Download Diagnosis And Management Of Skin And Soft Tissue Infections In

Diagnosis And Management
Of Skin And Soft Tissue
Infections In Children
It’s a typical busy ED afternoon, and the waiting room is full. Your
first patient is a two-year-old boy presenting with “bug bites.” As you
greet the patient’s mother, she tells you that she never should have
bought a home so close to the water, because she doesn’t remember her
oldest son getting as many bug bites as the child with her today. You
take the history and are surprised to learn that the bites are in the
patient’s diaper area. After removing the child’s diaper, you realize that
instead of bug bites he has three areas of cellulitis, one of which appears
fluctuant. You begin to consider what the likelihood is that this child
has contracted an infection with methicillin-resistant Staphylococcus
aureus and how you should best treat it if that is what it is….
S
kin and soft tissue infections are one of the most common
reasons for children to present to the emergency department
(ED). In one study, the authors estimated that over 11 million
ambulatory healthcare visits occur each year for skin and soft tissue infections due to Staphylococcus aureus (S. aureus) alone.1 Yet
these infections have also become some of the most difficult conditions to treat. This is due to new, rapidly emerging patterns of
resistance. When penicillin was first developed in 1941, all S.
aureus isolates were sensitive to it.2 Today, however, S. aureus is
virtually uniformly resistant to penicillin, and the majority of
community-associated staphylococcal infections are becoming
resistant to the semisynthetic penicillins as well. This new wave
of community-acquired methicillin-resistant S. aureus (CAMRSA) is rapidly making obsolete many of the pharmacologic
AAP Sponsor
Martin I. Herman, MD, FAAP,
FACEP
Professor of Pediatrics, UT
College of Medicine, Assistant
Director of Emergency
Services, Lebonheur Children’s
Medical Center, Memphis, TN
Editorial Board
Jeffrey R. Avner, MD, FAAP
Professor of Clinical Pediatrics,
Co-Director of Medical Student
Education in Pediatrics, Albert
Einstein College of Medicine;
Chief, Pediatric Emergency
Medicine, Children’s Hospital
at Montefiore, Bronx, NY
T. Kent Denmark, MD, FAAP,
FACEP
Residency Director, Pediatric
Emergency Medicine; Assistant
Professor of Emergency
Medicine and Pediatrics, Loma
Linda University Medical
Center and Children’s Hospital,
Loma Linda, CA
Michael J. Gerardi, MD, FAAP,
FACEP
Clinical Assistant Professor,
Medicine, University of
Medicine and Dentistry of New
Jersey; Director, Pediatric
Emergency Medicine,
Children’s Medical Center,
Atlantic Health System;
Department of Emergency
Medicine, Morristown Memorial
Hospital, Morristown, NJ
Ran D. Goldman, MD
Associate Professor,
Department of Pediatrics,
University of Toronto; Division
of Pediatric Emergency
Medicine and Clinical
Pharmacology and Toxicology,
The Hospital for Sick Children,
Toronto, ON
Mark A. Hostetler, MD, MPH
Associate Professor,
Department of Pediatrics;
Chief, Section of Emergency
Medicine; Medical Director,
Pediatric Emergency Department, The University of
Chicago, Pritzker School of
Medicine, Chicago, IL
Alson S. Inaba, MD, FAAP,
PALS-NF
Pediatric Emergency Medicine
Attending Physician, Kapiolani
Medical Center for Women &
Children; Associate Professor
of Pediatrics, University of
Hawaii John A. Burns School
of Medicine, Honolulu, HI;
Pediatric Advanced Life
Support National Faculty
Representative, American
Heart Association, Hawaii &
Pacific Island Region
Andy Jagoda, MD, FACEP
Vice-Chair of Academic Affairs,
Department of Emergency
Medicine; Residency Program
Director; Director, International
Studies Program, Mount Sinai
School of Medicine, New York,
NY
Tommy Y. Kim, MD, FAAP
Attending Physician, Pediatric
Emergency Department;
Assistant Professor of
February 2008
Volume 5, Number 2
Authors
Neil G. Uspal, MD
Physician, Department of Emergency Medicine and
Transport, Childrens Hospital Los Angeles, Los
Angeles, CA
Dewesh Agrawal, MD
Assistant Professor of Pediatrics and Emergency
Medicine, George Washington University School of
Medicine; Director, Pediatric Residency Training
Program, Children's National Medical Center,
Washington, DC
Peer Reviewers
Denis Pauze, MD, FACEP
Inova Fairfax Hospital, Falls Church, Virginia; Clinical
Assistant Professor of Emergency Medicine, The
George Washington University School of Medicine,
Washington, DC
Michael Witt, MD, MPH, FAAP
Attending Physician, Division of Emergency Medicine,
Children’s Hospital Boston; Instructor of Pediatrics,
Harvard Medical School, Boston, MA
CME Objectives
Upon completing this article, you should be able to:
1. Name the primary pathogens that cause skin and
soft tissue infections and identify factors which
increase their pathogenicity.
2. Understand the changing epidemiology and
virulence of CA-MRSA infections and discuss
empiric treatment strategies for presumed CA-MRSA
infections.
3. Identify the clinical manifestations of various skin
and soft tissue infections in children.
4. Discuss the controversies and changing paradigms
in medical treatment of skin and soft tissue
infections.
Date of original release: February 1, 2008
Date of most recent review: January 6, 2008
Termination date: February 1, 2011
Time to complete activity: 4 hours
Medium: Print & online
Method of participation: Print or online answer form
and evaluation
Prior to beginning this activity, see “Physician CME
Information” on back page.
Emergency Medicine and
Pediatrics, Loma Linda Medical
Center and Children’s Hospital,
Loma Linda, CA
Brent R. King, MD, FACEP,
FAAP, FAAEM
Professor of Emergency
Medicine and Pediatrics;
Chairman, Department of
Emergency Medicine, The
University of Texas Houston
Medical School, Houston, TX
Robert Luten, MD
Professor, Pediatrics and
Emergency Medicine,
University of Florida,
Jacksonville, FL
Ghazala Q. Sharieff, MD, FAAP,
FACEP, FAAEM
Associate Clinical Professor,
Children’s Hospital and Health
Center/University of California,
San Diego; Director of
Pediatric Emergency Medicine,
California Emergency
Physicians, San Diego, CA
Gary R. Strange, MD, MA,
FACEP
Professor and Head,
Department of Emergency
Medicine, University of Illinois,
Chicago, IL
Adam Vella, MD, FAAP
Assistant Professor of
Emergency Medicine, Pediatric
EM Fellowship Director, Mount
Sinai School of Medicine, New
York
Michael Witt, MD, MPH, FAAP
Attending Physician, Division of
Emergency Medicine,
Children’s Hospital Boston;
Instructor of Pediatrics,
Harvard Medical School,
Boston, MA
Research Editor
Christopher Strother, MD
Fellow, Pediatric Emergency
Medicine, Mt. Sinai School of
Medicine; Chair, AAP Section
on Residents, New York, NY
Accreditation: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education
(ACCME) through the joint sponsorship of Mount Sinai School of Medicine and Pediatric Emergency Medicine Practice. The Mount Sinai School of Medicine is accredited by the
ACCME to provide continuing medical education for physicians. Faculty Disclosure: Dr. Uspal, Dr. Agrawal, Dr. Pauze, and Dr. Witt report no significant financial interest or other
relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. Commercial Support: Pediatric Emergency Medicine does not
accept any commercial support.
strategies ED physicians have been using for these
infections. Additionally, other mutations in the
DNA of S. aureus have made it much more virulent
than before. Infections have become more aggressive, often requiring invasive treatment.
The emergence of CA-MRSA has created a great
deal of controversy about changing treatment paradigms. Many ED physicians now advocate never
using semisynthetic penicillins in treating skin and
soft tissue infections potentially caused by S. aureus,
arguing that it is pointless to treat infections with an
antibiotic to which many pathogens are resistant.
Conversely, others argue that since there have been
no changes in patient’s clinical outcomes on semisynthetic penicillins despite the emergence of CAMRSA, there is no need to change treatment regimens. Other controversies include the role of
incision and drainage (I&D) and the role of
hospitalization.
This issue of Pediatric Emergency Medicine Practice
will focus on the management of children with skin
and soft tissue infections based on the newest and
best available evidence from the literature. This will
include a reappraisal of both the reasons these bacteria have become so difficult to treat and the most
appropriate ways of treating the infections they
cause. This issue will also review some of the more
unusual presentations and pathogens involved in
skin and soft tissue infections and the best ways to
treat them.
STSS: Streptococcal Toxic Shock Syndrome
TMP-SMX: Trimethoprim-Sulfamethoxazole
TSS: Toxic Shock Syndrome
VRE: Vancomycin-Resistant Enterococcus
VRSA: Vancomycin-Resistant S. aureus
Abbreviations Used In This Article
It is difficult to pinpoint the exact number of skin
and soft tissue infections occurring annually, as
many patients are treated in ambulatory care
settings with empiric therapy. One study, based on
National Hospital Ambulatory Medical Care Survey
data, estimated that there were 11.6 million visits to
ambulatory care centers per year between 2001 and
2003 for skin and soft tissue infections, representing
410 visits annually per 10,000 persons.1 Compared
to the period from 1992 to 1994, emergency department visits for skin and soft tissue infections were
up 31%. This may be due to either more virulent
infections or changing patterns of treatment for similar infections. Another study showed that annual
disease incidence for skin and soft tissue infections
caused by MRSA varied between 18 to 26 per
100,000 people between three sites.3
Two specific bacteria, Staphylococcus aureus and
Streptococcus pyogenes (also known as group A streptococcus [GAS]), cause the vast majority of skin and
soft tissue infections. This is especially true in children, in whom one or both of these two pathogens
cause over 90% of these types of infections.4 They
share many of the same mechanisms of pathogenicity but also have a number of mechanisms unique to
each of them. They both also have the ability to
constantly adapt, allowing them to evade both the
Critical Appraisal Of The Literature
The literature review was performed using Ovid
MEDLINE and PubMed searches for articles on skin
and soft tissue infections published between 1950
and 2007, with emphases on literature published
within the past five years and dealing with children.
Keywords included cellulitis, skin disease, MRSA,
soft tissue infection, staphylococcal infections, and
streptococcal infections. Over 230 articles are referenced here, and additional articles were reviewed as
well.
There has been a flurry of articles over the past
five to ten years on MRSA infections, as well as a
healthy amount of literature published on group A
streptococcus and other pathogens. These articles
are typically focused on pathophysiology, although
there are a number of articles on treatment as well.
The literature is much less robust on decisions
regarding inpatient versus outpatient treatment, and
no significant, specific guidelines were found for
children dealing with hospitalization decisions in
the emergency department setting.
Epidemiology, Etiology, And Pathophysiology
APSGN: Acute Postreptococcal Glomerulonephritis
ARF: Rheumatic Fever
CA-MRSA: Community-Acquired (or CommunityAssociated) Methicillin-Resistant Staphylococcus
aureus
D test: Double-Disk Diffusion Test
GAS: Group A Streptococcus, or Streptococcus pyogenes
HA-MRSA: Hospital Acquired (or nosocomial)
Methicillin-Resistant S. aureus
Hib: Haemophilus influenzae type b
I&D: Incision And Drainage
LRINEC: Laboratory Risk Indicator For Necrotizing
Fasciitis
MHC: Major Histocompatibility Complex
MRSA: Methicillin-Resistant S. aureus
MSSA: Methicillin-Sensitive S. aureus
PANDAS: Pediatric Autoimmune Neuropsychiatric
Disorders Associated With Streptococci
PVL: Panton-Valentine Leukocidin Determinant
SCCmec: Staphylococcal Cassette Chromosome mec
SEs: Staphylococcal Enterotoxins
SLO: Streptolysin O
SLS: Streptolysin S
SSSS: Staphylococcal Scalded Skin Syndrome
Pediatric Emergency Medicine Practice©
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February 2008 • EBMedicine.net
body’s natural defenses as well as treatments prescribed and applied by physicians.
syndrome are principally the staphylococcal enterotoxins (SEs).16 They act as superantigens, binding to
both major histocompatibility complex (MHC) class
II molecules on antigen presenting cells and to T-cell
receptors. Staphylococcal scalded skin syndrome
(SSSS) is caused primarily by exfoliative toxins A
and B (ETA and ETB), which act as serum
proteases.17,18 These toxins may be expressed from
any colonizing site; expressed locally they cause
bullous impetigo, while acting systemically they
cause SSSS.
