Skin and Soft Tissue Infections: MRSA and Beyond Catherine Liu, M.D. - - PDF document

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Skin and Soft Tissue Infections: MRSA and Beyond

Catherine Liu, M.D. Assistant Clinical Professor Division of Infectious Diseases University of California, San Francisco

Overview

• Abscesses
• Cellulitis
• Recurrent SSTI
• Animal Bites
• Necrotizing fasciitis
• Other SSTI

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Case 1

20 y/o M presents 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

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Abscesses

• Incision and drainage is the primary treatment (AII).

– For simple abscesses or boils, I&D alone likely adequate

• Do antibiotics provide additional benefit?

0% 20% 40% 60% 80% 100% Rajendran'07 Duong'09 Schmitz'10 Antibiotic Placebo

1Rajendran AAC 2007; 2Duong Ann Emerg Med 2009; 3Schmitz G Ann Emerg Med 2010; Liu CID 2011; 52: 285-322

p=.25 p=.12 p=.52 cephalexin

TMP-SMX TMP-SMX

Clinical cure

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: 285‐322

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Microbiology of Purulent SSTIs: ER Patients

MRSA

59%

MSSA 17%

B‐hemolytic strep 3%

non‐B hemolytic strep 4%

• ther

8%

unknown 9%

MRSA 59% MSSA 16%

B‐hemolytic strep, 2% coag neg staph, 6% viridans strep, 2%

• ther/ unknown,

15%

Moran NEJM 2006; Talan CID 2011

2004 2008

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: 285‐322

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Outpatient purulent cellulitis: Empiric Rx for CA‐MRSA

MRSA MSSA ‐hemolytic strep Comments

TMP/ SMX 1‐2 DS tab BID + + ‐ Low rates of resistance Doxycycline, Minocycline 100 mg BID + + ‐ Low rates of resistance Clindamycin 300‐450 TID +/‐ ( resistance) + +  C. diff risk Linezolid 600 mg BID + + + Most expensive

• ption

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 2010

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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 study1, 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 study2

–  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

1Jeng et al Medicine 2010; 2Elliott et al Pediatrics 2009; Liu CID 2011; 52: 285‐322

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Cephalexin vs. Cephalexin + TMP‐SMX in patients with Uncomplicated Cellulitis

Pallin CID 2013; 56: 1754‐1762

N=146

Outpatient nonpurulent cellulitis: Empiric Rx for ‐hemolytic streptococci, +/‐ MRSA

MRSA MSSA ‐hemolytic strep

Penicillin V‐K 500 mg QID/ Amoxicillin 500 mg TID ‐ Rare +/‐ ‐ ‐ + Dicloxacillin 500 mg QID ‐ + + Cephalexin 500 mg QID ‐ + + Clindamycin 300‐450 mg TID +/‐ ( resistance) + + Linezolid 600 mg BID + + +

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Microbiology of SSTI: Hospitalized Patients

• 322 hospitalized patients

with cellulitis, abscess, complicated SSTI

• 97% of cases had S. aureus
• r Streptococcus spp.
• 74% S. aureus or

Streptococcus ONLY

Jenkins CID 2010; 51: 895‐903

Enterococci 3%

Antibiotic Utilization Following Implementation

• f a QI Project on Management of Inpatient SSTI

* * * * *p<.05

Jenkins Arch Intern Med 2011; 171: 1072‐9

*Recommended empiric vanco *Discouraged gram neg/ anaerobic *Suggested Rx for 7 days

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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: 1072‐9

Complicated SSTI

 Surgical debridement & empiric Rx for MRSA pending cx

Antibiotic Adult

Vancomycin 15‐20 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

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Summary: empiric management of SSTIs

Purulent

(MRSA)

Non‐purulent

(β‐hemolytic strep)

Uncomplicated

• I&D

Consider addition of anti‐MRSA antibiotic in select situations1

• Cephalexin 500 QID
• Dicloxacillin 500 QID

Consider MRSA active agent in select situations2

Complicated

• I&D plus vancomycin (or

alternative),no gram neg in most cases3

• Vancomycin (or

alternative), no gram neg in most cases3

• 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

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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: 285-322; Fritz ICHE 2011; 32:872-80

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 carriage.

• @ 1 month: 50% vs. 51% (p = 1.0)
• @ 12 months: 54% vs. 66% (p= .28)

Fritz CID 2012; 54:743‐51

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Recurrent SSTI among Cases and Household Contacts

Fritz CID 2012; 54: 743-51 p=.12 p=.02 p=.008 p=.02

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 2005

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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: 1695‐703

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.

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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
• 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 1999

Microbiology of Animal Bites: What’s in their mouth and on your skin

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• What you want to use but won’t work…

–cephalexin –dicloxacillin –clindamycin

• What works…

–Amoxicillin/ penicillin –doxycycline –fluoroquinolones

Antibiotic Coverage for Pasteurella

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)

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Rabies – what type of bites are high risk?

Animal Type Evaluation and disposure of animal Post‐exposure prophylaxis

Dog, cats, ferrets Suspected/confirmed rabid Healthy Animal lost Prophylaxis 10 days observation/test Contact DPH Skunk, raccoons, foxes, bats Regarded as rabid unless proven negative by lab test Immediate prophylaxis Livestock, small rodents, rabbits, large rodents Consider individually Almost never require prophylaxis

http://www.cdc.gov/mmwr/pdf/rr/rr57e507.pdf

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

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What would your empiric therapy be in this case?

• A. Admit, IV vancomycin and piperacillin‐

tazobactam

• B. Call surgery, IV vancomycin and clindamycin
• C. Call surgery, IV vancomycin, piperacillin‐

tazobactam, 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

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• IVDU
• Diabetes
• Obesity
• Chronic immunosuppression
• Often no precipitating factor

Anaya DA. Clin Infect Dis. 2007

Risk Factors for Necrotizing SSTI

Clinical Presentation

• Nonspecific

complaints: pain, GI (N/V/D), influenza‐like symptoms

• Physical exam difficult

to distinguish from cellulitis, sometimes

• nly mild local

erythema – pain out

• f proportion

Initial Diagnoses by PCP/ER No. Musculoskeletal Pain 6 (40%) Influenza 3 (20%) Gastroenteritis 2 (13%) Hemorrhoids 1 (6%) Gout 1 (6%) 1 burn 1 (6%) Varicella 1 (6%)

Wong CH Crit Care Med 2004 Bisno CID 2000

Missed Dx of Necrotizing Fasciitis

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Necrotizing soft tissue infections: physical findings on admission

Wong CH. Jour of Bone and Joint Surg. 2003

10 20 30 40 50 60 70 80 90 100 % of patients

Late findings n=89; 14% dx with nec fasc on admit

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):396.

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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

• f 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.

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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

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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

5/28/2013 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

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Which of the following reflect true infectious cellulitis?

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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 2005

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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, non‐ infectious etiologies), BIOPSY for culture and pathology.

Thank you!

catherine.liu@ucsf.edu