DOI: 10.1111/j.1468-3083.2011.04416.

x JEADV

REVIEW ARTICLE

Bacterial skin and soft tissue infections: review of the

epidemiology, microbiology, aetiopathogenesis and
treatment
A collaboration between dermatologists and infectivologists
L. Tognetti,,* C. Martinelli, S. Berti, J. Hercogova, T. Lotti,** F. Leoncini, S. Moretti

Division of Clinical, Preventive and Oncologic Dermatology, Department of Critical Care Medicine and Surgery, Florence
University, Florence, Italy

Infectious Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy

Department of Sciences for Woman and Childs Health, University of Florence, Florence, Italy

Dermatology department, 2nd Medical School, Charles University, Prague, Czech Republic
**Chair of Dermatology and Venereology, Guglielmo Marconi University, Rome, Italy
*Correspondence: L. Tognetti. E-mail: linda.tognetti@gmail.com

Abstract
Bacterial skin and soft tissues infections (SSTI) often determine acute disease and frequent emergency recovering,
and they are one of the most common causes of infection among groups of different ages. Given the variable
presentation of SSTI, a thorough assessment of their incidence and prevalence is difficult. The presence of patient-
related (local or systemic) or environmental risk factors, along with the emergence of multi-drug resistant pathogens,
can promote SSTI. These infections may present with a wide spectrum of clinical features and different severity, and
can be classified according to various criteria. Many bacterial species can cause SSTI, but Gram-positive bacteria
are the most frequently isolated, with a predominance of Staphylococcus aureus and Streptococcus pyogenes. The
diagnosis of SSTI requires an extended clinical history, a thorough physical examination and a high index of
suspicion. Early diagnosis is particularly important in complicated infections, which often require laboratory studies,
diagnostic imaging and surgical exploration. SSTI management should conform to the epidemiology, the aetiology,
the severity and the depth of the infection. Topical, oral or systemic antimicrobial therapy and drainage or
debridement could be necessary, along with treatment of a significant underlying disease. This review discusses the
epidemiology, the pathogenesis and the classification of bacterial SSTI, describes their associated risk factors and
their clinical presentations. The authors provide a rational diagnostic and therapeutic approach to SSTI in respect of
antibiotic resistance and currently available antimicrobial agents.
Received: 6 April 2011; Accepted: 24 November 2011

Conflict of interest
None.

Funding source
None.

Epidemiology ing for a substantial portion of emergency department visits and

Skin and soft tissue infections (SSTI) collectively refer to several
microbial invasions of the skin layers and of the underlying soft
tissues, inducing a host-response. SSTI can often determine acute
disease and they are one of the most common causes of infection
among groups of different ages.14 In particular, SSTI represent
the most common infection presentation in patients visiting emer-
gency room clinics in both hospitals and based practices, account-
hospital admissions.58 Despite that, it is difficult to make an
assessment of the exact incidence and prevalence of SSTI, probably
because of their variable presentation and their short duration.
Indeed, the majority of SSTI tend to resolve within 710 days.2
The estimated prevalence of SSTI among hospitalized patients was
710% in 2005, with 14.2 million ambulatory care visits, and the
incidence rate of SSTIs assessed in 2006 was 24.6 per 1000

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2 Tognetti et al.

person year.911 The increased number of patients with immuno-
suppressed status (due to immunosuppressive drugs, cancer,
transplant surgery and HIV AIDS), of invasive medical techniques
and of surgical wound infections, may have contributed to the
increasing incidence of severe SSTI over the last decades.35
Aetiopathogenesis and risk factors
Infections of the skin and underlying soft tissues can ensue from the
imbalance between the pathogenic power of a microorganism and
the immunological defenses of the host.12,13 Various physical and
chemical alterations of the skin can induce disruption of the cutane-
ous barrier, then predisposing to bacteria penetration, growth and
multiplication.1215 Once the bacteria has penetrated the skin layers
and their virulence factors have overcame local hosts defenses, tis-
sue invasion occurs. Subsequent dissemination of microorganisms
in viable tissue triggers a series of systemic host responses.3,4,8,9 A
loss of integrity of the skin layers may be caused by lacerations, bite
or surgical wounds, scratches, burns or ulcers, along with inflamma-
tory dermatoses and viral or fungal infections (e.g., tinea pedis can
predispose to leg cellulitits).16 Also variations of skin pH and tem-
perature, dryness and maceration should be considered.1216
Risk factors for SSTI development can be classified as patient-
related, local or systemic, or environmental1221: this classification
is reported in Table 1. Patient-related risk factors have been shown
to influence the course of the diseases and response to treatment,
but not to correlate with infection severity.2,3
Necrotizing soft tissue infections (NSTI) occurrence are
favoured by comorbidities, such as immunosuppression, cardio-
vascular or lung diseases and diabetes mellitus. Nevertheless, a nec-
rotizing infection can develop in immunocompetent people,
elicited by repetitive trauma (i.e. NSTI of the head and the neck)22
or infections of urinary tract or perianal retroperitoneal areas
(i.e. Fournier gangrene).1 In particular, about 20% of patients with
Fournier gangrene have no identifiable cause.1 The devitalised
tissue prevents cellular and humoral defence mechanisms from
reacting, by providing a growth medium for bacteria.1 Because of
its acidic pH, the necrotized tissue inactivates the antimicrobial
agents or prevents their delivering.7 NSTI may involve the fascia,
resulting in thrombosis of subcutaneous blood vessels and necrosis
of the underlying tissue.
Microbiology
The different bacterial pathogens which can colonize the skin and
determine SSTI can be divided into two categories: resident flora
and transient flora.12,13 Skin resident flora, also called microflora,
includes many bacterial species (Gram-positive and Gram-nega-
tive) that colonize epidermis and follicular pores. Microflora is
mainly distributed on anatomical sites presenting high moisture
level (i.e. axillae, groin and intertriginous areas) and depends on
age and gender.1214,23 Gram-positive aerobic bacteria, coagulase-
negative staphylococci, streptococci and micrococci typically
affects exposed skin areas, whereas Gram-positive anaerobic bacte-
ria are generally present on cutaneous pleats. Skin transient flora,
also called contaminant flora, includes Staphylococcus aureus,
which is mostly localized in the nose and other orificial areas,
and some Gram-negative bacteria of the Enterobacteriaceae and

