Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis

Cellulitis, abscess, or both are among the most common skin and soft tissue infections . Cellulitis
(which includes erysipelas) manifests as an area of skin erythema, edema, and warmth; it develops
as a result of bacterial entry via breaches in the skin barrier. A skin abscess is a collection of pus
within the dermis or subcutaneous space. Misdiagnosis of these entities is common, and possible
alternative diagnoses should be considered carefully

Cellulitis is observed most frequently among middle-aged and older adults. Erysipelas occurs in
young children and older adults Skin abscess may occur in healthy individuals with no predisposing
conditions.

Predisposing factors associated with risk of cellulitis and/or skin abscess include ●Skin barrier
disruption due to trauma (such as abrasion, penetrating wound, pressure ulcer, venous leg ulcer,
insect bite, injection drug use) ●Skin inflammation (such as eczema, radiation therapy, psoriasis)
●Edema due to impaired lymphatic drainage ●Edema due to venous insufficiency ●Obesity
●Immunosuppression (such as diabetes or HIV infection) ●Skin breaks between the toes ("toe web
intertrigo"); these may be clinically inapparent ●Pre-existing skin infection (such as tinea pedis,
impetigo, varicella)●Prior saphenous vein harvesting for coronary artery bypass graft surgery

Lymphatic compromise may occur following surgical procedures (such as saphenous venectomy or
lymph node dissection) or in the setting of congenital abnormalities
An additional risk factor for development of purulent skin and soft tissue infections is close contact
with others with methicillin-resistant S. aureus infection or carriage.

Cellulitis and erysipelas — The most common cause of cellulitis is beta-hemolytic streptococci
(groups A, B, C, G, and F), most commonly group A Streptococcus or Streptococcus pyogenes; S.
aureus (including methicillin-resistant strains) is a notable but less common. Gram-negative aerobic
bacilli are identified in a minority of cases.
The vast majority of erysipelas cases are caused by beta-hemolytic streptococci (diagnosed by
positive blood culture results or serologic testing for anti-streptolysin-O and anti-DNase-B
antibodies)

Less common causes of cellulitis include Haemophilus influenzae type b (buccal cellulitis), clostridia
and non-spore-forming anaerobes (crepitant cellulitis), Streptococcus pneumoniae, and Neisseria
meningitidis . In immunocompromised patients, the spectrum of potential pathogens is much
broader, and infectious disease consultation is warranted.

Pathogens implicated in special clinical circumstances include: ●Pasteurella multocida and

Capnocytophaga canimorsus ("Animal bites (dogs, cats ●Aeromonas hydrophila and Vibrio vulnificus
(water exposure") ●Pseudomonas aeruginosa ●Group B Streptococcus infection in neonates and
young infants ●Clostridium myonecrosis ●Erysipelothrix rhusiopathiae ●S. pneumoniae "Orbital
cellulitis") ●Cryptococcus neoformans ("Fever and rash in immunocompromised patients
●Streptococcus iniae ("Fever and rash in the immunocompetent patient")●Helicobacter cinaedi
( "Fever and rash in patients with HIV")●Mycobacterium abscessus

Skin abscess — The most common cause of skin abscess is S. aureus (either methicillin-susceptible or
methicillin-resistant S. aureus [MRSA]), which occurs in up to 75 percent of cases. A skin abscess can
be caused by more than one pathogen ; isolation of multiple organisms (including S. aureus together
with S. pyogenes and gram-negative bacilli with anaerobes) is more common in patients with skin
abscess involving the perioral, perirectal, or vulvovaginal areas. Organisms of oral origin, including
anaerobes, are seen most frequently among intravenous drug users

Unusual causes of skin abscess include nontuberculous mycobacteria, blastomycosis, nocardiosis,

and cryptococcosis

Most abscesses are due to infection. However, sterile abscesses can occur in the setting of injected
irritants. Examples include injected drugs (particularly oil-based ones) that may not be fully absorbed
and so remain at the site of injection, causing local irritation. Sterile abscesses can turn into hard,
solid lesions as they scar.

CLINICAL MANIFESTATIONS

Cellulitis and erysipelas — Cellulitis and erysipelas manifest as areas of skin erythema, edema, and
warmth; they develop as a result of bacterial entry via breaches in the skin barrier .Petechiae and/or
hemorrhage can be seen in erythematous skin, and superficial bullae can occur. Fever and other
systemic manifestations of infection may also be present. Cellulitis and erysipelas are nearly always
unilateral, and the lower extremities are the most common site of involvement ; bilateral
involvement should prompt consideration of alternative causes
Cellulitis involves the deeper dermis and subcutaneous fat; erysipelas involves the upper dermis and
superficial lymphatics . Cellulitis may present with or without purulence; erysipelas is nonpurulent
Patients with cellulitis tend to have a more indolent course with development of localized symptoms
over a few days.

Patients with erysipelas generally have acute onset of symptoms with systemic manifestations,
including fever, chills, severe malaise, and headache; these can precede onset of local inflammatory
signs and symptoms by minutes to hours. In erysipelas, there is clear demarcation between involved
and uninvolved tissue . There may be a raised, advancing border or erythema with central clearing.

Additional manifestations of cellulitis and erysipelas include lymphangitis and enlargement of

regional lymph nodes. Edema surrounding the hair follicles may lead to dimpling in the skin, creating
an appearance reminiscent of an orange peel texture ("peau d'orange"). Vesicles, bullae, and
ecchymoses or petechiae may be observed . Cutaneous hemorrhage can occur in the setting of
significant inflammation in the skin. Crepitant and gangrenous cellulitis are unusual manifestations
of cellulitis due to clostridia and other anaerobes. Severe manifestations with systemic toxicity
should prompt investigation for additional underlying sources of infection.

