Cellulitis and Soft Tissue
Infections (in the MRSA Era)
Bradley Allen, MD,PhD, FACP
Infectious Diseases Service
Indianapolis VAMC
Division of Infectious Diseases
Indiana University School of Medicine
IU Health – Arnett Hospital
Medicine Grand Rounds
October 24th, 2012
Disclosures

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Substantial personal holdings of both skin
and soft tissue
Investigator; Merck clinical trial
Pre Test
Q1. What organisms comprise the most
common cause of cellulitis?
1) Streptococcus species
2)
Pseudomonas aeruginosa
3)
Aeromonas species
4)
Vibrio vulnificans
Pre Test
Q2. The best agent to treat streptococcal
cellulitis is?
1) Trimethoprim/sulfamethoxazole
2) Doxycycline
3) Levofloxacin
4) Cephalexin
Pre Test
Q3. Which statement is true regarding
vancomycin?
1) Superior to nafcillin in MSSA treatment
2) Is more nephrotoxic then gentamycin
3) Should be dosed at 15-20 mg/kg
4) Trough goal dose should be 5-10 ug/ml
Historical perspective of skin
and soft tissue infection (SSTI)


“Skin infections have been around since
the invention of skin” Brad Spellberg, UCLA
Traitement de l’erysipele par la
chlorhydrate de sulfamido-chrysoidine.
Meyer-Heine and Huguenin. Presse Med
1936: 44:454-457
 One of the first clinical trials of an
antibacterial agent
Objectives
Review common skin and soft tissue
disease
 treatment concepts/new agents
 Review new IDSA Guidelines for SSTI and
MRSA treatment
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Liu, C, A Bayer, S Cosgrove, R Daum, S Fridkin, R Gorwitz, S Kaplan, AW
Karchmer, D Levine, BE Murray, MJ Rybak, D Talan, and HF Chambers.
Clinical Practice Guidelines by the Infectious Diseases Society of America
for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections
in Adults and Children Clin Infect Dis. (2011) 52(3): e18-e55
Infectious Diseases Society of America Guideline website
www.idsociety.org
Skin infection
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Mild to severe in spectrum
May reflect systemic process or be
localized to the skin
Must differentiate from non-infectious
etiology such as –
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vasculitis
connective tissue disease (e.g. SLE)
Neoplasm (Squamous cell ca., etc.)
Allergic Dermatitis – contact or TEN
Pyoderma gangrenosum
Non-infectious venous stasis changes
Skin infection
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Mild to severe in spectrum
May reflect systemic process or be
localized to the skin
Must differentiate from non-infectious
etiology such as –

Non-infectious venous stasis changes
Clinical scenario
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34 y.o. weekend warrior
Spectacular slide into 2nd base during softball game
Initial abrasions on knee, washed post game
Redness and warmth developed over next few
days in area of the abrasion
Low grade fevers and red streak noticed along
medial thigh
Cellulitis
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Often preceded by mild skin irritation or trauma
Dermal and subcutaneous involvement
Borders diffuse, non-elevated (compare to erysipelas)
May spread via lymphatics - lymphangitis
Overwhelming majority due to strep/staph
Poor venous or lymphatic drainage are risk
factors