Table 1 Risk factors for most common SSTIs

Patient related-risk factors Environmental risk factors

Local risk factors Systemic risk factors

Anatomical alterations Alcoholism Animal bites wounds caused by rats, dogs, cats,
spiders and reptiles
Chickenpox Chronic renal failure Close contact with an SSTI infected person: family,
school or work exposure
Fungal infections Cardiovascular diseases Exposure to hot tub, seawater or infected freshwater
(i.e. tinea pedis and onychomycosis)
Infected wounds Cirrhosis Human bites wounds
(surgical, traumatic, bite-related)
Inflammatory dermatoses Diabetes mellitus Invasive medical techniques: liposuction,
(i.e. contact dermatitis, atopic endoscopic procedures and cathethers insertion
eczema, psoriasis)
Lymphatic obstruction Elderly age i.v. Or subcutaneous drug abuse
Poor skin hygiene HIV-infection Piercing apposition
Pressure sores Iatrogenic immunosuppression
Pre-existing SSTI (e.g. cellulitis) Malnutrition
Repetitive trauma Neuropathy
Urinary tract infection Nicotine addiction
Perianal or retroperitoneal infection Obesity and sedentary lifestyle
Vascular ulcers Peripheral vascular insufficiency
Solid and haematologic tumours
SSTI, Skin and soft tissue infection.

