liu advances in id 4-12-14.ppt - ucsfcme.com.whsites.net · trauma/ surgery to area, tinea pedis...

4/16/2014

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Skin and Soft Tissue Infections: MRSA and Beyond

Catherine Liu, M.D.Assistant Professor of Clinical Medicine

Division of Infectious DiseasesUniversity of California, San Francisco

Overview

• Purulent SSTI

• Non‐purulent SSTI

• Recurrent SSTI

• Animal Bites

• Necrotizing soft tissue infections

• Potpourri of cases

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 cephalexin

C. Incision and drainage plus TMP‐SMX

D. Cephalexin

E. TMP‐SMX

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A. Incision and drainage alone

B. Incision and drainage plus cephalexin

C. Incision and drainage plus TMP‐SMX

D. Cephalexin

E. TMP‐SMX

Abscesses: Do antibiotics provide benefit over I&D alone?

0%

20%

40%

60%

80%

100%

Rajendran '07 Duong '09 Schmitz '10

% patients cured

Placebo

Antibiotic

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

Cephalexin TMP-SMX TMP-SMX

1Rajendran P AAC 2007; 2Schmitz G Ann Emerg Med 2010; 3Duong M Ann Emerg Med 2009

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

Liu C Clin Inf Dis 2011

Microbiology of Purulent SSTIs: ER Patients

Moran G NEJM 2006; Talan D Clin Inf Dis 2011

2004 2008

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Outpatient purulent cellulitis: Empiric Rx for MRSA

MRSA MSSA ‐hemolyticstrep

Comments

TMP/ SMX1‐2 DS tab BID

+ + ‐/? Low rates of resistance

Doxycycline, Minocycline100 mg BID

+ + ‐ Low rates of resistance

Clindamycin300‐450 TID

+/‐ + + C. diff risk

Linezolid600 mg BID

+ + + 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 2010


A. Clindamycin 300 mg PO TID

B. Cephalexin 500 mg QID

C. Cephalexin 500 mg QID and TMP/ SMX 2 DS tab PO bid


A. Clindamycin 300 mg PO TID

B. Cephalexin 500 mg QID

C. Cephalexin 500 mg QID and TMP/ SMX 2 DS tab PO bid

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Nonpurulent Cellulitis‐hemolytic strep vs. S. aureus?

• Prospective study, hospitalized patients (N=248)

Methods

– Acute and convalescent titers (ASO and anti‐DNaseB)

– Rx with ‐lactam antibiotics (cefazolin/oxacillin)

Results

– 73% due to ‐hemolytic strep; 27% no cause identified

– 96% response rate to ‐lactam antibiotic

Jeng A Medicine 2010

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

Pallin D Clin Inf Dis 2013

N=146

p=.66 p=.62p=1.0

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

MRSA MSSA ‐hemolytic strep

Penicillin V‐K500 mg QID/ Amoxicillin 500 mg TID

‐ Rare +/‐ ‐ ‐ +

Dicloxacillin500 mg QID

‐ + +

Cephalexin500 mg QID

‐ + +

Clindamycin300‐450 mg TID

+/‐ + +

Linezolid600 mg BID

+ + +

Microbiology of SSTI: Hospitalized Patients

Jenkins T Clin Inf Dis 2010

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Antibiotic Utilization Among Hospitalized Patients with SSTI: Baseline

Jenkins T Arch Intern Med 2011

N=169

Antibiotic Utilization Among Hospitalized Patients with SSTI: Post‐QI Intervention


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

p<.001

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


FDA Approved Agents for Treatment of Complicated SSTI

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(5 days)

•I&D

Consider addition of anti‐MRSA antibiotic in select situations1

• Cephalexin 500 QID• Dicloxacillin 500 QID

Consider MRSA active agent if no response

Complicated(5‐10 days)

•I&D plus vancomycin (or alternative2)

•Gram negative coverage not needed3

•Cefazolin, Nafcillin•Gram negative coverage not needed3

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. MRSA active PO antibiotic: TMP‐SMX, doxycycline, clindamycin

2. Daptomycin, linezolid, tigecycline, telavancin, ceftaroline3. 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

Recurrent Staphylococcal SSTI

Host

Environment Pathogen

Recurrent Staphylococcal SSTIManagement Strategies: Hygiene Education

• Cover draining wounds

• Wash hands after touching infected wound

• Avoid sharing personal items

• Use liquid pump/ pour soaps & lotions (vs. bar soaps)

• Launder towels and washcloths after each use, linens once weekly

• Clean high touch surfaces

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Recurrent Staphylococcal SSTIManagement Strategies: Decolonization

• Mupirocin: 5 days/ mth x 1 year↓ recurrent SSTI among 34 MSSA nasal carriers

• Chlorhexidine (CHG) washes alone: Not effective

• Mupirocin + CHG: Household >> individual decol

• Bleach baths: No benefit vs hygiene education

• Oral antibiotics: Mupirocin + hexachlorophene + TMP‐SMX or doxy x 10 d ↓ recurrent MRSA SSTI (31 pts); Anecdotal experience with rifampin‐based therapy