One of the great medical concerns of the past
few years has been the emergence of methicillinresistant S. aureus (MRSA). In 1941, all isolated
strains were susceptible to penicillin. By 1944,
however, the first penicillinase-producing strains of
S. aureus were described.2 The first strains of MRSA
were identified in 1961, and nosocomial MRSA (also
referred to as hospital acquired or HA-MRSA) infections were prevalent in large hospitals by the late
1970s.19 It was not until the late 1980s, however,
that community-acquired (also referred to as community-associated) MRSA (CA-MRSA) strains were
first reported.20 These infections were rare until the
1990s, when CA-MRSA began to increase exponentially in number. By 2004, one study found that CAMRSA was isolated in 59% of emergency department patients with skin and soft tissue infections.21
With the striking increase in CA-MRSA, there
initially existed a concern that nosocomial MRSA
had somehow escaped the hospital and become
prevalent in the community. Instead, the reality is
that CA-MRSA represents novel strains of MRSA
different than those found in the hospital. In both
nosocomial and CA-MRSA, the mecA gene encodes
an altered penicillin binding protein known as
PBP2a, which has decreased affinity for β-lactam
antibiotics.22 This gene is encoded within a mobile
genetic element know as the staphylococcal cassette
chromosome (SCC) mec, containing additional regulatory and insertion genes.23
Four types of SCCmec elements have been characterized. Types II and III contain multiple determinants for resistance to other non-β-lactam antibiotics, and they are typically found in staphylococci
associated with nosocomial MRSA isolates.24 Thus
nosocomial MRSA strains are usually resistant to
commonly used oral antibiotics in children, often
requiring intravenous antibiotic therapy with vancomycin. Type IV SCCmec, on the other hand, does
not contain resistance determinants for non-β-lactam antibiotics. First found in isolates of Staphylococcus epidermis in the 1970s, it was rarely described
in S. aureus isolates before 1990.25 Many identical
elements exist between the SCCmec type IV found in
S. epidermis and S. aureus, suggesting horizontal
exchange of the element between species.26 It is
therefore highly likely that SCCmec type IV crossed
Staphylococcus aureus
Staphylococcus aureus is a Gram-positive coccus present in air, dust, and fomites as well as colonizing
humans and animals.5 It is the most common cause
of skin and soft tissue infections in both adults and
especially children, accounting for over 70% of all
skin and soft tissue infections in the pediatric population.4,6 In humans, the primary site of colonization is the anterior nares,7 but it is also found
around the eyes, perineum, wound sites, circumcision wounds, and the umbilical stump.8 Carriage
rates in humans are extremely high, with 36% of
children documented as carriers in at least one population and over 10% of adults being persistently
colonized.9,10 This nasal carriage makes individuals
more susceptible to infection.11
S. aureus has numerous mechanisms by which it
causes invasive disease. While it is commensal with
other skin flora in a healthy host, a break to the skin
surface allows it access through this protective barrier, allowing it to cause infection. Once in the skin,
S. aureus produces a host of enzymes, such as proteases, lipases, coagulases, and hyaluronidases
which serve to destroy local tissue and may facilitate its spread.12 It also has numerous surface proteins, some of which act as adhesins,5 allowing for
colonization and invasion of host tissue.
A particular virulence factor associated with primary skin infections is the Panton-Valentine leukocidin determinant (PVL).13 While only seen in 2% of
all clinical staphylococcal isolates,14 it is present in
93% of strains associated with furunculosis, 55%
with cellulitis, and 50% with cutaneous abscesses.15
PVL produces two secretory proteins which are
associated with the destruction of human leukocytes
and erythrocytes.
S. aureus also produces toxins that promote systemic disease. Those that cause toxic shock
Figure 1. Staphylococcus aureus
Reprinted from
http://images.forbes.com/images/2004/05/05/staph_aureus_200x15
8.jpg. All rights reserved.
All images in this article are available in color at
http://ebmedicine.net/redirect/?topic=ped
EBMedicine.net • February 2008
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Pediatric Emergency Medicine Practice©
into S. aureus and became prevalent in the community independent of nosocomial MRSA. Multiple
studies show that these CA-MRSA strains with
SCCmec type IV grow faster and achieve higher
infection burdens than nosocomial MRSA.27 This
gives CA-MRSA a selective advantage, allowing it
to thrive in the community where nosocomial
MRSA cannot. The pan-resistance profile that nosocomial MRSA has creates too great a metabolic burden to thrive in the community at large.
CA-MRSA is very different from the nosocomial
MRSA that many feared would cross into the general public. CA-MRSA is a distinct strain of MRSA
presumably selected because of antibiotic use in the
community. As will be discussed later in this article,
non-life-threatening CA-MRSA may be safely and
successfully treated with non-beta-lactam antibiotics
without fear of the pan-resistance found in nosocomial MRSA isolates.
Not only does CA-MRSA have increased antibiotic resistance versus methicillin sensitive S. aureus
(MSSA), it also tends to be more virulent. In one
study looking at bacterial isolates from soft tissue
infections at eleven emergency departments, MRSA
isolates also carried the PVL gene 98% of the time,
while MSSA isolates carried the PVL gene only 42%
of the time.21 Therefore, CA-MRSA is much more
likely to cause aggressive disease than MSSA. This
is evident in the fact that a greater percentage of
skin infections presenting to medical attention contain CA-MRSA21 than is seen in asymptomatic
carriers.9
leading cause of skin and soft tissue infections in
children, accounting for 30% of these type of infections in one study.4 Toxins elaborated by GAS cause
a range of systemic illnesses, from simple scarlet
fever to life threatening toxic shock syndromes. It is
also associated with a number of serious immunologically mediated sequelae, including rheumatic
fever (ARF), acute postreptococcal glomerulonephritis (APSGN), and the controversial pediatric autoimmune neuropsychiatric disorders associated with
streptococci (PANDAS).
Traditionally, streptococci have been subgrouped
by their M protein, and the M protein is one of the
primary means by which GAS combats host immunity. It is a transcellular peptide with two hypervariable regions, both extracellular.30 Based on this
hypervariability, there are at least 124 M genotypes,
with more being described.31 The Lancefield serological classification system is based on M-typing.30
M proteins function primarily by helping GAS
avoid opsonization by the alternative complement
system, thereby preventing phagocytosis.32-34 M
proteins have also been shown to have a role in
GAS adherence35 to and colonization of36 mucosal
tissue.
It has been noted in the past that specific Mtypes of GAS have strong correlations with specific
types of infection and levels of virulence, such as
the association between M-types 1, 3, 12, and 28 and
toxic shock syndrome.37-41 This does not always
hold, however, as pathogenic M-types can often be
found in the throats of asymptomatic individuals.42
Virulence of specific M-types can be altered by the
presence of prophages, which carry virulence
factors horizontally between specific strains of
GAS.43 Additionally, sporadic mutations also alter
the M proteins.43 These factors cause the intra-Mtype variability found in specific strains of GAS.
Therefore, while M-type may have an association
with a specific disease pattern, it is not the only factor in GAS virulence.
Other factors serve to increase GAS infectivity as
well. The GAS capsule is associated with resistance
to phagocytosis.30 Levels of encapsulation vary
between strains of GAS, with those with greater
encapsulation having greater virulence. In one
study, while only 3% of GAS strains causing uncomplicated pharyngitis were capsule-producing
mucoid strains, 21% of the strains that caused serious infection and 42% of the strains that caused
rheumatic fever were.44 Streptolysin O (SLO) is a
protein that is lytic to numerous cell types, including polymorphonuclear leukocytes. It is produced
by almost all GAS strains,30 and immunity developed against it is the basis for the use of anti-streptolysin O titers to determine the past presence of
GAS infection. Streptolysin S (SLS) is similar to
SLO and is one of the most potent cytotoxins
Streptococcus pyogenes
Streptococcus pyogenes, otherwise known as group A
streptococcus (GAS), is a Gram-positive cocci
arranged in pairs and chains.28 It is found on
human skin and mucosal surfaces, is rarely found in
animals, and does not survive outside the human
host.29 In children, it is most commonly associated
with pharyngitis but is also responsible for a wide
range of illnesses, from simple impetigo to rapidly
progressive necrotizing infections. It is the second
Figure 2. Streptococcus pyogenes
Reprinted from
http://www.mgm.ufl.edu/~gulig/mmid/mmid-lab/labimage/spy1.jpg.
All rights reserved.
Pediatric Emergency Medicine Practice©
4
February 2008 • EBMedicine.net
known.45 It acts via direct contact of tissues with
GAS and is an important virulence factor in necrotizing soft tissue infections.46 GAS also secretes
streptokinase which then cleaves plasminogen into
its fibrinolytic plasmin form. Plasmin subsequently
breaks up the localized thrombi which the body utilizes to contain infection.47 In this manner GAS is
allowed improved access to the vascular system to
promote systemic infection. The ability of GAS to
cause systemic inflammatory responses, as in scarlet
fever and streptococcal toxic shock syndrome
(STSS), is mediated by a number of bacterial superantigens.
Finally, much like streptococcal pharyngitis,
streptococcal soft tissue infections can lead to postinfectious sequelae, such as rheumatic fever and
post-streptococcal glomerulonephritis. Most believe
that these disorders are caused by the molecular
mimicry of specific GAS proteins to host-specific
proteins, although the specific mechanism of this is
unknown. Different strains of GAS vary in their
rheumatogenic potential,48 explaining outbreaks of
these diseases after specific outbreaks of GAS infections in a community. APSGN appears to be caused
by a few select strains of GAS,30 while ARF seems to
be caused by GAS whose M protein molecules share
a specific surface exposed antigenic sequence.49
oral flora. Occasionally, oral trauma may allow
Actinomyces to invade soft tissue and cause
infection. Pulmonary and abdominal injury have
also allowed for actinomycotic infection. Disease
progresses from an acute, painful cellulitis to a
chronic, suppurative mass.53 Nocardia, like Actinomyces, is a member of the order Actinomycetales; it
is a common opportunistic infection of those with
weakened immune systems. It can cause cutaneous
infection via traumatic entry of foreign bodies into
the skin, usually soil or decaying vegetation. Infection is typically associated with farm labor.54
Although it is usually seen in the tropics, it can be
found in the southern United States.53 Clinical manifestations vary widely between patients and may
include acute cellulitis, keloid-like lesions, or pustular lesions. Lesions may exhibit periods of
dormancy or may chronically progress, causing
tumor-like masses known as actinomycetomas.55
Sporotrichosis is a fungal skin infection also
initiated by traumatic inoculation through thorns
and other vegetative matter. Infection begins with
formation of an ulcer or nodule at the site of inoculation, with satellite nodules forming along the path
of regional lymphatics.56 The infection may
progress slowly over months, often with significant
delays in diagnosis and treatment.
While S. aureus and GAS cause most wound
infections, atypical pathogens may cause wound
infections as well. Bite wounds present a distinct
set of flora from those found in typical cellulitis.
Human bite infections are composed of a wide
variety of bacterial flora, from Streptococcus viridans
and S. aureus to a wide variety of anaerobes.57
Infections from cat bites, which may cause serious
infection given the depth of cat tooth penetration,
contain predominantly Pasteurella multocida.58 While
dog bites are much more common than cat bites,
they tend to cause infection at a much lower rate.