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Bacterial skin and soft tissue infections
Table 2 Composition of skin resident and transient flora
Skin resident flora (microflora)
Staphylococcus spp.
S. epidermidis: exposed skin areas, nose, cutaneous pleats,
mouth, urethral orifice
S. saccharolyticus: upper trunk, forehead, forearms
S. saprophyticus: perineum
S. anginosus: cutaneous pleats
Streptococcus spp.
S. mitis, S. salivarius, S. mutans: mouth
Propionibacterium spp.
P. granulosum: sebaceous areas, follicular pores
P. acnes: sebaceous gland
Corynebacterium spp.: high moisture level areas as cutaneous
pleats, nose, mouth, urethral orifice and genital area
C. minutissimum: axillae, groin and intertriginous areas
C. xerosis: conjunctiva
Skin transient flora (contaminant flora)
Gram-positive species Gram-negative species
Staphylococcus spp: face, Enterobacteriaceae: mouth (E. coli)
scalp, nose and other Proteus spp: nose, conjunctiva,
orificial areas (S. aureus),
exposed skin areas (P. mirabilis)
exposed areas (S. warneri)
Streptococcus pyogenes:
exposed skin areas, mouth
Corynebacteria: cutaneous Pseudomonadaceae:
pleats (C. minutissimum) exposed skin areas (P. aeruginosa)
Pseudomonaceae groups.12,14,23 Skin microflora composition is
reported in Table 2.
As some bacteria can be pathogenic under specific circum-
stances, it is often difficult to give a thorough assessment of SSTIs
microbiology.24 Infections of traumatic or surgical wounds are
usually caused by a mixture of aerobic and anaerobic micro-
organisms. Moreover, Gram-negative bacteria are frequently pres-
ent in wound infections caused by animal bites, trauma or surgery
or exposed to infected water.1,2,1215 Hence, post-traumatic SSTI
often result in polymicrobial infections. A scheme of the most
common causative bacteria identified in SSTI is provided in
Table 3, where they are listed along with their associated risk fac-
tors and the type of infection they induce.
The predominant pathogens of SSTI are Gram-positive bacteria,
firstly S. aureus and Streptococcus pyogenes, followed by Enterococ-
cus faecalis and Corynebacterium species.24 S. aureus is the most
common identified causative agent, accounting for more than
40% of all SSTI cases in 2003, and represents a common cause of
cellulitis, abscesses and wound infections.1,4,1720 During the last
decades, S. aureus has increasingly become resistant to methicillin
(methicillin-resistant S. aureus, MRSA) and has spread worldwide
both in healthcare and community settings.1,7,2426 An increasing
prevalence of community-acquired MRSA (CA-MRSA) has been
assessed in many intensive care units and emergency departments
both in the United States and Europe,2730 and numerous studies
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have identified CA-MRSA as the most important cause of SSTI.3136
Moreover, some MRSA isolates, phenotypically similar to
CA-MRSA strains, are likely to determine healthcare-associated
MRSA (HA-MRSA) infections.37 A few cases can be attributed to
methicillin-sensitive S. aureus (MSSA).3,38
Regarding streptococci, those mostly associated with SSTIs fall
into groups A and B. Group A streptococci (S. pyogenes) often
cause necrotizing fasciitis or flesh-eating infections, whereas
group B streptococci (S. agalactiae) are frequently identified in
diabetic patients.1,2,4,39 Pseudomonas aeruginosa is often isolated
from lower extremity infections, particularly in cases with periph-
eral vascular disease or puncture wounds and in cases involving
hydrotherapy.
Classification
Several classification schemes have been proposed for SSTI, a lot
of them being complex and varied, and there is not an universally
accepted one yet.5,17,39 Every scheme organizes SSTI on the basis
of a specific variable, such as aetiological agent, anatomical locali-
zation, skin extension (localized or spread infection), rate of pro-
gression (acute or chronic disease), clinical presentation (primary
and secondary infection) and severity (presence of comorbidi-
ties).1,4,18
According to the depth of the infection (Fig. 1), SSTI can be
classified into superficial infections, involving epidermis and or
dermis, and deep infections, extending from deep dermis to sub-
cutaneous adipose tissue, muscular fascia and muscle.2,3,9,14
Skin and soft tissue infections can be further classified according
to the presence of complicating factors.68,17,18 This classification
scheme is the most used in clinical practice and generally coincides
with the previous one based on the depth of the infection, as
shown in Table 4. Indeed, uncomplicated infections (uSSTI) are
typically superficial, whereas complicated infections (cSSTI) usu-
ally have a deep involvement. As the description implies, cSSTI are
usually more severe, progress rapidly, involve deeper tissues such
as subcutaneous fat, deep fascia and muscle and possess a greater
risk of limb loss than uSSTI.39
Of particular concern is that, in most cases, an SSTI is uncom-
plicated at the time of initial presentation.6,7,18 Complicating fac-
tors such as diabetes mellitus and HIV-infection can easily
transform a mild infection into a life threatening condition, as
immunosuppression enables unusual or normally non-pathogenic
bacteria to cause infections or increase the likelihood of developing
fulminant infections.4,7,40,41 Moreover, lesions located on the groin
area, on fingers, toes and head are more likely to be complicated.
Finally, otherwise uncomplicated SSTI occurring in specific ana-
tomical sites (e.g. rectal abscesses) and involving anaerobic or
Gram-negative organisms are considered complicated.7,40
Diagnosis
Although specific bacteria may cause a particular type of infection,
a considerable overlap in clinical presentations remains.24 SSTI
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Table 3 Resident or transient bacteria species with their associated risk factors and SSTI

Causative bacteria Associated risk factors Type of infection

GRAM (+)
Clostridium spp.
Corynebacterium spp.
C. minutissimum
C. xerosis
Enterococcus faecalis
Propionibacterium spp.
P. granulosum
P. acnes
Staphylococcus spp.
S. aureus
S. epidermidis
S. aureus producing
exfoliative toxin
MRSA
S. saccharolyticus
S. saprophyticus
S. anginosus
Streptococcus spp.
Group A (S. pyogenes)
Groups B (S. agalactiae)
Group C, D and G
GRAM ()
Acinetobacter (dry areas)
Aeromonas hydrophila
Capnocytophaga canimorsus
Enterobacteriaceae spp.
Haemophilus influentiae
Nocardia spp.
Pseudomonas aeruginosa
Pasteurella multocida
Proteus spp.
Mycobacteria spp.
M. marinum
(exposed skin areas)
M. mucogenicum
(wounds, urethral orifice)
Mycobacterium ulcerans
SSTI, Skin and soft tissue infection; SSSS, Staphylococcal scalded skin syndrome.
Cellulitis, gas gangrene, necrotizing fasciitis
Human bites Erythrasma
Conjunctivitis
Immunosuppression Cellulitis, fasciitis, myositis, abscesses,
wound infections
Severe acne
Acne vulgaris
Neutropaenia, drug use, diabetic infections, Bullous impetigo, furuncles, myositis, folliculitis,
wounds, human bites purulent cellulitis
human bites, diabetic foot infections Wound infections
Immunosuppression, diabetes, SSSS
neutropaenia, i.v. drug use Abscesses, myositis, purulent cellulitis
Cellulitis
Perianal abscesses
Hidradenitis suppurativa
Human bite, wounds, poor hygiene, Impetigo, ecthyma, necrotizing fasciitis
diabetes mellitus
Diabetes mellitus Erysipelas
Stasis dermatitis, lymphoedema Wound infections, impetigo
Burn wounds
Wounds occurred in infected water Severe cellulitis
Dog bite wounds Cellulitis
Hidradenitis suppurativa, cellulitis necrotizing fasciitis
Orbital cellulites
Immunosuppression Abscesses
Neutropenia, i.v. drug abuse, hydrotherapy Cellulites, sepsis, hidradenitis suppurativa,
exposure (hot tub) surgical wounds hot water folliculitis
Cat bite wounds Cellulitis
Folliculitis, proteus syndrome
Exposure to infected water Cellulitis, granulomas
Exposure to peritoneal dialysis Post-traumatic SSTI
Wounds Chronic cutaneous ulcers

can present different features and severity according to their aetiol- status of the patient.1,18 As many SSTI can be easily confused with
ogy, severity and depth of the infection. An overview of most other clinical syndromes, a careful history is essential to develop
common clinical presentation of SSTI is provided in Table 5. an exact differential diagnosis.2