Raz Arch Intern Med 1996; Whitman ICHE 2010; Fritz ICHE 2012; Kaplan CID 2013; Miller AAC 2012

Mupirocin vs Mupirocin + Chlorhexidine vs Mupirocin + Bleach

N=229

Fritz S Inf Control Hosp Epi 2011*All groups received hygiene education

*

Household vs. Individual Decolonization w/Mupirocin + CHG x 5 days

Fritz S Clin Inf Dis 2012

p=.12 p=.02 p=.008 p=.02

*All groups received hygiene education

Bleach Baths + Hygiene vs. Hygiene

Bleach Baths: Twice weekly for 15 minutes x 3 monthsKaplan S Clin Inf Dis 2013

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Recurrent Streptococcal CellulitisManagement Strategies

• 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 every 2‐4 weeks

Stevens D Clin Inf Dis 2005

PCN 250 BID vs. Placebo For Prevention of Recurrent Cellulitis

Thomas K NEJM 2013

N=274

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 wounds on the calf.

In addition to wound care, what is the appropriate management of this patient?

A. No antibiotic prophylaxis needed

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

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In addition to wound care, what is the appropriate management of this patient?

A. No antibiotic prophylaxis needed

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 D NEJM 1999

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

• 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

– 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 TypeEvaluation and

disposure of animalPost‐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 individuallyAlmost never require prophylaxis

http://www.cdc.gov/rabies/resources/contacts.html

Case 4

• 39 yo M IVDU with L leg pain and erythema, worsening pain and swelling x 48 hours

• T 39.2 P 120 BP 90/60 R22 94%RA

• 18>38<90, Cr 2.4

What would your empiric therapy be in this case?

A. Vancomycin and piperacillin‐tazobactam

B. Vancomycin and piperacillin‐tazobactam, and

clindamycin

C. Call surgery, vancomycin and clindamycin

D. Call surgery, vancomycin, piperacillin‐

tazobactam, clindamycin

What would your empiric therapy be in this case?

A. Vancomycin and piperacillin‐tazobactam

B. Vancomycin and piperacillin‐tazobactam, and

clindamycin

C. Call surgery, vancomycin and clindamycin

D. Call surgery, vancomycin, piperacillin‐

tazobactam, clindamycin

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Cultures return positive for Group A streptococci. What changes, if any, would

you make to your antibiotics?

A. No changes, as patient remains critically ill, continue vancomycin, pip‐tazo, clindamycin

B. Vancomycin

C. Penicillin

D. Penicillin and clindamycin

Cultures return positive for Group A streptococci. What changes, if any, would

you make to your antibiotics?

A. No changes, as patient remains critically ill, continue vancomycin, pip‐tazo, clindamycin

B. Vancomycin

C. Penicillin

D. Penicillin and 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

Risk Factors for Necrotizing SSTI

• IVDU

• Diabetes

• Obesity

• Chronic immunosuppression

• Often no precipitating factor

Anaya DA. Clin Infect Dis. 2007

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Why is early diagnosis so important?

Wong CH. Jour of Bone and Joint Surg. 2003

Mortality rate: > 30%

Necrotizing soft tissue infections: physical findings on admission

Wong CH. Jour of Bone and Joint Surg. 2003

0

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 J Fam Pract. 2006

Special consideration for the treatment of invasive Group A strep?

• Protein synthesis inhibitors (clindamycin)

– Decrease toxin production

– Not affected by inoculum size

– Acts on bacteria in stationary phase of growth

• IVIG (in toxic shock syndrome)– May be able to bind toxin

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Is IVIG useful in strep toxic shock syndrome?

Observational Study – ‘99•Improved 7 day survival and 30 day survival•But…Cases > Controls

– Clindamycin (95% vs. 55%, P=0.01)– Surgery (67% vs. 38%, P=0.04)

Double‐Blinded RCT – ‘03•Ended early due to poor enrollment, 21 patients

– Mortality (36% placebo vs. 10% IVIG, p=NS)

– 13 pts with nec fasc‐ no in time to no further progression of necrotizing fasciitis

Kaul R. Clin Infect Dis. 1999; Darenberg J. Clin Infect Dis. 2003

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 with 9 day h/o 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, no improvement after 3 days

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

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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

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

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

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26 yo M with 6 week history of R hand papule ulcer

Multiple visits to ED and urgent care, Receives several courses of abx, noimprovement Leishmania panamensis

Which of the following reflect true infectious cellulitis?

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David Derm Online J 2011



B





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True cellulitis Acute on chronic stasis dermatitis

Acute stasis dermatitis

Contact dermatitis


“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

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!

[email protected]

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