e.g. saphenous vein graft harvest sites, prior lymph
node dissection or obstruction
Lymphangitic spread –
more common with strep v. staph disease
Diagnosis/etiology of cellulitis
•
History important
•
•
•
Risk factors for resistant organisms?
•
•
•
•
•
•
•
pace of illness
severity of sxs
MRSA history
Antibiotic exposure
Causitive agents :
Group A streptococci
Staphylococcus aureus
Group C,G, and B strep (-hemolytic strep)
These organisms represent 80-97% of cultured
organisms associated with routine cellulitis and
“non-purulent” skin and soft tissue infection
Pathogens Associated With
complicated * SSTI Clinical Scenarios
• Diabetes: S. aureus, strep > anaerobes, GN bacilli
• Cirrhosis: Campylobacter fetus, coliforms, Vibrio
vulnificus, Capnocytophaga canimorsus
• Neutropenia: Pseudomonas aeruginosa
• Human bite: Eikenella corrodens
• Cat bite: Pasteurella multocida
• Dog bite: P. multocida, C. canimorsus
• Rat bite: Streptobacillus moniliformis
• Hot tub exposure: P. aeruginosa
• Fresh water laceration: Aeromonas hydrophila
• Fish tank exposure: Mycobacterium marinum
• IV drug use: MRSA, P. aeruginosa
* Purulent process, open wound, deep collection, etc
Streptococcus pyogenes
Streptococcus pyogenes
Staphylococcus aureus
Staphylococcus aureus
Risk Factors for Skin and
Soft-Tissue Infection
• Trauma (lacerations, burns, abrasions, crush, open fx)
• Intravenous drug use
• Human or animal bites
• Conditions that predispose to infection
DM, alcoholism, chronic renal disease, cirrhosis,
neutropenia, hypogammaglobulinemia, arterial or
chronic venous insufficiency, lymphedema
• Past cellulitis (especially with tinea pedis)
• Radical mastectomy with axillary LN dissection
• Saphenous vein harvesting
Cellulitis and Soft-tissue infections. American College of Physicians; In the Clinic,
Annals of Internal Medicine. 2009. 150(1):ITC1-14.
Annual visits to US EDs for SSTIs during the emergence of
community- associated (CA) MRSA from 1993 - 2005
3-fold increase
1.2 to 3.4 million
visits/year
7 to 38% of abx
regimens active
against MRSA
Boucher H et al. Clin Infect Dis. 2010;51:S183-S197
© 2010 by the Infectious Diseases Society of America
Clinical Outcomes of Hospitalized SSTI 2007
Jenkins T C et al. Clin Infect Dis. 2010;51:895-903
© 2010 by the Infectious Diseases Society of America
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SSTI requiring hospitalization: Opportunities for
antimicrobial (and resource) stewardship
322 patients admitted to academic center
IVDA, DM, alcoholism common comorbidities
150 culture positive, 97% S. aureus or streptococci.
Antibiotics with broad aerobic GNR and anaerobic
bacteria used in 83% of patients
Imaging results yielded new information <4%
Cellulitis
Cutaneous Abscess
cSSTI
Antibiotic Duration (days)
13
14
13
Imaging (20% CT or MRI)
94%
Failure < 30 days (%)
12.1
86%
4.9
Jenkins TC et al. Clin Infect Dis. 2010;51:895-903
© 2010 by the Infectious Diseases Society of America
9.2
Treatment of cellulitis