The interdigital toe spaces should be examined for fissuring or maceration; minimizing these
conditions may reduce the likelihood of recurrent lower-extremity cellulitis.

Other forms of cellulitis include orbital cellulitis, abdominal wall cellulitis (in patients with morbid
obesity), buccal cellulitis (due to S. pneumoniae and, prior to the conjugate vaccine era, H.
influenzae type b) and perianal cellulitis (due to group A beta-hemolytic Streptococcus) [54,55].
Rarely, infections involving the medial third of the face (ie, the areas around the eyes and nose) can
be complicated by septic cavernous thrombosis, since the veins in this region are valveless (

Laboratory findings are nonspecific and may include leukocytosis and elevated inflammatory
markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)

Skin abscess — A skin abscess is a collection of pus within the dermis or subcutaneous space . It
manifests as a painful, fluctuant, erythematous nodule, with or without surrounding cellulitis.
Spontaneous drainage of purulent material may occur. Regional adenopathy may be observed.
Fever, chills, and systemic toxicity are unusual. A skin abscess may develop via deep infection of a
hair follicle (known as a furuncle or boil), which reflects extension of purulent material through the
dermis into the subcutaneous tissue. Multiple furuncles can coalesce to form carbuncles, which may
be associated with systemic symptoms. Common areas of involvement include the back of the neck,
face, axillae, and buttocks.

Complications — Complications of cellulitis and abscess include bacteremia, endocarditis, septic

arthritis or osteomyelitis, metastatic infection, sepsis, and toxic shock syndrome

DIAGNOSIS The diagnosis of cellulitis, erysipelas, and skin abscess is usually based upon clinical
manifestations. Cellulitis and erysipelas manifest as areas of skin erythema, edema, and warmth .
Erysipelas lesions are raised above the level of surrounding skin with clear demarcation between
involved and uninvolved tissue. A skin abscess manifests as a painful, fluctuant, erythematous
nodule, with or without surrounding cellulitis

Laboratory testing is not required for patients with uncomplicated infection in the absence of
comorbidities or complications. Patients with drainable abscess should undergo incision and
drainage . Routine culture of debrided material is not necessary in healthy patients who do not
receive antibiotics.

Cultures of debrided material and blood cultures (prior to addition of antibiotic therapy) are
warranted in the following circumstances ●Severe local infection (eg, extensive cellulitis) ●Systemic
signs of infection (eg, fever) ●History of recurrent or multiple abscesses ●Failure of initial antibiotic
therapy ●Extremes of age (young infants or older adults) ●Presence of underlying comorbidities
(lymphedema, malignancy, neutropenia, immunodeficiency, splenectomy, diabetes) ●Special
exposures (animal bite, water-associated injury) ●Presence of indication for prophylaxis against
infective endocarditis ●Community patterns of S. aureus susceptibility are unknown or rapidly
changing

Positive blood cultures can impact antibiotic selection or prompt evaluation for additional infections
(eg, osteomyelitis, endocarditis). A skin biopsy may be warranted if the diagnosis is uncertain;
cultures of skin biopsy specimens yield a pathogen in 20 to 30 percent of cases. Cultures of swabs
from intact skin are not helpful and should not be performed

Radiographic examination can be useful to determine whether a skin abscess is present (via
ultrasonography) and for distinguishing cellulitis from osteomyelitis (via magnetic resonance
imaging) . Radiographic evaluation may be warranted in patients with underlying
immunosuppression, diabetes, venous insufficiency, or lymphedema and in patients with persistent
systemic symptoms. Radiographic examination cannot reliably distinguish cellulitis from necrotizing
fasciitis or gas gangrene; if there is clinical suspicion for these entities, radiographic imaging should
not delay surgical intervention

In patients with recurrent cellulitis, serologic testing for beta-hemolytic streptococci may be a useful
diagnostic tool. Assays include the anti-streptolysin-O (ASO) reaction, the anti-deoxyribonuclease B
test (anti-DNAse B), the anti-hyaluronidase test (AHT), or the Streptozyme antibody assay . Anti-
DNase B and AHT responses are more reliable than the ASO response following group A
streptococcal skin infections.

MRSA risk : Health care exposures during the prior 12 months: Recent hospitalization/ Residence
in a long-term care facility / Recent surgery / Hemodialysis
Patient-specific risk factors: Known MRSA colonization or past infection with MRSA/ Recent close
contact with a person colonized or infected with MRSA/ HIV infection / Injection drug use /
Homelessness / Men who have sex with men / Antibiotic use within prior 6 months
Environmental exposures associated with outbreaks of MRSA skin abscesses*: Incarceration or
working as prison guard / Military service / Attending schools or living in communities with high
colonization rates/ Living in crowded conditions/ Attending or working in childcare centers/
Playing contact sports or sharing sporting equipment/ Sharing needles, razors, or other sharp
objects

DIFFERENTIAL DIAGNOSIS

Rapidly progressive erythema with signs of systemic toxicity should prompt consideration of severe
infection, including:

●Necrotizing fasciitis – Necrotizing fasciitis is a deep infection that results in progressive destruction
of the muscle fascia. The affected area may be erythematous, swollen, warm, and exquisitely tender.
Pain out of proportion to exam findings may be observed. The diagnosis is established surgically with
visualization of fascial planes.

