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Skin, Skin Structure, and Soft Tissue Infection Diagnosis and Treatment - Adult - Inpatient/Ambulatory

Skin, Skin Structure, and Soft Tissue Infection Diagnosis and Treatment - Adult - Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Infection and Isolation


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Skin, Skin Structure, and Soft Tissue Infection
Diagnosis and Treatment – Adult –
Inpatient/Ambulatory
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 4
DEFINITIONS ............................................................................................................................ 5
INTRODUCTION ....................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................. 6
TABLE 1. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP. .................. 9
TABLE 2. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP. AND MSSA9
TABLE 3. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP., MSSA, AND
MRSA .......................................................................................................................................10
TABLE 4. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP., MSSA,
MRSA, AND GRAM-NEGATIVES ............................................................................................10
TABLE 5. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP., MSSA,
MRSA, GRAM-NEGATIVES (EXCEPTING P. AERUGINOSA), AND ANAEROBES ...............12
TABLE 6. ANTIMICROBIAL AGENTS DIRECTED AT STREPTOCOCCUS SPP., MSSA,
MRSA, GRAM-NEGATIVES (INCLUDING P. AERUGINOSA), AND ANAEROBES ................13
TABLE 7. ANTIMICROBIAL AGENTS FOR SKIN INFECTIONS CAUSED BY ANIMAL OR
HUMAN BITES .........................................................................................................................14
TABLE 8. RECOMMENDED AGENTS FOR NECROTIZING FASCIITIS ................................15
UW HEALTH IMPLEMENTATION ............................................................................................15
REFERENCES .........................................................................................................................16
FIGURE 1. OUTPATIENT MANAGEMENT OF SKIN AND SOFT TISSUE INFECTIONS ........19
FIGURE 2: INPATIENT MANAGEMENT OF SKIN AND SOFT TISSUE INFECTIONS ...........20
APPENDIX A. DIAGNOSIS AND TREATMENT OF GRAM POSITIVE BACTERIAL SKIN AND
SOFT TISSUE INFECTIONS – TOP TEN MYTHS ...................................................................22
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CPG Contact for Changes:
Philip Trapksin, PharmD, BCPS, Drug Policy Program Manager
Phone Number: 608-263-1328
E-mail address: PTrapskin@uwhealth.org
CPG Contact for Content:
Lucas Schulz, PharmD, BCPS AQ-ID
Phone Number: 608-890-8617
E-mail address: LSchulz2@uwhealth.org
Guideline Authors:
Melissa Heim, PharmD
Lucas Schulz, PharmD, BCPS
2015 Revision Guideline Authors:
Lucas Schulz, PharmD, BCPS
Joshua Vanderloo, PharmD
Coordinating Team Members:
Joshua Vanderloo, PharmD, Drug Policy Program
Review Individuals:
Barry Fox, MD; Alex Lepak, MD
Committee Approvals/Dates:
Antimicrobial Use Subcommittee December 2015
Pharmacy and Therapeutics Committee April 2013; January 2016
Release Date: January 2016
Next Review Date: January 2019
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Executive Summary
Guideline Overview:
This clinical practice guideline is designed to lead prescribers through the evaluation, diagnosis, and
treatment of skin, skin structure, and soft tissue infection (SSTI). It will focus on difficult diagnostic and
treatment scenarios and is intended for use throughout the continuum of care, including outpatient clinics,
emergency department, and inpatient wards.
Key Practice Recommendations
1. Consider alternative diagnoses, such as DVT and venous stasis dermatitis in patients. In obese
patients, consider venous insufficiency lymphedema. Avoid antibiotics in these non-SSTI diagnoses.
(Class I, Level A)
2. Staphylococcus and Streptococcus species are the most common causes of SSTI. MRSA nasal
AND pooled axilla/groin PCR should be obtained for patients with risk factors for MRSA or to reduce
the probability that infection is caused by MRSA. (Class I, Level B)
3. Gram-negative bacteria, especially Pseudomonas species, are unlikely the cause of an SSTI. Anti-
Pseudomonal treatment should be used conservatively in clinically stable patients. (Class IIb, Level
C)
4. Non-pharmacologic treatments, including elevation and compression of lower extremities, should be
used whenever possible. (Class I, Level C)
5. Erythematous area marked by pen may extend beyond margins during the first 48 hours. This should
not be considered treatment failure if the patient is otherwise improving. (Class I, Level C)
6. Incision and drainage, if possible, should be performed for abscesses. (Class I, Level A)
7. Outpatient management of Streptococcus or MSSA can be achieved with cephalexin or dicloxacillin.
(Class I, Level A)
a. If MRSA is suspected, antibiotic coverage with TMP/SMX or doxycycline/minocycline PLUS
amoxicillin is recommended. (Class I, Level A )
8. Inpatient management of Streptococcus or MSSA can be achieved with cefazolin or oxacillin. (Class
I, Level A)
a. If MRSA is suspected, additional antibiotic coverage with vancomycin is recommended and
MRSA PCRs should be obtained. (Class I, Level A)
b. If Gram-negative organisms are suspected, the selection of ceftriaxone is reasonable. (Class IIa,
Level B)
Companion Documents
ξ Renal Function-based Dose Adjustments ± Adult ± Inpatient ± Clinical Practice Guideline
ξ Antibiotics for the Treatment of Gram-negative Infections ± Adult ± Inpatient Clinical Practice
Guideline
ξ Intravenous Vancomycin Use ± Adult ± Inpatient Clinical Practice Guideline
ξ Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics ± Adult ± Inpatient Clinical
Practice Guideline
ξ Medication Route Interchange ± Adult ± Inpatient ± Clinical Practice Guideline
ξ UWHC Antibiograms
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Scope
Disease/Condition:
This clinical practice guideline is designed to lead prescribers through the evaluation, diagnosis, and
treatment of skin, skin structure, and soft tissue infection (SSTI).

Clinical Specialty
All medical specialities

Intended Users
Physicians, Advanced Practice Providers, Nurses, and Pharmacists

Objective
To optimize diagnosis, evaluation, treatment, and antibiotic utilization for the treatment of SSTI.

Target Population
Patients with signs and symptoms of skin, skin structure, or soft tissue infections cared for in outpatient
clinics, the emergency department, and inpatient wards.

Interventions and Practices Considered
Diagnosis of skin, skin structure, or soft tissue infections; treatment of skin, skin structure, or soft tissue
infections; and avoidance of antimicrobial use in patients without skin, skin structure, or soft tissue
infections following evaluation.

Major Outcomes Considered
1. Number of MRSA PCRs ordered for patients being managed for SSTI.
a. Discontinuation of anti-MRSA therapy with negative PCR results.
2. Successful management of skin, skin structure, or soft tissue infections measured by resolution of
infection.
a. Avoidance of treatment failure as indicated by additional courses of antimicrobials.
3. Avoidance of antimicrobial use in patients without skin, skin structure, or soft tissue infections
4. Antibiotic utilization (by class) for SSTI treatment.

Methodology
Electronic database searches (i.e., PUBMED) were conducted and workgroup members to collect
evidence for review. Expert opinion, clinical experience, and regard for patient safety/experience were
also considered during discussions of the evidence. A modified Grading of Recommendations
Assessment, Development, and Evaluation (GRADE) developed by the American Heart Association and
American College of Cardiology (Figure 1) has been used to assess the Quality and Strength of the
Evidence in this Clinical Practice Guideline.1

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Figure 1. Quality of Evidence and Strength of Recommendation Grading Matrix



Definitions2,3
1. Carbuncle: infection of several adjacent hair follicles producing a coalescent inflammatory mass with
pus draining from multiple follicular orifices
2. Cellulitis: diffuse, spreading skin infection of the deeper dermis as well as subcutaneous fat that lacks
distinctive anatomical features. It may be accompanied by lymphangitis and inflammation of the
regional lymph nodes
3. Complicated infection: infection involving deeper soft tissues necessitating major abscesses, or an
underlying disease state that complicates the response to treatment (e.g. diabetes mellitus)
4. Cutaneous abscess: collection of pus within the dermis and deeper skin tissues which is usually
painful, tender, and has fluctuant red nodules often surmounted by a pustule and surrounded by a rim
of erythematous swelling
5. Erysipelas: diffuse, spreading skin infection of the upper dermis including the superficial lymphatics.
Lesions are fiery red, tender, painful plaques with well-demarcated edges that are raised above the
level of the surrounding skin. It may be accompanied by lymphangitis and inflammation of the
regional lymph nodes
6. Furuncle: infection of the hair follicle in which suppuration extends through the dermis into the
subcutaneous tissue where a small abscess forms
7. Impetigo: skin infection consisting of discrete purulent lesions
8. Necrotizing fasciitis: subcutaneous infection that tracks along fascial planes and extends well beyond
the superficial signs of infection, such as erythema or other skin changes
9. Skin and skin structure infection (SSSI): infection of skin and its supporting structures, but excluding
deep tissues such as fascia and muscle and necrotizing infections (term utilized by Food and Drug
Administration for therapeutic trials)
10. Skin and soft tissue infection (SSTI): infection involving the skin, subcutaneous connective tissue,
fascia, or muscle
11. Systemic inflammatory response syndrome (SIRS):4 a clinical response to a non-specific insult of
either infectious or noninfectious origin. Two of the following variables:
a. Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
b. Heart rate of more than 90 beats per minute
c. Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of
less than 32mm Hg or the requirement of invasive mechanical ventilation for an acute process
d. Abnormal white blood cell count (>12,000/µL or < 4,000/µL or >10% immature [band] forms)
12. Uncomplicated infection: simple abscess, such as impetiginous lesions, furuncles, and cellulitis