They also tend to contain Pasteurella species, as well
as S. aureus.59
Other gram-negative and anaerobic bacteria may
cause soft tissue infection as well. These infections
are often times in the perioral or perianal areas,
when these bacteria can be found as part of the normal flora.60 They may also cause secondary infections when the primary condition allows entrance
into the skin, as in eczema, varicella, or trauma.61
Infections caused by these bacteria may range from
simple cellulitis to fulminant necrotizing fasciitis.
Pseudomonas aeruginosa is often associated with
ecthyma, a painful, localized, necrotic infection of
the dermis. Lesions caused by P. aeruginosa are distinct, for often times they have an abscess with a
greenish discharge and a distinct odor.62 In immunocompromised patients, P. aeruginosa septicemia
may cause ecthyma gangrenosum, a condition
where multiple ecthyma are disseminated
Other Pathogens
In the current era of immunization, most simple soft
tissue infections in children are caused by one of the
two organisms described previously. This was not
always the case, however. At one time, Haemophilus
influenzae type b (Hib) was responsible for 25% of
the cases of facial cellulitis in children 3-24 months
of age;50 it is now rare. Nevertheless, there are certain situations where organisms beside the aforementioned two may be causative. In most
instances, the possibility of the presence of these
other organisms may be ascertained through a thorough history and physical examination.
While S. pneumoniae is rarely a cause of primary
skin and soft tissue infections, it may be spread
hematogenously to these areas. There have been a
total of 239 documented cases of pneumococcal cellulitis since 1966, predominantly in children less
than three years old.51 These infections were mostly
periorbital or buccal, with the rest associated with
another localized infection. This may be the tip of
the iceberg for pneumococcal periorbital cellulitis,
however, as most cases of periorbital cellulitis do
not yield positive blood cultures.52 With the advent
of the 7-valent pneumococcal conjugate vaccine, the
number of invasive pneumococcal infections resulting in cellulitis will undoubtedly diminish.
Actinomyces israelii is a slow growing, anaerobic,
gram-positive bacteria which is found in the normal
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Pediatric Emergency Medicine Practice©
throughout the dermis. In an immunocompromised
patient, mortality is high, between 38% and 77%.63,64
Although typically found in patients known to be
immunocompromised, ecthyma gangrenosum may
be the initial presentation of an underlying immunocompromised state.65 P. aeruginosa can also cause
localized soft tissue infection in other circumstances,
including exposure to fresh water or hot tubs, exposure of ear cartilage, or secondary to a puncture
wound through a sneaker.66
Aquatic environments contain bacterial flora distinct from those found in terrestrial areas, which can
cause significant infection. These wounds are still
primarily infected with S. aureus and GAS, but they
can have other pathogens as well. Salt water
wounds may become infected with Vibrio species,
which are facultative anaerobic gram negative
rods.67 Vibrio causes highly aggressive, necrotizing
soft tissue infections that often require surgical
debridement.68 After Hurricane Katrina, at least
seven cases of Vibrio vulnificus infection were
reported, and four of those seven patients died from
their infection.69 Aeromonas hydrophila is another
facultative anaerobic gram-negative rod found in
freshwater sources that causes aggressive
infections.67
Finally, mycobacteria may be responsible for
wound infections not responsive to conventional
antibiotic therapy. Mycobacterium marinum is often
responsible for a slowly progressive, granulomatous
infection in those exposed to aquatic environments;
the infection itself is often referred to as “swimming
pool” or “fish tank” granuloma.70 Other non-tuberculous mycobacteria may also cause infection at
contaminated wound sites several weeks after
trauma.71
epidermolytic toxin into the local tissues.74 The
lesions are superficial, thin walled, fluid filled, and
range in size from 0.5 to 3 cm. They may be found
anywhere on the body. The bullae may rupture,
draining fluid ranging from serous to purulent.75
Fluid aspirated from the lesions may grow S.
aureus.76
Folliculitis, Furuncles, And Carbuncles
Folliculitis represents acute infection of hair follicles,
usually after some sort of chemical or physical
trauma. It is usually caused by S. aureus.77 The
lesion evolves from a superficial erythematous nodule into a central, thin walled pustule with a surrounding red rim.62 The lesions often appear in
clusters and can occur at any age.78 Furuncles, otherwise known as boils, are infections deeper within
the hair follicle. They are painful, erythematous
lesions with a central collection of purulent material
within the hair follicle.12 They are also usually
caused by S. aureus, and their incidence increases
with patient age. As the infection matures, it eventually makes its way to the surface of the skin, and
often drains spontaneously.62 Adjoining furuncles
may coalesce to form a carbuncle, a loculated collection of purulent material that often has multiple
points of drainage.
With the increased prevalence of CA-MRSA in
the community, there has been a recent increase in
skin and soft tissue abscesses, particularly in young
children. As in our opening vignette, the mechanism of infection is often claimed to be a “bug bite,”
although the actual bite is not often witnessed.79 In
fact, many clinicians will erroneously make a diagnosis of “spider bite” instead of bacterial infection.80
Although these abscesses do not originate at the
hair follicle, they too can evolve into either simple
or loculated collections of purulent material.
Differential Diagnosis
Non-Bullous Impetigo
Impetigo, or pyoderma, is a superficial, localized
infection of the skin that is most prevalent in warm
and humid climates. It is extremely common, with
peak incidence between two and six years of age.72
It was believed for many years that GAS was the
primary cause of impetigo; however, numerous
studies have subsequently shown that S. aureus is
isolated in the majority of cases, with GAS present
only in about one-third of cases, usually in association with S. aureus.73 The lesions usually begin as
vesicles that progress to pustules and then to the
characteristic “honey crusted” lesions after rupturing.30 Systemic symptoms are infrequent.
Figure 3. Impetigo
Bullous Impetigo
Bullous impetigo is a disease entity caused exclusively by S. aureus, where the bacteria releases
Pediatric Emergency Medicine Practice©
Reprinted from
http://www.fda.gov/consumer/updates/pics/impetigo_face.jpg.
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February 2008 • EBMedicine.net
Cellulitis
empyema, and brain abscess if not treated promptly
and aggressively.87 Unlike periorbital cellulitis, it is
almost always a secondary complication of sinusitis,
with bacteria crossing the thin lamina papyracea to
infect the orbit. In one series of 41 pediatric
patients, all 41 cases of orbital sinusitis were associated with sinusitis.88 The causative bacterial flora is
therefore the same as that in sinusitis; namely S.
pneumoniae, GAS, S. aureus, non-typeable H. influenzae, M. catarrhalis, and anaerobic bacteria of the
upper respiratory tract.88,89 Clinically, orbital cellulitis presents with the symptoms of periorbital cellulitis but also presents with fever in addition to orbital
manifestations including proptosis, chemosis
(edema of the bulbar conjunctiva), ophthalmoplegia,
pain with extraocular movement, and decreased
visual acuity.90 Diagnosis is often confirmed with
contrast-enhanced orbital computed tomography.
While orbital cellulitis is now occasionally managed
medically,91 early surgical consultation is critical to
possibly prevent the previously mentioned
complications.
Cellulitis is an acute, spreading infection of the dermis of the skin, with minimal involvement of the
epidermis. It typically presents as a painful area of
erythema, swelling, and tenderness. The borders of
the infection site are often not distinct. It most commonly affects the legs and the digits but can also
affect the face, feet, hands, torso, neck, and
buttocks.12 It is typically initiated by some sort of
minor trauma or bite to the skin, which gives bacteria a passageway to invade the soft tissues. Initiating factors in adults, as found in a multivariate
analysis, include obesity, local wounds, and
edema.81 No similar studies exist in children. The
causative pathogen is typically S. aureus but in certain circumstances can also be GAS, Pasteurella spp.,
Aeromonas hydrophila, and Vibrio spp, amongst others.
Systemic symptoms, including fever, may also be
present.
Cellulitis at specific sites has different etiologic
and clinical characteristics and deserves special
mention. Perianal cellulitis appears as a tender,
bright red area circumscribing the anus. It was initially thought to be principally caused by GAS,
based on anal skin cultures.82 More recent research,
performed by needle aspiration, has shown a variety of flora, including Escherichia coli, Peptostreptococcus species, S. aureus, and Bacteroides fragilis.83 It is
important to be able to distinguish perianal cellulitis
from sexual abuse. Odontogenic infections often
cause a profound ascending cellulitis. GAS is the
most common cause of these infections, followed by
Neisseria and diphtheroids.84,85 Patients have typically had chronic dental caries prior to the onset of
acute infection. These infections are typically
treated both with antibiotics and with dental extraction, though extraction may be deferred until after
the infection has been treated.86
Erysipelas
Erysipelas is a soft tissue infection distinct in character from typical cellulitis. It is an infection of layers
of skin and cutaneous lymphatics that are superficial to the typical area of cellulitis infection. The
area of infection is raised compared to the surrounding skin, and there is a distinct margin between
affected and non-affected areas.30 The skin itself is
fiery red and has what is often described as a “peau
d’orange” appearance.28 Contrary to conventional
wisdom, over 85% of cases of erysipelas occur in the
arms and legs and not in the face.92 It is caused
almost universally by streptococcal species, usually
GAS.
Necrotizing Fasciitis
Periorbital And Orbital Cellulitis
Necrotizing fasciitis, while rare, is the most aggressive manifestation of skin and soft tissue infections
Periorbital, or preseptal cellulitis, is a superficial
infection of the soft tissues anterior to the orbital
septum. It presents with tenderness, swelling, and
induration of the peri-orbital tissues but does not
involve the globe or retro-orbital structures. It can
arise either from the ascension of soft tissue infection inferior to the eye, direct inoculation, or
hematogenously. Less commonly, periorbital cellulitis may result as a complication of sinusitis. Over
75% of reported cases of pneumococcal cellulitis in
children are periorbital.51 It may be treated
medically with antibiotics.
Periorbital cellulits must be distinguished from
orbital cellulitis, which involves infection of the soft
tissues posterior to the orbital septum. Orbital cellulitis is an emergency, as it can cause blindness,
cavernous sinus thrombosis, meningitis, subdural
EBMedicine.net • February 2008
Figure 4. Periorbital Cellulitis
Reprinted from
http://www.icoph.org/med/medimages/H43.jpg. All rights reserved.
7
Pediatric Emergency Medicine Practice©
and can cause significant morbidity and mortality.
It is an infection of the superficial fascia, often initiated by trauma to the integumentary system, such
as a laceration, insect bite, needle puncture, or surgical wound.93 In children, risk factors for necrotizing
fasciitis include malnutrition and varicella infection,61 although it also occurs in young people with
no risk factors.94 A wide variety of bacteria can
cause necrotizing fasciitis, with multiple organisms
typically found at the infection site. GAS is the
most common organism found in necrotizing fasciitis in both children61 and adults,95 with enterococcus, enterobacteriaceae, and anaerobic species
common as well. Recently, S. aureus, particularly
CA-MRSA, has been causing an increasing number
of cases of necrotizing fasciitis as well.96
While late manifestations of necrotizing fasciitis
are clinically obvious, early disease is difficult to
distinguish from more typical cellulitis. In some
instances a rash may not be present at all.97 Unlike
patients with simple cellulitis, however, patients
with necrotizing fasciitis tend to have pain that is
out of proportion to their other clinical symptoms.
Patients often reportedly complain of aches, chills,
and feverishness.97 Additionally, many adult
patients have abnormal vital signs at presentation.