●Toxic shock syndrome – Toxic shock syndrome typically presents with pain that precedes physical
findings. Clinical signs of soft tissue infection consist of local swelling and erythema followed by
ecchymoses and sloughing of skin. Fever is common. Patients may be normotensive on presentation
but subsequently become hypotensive. (Invasive group A streptococcal infection and toxic shock
syndrome)

●Gas gangrene or myonecrosis – Gas gangrene should be suspected in the setting of fever and
severe pain in an extremity, particularly in the setting of recent surgery or trauma. The presence of
tissue crepitus favors clostridial infection. Gas gangrene can also be detected radiographically.

Cellulitis must be distinguished from other infections including:

●Erythema migrans – Erythema migrans is an early manifestation of Lyme disease; it consists of a

region of erythema at the site of a tick bite, often with central clearing and a necrotic center . The
diagnosis is established based on serologic testing, although sensitivity in early disease is low. A
similar lesion may occur in patients with Southern tick–associated rash illness.STARI

●Herpes zoster – The rash of herpes zoster begins as erythematous papules that evolve into grouped
vesicles . The rash is generally limited to one dermatome but can affect two or three neighboring
dermatomes. The diagnosis is established by polymerase chain reaction

●Septic arthritis – Cellulitis may overlie a septic joint. Clinical manifestations include joint pain,
swelling, warmth, and limited range of motion. The diagnosis of septic arthritis is established based
on synovial fluid examination.

●Septic bursitis – Cellulitis may precede or accompany septic bursitis. Distinguishing cellulitis with
and without bursitis depends on skilled palpation. Radiographic imaging is warranted if septic
bursitis is suspected.

●Osteomyelitis – Osteomyelitis may underlie an area of cellulitis. It is prudent to pursue imaging for
assessment of bone involvement in the setting of chronic soft tissue infection that fails to improve
with appropriate antibiotic therapy.
●Mycotic aneurysm – Mycotic aneurysm should be suspected in the setting of erythema, swelling,
and tenderness at an intravenous drug injection site such as antecubital fossa

Noninfectious masqueraders of cellulitis (unilateral) include:

●Contact dermatitis – Contact dermatitis may be distinguished from cellulitis in that the contact
dermatitis lesions are pruritic. Clinical features include erythema, edema, vesicles, bullae, and
oozing. The reaction is generally limited to the site of contact and is associated with burning,
stinging, or pain

●Acute gout – Acute gouty arthritis consists of severe pain, warmth, erythema, and swelling
overlying a single joint. The diagnosis can be established by synovial fluid analysis, which should
demonstrate the characteristic urate crystals of gout or the calcium pyrophosphate crystals of
pseudogout. Additional clues suggestive of gout include involvement of the first
metatarsophalangeal joint, prior self-limited attacks of arthritis, and presence of tophi.

●Drug reaction – A drug reaction presents with an erythematous maculopapular rash that involves
the trunk and proximal extremities. It may be accompanied by pruritus, low-grade fever, and mild
eosinophilia. The diagnosis is suspected in a patient receiving drug treatment who presents with a
rash of recent onset. The clinical suspicion can be substantiated by histopathologic examination of a
skin biopsy.

●Vasculitis – The morphology of cutaneous lesions of vasculitis is variable. Macular and papular
(including palpable purpura) lesions are characteristically nonblanchable due to the presence of
extravasated erythrocytes in the dermis, which occurs as a result of damaged vessel walls. The
diagnosis is established by skin biopsy.

●Insect bite – An insect bite triggers an inflammatory reaction at the site of the punctured skin,
which appears within minutes and consists of pruritic local erythema and edema. In some cases, a
local reaction is followed by a delayed skin reaction consisting of local swelling, itching, and
erythema.

●Deep venous thrombosis –

●Panniculitis – Panniculitis refers to inflammation of subcutaneous fat and may have many causes,
both infectious and noninfectious . The diagnosis is confirmed via biopsy.

●Vaccination site reaction – A local reaction to vaccination manifests with erythema, swelling, and
tenderness at the injection site; these are typically self-limited.

●Erythema ab igne - Erythema ab igne is an erythematous pigmented dermatosis resulting from

repeated exposures to moderate heat or infrared radiation. The diagnosis is established clinically
and may be confirmed by biopsy.

Noninfectious masqueraders of cellulitis (bilateral) include:

●Stasis dermatitis – Stasis dermatitis is an inflammatory dermatosis of the lower extremities that
occurs in patients with chronic venous insufficiency. It is usually bilateral but can be unilateral in the
setting of anatomic asymmetry. The diagnosis is usually established clinically

●Lipodermatosclerosis – Lipodermatosclerosis is a fibrosing panniculitis of the subcutaneous tissue

that can develop in the setting of chronic venous insufficiency following severe cases of deep venous
thrombosis or associated with lymphatic compromise. Typically the overlying skin is heavily
pigmented and bound down to the subcutaneous tissues. (
●Lymphedema – Lymphedema is abnormal accumulation of interstitial fluid resulting from injury or
anatomic abnormality of the lymphatic system. The diagnosis is usually established clinically

Skin abscess — Skin lesions that should be distinguished from skin abscess include:

●Epidermoid cyst – An epidermoid cyst is a skin-colored cutaneous nodule. The diagnosis is usually
clinical, based on the clinical appearance of a discrete cyst or nodule, often with a central punctum,
that is freely movable on palpation. Epidermoid cysts may become secondarily infected.

●Folliculitis – Folliculitis refers to inflammation of one or more hair follicles. The diagnosis is often
established clinically; rarely, Gram stain and culture or skin biopsy may be warranted to differentiate
folliculitis from other conditions.