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Introduction
Skin, skin structure, and soft tissue infections are common in hospitalized patients; many opportunities for
antimicrobial stewardship including cost-effective diagnosis and treatment exist.5,6, 7 Development of
cellulitis algorithm has demonstrated reduction in institutional and medication costs, decreased length of
stay without increasing length of stay.8 Although staphylococci and streptococci are the causative
organisms in the majority of cases of community-based skin, skin structure, and soft tissue infections,
many patients receive broad-spectrum Gram-negative and anaerobic therapy and are treated longer than
the recommended 7 to 14 days. Additionally, unnecessary low-yield laboratory testing (erythrocyte
sedimentation rate) and radiographic imaging (plain film x-rays) are being ordered for patients despite
limited utility for uncomplicated SSTI. The intent of this guideline is to guide treatment towards
appropriate antibiotics, duration of treatment, and reduce excessive lab and radiographic testing.

Recommendations
1. Presentation and diagnosis
1.1. /RFDO�SUHVHQWDWLRQ�RI�HGHPD��HU\WKHPD��KHDW��³RUDQJH�SHHO´�DSSHDUDQFH��YHVLFOHV��EXOODH��
petechiae, and pain should lead to a diagnosis of skin and skin structure infection.2,3,9,10 (Class
I, Level A)
1.1.1. Diagnoses of deep venous thrombosis, venous stasis dermatitis, venous insufficiency,
lymphedema, contact dermatitis, gout, herpes zoster, acute lipodermatosclerosis,
septic arthritis, and osteomyelitis should be excluded.2,3,9,10 (Class I, Level A)
1.2. In most cases of uncomplicated SSTI, erythrocyte sedimentation rate and radiographic imaging
studies are of questionable diagnostic use and should not be obtained.9,11-14 (Class III, Level B)
1.3. Obtaining laboratory studies should not delay empiric antimicrobial/surgical therapy. (Class I,
Level A)
1.4. The majority of cellulitis cases do not lead to systemic infection. In the absence of systemic
infection, the utility of blood/wound cultures, needle aspirations, skin biopsies, complete blood
count with differential, creatinine, bicarbonate, creatine phosphokinase, and C-reactive protein
levels is not well established and should not be obtained.2 (Class III, Level B)
1.4.1. Aspiration of the skin is not helpful in 75-80% of cases of cellulitis.15-23
1.4.2. Results of blood cultures are positive in fewer than 5% of cases.24

2. Epidemiology
2.1. Staphylococcus spp.
2.1.1. Furuncles, carbuncles, and abscesses are usually caused by Staphylococcus
aureus.25-27
2.1.2. Cellulitis or abscess that is fluctuant, has penetrating trauma, and/or with open ulcer
with surrounding erythema is more likely caused by Staphylococcus species than
Streptococcus species.25-28
2.1.2.1. Risk factors for community-acquired MRSA (CA-MRSA) include:29
ξ History of MRSA infection or colonization in patient or close contact
ξ High prevalence of CA-MRSA in local community or patient population
ξ Recurrent skin disease
ξ Crowded living conditions (e.g. homeless shelters, military barracks)
ξ History of incarceration
ξ Participation in contact sports
ξ Skin or soft tissue infection with poor response to beta-lactam antibiotics
ξ Recent and/or frequent antibiotic use
ξ Injection drug use
ξ Member of Native American, Pacific Island, Alaskan Native populations
ξ Male with history of having sex with men
ξ Shaving of body hair

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2.1.2.2. Risk factors for hospital-acquired MRSA (HA-MRSA):30
ξ Nasal colonization
ξ Presence of indwelling devices such as catheters, tracheostomies, and
nasogastric tubes
ξ Hospital admission within past 90 days
ξ Prolonged hospitalization
ξ Residence in long-term care facility
ξ Antibiotic therapy in past 90 days
ξ Diabetes mellitus
ξ Hemodialysis
ξ HIV infection/immunosuppression
2.1.3. MRSA nasal AND pooled axilla/groin PCR should be obtained for patients with risk
factors for MRSA or to reduce the probability that infection is caused by MRSA.31-34
(Class I, Level B)
2.1.3.1. If MRSA PCRs are negative, deescalating to narrower spectrum antibiotics
not covering MRSA is reasonable. (Class IIa, Level B)
2.2. Streptococcus spp.
2.2.1. Impetigo, erysipelas, and cellulitis are commonly caused by Group A or other beta-
hemolytic Streptococcus (but Staphylococcus aureus may also be present, see
sections above describing MRSA risk factors).35,36
2.2.2. Cellulitis that is diffuse or unassociated with a defined portal, erythematous, and non-
purulent WITH lymphangitic spread is more commonly caused by Streptococcus
species than Staphylococcus species.35
2.3. Gram-negative organisms
2.3.1. The majority of skin, skin structure, and soft tissue infections (60-90%) are caused by
Gram-positive organisms.25-28,35,37,38
2.3.1.1. Complicating factors that increase suspicion of Gram-negative organisms:9
ξ Infection caused while swimming
ξ Infections near groin or rectum
ξ Ulcers soaked in water
ξ Diabetes mellitus
ξ Vascular insufficiency
ξ Periorbital cellulitis
ξ Immunosuppression
ξ Healthcare system contact within the past 90 days
2.4. Pseudomonas spp.
2.4.1. Only 5% of chronic diabetic foot infections involve Pseudomonas spp.39
2.4.1.1. Risk factors for infections caused by Pseudomonas aeruginosa:39
ξ Nosocomial or healthcare-associated infection
ξ Soaking of open wound in tap water
2.5. Anaerobes
2.5.1. Risk factors for infections caused by anaerobic organisms:2,3,9,25-28,35,37,38
ξ Diabetes mellitus
ξ Vascular insufficiency
ξ Necrotizing fasciitis
ξ Surgical procedures involving the bowel or penetrating abdominal trauma
ξ Decubitus ulcer
ξ Perianal abscess
ξ Site of injection in injection drug users
ξ Spread from vulvovaginal infection
ξ Human bite wound

3. General principles for treatment
3.1. Patients should elevate the affected area in order to quicken improvement by promoting gravity
drainage of the edema and inflammatory substances. (Class I, Level C)
3.2. The erythematous area should be outlined with pen daily. (Class I, Level C)
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3.2.1. The erythema may extend beyond pen margins within the first 24 to 36 hours
without representing treatment failure.
3.3. If lower extremities are edematous, ACE wrap should be applied from toes to thighs every eight
hours for lower extremity infections to assist in reduction of lymphedema. (Class I, Level C)
3.4. Blood culture results are positive in fewer than 5% of cases of outpatient cellulitis and should
not routinely be obtained for patients being treated as outpatients.24 (Class I, Level B)
3.4.1. If a patient is hospitalized, blood cultures should usually be considered. (Class I, Level
C)
3.5. Needle aspiration cultures and punch biopsy specimens provide variable results (5-30% yield)
and should not routinely be obtained for outpatients.15-23 (Class I, Level B)
3.5.1. Needle aspiration may be considered for hospitalized patients and
immunocompromised hosts where the diagnostic yield is higher.2 (Class I, Level B)