In one series of 15 mostly adult patients whose
necrotizing fasciitis was missed at initial presentation, 73% were tachycardic (HR > 90) and 18% were
hypotensive (SBP < 90).97 Laboratory values are
often abnormal, and normal laboratory values may
be used to rule out necrotizing fasciitis. In the adult
population, a tool called the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score has
been developed. It looks at variables such as CRP,
WBC count, hemoglobin, creatinine, and glucose in
order to not miss patients at risk for having necrotizing fasciitis early in their disease course.98 In subsequent studies using the LRINEC, it had a positive
predictive value of 40% and, more importantly, a
negative predictive value of 95%.99
Once necrotizing fasciitis reaches an advanced
stage, the diagnosis becomes more apparent. Within
48-72 hours of the onset of symptoms, the overlying
skin develops either serous discharge or hemorrhagic blistering.61 Soon after, necrosis develops; by
the fifth or sixth day of disease, a necrotic plaque
develops over the affected area.100 Localized anesthesia due to nerve damage may be present as well.
Patients can become septic during this time, often
with high fevers, mental status changes, and multiple organ failure.61 Mortality rates are highly variable, with reports in children ranging from 18% to
45%.61,101
Toxin-Mediated Diseases
While not skin infections per se, superantigen mediated diseases often are secondary to localized skin
infections and merit mention. Staphylococcal
scalded skin syndrome (SSSS) is a blistering skin
disorder caused by exfoliating toxins produced by
S. aureus.102 Individuals with antibodies to these
toxins have merely the localized reaction of bullous
impetigo. Individuals without these antibodies,
however, have release of these toxins into the blood
stream, causing systemic disease. Affected individuals are usually children under five years of age.75
Clinical manifestations include fever and erythema
that evolves into easily ruptured blisters, leaving
denuded skin.12 This denuded skin surface may
serve as a pathway for secondary infection.
Toxic shock syndrome (TSS) is a superantigen
mediated disease causing fever, rash, hypotension,
and potentially multi-organ failure. It may be
caused either by S. aureus or GAS. While outbreaks
of staphylococcal TSS were initially associated with
super-absorbent tampon uses, staphylococcal TSS is
now more typically associated with skin infection,
post-partum trauma, and pneumonia.103 The annual incidence of staphylococcal TSS is now only 0.5
Figure 5. Orbital Cellulitis
Figure 6. Necrotizing Fasciitis
(a) proptosis, (b) soft tissue inflammation, (c) choroidal detachment,
(d) retrobulbar inflammation, and (e) optic nerve sheath
enhancement. Reprinted from
http://www.nature.com/eye/journal/v21/n7/images/6702815f1.jpg.
All rights reserved.
Pediatric Emergency Medicine Practice©
Reprinted from
http://www.jyi.org/articleimages/463/originals/img0.jpg. All rights
reserved.
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February 2008 • EBMedicine.net
Children who have had extensive hospitalizations
may be colonized with nosocomial MRSA,109 and
this may affect empiric antibiotic choice and
effectiveness.
Another critical question to ask is whether or not
a patient has a history of trauma at the site of infection. Bites, be they animal or human, introduce
unique pathogens into soft tissues, which may cause
infection. If a hand infection is being treated, it is
important to ascertain a history of physical altercation and trauma caused by clenched-fist injuries57
especially in male adolescents, as lacerations resulting from contact with teeth must be treated similar
to bite wounds. Wounds which are deeper than
subcutaneous tissue, have jagged edges, are visibly
contaminated, or contain foreign bodies have all
been shown to have significantly increased rates of
infection.110 Dirty wounds may lead to infection
with gram negative bacteria, anaerobes, or
mycobacteria, especially if a significant amount of
time since the trauma has elapsed before presentation,71 complicating antimicrobial treatment.
Wounds obtained in aquatic environments are especially worrisome for unique pathogens, so a history
of trauma in this kind of environment should be
determined.
On physical examination, the general appearance of the patient should first be noted. Ill appearing children, especially infants, necessitate a more
complete workup and more aggressive therapy.
Mental status changes especially may be the result
of toxic shock or septic shock. The appearance of a
generalized rash may indicate a toxin-mediated illness or could point to the primary cause of a
secondary bacterial infection, as in varicella and
eczema. Vital signs should be observed for fever,
tachycardia, and changes in blood pressure. The
site of the infection should be examined, with careful attention paid to the characteristics and size of
the lesion. In the adult population, an area of erythema greater than 0.1 m2 (1000 cm2) has been associated with increased length of hospital stay.111 The
area of infection should be palpated, taking note of
any fluctuance indicating the need for incision and
drainage of the infection site. Additionally, pain out
of proportion with the clinical finding is concerning
for necrotizing fasciitis.
cases per 100,000.104 In staphylococcal TSS, patients
develop acute onset of fever, chills, malaise, muscle
tenderness, hypotension, and a diffuse macular
rash.105 Disseminated intravascular coagulation
(DIC) and end organ failure may develop, as well as
anemia, thrombocytopenia, and leukocytosis. Skin
desquamation occurs 7-14 days after disease
onset.105 Mortality ranges from 3% to 5%.105
Streptococcal TSS has a few key features that distinguish it from staphylococcal TSS. Most patients
are previously healthy but present with a deepseated GAS infection. About 50% of adult patients
have necrotizing fasciitis at presentation,106 but children tend to present with different infections, such
as bacteremia without focus, osteomyelitis, or a
CNS infection.107 Patients with streptococcal TSS,
unlike those with staphylococcal TSS, often present
with severe, localized pain that often precedes localized evidence of infection.103 Patients also present
with high fevers, confusion, and striking vital sign
changes, with hypotension and tachycardia common.37,108 Bacteremia is much more common in
children with streptococcal TSS, around 60%, and
mortality is also higher in children with streptococcal than in staphylococcal TSS, with rates ranging
from 5% to 10%.105
Prehospital Care
Most children with skin and soft tissue infections
will walk into the emergency department; however,
this does not preclude the possibility of a critically
ill child with the skin and soft tissue as the primary
source of his or her infection. First, as always, a
quick evaluation of airway, breathing, and circulation should be undertaken. Children with septic
shock, toxic shock, or with rapidly progressive,
necrotizing infections require rapid resuscitation. In
these patients, fluid management is the most important initial management step, especially in the field.
The use of pressors is also indicated if multiple
boluses of crystalloid or colloid fail to stabilize the
patient’s blood pressure. If a child is critically ill,
transport to a pediatric facility with the appropriate
critical care facilities is essential.
ED Evaluation
As with most conditions, a through history and
physical examination are the most important aspects
of diagnosis. A generalized medical history is
important in order to ascertain whether or not a
patient has any medical problems that may affect
disease progression, such as HIV and other sources
of immunocompromised status, including malignancies, sickle cell anemia, diabetes mellitus, asplenia, and iatrogenic immunosuppression. One of the
most critical questions that can be asked is whether
or not a patient has had a recent hospitalization.
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Diagnostic Studies
Laboratory and diagnostic tests will vary based on
the severity of the infection. For simple skin infections without systemic symptoms, such as impetigo,
no laboratory workup will be needed in most children. Simple cellulitis may be treated without significant laboratory work-up up as well. Multiple
studies have evaluated the utility of blood cultures
in cellulitis. In general, blood cultures are rarely, if
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Pediatric Emergency Medicine Practice©
ever, useful in cellulitis cases. Cultures were positive in only 2-8.3% of immunocompetent adults
with cellulitis, with none documented as leading to
changes in antibiotic therapy as a result of positive
blood cultures.112-117 In children, one study showed
similar results, with only 2% of blood cultures being
positive, while 5.4% contained contaminants. Only
one positive culture out of 243 total, in a patient
who also had a septic hip and psoas abscess,
resulted in a change to the antibiotic regimen.118
Fine needle aspiration of cellulitis sites for culture does have a higher yield than blood cultures,
yet results are still only positive 28.5-51.7% of the
time.119-121 In children, aspiration yields have been
shown to be greatest at the point of maximal inflammation of the cellulitis and not at the leading edge
of infection as previously thought.121 In adults, the
yield of fine-needle aspiration has been shown to be
greatest in patients with concurrent medical conditions that lead to cellulitis;122 however, these conditions are uncommon in children. Results of positive
cultures were usually either S. aureus or GAS, with
the lone exception in a pediatric study being H.
influenzae121 in a sample obtained prior to the use of
the Hib vaccine.
For more concerning infections, blood tests may
be warranted. In a study in the adult population,
length of hospital stay independently increased with
absolute neutrophil count greater than
10,000/mm3.111 In one study, children with necrotizing fasciitis tended to be anemic (mean hematocrit
of 29%), have elevated WBC counts (mean WBC of
16,552/mm3), and have a bandemia (mean percentage bands of 4%).61 In adults, abnormalities in laboratory values in patients with necrotizing fasciitis
are even more striking, with significant abnormalities in WBC count (24.5 ± 16.0 x 109/L), sodium (133
± 5 mmol/L), and BUN (22 ± 16 mg/dL).123 Toxic
shock syndrome can also manifest in highly abnormal laboratory values. While in TSS the total WBC
count may be normal, there may exist a striking
bandemia, with immature forms exceeding 50%.108
Additionally, particularly in late disease, end organ
hypoperfusion may manifest in elevated creatinine
levels37,108 and other markers of multiorgan failure.
Radiology may have a small but significant role
in the evaluation of soft tissue infections. Plain
roentgenograms have been shown to reveal
subcutaneous emphysema in 39% of patients with
necrotizing fasciitis;123 however, the low sensitivity
of this test makes it of low utility. Plain films may
also be useful when trying to distinguish between a
chronic cellulitis and an osteomyelitis and to look
for retained, radio-opaque foreign bodies in trauma.
Computerized tomography has been demonstrated
to have a higher yield than plain films in identifying
subcutaneous gas in necrotizing fasciitis.124 CT is
also the modality of choice to distinguish periorbital
Pediatric Emergency Medicine Practice©
from orbital cellulitis.125 MRI is excellent in distinguishing necrotizing fasciitis from cellulitis. In one
study, it had 100% sensitivity and 86% specificity.126
However, its frequent lack of immediate availability
and the need for sedation in children make it
impractical when rapid surgical intervention may be
needed.
Ultrasound has also been advocated for diagnostic purposes. Chao et al demonstrated that
ultrasound findings of tissue distortion with or
without pus accumulation in children with cellulitis
correlated with longer duration of symptoms and
the presence of higher fever, WBC counts, and Creactive protein level.127 The study did not show
how these findings affected clinical decision making, however. The study also found that patients
who underwent either ultrasound-guided or surgical drainage of abscesses had shorter hospital stays
and fever duration then those who were just treated
medically with antibiotics.127
Tayal et al showed how ultrasound of patients
with clinical cellulitis in the emergency department
could change patient management. In this study of
adult patients, 56% (71/126) had their pretest management plan altered after ultrasound of the
cellulitic area, with some patients receiving previously unplanned drainage, some having drainage
deferred, and some receiving further diagnostics or
consultation. The pretest probability of the presence
of fluid before drainage increased from 10% to 90%
after ultrasound.128 As more pediatric emergency
room physicians become acquainted with bedside
ultrasound, the use of this technology will undoubtedly increase.
Treatment
Impetigo
A wide variety of treatments have been suggested
for simple, non-bullous impetigo, ranging from
observation to systemic antibiotics. A Cochrane systematic literature review was recently performed on
the treatment for impetigo.129 It showed that topical
mupirocin and fusidic acid (which is not
commercially available in the United States) are
either as effective as or more effective than systemic
antibiotics with less side effects. Interestingly, bacitracin seems to be inferior to mupirocin and fusidic
acid. No evidence exists to support the use of disinfectants, such as chlorhexidine, in the treatment of
impetigo.130,131
Simple Abscesses And Cellulitis
A mainstay of therapy in the treatment of soft tissue
abscesses is incision and drainage (I&D) of the fluid
collection. Controversy has existed for some time as
to the efficacy of I&D alone in the treatment of
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February 2008 • EBMedicine.net
simple soft tissue abscesses. In the pre-MRSA era, a
number of trials demonstrated that I&D by itself
was equivalent to I&D plus oral antibiotics in the
management of soft-tissue infections.132-134 However, there have been no comparable studies in the
CA-MRSA era. With the associated increase in virulence often seen in strains of MRSA, many are hesitant to treat abscesses that may be infected with
MRSA solely with I&D for fear of inadequately
treating a highly virulent pathogen. A number of
studies, however, have illustrated that many physicians are treating skin abscesses which eventually
grow MRSA with first and second generation
cephalosporins.3,135,136 In these cases, no adverse
outcomes have been reported despite the pathogen’s
resistance to the prescribed antibiotics.