Clinical history Physical examination

To get an exact and early diagnosis, it is important to obtain an
extended clinical history including information about patients
travel, hobbies, trauma, animal bites and exposure to fresh or
saltwater. Medical history should always investigate the occurrence
of previous SSTI (i.e. recurrent cellulitis)11,16 and the immune
Diagnosis of most bacterial SSTI is based on clinical impression,
hence, a thorough physical examination is of basic importance in
making a correct clinical assessment and estimating the severity of
the infection.1 The minimum diagnostic criteria are a skin lesion
with the typical tetrad, that is erythema, oedema, warmth and pain

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Bacterial skin and soft tissue infections
Figure 1 Distribution of most common SSTIs by the depth of
the infection. (Modified from: Maleville J, Traibe A, Massicot P.
Infections bacteriennes communes. In: Dermatologie et Vn-
reologie. Saurat JH, Grooshans E, Laugier P, Lachapelle JM,
eds; 2nd edn. Fribourg: Masson, 1990: 117120.)
Figure 2 Bullous impetigo in a six-month-old baby. (Courtesy of
dra. S Berti)
or tenderness.2 Local signs that would suggest a severe SSTI
include erythema, oedema, bullae, haemorrhagic lesions, crepitus;
then, when a NSTI has developed, we will observe dysfunction of
the affected area and skin discoloration (due to tissue ischaemia
from locally thrombosed vessels).14 Systemic symptoms such as
hypotension, tachycardia, hypothermia or fever and altered mental
status are suggestive of a more serious infection and the presence
of two or more of these signs is usually associated with worse
prognosis.1,8,40 A necrotizing infection should be suspected on
clinical grounds only and an early diagnosis is essential to protect
limbs and to save lives.7,12,18 Indeed, NSTI are generally fulminant
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Figure 3 Non-bullous impetigo in a five-month-old baby with
atopic dermatits. (Courtesy of dra. S Berti)
Figure 4 Erysipelas of the upper trunk spreading to the right
arm in a 62-year-old man. (Courtesy of dra. S Berti)
(they typically progress within 2448 h) and often life-threatening,
and they can have devastating consequences such as the destruc-
tion, with a widespread loss of tissue, of the underlying fat, the
fascia and the muscle.6,9,17,18 Clinical appearance of impetigo and
erysipelas infection is showed in Figs 2, 3 and 4.
Laboratory studies
Laboratory investigations including blood cultures, needle aspira-
tion and tissue swab with culture, can help confirm diagnostic
suspicion.14,12 Although the yield is very low in cSSTI, patients
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6 Tognetti et al.