4. Specific disease state management
4.1. Impetigo/erysipelas/cellulitis – superficial/subcutaneous cellulitis
4.1.1. Cellulitis that is diffuse or unassociated with a defined portal, erythematous, and non-
purulent with lymphangitic spread is most commonly caused by Streptococcus
species.35
4.1.2. Cellulitis or abscess that is fluctuant, has penetrating trauma, and/or with open ulcer
with surrounding erythema is more likely caused by Staphylococcus than by
Streptococcus species.28
4.1.2.1. See Epidemiology section for MRSA risk factors.
4.1.3. Risk factors for developing impetigo, erysipelas, or cellulitis include obesity, previous
cutaneous damage (from trauma, preexisting skin infections, ulceration, and other
causes), and edema from venous insufficiency or lymphatic obstruction.40
4.1.4. An antistreptolysin O (ASO) titer is indicated as an adjunct for diagnosis of certain beta-
hemolytic streptococcal infections.2 (Class I, Level B)
4.1.5. MRSA nasal and pooled axilla/groin PCR should be obtained for patients with risk
factors for MRSA or patients receiving anti-MRSA therapy.31-34 (Class I, Level B)
4.1.5.1. If MRSA PCRs are negative, deescalating to narrower spectrum antibiotics
not covering MRSA is reasonable. (Class IIa, Level B)
4.1.6. For patients with erythematous, non-purulent cellulitis with extensive lymphangitic
spread, the recommended antimicrobial treatments directed at Streptococcus species
only are listed in Table 1 (antibiotics are listed in order of preference).2,3,9,10 (Class I,
Level A)
4.1.7. For superficial or subcutaneous cellulitis or abscess that is fluctuant, has penetrating
trauma, and/or with open ulcer with surrounding erythema, the recommended
antimicrobial treatments directed to cover Streptococcus spp. and MSSA with a low risk
for MRSA are listed in Table 2 (antibiotics are listed in order of preference).2,3,9,10
(Class I, Level A)
4.1.8. For cellulitis or abscess that is fluctuant, has penetrating trauma, and/or with open ulcer
with surrounding erythema, the recommended antimicrobial treatment directed to cover
Streptococcus spp. and Staphylococcus spp. are listed in Table 3 (antibiotics are listed
in order of preference).2,3,9,10 (Class I, Level A)
4.1.8.1. For patients requiring IV therapy or for MRSA infections, vancomycin IV with
a goal trough concentration of 10-15 mcg/mL is reasonable.2,3,9,10 (Class IIa,
Level B)
4.1.8.1.1. Refer to Intravenous Vancomycin Use ± Adult ± Inpatient Clinical
Practice Guideline
4.1.8.2. Ceftaroline, daptomycin, or linezolid can be effective alternative agents in
specific patient types and if the skin infection is the rate limiting factor for
hospital discharge.2,3,9,10,41-43 (Class IIa, Level B)
4.1.8.3. Long-acting lipoglycopeptide antibiotics, such as oritavancin or dalbavancin,
are indicated to facilitate discharging patients or for outpatient
management.44,45 (Class I, Level B)
4.1.8.3.1. Insurance coverage should be evaluated to ensure coverage of
medications.
4.1.8.4. Tedizolid is reasonable for outpatient management.46,47 (Class IIa, Level B)
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4.1.8.4.1. Tedizolid should not be used in neutropenic patients.48 (Class III,
Level B)
4.1.9. For cellulitis or abscess that is fluctuant, has penetrating trauma, and/or with open ulcer
with surrounding erythema, the recommended antimicrobial treatment directed to cover
Streptococcus spp, MSSA, MRSA, and Gram-negative organisms (except
Pseudomonas spp.) are listed in Table 4 (antibiotics are listed in order of
preference).2,3,9,10,41-43 (Class IIa, Level B)
4.1.10. Refer to Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics ±
Adult ± Inpatient Clinical Practice Guideline for more information in patients with
reported allergies.
4.1.11. Clindamycin may exhibit inducible resistance to MRSA; caution should be used when
prescribing this agent for CA-MRSA.2,3,9,10 (See UWHC Antibiograms) (Class IIa, Level
B)
4.1.12. Trimethoprim/sulfamethoxazole has activity against most MRSA strains; however,
activity against Streptococcus spp. is variable. Alternative agents (including
combination therapy) should be considered for the treatment of possible streptococcal
infection. (Class I, Level C)
4.1.13. For outpatient management with oral treatment, five days of oral antibiotic therapy is
usually as effective as a ten-day course. A duration of therapy of five days should be
used depending on initial response.7 (Class IIa, Level A)
4.1.14. For treatment of erysipelas/cellulitis initially requiring IV antimicrobial therapy or
hospitalization, total antibiotic treatment duration of seven days is usually appropriate
and total duration of antimicrobial therapy should generally be considered for this
duration for most patients.2,9,10 (Class IIb, Level C)

Table 1. Antimicrobial agents directed at Streptococcus spp. (erythematous, non-purulent SSTI with
lymphangitic spreading)A,B
PO IV
ξ Amoxicillin 500 mg PO TIDC
ξ Cephalexin 500 mg PO QIDC
ξ Clindamycin 300-450 mg PO TID-QID
ξ Penicillin G 4 million units IV Q4hrC
ξ Cefazolin 1-2 g IV Q8hrC
ξ Clindamycin 600-900 mg IV Q6-8hr
A Treatment for 5-7 days duration is usually sufficient depending on initial response
B The activity of TMP/SMX is not sufficient to recommend monotherapy treatment of Streptococcus spp.
infection
C
Requires renal dosing adjustment

Table 2. Antimicrobial agents directed at Streptococcus spp. and MSSA (abscess, fluctuance,
penetrating trauma, and/or open ulcer with surrounding erythema)A
PO IV
ξ Dicloxacillin 500 mg PO QIDB
ξ Cephalexin 500 mg PO QIDB
ξ Clindamycin 300-450 mg PO TID-QID
ξ Oxacillin 1-2 g IV Q4hr
ξ Cefazolin 1-2 g IV Q8hrB
ξ Clindamycin 600-900 mg IV Q6-8hr
A
Treatment for 5-7 days duration is usually sufficient depending on initial response
B Requires renal dosing adjustment


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Table 3. Antimicrobial agents directed at Streptococcus spp., MSSA, and MRSA (abscess,
fluctuance, penetrating trauma, and/or open ulcer with surrounding erythema and patient has risk factors
for, history of, or confirmed MRSA)
PO IV
ξ Trimethoprim-sulfamethoxazole 160-800
mg to 320-1600 mg PO BIDA PLUS
consideration of an antimicrobial agent
from Table 1 for Streptococcus coverage
ξ Doxycycline/minocycline 100 mg PO BID
PLUS consideration of an antimicrobial
agent Table 1 for Streptococcus coverage
ξ Clindamycin 300-450 mg PO TID-QID
ξ Linezolid 600 mg PO BID
ξ Vancomycin IVA (goal trough
concentration 10-15 mcg/mL)
ξ Clindamycin 600-900 mg IV Q6-8hr
ξ Ceftaroline 600 mg IV Q12hrA
ξ Daptomycin 4 mg/kg IV Q24hrA
ξ Linezolid 600 mg IV Q12hr
ξ Oritavancin 1200 mg IV once
A
Requires renal dosing adjustment

Table 4. Antimicrobial agents directed at Streptococcus spp., MSSA, MRSA, and Gram-negatives
(excepting P. aeruginosa) (abscess, fluctuance, penetrating trauma, and/or open ulcer with surrounding
erythema and risk factors for gram-negatives)
PO
Streptococcus spp., MRSA, Gram-negative
(excepting P. aeruginosa)
Streptococcus spp., MSSA, Gram-negative
(excepting P. aeruginosa); MRSA low suspicion
after testing
ξ (Doxycycline/minocycline 100 mg PO BID OR
Trimethoprim-sulfamethoxazole 160-800 to
320-1600 mg PO BIDA) PLUS Moxifloxacin 400
mg PO daily
ξ Clindamycin 300-350 mg PO TID-QID PLUS
(Cefpodoxime 400 mg PO BIDA OR Cefuroxime
500 mg PO BIDA)
ξ Linezolid 600 mg PO BID PLUS Moxifloxacin
400 mg PO daily
ξ Cefuroxime 500 mg PO BIDA
ξ Cefpodoxime 400 mg PO BIDA
ξ Moxifloxacin 400 mg PO daily
IV
Streptococcus spp., MRSA, Gram-negative
(excepting P. aeruginosa)
Streptococcus spp., MSSA, Gram-negative
(excepting P. aeruginosa); MRSA low suspicion
after testing
ξ Vancomycin IVA (trough goal concentration 10-
15 mcg/mL) PLUS (Ceftriaxone 1-2 g IV Q24hr
OR Cefazolin 1-2 g IV Q8hrA)
ξ Ceftaroline 600 mg IV Q12hrA
ξ Daptomycin 4 mg/kg IV Q24hrA PLUS
(Ceftriaxone 1-2 IV Q24hr OR Cefazolin 1-2 g
IV Q8hrA)
ξ Ceftriaxone 1-2 g IV Q24hr
ξ Cefazolin 1-2 g IV Q8hrA
ξ Moxifloxacin 400 mg IV Q24hr
A
Requires renal dosing adjustment