Some have therefore proposed that this is adequate evidence that small (< 5 cm) abscesses without surrounding cellulitis in immunocompetent
children may be treated with I&D alone and without antibiotics.135 The lack of a definitive study confirming this hypothesis, however, means that adequate patient follow-up must be assured prior to
discharging patients after draining abscesses without antibiotic prescription.
Controversy also continues to exist regarding
antibiotic choice in the treatment of skin and soft
tissue infections. Rates of MRSA have grown exponentially over the past 10 years. Despite this, many
practitioners have continued to treat patients with
cephalosporins, which should in theory not adequately treat these infections. Yet there has not been
a documented concomitant increase in complications from skin and soft tissue infections. In one
study comparing cefdinir versus cephalexin, (two
cephalosporins to which CA-MRSA should be resistant) in a variety of skin and soft tissue infections in
immunocompetent patients, clinical cure rates were
93% and 91% for the two antibiotics when treating
MSSA, but also 91% and 90% when treating CAMRSA.137 Even in infections that were treated without incision and drainage, there existed in another
study no significant difference in need for follow up
visits, subsequent incision and drainage, or
antibiotic change in patients prescribed either active
or inactive therapy.3 It is unclear whether or not
this is due to the self-limited nature of most simple
skin and soft tissue infections or some partial in vivo
efficacy of cephalosporins in treating CA-MRSA
despite its resistance pattern in vitro.
Without the existence of studies treating cellulitis
with observation only, cellulitis of any significance
still merits systemic antibiotic therapy. Phillips et al
recently did a cost analysis of empiric antimicrobial
strategies for cellulitis in adults in the MRSA era
based on medication costs, MRSA prevalence, and
probabilities for treatment failure.138 The authors
concluded that for what they considered the base
EBMedicine.net • February 2008
prevalence for MRSA (27%), cephalexin was the
most cost-effective antimicrobial therapy. The major
flaw with this study, however, is that it underestimates the ever increasing prevalence of MRSA in
the community. While some authors are still
reporting recent base prevalences of MRSA at
around 20%,3 many others are reporting rates up to
37%,139 51%,140 and 74%.21 In the ED-based study
by Moran et al, 9 of 11 communities have MRSA
base prevalence rates of 50% or greater.21 Additionally, the Phillips et al study used only a 37% likelihood that cellulitis is caused by S. aureus.138 While
this figure may be appropriate in adults, it is not
applicable in children, where the likelihood of S.
aureus being the etiologic agent in skin infections is
much higher (> 70%)4,6 than 37%. After adjusting
the likelihood of S. aureus to 70%, as appropriate for
children, and the base prevalence of MRSA to a
more realistic 50%, the model employed by Phillips
et al would make empiric treatment with
clindamycin more cost effective than cephalexin for
cellulitis. That, along with the intrinsic sense it
makes to use an antibiotic that MRSA is sensitive to
in vitro to treat cellulitis, makes a non-beta-lactam
antibiotic the preferable therapy for skin and soft
tissue infections in children.
Of the non-beta-lactam antibiotics available, clindamycin has many advantages for empiric treatment. It is active against both aerobic gram-positive
(including GAS and S. aureus) and anaerobic bacteria.19 Clindamycin is highly active against CAMRSA, with susceptibilities ranging from 83% to
97%.3,136,141-143 It does have a few down sides,
though. Dosing is every six to eight hours, and the
liquid formulation has a poor taste that may affect
compliance in children. Additionally, a proportion
of CA-MRSA that are resistant to erythromycin have
inducible clindamycin resistance. In these bacteria,
the mutation that causes erythromycin resistance
may evolve to also cause clindamycin resistance
during clindamycin therapy.144 To exclude
inducible clindamycin resistance, the double-disk
diffusion test (D test) should be performed on all
clindamycin isolates that are resistant to
erythromycin to exclude this inducible resistance.145
There exists a wide variation in reported rates of
inducible resistance to clindamycin in erythromycin-resistant MRSA, with some studies having rates
below 10%,141,142,146 while others had rates that were
significantly higher.147-149
Trimethoprim-sulfamethoxazole (TMP-SMX)
also has high activity against CA-MRSA, with susceptibilities between 83% and 99% at different
sites.3,136,141-143 TMP-SMX, unlike clindamycin, is
not active against GAS. Therefore, it should not be
used as monotherapy when GAS infection is in the
differential diagnosis. Rifampin is another antibiotic to which CA-MRSA is highly susceptible.3,142,143
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Pediatric Emergency Medicine Practice©
It is potentially hepatotoxic,19 however, and may
induce resistance if used as monotherapy.150 CAMRSA is also usually susceptible to tetracycline and
doxycycline, with susceptibilities in CA-MRSA
ranging from 55% to 92%.3,136,143 However, tetracycline antibiotics are contraindicated in pediatric
patients under eight years of age, due to concerns
for tooth staining and decreased bone growth. CAMRSA is highly resistant to erythromycin,3,141-143
and it should not be used in the treatment of skin
and soft tissue infections. Likewise, rising GAS
resistance to erythromycin has been reported.151
observed for disease improvement. Intravenous
clindamycin is often given empirically in this setting
not only for its excellent coverage of GAS and CAMRSA infection, but also for its ability to inhibit
protein toxin production.
Those patients who do appear septic, however,
should be treated with antibiotics to which grampositive bacteria are highly susceptible. Intravenous
vancomycin has traditionally been the mainstay of
therapy for empiric treatment of serious life- or
limb-threatening skin and soft tissue infections.
Concern continues to grow, however, about the
development of vancomycin-resistant S. aureus
(VRSA). At least three cases of VRSA have been
reported in the literature in the United States so
far.154-156 Additionally, vancomycin has been shown
to be less effective than beta-lactams in the
treatment of MSSA endocarditis.157 Therefore, the
addition of rifampin or gentamicin should be considered for synergistic effect in treating serious
infections thought to be secondary to S. aureus.19
Linezolid is another option in the treatment of
serious skin and soft tissue infections. It has activity
against MRSA, GAS, S. pneumoniae, vancomycinresistant enterococcus (VRE), anaerobic bacteria,
and some activity against rapidly growing mycobacteria.12 Linezolid comes in both oral and parenteral
forms. There exists mixed evidence on the comparative effectiveness of vancomycin and linezolid in
the treatment of serious soft tissue infections. Two
studies showed linezolid to be significantly superior
to vancomycin in seven day cure rates of surgical
site infections158 and complicated skin and soft tissue infections159 in adults. Other studies, however,
have shown no significant difference between linezolid and vancomycin in the treatment of soft tissue
infections in children160 or adults.161 Some theorize
that there exists intermediate resistance to vancomycin in some MRSA isolates, and this explains the
apparent superior efficacy of linezolid in the treatment of MRSA infections in some studies.162
Other antibiotics have been used in the treatment of serious MRSA infections as well.
Quinupristin-dalfopristin is bacteriocidal against
gram-positive bacteria, including MRSA and VRE.
It is approved for treatment of complicated skin and
soft tissue infections and right-sided bacterial
endocarditis in adults.163 Its use in children, however, has been highly limited.164 Another potentially
useful antibiotic is tigecycline. It is also active
against gram-positive bacteria, including MRSA and
VRE, as well as gram-negative, anaerobic, and atypical bacteria. There is currently no data supporting
its use in children under 18 years of age.19 No matter what therapy is chosen, it is important to obtain
emergent infectious disease consultation prior to
initiating any of these therapies in severe infections.
Orbital And Periorbital Cellulitis
Treatment of periorbital cellulitis may vary depending on the source and severity of infection. Most
cases of periorbital cellulitis can be safely managed
in the outpatient setting with oral antibiotics such as
amoxicillin-clavulanate, cephalosporins, or
clindamycin. If the source of the cellulitis is clearly
local trauma, then the antibiotic regimen should
cover gram-positive organisms.90 If the patient is
systemically ill, however, the causative organism is
very likely Streptococcus, and both GAS and Streptococcus pneumoniae should be empirically covered in
the inpatient setting with intravenous antibiotics
such as ceftriaxone, ampicillin-sulbactam, or
clindamycin.152
Orbital cellulitis, on the other hand, is a much
more serious condition and requires more aggressive inpatient treatment. Orbital cellulitis originates
almost uniformly from sinusitis; for this reason,
antibiotics that cover S. pneumoniae and other organisms found in the sinuses are indicated. Typical
choices for empiric intravenous therapy include
ampicillin-sulbactam or ceftriaxone, either alone or
with the addition of clindamycin. Since orbital cellulitis often requires surgical intervention, immediate consultation with pediatric ophthalmology and
otolaryngology should be sought.153 While the therapeutic approach to orbital cellulitis in the past had
been mostly surgical, conservative medical management with broad spectrum antibiotic therapy is
being increasingly used with good success,91 with
one small study showing successful outcomes in 9
of 10 patients treated with medical therapy alone.
Severe Skin And Soft Tissue Infections
Patients with vital sign abnormalities, mental status
changes, lethargy, rapidly progressing disease, fever,
chills, or any other concerning symptoms should be
treated aggressively with parenteral antibiotics.50
Also, children with significant comorbidities, such
as asplenia or immunocompromised status, should
be treated with IV antibiotics as well. Patients who
have concerning infections but otherwise do not
appear septic may be treated with IV antibiotics and
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Clinical Pathway: Management Of Children With Skin
And Soft Tissue Infections In The CA-MRSA Era
Concern for necrotizing fasciitis?
Emergent surgical
consultation. (Class I)
YES
NO
Toxic appearance OR
Immunocompromised OR
Limb-threatening infection?
• Hospitalize.
• Fluid and/or vasopressor support as
needed. (Class I)
• Empiric IV vancomycin. (Class II)
• Infectious disease consult. (Class III)
YES
NO
• Incision & drainage (as
indicated). (Class I)
• Obtain specimen for culture and
susceptibility testing. (Class III)
Simple impetigo?
YES
Discharge on
topical mupirocin.
(Class I)
YES
Febrile or ill
appearing?
NO
Bite wound?
YES
NO
If no surrounding
cellulitis, I&D alone
may be adequate
treatment. (Class III)
YES
Afebrile, previously
healthy patient and
lesion of reasonable
size?
NO
• Oral antibiotic Rx. (Class II)
TMP/SMX + amoxicillin
Or
Clindamycin
Or
Doxycycline ( ≥ 8 years
of age)
• Close follow-up
Admit on
empiric
ampicillinsulbactam
OR
ticarcillinclavulanate.
(Class II)
NO
Discharge on
amoxicillinclavulanic
acid.
(Class II)
• IV clindamycin or IV vancomycin.
(Class II)
• Consider admission to observation
unit or inpatient floor. (Class II)
• Infectious disease consult if no
improvement in 24 hours. (Class III)
The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely
recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III:
May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a
patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2008 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of
EB Practice, LLC.
EBMedicine.net • February 2008
13
Pediatric Emergency Medicine Practice©
Necrotizing Fasciitis
In toxic shock syndrome (TSS), the first priority
of therapy is establishing hemodynamic stability in
patients. Patients are often in profound shock secondary to capillary leakage and require multiple
boluses of crystalloid or colloid.103 Vasopressors
may also be indicated. Possible sources of infection
must be investigated and addressed. A vaginal
examination should be performed on all female
patients to ensure a foreign body is not the nidus of
infection. Areas of necrotizing fasciitis or abscess
should be urgently debrided or incised and
drained.105 Clindamycin is a mainstay of therapy
for TSS whether caused by GAS or staphylococcus.
