Cellulitis

I. What every physician needs to know

Cellulitis is a bacterial infection of the deep dermis and subcutaneous tissue.
Infection begins when pathogens gain entry via cutaneous disruption.
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Cellulitis presents with relatively acute onset of poorly demarcated inflammation and erythema, most commonly on a unilateral lower extremity.
Cellulitis must be distinguished from other soft tissue infections as well as life-threatening conditions such as necrotizing fasciitis.
Clinical distinction between purulent vs nonpurulent cellulitis is essential as it guides management: antimicrobial coverage of purulent cellulitis must cover MRSA while antimicrobial coverage for nonpurulent cellulitis requires coverage for strep and MSSA.
Hospitalization is indicated in immunocompromised patients, concern for poor adherence to antimicrobial therapy, if outpatient therapy has failed, if concern exists for complication, or if patient has hemodynamic instability or altered mental status.
Parenteral antibiotics should be transitioned to oral antibiotics after 48 hours of apyrexia and regression of soft tissue inflammation.

II. Diagnostic Approach

As cellulitis is typically nonculturable, the diagnosis is a clinical one. Cellulitis presents with relatively acute onset of a poorly demarcated area of skin erythema, induration, warmth, and pain. In moderate or severe cellulitis, systemic symptoms such as fever or hypotension may be present.

A. History

Epidemiology

Incidence increasing, both for outpatient cases as well as hospitalizations.

There is no statistically significant difference between sexes.

Over 65,000 patients hospitalized yearly in the U.S. for cellulitis.
Risk Factors

Disruption of cutaneous barrier

Direct disruption (trauma, bites, IVDU)

Edema (venous congestion, h/o saphenous vein removal, lymphatic disruption)

Inflammation (infection such as dermatitis, radiation therapy)

Increasing age: the typical patient is middle aged or elderly, although it can occur in all age groups.
History of Present Illness

Symptoms: The patient may complain of an area of inflamed skin – redness, swelling and pain. Fever or malaise may also be present. The lower legs are most common although any part of the skin could be affected.

Ask about cellulitis risk factors (above)

Ask about possible point of bacterial entry, although this is often occult

Ask about patient risk factors for severe disease: immunocompromised, failed outpt therapy

Ask about systemic symptoms (altered mental status, lightheadedness/dizziness, fevers)

B. Differential Diagnosis

Infectious

Erysipelas: soft tissue infection involving the upper dermis and superficial lymphatics. Presents with sharply demarcated, raised plaques.

Abscess: tender, fluctuant collection of pus; requires drainage

Septic arthritis or bursitis: may be present concomitantly with cellulitis

Osteomyelitis: may be present concomitantly with cellulitis

Erythema Migrans

Severe, life-threatening infections

Necrotizing fasciitis: rapidly progressing infection of the subcutaneous tissue and fascia; requires emergent surgical intervention. Typically presents with pain out of proportion to physical exam findings.

Gas gangrene: Recent instrumentation or trauma should raise suspicion. Crepitus may be found on exam or radiographically.

Vascular conditions

Superficial thrombophlebitis: usually associated with IV access

Erythematous, indurated area with tender cord palpable along course of superficial vein

Deep vein thrombosis: unilateral leg erythema, warmth, and edema. Risk factors for thrombus (malignancy, hypercoagulable state, travel) suggest this possibility.

Stasis dermatitis: often bilateral in patient with chronic venous edema

Dermatologic conditions

Contact dermatitis: history of exposure to offending agent. Sharply demarcated lesion, nontender, with pruritus.

Drug reaction: requires review of potential exposure to culprit agents. Typically a fixed eruption.

Insect bite: presence of pruritus can help differentiate along with history of exposure or pattern of exposure on exposed skin.

Noninfectious

Stasis Dermatitis: most common mimicker of cellulitis

Gout

Bursitis

Hematoma

Vasculitis

Panniculitis

Calciphylaxis

C. Physical Examination

Cellulitis is typically unilateral; bilateral presentation should prompt evaluation for other diagnoses.
Lower extremities are most commonly affected although any part of the skin can be involved.
Providers should outline the margins of the involved area at diagnosis to allow accurate monitoring of soft tissue inflammation and response to therapy
Vital signs: monitor for systemic symptoms, particularly hypotension or fever.
Local area: skin erythema, edema, warmth and tenderness. The margins are diffuse and non-discrete. There may also be dimpling around hair follicles, vesicles, or clear bullae.
Assess for the following:

Risk factors for developing cellulitis: edema, inflammation, trauma

Point of bacterial entry (fissure, ulcer, interdigit maceration)

Associated findings: peau d’orange (from involvement of lymphatics), regional lymph node involvement

Purulent drainage or abscess formation with careful palpation

Signs that would suggest alternative diagnosis, including crepitus (suggest necrotizing infection)

D. Diagnostic tests

1. Laboratory Studies

Diagnosis is clinical; laboratory studies may support the diagnosis but are not required:

Nonspecific but supportive laboratory findings: leukocytosis, elevated erythrocyte sedimentation rate, elevated C-reactive protein
Skin surface swab, blood cultures, cutaneous aspirates are NOT routinely recommended

Recommended ONLY if malignancy undergoing chemotherapy, neutropenia, severe cell-mediated immunodeficiency, immersion injury, or animal bites

2. Imaging Studies

Diagnosis is clinical; imaging is not required to make the diagnosis.