4.2. Cutaneous abscess with or without cellulitis/furuncles/carbuncles
4.2.1. These infections are typically polymicrobial, including Staphylococcus aureus.25-27
4.2.2. Risk factors for developing cutaneous abscesses include diabetes mellitus, vascular
insufficiency, or traumatic injury.25-27
4.2.3. Primary treatment should be incision and drainage.2,3,9 (Class I, Level A)
4.2.3.1. For simple abscesses and boils (fewer than 5 cm in diameter of erythema
and abscess), incision and drainage alone is likely adequate as sole
treatment and no treatment with antibiotics may be reasonable.29 (Class
IIb, Level B)
4.2.3.2. For patients with abscesses/erythema (combination diameter) greater than 5
cm, multiple lesions, cutaneous gangrene, signs of systemic infection, rapid
progression of cellulitis, areas that are difficult to drain (face, hand, genitalia),
and/or risk factors for reduced ability to heal, such as diabetes or
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immunosuppression, treatment with antibiotic therapy is probably
recommended.29 (Class IIa, Level B)
4.2.4. Patients should be assessed for risk factors for MRSA, Gram-negatives, Pseudomonas
species, and anaerobes (see Epidemiology section). (Class I, Level C)
4.2.4.1. If the decision is made to treat with antimicrobials, MRSA nasal and pooled
axilla/groin PCR should be obtained for patients with risk factors for MRSA.31-
34
(Class I, Level B)
4.2.4.1.1. If MRSA PCRs are negative, deescalation to narrower spectrum
antimicrobials not covering MRSA is reasonable. (Class IIa,
Level B)
4.2.5. If the decision is made to treat with antimicrobials, coverage should be directed at
Staphylococcus species, the recommended treatment agents are listed in Table 3
(antibiotics are listed in order of preference).2,3,9,10 (Class IIa, Level B)
4.2.5.1. For patients requiring IV therapy or for HA-MRSA infections, vancomycin IV
with trough goal concentration of 10-15 mcg/mL is reasonable.2,3,9,10 (Class
IIa, Level B)
4.2.5.1.1. Refer to Intravenous Vancomycin Use ± Adult ± Inpatient Clinical
Practice Guideline
4.2.5.2. Ceftaroline, daptomycin, or linezolid or tedizolid can be effective alternative
agents in specific patient types and if the skin infection is the rate limiting
factor for hospital discharge.2,3,9,10,41-43 (Class IIa, Level B)
4.2.5.3. Long-acting lipoglycopeptide antibiotics, such as oritavancin or dalbavancin,
are indicated to facilitate discharging patients or for outpatient
management.44,45 (Class I, Level B)
4.2.5.3.1. Insurance coverage should be evaluated to ensure coverage of
medications.
4.2.5.4. Tedizolid is reasonable for outpatient management.46,47 (Class IIa, Level B)
4.2.5.4.1. Tedizolid should not be used in neutropenic patients.48 (Class III,
Level B)
4.2.6. If the patient has risk factors for Gram-negative organisms, the recommended
antimicrobial treatment directed to cover Streptococcus spp, MSSA, MRSA, and Gram-
negative organisms (excepting Pseudomonas aeruginosa) are listed in Table 4
(antibiotics are listed in order of preference).2,3,9,10,41-43 (Class IIa, Level B)
4.2.7. If the patient has risk factors for anaerobic organisms, treatment options directed to
cover Streptococcus spp., MSSA, MRSA, Gram-negative organisms (excepting
Pseudomonas aeruginosa), and anaerobes are listed in Table 5 (treatment regimens
are listed in order of preference).2,3,9,10,41-43 (Class IIa, Level B)
4.2.8. If the patient has risk factors for Pseudomonas aeruginosa, treatment options directed
to cover Streptococcus spp., MSSA, MRSA, and Gram-negatives (including
Pseudomonas aeruginosa), and anaerobes are listed in Table 6 (treatment regimens
are listed in order of preference).2,3,9,10 (Class IIa, Level B)
4.2.9. Refer to Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics ±
Adult ± Inpatient Clinical Practice Guideline for more information in patients with
reported allergies.
4.2.10. For treatment of cutaneous abscess/furuncles/carbuncles, if incision and drainage is
not sufficient and antibiotic therapy is used, antibiotic duration not exceeding 14 days
may be considered.2,3,7,9,37 (Class IIb, Level B)


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Table 5. Antimicrobial agents directed at Streptococcus spp., MSSA, MRSA, Gram-negatives
(excepting P. aeruginosa), and anaerobes (abscess, fluctuance, penetrating trauma, and/or open ulcer
with surrounding erythema and risk factors for anaerobes)
PO
Streptococcus spp., MRSA, Gram-negative
(excepting P. aeruginosa) and anaerobes
Streptococcus spp., MSSA, Gram-negative
(excepting P. aeruginosa), anaerobes; MRSA
low suspicion after testing
ξ (Trimethoprim-sulfamethoxazole 160-800 to
320-1600 mg PO BIDA OR Doxycycline 100 mg
PO BID) PLUS (Augmentin XRA,B 2000-125 mg
PO BID OR Moxifloxacin 400 mg PO daily)
ξ (Trimethoprim-sulfamethoxazole 160-800 to
320-1600 mg PO BIDA OR Doxycycline 100 mg
PO BID) PLUS (Cefuroxime 500 mg PO BIDA
OR Cefpodoxime 400 mg PO BIDA) PLUS
Metronidazole 500 mg PO TID
ξ Clindamycin 300-450 mg PO TID-QID PLUS
(Cefpodoxime 400 mg PO BIDA OR Cefuroxime
500 mg PO BIDA)
ξ Linezolid 600 mg PO BID PLUS Moxifloxacin
400 mg PO daily
ξ Augmentin XRA,B 2000-125 mg PO BID
ξ Moxifloxacin 400 mg PO daily
IV
Streptococcus spp., MRSA, Gram-negative
(excepting P. aeruginosa) and anaerobes
Streptococcus spp., MSSA, Gram-negative
(excepting P. aeruginosa), anaerobes; MRSA
low suspicion after testing
ξ Vancomycin IVA (goal trough concentration 10-
15 mcg/mL) PLUS Ceftriaxone 1-2 g IV Q24hr
PLUS Metronidazole 500 mg IV Q8hr
ξ Ceftaroline 600 mg IV Q12hrA PLUS
Metronidazole 500 mg IV Q8hr
ξ Ertapenem 1 g IV Q24hrA PLUS Vancomycin
IVA (goal trough concentration 10-15 mcg/mL)
ξ Ertapenem 1 g IV Q24hrA PLUS Daptomycin 4
mg/kg IV Q24hrA
ξ Tigecycline 100 mg IV x 1, then 50 mg IV
Q12hr
ξ Ampicillin-sulbactam 1.5-3 g IV Q6hrA
ξ Ceftriaxone 1-2 g IV Q24hr PLUS
Metronidazole 500 mg IV Q8hr
ξ Cefoxitin 2 g IV Q6hrA
ξ Moxifloxacin 400 mg IV Q24hr
A Requires renal dosing adjustment
B Augmentin XR is the preferred agent, but based on ability to pay amoxicillin-clavulanate 500-125 mg PO
BID with or without addition of amoxicillin 500-1000 mg PO QID may be considered as an alternative


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13
Table 6. Antimicrobial agents directed at Streptococcus spp., MSSA, MRSA, Gram-negatives
(including P. aeruginosa), and anaerobes (abscess, fluctuance, penetrating trauma, and/or open ulcer
with surrounding erythema and risk factors for P. aeruginosa)
PO
Streptococcus spp., MRSA, Gram-negatives
(including P. aeruginosa) and anaerobes
Streptococcus spp., MSSA, Gram-negatives
(including P. aeruginosa) and anaerobes;
MRSA low suspicion after testing
ξ (Trimethoprim-sulfamethoxazole 160-800 to
320-1600 mg PO BIDA OR Doxycycline 100 mg
PO BID) PLUS Levofloxacin 500-750 mg PO
dailyA PLUS consider Metronidazole 500 mg
PO TID
ξ Clindamycin 300-450 mg PO TID-QID PLUS
Ciprofloxacin 500 mg PO BIDA
ξ Linezolid 600 mg PO BID PLUS Levofloxacin
500-750 mg PO dailyA PLUS consider
Metronidazole 500 mg PO TID
ξ Augmentin XRA,B 2000-125 mg PO BID
PLUS Ciprofloxacin 500 mg PO BIDA
ξ Levofloxacin 500-750 mg PO dailyA PLUS
Metronidazole 500 mg PO TID
ξ Clindamycin 300-450 mg PO TID-QID
PLUS Ciprofloxacin 500 mg PO BIDA
IV
Streptococcus spp., MRSA, Gram-negatives
(including P. aeruginosa) and anaerobes
Streptococcus spp., MSSA, Gram-negatives
(including P. aeruginosa) and anaerobes;
MRSA low suspicion after testing
ξ Piperacillin-tazobactamC PLUS Vancomycin IV
(goal trough concentration 10-15 mcg/mL)
ξ CefepimeC PLUS Vancomycin IV (goal trough
concentration 10-15 mcg/mL) PLUS
Metronidazole 500 mg IV Q8hr
ξ MeropenemC PLUS Vancomycin IV (goal
trough concentration 10-15 mcg/mL)
ξ Piperacillin-tazobactamC
ξ CefepimeC PLUS Metronidazole 500 mg
IV Q8hr
ξ MeropenemC
A Requires renal dosing adjustment
B
Augmentin XR is the preferred agent, but based on ability to pay amoxicillin-clavulanate 500-125 mg PO
BID with or without addition of amoxicillin 500-1000 mg PO QID may be considered as an alternative
C
See Antibiotics for the Treatment of Gram-negative Infections ± Adult ± Inpatient Clinical Practice
Guideline for dosing guidance