Since clindamycin works by reducing protein
synthesis, it acts to halt toxin production, thereby
limiting disease.176 If GAS is known to be the cause
of TSS in a patient, clindamycin may be used along
with parenteral penicillin in treatment. In patients
in whom S. aureus-associated TSS is suspected,
vancomycin should be added to clindamycin in
areas where MRSA infections are common;177 otherwise, a beta-lactamase resistant anti-staphylococcal
antibiotic may be used.
Patients with necrotizing fasciitis often deteriorate
extremely rapidly. Morbidity and mortality rates in
necrotizing fasciitis remain extremely high, with one
recent study reporting a 17% mortality rate, with
limb loss occurring in an additional 26% of adult
patients.165 A recent pediatric series reported
similar data, with mortality at 18%.61 Immediate
stabilization begins with circulatory support with
vasopressors in addition to crystalloid infusions if
the patient presents in shock.166 Once hemodynamically stabilized, the patient should be taken to
the operating room as soon as possible for surgical
debridement of affected tissue. One study demonstrated a doubling of adult patient mortality when
surgical debridement was delayed for more than 24
hours.167
Antibiotics have little effect prior to surgical
debridement, secondary to the poor vascular supply
reaching necrotic tissue.168 If antibiotics are initiated
in the emergency department, however, they should
cover gram-positive organisms and gram-negative
aerobes and anaerobes. For many years, a broad
spectrum beta-lactam antibiotic along with
clindamycin was thought to be adequate therapy;
however, with the reported emergence of MRSA as
a causative pathogen of necrotizing fasciitis,96 it is
no longer so. A regimen consisting of vancomycin,
clindamycin, and a broad spectrum antibiotic covering gram-negative and anaerobic organisms would
be appropriate therapy. Clindamycin is added for
“the Eagle effect:” its ability to control toxin production in slowly metabolizing bacteria.169 Hyperbaric
oxygen therapy has also been used to treat necrotizing fasciitis, but its efficacy is controversial.170
Atypical Pathogens
The vast majority of these pathogens will be difficult to identify in a busy emergency department.
Consultation with an infectious disease specialist is
recommended prior to initiating treatment. Nevertheless, knowledge of the treatments of these
pathogens may be helpful both in initiating new
therapy and treating patients who have already
begun therapy but have returned to the emergency
department for further treatment.
Actinomyces causes the chronic presence of
“wooden” appearing, suppurative nodules in skin
and soft tissues. It may be identified by either the
“sulfur granule” like material that it drains or by
culture.178 Treatment is high dose intravenous penicillin for two to six weeks, followed by oral penicillin for an additional 6-12 months.53 Similarly,
Nocardia can cause a chronic, suppurative cellulitis
or pyoderma that may be cultured on simple media.
Treatment is with sulfonamides, such as TMP-SMX,
for one to three months.53 Subcutaneous infection
from Sporothrix schenckii causes sporotrichosis, characterized by either a solitary nodule or group of
nodules along the local lymphatic track. It may be
treated with either itraconazole or saturated solution of potassium iodide, with treatment lasting
three to six months.179
Anaerobic infections are often associated with
abscesses or necrotizing fasciitis, so drainage or surgical debridement of affected areas is essential. For
many years, penicillins were the treatment of choice
for anaerobic infections, but resistance to these
antibiotics is increasing.60 Treatment for most
Toxin-Mediated Disease
The primary treatment for staphylococcal scalded
skin syndrome (SSSS) is medical pharmacotherapy.
Most children without extensive skin involvement
can be managed with outpatient oral antibiotics.
While multi-drug resistance is rare in the
staphylococcal strains causing SSSS,171 there have
been multiple reports of MRSA causing SSSS.172-174
Therefore, if a cephalosporin or anti-staphylococcal
penicillin is used to treat SSSS, careful follow-up
must be assured. New lesions may appear 24-48
hours after the initiation of therapy, but should not
be observed thereafter.102 Blisters from the rash
should be kept intact; areas where blisters have
erupted may be dressed with petroleumimpregnated gauze.171 More severely affected
patients may need to be admitted for parenteral
antibiotics as well as pain, temperature, fluid, electrolyte, and nutritional management. Very badly
affected patients may require admission to a burn
unit for further management.175
Pediatric Emergency Medicine Practice©
14
February 2008 • EBMedicine.net
anaerobic skin and soft tissue infections should also
cover aerobic gram-positive bacteria, since they are
often concomitant pathogens. Simple infections
may be treated with clindamycin, with optional
addition of a second or third generation cephalosporin for additional gram-negative coverage.
Ertapenem is a newer class I carbapenem with good
coverage against both aerobic and anaerobic
organisms180 and may be used as well. Other
options include penicillin-beta-lactamase-inhibitor
combinations (such as ampicillin-sulbactam,
piperacillin-tazobactam, or ticarcillin-clavulanate)
and linezolid for severe infections.66
Pseudomonas infections require treatment with
antibiotics with anti-pseudomonal activity. Ill
children with ecthyma gangrenosum should be recognized immediately as having a potentially lifethreatening condition and should be treated aggressively,181 particularly in immunocompromised
children. For severe or systemic infections, an
aminoglycoside, such as tobramycin, amikacin, or
gentamicin, plus an anti-pseudomonal cephalosporin, such as ceftazidime or cefepime, as
indicated.182 For more localized infections, topical
antibiotics or hot compresses with 2% acetic acid
may be used.183 In patients age 18 or over,
ciprofloxacin is a useful antibiotic as well, as it is
available in both oral and intravenous formulations.
Salt water wounds infected with Vibrio species
must be treated aggressively because even superficial wounds can progress to necrotizing soft-tissue
infections.68 Wounds exposed to seawater demonstrating a rapidly progressing cellulitis should be
treated as Vibrio infectious until proven otherwise.67
Immediate surgical debridement should be undertaken, and patients should be treated with parenteral antibiotics. In children eight years of age or
greater, the recommended antibiotic regimen is a
tetracycline, typically doxycycline, and ceftazidime.67 In children under this age, treatment decisions are more difficult. While Vibrio is sensitive to
all third-generation cephalosporins,184 the severity
of patient illness may dictate using a tetracycline as
well. In at least one case report, doxycycline was
used in this manner.185 Aeromonas hydrophila
infected wounds can also develop rapidly progressive cellulitis or myonecrosis.28 Rapidly progressing
wounds exposed to freshwater in children should be
treated with a third or fourth generation cephalosporin that also covers Pseudomonas.186
Treatment for atypical mycobacterial infections
varies based on the species identified. No specific
treatment regimen has been established for Mycobacterium marinum infections. Examples of regimens
that have been used in clinical practice include
tetracyclines, TMP-SMX, and rifampin plus ethambutol.70 Other non-pulmonary mycobacterial infections are treated on the basis on antimicrobial
EBMedicine.net • February 2008
susceptibility testing, but regimens often include
amikacin and clarithromycin.187
Special Circumstances
Bites (Human And Animal)
Human bites are occasionally a cause of infection in
the pediatric emergency department, either via
clenched-fist injury or occlusive bite. In children, a
recent study showed about 50% of bites occurring
during play and 41% occurring during altercations,
with the latter increasing with increasing age.188
Several studies have been performed on the bacteriology of human bite infections. Talan et al analyzed
the results of infected human bite wounds in 50
patients.57 They found that the median number of
isolates per wound was four, with both aerobes and
anaerobes typically isolated. Typical species
included Streptococcus anginosus, Staphylococcus
aureus, and Eikenella corrodens as well as other
anaerobes. Similar results have been found in other
studies as well.189 While significant resistance was
encountered to penicillin and other antibiotics, virtually all species tested were sensitive to beta-lactamase-resistant penicillins, making them the recommended treatment for infected human bites. We
recommend empiric treatment with amoxicillinclavulanate for oral therapy, and empiric treatment
with either ampicillin-sulbactam, ticarcillin-clavulanate, or cefoxitin for intravenous therapy.
Dogs are responsible for the vast majority of animal bites presenting to emergency departments.
Cat bites, on the other hand, are less common but
are more likely to be infected. Like human bite
infections, bacterial isolates from infected dog and
cat bites are polymicrobial. One multicenter study
showed common pathogens in infected dog and cat
bites to be Pasteurella, Streptococcus, Staphylococcus,
Fusobacterium, and Bacteroides.190 The drug of choice
Figure 7. Clenched Fist Fighting Injury from
Contact with Human Tooth
Reprinted from
http://www.aafp.org/afp/20031201/2167.html. All rights reserved.
15
Pediatric Emergency Medicine Practice©
Risk Management Pitfalls For Skin And Soft Tissue Infections
even previously healthy patients should be presumed to have MRSA and should be treated
accordingly pending pathogen culture and sensitivity results.
1. “The patient looked well, so I didn’t think the
abscess needed to be drained.”
Incision and drainage of abscesses is a mainstay
of therapy in the treatment of soft tissue infections. In fact, many of these infections will
improve with simple I&D alone. Failure to drain
an abscess may result in treatment failure and
complications for patients.
6. “I went ahead and treated the infected cat bite
as I would any infected wound.”
Clindamycin is not recommended therapy for
Pasteurella infections. Instead, these patients
should be treated with either amoxicillin-clavulanate or ampicillin-sulbactam.
2. “There was no crepitus, so I didn’t consider
necrotizing fasciitis in my differential
diagnosis.”
7. “I forgot to ask the patient about exposure to
fresh or saltwater.”
Necrosis and crepitus are late findings in
patients with necrotizing fasciitis. Morbidity
and mortality increase with delay in diagnosis of
necrotizing fasciitis. Therefore, if any patient
presents with concerning symptoms, such as
pain disproportionate to the size of the lesion,
prompt surgical consultation should be
obtained.
Vibrio vulnificus and Aeromonas hydrophila are
bacteria found in salt and freshwater, respectively. They can rapidly progress to necrotizing soft
tissue infections. Infections originating from
wounds obtained in these environments merit
careful observation and follow-up.
3. “I thought the patient might have necrotizing
fasciitis, but I decided to start antibiotics and
wait for the final read on the imaging before
consulting surgery.”
8. “I decided to treat empirically without obtaining a wound culture.”
Culture results may lead empiric treatment regimens to be either narrowed or altered. Bacteria
may be resistant to appropriate empiric
regimens. Cultures should be obtained on all
wound cultures prior to treatment.
Antibiotics have little effect prior to surgical
debridement, secondary to the poor vascular
supply reaching necrotic tissue. Therefore, the
only definitive treatment for necrotizing fasciitis
is surgery. These infections progress rapidly, so
delays in treatment increase the probability of
patient morbidity and mortality. Any patient
who is suspected to have necrotizing fasciitis
should have an emergent surgery consult.
9. “I treated his cellulitis with clindamycin without ordering a double disk diffusion test.”
CA-MRSA that are initially resistant to erythromycin and sensitive to clindamycin may subsequently develop inducible clindamycin
resistance upon treatment. Therefore, it is necessary to test for this inducible clindamycin resistance with the double-disk diffusion test (D test).
If this resistance is present, clindamycin should
not be used.
4. “I didn’t think that CA-MRSA had reached my
area of the country yet.”
High rates of CA-MRSA infections have been
documented in places as diverse as Los Angeles,
Baltimore, Atlanta, Minnesota, and Texas. Unless
you know the resistance pattern of bacteria in
your community, presume a high burden of CAMRSA in your patients, and treat them
accordingly.
10. “The neonate clearly had simple cellulitis, so I
discharged him on oral clindamycin.”