If alterative diagnoses are being considered, the following imaging may be helpful:

Plain X-ray: May show cortical erosion or periosteal reaction to suggest osteomyelitis. The presence of subcutaneous gas suggests a necrotizing infection. This is a relatively specific but insensitive finding.
Doppler ultrasound: Use if DVT is suspected. Also may be useful in ruling out underlying abscess.
Computed tomography (CT): May show soft tissue gas as well as deep tissue abscess.

Magnetic resonance imaging (MRI): Is superior to CT in detecting necrotizing infections and osteomyelitis. Tip: if there is clinical suspicion for necrotizing fasciitis or gas gangrene, radiographic imaging should not delay surgical intervention.

E. Over-utilized or “wasted” diagnostic tests associated with this diagnosis

Routine blood cultures, which are positive in less than 5% of cases
Routine skin swabs, skin biopsies, or needle aspirates. Routine soft tissue ultrasound.

III. Management

Distinguish purulent vs nonpurulent cellulitis

This is essential to appropriate management as this determination will guide antimicrobial therapy.
Purulent cellulitis has purulent drainage or exudate without a drainable abscess.
Nonpurulent cellulitis has no purulent drainage or exudate.

Determine severity

Mild Cellulitis

No systemic signs of infection
Moderate

1 or more SIRS criteria (temperature >38C or <36C, HR>90/min, RR>20, WBC >12K or <4K)
Severe

2 or more SIRS criteria PLUS hypotension, immunocompromised, or rapid progression

Determine need for inpatient admission

Indicated in immunocompromised patients, concern for poor adherence to antimicrobial therapy, if outpatient therapy has failed, if concern exists for complication, or if systemic symptoms (hypotension, altered mental status)

Antimicrobial selection and duration of therapy

General principles

Purulent cellulitis: requires coverage for MRSA

Nonpurulent cellulitis: requires coverage for strep and MSSA

If systemic symptoms are present, hospitalization and parenteral antibiotics are indicated

MRSA + strep coverage indicated if severe cellulitis, penetrating trauma, MRSA infection elsewhere, MRSA nasal colonization, or IVDU

Nonpurulent cellulitis: empiric coverage for strep and MSSA

Mild: oral antibiotics

First line: cephalexin, dicloxacillin, penicillin VK, amoxicillin/clavulanate

If penicillin allergy: clindamycin

Moderate: clinical determination of oral vs. intravenous therapy

Oral antibiotics

Cephalexin, dicloxacillin, penicillin VK, amoxicillin/clavulanate

If penicillin allergy: clindamycin

Intravenous antibiotics

Cefazolin, ceftriaxone, penicillin G

If penicillin allergy: clindamycin

Severe: intravenous antibiotics

Broad spectrum coverage with vancomycin + piperacillin-tazobactam or imipenem/meropenem

Purulent cellulitis: empiric coverage for MRSA

Mild: oral antibiotics

Trimethoprim-sulfamethoxazole, doxycycline, minocycline

If penicillin allergy: clindamycin or linezolid

Moderate: clinical determination of oral vs. intravenous therapy

Oral antibiotics

Trimethoprim-sulfamethoxazole, doxycycline, minocycline

If penicillin allergy: clindamycin

Intravenous antibiotics

Vancomycin, clindamycin, linezolid

Severe: intravenous antibiotics

Broad spectrum coverage with vancomycin + piperacillin-tazobactam or imipenem/meropenem

Duration of therapy: 5 days, although treatment should be extended if infection not improving

Other considerations

Evaluate and treat underlying conditions

Evaluate carefully for predisposing conditions (edema, eczema, toe web portal of entry, tinea pedis) and treat all conditions to minimize risk of further episodes of cellulitis.
Supportive management: elevate affected area
Recurrent cellulitis

Evaluate and treat any predisposing conditions.

Consider prophylactic antibiotics if risk factors and predisposing conditions are being treated and patient is still having 3-4 episodes of cellulitis per year. Antibiotics should be continued as long as predisposing factors for cellulitis persist.

