Infectious Disease · PANCE / PANRE

Cellulitis

Acute bacterial infection of the dermis and subcutaneous tissue, most often caused by beta-hemolytic streptococci or Staphylococcus aureus.

Also known as: cellulitis, skin infection, soft tissue infection, SSTI

Overview

Non-purulent or purulent bacterial infection of the deeper dermis and subcutaneous fat, characterized by warm, erythematous, edematous, tender skin without sharp borders. Distinguished from erysipelas (more superficial, sharply demarcated) and necrotizing fasciitis (deep, rapidly progressive, systemic toxicity).

Epidemiology

Among the most common reasons for emergency visits and hospitalization for skin and soft tissue infection. Annual incidence ~200 per 100,000. Recurrence common (~30% within 3 years) especially in patients with lymphedema or prior cellulitis.

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Risk factors

Skin barrier breakdown: tinea pedis, eczema, trauma, surgical wounds, IV drug use, insect bites
Chronic edema/lymphedema (post-mastectomy, post-saphenous vein harvest, filariasis, obesity)
Venous insufficiency, peripheral arterial disease
Diabetes mellitus (especially with peripheral neuropathy)
Immunocompromise

Pathophysiology

Bacteria enter through breaks in the skin and proliferate in the dermal/subcutaneous space. Streptococcal cellulitis spreads rapidly via hyaluronidase and streptokinase, often without purulence. Staphylococcal infection (including MRSA) more often produces abscess and purulent drainage. Systemic toxicity reflects cytokine release and bacteremia in severe cases.

Clinical presentation

Symptoms

Localized warmth, erythema, edema, tenderness — usually a single extremity
Spreading borders without sharp demarcation
Fever, chills, malaise in moderate/severe disease
Possible regional lymphangitis ('red streaking') and lymphadenopathy

Signs / physical exam

Warm, indurated, erythematous skin with poorly defined edges
Possible purulent drainage from puncture site or abscess
Lymphangitic streaking toward draining nodes
Look for portal of entry (tinea pedis, ulceration, IV site)

Classic findings

Unilateral lower-leg cellulitis is extremely common; bilateral lower-leg 'cellulitis' is almost never cellulitis — consider stasis dermatitis, lipodermatosclerosis, or contact dermatitis.

Differential diagnosis

DVT — Unilateral leg swelling and pain, calf tenderness, Homans sign — but erythema usually less prominent; duplex ultrasound
Stasis dermatitis — Bilateral, chronic, hemosiderin staining, weeping/crusting; not warm or tender; often misdiagnosed as cellulitis
Contact or allergic dermatitis — Pruritic > tender, vesicular or scaling, sharp borders matching exposure
Necrotizing fasciitis — Pain out of proportion, rapid progression, bullae, crepitus, systemic toxicity; surgical emergency
Erysipelas — Bright red, sharply raised borders ('orange peel'), more superficial; usually streptococcal
Septic arthritis — Joint effusion, restricted ROM; arthrocentesis
Gout — Acute monoarticular, especially first MTP; uric acid crystals on synovial fluid

Diagnostic workup

Diagnostic criteria

Clinical diagnosis. IDSA stratifies into mild, moderate, severe and purulent vs non-purulent for treatment selection.

Labs

CBC, BMP, lactate if systemic toxicity
Blood cultures only if severe sepsis, immunocompromise, water exposure, animal/human bites, or unusual organism suspected
Wound culture if purulent drainage or abscess (incise and drain first)
Consider HSV/HSV PCR if recurrent 'cellulitis' on the face/genitals

Imaging

Bedside ultrasound to differentiate cellulitis (cobblestoning) from abscess (anechoic collection)
Plain films for foreign body, soft tissue gas (necrotizing infection), or osteomyelitis
CT/MRI if necrotizing fasciitis suspected (but do NOT delay surgical consultation for imaging)

Diagnostic algorithm

Presentation	Likely Pathogen	First-line Outpatient	First-line Inpatient
Non-purulent, mild	Beta-hemolytic strep	Cephalexin or dicloxacillin	Cefazolin
Non-purulent, severe	Strep ± gram-negative	Hospitalize	Vancomycin + piperacillin-tazobactam
Purulent/abscess	S. aureus (MRSA possible)	I&D + TMP-SMX or doxycycline	I&D + vancomycin
Cat/dog bite	Pasteurella	Amoxicillin-clavulanate	Ampicillin-sulbactam
Water exposure	Aeromonas / Vibrio	Doxycycline + ciprofloxacin	Doxycycline + ceftriaxone

Empiric antibiotic selection for cellulitis stratified by clinical presentation and exposure.

Treatment

First-line

Non-purulent cellulitis (likely beta-hemolytic strep):
• Mild outpatient: oral beta-lactam — cephalexin 500 mg PO QID, dicloxacillin 500 mg PO QID, or penicillin VK
• Moderate: IV cefazolin or ceftriaxone
• Severe (systemic toxicity, rapid progression): IV vancomycin + piperacillin-tazobactam pending evaluation for necrotizing infection
Purulent cellulitis / abscess (MRSA coverage required):
• Incision and drainage is the cornerstone for abscess
• Outpatient MRSA-active oral options: TMP-SMX DS 1-2 tabs PO BID, doxycycline 100 mg PO BID, clindamycin 300-450 mg PO QID, linezolid 600 mg PO BID
• Inpatient MRSA coverage — vancomycin, linezolid, daptomycin
• Beta-lactam for skin — cefazolin, cephalexin, dicloxacillin (for strep coverage when MRSA also possible — pair with TMP-SMX or doxycycline)
Typical duration 5-7 days; extend if slow response (DICE/Aboltins data support 5 days for uncomplicated cellulitis)

Second-line / adjunct

Special exposures:
• Water exposure: add coverage for Aeromonas (freshwater) or Vibrio (saltwater) — doxycycline + ceftriaxone or fluoroquinolone
• Cat/dog bite: amoxicillin-clavulanate (Pasteurella multocida)
• Human bite: amoxicillin-clavulanate (Eikenella corrodens)
Recurrent cellulitis (≥3 episodes/year) — consider chronic prophylaxis with low-dose penicillin or erythromycin (PATCH trial)

Complications

Bacteremia and sepsis
Local abscess formation
Necrotizing fasciitis (if missed or progressing)
Lymphangitis, lymphedema (recurrent), elephantiasis nostras verrucosa
Endocarditis (especially with bacteremic Staphylococcus aureus)
Osteomyelitis (especially diabetic foot)

PANCE pearls

Treat predisposing tinea pedis — interdigital fissures are a recurrent portal of entry; eradicating the entry portal reduces recurrence (note: the PATCH trials demonstrated benefit from prophylactic penicillin, not antifungals).
Bilateral lower-extremity 'cellulitis' is rare; reconsider the diagnosis (stasis dermatitis is the great mimicker).
Cellulitis often appears worse on day 1-2 of antibiotics as bacterial lysis releases mediators — do not switch antibiotics for warmth/redness alone in the first 48 hours.
Outline the erythema with a marker on admission to monitor progression objectively.
Severe pain out of proportion, bullae, crepitus, or systemic toxicity → necrotizing fasciitis; immediate surgical consult.

References

IDSA 2014 — Stevens et al., Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections (Clin Infect Dis)
PATCH I/II — Thomas et al., Penicillin to prevent recurrent leg cellulitis (NEJM 2013)
Aboltins 2014/Hepburn — Trials supporting 5-7 day antibiotic courses for uncomplicated cellulitis

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