Skin and soft tissue infections in neonates can be
caused by gram-negative pathogens, such as E.
coli and Klebsiella. For this reason, clindamycin
may be inadequate coverage for these neonatal
infections as it has poor gram-negative coverage.
Additionally, neonates may appear relatively
well, yet have a severe, systemic infection.
Neonates with all but the most trivial skin infections should have a full sepsis workup and
should be hospitalized on IV antibiotics.
5. “My patient had no risk factors for MRSA, so I
treated him with amoxicillin.”
Amoxicillin is never appropriate therapy for S.
aureus infection. S. aureus is virtually uniformly
resistant to penicillin and amoxicillin therapy. In
addition, studies have shown that the prevalence
of CA-MRSA is high even in patients with no
‘risk factors’ for MRSA infection. Therefore,
Pediatric Emergency Medicine Practice©
16
February 2008 • EBMedicine.net
for the treatment of isolated Pasteurella infection is
penicillin. However, given the existence of beta-lactamase-producing Pasteurella191 as well as the betalactamase activity of anaerobic pathogens also
associated with mammalian bite infections,192 betalactamase resistant penicillins are the best choice for
treatment of these infections. As with human bites,
we recommend empiric treatment with amoxicillinclavulanate for oral therapy, and empiric treatment
with either ampicillin-sulbactam or ticarcillin-clavulanate for intravenous therapy. Clindamycin should
not be used for Pasteurella infections. For both
human and animal bites, penicillin allergic adolescents may be treated with quinolones, which have
efficacies similar to amoxicillin-clavulanate.
Younger children with a penicillin allergy may be
treated with a combination of TMP-SMX and clindamycin.193 Monotherapy with azithromycin may
also be used,194 although these infections will need
closer followup as macrolides are not as effective in
vitro against bite pathogens when compared to
amoxicillin-clavulanate.195
necrotizing fasciitis in these adult diabetic
patients.198 Nevertheless, there is no evidence that
children with diabetes mellitus are at greater risk for
skin infections or their complications. Therefore,
pediatric patients with diabetes mellitus who are
reasonably well controlled and have had no endstage complications from their disease may be
treated like their non-diabetic counterparts.
Children with neoplasms are at risk of both skin
infections caused by unique pathogens as well as
aggressive infection caused by typical pathogens
due to their level of immunocompromise. Adults
with Hodgkin’s disease may present with pruritis,
new onset eczema, or secondary S. aureus infections.199 As stated previously, children with immunodeficiencies are at risk for ecthyma gangrenosum, a
cutaneous manifestation of systemic sepsis. It is
typically caused by Pseudomonas aeruginosa but may
also be caused by Aeromonas hydrophila, S. aureus,
Serratia marcescens, Aspergillus spp. and Mucor
spp.200 Ecthyma gangrenosum rarely may represent
the first manifestation of malignancy.201 Neutropenic patients are also at greater risk for primary
fungal infections, but these remain uncommon and
usually present in a similar manner to those found
in healthy individuals.202
Children with malignancies who present with
fever and soft tissue infections, particularly those
who present with neutropenia, need to be treated
aggressively, with prompt, broad spectrum parenteral antibiotics such as ceftazidime or piperacillintazobactam either alone or with vancomycin.203
Immunocompromised Patients
A number of pre-existing conditions may complicate
the disease course and therefore treatment of soft
tissue infections. In the adult community, patients
with diabetes mellitus are at greater risk for both
skin infections196 and S. aureus bacteremia developing from those skin infections197 than their non-diabetic counterparts. There also exists a greater risk of
Cost-Effective Strategies
3. Use antibiotics appropriate for CA-MRSA
infections.
In the new era of CA-MRSA, clindamycin and
trimethoprim-sulfamethoxazole are more efficacious and less expensive than third-generation
cephalosporins. By using non-beta-lactam
antibiotics, you may decrease medication costs
and prescribe a more efficacious treatment
regimen.
1. Avoid unnecessary laboratory tests.
Multiple studies have demonstrated the lack of
utility of blood cultures in treating simple cellulitis. Fine needle aspiration of areas of cellulitis also have a low yield. If a patient is without
fever and is clinically well, cellulitis and other
skin infections may be treated empirically without any laboratory tests.
2. Consider incision and drainage without antibiotics in simple skin abscesses without
surrounding cellulitis.
I&D without antibiotic treatment was demonstrated to be equivalent to I&D plus oral antibiotics in the management of soft-tissue infections
in the pre-MRSA era. While no studies have
been completed on this strategy more recently,
the high cure rates seen in MRSA infections
when treated with first generation cephalosporins suggest that I&D alone remains an effective therapeutic strategy.
EBMedicine.net • February 2008
4. Utilize the availability of observation units.
Observation units are an excellent way to
ensure therapeutic efficacy without the cost of
an inpatient admission. The vast majority of
patients admitted to observation units with skin
infections have been shown to be able to be discharged within 24 hours.
17
Pediatric Emergency Medicine Practice©
Patients without fever but with soft tissue infection
should be treated aggressively as well, as even
seemingly insignificant infection may rapidly
worsen. At least one study has also demonstrated
an increased risk of skin infections in individuals
with hemoglobinopathies, such as sickle cell
anemia.204 Patients with skin infections and fever,
however, should be treated as any patient with
sickle cell anemia and fever: with empiric broad
spectrum antibiotics while blood cultures are
pending.205
While pediatric patients with HIV are also at
greater risk for serious skin and soft tissue infection,
they tend to have similar infections to healthy children.206 This is unlike adults, who tend to also
develop opportunistic infections.207 Patients with
bacterial soft tissue infections generally can be
treated as their healthy counterparts would be, often
with oral antibiotics.208 In addition to bacterial
infections, patients with HIV often have serious fungal skin infections. Patients often develop significant cutaneous candidal infections, frequently with
widespread papules and pustules as well as significant dermatophytoses.208
communities and hospitals as well.210,211 Neonates
with histories of prematurity, low birth weight,
chronic underlying diseases, prolonged hospitalization, invasive or surgical procedures, indwelling
catheters, or prolonged use of antimicrobial agents
are at particular risk of infection with S. aureus.211
Toxin-mediated diseases, such as staphylococcal
scalded skin syndrome, are common in neonates
and have often been seen as early as within the first
week of life.212,213 Epidemics of neonatal SSSS can
occur and have been traced to an individual healthcare worker in at least one instance.214
Unlike older children, neonates with nosocomial
skin and soft tissue infections often have infections
caused by gram-negative bacteria. These pathogens
are often transferred from the mother either in utero
or during passage through the birth canal. In a
study of 49 mostly preterm neonates with bacteremia, 22% had subcutaneous abscesses as the source
of their infection.215 Of the 10 neonates with
abscesses, nine had gram-negative pathogens grow
from their abscess cultures.
In neonates, the umbilical stump can be the initial source of bacterial skin infections. Major risk
factors for omphalitis include inadequate umbilical
stump care and low birth weight, and it is much
more common in the developing than the developed
world.216 Common causative pathogens include S.
aureus, Staphylococcus epidermidis, groups A and B
Streptococcus, Escherichia coli, Klebsiella, Pseudomonas,
and Clostridium difficile.217 It may be characterized
by the extent of infection, ranging from simple
purulent discharge to extension into the deep fascia.
The presence of cord vessels makes systemic spread
and septicemia of particular concern.217
Neonatal Infection
Neonates are also at risk for MRSA infection. Fortunov et al demonstrated this in a series of 89 cases
of neonatal S. aureus infection at Texas Children’s
Hospital between August 2001 and March 2005. Of
the 89 documented cases, 61 were of MRSA, most
clinically diagnosed as having either pustulosis or
cellulitis/abscess.209 Outbreaks of CA-MRSA infections in neonates have been noted in a number of
Key Points For Skin And Soft Tissue Infections
soft tissue infections to determine if they have
either a complicating past medical history or a
history of present illness which would suggest an
atypical pathogen.
• Have a high clinical suspicion for necrotizing
fasciitis since findings classically associated with it
are often only present late in the disease course.
• Incision and drainage is an essential part of any
therapeutic strategy for skin and soft tissue infections associated with focal collections of purulent
material.
• Treat simple skin and soft tissue infections with
clindamycin pending wound cultures and sensitivities; alternatively, use a combination of
trimethoprim-sulfamethoxazole and amoxicillin.
• Impetigo may be treated without systemic antibiotics; topical mupirocin is usually sufficient. Simple cellulitis and cellulitis surrounding an abscess
warrant systemic antimicrobial therapy.
• Remember that strains of Staphylococcus aureus
causing skin and soft tissue infections have
become more virulent and resistant to antibiotics
over the past ten years.
• CA-MRSA, unlike HA-MRSA, is usually susceptible to common oral non-beta-lactam antibiotics.
• Skin and soft tissue infections should be
presumed to be caused by CA-MRSA and treated
as such until clinical and laboratory evidence
proves otherwise.
• GAS represents a smaller but significant cause of
skin and soft tissue infections, and infections
caused by it are often indistinguishable from those
caused by S. aureus. Treatment of GAS is often
much easier, as GAS is universally sensitive to
penicillin and amoxicillin.
• Consider atypical pathogens in atypical cases of
skin and soft tissue infections.
• Take a thorough history of patients with skin and
Pediatric Emergency Medicine Practice©
18
February 2008 • EBMedicine.net
Necrotizing fasciitis can complicate skin and soft
tissue infection in neonates as well. In one metaanalysis of 66 reported cases of neonatal necrotizing
fasciitis in the literature, 71% were secondary to
omphalitis.218 Infections were polymicrobial in 74%
of cases, with typical pathogens including S. aureus,
Escherichia coli, Clostridium spp. and Bacteroides spp.
Mortality occurred in 59% of cases, with death usually secondary to shock, disseminated intravascular
coagulation, or multiorgan failure. Treatment
includes surgical debridement and broad spectrum
antibiotics.
Treatment of all skin and soft tissue infections
should be aggressive, given the immature immune
system of neonates. A full sepsis evaluation should
be performed in neonates with all but the most simple of infections. Given the wide range of pathogens potentially affecting neonates, broad spectrum
parenteral antibiotics should be used. Vancomycin
should be used for empiric gram-positive coverage
in significant infections, while a third-generation
cephalosporin, such as cefotaxime or ceftazidime,
should be used for broad gram-negative coverage.
Controversies/Cutting Edge
Home IV Antibiotics
A number of programs have recently been developed to provide parenteral therapeutics in the home
setting rather than in the hospital.222 This type of
therapy has also been utilized in adult patients with
cellulitis requiring IV antibiotics. In one study, 125
patients were discharged from the emergency
department with once-daily IV ceftriaxone or
teicoplanin arranged for at home use. This resulted
in both high cure rates (98.4%) and significant savings.223 A second study utilized primarily cefazolin
twice daily in 124 patients with a reasonably good
rate of cure (84.7%).224
In pediatric populations, this kind of therapy
presents a number of problems. First, therapy was
administered through an IV, which is impractical in
active children who are highly likely to remove their
IVs at home. Secondly, these studies were performed at a time when rates of CA-MRSA were
lower than they are today. Home therapy would
now require clindamycin, which is dosed at least
three times a day. Finally, home therapy required
the presence of a team of nurses on hand that can
administer therapy and evaluate patients at home.
This is a system that is not in place at many pediatric hospitals. Nevertheless, home therapy may be
an option in select adolescent patients seen at facilities where the resources are in place to implement it.