4.3. Infection caused by animal (dog and cat) bites
4.3.1. Aerobic and anaerobic bacteria such as Pasteurella, Staphylococcus aureus,
Bacteroides tectum, Fusobacterium species, Capnocytophaga species, and
Porphyromonas species are the likely pathogens.2,3,9,10
4.3.2. Not all bite wounds become infected or require treatment. Risk factors for bite
wounds that are at high risk of infection include a deep puncture, crushing injury, cat
bites, or heavy contamination.2,3,9,10 (Class I, Level C)
4.3.3. See Table 7 for antimicrobial agents that are reasonable for treatment.2,3,9,10 (Class IIa,
Level B)
4.3.4. Refer to Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics ±
Adult ± Inpatient Clinical Practice Guideline for more information in patients with
reported allergies.
4.3.5. Total antibiotic treatment duration of seven days may be reasonable and antimicrobial
therapy limited to this duration may be considered for most patients.2,9,10 (Class IIb,
Level C)
4.3.6. The need for tetanus vaccine and rabies vaccine and/or immune globulin should be
assessed. (Class I, Level C)

4.4. Infection caused by human bites
4.4.1. Aerobic and anaerobic bacteria such as streptococci, Staphylococcus aureus, Eikenella
corrodens, Fusobacterium, Peptostreptococcus, Prevotella, and Porphyromonas are
the likely pathogens causing infection.2,3,9,10
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4.4.2. Not all bite wounds become infected or require treatment. Risk factors for bite
wounds that are at high risk of infection include a deep puncture, crushing injury, heavy
contamination, or location on a hand.2,3,9,10 (Class I, Level C)
4.4.2.1. Due to resistance of Eikenella corrodens to first-generation cephalosporins,
macrolides, clindamycin, and aminoglycosides, treatment with these agents
is not recommended.2,3,9,10 (Class I, Level B)
4.4.3. See Table 7 for antimicrobial agents that should be used for treatment (antibiotics are
listed in order of preference).2,3,9,10 (Class IIa, Level B)
4.4.4. Refer to Treatment of Patients with Reported Allergies to Beta-Lactam Antibiotics ±
Adult ± Inpatient Clinical Practice Guideline for more information in patients with
reported allergies.
4.4.5. Total antibiotic treatment duration of seven days may be reasonable and antimicrobial
therapy limited to this duration for most patients may be considered.2,9,10 (Class IIb,
Level C)

Table 7. Antimicrobial agents for skin infections caused by animal or human bitesA,B
PO IV
ξ Augmentin XR 2000-125 mg PO BIDC,D
ξ Moxifloxacin 400 mg PO daily
ξ (Cefuroxime 500 mg PO BIDD OR Cefpodoxime
400 mg PO BIDD OR Trimethoprim-
sulfamethoxazole 160-800 mg to 320-1600 mg
PO BIDD OR Doxycycline 100 mg PO BID OR
Ciprofloxacin 500 mg PO BIDD)
PLUS
(Clindamycin 300-450 mg PO TID-QID OR
Metronidazole 500 mg PO TID)
ξ Ampicillin-sulbactam 1.5-3 g IV Q6hrD
ξ Cefoxitin 2 g IV Q6hrD
ξ (Ceftriaxone 1-2 g IV Q24hr OR
Ciprofloxacin 400 mg IV Q12hrE) PLUS
(Metronidazole 500 mg IV Q8hr OR
Clindamycin 600-900 mg IV Q6-8hr)
ξ Ertapenem 1 g IV Q24 hr
ξ Moxifloxacin 400 mg IV Q24hr

A
Not all animal bites will cause infection
B
Assess need for tetanus vaccine and rabies vaccine and/or immune globulin
C
Augmentin XR is the preferred agent, but based on ability to pay amoxicillin-clavulanate 500-125 mg PO
BID with or without addition of amoxicillin 500-1000 mg PO QID may be considered as an alternative
D Requires renal dosing adjustment
E See Antibiotics for the Treatment of Gram-negative Infections ± Adult ± Inpatient Clinical Practice
Guideline for dosing guidance

4.5. Necrotizing fasciitis
4.5.1. Findings of purple bullae, sloughing of skin, marked edema, and systemic toxicity
prompt surgical intervention is recommended.2,3,9,10 (Class I, Level A)
4.5.2. Recent surgery, peripheral vascular disease, diabetes mellitus, decubitus ulcers, and
spontaneous mucosal tears of the gastrointestinal or genitourinary tract increase the
likelihood of polymicrobial infection with mixed aerobic and anaerobic organisms.2,3,9,10
4.5.3. Surgical debridement should be the primary treatment.3 (Class I, Level A)
4.5.4. The recommended agents to be used for treatment are listed in Table 8.3 (Class IIa,
Level B).
4.5.4.1. Clindamycin should only be continued beyond 72 hours if Group A
Streptococcus is isolated and the patient remains hypotensive in order to
block TSS protein synthesis.3 (Class I, Level B)
4.5.4.2. Vancomycin may be considered for patients with risk factors for, history of, or
confirmed MRSA, or until MRSA is excluded from cultures. (Class IIb, Level
B)
4.5.5. Antibiotic duration determination by the extent of surgical incision and response to
antibiotics post-operatively may be reasonable.3 (Class IIb, Level B)


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15
Table 8. Recommended agents for necrotizing fasciitis
IV
ξ (Ampicillin-sulbactam 1.5-3 g IV Q4hrA OR Piperacillin-tazobactamB) PLUS Ciprofloxacin 400 mg IV
Q12hrB PLUS ClindamycinC 600-900 mg IV Q6-8hr
ξ Vancomycin IV (goal trough concentration 10-15 mcg/mL) PLUS Ciprofloxacin 400 mg IV q12hrA
PLUS ClindamycinB 600-900 mg IV q6-8hr
A
Requires renal dosing adjustment
B
See Antibiotics for the Treatment of Gram-negative Infections ± Adult ± Inpatient Clinical Practice
Guideline for dosing guidance
C
Clindamycin should only be continued if Group A Streptococcus is isolated and should only be
continued for 48-72 hours (If anaerobic coverage is still desired, consider substituting with
metronidazole)

5. Prevention of recurrent infection
5.1. Causes of infection such as Tinea pedis should be treated to prevent recurrence.49 (Class I,
Level B)
5.2. Skin should be kept well hydrated with emollients to avoid dryness and cracking. (Class I, Level
B)
5.3. Underlying edema should be reduced by elevating the infected extremity and by the use of
compression stockings. (Class I, Level B)
5.4. Penicillin VK 500 mg orally twice daily or 1 g orally daily or similar antibiotics daily may be
considered for patients with recurrent Streptococcus or Staphylococcus cellulitis, especially
patients with recurrent lymphedema and lymphangitis.50-52 (Class IIb, Level B)

6. Daily monitoring checklist
6.1. Daily monitoring for signs and symptoms of improvement should be done.(Class I, Level C)
6.1.1. Cessation of lesion spread at 48 to 72 hours denotes improvement.
6.1.1.1. Lesions may spread within the first 24 to 36 hours without representing
treatment failure.
6.1.1.2. 7KH�³TXDOLW\´�RI�HU\WKHPD�PD\�DOVR�LQGLFDWH�LPSURYHPHQW�ZLWKRXW�UHJUHVVLRQ�
of margins (e.g. fire engine red to pink may indicate improvement).
6.1.2. Fever is not worsening 48 to 72 hours after initiation of therapy denotes improvement.
6.2. Monitoring culture results and MRSA test results is reasonable.(Class IIa, Level C)
6.2.1. Ensure patient is receiving adequate coverage from antibiotics for isolated organisms.
6.2.2. Antibiotics should be narrowed to target offending agent based on culture/laboratory
results to narrowest effective treatment.
6.2.2.1. If MRSA PCRs are negative, deescalation to narrower spectrum
antimicrobials not covering MRSA is reasonable. (
6.3. Transition from intravenous to enteral antimicrobial therapy should be evaluated.
6.3.1. See Medication Route Interchange ± Adult ± Inpatient ± Clinical Practice Guideline.

UW Health Implementation
Benefits/Harms of Implementation
ξ Implementation of this guideline will standardize the care of patients treated for urinary tract
infections.
ξ Utilization of this guideline drives prescribing towards narrow spectrum agents. This reduces
antimicrobial pressure on the bacterial biomass and reduces the emergence of bacterial resistance.

Implementation Strategy
ξ This guideline will be disseminated to clinical staff and available electronically.
ξ This guideline will serve as a resource for clinical inservices.

Implementation Tools/Plan
ξ This clinical practice guideline will be posted for reference in UConnect.
ξ Links to this clinical practice guideline will be available electronically at point of use sites.

