. aureus 1 month: 50% vs. 51% (p = 12 months: 54% vs. 66% (p=.28) Fritz CID 2012; 54:

12 Recurrent SSTI among Cases and Household Contacts p=.008 p=.02 p=.02 p=.12 Fritz CID 2012; 54: Recurrent Cellulitis Is there a role for antibiotic prophylaxis? Most patients have predisposing factor: Obesity, lymphedema, venous insufficiency, prior trauma/ surgery to area, tinea pedis Management approach: Treat underlying conditions whenever possible (e.g. compressive stockings, Rx interdigital maceration/ tinea, emollients to avoid dryness/ cracking, diuretics) Prophylactic antibiotics if frequent recurrence Penicillin VK 250 mg PO twice daily Benzathine PCN 1.2 MU IM monthly Stevens CID

13 PCN for Prevention of Recurrent Cellulitis Multicenter, double blind RCT 274 pts with recurrent cellulitis Penicillin 250 mg BID vs. placebo x 12 mths Patient characteristics: Chronic edema (66%), venous stasis (25%), tinea pedis (36%) Outcomes: Recurrent cellulitis: 22% (PCN) vs. 37% (placebo), p=.01 After treatment stopped, no difference Thomas NEJM 2013; 368: Case 3 21 yo M is tossing a ball in Golden Gate Park with a friend. As he goes after the ball, he passes close to a dog that was resting in the shade with his owner. The dog jumps up and bites him on the leg inflicting several puncture wounds on the calf. 13

14 In addition to wound care, what is the appropriate management of this patient? A. No antibiotic prophylaxis is necessary B. Antibiotic prophylaxis with clindamycin C. Antibiotic prophylaxis with amoxicillin/ clavulanate D. Administer rabies immunoglobulin and rabies vaccine for post exposure prophylaxis E. C and D Microbiology of Animal Bites: What s in their mouth and on your skin Average 5 organisms (range 0 16) per wound Dogs Cats Pasturella sp 50% 75% Streptococcus sp. 46% 46% Staphylococcus aureus 20% 4% Anaerobes mixed w/ aerobes 48% 63% Anaerobes alone 1% 0% Talan NEJM

15 Antibiotic Coverage for Pasteurella What you want to use but won t work cephalexin dicloxacillin clindamycin What works Amoxicillin/ penicillin doxycycline fluoroquinolones Animal bites Empiric treatment regimens Amoxicillin/clavulanic acid +/ anti MRSA Pen allergy: cipro + clindamycin or moxifloxacin Prophylaxis? Moderate severe bites w/ crush injury Deep puncture wounds (i.e. cat bites, 50% infection risk) Bites involving face, hands Immunocompromised (splenectomized) 15

16 Rabies what type of bites are high risk? Animal Type Dog, cats, ferrets Skunk, raccoons, foxes, bats Livestock, small rodents, rabbits, large rodents Evaluation and disposure of animal Suspected/confirmed rabid Healthy Animal lost Regarded as rabid unless proven negative by lab test Consider individually Post exposure prophylaxis Prophylaxis 10 days observation/test Contact DPH Immediate prophylaxis Almost never require prophylaxis Case 4 39 yo M IVDU with 1 day h/o L leg pain and erythema, worsening pain and swelling x 48 hours T 39.2 P120 BP96/60 R22 98%RA 18>40<425, left shift 16

17 What would your empiric therapy be in this case? A. Admit, IV vancomycin and piperacillintazobactam B. Call surgery, IV vancomycin and clindamycin C. Call surgery, IV vancomycin, piperacillintazobactam, clindamycin Necrotizing skin and soft infections Monomicrobial (Group A strep > S. aureus, Clostridia, gram neg rare) Polymicrobial (gram +, gram, anaerobes) associated w/ abdominal surgery, decub ulcers, IVDU, spread from GU tract 17