●Hidradenitis suppurativa – Hidradenitis suppurativa is a chronic suppurative process involving the

skin and subcutaneous tissue of intertriginous skin. The diagnosis is usually established clinically.

●Nodular lymphangitis – Nodular lymphangitis presents as nodular subcutaneous swellings along the
course of the lymphatic channels.

●Botryomycosis – Botryomycosis is a chronic, suppurative infection characterized by a

granulomatous inflammatory response to S. aureus and other bacteria; it occurs most commonly in
immunocompromised patients. The diagnosis is established via Gram stain, culture, or examination
of pus for granules.

●Myiasis – Myiasis presents as an enlarging nodular mass associated with an insect bite; it is caused
by penetration of fly larvae into subdermal tissue. The diagnosis is established via clinical
manifestations in the setting of epidemiologic exposure to tropical and subtropical areas.
Acute cellulitis and erysipelas in adults: Treatment

Effective treatment of cellulitis and erysipelas depends on determining the most likely
microorganism causing the infection. Beta-hemolytic streptococci cause the vast majority of
erysipelas infections and most cellulitis infections, but cellulitis is sometimes caused by
Staphylococcus aureus and occasionally by a multitude of other organisms.

Examination and clinical features cannot always differentiate erysipelas from cellulitis, so treat for
cellulitis whenever are uncertain. Both erysipelas and cellulitis manifest as areas of skin erythema,
edema, and warmth. On physical examination, classic erysipelas presents as a bright red patch of
skin with a clearly demarcated raised border. Cellulitis involves deeper layers of the skin, so it
classically presents with indistinct borders that are not raised.

"Red-flag" conditions that warrant hospitalization — Red-flag conditions warrant immediate

hospitalization, and some require urgent surgical intervention. Findings that increase suspicion for
these conditions include severe sepsis or septic shock, rapidly progressive infection, or pain out of
proportion to exam findings. ●Toxic shock syndrome ●Necrotizing fasciitis ●Joint involvement (with
or without prosthesis) ●Involvement of vascular graft ●Pyomyositis ●Clostridial myonecrosis (gas
gangrene) ●Compartment syndrome

For individuals with cellulitis or erysipelas without red-flag conditions, we suggest initial treatment
with parenteral antibiotics in the following circumstances:●Systemic signs of toxicity such as fever
>100.5°F/38°C, hypotension, or sustained tachycardia (refractory hypotension should prompt
consideration of toxic shock syndrome) ●Rapid progression of erythema (eg, doubling of the
affected area within 24 hours; in particular, expansion over a few hours with severe pain should
prompt consideration of necrotizing fasciitis)●Extensive erythema●Immunocompromising condition
(eg, neutropenia, immunosuppressive drugs such as chemotherapy for malignancy)●Inability to
tolerate or absorb oral therapy . For patients with lymphangitis accompanying cellulitis, some would
administer parenteral antibiotics because they believe that lymphangitis may be indicative of
imminent bacteremia

ACUTE CELLULITIS The pillars of cellulitis treatment are antibiotic therapy and management of
exacerbating conditions, including the point of entry of infection. At the time of presentation,
selection of empiric antibiotic therapy is based on determining the most likely pathogen Factors that
should be considered when choosing antibiotics for acute cellulitis include the severity and location
of the cellulitis and whether coverage for methicillin-resistant S. aureus (MRSA) or atypical
organisms is necessary.

Pathogens to always cover — Empiric antibiotics for cellulitis should always cover beta-hemolytic
streptococci and methicillin-sensitive S. aureus (MSSA), which are the two most common pathogens
of cellulitis .
Empiric coverage for MRSA is indicated for patients with MRSA risk factors and those who have
increased morbidity if suboptimal antibiotics are administered. Conditions that warrant MRSA
coverage include the following ●Systemic signs of toxicity (eg, fever >100.5°F/38°C, hypotension,
sustained tachycardia)●Cellulitis with purulent drainage or exudate ●Immunocompromising
condition (eg, neutropenia, immunosuppressive drugs such as chemotherapy for malignancy)
Presence of risk factor(s) for MRSA infection (eg, known MRSA colonization or past infection, recent
health care exposure, recent antibiotic use, intravenous drug use)

Wounds and exposures that warrant specific coverage — A broad range of organisms can cause
cellulitis in individuals with wounds, injuries, or certain environmental exposures. Antibiotic
regimens for these conditions are distinct ●Wounds and injuries/ •Diabetic foot ulcers /•Animal
bites /•Human bites /•Puncture wounds other than bites /•Pressure injury or pressure ulcer
/•Surgical wound /●Environmental exposures/•Water exposures /•Travel-related skin infections

Anatomic site of infection — Cellulitis can occur on any part of the body. Depending on the location
of cellulitis, antibiotic selection and other interventions, including surgery, can vary. ●Cellulitis of the
extremities – The extremities are the most common site of cellulitis. In the absence of a red-flag
condition or other indication for broadened antibiotic coverage, treatment focuses on beta-
hemolytic streptococci and S. aureus/ If cellulitis involves the hand, hospitalization is typically
recommended along with evaluation by a surgeon ●Facial cellulitis – Facial skin infections are more
often due to erysipelas than cellulitis. Treatment of facial cellulitis focuses on beta-hemolytic
streptococci and S. aureus. If the area around the eye is cellulitic, differentiation of preseptal
(periorbital) from orbital cellulitis is paramount. Preseptal cellulitis is generally a mild infection of the
skin around the eye, whereas orbital cellulitis involves the deeper tissues of the eye and can lead to
loss of vision or even loss of life. Rarely, infections involving the medial third of the face (ie, the areas
around the eyes and nose) can be complicated by septic cavernous thrombosis
●Neck cellulitis – Cellulitis of the neck is uncommon. When present, consideration should be given to
underlying deep neck space infection or submandibular space infection (Ludwig angina)

