Management of Skin and Soft Tissue Infections in

Management of Skin and Soft Tissue
Infections in the MRSA Era
April 2011
Brian S. Schwartz, MD
Assistant Clinical Professor
UCSF, Division of Infectious Diseases
32 y/o M with 3 days of an
enlarging, painful lesion
on his L thigh that he
attributes to a “spider
bite”
T 36.9 BP 118/70 P 82
Case 1
Overview
• 2011 IDSA MRSA Treatment Guidelines
– Skin and soft tissue infections (SSTIs)
• Management of Recurrent SSTIs
• Necrotizing soft tissue infection
• Management of Animal Bites
How would you manage this
patient?
A. Incision and drainage
alone
B. Incision and drainage plus
oral anti-MRSA
antimicrobial agent
C. Oral anti-MRSA
antimicrobial agent
40%
51%
10%
A. B. C.
4/12/2011
1

Microbiology of Purulent SSTIs
Moran NEJM 2006
Is treatment failure the only
important endpoint? Recurrent SSTI?
• Duong : 10 days
– 9% TMP-SMX vs. 28% placebo , p = .02
• Schmitz: 30 days
– 13% TMP-SMX vs 26% placebo, p= .04
Schmitz G Ann Emerg Med 2010; Duong Ann Emerg Med 2009
% patients cured
Abscesses: Do antibiotics provide
benefit over I&D alone?
100%
80%
60%
40%
20%
0%
p=.25 p=.12 p=.52
Cephalexin TMP-SMX TMP-SMX
Rajendran '07 Duong '09 Schmitz '10
Placebo
Antibiotic
1 Rajendran AAC 2007; 2 Schmitz G Ann Emerg Med 2010; 3 Duong Ann Emerg Med 2009
Antibiotic therapy is recommended
for abscesses associated with:
• Severe disease, rapidly progressive with
associated cellulitis or septic phlebitis
• Signs or symptoms of systemic illness
• Associated comorbidities, immunosuppressed
• Extremes of age
• Difficult to drain area (face, hand, genitalia)
• Failure of prior I&D
Liu C. Clin Infect Dis. 2011
4/12/2011
2

When to culture a purulent SSTI?
• Patients Rx with antibiotics
• Patients with severe local infections
• Patients with signs of systemic illness
• Patient has not responded to initial Rx
• Concern for outbreak or cluster
28 y/o woman presents
with erythema of her left
foot over past 48 hrs
No purulent drainage,
exudate , or fluctuance.
T 37.0 BP 132/70 P 78
Case 2
Liu C. Clin Infect Dis. 2011
Eels SJ et al Epidemiology and Infection 2010
Empiric oral antibiotic Rx
for uncomplicated purulent SSTI
Drug Adult Dose
TMP/SMX DS 1-2 BID
Doxycycline, Minocycline 100 BID
Clindamycin 300-450 TID
Linezolid 600 BID
*Rifampin is NOT recommended for routine treatment of SSTIs
How would you manage this
patient?
A. Clindamycin 300 mg TID
B. Cephalexin 500 mg QID,
monitor clinically with addition
of TMP/SMX if no response
C. Cephalexin 500 mg QID + TMP/
SMX 2 DS BID
21%
54%
25%
A. B. C.
4/12/2011
3

Nonpurulent Cellulitis: pathogen?
β-hemolytic strep vs. S. aureus?
• Prospective study, hospitalized patients (N=248)
Methods
– Acute and convalescent titers (ASO and anti-DNaseB)
– Rx with β -lactam antibiotics (cefazolin/oxacillin)
Results
– 73% due to β-hemolytic strep; 27% none identified
– 96% response rate to β-lactam antibiotic
Siljander T. Clin Infect Dis. 2008 Jeng A. Medicine 2010. Elliott Pediatrics 2009
Summary: empiric management of SSTIs
Uncomplicated
Complicated
•I&D
Purulent
(MRSA)
Consider addition of anti-MRSA
antibiotic in select situations 1
•I&D plus vancomycin (or
alternative) 2
Non-purulent
(β-hemolytic strep)
• Cephalexin 500 QID
• Dicloxacillin 500 QID
Consider addition of MRSA active
agent if no response 1
•Vancomycin (or
alternative) 2
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 DS BID, Clindamycin 300 mg TID, Doxycycline 100 PO BID
2. Daptomycin, linezolid, telavancin, ceftaroline
Empiric treatment of uncomplicated
nonpurulent cellulitis?
• Anti-β-hemolytic strep antibiotic (+/- anti-MSSA)
Drug Adult Dose
Cephalexin 500 QID
Dicloxacillin 500 QID
Clindamycin* 300-450 TID
Linezolid* 600 BID
*Have activity against MRSA
• If poor response, add anti-MRSA antibiotic
Empiric antibiotics for complicated SSTI
Antibiotic Adult Pediatric
Vancomycin 15-20 mg/kg IV Q8-12 15 mg/kg IV Q6
Linezolid 600 mg PO/ IV BID 10 mg/kg PO/IV Q8
Daptomycin 4 mg/kg IV QD Ongoing study
Telavancin 10 mg/kg IV QD *No data
Ceftaroline 600 mg IV Q12 *No data
4/12/2011
4