18 Risk Factors for Necrotizing SSTI IVDU Diabetes Obesity Chronic immunosuppression Often no precipitating factor Anaya DA. Clin Infect Dis Clinical Presentation Nonspecific complaints: pain, GI (N/V/D), influenza like symptoms Physical exam difficult to distinguish from cellulitis, sometimes only mild local erythema pain out of proportion Missed Dx of Necrotizing Fasciitis Initial Diagnoses by No. PCP/ER Musculoskeletal Pain 6 (40%) Influenza 3 (20%) Gastroenteritis 2 (13%) Hemorrhoids 1 (6%) Gout 1 (6%) 1 burn 1 (6%) Varicella 1 (6%) Bisno CID 2000 Wong CH Crit Care Med

19 % of patients Necrotizing soft tissue infections: physical findings on admission Late findings n=89; 14% dx with necfascon admit Wong CH. Jour of Bone and Joint Surg Necrotizing soft tissue infections: radiographic techniques Plain films Low sensitivity Helpful if gas present CT and ultrasound May identify other Dx (abscess) MRI Enhanced sensitivity, low specificity Dufel S, Martino M. J Fam Pract. 2006;55(5):

20 Summary: Management of necrotizing skin and soft tissue infections Early surgical consult/ intervention Empiric antimicrobial therapy Piperacillin/tazobactam or carbapenem (group A strep, other gram pos, gram negs and anaerobes) plus Clindamycin (group A strep toxin inhibition) plus Vancomycin (MRSA) Case 5 53 yo M ER physician presents with 9 day history of progressive cellulitis of L forearm. Initially noted a pustule self I&D, started keflex + clindamycin x 4 days. Progressive erythema and drainage. Started IV vanco + ceftriaxone with no improvement after 3 days. 20

21 Further history History of chronic benign neutropenia 3 weeks ago, trip to Arizona where cleared brush in order to replace a water drip line and scraped his arm 2 weeks ago, worked in home (Merced) vegetable garden clearing eggplant and pepper brushes 7 days ago, cleaned his fish tank No animal or tick bites Only recent travel to Arizona All of the following are possible causes of his infection EXCEPT: A. Mycobacterium marinum B. Coccidioides immitis C. Nocardia brasiliensis D. Brucella melitensis E. Sporothrix schenkii 21

22 Gram stain from wound culture Nocardia brasiliensis Nocardia Soil inhabitant Worldwide distribution Incubation period: <1 6 weeks Often with mild systemic symptoms Nocardia brasiliensis > asteroides for cutaneous disease Diagnosis: biopsy and culture Partially acid fast, gram variable branching rods. Treatment: TMP SMX x 4 6 months 22

23 26 yo M with 6 week history of R hand papule ulcer Multiple visits to ED and urgent care, Receives several courses of abx, no improvement Leishmania panamensis 23

24 Which of the following reflect true infectious cellulitis? 24

25 Which of the following reflect true infectious cellulitis? True cellulitis Acute on chronic stasis dermatitis Acute stasis dermatitis Contact dermatitis David Derm Online J 2011 Masqueraders of Infectious Cellulitis Stasis dermatitis Superficial thrombophlebitis and deep venous thrombosis Contact dermatitis Insect stings/tick bites Drug reactions Gouty arthritis Foreign body reaction (e.g. surgical mesh, orthopedic implants) Lymphedema Malignancy (e.g. T cell lymphoma) Falagas ME Ann Intern Med

26 Summary Drainage/ debridement is the mainstay of therapy of all purulent skin and soft tissue infections. For purulent cellulitis, cover for CA MRSA. For non purulent cellulitis, cover for hemolytic strep For most hospitalized patients with SSTI, coverage against S. aureus and streptococci is adequate; gram negative and anaerobic coverage unnecessary. If no response to standard antibiotic therapy, consider alternative diagnoses (e.g. unusual infections, noninfectious etiologies), BIOPSY for culture and pathology. Thank you! 26

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