●Breast cellulitis – Breast cellulitis is usually due to beta-hemolytic streptococci or S. aureus and is
managed similarly to uncomplicated cellulitis,
●Cellulitis of the abdominal wall – Most reports are in individuals with surgical site infection,
abdominal-wall mesh infection, or intra-abdominal conditions such as appendicitis or colon cancer.
In each of these situations, both surgical intervention and antibiotic therapy are usually necessary
Few reports of idiopathic abdominal-wall cellulitis exist, but the infection is probably more common
We suggest treating underlying dermatologic and other contributing conditions, such as intertrigo,
while the patient is receiving antimicrobial therapy.

●Cellulitis of the perineum or genitalia – Skin infections of the perineum and genitals can be due to
cellulitis, folliculitis, or other etiologies. Of most concern is Fournier gangrene, a polymicrobial
necrotizing fasciitis of the perineum that can involve the lower abdominal wall, the penis and
scrotum in men, and the labia in women. Fournier gangrene is a medical and surgical emergency
with a high fatality rate.

Selecting an antibiotic regimen — The first step when selecting an initial antibiotic regimen for
cellulitis is to determine whether providing coverage beyond beta-hemolytic streptococci and S.
aureus is necessary. Certain conditions, exposures, or anatomic sites often require broader antibiotic
coverage than standard regimens For most patients with cellulitis who don't have features that
warrant specific management, approach depends on the severity of illness and risk for MRSA

Patients with severe sepsis or an immunocompromising condition — In the setting of severe sepsis
or immunocompromise, rapid administration of empiric broad-spectrum antibiotics is indicated
because delay or lack of adequate coverage increases mortality ●Initial therapy – •Intravenous
vancomycin PLUS Cefepime 2 g intravenously (IV) every eight hours

Other regimens may be more appropriate in certain situations:

•For patients who are known or suspected of having an infection due to an organism with an
extended-spectrum beta-lactamase (ESBL), we suggest using an empiric carbapenem (eg,
meropenem 1 g IV every eight hours) in conjunction with vancomycin.

•For patients with reported beta-lactam allergies, empiric antibiotic selection depends on the type
and severity of the reaction . Patients with mild, non-immunoglobulin (Ig)E-mediated reactions to
penicillins (eg, maculopapular rash) can usually receive cephalosporins safely . For patients who
cannot take any beta-lactam agent, suggest intravenous vancomycin paired with either levofloxacin
(750 mg IV once daily) or aztreonam (2 g IV every six to eight hours). Note that individuals with a
history of life-threatening or anaphylactic reaction to ceftazidime should not be given aztreonam,
but levofloxacin is generally safe.

●Oral step-down therapy – Once clinical improvement and resolution of sepsis occur, it is generally
appropriate to transition to an oral regimen. If a pathogen is identified during the course of therapy,
antibiotics should be narrowed to coverage specific for that pathogen. •For immunocompromised
patients without an identified pathogen, we suggest amoxicillin-clavulanate (875 mg orally every 12
hours) plus either doxycycline (100 mg orally twice daily) or trimethoprim-sulfamethoxazole (TMP-
SMX; one to two double-strength tablets orally twice daily). For individuals with serious beta-lactam
allergies, levofloxacin (750 mg orally once daily) is a reasonable replacement for amoxicillin-
clavulanate in this regimen. •Stable patients who are not immunocompromised can generally be
transitioned to one of the narrower oral agents described below.

The rationale for using a spectrum that covers pathogens in addition to streptococci and S. aureus in
these populations is the risk of poor outcomes with a narrower spectrum of empiric therapy in
severely ill patients if other pathogens are involved; in particular, those who have certain
immunocompromising conditions are at risk for a wide range of pathogens. However, there is a
spectrum of immunocompromising conditions and some do not substantially increase that risk.
For immunocompromised patients at risk of infection due to a variety of pathogens, a dermatologic
evaluation and skin biopsy performed early in the course of therapy can help to guide therapy,
especially when nodular or ulcerative lesions are present.

Immunocompetent patients without severe sepsis —divide this group of patients into those who
warrant MRSA coverage and those who do not

Without an indication for MRSA coverage — For most patients, antibiotic regimens that cover beta-
hemolytic streptococci and MSSA are effective, and coverage for MRSA is not necessary ●Oral
antibiotic regimens – Many patients with cellulitis of the lower extremity can be managed with oral
antibiotics in the outpatient setting ,suggest one of the following regimens: •Dicloxacillin 500 mg
orally every six hours •Cephalexin 500 mg orally every six hours •Cefadroxil 500 mg orally every 12
hours or 1 g orally once daily

●Parenteral antibiotic regimens – •Cefazolin 1 to 2 g IV every eight hours •Nafcillin 1 to 2 g IV every

four hours•Oxacillin 1 to 2 g IV every four hours •Flucloxacillin 2 g IV every six For cefazolin, nafcillin,
and oxacillin, we usually favor the higher dosages listed above (ie, 2 g) for treatment of these
infections. Once there is evidence of clinical improvement, parenteral antibiotics should be switched
to one of the oral regimens listed above. Studies suggest that most patients with cellulitis do not
need MRSA coverage:

With an indication for MRSA coverage — MRSA coverage is indicated if certain conditions are
present (see 'Indications for MRSA coverage' ●Oral antibiotic regimens – For many patients,
treatment in the outpatient setting with oral antibiotics is effective •TMP-SMX (one to two double-
strength tablets orally twice daily; for patients who weigh more than 70 kg and have normal renal
function, we favor two double-strength tablets twice daily). •Amoxicillin (875 mg orally twice daily)
plus doxycycline (100 mg orally twice daily).