Non-pharmacologic interventions
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Elevation is critical!
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decrease dependent edema
Improves  venous drainage
 arterial flow to soft tissue
 Oxygen and nutrients
 antibiotic delivery
 WBC delivery
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Address risk factors to prevent recurrences
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Treat tinea pedis
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Optimize skin health in general
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Moisturize, minimize trauma such as shaving, etc
Is antimicrobial treatment of cellulitis needed at all?
Mortality rates associated with erysipelas before and after the
introduction of antimicrobial agents.
Hoyne et al. Mortality
16%
rates in the treatment
of 998 erysipelas
patients. JAMA
1939;113:2279-81.
Cook County Hospital
2%
Madsen S.T.
100
10
0
Spellberg B et al. Clin Infect Dis. 2009;49:383-391
© 2009 by the Infectious Diseases Society of America
Scarlet fever and
erysipelas in Norway
during the last hundred
years. Infection
1973;1:76-81.
Antibiotic management and treatment failure rates for
nondrained noncultured SSTIs in 2002-2007
2096 patients, 104 with failures
Elliott, D. J. et al. Pediatrics 2009;123:e959-e966
Note that failure rate did not change over time
despite change in antibiotic choices
Copyright ©2009 American Academy of Pediatrics
Case-cohort trial of 2096 kids with uncomplicated skin infections
Cultures of SSTI in the community indicated MRSA in >50%
Predicted probability of treatment failure
104 failures compared to 480 controls
* P < .05
Risk Factors
- Fever
- Abscess
- ED visit
- Prior abx
Elliott, D. J. et al. Pediatrics 2009;123:e959-e966
- Empiric CA-MRSA coverage was not associated with improved outcomes in
the outpt mgt of nondrained noncultured SSTIs.
- Monotherapy with tmp-smz may increase the risk of treatment failure
- β-Lactam therapy remains the preferred empiric therapy for
uncomplicated SSTI , even with high prevalence of CA-MRSA.
Copyright ©2009 American Academy of Pediatrics
How long to treat simple cellulitis?
Serial composite scores for cellulitis with 5 vs 10 days of therapy,
randomized, double-blind, placebo-controlled trial in 87 military
hospital cases of acute cellulitis
Hepburn, M. J. et al. Arch Intern Med 2004;164:1669-1674.
Copyright restrictions may apply.
What is the management of
outpatients with “non-purulent”
cellulitis?
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Empirical therapy for infection due to βhemolytic streptococci is recommended
(A-II).
The role of CA-MRSA is unknown.
Coverage for CA-MRSA is recommended in
patients who do not respond to β-lactam
therapy and those with systemic toxicity.
Five - 10 days of therapy is recommended
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
World leader – irritable, aggressive behavior
Furunculosis
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Arises from folliculitis
Pus collection
Surrounding cellulitis
Risks – DM, obesity,
steroids, poor PMN
function
S. aureus most common
Rx - Drainage, heat, +/abx
Skin v. Soft tissue infection –
Include combinations of skin, subcutaneous tissue,
fascia and/or muscle and bone.
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May be localized or rapidly progressive
Systemic, multi-organ involvement may
develop
Higher mortality than skin infections
Higher rate of associated bacteremia
Need more aggressive treatment
May need surgical drainage/debridement
Antibiotics are recommended for
abscesses associated with (A-III):
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severe or extensive
disease (eg, involving
multiple sites of infection)
rapid progression in
presence of associated
cellulitis, signs and
symptoms of systemic
illness
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Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
associated comorbidities
or immunosuppression
extremes of age
areas difficult to drain
(eg, face, hand, and
genitalia)
septic phlebitis
lack of response to
incision and drainage
What is the management of
outpatients with purulent cellulitis?
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Empirical therapy for CA-MRSA is
recommended pending culture results.
Empirical therapy for infection due to βhemolytic streptococci is likely to be
unnecessary (A-II).
Five - 10 days of therapy is recommended
but should be individualized on the basis
of the patient's clinical response.
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
The Rise of MRSA and
antibiotic resistant
Staphylococcus aureus
1928 to present…