Disclaimer
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16
CPGs are described to assist clinicians by providing a framework for the evaluation and treatment of
patients. This Clinical Practice Guideline outlines the preferred approach for most patients. It is not
LQWHQGHG�WR�UHSODFH�D�FOLQLFLDQ¶V�MXGJPHQW�RU�WR�HVtablish a protocol for all patients. It is understood that
some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely
establish the only appropriate approach to a problem.

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57. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med. Apr 24
1995;98(4a):15S-23S; discussion 23S-24S.
58. Karppelin M, Siljander T, Huhtala H, et al. Recurrent cellulitis with benzathine penicillin prophylaxis is
associated with diabetes and psoriasis. Eur J Clin Microbiol Infect Dis. Mar 2013;32(3):369-372.
59. Pauszek ME. Prophylaxis for recurrent cellulitis complicating venous and lymphatic insufficiency. Indiana
Med. Apr 1991;84(4):252-253.
60. Koster JB, Kullberg BJ, van der Meer JW. Recurrent erysipelas despite antibiotic prophylaxis: an analysis
from case studies. Neth J Med. Mar 2007;65(3):89-94.
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18
61. Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus
trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a
randomized controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases
Society of America. Jun 2013;56(12):1754-1762.
62. Stein GE, Throckmorton JK, Scharmen AE, et al. Tissue penetration and antimicrobial activity of standard-
and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection. The
Journal of antimicrobial chemotherapy. Dec 2013;68(12):2852-2858.
63. Marra F, Patrick DM, Chong M, McKay R, Hoang L, Bowie WR. Population-based study of the increased
incidence of skin and soft tissue infections and associated antimicrobial use. Antimicrob Agents Chemother.
Dec 2012;56(12):6243-6249.
64. Wood JB, Smith DB, Baker EH, Brecher SM, Gupta K. Has the emergence of community-associated
methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?:
a 10-year time series analysis. Antimicrob Agents Chemother. Nov 2012;56(11):5655-5660.



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19
Figure 1. Outpatient Management of Skin and Soft Tissue Infections
Local presentation (at least 3 of the following)
Edema Erythema Heat
Bullae Petechiae Pain
³2UDQJH�SHHO´�DSSHDUDQFH Vesicles
Bites
Oral options
Augmentin XR 2000/125 mg PO BID
Moxifloxacin 400 mg PO daily
IV and Oral Alternatives in Table 7
ASO titer may be useful in some
types of beta streptococcus
Superficial cellulitis, open
shallow ulcer/blister
Deep, ulcerative, and/or
chronic cellulitis or
penetrating trauma
Yes Consider alternative diagnosisNoDetermine type of skin, skin structure, or soft tissue infection
Non-purulent with extensive
lymphangitic spread
Streptococcus sp most likely
Cutaneous abscess (traumatic and non-traumatic)
with or without surrounding cellulitis
Impetigo/superficial or subcutaneous
cellulitis
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c
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Incision & drainage
T
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m
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t

c
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s
i
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r
a
t
i
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s
”�5 cm
Consider abx therapy and culturing aspirate (to
guide de-escalation) if:
ü Multiple lesions
ü Cutaneous gangrene
ü Signs of systemic infection
ü Rapid progression of cellulitis
ü Areas that are difficult to drain (face, hand,
genitalia)
ü Risk factors for reduced ability to heal (diabetes or
immunosuppression
Assess for MRSA**
Majority of SSTIs (60-90%) are caused by Gram postive
organisms.
OUTPATIENT TREATMENT DOES NOT USUALLY REQUIRE
COVERAGE OF GRAM NEGATIVE ORGANISMS
Amoxicillin 500mg PO TID
Alternatives in Table 1
M
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s
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MRSA Risk Factors
TMP/SMX DS 1-2 tabs PO BID OR
doxy/minocycline 100mg PO BID
PLUS amoxicillin 500mg PO TID
Alternatives in Table 3
Dicloxacillin 500mg PO QID OR
Cephalexin 500mg QID
Alternatives in Table 2
*Consider x1 dose of IV/IM ceftriaxone
NO MRSA Risk Factors
Recommended non-pharmacologic options:
ü Elevate limb (wedge pillow)
ü Outline erythematous area with pen daily
(erythema may extend beyond margins within the first 24-36 hours without representing
treatment failure)
ü If edematous, apply ACE wrap from toes to thighs every 8 hours for lower extremity infections
ξ Lesion spread and fever may take 48-72 hours to abate. If no improvement after 72-96 hours or
worsening, consider IV therapy, expanding coverage, or alternative diagnosis (see inpatient
algorithm)
ξ 7KH�³TXDOLW\´�RI�HU\WKHPD�PD\�DOVR�LQGLFDWH�LPSURYHPHQW�ZLWKRXW�UHJUHVVLRQ�RI�PDUJLQV�(i.e. fire
engine red to pink)
Risk factors for CA-MRSA
ü H/o MRSA infection or colonization in patient or
close contact
ü High prevalence of CA-MRSA in local community
or patient population
ü Recurrent skin disease
ü Crowded living conditions (eg homeless shelter or
military barracks)
ü H/o incarceration
ü Contact sports
ü Injection drug use
ü Native American, Pacific Islander, Alaskan Native
ü Male with h/o having sex with men
ü Shaving body hair
ü Recent/frequent antibiotic use
ü Skin or soft tissue infection with poor response to
beta-lactam antibiotics
Risk factors for HA-MRSA
ü Nasal colonization
ü Presence of indwelling devices such as
catheters, tracheostomies, and
nasogastric tubes
ü Hospital admission within past 90 days
ü Prolonged hospitalization
ü Residence in long-term care facility
ü Antibiotic therapy in past 90 days
ü Diabetes mellitus
ü Hemodialysis
ü HIV infection
ü Immunosuppression


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20
Figure 2: Inpatient Management of Skin and Soft Tissue Infections
Inpatient Diagnosis and Treatment of Skin and Soft Tissue Infections in Adult Patients
Local presentation (at least 3 of the following)
Edema Erythema Heat
Bullae Petechiae Pain
³2UDQJH�SHHO´�DSSHDUDQFH Vesicles
Bites
Necrotizing
fasciitis
ASO titer may be useful in some
types of beta streptococcus
Primary therapy:
surgical debridement
Aspirate and send for
culture
Superficial cellulitis, open
shallow ulcer/blister
Deep, ulcerative, and/or
chronic cellulitis or
penetrating trauma
Assess for Gram negative
‚

and anaerobe
Á�
risk factors
MRSA risk factors Present
or MRSA history/positive?
Yes Consider alternative diagnosisNoDetermine type of skin, skin structure, or soft tissue infection
Non-purulent with extensive
lymphangitic spread
Streptococcus sp most likely
Cutaneous abscess (traumatic and
non-traumatic) with or without
surrounding cellulitis
No
Impetigo/superficial or
subcutaneous cellulitis
(Unable to be easily cultured)
D
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g
n
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c
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s
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a
t
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Incision & drainage
T
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m
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c
o
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s
i
d
e
r
a
t
i
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s
”�5 cm
Consider abx therapy and
culturing aspirate (to guide
de-escalation) if:
ü Multiple lesions
ü Cutaneous gangrene
ü Signs of systemic infection
ü Rapid progression of
cellulitis
ü Areas that are difficult to
drain (face, hand, genitalia)
ü Risk factors for reduced
ability to heal (diabetes or
immunosuppression
Assess for
MRSA**
>5 cm
Assess for
MRSA**
Penicillin G 4 million units IV or
amoxicillin 500mg PO TID
Alternatives in Table 1
Yes
Order MRSA nasal
AND pooled axilla/
groin PCR OR anti-
MRSA agent started
Vancomycin (Goal Trough 10-15)
Alternatives in Table 3
Oxacillin 1-2gm IV q4hr OR
Dicloxacilin 500mg PO QID
Alternatives in Table 2
No
UNLIKELY Gram Negative,
see risk factors
Add cefazolin 1-2gm IV
q8hr OR ceftriaxone 1-
2gm IV q24hr
Alternatives in Table 4
Add metronidazole
500mg IV/PO q8hr
Alternatives in Table 5
Gram Neg
Anaerobe
Add Pip/tazo 3.375gm
IV q8hr
Alternatives in Table 6
Pseudomonas
Oral options
Augmentin XR 2000/125 mg PO BID
Moxifloxacin 400 mg PO daily
IV options
Ampicililn/sulbactam 1.5-3gm IV q6hr
Cefoxitin 2gm IV q6hr
Alternatives in Table 7
Empiric Therapy
Vancomycin (Goal Trough 15-20)
Pip/tazo 3.375gm IV q8hr
Clindamycin 600mg IV
De-escalate based on culture
results.
D/C clindamycin when non-Group
A strep organism identified or
patient becomes normotensive
ü Cessation of lesion spread OR improvement in “quality of erythema after 48-72 hours?
ü Worsening fever at 48 to 72 hours?
ü Culture or MRSA test results indicating antibiotics can be de-escalated from broad-spectrum to narrow-spectrum
or anti-MRSA to oxacillin or cefazolin?
ü Transition from IV to PO therapy?
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a
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s
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21
** Risk Factors for Community-Acquired MRSA29
ξ H/o MRSA infection or colonization in patient or close contact
ξ High prevalence of CA-MRSA in local community or patient population
ξ Recurrent skin disease
ξ Crowded living conditions (e.g. homeless shelter or military barracks)
ξ H/o incarceration
ξ Contact sports
ξ Injection drug use
ξ Native American, Pacific Islander, Alaskan Native
ξ Male with h/o having sex with men
ξ Shaving body hair
ξ Recent/frequent antibiotic use
ξ Skin or soft tissue infection with poor response to beta-lactam antibiotics