Table 4 Classification schemes based on the depth of the exploration of deeper soft-tissues, hence, they are particularly
infections and on the presence of complicating factors beneficial in patients with rapidly progressive infections. CT is
Uncomplicated Complicated infections helpful in identifying gas and fluid collections or foreign objects.
infections MRI can exactly reveal even little changes associated with NSTI and
Superficial Impetigo Erysipelas it is superior to CT in detecting the muscular fascia involvement.
infections Ecthyma Lymphangitis Hence, MRI is helpful when myositis or necrotizing fasciitis is
Folliculitis Diabetic foot infections suspected.44
Furunculosis Venous stasis ulcers Concerning cellulitis diagnosis: X-ray and CT are useful tools
Carbuncles Infected pressure sores in complicated cases (e.g., when underlying osteomyelitis is
Abscess Staphylococcal scalded
suspected), while they are usually not necessary in uncomplicated
skin syndrome (SSSS)
Hidradenitis
cellulitis.11,20 Moreover, US can help detecting a subcutaneous
supppurativa abscess consequent to cellulitis, and guiding tissue aspiration.
Deep Cellulitis Otherwise, when cellulitis complicates a chronic lymphoedema
infections Myositis and the affected extremity rapidly increases in volume, gallium-
Necrotizing soft-tissue infections 67-scintigraphy should be performed. Because CT and US are not
Necrotising cellulitis sufficient to differentiate between cellulitis and necrotizing fasciitis,
Necrotizing fasciitis MRI is the investigation of choice for this specific differential diag-
Myonecrosis nosis.12 When using contrast enhanced MRI, the main diagnostic
Pyomiositis criterion for necrotizing fasciitis (NF) is the involvement of deep
Phlegmon muscular fascia: as a fluid collection occurred, the fascia results
Post-operative wounds infections
thickened after contrast agent absorption.
SSSS, staphylococcal scalded skin syndrome
Surgical exploration
who present with severe infection or sepsis syndrome should have Surgical exploration has a diagnostic and therapeutic role therefore
blood cultures obtained.18 Other blood tests may be helpful for it should be not delayed once the disease is suspected.17,18 Surgical
diagnosis, including abnormal findings, such as elevated white exploration can provide the definitive identification of necrotizing
blood cell count, anaemia and thrombocytopenia.39 Tissue speci- soft tissue infection, by revealing loss of fascial integrity, lack of
mens obtained by biopsy or curettage are preferred to swabs of bleeding and dishwater fluid in the surgical incision wound.12 No
superficial skin lesions or drainage, which may be contaminated investigations or preparations should delay operative intervention,
with normal skin flora. If there is no open wound, needle aspira- and early specialist surgical consultation for radical, repeated
tion of fluid at the leading edge of infection may be helpful. debridement takes precedence. The finger test represents a very
Cultures of the skin rarely yield a definitive pathogen in most specific surgical exploration technique for NF diagnosis, and it is
uSSTI. Otherwise, gram staining and culture specimens obtained performed as follows: the apparently healthy skin surrounding the
from complicated wounds usually help guide therapy, especially lesion is incised vertically up to the muscular fascia level, then the
when MRSA is a suspected pathogen.1,40 index finger is introduced until it reaches the subcutis-muscular
In patients with erysipelas, laboratory investigations reveal fascia junction. If this junction is altered, with subcutis and fascia
elevation of erythrocyte sedimentation rate (ESR) and reactive detached instead of normally tight fitting, the test is positive.
C protein (RCP) and leukocytosis with neutrophilia. Because of Other diagnostic signs that can be observed are moderate bleeding
the superficial nature of the infection, bacteriemia is often not and pus ooze from the surgical incision (generally 2 cm deep),
found, making blood culture unnecessary, whereas more useful that is consequently used for necrotic debridement and or
are the cultures from bullae fluid, which give positive responses in drainage.45
540% cases.41,42
Treatment
Diagnostic imaging The management of SSTI should conform to the aetiology, the epi-
To obtain more information, SSTI sometimes require diagnostic demiology and the distribution by the depth of the infection.1,12,17
imaging. X-ray radiography (x-ray) and ultrasonography (US) are The choice between oral and parenteral therapy is generally sug-
used to explore subdermal involvement: x-ray can reveal air fluid gested by the severity of the infection. Parenteral therapy is pre-
levels or air presence in the soft tissues, suggesting the need for ferred when the infection is rapidly spreading and comorbidities
urgent debridment, whereas US detects abscess or fascial inflamma- (i.e. diabetes mellitus, neutropenia, heart failure, hepatic cirrhosis
tion. X-ray is indicated in patients with diabetic foot infection to and renal failure) are present. Moreover, parenteral therapy is cho-
adscertain the presence of osteomyelitis.43 Computered tomography sen, at least initially, to ensure rapid serum and tissue antimicrobial
(CT) and magnetic resonance imaging (MRI) give a more detailed levels.1,17,18