TMP-SMX has activity against both Streptococcus and S. aureus, including MRSA. Doxycycline
provides coverage for S. aureus, including MRSA; amoxicillin is added to it for streptococcal
coverage. Cellulitis cure rates with TMP-SMX range from 78 to 83 percent

Linezolid (600 mg orally every 12 hours) is acceptable if the above agents cannot be used. linezolid
has at least equivalent outcomes for skin and soft tissue infections (including MRSA infections) when
compared with intravenous vancomycin . elevated rates of nausea, vomiting, and thrombocytopenia
when linezolid was administered; we suggest weekly complete blood counts for patients receiving
linezolid for longer than two weeks.

Clindamycin (450 mg orally every eight hours) may have activity against both Streptococcus and S.
aureus and is an acceptable alternative. However, we generally avoid it due to risk for Clostridioides
difficile infection and the possibility of streptococcal and staphylococcal resistance. Local rates of
resistance to clindamycin should be considered before prescribing

●Parenteral antibiotic regimen – •Intravenous vancomycin •Daptomycin 4 to 6 mg/kg IV every 24

hours (alternative). For patients who cannot take vancomycin or daptomycin, alternative agents can
be used and are listed in the table . Once there is evidence of clinical improvement, parenteral
antibiotics should be switched to one of the oral regimens listed above.

Parenteral antimicrobial therapy for treatment of skin and soft tissue infections due to methicillin-
resistant Staphylococcus aureus (MRSA) in adults

Drug Adult dose

Antibiotics of choice*

Vancomycin¶ 15 to 20 mg/kg/dose every 8 to 12 hours

DaptomycinΔ 4 to 6 mg/kg IV once daily

Alternative agents

Short-acting agents with parenteral or oral dosing

Linezolid 600 mg IV (or orally) twice daily

Tedizolid 200 mg IV (or orally) once daily

Delafloxacin 300 mg IV twice daily (or 450 mg orally twice daily)

Omadacycline◊ 100 mg IV once daily (or 300 mg orally once daily)

Short-acting agent with parenteral dosing§

Ceftaroline 600 mg IV every 12 hours

Telavancin 10 mg/kg once daily

Long-acting agents with parenteral dosing

Dalbavancin
Single-dose regimen: 1500 mg once

Two-dose regimen: Initial dose 1000 mg, followed by 500 mg dose one week later

Oritavancin 1200 mg IV as a single dose

* In areas outside the United States where teicoplanin is available, some use it as the drug of choice
for initial therapy of gram-positive pathogens, while others favor its use for patients with intolerance
to vancomycin.

¶ For severely ill patients, a vancomycin loading dose (20 to 35 mg/kg) is appropriate[1]; within this
range, we use a higher dose for critically ill patients. The loading dose is based on actual body
weight, rounded to the nearest 250 mg increment and not exceeding 3000 mg. The initial
maintenance dose and interval are determined by nomogram (typically 15 to 20 mg/kg every 8 to 12
hours for most patients with normal renal function). Subsequent dose and interval adjustments are
based on AUC-guided or trough-guided serum concentration monitoring.

Δ Dosing of daptomycin for treatment of skin and soft tissue infection is 4 to 6 mg/kg IV once daily;
dosing for treatment of bacteremia is at least 6 mg/kg IV once daily.

◊ A loading dose may be used: 200 mg IV over 60 minutes OR 100 mg IV over 30 minutes twice.

§ Ceftobiprole has broad-spectrum activity against gram-positive and gram-negative organisms and
is available in some countries outside the United States.

Alternatives for serious beta-lactam allergy — Although many patients have reported beta-lactam
allergies, most do not have allergies that would prohibit the use of beta-lactams. In particular, many
with penicillin allergies can still take a cephalosporin For immunocompetent patients without
severe sepsis who have serious allergies that preclude use of beta-lactams, we suggest one of the
following regimens ●Oral antibiotic regimen – If no indication for parenteral antibiotics is present,
we suggest either of the following:•TMP-SMX (one to two double-strength tablets orally twice
daily).•Linezolid (600 mg orally every 12 hours / An alternative is clindamycin (450 mg orally every
eight hours), but we generally avoid it due to risk of C. difficile infection and the possibility of
streptococcal and staphylococcal resistance . We do not recommend macrolides, such as
azithromycin, due to high resistance rates among beta-hemolytic streptococci
●Parenteral antibiotic regimen –intravenous vancomycin

Duration of antibiotic therapy — The duration of therapy should be individualized depending on

clinical response. In general, five to six days of therapy is appropriate for patients with
uncomplicated cellulitis whose infection has improved . Extension of antibiotic therapy (up to 14
days) may be warranted in the setting of severe infection, slow response to therapy, or
immunosuppression.