Classic impetigo
Ecythema
Impetigo
Case 3
Bullous impetigo
• Patient presents with 4 th abscess in 4 months
• Prior abscesses have been treated with I&D
and antibiotics with resolution
• He asks if there is anything he can do to
prevent recurrences
Impetigo
• Definition: superficial, intra-epidermal infection
• Epi: Common in children, highly communicable
• Pathogens: S. aureus, Group A strep
• Treatment:
– Few lesions (topical = systemic)
• Mupirocin or Retapamulin ointment
– Multiple lesions (systemic >> topical)
• Pick agent(s) active against CA-MRSA and Group A strep
How would you manage this
patient?
A. Emphasize personal hygiene
measures
B. Decolonize with mupirocin and
chlorhexidine
C. Decolonize with TMP-SMX and
rifampin
D. All the above
9%
65%
11%
15%
A. B. C. D.
4/12/2011
5

How to Manage Recurrent Skin and
Soft Tissue Infections?
Host
Environment Pathogen
Decolonization strategies
• Intranasal mupirocin
• Chlorhexidine washes
• Suppressive oral antibiotics
• Oral therapy with rifamycins
What is the Management of Recurrent Skin and
Soft Tissue Infections?
Environmental Hygiene (CIII)
-Clean high-touch surfaces
Personal Hygiene Hygiene/ Wound Care (AIII)
Host
Environment Pathogen
-Cover draining wounds
-Hand hygiene
-Avoid sharing if active infection
Decolonization*
Decolonization (CIII)
Liu C. Clin Infect Dis. 2011
Intra-nasal mupirocin to prevent
recurrent MSSA SSTI?
• Methods:
– ≥ 3 SSTIs in 2 years plus S. aureus nasal carriage
– Randomized study
– Intervention: Nasal mupirocin BID 1 wk/mo x 1 yr
• Results: (N=40)
– Primary endpoint: recurrent SSTI
– 6% (mupirocin) vs. 47% (placebo); p < 0.02
Raz R. Arch Int Med. 1996
4/12/2011
6

Intra-nasal mupirocin to prevent
CA-MRSA SSTI?
• 1° prophylaxis (prospective RCT)
– 134 soldiers with CA-MRSA nasal colonization
– Mupirocin (5d) vs. placebo
– SSTI: 10.6% mupirocin vs. 7.7% placebo
• 2° prophylaxis (retrospective)
– 38 HIV+ with CA-MRSA SSSI and nasal colonization
– Mupirocin vs. no treatment
– Recurrent SSTI: 32% mupirocin vs. 52% no treatment
Ellis et al, AAC ’07. Rahimain et al, ICHE ’07
Daily clindamycin to prevent
recurrent SSTI?
• Subjects: ≥3 abscesses in prior 6 months
• Rx: clindamycin 150 mg QD vs. placebo
• Results: Abscess during Rx period
– 33% (clinda) vs. 81% (placebo); p=0.04
– High recurrence rate after stopping clindamycin
Klempner MS. JAMA 1988.
Chlorhexidine to prevent SA SSTI
• RCT of military recruits to prevent SSTI
• Chlorhexidine wipes vs. placebo 3 x/week
• Results: SSTI rate at 6 weeks
•
% S. aureus carriage
– 9.4% (chlorhexidine) vs. 7.1% (placebo); p=0.13
• Results: S. aureus colonization (45% baseline)
100
90
80
70
60
50
40
30
20
10
0
– 52.6% (chlorhexidine) vs. 67% (placebo)
Whitman TJ. Infect Control Hosp Epidemiol. 2010
Rifampin for eradication of
S. aureus colonization?
Rx period
Control
Rifampin
Cloxacillin
Rifampin and Cloxacillin
0 0.5 1 2 3 4 5 6 7 8 9 10 11 12
Weeks
Wheat J. JID. 1981.
4/12/2011
7