** Risk Factors for Hospital-Acquired MRSA30 (most likely clindamycin-resistant)
ξ Nasal colonization
ξ Presence of indwelling devices such as catheters, tracheostomies, and nasogastric tubes
ξ Hospital admission within past 90 days
ξ Prolonged hospitalization
ξ Residence in long-term care facility
ξ Antibiotic therapy in past 90 days
ξ Diabetes mellitus
ξ Hemodialysis
ξ HIV infection
ξ Immunosuppression

‚Risk factors for Gram-negative organisms9
ξ Infection caused while swimming
ξ Infections near groin or rectum
ξ Ulcers soaked in water (at risk for Pseudomonas)
ξ Diabetes mellitus with ulceration
ξ Vascular insufficiency with ulceration
ξ Periorbital cellulitis
ξ Immunosuppression
ξ Healthcare system contact within the past 90 days (at risk for Pseudomonas)

Á5LVN�IDFWRUV�IRU�DQDHUREHV2,3,9,25-28,35,37,38
ξ Diabetes mellitus with ulceration
ξ Vascular insufficiency with ulceration
ξ Necrotizing fasciitis
ξ Surgical procedures involving the bowel or penetrating abdominal trauma
ξ Decubitus ulcer
ξ Perianal abscess
ξ Site of injection of IV drug users
ξ Spread from vulvovaginal infection


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22

Appendix A. Diagnosis and Treatment of Gram Positive Bacterial Skin and Soft Tissue
Infections – Top Ten Myths
Authors: Lucas Schulz, PharmD; Robert Hoffman, MD; Jeffrey Pothof, MD; Barry Fox, MD

Myth 1: Skin that is red and swollen is definitely cellulitis

Truth 1���/RFDO�SUHVHQWDWLRQ�RI�HGHPD��HU\WKHPD��KHDW��³RUDQJH�SHHO´�DSSHDUDQFH��YHVLFOHV��EXOODH�
petechiae, and pain should lead to a diagnosis of skin and skin structure infection.2,3,9,10
a. Diagnoses of deep venous thrombosis, venous stasis dermatitis, venous insufficiency,
lymphedema, contact dermatitis, gout, herpes zoster, acute lipodermatosclerosis, non-
infectious phlebitis and fixed drug reaction should be excluded.
b. All inflammatory responses include hyperemia, warmth, swelling, and usually pain
c. A simple physical exam skill that can help differentiate true cellulitis from other etiologies of
erythema of the lower extremity is to have the patient lie horizontally on exam table/bed,
manually elevate leg at 45 degree angle or higher, and hold it there for 1-2 minutes while
observing whether the erythema abates. Cellulitis erythema will persist upon elevation
whereas erythema due to other etiologies often disappears with elevation.

Myth 2: Bilateral leg swelling and redness always means bilateral leg cellulitis

Truth 2: Bilateral leg swelling is usually due to other disease states and does not mean that the patient
has developed bilateral cellulitis.40,53 Statistical probability would also make this occurrence exceedingly
rare.
a. Risk factors for developing erysipelas or cellulitis include obesity, previous cutaneous
damage (from trauma, preexisting skin infections, ulceration, and other causes), and edema
from venous insufficiency or lymphatic obstruction or disruption of lymphatic drainage, such
as following lymph node dissection.
1. Of 99 patients with bilateral leg swelling, 17 patients (17%) were found to have acute
deep vein thrombosis by venous duplex ultrasound. 2
b. Patients should elevate the affected area in order to hasten improvement by promoting
gravity drainage of the edema and inflammatory substances.
c. If edematous, apply ACE wrap from toes to thighs every 8 hours for lower extremity infections
to assist in reduction of lymphedema.

Myth 3: Patients with no risk factors for community acquired- methicillin-resistant
Staphylococcus aureus (CA-MRSA) cannot get MRSA

Truth 3: Any patient may develop cellulitis caused by CA-MRSA. The likelihood is increased if the
patient has risk factors for MRSA.

a. Between 2006 and 2009, a microbiologic study of skin and soft-tissue infections examined
the etiology of skin and soft tissue infections (SSTI) in a general population. A culture was
obtained in 23% (149,200/ 648699) of SSTI episodes, and a pathogen was identified in 58%
(87,839/149,200) of the cultures. Staphylococcus aureus was the pathogen in 80% of the
positive cultures 70,026/87,839), with 50% (35,180/70,026) of the Staphylococcus aureus
isolates being MRSA.54
b. Risk factors for community-acquired MRSA (CA-MRSA) include:29
ξ History of MRSA infection or colonization in patient or close contact
ξ High prevalence of CA-MRSA in local community or patient population
ξ Recurrent skin disease
ξ Crowded living conditions (e.g. homeless shelters, military barracks)
ξ History of incarceration
ξ Participation in contact sports
ξ Skin or soft tissue infection with poor response to beta-lactam antibiotics
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ξ Recent and/or frequent antibiotic use
ξ Injection drug use
ξ Member of Native American, Pacific Island, Alaskan Native populations
ξ Male with history of having sex with men
ξ Shaving of body hair

c. Risk factors for hospital-acquired MRSA (HA-MRSA) include:30
ξ Nasal colonization
ξ Presence of indwelling devices such as catheters, tracheostomies, and nasogastric tubes
ξ Hospital admission within past 90 days
ξ Prolonged hospitalization
ξ Residence in long-term care facility
ξ Antibiotic therapy in past 90 days
ξ Diabetes mellitus
ξ Hemodialysis
ξ HIV infection/immunosuppression

d. In the absence of cultured abscess samples, MRSA nasal AND pooled axilla/groin PCR or
culture should be obtained for inpatients with risk factors for MRSA or to determine the
likelihood that infection is caused by MRSA31-34,55
1. If MRSA PCRs or cultures are negative, medications covering for MRSA may
potentially be de-escalated to beta-lactam antibiotics.55

Myth 4: All cellulitis needs to be treated with antibiotics

Truth 4: Not all cellulitis needs to be treated with antibiotics.
a. For simple abscesses and boils (less than 5 cm in diameter of erythema and abscess),
incision and drainage alone is likely adequate as sole treatment and no treatment with
antibiotics are necessary2,3,9,29
b. For patients with abscesses/erythema (combination diameter) greater than 5 cm, multiple
lesions, cutaneous gangrene, signs of systemic infection, rapid progression of cellulitis, areas
that are difficult to drain (face, hand, genitalia), and/or risk factors for reduced ability to heal,
such as diabetes or immunosuppression, treatment with antibiotic therapy should be
considered29

Myth 5: All hospitalized patients need to be treated as though they have MRSA infection

Truth 5: Hospitalized patients should be treated with antibiotics to cover organisms based on individual
characteristics of the infection and risk factors for organisms.
a. Of 322 hospitalized patients with SSTIs, 47% (150/322) had a positive culture result and of
those with result, 43% (64/150) grew MRSA.5
b. Impetigo, erysipelas, and cellulitis that is diffuse or unassociated with a defined portal,
erythematous, non-purulent with extensive lymphangitic spread is more commonly caused by
Group A or other beta-hemolytic Streptococcus than Staphylococcal species (but
Staphylococcus aureus may also be present)35,36
c. For cellulitis with abscess that is fluctuant, has penetrating trauma, shallow ulcer or blister
with surrounding erythema, Streptococcus spp. and Staphylococcus spp. should be targeted
with antimicrobial therapy (including MRSA). 2,3,9,10
1. Abscess material should be obtained for culture whenever possible.
2. MRSA nasal and pooled axilla/groin PCR or culture should be obtained in the absence
of culture material for patients with risk factors for MRSA or patients receiving anti-
MRSA therapy31-34
3. If MRSA PCR or culture are negative, medications covering for MRSA may potentially
be de-escalated to more narrow-spectrum antibiotics
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d. Severity of illness and co-morbidities, as well as risk factors for MRSA plays a large role in
determining whether or not to empirically treat for MRSA.