Evolution of Drug Resistance in S. aureus
Penicillin
Methicillin
MethicillinPenicillin-resistant
S. aureus
resistant
[1950s]
[1970s]
S. aureus
S. aureus (MRSA)
[1997]
Vancomycin
[1990s]
Vancomycin
resistant
S. aureus
[2002] Vancomycin
intermediateresistant
Vancomycin-resistant
enterococci (VRE)
S. aureus
(VISA)
http://www.cdc.gov/ncidod/hip/ARESIST/visa.htm
Methicillin Resistant S.aureus (MRSA)
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Methicillin MIC ≥ 16 mcg/ml, oxacillin ≥ 4
MR is encoded by the mecA gene
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a low-affinity binding protein, PBP-2a
All β-lactam agents are affected (cefazolin,
dicloxacillin, imipenem, aztreonam, etc.)
Other species of Staphylococci are > 50%
Methicillin-resistant
 Coagulase-negative Staph group
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S.epidermidis, S.haemolyticus,
S.hominis, and S.saprophyticus
CA-MRSA antibiotic susceptibility
USA300: nationwide vs. Iowa
Agent
Erythromycin
Clindamycin*
Levofloxacin
Tetracycline
TMP-SMX
EMERGency
N=226
6
95
60
92
100
Iowa 2000-2007
N=167
6
93
63 AVOID!
95
100
*includes testing for inducible clindamycin resistance
Moran, et al. N Engl J Med 2006;355:666-74., Iowa data compliments Daniel Diekema
Empirical oral options for coverage
of CA-MRSA with SSTI?
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clindamycin (A-II)
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Poorly tolerated, 4 x daily
TMP-SMX (A-II)
tetracycline (doxy or
minocycline) (A-II)
linezolid (A-II)
Use of rifampin as single
agent or SSTI adjunctive
therapy is not
recommended (A-III)
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Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
To cover both βhemolytic streptococci
and CA-MRSA:
clinda alone (A-II)
TMP-SMX or tet in
combination with a βlactam (e.g. amoxicillin,
cephalexin) (A-II)
linezolid alone (A-II)
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> $1000 per 10 day course
TMP/SMX & doxycycline
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Both
Both
Both
Both
Both
agents maintain activity against CA MRSA
agents are second-line for streptococci
increase sun sensitivity
agents are bacteriostatic, not bacteriocidal
are to be avoided in infants
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TMP/SMX can be bacteriocidal at higher doses, but is
inferior to vanco in head-to-head trials
DS tablet twice daily may be as effective as two tabs bid
Cautious use in elderly and with renal insufficiency
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Doxycyline is overall well tolerated
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Does MRSA v. MSSA impact infection outcomes?
Meta-analysis of 40 studies: mortality associated with
nosocomial MRSA with MSSA.
Boucher H et al. Clin Infect Dis. 2010;51:S183-S197
© 2010 by the Infectious Diseases Society of America
Hospitalized patients with
complicated SSTI?
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cSSTI; defined as patients with deeper
soft-tissue infections, surgical/traumatic
wound infection, major abscesses, and
infected ulcers and burns
in addition to surgical debridement and
broad-spectrum antibiotics, empirical
therapy for MRSA should be considered
pending culture data.
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Options for MRSA coverage in
complicated SSTI?
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IV vancomycin (A-I)
linezolid 600 mg bid, oral
or IV (A-I),
daptomycin 4 mg/kg/ IV
daily (A-I)
telavancin 10 mg/kg/dose
IV once daily (A-I)
clindamycin 600 mg IV or
PO 3 times a day (A-III)
7 - 14 days of therapy
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Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Cultures from
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abscesses and other
purulent SSTIs
severe local infection
signs of systemic illness
inadequate response
concern for a cluster or
outbreak (A-III).
Vancomycin
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IV formulation, E.C. Kornfeld, Lilly 1958
Bacteriocidal activity equivocal
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Poor head-head comparisons to nafcillin or
cefazolin in clinical trials of MSSA treatment
Red-man syndrome and true allergies
Renal and ototoxicity
Borneo
Amycolatopsis orientalis
Vancomycin
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Therapeutic levels initially correlated to
toxicity in early formulations of the drug –
Mississippi Mud!
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Newer formulations lack high risk of renal or
ototoxicity, so aggressive dosing is possible
Trough levels 15-20 needed instead
of previously recommended
5-10 ug/ml.