Case 4
• 34 y/o M comes in with
arm pain, fever
• Temp 38.9, HR 105, SBP
100, RR 20
• Appears ill and in more
pain than what you
would expect for
cellulitis
Necrotizing skin and skin structure
infections
• Definition: infections of any layer within the soft
tissue compartment that are associated with
necrotizing changes
• Monomicrobial
– associated w/ minor injuries
• Polymicrobial
– associated w/ abdominal surgery, decub ulcers,
IVDU, spread from GI tract
What would your empiric therapy
be in this case?
A. Cephalexin plus TMP-SMX, send
home
B. Clindamycin, piperacillintazobactam,
and vancomycin
C. Call surgery, vancomycin and
ceftriaxone
D. Call surgery, clindamycin,
piperacillin-tazobactam, and
vancomycin
0%
13%
40%
47%
A. B. C. D.
Necrotizing soft tissue infections:
risk factors
• IVDU
• Diabetes
• Obesity
• Chronic immune suppression
Anaya DA. Clin Infect Dis. 2007
4/12/2011
8

Why is early diagnosis so important?
Wong CH. Jour of Bone and Joint Surg. 2003
Mortality rate: > 30%
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
% of patients
100
90
80
70
60
50
40
30
20
10
0
Necrotizing soft tissue infections:
clinical clues
Wong CH. Jour of Bone and Joint Surg. 2003
Late findings
Necrotizing Skin and Soft Tissue Infection:
Pathogens
Monomicrobial Polymicrobial
Group A strep
Staphylococcus aureus
Clostridia sp
Gram negatives
Vibrio vulnificus
Aerobic gram +/gram -
PLUS
.
Anaerobes
Wong CH. J Bone and Joint Surg. 2003
4/12/2011
9

Empiric treatment of necrotizing soft
tissue infections
• Early surgical intervention
• Antimicrobial therapy
– Piperacillin/tazobactam or carbapenem
(anaerobes, GNR, streptococci)
plus
– Vancomycin (MRSA)
plus
– Clindamycin (GAS)
*Consider IVIG in severe
cases of streptococcal
toxic shock syndrome
Which antibiotic regimen would be most
appropriate for this patient ?
A. Amoxicillin/clavulanic acid
B. Cephalexin
C. Clindamycin
D. Metronidazole
E. No antibiotics needed
73%
7%
16%
2%
2%
A. B. C. D. E.
37 y/o male presents
to clinic 4 days after
receiving a dog bite to
his forearm. He
complains of pain,
some purulent
drainage.
Case 5
Animal Bites
• 50% of Americans are bit by animals
• 20% require medical attention
• Animal bites account for 1% of ER visits
• Bites result in 10,000 inpt admits/year
4/12/2011
10

Animal bites: bacteriology
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%
Animal bites
• Empiric treatment regimens
Talan DA. NEJM. 1999
– Amoxicillin/clavulanic acid +/- MRSA agent
– Pen allergy: cipro + clindamycin or moxifloxacin
• Prophylaxis?
– Moderate-severe bites or on face/hands
– Immunocompromised (splenectomized)
– Cat bites
Antibiotic coverage for Pasturella
• What you want to use but won’t work…
– 1 st generation cephalosporin
– anti-staphylococcal penicillins
– clindamycin
• What works…
–amoxicillin
–doxycycline
–fluoroquinolone
• Bacteriology
Human bites
– Mixed infection with streptococci, anaerobes and
gram negatives (Haemophilus sp., Eikinella sp.)
– High rates of infection
• Treatment
– Same as animal bites
• Prophylaxis – everyone, same as animal bites
4/12/2011
11

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
http://www.cdc.gov/rabies/resources/contacts.html
45 y/o man presents
with several weeks of
progressive painful
“bumps” spreading up
his left forearm.
Case 6
Rabies - Post-exposure prophylaxis
• Wound cleansing: virucidal agent (iodine)
• Rabies Immune Globulin
– 20 IU/kg body weight
– Infiltrated full dose around the wound(s) and
remaining volume IM at site distant from vaccine
• Vaccinate: Days 0,3,7, and 14
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e507a1.htm,
http://www.cdc.gov/mmwr/pdf/rr/rr5902.pdf
Which of these questions
should you ask?
A. Do you have a fish tank?
B. Have you been around a sick rabbit?
C. Do you garden?
D. Have you been traveling in S.
America?
E. All of the above
5%
1%
25%
21%
48%
A. B. C. D. E.
4/12/2011
12

Nodular lymphangitis:
management?
• Take a good history
• Obtain biopsy
– Pathology: stain for fungi and mycobacteria
– Cultures: bacterial, fungal, and mycobacterial
• Consider empiric therapy based on severity of
disease and history prior to biopsy results
Nodular Lymphangitis: DDx
• Short incubation (days)
– Francisella tularensis (rabbits, ticks)
• Medium incubation (2-4 weeks)
– Nocardia (brasiliensis >> asteroides) (soil)
• Long incubation (weeks-months)
– Mycobacterium marinum (fish tanks)
– Sporothrix schenkii (vegetation)
– Leishmania sps (sandfly)
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13