Hand Infections
Extra care must be taken when evaluating hand
infections due to the possibility of extension of
infection into the tendon sheaths. The soft tissue of
the dorsum of the hand is generally loose, and
infection generally remains dorsal to the extensor
tendons.219 Prompt medical management is
required however, as infection may spread to the
deeper tendons. In addition to antibiotic therapy,
hand infections managed medically require immobilization and elevation. Hand movement may
spread infection; therefore, infected hands should be
splinted in a functional position, while elevation
will reduce edema.219 The splint should be removed
once the acute infection is controlled, as prolonged
splinting increases the risk of contracture. Antibiotic treatment of hand infections is equivalent to
other skin and soft tissue infections, although consideration of mycobacterial infection should be
made in cases of penetrating trauma.220
Infections of the palmar aspect of individual digits are extremely concerning, as these infections may
rapidly involve the flexor tendons. Four criteria
have been classically used to diagnose tenosynovitis. They are: (1) uniform, symmetric digit swelling;
(2) at rest, digit is held in partial flexion; (3)
excessive tenderness along the entire course of the
flexor tendon sheath; and (4) pain along the tendon
sheath with passive digit extension.221 Tenosynovitis is generally associated with penetrating trauma
to the hand. In cases of tenosynovitis, prompt
surgical consultation is warranted, with exposure
and copious irrigation of the tendon sheath.220
EBMedicine.net • February 2008
Treatment Of Carrier State
Studies have shown that individuals with S. aureus
infection often have the same strain of the bacteria
in their nares,225 and persistent nasal carriage of S.
aureus is associated with a higher rate of staphylococcal soft tissue infection.226 At least one study,
performed in soldiers, showed a strong association
between MRSA carriage and subsequent MRSA
infection.227 A number of studies have been performed looking at ways to reduce staphylococcal
nasal carriage in the hopes of reducing recurrent
staphylococcal infections, often with discouraging
results. Perl et al performed a double-blind,
randomized control study on pre-operative patients,
treating those with nasal carriage of S. aureus with
either nasal mupirocin or placebo prior to
surgery.228 There was no significant difference in
the rates of post-operative wound infections
between the two groups of patients. Other studies
have also found a lack of significant effect.229,230
One study did show a reduction in MRSA infections
during an outbreak at a child care center when children, staff, and family members were treated.231
Nevertheless, carrier state treatment as prophylaxis
19
Pediatric Emergency Medicine Practice©
for MRSA infection cannot definitively be
recommended in the ED setting at this time.
should be made as well. Patients exposed to fresh
or saltwater may merit inpatient observation to rule
out aggressive infections from either Vibrio species
or Aeromonas hydrophila. Patients who have primary
varicella and a secondary bacterial skin infection
may need to be monitored closely secondary to the
higher incidence of necrotizing fasciitis in this
patient group.61 Finally, infections of the hand and
face merit closer observation secondary to their
ability to progress to more severe infection.
Physical examination findings may influence
admission decisions as well. Fever may serve as an
indicator of systemic infection. The size of the area
of infection is also often a determinant in whether to
admit, although there exists no specific criteria for
admission based on lesion size. The presence of
extreme pain, anesthesia at the site of infection, or
crepitus suggest necrotizing fasciitis, although these
are all late findings. Finally, the presence of laboratory findings, such as elevated ANC, bandemia, or
an elevated CRP, may all suggest more severe
infection.
One option for many patients with skin and soft
tissue infections of unclear severity is a brief admission to an observation unit. In one study, skin and
soft tissue infections were the third leading diagnosis in adult patients admitted to an observation unit,
and 85% of those admitted were discharged within
24 hours.237 A similar rate of discharge (73%) was
found in another study of adult patients with skin
and soft tissue infections.238 Admitting patients to
an observation unit allows the ED physician reassurance that the patient’s infection is improving
without incurring the significant costs of inpatient
hospitalization.
Vaccines
Given the continued emergence of MRSA as a
health threat in both children and adults, renewed
attention has been focused on developing a vaccine
against S. aureus. Most research has centered on
developing a vaccine against the capsular
polysaccharides of S. aureus, as similar techniques
were used to develop pneumococcal vaccines.232 A
phase III trial was performed on a staphylococcal
vaccine in patients with end-stage renal disease that
showed partial immunity to S. aureus at 40 weeks
postimmunization but loss of that immunity at 54
weeks postimmunization.233 Additional studies on
both this and other types of vaccines are continuing.
A vaccine is also in development for GAS infections. A phase I study of a multivalent recombinant
M protein peptide fragment vaccine has shown success in eliciting an antibody response.234 Development of this type of vaccine is complicated,
however, by the large numbers of M proteins associated with GAS.29 Additional research is continuing
in developing a vaccine based on conserved regions
of the streptococcal M protein.
Disposition
The decision to admit a patient with a skin or soft
tissue infection is multifactorial, as there is no one
criterion alone that determines whether or not a
patient merits admission. Additionally, data on
rates of and criteria for admission to the hospital
from the emergency department are scant. One
study of adults with MRSA infections found an
admission rate of 15%.21 A Canadian study
described an admission rate of only 7% of adults
with cellulitis in a series of 414 patients, although
patients made a median of four return visits to the
ED for their illness.235
Any patient showing signs of septicemia, including vital sign instability or mental status changes,
should be admitted, possibly to an intensive care
unit. A patient’s medical history should influence
admissions decisions. Patients with neutropenia
should be admitted automatically for all but the
most insignificant of infections. Other medical
problems that may lead to poorer medical
outcomes, such as HIV, sickle cell anemia, other
immunodeficiencies, and malnutrition, should be
considered as well.236 Patients with histories of prolonged hospitalizations are at risk for nosocomial
MRSA and may merit hospitalization. Recent exposure to antibiotics, steroids, or other immunomodulators may also make infections more aggressive or
difficult to treat.
Consideration as to the nature of the infection
Pediatric Emergency Medicine Practice©
Summary
Skin and soft tissue infections are an extremely common reason for children to present to the pediatric
emergency department. They range in severity
from the innocuous impetigo to the potentially fatal
necrotizing fasciitis. The continued evolution of the
pathogens that cause skin and soft tissue infections
has made determining the appropriate therapy for
them a constant challenge. Resistance patterns of
the bacteria causing these infections are continually
changing. Additionally, the virulence of the infections caused by these bacteria is increasing as well.
With a strong knowledge of resistance patterns and
potential therapeutic pitfalls, however, these infections may be treated appropriately and safely.
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20
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CME Questions
1. Which pathogen is associated with over 70%
of skin and soft tissue infections in children?
a. Streptococcus pyogenes
b. Streptococcus pneumoniae
c. Staphylococcus epidermis
d. Staphylococcus aureus
e. Pasteurella multocida
2. Which of these virulence factors is associated
with GAS infection?
a. Panton-Valentine leukocidin determinant
(PVL)
b. Streptolysin O
c. Exfoliative toxins A and B (ETA and ETB)
d. Penicillin binding protein 2a (PBP2a)
e. Beta-lactamase production
3. Actinomyces israelii is found living with the
normal flora in which area of the body?
a. Lower respiratory tract
b. Colon
26
February 2008 • EBMedicine.net
4.
5.
6.
7.
8.
9.
10.
11.
c. Oral cavity
d. Anterior nares
e. Skin
Which of the following bacteria is most
typically associated with infected cat bites?
a. Streptococcus pyogenes
b. Streptococcus pneumoniae
c. Staphylococcus epidermis
d. Staphylococcus aureus
e. Pasteurella multocida
Ecthyma gangrenosum is the dermatologic
manifestation of systemic infection with
which of the following pathogens?
a. Aeromonas hydrophila
b. Mycobacterium marinum
c. Pasteurella multocida
d. Haemophilus influenzae
e. Pseudomonas aeruginosa
Orbital cellulitis is predominantly a
complication of what condition?
a. Odontogenic infection
b. Bacteremia
c. Meningitis
d. Sinusitis
e. Cavernous sinus thrombosis
Erysipelas is cause by what pathogen?
a. Streptococcus pyogenes
b. Streptococcus pneumoniae
c. Staphylococcus epidermis
d. Staphylococcus aureus
e. Pasteurella multocida
Which of the following is a significant risk
factor for necrotizing fasciitis in children?
a. Varicella infection
b. Eczema
c. Obesity
d. Edema
e. Staphylococcus aureus infection
What treatment for non-bullous impetigo has
been shown in systematic reviews to have a
high cure rate while minimizing systemic side
effects?
a. Observation only
b. Disinfection with chlorhexidine
c. Topical bacitracin
d. Topical mupirocin
e. Systemic cephalexin
Which of the following antibiotics is MRSA
typically resistant to?
a. Clindamycin
b. TMP-SMX
c. Erythromycin
d. Vancomycin
e. Linezolid
What is the most effective therapy for
necrotizing fasciitis?
a. Intravenous clindamycin
b. Oral cephalexin
EBMedicine.net • February 2008
12.
13.
14.
15.
16.
27
c. Intravenous vancomycin
d. Intravenous rifampin and gentamycin
e. Surgical debridement
Which is not a classic symptom of
tenosynovitis?
a. Uniform, symmetric digit swelling
b. Digit held in partial flexion at rest
c. Prolonged capillary refill time of the
affected digit
d. Excessive tenderness along the entire
course of the flexor tendon sheath
e. Pain along the tendon sheath with passive
digit extension
Localized release of epidermolytic toxin
causes which of the following conditions?
a. Non-bullous impetigo
b. Bullous impetigo
c. Scalded skin syndrome
d. Toxic shock syndrome
e. Furunculosis
“Fish tank” granuloma is the common name
for one of the clinical manifestations of
dermatologic infection by what slow-growing
organism?
a. Aeromonas hydrophila
b. Mycobacterium marinum
c. Vibrio vulnificus
d. Haemophilus influenzae
e. Pseudomonas aeruginosa
What is the relationship between hospitalacquired MRSA (HA-MRSA) and communityacquired MRSA (CA-MRSA)
a. CA-MRSA evolved from HA-MRSA
b. HA-MRSA evolved from CA-MRSA
c. CA-MRSA and HA-MRSA most likely
evolved independently
d. HA-MRSA and CA-MRSA are in a constant
exchange of virulence and resistance factors
e. HA-MRSA is more easily treated than CAMRSA
The term “inducible clindamycin resistance”
describes what phenomenon?
a. The presence of clindamycin resistance in
MRSA when found in the hospital setting
b. The development of clindamycin resistance
in polymicrobial infections
c. The development of clindamycin resistance
in previously erythromycin resistant,
clindamycin sensitive S. aureus when
treated with clindamycin
d. The development of clindamycin resistance
in GAS infections when they are not treated
for a full ten days
e. The presence of clindamycin resistance by
S. aureus that can be overcome with the use
of high-dose clindamycin therapy
Pediatric Emergency Medicine Practice©
Physician CME Information
Free Report:
“Evidence-Based Medicine:
A Guide For Physicians”
Date of Original Release: February 1, 2008. Date of most recent review:
January 6, 2008. Termination date: February 1, 2011.
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Class Of Evidence Definitions
Each action in the clinical pathways section of Pediatric Emergency
Medicine Practice receives a score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and
effectiveness
Level of Evidence:
• One or more large prospective
studies are present (with rare
exceptions)
• High-quality meta-analyses
• Study results consistently
positive and compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels of
evidence
• Non-randomized or retrospective
studies: historic, cohort, or case
control studies
• Less robust RCTs
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or alternative
treatments
Level of Evidence:
• Generally lower or intermediate
levels of evidence
• Case series, animal studies,
consensus panels
• Occasionally positive results
Indeterminate
• Continuing area of research
• No recommendations until further
research
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent, contradictory
• Results not compelling
Significantly modified from: The
Emergency Cardiovascular Care
Committees of the American Heart
Association and representatives
from the resuscitation councils of
ILCOR: How to Develop EvidenceBased Guidelines for Emergency
Cardiac Care: Quality of Evidence
and Classes of Recommendations;
also: Anonymous. Guidelines for
cardiopulmonary resuscitation and
emergency cardiac care. Emergency Cardiac Care Committee
and Subcommittees, American
Heart Association. Part IX. Ensuring
effectiveness of community-wide
emergency cardiac care. JAMA
1992;268(16):2289-2295.
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February 2008 • EBMedicine.net