Heteroresistance in MRSA strains
• MRSA contain subpopulations with reduced in
vitro killing by vancomycin
• MIC is still in susceptible range (<4 mcg/ml)
– Tend to be in the MIC = 2 range
• Human and animal data indicate higher level
of clinical failures when infected with hVISA
strains
Point: Vancomycin Is Not Obsolete for the Treatment of Infection Caused by
Methicillin-Resistant Staphylococcus aureus
Mohr and Murray, 2007 Clin Inf Dis, 44:1536
HeterotypicVISA are increasing
Mohr and Murray, 2007 Clin Inf Dis, 44:1536
Vancomycin Therapeutic Guidelines: Rybak,
et al. 2009. Clin Infect Dis; 49:325–27
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Trough serum vancomycin concentrations of
15 – 20 mg/L are recommended
This trough level generates AUC/MIC of >400 if
the MIC of the MRSA isolate is <1 mg/L
Vancomycin dosages of 15–20 mg/kg (actual
body weight) given every 8–12 h for most
patients with normal renal function.
For rapid target concentrations, a loading dose
of 25–30 mg/kg (actual body weight) can be
considered.
Vancomycin Therapeutic Guidelines: Rybak,
et al. 2009. Clin Infect Dis; 49:325–27
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AUC/MIC of >400 is not achievable if the
vancomycin MIC is 2 mcg/ml.
Therefore, alternative therapies should be
considered.
When individual doses exceed 1 g (e.g.,
1.5 and 2 g), the infusion period should
be extended to 1.5–2 h.
Cost ~ $13/day
SSTI in the MRSA Era Conclusions
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Most SSTI is due to staph and strep
Non-purulent SSTIs do not need initial
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MRSA coverage
Gram-negative coverage
Imaging (unless suspicion of foreign body, fluid)
β-hemolytic streptococci are still a major
cause of cellulitis and respond best to βlactam agents
β-hemolytic streptococci respond slowly to
TMP/SMX and doxy
SSTI in the MRSA Era Conclusions
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Guidelines: start with β-lactam agent and
change to MRSA agents if no response
Duration of treatment for cellulitis and
SSTI should be short, 5-10 days
Quinolones are not good agents for SSTI
CA-MRSA infections are common
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Majority are relatively minor SSTIs
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Most can be managed with I&D, & oral TMP/SMX
or doxycycline IF NEEDED
cSSTI in the MRSA Era Conclusions
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Vancomycin is a less potent cell-wall
active drug compared to β-lactam agents
Vancomycin trough levels need to be
pushed to the 15-20 mcg/ml range to be
effective
Dose vanco aggressively, 15-25 mg/kg
MRSA with vancomycin MICs of  2 are
likely to fail vancomycin therapy
SSTI in the MRSA Era Conclusions
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Nafcillin or 1st cephalosporin are still
superior drug choices for methicillinsensitive S.aureus
Empiric vanco is reasonable – but
change asap if sensitivities show MSSA
Consider alternatives pathogens if
clinical failure
Surgical co-management is critical for
abscess drainage or suspected tissue
necrosis
Bonus Slides
Linezolid
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Cost ~ $100/day
Q 12 hr or BID; IV and PO oxazolidinone, bacteriostatic
Novel class, some resistance in MRSA and VRE
Adverse events – post marketing
 Thrombocytopenia – after 14 days, reversible
 Serotonin syndrome – do not use with SSRIs
 Fever, tachycardia, blood pressure, CNS sxs, etc.
 Need 14 day wash-out of SSRI to avoid
 Peripheral/Optic neuropathy – long courses >4 weeks,
irreversible in some cases
 Metabolic acidosis – case reports with longer
treatment courses (osteomyelitis, mycobacterial
diseases, etc.)
Cost ~ $130/day
Daptomycin : Overview
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Lipopeptide
Activity in Gram-positive organisms
Leads to membrane disruption
Bactericidal in vitro and in vivo
Most common side effect - myopathy
 Baseline and weekly CPK
Once-daily IV dosing, 4-6 mg/kg
Ineffective in pneumonia due to interaction with
surfactant
Some resistance in MRSA arising, even during
therapy
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Cost ~ $130/day
Telavancin – not currently being produced
bactericidal lipoglycopeptide, IV only
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active against MRSA, VISA and VRSA
Industry-spons, randomized, double-blind phase
II study compared i.v. telavancin (10 mg/kg
daily) against vancomycin or antistaphylococcal
penicillin in 195 SSTI pts
Clinical cure rate overall 82% for telavancin v.
85% ; and 83% and 82% in the 108 S. aureusinfected patients
Severe AEs similar (6% and 4%)