Myth 6: If the redness extends beyond the drawn wound margin in a patient with cellulitis, the
patient is getting worse

Truth 6: Because of the sub-acute spread of redness, edema, and/or induration in some patients at the
time of presentation with SSTI, the lesion may continue to spread during a short period of time after
administration of the first doses of antibacterial drug therapy.56
a. The erythema may extend beyond pen margins within the first 24 to 36 hours without
representing treatment failure. The intensity of the erythema is often a more important
variable, with improving cases resulting in less intensely red inflammation.
b. If erythema and fever continue beyond 48 to 72 hours, this is usually considered treatment
failure and antimicrobial therapy should be reassessed. Exceptions may include beta
hemolytic streptococcal infections where lymphangitis and lymphadenopathy may continue to
evolve over multiple days.

Myth 7: All patients with tick bites and surrounding redness have cellulitis

Truth 7: Local tick bite reactions are predictable and do not indicate that a patient has cellulitis.57 These
are usually no more than a few cm in size.
a. Erythema surrounding a tick bite can be differentiated from streptococcal and staphylococcal
cellulitis based the characteristics of erythema. Erythema due to tick bites usually remains
localized with limited spread to the site of the bite, while bacterial cellulitis and erythema
migrans from Borellia will continue to extend several cm beyond the bite site.

Myth 8: Patients should never have another infection if they are taking antibiotic prophylaxis for
recurrent infections,
Truth 8: Antibiotic prophylaxis may suppress infection, but recurrence may occur despite adherence to
therapy. Treatment of causes of infection and optimization of treatment of other disease states may
decrease the risk of recurrence.50-52
a. Of 398 patients, 40% (158/398) of patients reported cellulitis recurrence despite prophylactic
treatment of benzathine penicillin58
b. Causes of infection such as tinea pedis should be treated to prevent recurrence49,59
c. The management of other disease states, such as diabetes mellitus and especially
lymphedema, should be optimized in order to decrease the risk of recurrence.58
d. Skin should be kept well hydrated with emollients to avoid dryness and cracking
e. Underlying edema should be reduced by elevating the infected extremity and by the use of
compression stockings59
f. Reconfirmation of the diagnosis of cellulitis, appropriateness of antibiotic, dosing, timing, and
adherence should also be assessed60

Myth 9: Since one cannot tell whether cellulitis is caused by Streptococcus, Staphylococcus, or
CA-MRSA, each patient need two types of anti-infectives

Truth 9: Antimicrobial therapy should be selected based on characteristics of the infection and patient-
specific risk factors for different organisms, and the severity of the patients illness. Most uncomplicated
cellulitis will not need combination therapy with a beta- lactam and anti- MRSA anti-infective5,61
a. Cellulitis that is diffuse or unassociated with a defined portal, erythematous, and non-purulent
with extensive lymphangitic spread is most commonly caused by Streptococcal species35
b. Cellulitis with abscess that is fluctuant, has penetrating trauma, and/or open ulcer with
surrounding erythema is more likely caused by Staphylococcus than by Streptococcus
species 28
c. Dicloxacillin and cephalexin exhibit antimicrobial activity against MSSA and Streptococcus
2,3,9,10

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25
d. For patients with risk factors for MRSA, trimethoprim-sulfamethoxazole has activity against
most MRSA strains; however, activity against Streptococcal spp. is variable. One recent
study found it very active for beta- hemolytic strep.62 Alternative agents (including
combination therapy) should be considered for the treatment of possible Streptococcal
infection.2,3,9,10 Doxycycline is not active for beta- hemolytic streptococci.
e. Clindamycin has activity against Streptococcus, MSSA, and some strains of MRSA, although
the sensitivity to MRSA is declining (see myth 10).2,3,9,10

Myth 10: Clindamycin is the most effective empiric antibiotic for CA-MRSA

Truth 10: Clindamycin may exhibit inducible resistance to MRSA, and caution should be used when
prescribing this agent for CA-MRSA. Microbiology labs are now routinely testing for this induceability, and
will report clindamycin as resistant. Resistance rates to clindamycin of greater than 35% have been
reported for CA-MRSA, and 100% of H-MRSA are resistant. Trimethoprim-sulfamethoxazole and
doxycycline resistance rates remain at less than 10% in most communities. 2,3,9,10,63,64 Clindamycin also
has the highest odds ratio for the development of Clostridium difficile.

References for Appendix A
1. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue. Clin
Infect Dis. Nov 15 2005;41(10):1373-1406.
2. May AK, Stafford RE, Bulger EM, et al. Treatment of complicated skin and soft tissue infections. Surg Infect (Larchmt). Oct
2009;10(5):467-499.
3. Swartz MN. Clinical practice. Cellulitis. N Engl J Med. Feb 26 2004;350(9):904-912.
4. Bailey E, Kroshinsky D. Cellulitis: diagnosis and management. Dermatol Ther. Mar-Apr 2011;24(2):229-239.
5. Dupuy A, Benchikhi H, Roujeau JC, et al. Risk factors for erysipelas of the leg (cellulitis): case-control study. Bmj. Jun 12
1999;318(7198):1591-1594.
6. Glover JL, Bendick PJ. Appropriate indications for venous duplex ultrasonographic examinations. Surgery. Oct
1996;120(4):725-730; discussion 730-721.
7. Ray GT, Suaya JA, Baxter R. Microbiology of skin and soft tissue infections in the age of community-acquired methicillin-
resistant Staphylococcus aureus. Diagn Microbiol Infect Dis. May 2013;76(1):24-30.
8. Stryjewski ME, Chambers HF. Skin and soft-tissue infections caused by community-acquired. Clin Infect Dis. Jun 1 2008;46
Suppl 5:S368-377.
9. Doebbeling BN. The epidemiology of methicillin-resistant Staphylococcus aureus colonisation and. J Chemother. Jul 1995;7
Suppl 3:99-103.
10. Schleyer AM, Jarman KM, Chan JD, Dellit TH. Role of nasal methicillin-resistant Staphylococcus aureus screening in the. Am J
Infect Control. Oct 2010;38(8):657-659.
11. Robicsek A, Suseno M, Beaumont JL, Thomson RB, Jr., Peterson LR. Prediction of methicillin-resistant Staphylococcus aureus
involvement in disease. J Clin Microbiol. Feb 2008;46(2):588-592.
12. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency. N
Engl J Med. Aug 17 2006;355(7):666-674.
13. Reber A, Moldovan A, Dunkel N, et al. Should the methicillin-resistant Staphylococcus aureus carriage status be used as. J
Infect. May 2012;64(5):513-519.
14. McKinnell JA, Huang SS, Eells SJ, Cui E, Miller LG. Quantifying the impact of extranasal testing of body sites for methicillin-
resistant Staphylococcus aureus colonization at the time of hospital or intensive care unit admission. Infection control and
hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. Feb 2013;34(2):161-170.
15. Jenkins TC, Sabel AL, Sarcone EE, Price CS, Mehler PS, Burman WJ. Skin and soft-tissue infections requiring hospitalization
at an academic medical center: opportunities for antimicrobial stewardship. Clinical infectious diseases : an official publication
of the Infectious Diseases Society of America. Oct 15 2010;51(8):895-903.
16. Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med. Jan 25 1996;334(4):240-245.
17. Chartier C, Grosshans E. Erysipelas. Int J Dermatol. Sep 1990;29(7):459-467.
18. US Department of Health and Human Services Food and Drug Administration. Center for Drug Evaluation and Research
(CDER). Guidance for Industry- acute bacterial skin and skin structure infections: developing drugs for treatment. Draft
Guidance.August 2010.
19. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med. Apr 24 1995;98(4a):15S-23S; discussion
23S-24S.
20. Babb RR, Spittell JA, Jr., Martin WJ, Schirger A. Prophylaxis of recurrent lymphangitis complicating lymphedema. Jama. Mar 7
1966;195(10):871-873.
21. Kremer M, Zuckerman R, Avraham Z, Raz R. Long-term antimicrobial therapy in the prevention of recurrent soft-tissue. J
Infect. Jan 1991;22(1):37-40.
22. Sjoblom AC, Eriksson B, Jorup-Ronstrom C, Karkkonen K, Lindqvist M. Antibiotic prophylaxis in recurrent erysipelas. Infection.
Nov-Dec 1993;21(6):390-393.
23. Karppelin M, Siljander T, Huhtala H, et al. Recurrent cellulitis with benzathine penicillin prophylaxis is associated with diabetes
and psoriasis. Eur J Clin Microbiol Infect Dis. Mar 2013;32(3):369-372.
24. Semel JD, Goldin H. Association of athlete's foot with cellulitis of the lower extremities. Clin Infect Dis. Nov 1996;23(5):1162-
1164.
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
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26
25. Pauszek ME. Prophylaxis for recurrent cellulitis complicating venous and lymphatic insufficiency. Indiana Med. Apr
1991;84(4):252-253.
26. Koster JB, Kullberg BJ, van der Meer JW. Recurrent erysipelas despite antibiotic prophylaxis: an analysis from case studies.
Neth J Med. Mar 2007;65(3):89-94.
27. Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-
sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clinical
infectious diseases : an official publication of the Infectious Diseases Society of America. Jun 2013;56(12):1754-1762.
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