Oral penicillin or erythromycin BID for 4-52 weeks

IM benzathine penicillin every 2-4 weeks
Glucorticoid administration

If nondiabetic patient, may consider systemic corticosteroids: prednisone 40 mg po qd x7 days (IDSA 2014)
Unusual exposure

Cat and dog bites: Polymicrobial. Including Pasteurella species. Irrigate thoroughly. Treat with amoxicillin-clavulanate or intravenous ampicillin sulbactam. For penicillin allergy, use oral or intravenous doxycycline, or fluoroquinolone plus clindamycin.

Human bite: Bacteria composition is complex. Includes Eikenella corrodens. Irrigate thoroughly. Treat with ampicillin-sulbactam or cefoxitin.

Fresh water lacerations: consider treatment for aeromonas hydrophila. Cipro 400 mg IV every 12 hours.

Physical Examination Tips to Guide Management / Monitor for clinical worsening

Local spread of infection, indicated by expansion of affected area, worsening inflammation, new blistering or bullae

Abscess formation, which would require drainage
Monitor for systemic symptoms such as tachycardia, fever, hypotension

Laboratory Tests to Monitor Response To, and Adjustments in, Management

Laboratory tests not routinely needed. Daily clinical exams typically sufficient to confirm clinical improvement.
If clinical worsening, consider obtaining CBC with differential. Some antibiotics e.g., vancomycin require serum monitoring to ensure therapeutic levels.

Common Pitfalls and Side Effects of Management

Recurrent cellulitis: carefully evaluate and treat predisposing factors (i.e., edema) to break the cycle of recurrence.

Nonpurulent cellulitis: broad spectrum antibiotics rarely needed. Carefully evaluate need prior to initiation.

For patients who do not respond to empiric therapy:

Consider alternate diagnoses and re-evaluate patient

Retake history and rule out unusual exposures

Search for abscess, consider using imaging
Evaluate and treat predisposing factors, such as edema and tinea pedis
Ensure correct antimicrobial coverage

Evaluate for risk factors for resistance or MRSA

Ensure correct dosing of antibiotics

IV. Management with Co-Morbidities

Renal Insufficiency

Care should be taken to adjust medication doses.

Diabetes

Treatment of diabetic foot ulcers are addressed separately.

Dementia or Psychiatric Illness

Evaluate for ability to adhere to prescribed therapy; consider hospitalization if patient unable to complete outpatient therapy. Evaluation for supervised care at home or in a residential facility may be required.

V. Transitions of Care

Sign-out considerations While Hospitalized.

Describe the size of the infection. Mark the margins.
Describe presence or absence of bullae, ecchymosis or any erosions.
If worsening signs or worsening systemic symptoms, consider Infectious Disease and/or surgical consultation.

Anticipated Length of Stay

Average length of stay for patients hospitalized in the US for cellulitis is 4.5 days.

Assessing Discharge Readiness. Parenteral antibiotics should be transitioned to oral antibiotics after 48 hours of apyrexia and regression of soft tissue inflammation.

Discharge is appropriate when patient clinically improving and can transition to and tolerate oral antibiotics.

Arranging for Clinic Follow-up

Follow-up should be arranged with a primary care physician to ensure resolution.

1. When should clinic follow up be arranged and with whom.

Follow-up in 1-2 weeks with a primary care physician.
If diabetic, follow-up also should be arranged with a podiatrist.
Instruct patients to call immediately if cellulitic area becomes larger, more swollen or more tender.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

If uncomplicated and clinically improving, no additional testing is required prior to discharge.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

A thorough examination should be performed at the visit. For most cases, no additional testing is required prior to the clinic visit.

Placement Considerations.

Most patients with uncomplicated cellulitis can be discharged home after transitioning to oral antibiotics.
Patients who undergo surgical debridement or who are severely debilitated should get functional assessment. Rehabilitation may be required.
Patients in whom ability to comply with treatment is a concern may also require longer hospital stay, home nurse, or rehabilitation facility placement.

Prognosis and Patient Counseling.

Counsel patients on underlying conditions that may predispose to recurrence:

Personal hygiene and appropriate wound care are recommended.
If diabetes is present, instruct on daily foot exam and aggressive treatment of superficial ulcers.
Instruct patients with chronic venous stasis and chronic lymphedema on early signs of cellulitis.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

No current core measure for cellulitis or other soft tissue infections.
For patients undergoing surgical procedures, prophylactic antibiotics should be given within 1 hour before incision (2 hours for vancomycin or fluoroquinolones)

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Prevent wound infection following surgery by using proper technique and antibiotic prophylaxis.
Prevent infection of diabetic foot ulcers through regular foot care.
Prevent cracks in the skin by keeping well hydrated using emollients.
Treat tinea pedis if present.
Treat chronic venous stasis if present.

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