Nausea, hypokalemia, creatinine rise, QTc prolonged
Stryjewski ME et al. Telavancin versus standard therapy for treatment of complicated
skin and skin structure infections caused by gram-positive bacteria: FAST 2 study.
Antimicrob Agents Chemother 2006 Mar; 50:862-7.
Ceftaroline
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Cost ~ $85/day
New cephalosporin with high affinity for PBP 2a
(mecA gene product)
MRSA MIC90 - 1 µg/mL, also gram-negative activity
Randomized, double-blind trial of 1378 pts with
cSSSI, ceftaroline (600 mg every 12 hrs for 5–14
days) was similar with ITT rates (85.9 v. 85.5%)
compared to vancomycin plus aztreonam (1000 mg
every 12 hours).
Success rates similar among patients with MRSA
infections (93.4 vs. 94.3%).
Corey GR, et al. Integrated analysis of CANVAS 1 and 2: Phase 3, Multicenter,
Randomized, double-blind studies to evlautate the saftey and efficacy of Ceftaroline
versus vancomycin plus aztreonam in complicated skin and skin-structure infection.
Clin Infect Dis 2010 ; 51:641-650.
Dalbavancin
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bactericidal lipoglycopeptide, IV only
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Cost ~ $priceless
active against MRSA, VISA and VRSA
Once weekly dosing based on pharmacokinetics
Industry-spons, randomized, double-blind phase
II study, i.v. dalbavancin showed equivalence
with vancomycin in catheter infections
Phase III trial indicated equivalence to linezolid in
SSSI.
New phase III trial in progress. Not FDA-approved
Severe AEs minimal so far - Fever, headache, nausea
Jauregui LE, Babazadeh S, Seltzer E. Randomized, double-blind comparison of
once-weekly dalbavancin versus twice-daily linezolid therapy for the treatment of
complicated skin and skin structure infections. Clin Infect Dis 2005; 41: 1407-1415.
References/Resources
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Liu, C, A Bayer, S Cosgrove, R Daum, S Fridkin, R Gorwitz, S Kaplan, AW Karchmer, D Levine, BE
Murray, MJ Rybak, D Talan, and HF Chambers. Clinical Practice Guidelines by the Infectious
Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus
Infections in Adults and Children Clin Infect Dis. (2011) 52(3): e18-e55
Hayashi, Y, and DL Paterson. Strategies for Reduction in Duration of Antibiotic Use in Hospitalized
Patients. Clin Infect Dis. (2011) 52(10): 1232-1240
Jenkins, TC, AL Sabel, EE Sarcone, CS Price, P Mehler, and WJ Burman. Skin and Soft-Tissue
Infections Requiring Hospitalization at an Academic Medical Center: Opportunities for Antimicrobial
Stewardship Clin Infect Dis. (2010) 51(8): 895-903
Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of
short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med
2004;164:1669-74.
Elliot, DJ, et al. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the
Era of Methicillin-Resistant Staphylococcus aureus. (2009) PEDIATRICS 23 (6): e959-e966
Boucher, H., L. Miller, and R. Razonable. Serious Infections Caused by Methicillin-Resistant
Staphylococcus aureus Clin Infect Dis. (2010) 51(Supplement 2): S183-S197
van Rijen M, Bonten M, Wenzel R, Kluytmans J. Mupirocin ointment for preventing Staphylococcus
aureus infections in nasal carriers. Cochrane Database of Systematic Reviews 2008, Issue 4.
Cellulitis and Soft-tissue infections. American College of Physicians; In the Clinic, Annals of Internal
Medicine. 2009. 150(1):ITC1-14.
Stevens DL, Bisno AL, Chambers HF, et al. Infectious Diseases Society of America. Practice
guidelines for the diagnosis and management of skin and soft-tissue infections.
Clin Infect Dis. 2005;41:1373-406.
Mandell, G.L. Atlas of Infectious Diseases, Volume II. Dennis Stevens ed., Current Medicine.
http://dermatlas.med.jhmi.edu/derm/index.cfm
Super Bonus Slides
Recurrent MRSA: Prevention –
favored initial approach
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Consistent hand hygiene
antibacterial soap (e.g., Dial®)
Chlorhexidine (Hibiclens®) showers twice
weekly
Avoid cosmetic body shaving
Optimize treatment of skin conditions (e.g.,
eczema and tinea)
Clean cuts & abrasions with soap & water
Cover wounds with clean, dry dressings
Recurrent skin infections –
possible steps to eradicate
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MRSA carrier state eradication difficult
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Mupiricin 2% ointment, twice daily, 5-10 days
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Consider only if multiple infections, evidence of
contact spread, or before major surgeries
Resistant strains arise with frequent use
Use of chlorhexidine soaps
Meticulous cleaning of contact surfaces in the
home, school, workplace with detergent or
dilute bleach
Laundering of all clothes, outerwear, bedding
“Modified head lice approach”
van Rijen M, Bonten M, Wenzel R, Kluytmans J. Mupirocin ointment for preventing
Staphylococcus aureus infections in nasal carriers. Cochrane Database of Systematic Reviews 2008, Issue 4.
Management of recurrent MRSA SSTIs
 Preventive educational messages:



i. Keep draining wounds covered with clean,
dry bandages (A-III).
ii. Maintain good personal hygiene with
bathing and hand cleaning with soap and
water or an alcohol-based hand gel (A-III)
iii. Avoid reusing or sharing personal items
(eg, razors, towels) (A-III)
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Environmental hygiene recurrent MRSA
SSTIs
i. Cleaning efforts on high-touch surfaces (ie,
counters, door knobs, bath tubs, and toilet
seats) (C-III)
ii. Commercially available cleaners or
detergents appropriate for the surface being
cleaned should be used according to label
instructions for routine cleaning of surfaces
(C-III)
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Decolonization with recurrent MRSA SSTIs
 May be considered in selected cases if:
i.
A patient develops a recurrent SSTI despite
optimizing wound care and hygiene (C-III).
ii. Ongoing transmission is occurring among
household members or close contacts despite
optimizing wound care and hygiene (C-III).

Should be offered in conjunction with
ongoing reinforcement of hygiene
measures ;
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Decolonization with recurrent MRSA SSTIs
i.


Nasal decolonization with mupirocin twice daily for
5–10 days (C-III).
ii. Nasal decolonization with mupirocin twice daily
for 5–10 days and topical body decolonization
regimens with a skin antiseptic solution (eg,
chlorhexidine) for 5–14 days or dilute bleach baths.
(1 tsp/gal water for 15 min twice weekly for ∼3
months) (C-III)
Oral antimicrobial therapy NOT routinely
recommended for decolonization (A-III).
Rifampin , if the strain is susceptible, may be
considered for decolonization if infections recur
despite above measures (CIII).
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Decolonization with suspected household or
interpersonal transmission




i. Personal and environmental hygiene
measures in the patient and contacts (A-III)
ii. Evaluate contacts for S. aureus infection:
a. Symptomatic contacts should be
evaluated and treated (A-III); nasal and
topical body decolonization strategies may be
considered following treatment of active
infection (C-III).
b. Nasal and topical body decolonization of
asymptomatic household contacts may be
considered (C-III).
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Role of cultures in the management of
recurrent SSTI is limited
i.
Screening cultures prior to decolonization
are not routinely recommended if at least 1 of
the prior infections was documented as due to
MRSA (B-III)
ii.
Surveillance cultures following a
decolonization regimen are NOT routinely
recommended in the absence of an active
infection (B-III)
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55
Precautions for Resistant Organisms
- MRSA
Readmit known MRSA carriers to
appropriate level of isolation
 If newly cultured, move to private room
 Notify Infection Control to facilitate
To remove patient from isolation  Needs 2 sets of negative cxs from
previously positive sites AND anterior
nares


