How are soft tissue infections, including those with suspected methicillin-resistant Staphylococcus aureus (MRSA), typically classified and treated in patients with varying severity and medical history?

Classification of Soft Tissue Infections

Soft tissue infections should be classified using four independent assessment criteria: necrotizing versus non-necrotizing character, anatomical depth, purulent versus non-purulent characteristics, and patient clinical severity—with this multidimensional approach guiding both treatment intensity and site of care decisions. 1

Primary Classification Framework

By Complexity (FDA/Clinical Framework)

Uncomplicated SSTIs include superficial infections (cellulitis, simple abscesses, impetigo, furuncles) that carry low risk for life- or limb-threatening complications when properly treated, requiring only antibiotics or simple surgical drainage. 1, 2

Complicated SSTIs encompass deep soft-tissue infections (necrotizing infections, infected ulcers, infected burns, major abscesses) with high risk for life-threatening infection, mandating broad-spectrum empiric antibiotics and significant surgical intervention with drainage and debridement. 1, 2

By Purulence and Necrosis (IDSA Framework)

The IDSA divides infections based on three characteristics: presence of purulence, clinical severity (mild/moderate/severe), and presence of tissue necrosis. 1, 2, 3

Purulent infections:

• Mild: Localized without systemic signs, no significant comorbidities—incision and drainage alone suffices without antibiotics in most cases 2, 4
• Moderate: Systemic signs present (fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min, or abnormal WBC count)—requires incision and drainage plus systemic antibiotics 2, 4
• Severe: Treatment failure with oral antibiotics, systemic signs, immunocompromised status, or signs of deep infection (bullae, skin sloughing, hypotension, organ dysfunction)—requires IV therapy and possible hospitalization 2, 4

Non-purulent infections are classified similarly by severity but typically do not require drainage. 1, 2

By Anatomical Depth

Superficial infections (erysipelas, impetigo, folliculitis, furuncles, carbuncles) are located at the epidermal and dermal layers. 1, 3

Cellulitis involves the dermis and subcutaneous tissue. 1, 3

Deep infections extend below the dermis, involving subcutaneous tissue, fascial planes, or muscular compartments, presenting as complex abscesses, fasciitis, or myonecrosis. 1, 3

Clinical Severity Classification (Eron System)

This four-class system guides management, treatment, and admission decisions based on systemic toxicity and comorbidities: 1, 2, 3

• Class 1: No systemic toxicity or comorbidities—outpatient oral antibiotics
• Class 2: Either systemically unwell with stable comorbidities OR systemically well but with complicating comorbidity (diabetes, obesity)—may require hospitalization or close outpatient monitoring
• Class 3: Toxic appearance (fever, tachycardia, tachypnea, and/or hypotension)—requires hospitalization and IV antibiotics
• Class 4: Sepsis syndrome or life-threatening infection (e.g., necrotizing fasciitis)—requires ICU admission, aggressive resuscitation, and emergent surgical consultation

Critical Warning Signs Requiring Immediate Escalation

The following signs indicate severe deep soft-tissue infection or necrotizing infection, mandating emergent surgical evaluation regardless of other classification criteria: 1, 2, 4

• Pain disproportionate to physical findings
• Violaceous bullae or cutaneous hemorrhage
• Skin sloughing or anesthesia
• Rapid progression or rapid extension of erythema
• Gas in tissue
• Hypotension or elevated creatinine
• Low serum bicarbonate or elevated creatine phosphokinase (2-3× upper limit of normal)
• C-reactive protein >13 mg/L with marked left shift

Laboratory Assessment for Severe Infections

For patients with systemic toxicity (fever/hypothermia, tachycardia >100 bpm, hypotension <90 mmHg systolic), obtain: 1

• Blood cultures with susceptibility testing
• Complete blood count with differential
• Creatinine, bicarbonate, creatine phosphokinase, C-reactive protein levels
• Consider Gram stain and culture of needle aspiration or punch biopsy specimens

Hospitalization should be considered when: hypotension and/or elevated creatinine, low bicarbonate, elevated CPK, marked left shift, or CRP >13 mg/L are present. 1

Special Populations

Immunocompromised patients (diabetes, HIV, immunosuppressive therapy) are automatically classified as severe due to unpredictable progression and higher mortality risk, regardless of initial clinical appearance. 2, 4

FDA Definition for Clinical Trials

Acute Bacterial Skin and Skin-Structure Infection (ABSSSI) is defined as bacterial infection with lesion size area ≥75 cm² (measured by area of redness, edema, or induration), including cellulitis/erysipelas, wound infections, and major cutaneous abscesses. 1, 3

Common Pitfalls

Treatment failure is itself a severity marker indicating either resistant organisms (particularly MRSA), inadequate source control, or deeper infection than initially recognized—requiring escalation to IV therapy. 2, 4

Reevaluation at 24-48 hours is mandatory for patients discharged on oral antibiotics, as progression despite treatment suggests resistant microbes or unrecognized deep infection. 1

Signs of necrotizing infection often appear late in the course—maintain high clinical suspicion and low threshold for surgical consultation when any warning signs are present. 1, 2