What are the diagnostic criteria and treatment approach for a patient suspected of having cellulitis, considering factors like age, diabetes, and immunocompromised status?

Cellulitis Diagnosis

Cellulitis is a clinical diagnosis based on the presence of expanding erythema, warmth, tenderness, and swelling of the skin, without requiring laboratory or imaging confirmation in typical cases. 1, 2

Clinical Diagnostic Criteria

The diagnosis requires identifying the cardinal features of cellulitis through physical examination:

• Expanding erythema with poorly demarcated borders, distinguishing it from erysipelas which has raised, sharply demarcated edges 1, 2
• Warmth and tenderness over the affected area, indicating inflammation of the deep dermis and subcutaneous tissue 2
• Edema and induration of the involved skin, reflecting the inflammatory response 1, 3
• History of preceding skin trauma, such as minor abrasion, insect bite, or injection site that served as the portal of entry 1

Measure and document the extent of erythema, warmth, and surrounding induration to track progression or improvement during treatment. 1

Essential Assessment for Risk Stratification

Age-Related Considerations

• Elderly patients require assessment for underlying venous insufficiency, lymphedema, and chronic edema, which are major predisposing factors in this population 1
• Children <6 months old with moderate-to-severe cellulitis require hospitalization 1

Diabetes-Specific Evaluation

• Perform comprehensive vascular assessment including ankle-brachial index (ABI) to detect peripheral vascular disease in diabetic patients 1
• Test for peripheral neuropathy using a 10-g monofilament to detect loss of protective sensation 1
• Obtain tissue specimens (not swabs) for culture in diabetic foot infections for more accurate pathogen identification 1
• Consider plain radiographs or MRI when osteomyelitis is suspected based on probing to bone or chronic non-healing wounds 1

Immunocompromised Status Assessment

• Immunocompromised patients have specific MRSA risk factors that mandate empirical MRSA-active therapy regardless of whether drainage is purulent 1
• Severe immunocompromise or neutropenia requires hospitalization 1
• Obtain blood cultures in patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1

Critical Warning Signs Requiring Immediate Surgical Consultation

Severe pain out of proportion to examination findings, skin anesthesia, rapid progression, or "wooden-hard" subcutaneous tissues suggest necrotizing fasciitis and require emergent surgical evaluation. 1, 4

Additional red flags include:

• Gas in tissue on palpation or imaging 1
• Bullous changes or skin necrosis 1
• Systemic toxicity with hypotension, altered mental status, or organ dysfunction 1, 4

Distinguishing Cellulitis from Purulent Collections

The distinction between cellulitis and purulent collections is clinically crucial, as cellulitis requires antibiotics as primary treatment, while purulent collections require drainage with antibiotics having a subsidiary role. 1

• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics 1
• Furuncles (boils) are localized purulent collections that require incision and drainage, not antibiotics alone 1
• Septic bursitis requires drainage plus antibiotics 1

Common Cellulitis Mimics to Consider

The accuracy of cellulitis diagnosis is approximately only 33%, requiring thorough evaluation of differential diagnoses. 5

Critical mimics with high morbidity if missed include:

• Deep vein thrombosis presenting with unilateral leg swelling, warmth, and erythema 3
• Necrotizing fasciitis with severe pain, rapid progression, and systemic toxicity 3
• Septic arthritis or septic bursitis with joint involvement 3
• Pretibial abscess presenting as erythematous skin without improvement on antibiotics 5
• Stasis dermatitis, venous eczema, or contact dermatitis mimicking bilateral cellulitis 1

Diagnostic Testing: When and What to Order

Blood cultures are positive in only 5% of cases and are unnecessary for typical cellulitis. 1

Obtain blood cultures only in specific high-risk scenarios:

• Patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1
• Presence of systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1

The majority of cellulitis cases (85%) are nonculturable, and causative bacteria remain unknown. 2 In the 15% where organisms are identified, most are β-hemolytic Streptococcus and methicillin-sensitive Staphylococcus aureus 2

Predisposing Factors to Document

Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, as treating these eradicates colonization and reduces recurrent infection 1, 4

Document presence of:

• Venous insufficiency and lymphedema 1, 4
• Chronic edema, obesity, or eczema 1
• Recent trauma, injection drug use, or penetrating injury 1
• Known MRSA colonization or previous MRSA infection 1

Hospitalization Criteria

Admit patients with any of the following: 1, 4

• Systemic inflammatory response syndrome (SIRS): fever, hypotension, or altered mental status
• Severe immunocompromise or neutropenia
• Concern for deeper or necrotizing infection
• Failure of outpatient treatment after 24-48 hours
• Inability to take oral antibiotics or poor adherence to treatment

Treatment Approach Algorithm

For Typical Nonpurulent Cellulitis (No MRSA Risk Factors)

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, successful in 96% of patients. 1

• Oral options: cephalexin 500 mg every 6 hours, dicloxacillin 250-500 mg every 6 hours, or amoxicillin 1
• IV options for hospitalized patients: cefazolin 1-2 g IV every 8 hours or oxacillin 2 g IV every 6 hours 1
• Duration: 5 days if clinical improvement occurs, extending only if symptoms have not improved 1, 4

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Evidence of MRSA infection elsewhere or nasal MRSA colonization
• Systemic inflammatory response syndrome (SIRS)
• Failure to respond to beta-lactam therapy after 48-72 hours

MRSA coverage options: 1

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA, use only if local resistance <10%)
• Trimethoprim-sulfamethoxazole 1-2 DS tablets twice daily PLUS a beta-lactam
• Doxycycline 100 mg twice daily PLUS a beta-lactam

For Severe Cellulitis with Systemic Toxicity

Mandatory broad-spectrum combination therapy includes vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours. 1, 4

• Duration: 7-10 days with reassessment at 5 days 1
• Alternative: linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1

Special Population Considerations

Diabetic Patients

• Require longer treatment duration compared to non-diabetic patients 1
• Avoid systemic corticosteroids despite evidence showing benefit in non-diabetic adults 1
• For moderate diabetic foot infections: amoxicillin-clavulanate, levofloxacin, ceftriaxone, or ampicillin-sulbactam 1

Immunocompromised Patients

• Empirical MRSA coverage is mandatory regardless of purulent drainage 1
• Lower threshold for hospitalization and IV therapy 1

Essential Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 4

• Elevate limb above heart level for at least 30 minutes three times daily 1, 4
• Treat tinea pedis and toe web abnormalities to reduce recurrence 1, 4
• Address venous insufficiency, lymphedema, and chronic edema 1, 4

Follow-Up and Reassessment

Reassess within 24-48 hours for outpatients to ensure clinical improvement. 1, 4

If no improvement with appropriate first-line antibiotics, consider:

• Resistant organisms (add MRSA coverage)
• Cellulitis mimics (DVT, necrotizing fasciitis, abscess)
• Underlying complications requiring surgical intervention

Prevention of Recurrent Cellulitis

For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics: 1, 4

• Penicillin V 250 mg orally twice daily, or
• Erythromycin 250 mg orally twice daily