Done > 3 days apart
Obtained more than 48 hrs off antibiotics
Ceftobiprole





A new cephalosporin with high affinity for PBP 2a
MRSA MIC90 - 2 µg/mL
Randomized, double-blind trial of 828 pts with
complicated skin and soft-tissue infections,
ceftobiprole (500 mg every 8 hrs for 7–14 days) was
similar with ITT rates over 80% compared to
vancomycin (1000 mg every 12 hours) plus
ceftazidime (1000 mg every 8 hours).
Rates also similar among patients with MRSA
infections (90% vs. 86%)
FDA approval is lagging, may not succeed
Noel GJ et al. A randomized, double-blind trial comparing ceftobiprole medocaril with
vancomycin plus ceftazidime for the treatment of patients with complicated skin and
skin-structure infections. Clin Infect Dis 2008 Mar 1; 46:647.
Case Presentation
11 a.m. -36 healthy man turned his ankle
at work, mild pain
Hour 5 - Onset of nausea, fever, and leg pain.
Developed chills.
DAY 2
Hour 18 - Evaluated in ER for severe ankle pain,
Xray (-). Thought to have “flu”
WBC 12,900 (94% neutrophils).
Hour 24 -No relief of pain, redness starts over
ankle, wife thinks he looks “blue”
Temp 103.4, WBC 1,800; creatinine 2.4
Case Presentation –
cont’d day 2
Hour 26 - Admitted for antibiotics, low BP (82/50).
Hemoglobin  from 15.4 to 18.5, redness to knee
Day 3-5
Creatinine 4.2; WBC 4,600 (73% bands); abnormal
liver tests
- Redness to thigh
No improvement despite multiple antibiotics
Weight increased from 205 to 237 lbs
Day 5
Hospital Course


Evaluated by Infectious Disease and Surgery
Antibiotics to cover Group A streptococci and
Staphylococcus aureus




Debridement of non-viable skin and subcutaneous
fat to the muscle. No pus or pockets of infection.
Cultures and stains (-).
Split-thickness skin grafting done a week later
Anti-streptococcal antibody (ASO titer) elevated
Dx – streptococcal necrotizing fasciitis and toxic
streptococcal shock syndrome
Post op pics
Post-debridement & graft
Pre debridement
Serious infections of deeper skin structures
Aggressive soft tissue infections

Necrotizing Fasciitis type 2 - Group A Strep
 severe pain often out of context with initial
superficial appearance
 treatment is surgical and medical
prompt debridement
 penicillin G plus clindamycin (stop toxin
production)
 Pooled IVIG if severe or progressive


Toxin-mediated disease – goal to neutralize toxin
Clinical Failure Rates of Antibiotic Treatments for Uncomplicated Cellulitis
Clinical Failures/Patients
Antibiotic or Antibiotic Group
Treated (% Failure)
All β-lactams
93/631 (14.7)
Cephalexin
54/359 (15.1)
All other β-lactams
39/272 (14.3)
Dicloxicillin
25/169 (14.8)
Amoxicillin/clavulanate
13/88 (14.8)
Other β-lactams
1/15 (6.7)
Non-β-lactams
39/230 (17.0)
Clindamycin
14/86 (16.3)
Trimethoprim/sulfamehoxazole
8/43 (18.6)
Fluoroquinolones
8/33 (24.2)
Macrolides
3/16 (18.8)
Tetracyclines
1/11 (9.1)
Combinations
5/41 (12.2)
Madaras-Kelly KJ - Am J Med - 01-MAY-2008; 121(5): 419-25
Vancomycin Intermediate- or Resistant SA


Mainly see in patients with extensive
vanco exposure (dialysis, etc) …
Vancomycin-intermediate SA (VISA)




MIC = 8-16
Altered cell wall limits drug penetration into bacterium
Reduced response to vancomycin
Vancomycin-resistant SA (VRSA)



MIC ≥ 32
Initial case in 2002, only a few worldwide
Resistance acquired from VRE

7 gene cluster transfer
Pediatric considerations in SSTI





For children with minor skin infections (such as
impetigo) and secondarily infected skin lesions
 mupirocin 2% topical ointment (A-III)
Tetracyclines should not be used in children <8 years of
age (A-II)
Hospitalized children, vancomycin is recommended (AII).
If patient stable, empiric clindamycin is an option if the
clindamycin resistance rate is low (eg, <10%) with
transition to oral if strain is susceptible (A-II)
Linezolid 600 mg PO/IV twice/d for children ≥12 years,
10 mg/kg/dose PO/IV every 8 h for children <12 (A-II)
Liu et al. Clin Infect Dis. (2011) 52(3): e18-e55