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Bacterial skin and soft tissue infections
Table 5 Most common clinical presentation of SSTI
SSTI Aetiopathogenesis
Impetigo Patients: children aged 25 years (peak of
incidence), newborns, adults in economically
disadvantaged areas. Atopic dermatitis is an
important risk factor
Transmission: person-to-person or via fomites. The
infection takes 10 days after skin colonization to
become clinically apparent
Localization: exposed body areas, orificial areas,
face, scalp and the back of the hands
(non-boullous impetigo); skin folds
(bullous impetigo)
Ecthyma Patients: healthy people living in tropical areas
(or in tourists came back from these) and
immunosuppressed people
Pathogenesis: b-haemolytic Streptococci penetrates
the skin barrier through even minimal trauma
leading to an inflammation of the epidermic and
dermal layers
Erysipelas Patients: childhood and adults aged 5667
(two peaks of incidence)
Localization: lower extremities (adults); face (adults
and children), especially the butterfly area, with
oedematous and closed eyelids
Course of infection: short, infrequent relapses
Cellulitis Localization: extremities, face
Course of infection: long, frequent relapses, local
complications; recurrent cellulitits is usually caused
by Staphylococcus and Streptococcus spp.
Necrotizing Patients: adults aged 5060
fasciitis (NF) Localization: extremities, abdomen, perineum
Pathogenesis: streptococcal haemolytic toxins
(streptolysin O and S) damage
Risk factors: immunosuppression, chickenpox
Myonecrosis Patients: traumatologic or oncologic
(MN) MN is an acute life-threatening infection that can
complicates with many conditions, most common
being gangrene
SSTI, skin and soft tissue infection; NF, necrotizing fasciitis; MN, myonecrosis.
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Clinical features
Non-bullous impetigo (contagious impetigo): papules surrounded
by an area of erythema that become superficial vesicles and then
pustules which gradually enlarge and break down over a period
of 46 days to form characteristic thick, honey-coloured crusts.
Multiple spread lesions (auto-inoculation). Caused by
S. pyogenes or S. aureus or both
Bullous impetigo: caused by toxin-producing S. aureus, is a
localized form of staphylococcal scalded skin syndrome. Vesicles
that rapidly evolve into flaccid bullae filled with clear yellow fluid.
Then the fluid becomes darker, more turbid and, sometimes,
purulent. The bullae can easily break leaving a thin
yellow-brownish crust with oozing result
Pathognomonic finding: collarette of scale surrounding the blister
roof at the periphery of ruptured lesions
A vesicle or pustule overlying an inflamed area of skin that
deepens into a dermal ulceration with overlying grey-yellow crust.
A shallow, punched-out ulceration appears when adherent crust
is removed (which rapidly form a hard brown-blackish crust
covering the underlying ulceration). Then, lesion become multiple,
mostly localized on the legs
Ecthyma gangrenosum: necrotic skin ulcer which can pass as a
primary or secondary infection; secondary infection set in
typically in course of sepsis caused by P. aeruginosa, among
transplanted, neutropenic or diabetic patients.
Elevate fever with heat and shiver can precede skin
manifestations, consisting in intense, warm and aching erythema
and oedema that rapidly extend to the surrounding skin areas
with a well-demarcated erythematous border (step sign). Flaccid
vesicles and bullae filled with purulent fluid may appear on
2 3 days after infection. Lymphangitis and regional lymph nodes
inflammation are often associated
Erythema, oedema, warmth and tenderness of the affected area,
tender lymphadenopathy and fever. The involved area is poorly
demarcated
S. aureus and Bacterioides spp.: cellulitis in diabetic patients
Pseudomonas spp. and Enterobacteriaceae: in hospitalized
patients
Clostridium spp: in exposed fractures and penetrating trauma
Streptococcus spp. plus Haemophilus influentiae: orbital cellulitis,
occurring as a primary infection in healthy children aged under
5 years, or as secondary infection after sinusitis
Disproportion between ache and skin manifestation
NF type 1: polymicrobial infection, destroys the subcutaneous fat
and the muscular fascia, sometimes sparing the skin of the lower
extremities, perineum and abdominal wall
NF type 2 (streptococcal gangrene): caused by S. pyogenes
alone or associated with S. aureus, presents with severe local
pain and rapidly spreading erythema followed by necrosis.
Fascial necrosis and myonecrosis may occur, with no gas
production
Gas gangrene: slowly expanding ulceration confined to the
superficial fascia, determines necrosis of muscle, gas in the
tissues and systemic toxicity; is caused by Clostridium spp.
Traumatic gangrene: becomes clinically apparent after an
incubation period that can range from 6 h to 4 days, presents
with acute severe pain on the wound area, where the skin is
initially pale-pink, then becomes bronze and finally purple-reddish
with bullae, oedema and crepitus. The patient rapidly develops
signs of sepsis as tachycardia, rapid breathing, mental confusion
and fever
2012 The Authors
8 Tognetti et al.
Uncomplicated SSTI
Superficial uSSTI typically respond to topical treatment, as they
generally can be managed with a topical antibiotic agent, heat
packs or incision and drainage, and, when necessary, with one
cycle of oral antibiotics. They seldom require oral antimicrobial
treatment and patients hospitalization.2,5,6,39
Complicated SSTI
Otherwise, deep cSSTI including infected ulcers, burns, major
abscesses, infections in diabetics and deep-space wound infections,
often require debridement and systemic antibiotic therapy along
with hospitalization.1,79 Moreover, hyperbaric oxygen is also
believed to enhance wound healing.46 Surgical incision followed
by drainage is a mainstay in the treatment of abscesses, as it
removes a large portion of the microbes causing the infection
along with the purulent material.39,40,47 Antibiotic therapy for
abscesses and wound infections is then recommended when there
is no response to incision and drainage (e.g. when abscesses are
localized in areas difficult to drain) and in the following condi-
tions: >5 cm erythema around the wound, rapid progression,
associated cellulitis or phlebitis, signs of systemic infection (tem-
perature >38 !C, tachycardia, leukocytosis), comorbidities, immu-
nosuppression.7,3840,48 Systemic treatment for major abscesses
and complicated wound infections may require one therapy cycle
with b-lactam antibiotics, associated or not with clindamycin.49
The management of NSTI include an immediate surgical inter-
vention along with parenteral antibiotic therapy.17,18,39
Several antibiotic classes have been shown to be effective, alone
or in combination, in treating cSSTI: a treatment scheme is
provided in Table 6.
Empirical treatment
In many cases, an aetiologic diagnosis is difficult at presentation
time, thus most patients are initially treated empirically, pending
culture results. The empiric choice of antibiotic therapy must
cover the most likely organisms, thus it is important to consider
where and how the infection was acquired. An empirical antibiotic
treatment is also recommended when mixed flora polymicrobical
infection is suspected: for example, infections of the surgical site
after intra-abdominal procedures need extended spectrum penicil-
lins or carbapenems.13,7 Agents that provide coverage for both
S. aureus and S. pyogenes (e.g. penicillins, cephalexin, oxacillin)
are commonly used as empiric therapy for both uSSTI and
cSSTI.13,7,48 Clindamycin or metronidazole can be added to a
regimen to cover for anaerobes, depending on the clinical situation
and spectrum of other agents being used.2,7 Beta-lactams (i.e.
amoxicillin clavulanic, cefazolin) are indicated when Gram-
negative are likely to be involved (e.g. animal or human bites,
surgical infections and intravenous drug users).13,7 However,
broad-spectrum antibiotics (e.g. fluoroquinolones, cephalosporins)
should be reserved for severe or polymicrobial infections, or if
organisms are resistant to the more narrow spectrum agents.1,7
JEADV 2012 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Once the causative agent and its susceptibility has been identified,
clinicians must switch to narrow-spectrum antibiotics.
Antibiotic resistance
Antibiotic resistance is a concern, given that many SSTIs are
caused by MRSA and multidrug resistance is common with both
CA-MRSA and HA-MRSA infections.5 HA-MRSA is generally sus-
ceptible to vancomycin, linezolid and trimethoprim-sulphameth-
oxazole (that will also cover Streptococcus spp. and Gram-negative
organisms), whereas CA-MRSA is usually sensitive to these anti-
microbial agents as well as to clyndamicin, quinolones and tetracy-
clines.13,7,48 Pending culture data, an empirical therapy in
hospitalized patients with cSSTI should be based on vancomycin
or linezolid or daptomycin or telavancin or clindamycin. For
empirical coverage of CA-MRSA in outpatients with SSTI (i.e.
purulent cellulitis) or in patients that do not respond to b-lactams,
the current IDSA guidelines recommend one of the following:
trimetoprim-sulphamethoxazole, doxycicline or minocycline and
linezolid.48 Tigecycline (a semi-synthetic glycylcycline), also has
broad spectrum activity against MRSA.7
Macrolide resistance among group A and group B streptococci
has also risen, but organisms have remained susceptible to penicil-
lins and cephalosporins.1,2,6 Management of non-purulent cellulitis
should include empirical coverage for S. pyogenes.48 Once S. pyoge-
nes is isolated in necrotizing fasciitis or myonecrosis, patients
should be treated high dose G penicillin and clyndamicin.49
Treatment duration
There are no guideline indications for duration of SSTI therapy. In
general, short-course therapy for uSSTI is the standard of care.
Treatment duration for cSSTI is variable, and depends on patient
response (influenced by immunological status, comorbidities, age,
etc.), severity of infection and causative agent. On average, treat-
ment for most lesions requires 714 days of antibiotics therapy.13,7
Immunoglobulin therapy
The use of intravenous immunoglobulin (IVIG) is based on the
theoretical mechanism that IG can promote clearance of S. pyoge-
nes by the immune system, neutralize streptococcal superantigens
and act as an immunomodulatory agent, through the binding with
streptococcal derived exotoxin.5052 Some positive results have
been reported in myonecrosis and necrotizing fasciitis caused by
S. pyogenes.50,51,53 However, all of these patients would require
additional surgical debridement. Suggested IVIG dosage varies,
but most authors recommend 2 g kg with an option of a second
dose, if necessary after 24 h.52 Side effects are seldom reported, but
the major contraindications include selective IgA deficiency or a
history of anaphylaxis with immunoglobulins.50,51
Treatment recommendations
Some medication-related factors, including route of delivery,
patient allergies, side effect profile, drug interaction potential,
2012 The Authors
Bacterial skin and soft tissue infections 9