Adjunctive treatments — When treating cellulitis of the lower extremities, management of

exacerbating conditions and any points of entry for microorganisms is paramount.Elevation and
edema management — Edema, a common manifestation of cellulitis, can impair antibiotic
penetration into infected tissue and prevent resolution of infection. For lower extremity cellulitis,
elevation of the affected limb hastens improvement by allowing gravity drainage of edema and
inflammatory substances . To optimize the effect of gravity, we instruct patients to elevate the heel
of the foot above the knee and the knee above the hip.
Lymphedema and venous insufficiency are commonly associated with lower extremity cellulitis,
especially in individuals who are obese. In addition to elevation, compression therapy can be used to
treat both lymphedema and venous insufficiency. While compression therapy has been shown to be
effective for preventing recurrences of cellulitis in individuals with lymphedema, the efficacy of
compression therapy during acute cellulitis is uncertain, and clinical practice varies. Traditionally,
compression therapy was felt to be contraindicated during episodes of acute cellulitis for fear of
compromising vascular function, although no data support this contraindication. Limited data
suggest that individualized compression therapy applied by specialized lymphedema
physiotherapists may not be harmful and does not compromise microcirculation in patients with
active cellulitis. Compression therapy should be avoided in individuals with known or suspected
arterial insufficiency.

Skin management — Treatment of skin conditions and the point of microorganism entry can
expedite resolution of cellulitis.The point of entry of microorganisms should be identified and
managed at the time of diagnosis of cellulitis. Common points of entry include intertrigo in the toe
webs of the feet, tinea pedis, onychomycosis, and lower extremity ulcers. As cellulitis evolves, skin
can begin to weep, blister, flake, or crack. Dermatologists and wound care specialists can provide
assistance with management of these conditions. Numerous underlying skin conditions are risk
factors for the development of cellulitis including atopic dermatitis (eczema) and psoriasis. Such
conditions should be optimally managed in conjunction with standard cellulitis treatment.

TREATMENT OF ERYSIPELAS Management of erysipelas primarily consists of antibiotic therapy along

with the adjunctive therapies described above. Oral antibiotics for erysipelas — Most cases of
erysipelas can be managed with oral antibiotics in the outpatient setting. For patients with
unambiguous erysipelas who do not meet criteria for parenteral antibiotics, empiric oral antibiotics
active against beta-hemolytic streptococci should be administered ●Penicillin V potassium 500 mg
orally every six hours ●Amoxicillin 875 mg orally every 12 hours ●Cephalexin 500 mg orally every six
hours●Cefadroxil 500 mg orally every 12 hours or 1 g orally once daily

For patients with serious beta-lactam allergies that preclude use of the above regimens, oral options
are the same as those listed above for cellulitis.

Parenteral antibiotics for erysipelas —cover beta-hemolytic streptococci and S. aureus for patients
with erysipelas who have an indication for parenteral. Differentiating erysipelas from cellulitis is not
always straightforward, so we believe that adding staphylococcal coverage is prudent in individuals
who are ill enough to warrant parenteral therapy. For such patients, appropriate regimens include
those described in the above discussion about antibiotic therapy for cellulitis. If a microbiologic
diagnosis of beta-hemolytic Streptococcus is subsequently established (eg, by a positive blood
culture), then recommend switching to parenteral aqueous crystalline penicillin G (4 million units
intravenously [IV] every four hours).
For patients in whom outpatient parenteral antibiotic is desired, ceftriaxone (1 to 2 g IV once daily) is
an alternative that allows for convenient once-daily outpatient administration.Once there is
evidence of clinical improvement, parenteral antibiotics should be switched to oral antibiotics that
cover streptococci. •TMP-SMX (one to two double-strength tablets orally twice daily; for patients
who weigh more than 70 kg and have normal renal function, we favor two double-strength tablets
twice daily). •Amoxicillin (875 mg orally twice daily) plus doxycycline (100 mg orally twice daily).
MONITORING RESPONSE TO THERAPYPatients with cellulitis or erysipelas typically have symptomatic
improvement within 24 to 48 hours of beginning antimicrobial therapy, although visible
improvement of skin manifestations can take 72 hours or longer
It is useful to document the baseline appearance of the physical findings at the start of antibiotic
therapy. We obtain a baseline digital photograph to help monitor progress. Some experts outline the
area of infection with an indelible marker at the time of treatment initiation to allow objective
monitoring of progress. In the early stages of treatment, erythema may expand beyond the initial
margins of infection as the infection dissipates. Deepening of erythema may be observed due to
destruction of pathogens that can enhance local inflammation. These findings should not be
mistaken for therapeutic failure. Clues that the infection is improving include reductions in fever,
pain, brightness or intensity of erythema, peripheral white blood cell count, and other signs of
infection. As cellulitis evolves, skin can begin to weep, blister, flake, or crack. None of these findings
are necessarily indications of worsening infection., wound care specialists or dermatologists can help
to manage these conditions. Residual skin inflammation is a common finding after completion of
effective therapy , more than half had residual inflammation at the end of therapy

REFRACTORY INFECTION Worsening erythema or systemic symptoms after 24 to 48 hours should

prompt a search for possible reasons for treatment failure. Evaluation should consider multiple
possibilities:●Red-flag condition – Any time cellulitis progresses rapidly or clinical symptoms,
especially pain, seem to be out of proportion to physical exam, red-flag conditions should be
considered. A low threshold for surgical consultation to evaluate for these conditions is prudent.
●Inadequate dosing or tissue penetration of antibiotics – Conditions at the site of infection, such as
edema or peripheral artery disease, can reduce the ability of antibiotics to penetrate into soft tissue.
To optimize tissue penetration of the antibiotics, management of these conditions is paramount.
In patients failing oral antibiotics, switching from oral to intravenous antibiotics can markedly
increase antibiotic delivery to the site of infection. This is especially the case for antibiotics with poor
bioavailability (such as beta-lactam agents) or for patients whose ability to absorb oral medications
is uncertain.
In select situations, using higher antibiotic dosages may be beneficial. Obesity can increase drug
clearance from circulation and thereby limit the amount of antibiotic that reaches the site of
infection. Moreover, certain bacteria, such as Pseudomonas spp, require higher antibiotic dosages to
achieve bacterial killing.

