What is the best course of treatment for a patient with a large rash on the lateral left chest wall and posterior upper left arm consistent with cellulitis, considering potential allergies and previous reactions to antibiotics, and possible history of Methicillin-resistant Staphylococcus aureus (MRSA) or other resistant organisms?

Differential Diagnosis for Large Rash on Lateral Left Chest Wall and Posterior Upper Left Arm

Primary Differential Considerations

The most critical initial distinction is between true cellulitis and its mimickers, as misdiagnosis leads to unnecessary antibiotic exposure in up to 30% of cases. 1

Infectious Etiologies

• Typical nonpurulent cellulitis - Acute onset of erythema, warmth, swelling, and tenderness without purulent drainage, most commonly caused by β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus 1
• Purulent cellulitis with MRSA - Cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess, requiring empirical CA-MRSA coverage 2
• Abscess or furuncle - Fluctuant, localized purulent collection requiring incision and drainage as primary treatment rather than antibiotics alone 2
• Herpes zoster (shingles) - Vesicular rash in dermatomal distribution on chest wall and arm, particularly if unilateral and following nerve distribution 1
• Necrotizing fasciitis - Severe pain out of proportion to examination, skin anesthesia, rapid progression, gas in tissue, systemic toxicity, or bullous changes requiring emergent surgical consultation 3

Non-Infectious Mimickers (Pseudocellulitis)

• Contact dermatitis - Pruritic rash with history of exposure to allergen or irritant, often with vesicles or scaling rather than warmth 1
• Venous stasis dermatitis - Bilateral lower extremity involvement more common, but can present unilaterally with chronic edema, hyperpigmentation, and scaling 1
• Eczema/atopic dermatitis - Chronic, pruritic condition with lichenification and excoriation, lacking acute warmth and rapid progression 1
• Lymphedema - Chronic swelling without acute warmth or tenderness, often with history of surgery, radiation, or trauma 3
• Erythema migrans (Lyme disease) - Expanding erythematous patch with central clearing, history of tick exposure, typically not warm or tender 1

Critical Assessment Points to Distinguish Cellulitis from Mimickers

• Assess for purulent drainage or exudate - If present, this mandates MRSA coverage and consideration of abscess requiring drainage 2, 4
• Evaluate for systemic toxicity - Fever >38°C, hypotension, tachycardia >90 bpm, altered mental status, or SIRS criteria indicate severe infection requiring hospitalization and broad-spectrum IV antibiotics 3, 4
• Examine for fluctuance - Any fluctuant area requires ultrasound evaluation and likely incision and drainage, as antibiotics alone will fail 3
• Check for dermatomal distribution - Unilateral vesicular rash following nerve distribution suggests herpes zoster rather than cellulitis 1
• Look for "wooden-hard" subcutaneous tissues - This suggests necrotizing infection requiring emergent surgical consultation 3

MRSA Risk Factor Assessment

If any of the following are present, empirical MRSA coverage is mandatory: 2, 3

• Penetrating trauma or injection drug use 2, 3
• Purulent drainage or exudate visible 2, 3
• Known MRSA colonization or previous MRSA infection 3
• Failure to respond to β-lactam therapy within 48-72 hours 2, 3
• Systemic inflammatory response syndrome (SIRS) 3

Treatment Algorithm Based on Diagnosis

If Typical Nonpurulent Cellulitis (No MRSA Risk Factors)

Beta-lactam monotherapy is the standard of care, successful in 96% of cases, and MRSA coverage is unnecessary. 3

• Outpatient oral options: Cephalexin 500 mg every 6 hours, dicloxacillin 250-500 mg every 6 hours, or amoxicillin for 5 days if clinical improvement occurs 3
• Hospitalized patients: IV cefazolin 1-2 g every 8 hours 3

If Purulent Cellulitis or MRSA Risk Factors Present

Empirical CA-MRSA coverage is mandatory pending culture results. 2

• Outpatient oral options: Clindamycin 300-450 mg every 6 hours (if local resistance <10%), TMP-SMX 1-2 double-strength tablets twice daily PLUS a β-lactam, or doxycycline 100 mg twice daily PLUS a β-lactam 2, 3
• Hospitalized patients: Vancomycin 15-20 mg/kg IV every 8-12 hours, linezolid 600 mg IV twice daily, or daptomycin 4 mg/kg IV once daily 2, 4

If Severe Infection with Systemic Toxicity

Broad-spectrum combination therapy is mandatory with vancomycin or linezolid PLUS piperacillin-tazobactam, a carbapenem, or ceftriaxone plus metronidazole for 7-14 days. 3

Common Pitfalls to Avoid

• Do not add MRSA coverage reflexively - MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and unnecessary coverage increases resistance 3
• Do not use doxycycline or TMP-SMX as monotherapy - These lack reliable activity against β-hemolytic streptococci and will fail in typical cellulitis 3
• Do not continue ineffective antibiotics beyond 48 hours - Progression despite appropriate therapy indicates resistant organisms or deeper infection requiring reassessment 3
• Do not miss necrotizing fasciitis - Any severe pain out of proportion to examination, rapid progression, or systemic toxicity requires emergent surgical consultation 3