Table 6 Antimicrobial agents commonly used in patients with SSTIs

Antibiotics Usual dose Notes

Impetigo
Amoxicillinclavulanic acid 500 mg p.o. q812 h qid for 10 days The therapy prevents post-streptococcal
glomerulonefritis
Erythromycin 250500 mg p.o. q6 h Efficacy reduced in erythromycin-resistant
S. aureus strains
Cefalexin 500 mg p.o. q12 h
Mupirocin (ointment) 1 application q12 h
Fusidic acid (ointment) 1 application q8 h
Erysipelas
Amoxicillinclavulanic acid 1 g p.o. q8 h
Ampicillinsulbactam 3 g i.v. q6 h
Cefalexin 500 mg p.o. q8 h
Cefazolin 11.5 g i.v. q8 h
Ceftriaxone 12 g i.v. 24 h
Erythromycin 250500 mg p.o. qid for 10 days
Penicillin G procaine 0.61.2 millionU i.m. qid for 10 days
Cellulitis
Ampicillinsulbactam 3 g i.v. q6 h
Ceftriaxone 12 g i.v. q24 h
Daptomycin 46 mg kg i.v. q24 h
Ertapenem 1 g i.v. q24 h
Levofloxacin 750 mg i.v. or p.o. q24 h
Linezolid 600 mg p.o. or i.v. q12 h
Moxifloxacin 400 mg i.v. or p.o. q24 h
Oxacillin 2 g i.v. q4 h
Piperacillintazobactam 3.375 g i.v. q6 h First choice awaiting culture test results in
hospital-acquired SSTIs
Tygeciclin 100 mg i.v. 1dose, then 50 mg i.v. q12 h
Vancomycin 1520 mg kg q12 h or 400 mg q24 h First choice awaiting culture test results in
hospital-acquired SSTIs
Necrotizing fasciitis and myonecrosis
Penicillin G 4 or 810 million U day divided q4 h For community-acquired SSTIs
+ Clindamicyn 600 mg i.v. q6 h or 900 mg i.v. q8 h For community-acquired SSTIs
Oxacillin 2 g i.v. q4 h
+ Gentamycin 3 mg kg day i.v. divided q8 h If penicillin is controindicated
Metronidazole 15 mg kg i.v. 1dose, then 500 mg i.v. q68 h First choice awaiting culture test results
+ Imipenem meropenem 500 mg i.v. q6 h or 1 g i.v. q12 h First choice awaiting culture test results
+ Vancomycin 1 g i.v. q12 h First choice awaiting culture test results
SSTIs, skin and soft tissue infections.