●Abscess – As cellulitis responds to antibiotic therapy, sometimes the infection can coalesce to form
an abscess below the surface. Abscess should be suspected when focal tender fluctuance is found on
exam, and ultrasound can aid in detection. If present, surgical consultation for incision and drainage
is recommended.

●Diagnosis other than cellulitis or erysipelas – Failure to respond to appropriate therapy should
prompt consideration that the initial diagnosis of cellulitis is incorrect. Cellulitis is often confused
with other infectious and noninfectious illnesses, and misdiagnosis is perhaps the most common
cause of lack of response to therapy

●Resistant pathogen – Re-evaluating for the possibility of resistant microorganisms and reviewing
past culture data can help guide antibiotic change. Methicillin-resistant S. aureus (MRSA) or other
organisms associated with certain conditions or environmental exposures should be considered.

In immunocompromised individuals, cellulitis can be due to a multitude of organisms including

atypical bacteria, fungi, viruses, and parasites. If these individuals fail to respond to broad-spectrum
antibiotic therapy, a dermatologic evaluation and skin biopsy can be beneficial. Nodular or ulcerative
lesions should be biopsied early during the clinical course in highly immunocompromised individuals,
especially for those who are septic or have rapidly progressive illness

RECURRENT Infections Recurrent erysipelas and cellulitis are not uncommon occurrences.
Recurrences have been reported to occur in 14 percent of cellulitis cases within one year and up to
45 percent of cases within three years, usually in the same location During the active stage of
infection, management of recurrent episodes is the same as the approach for initial episodes. For
individuals who have frequent or severe recurrences, prefilled prescriptions for treatment doses of
antibiotics can be provided so that patients can self-initiate antibiotic therapy at the onset of
symptoms while seeking immediate medical attention. Prevention of recurrences — Potential tools
for prevention of recurrent cellulitis include alleviation of predisposing conditions (such as use of
compression therapy for management of edema), antibiotic suppression, and S. aureus
decolonization. ●Edema. Elevation of the affected area and diuretic therapy can help to alleviate
edema. Compression therapy has been shown in studies to be highly effective for lymphedema and
venous insufficiency ●Foot infections including intertrigo in the toe webs of the feet, tinea pedis, and
onychomycosis. ●Lower extremity ulcers ●Chronic skin conditions, such as eczema and psoriasis.
●Obesity ●Immunosuppression.

Compression therapy — For patients with recurrent episodes of cellulitis in the setting of chronic
lower extremity venous insufficiency or lymphedema, compression therapy is an essential
component of management that has been shown to be effective in reducing episodes of recurrent
cellulitis The compression therapy was provided by specialized lymphedema physiotherapists and
usually consisted of prescription knee-high stockings that included the foot and were worn
throughout the day. The compression therapy was provided only when no active cellulitis was
present

Antibiotic suppression for selected patients — For patients who optimize predisposing conditions
but still develop recurrent cellulitis in the same anatomic site, we suggest suppressive antibiotic
therapy . Although infrequent, there are scenarios (eg, complicated bacteremia in patients with a
prosthetic device) when initiation of suppressive therapy after an initial bout of cellulitis may be
warranted; consultation of clinicians with experience in these cases is suggested.For suppressive
therapy, we suggest one of the following antibiotic regimens:●For patients with known or presumed
beta-hemolytic streptococcal infection•Penicillin V (250 to 500 mg orally twice daily)•Penicillin G
benzathine intramuscular (IM) injections (1.2 to 2.4 million units IM every four weeks; shorten
interval to every two weeks if longer interval is not effective) ●For patients with known or presumed
staphylococcal infection:•Cefadroxil (500 mg orally twice daily)•Cephalexin (500 mg orally four times
daily)•Trimethoprim-sulfamethoxazole (TMP-SMX; one double-strength tablet orally twice daily)
Cefadroxil and cephalexin have no activity against methicillin-resistant S. aureus (MRSA) and should
only be used if recurrent methicillin-sensitive S. aureus (MSSA) infection is suspected.For patients
with reported beta-lactam allergies, we suggest referral to an allergist. If beta-lactam allergy is
confirmed and TMP-SMX is not an option, we try doxycycline (100 mg orally twice daily). We avoid
clindamycin (150 mg orally once daily) unless there are no other options due to risk of C. difficile
infection Other than penicillin and clindamycin, minimal data exist to support the options listed
above as suppressive agents. The optimal dosing for these antibiotics when used as suppression is
unknown and may be lower than the suggested doses. Titration to lower dosages over time may
allow determination of the best dose for individual patients.
Serologic testing for beta-hemolytic streptococci may be a useful diagnostic tool to help guide the
choice of suppressive antibiotic therapy. Such tests include the anti-streptolysin-O reaction and the
anti-deoxyribonuclease B test (anti-DNAse B). Suppressive therapy may be continued for several
months to years with interval assessments for efficacy and tolerance. Patients in whom recurrent
cellulitis occurs while on suppressive therapy should undergo re-evaluation of predisposing
conditions and antimicrobial agents.

S. aureus decolonization — For patients with suspected recurrent S. aureus infection, we suggest an
attempt at S. aureus decolonization.
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