How do I differentiate staph cellulitis from strep cellulitis?

Differentiating Staph from Strep Cellulitis

In clinical practice, you cannot reliably differentiate staphylococcal from streptococcal cellulitis based on clinical features alone, and the IDSA acknowledges that pathogen identification in nonpurulent cellulitis occurs in less than 20% of cases. 1

The Clinical Reality

β-hemolytic streptococci (groups A, C, or G) cause the vast majority (72-85%) of typical cellulitis cases, making streptococcal infection the default assumption for nonpurulent cellulitis. 2 This predominance holds true across all clinical presentations, including cases that lack the classic sharply demarcated borders traditionally associated with streptococcal infection. 2

Key Clinical Patterns

Features Suggesting Streptococcal Etiology:

• Rapidly spreading erythema with poorly demarcated or sharply demarcated borders 3, 4
• Lower extremity involvement (where group C/G streptococci predominate over group A streptococci) 2
• Absence of purulence or abscess formation 3, 4
• Acute onset with systemic symptoms (fever, malaise) 3

Features Suggesting Staphylococcal Involvement:

• Presence of purulent drainage or abscess formation 3, 4
• Association with penetrating trauma, surgical wounds, or indwelling devices 3
• History of MRSA risk factors: athletes, incarcerated individuals, military recruits, men who have sex with men, IV drug users, long-term care facility residents, or prior MRSA colonization 3

Critical Diagnostic Limitations

The IDSA explicitly states that rapid and specific diagnostic assays are needed because current methods leave clinicians with an unconfirmed diagnosis 80% of the time in nonpurulent cellulitis. 1 This represents a major gap in clinical practice that forces reliance on empiric treatment strategies.

Common Pitfall to Avoid:

Do not assume Staphylococcus aureus is the causative pathogen simply because it grows from a skin swab. In one prospective study, 64% of cases with S. aureus isolated as a single pathogen from swabs actually had confirmed β-hemolytic streptococcal etiology by serology or blood culture. 2 Surface colonization does not equal causation.

Practical Approach to Diagnosis

When Microbiologic Diagnosis Is Needed:

• Obtain tissue aspiration or biopsy (not just swabs) in immunocompromised patients, treatment failures, or atypical presentations 1
• Blood cultures have low yield but should be obtained in severe cases or when systemic toxicity is present 1
• Paired serology (anti-streptolysin O and anti-DNase B antibodies) can retrospectively confirm streptococcal etiology in 72% of cases 2

Clinical Decision-Making:

Since individual clinical features have positive likelihood ratios that do not exceed 2.1 for predicting β-hemolytic streptococcal disease 2, you should base your empiric antibiotic selection on the presence or absence of purulence rather than attempting to distinguish staph from strep clinically:

• Nonpurulent cellulitis: Treat for streptococci with penicillin, amoxicillin, or cephalexin 3, 4
• Purulent cellulitis or abscess: Add MRSA coverage only if specific risk factors are present 3

Treatment Implications

The IDSA emphasizes that both S. aureus and streptococcal species together account for the vast majority of skin and soft tissue infections, but the rising resistance patterns make pathogen identification increasingly important for optimal treatment. 1 However, since this identification is rarely achievable in real-time, empiric therapy targeting streptococci remains the standard for typical nonpurulent cellulitis. 3, 4