pharmacodynamics and cost, have to be considered when select- b-Lactam antibiotics Several b-lactam antibiotics, such as semi-
ing an antimicrobial agent.2,6,47,54 To prevent recurrent SSTI, it synthetic penicillins (e.g., nafcillin, dicloxacillin) or first-generation
is recommended to maintain good personal hygiene and keep cephalosporins (e.g., cephalexin, cefazolin) are still effective against
draining wounds covered with clean, dry bandages.48 Finally, it MSSA and streptococci13,55 Although staphylococci are now
is essential to manage a significant underlying disease (e.g. diabe- almost universally resistant, streptococci remain sensitive to peni-
tes mellitus, peripheral vascular disease, ischaemic ulceration and cillin. Regarding MRSA, therapy with a b-lactam drug is generally
chronic lymphoedema) that may complicate the therapy no longer sufficient.7,18,19,48
response.1,8,17,18
Clindamycin Clindamycin can suppress bacterial toxin produc-
Antibiotic drugs tion, including streptococcal pyrogenic exotoxin A, PVL, and
The following provides an overview of the antimicrobial agents staphylococcal enterotoxin B.1,3 Thus, it represents an important
used to treat SSTIs. adjunct to therapy. After exposure to clindamycin, however,

2012 The Authors

JEADV 2012 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
10
MRSA can become resistant via an inducible erm gene. Hence, it
is useful to perform a disc diffusion test, known as a D-test, to
determine if inducible resistance is present.56
Daptomycin Daptomycin is approved for the treatment of cSSTI
caused by susceptible strains of S. aureus (including MRSA),
S. pyogenes, S. agalactiae, Streptococcus dysgalactiae and vancomycin-
susceptible strains of E. faecalis, as 46 mg kg intravenous
daily.39,57 The most common adverse events seen with dapto-
mycin include constipation, nausea, injection site reactions
and headache. An advantage of daptomycin is a once-daily
dosing, which is allowed by its long half-life and its prolonged
postantibiotic effect.
Ertapenem With a spectrum of activity similar to other carba-
penems, it is active against Gram-positive, Gram-negative and
anaerobic bacteria, such as S. aureus (MSSA), S. pyogenes, S. pneu-
moniae, E. coli, K. pneumoniae and Peptostreptococcus species;
however, ertapenem lacks activity against P. aeruginosa.58 It is also
efficacious for the treatment of mixed anaerobic and aerobic cSS-
TIs.59 Ertapenem, 1 g intravenous daily, is approved for cSSTI due
to S. aureus (MSSA), S. pyogenes, E. coli and Peptostreptococcus
species. The most common adverse events include nausea, diar-
rhoea, infusion-related reactions and headache.
Linezolid It is active against many Gram-positive organisms
including S. aureus (MRSA and MSSA), coagulase-negative staph-
ylococci, vancomycin-susceptible and vancomycin-resistant E. fae-
cium and E. faecalis and streptococci (including penicillin-
resistant strains). Linezolid, 600 mg b.i.d. intravenous or oral, is
approved for the use of cSSTI without osteomyelitis caused by
S. pyogenes, S. agalactiae and MSSA or MRSA.60 Another advan-
tage of using linezolid is the ability to continue therapy as an out-
patient, thus decreasing the length of stay and overall cost.
Although it may be given as first-line therapy, linezolid is best
used for transitioning of care to outpatient status and as an alter-
native to standard therapy.
Tigecycline Many organisms that in the past had acquired resis-
tance to tetracycline are now susceptible to tigecycline. The spec-
trum of activity of tigecycline includes many clinically important
bacteria, such as Streptococcus species, MSSA and MRSA, Enterococ-
cus species, Enterobacteriaceae and anaerobic bacteria.61 It is gener-
ally well tolerated, with mild to moderate nausea and vomiting
being the most commonly encountered adverse effects. Although
more studies are needed to test tigecycline against other commonly
used comparator regimens, tigecycline has shown promise as an
alternative for the initial empiric treatment of cSSTIs.
Conclusions
The emergence of antibiotic-resistance has been reported by
numerous studies in the field of bacterial SSTI. Nevertheless,
JEADV 2012 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Tognetti et al.
several recent antibiotics classes with narrow activity spectrum are
available at present time, but their side effect has to be considered.
Hence, a collaboration between dermatologists and infectivologists
can promote a rational approach to the aetiology and epidemiol-
ogy of SSTI and a more functional therapeutic approach, which
are necessary in clinical practice.
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