What is the recommended treatment for inpatients with skin infections?

Treatment of Inpatient Skin Infections

For hospitalized patients with skin and soft tissue infections, empiric antibiotic therapy should be vancomycin (15-20 mg/kg IV every 8-12 hours) plus either piperacillin-tazobactam (3.375-4.5g IV every 6-8 hours) or a carbapenem (imipenem-meropenem 500mg-1g IV every 6-8 hours) to cover MRSA, streptococci, gram-negative organisms, and anaerobes. 1

Initial Assessment and Risk Stratification

Before initiating therapy, determine the infection severity and patient risk factors:

• Assess for systemic signs of infection (SIRS criteria): fever, tachycardia, altered mental status, or hemodynamic instability—these mandate hospitalization and broad-spectrum IV antibiotics 1, 2
• Classify the infection type: purulent (with abscess/drainage) versus non-purulent (cellulitis without purulent drainage) 1, 3
• Identify high-risk features requiring MRSA coverage: penetrating trauma, evidence of MRSA infection elsewhere, nasal MRSA colonization, injection drug use, purulent drainage, or presence of SIRS 1, 3
• Evaluate for deeper/necrotizing infection: rapidly spreading erythema, bullae, crepitus, severe pain out of proportion to exam, or skin necrosis require immediate surgical consultation 1, 2

Empiric Antibiotic Regimens by Clinical Scenario

Severe Non-Purulent Cellulitis with Systemic Signs

First-line regimen: Vancomycin PLUS piperacillin-tazobactam OR imipenem-meropenem 1, 2

• This combination provides coverage against MRSA, beta-hemolytic streptococci, gram-negative organisms including Pseudomonas, and anaerobes 2
• Alternative MRSA coverage if vancomycin cannot be used: linezolid 600mg IV/PO twice daily or daptomycin 4mg/kg IV once daily 1, 4, 5

Moderate Non-Purulent Cellulitis Without Systemic Signs

For typical cellulitis without SIRS, many clinicians can use agents active against streptococci alone, though MRSA coverage may be included based on local epidemiology 1

Severely Immunocompromised Patients

For neutropenic patients (ANC <500 cells/µL) with initial fever episode:

• Vancomycin PLUS antipseudomonal antibiotics: cefepime, carbapenem (imipenem-cilastatin, meropenem, or doripenem), or piperacillin-tazobactam 1
• Gram-negative bacteria are the primary target due to high mortality risk 1
• Add vancomycin only if physical findings suggest skin/soft tissue inflammation, hemodynamic instability present, or MRSA risk factors identified 1

For persistent or recurrent neutropenic fever (beyond 4-7 days):

• Add empiric antifungal therapy (fluconazole 400mg daily, voriconazole, posaconazole, or liposomal amphotericin B) to the antibacterial regimen, as yeasts and molds become the primary concern 1

Special Populations: IV Drug Users

• Empiric MRSA coverage is mandatory due to higher colonization rates 3
• Consider polymicrobial infections including anaerobes, especially near injection sites 3
• Recommended regimen: vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam, carbapenem, or ceftriaxone plus metronidazole 3
• Higher risk of bacteremia and metastatic infections (endocarditis, septic thrombophlebitis, osteomyelitis) requires thorough evaluation 3

Infections with Foreign Body or Treatment Failure

• Broad-spectrum coverage is essential: vancomycin PLUS piperacillin-tazobactam or carbapenem 6
• Foreign bodies create biofilms harboring MRSA and gram-negatives; source control (foreign body removal) is mandatory for cure 6
• Consider adding metronidazole 500mg IV every 8 hours if signs of anaerobes, necrotic tissue, or bullae suggest necrotizing infection 6

Culture and Diagnostic Approach

Blood cultures are recommended before initiating antibiotics in patients with systemic signs of infection 1, 2

• Obtain at least 2 sets of blood cultures 1
• Cutaneous cultures (aspirates, biopsies, or swabs) should be obtained in patients with malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, animal bites, or treatment failure 1, 6
• For neutropenic patients, aggressively pursue etiology through aspiration and/or biopsy of skin lesions for cytological/histological assessment, microbial staining, and cultures 1
• Routine cultures are NOT recommended for typical cellulitis without systemic signs 1

Treatment Duration

• Standard duration: 7-14 days for most bacterial skin infections 1, 3
• Minimum 5 days, but extend if infection has not improved within this timeframe 1
• For infections with foreign body and treatment failure: minimum 7-10 days with reassessment at 48-72 hours 6
• Longer duration may be needed if bacteremia or deeper infection is present 3

Surgical Management

Incision and drainage is the primary treatment for abscesses 3

• Surgical intervention is recommended for drainage of soft tissue abscess after marrow recovery in neutropenic patients, or for progressive polymicrobial necrotizing fasciitis or myonecrosis 1
• Prompt surgical consultation for suspected necrotizing infections is critical 3, 2
• Consider imaging (ultrasound, CT, MRI) to evaluate for deeper collections, foreign bodies, or necrotizing process 2, 6

Adjunctive Measures

• Elevation of the affected area above heart level to reduce edema and promote drainage 1, 6
• Examine interdigital toe spaces in lower extremity cellulitis; treat fissuring, scaling, or maceration (tinea pedis) to eradicate pathogen colonization and reduce recurrence 1, 6
• Treatment of predisposing factors: edema, obesity, eczema, venous insufficiency 2
• Systemic corticosteroids (prednisone 40mg daily for 7 days) may be considered in non-diabetic adults to reduce inflammation 2

Monitoring and Transition to Oral Therapy

• Reassess within 48-72 hours to evaluate response to therapy 3, 2, 6
• Consider switching to oral therapy once clinically improving 3
• Document antimicrobial susceptibilities and adjust therapy accordingly 1

Critical Pitfalls to Avoid

• Do not delay broad-spectrum antibiotics in patients with severe cellulitis and systemic signs of infection 2
• Do not rely solely on beta-lactam antibiotics (e.g., cefazolin) for severe infections without adding MRSA coverage 2, 6
• Do not use beta-lactam monotherapy in cases with high-risk features such as foreign body, IV drug use, or treatment failure 6
• Failure to consider MRSA as a causative pathogen in hospitalized patients is a common error 3
• Inadequate surgical drainage of abscesses leads to treatment failure regardless of antibiotic choice 3
• Missing deeper or necrotizing infections requiring urgent surgical intervention can be fatal 3, 2
• Colony-stimulating factor therapy (G-CSF, GM-CSF) or granulocyte transfusions are NOT routinely recommended for neutropenic patients 1