What is the appropriate treatment for an adult patient with a skin infection on the legs, considering potential underlying conditions such as diabetes or poor circulation?

Treatment of Skin Infection on Legs

For an adult with a skin infection on the legs, immediately assess for diabetes and peripheral arterial disease, then initiate empiric oral antibiotics targeting S. aureus and streptococci (amoxicillin-clavulanate as first-line) for mild infections, while moderate-to-severe infections require parenteral broad-spectrum therapy with piperacillin-tazobactam plus urgent surgical debridement. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, perform a structured three-level evaluation:

• Patient-level assessment: Check for diabetes mellitus, immunosuppression, recent hospitalizations, and prior antibiotic use, as these significantly alter pathogen likelihood and treatment approach 1
• Limb-level assessment: Evaluate for peripheral arterial disease using ankle-brachial index (ABI <0.6 indicates severe ischemia requiring revascularization), assess for venous insufficiency causing edema, and test for neuropathy using 10-g monofilament 1
• Wound-level assessment: Classify infection severity based on presence of purulent discharge, erythema extent, warmth, tenderness, and depth of tissue involvement 1

Infection Severity Classification

Use the IWGDF/IDSA classification system to guide treatment intensity 1:

• Mild (Grade 2): Local swelling, erythema <2 cm from wound edge, tenderness, warmth, or purulent discharge without systemic signs 1
• Moderate (Grade 3): Erythema ≥2 cm from wound margin and/or involvement of deeper tissues (tendon, muscle, joint, bone) without systemic toxicity 1
• Severe (Grade 4): Any infection with systemic inflammatory response syndrome (SIRS): temperature >38°C or <36°C, heart rate >90 bpm, respiratory rate >20 breaths/min, or WBC >12,000/mm³ or <4,000/mm³ 1

Empiric Antibiotic Selection by Severity

Mild Infections

First-line choice: Oral amoxicillin-clavulanate provides optimal coverage for S. aureus, streptococci, and anaerobes 2, 3

Alternative oral options if amoxicillin-clavulanate is contraindicated 2:

• Dicloxacillin or cephalexin (for non-MRSA gram-positive coverage)
• Trimethoprim-sulfamethoxazole (covers community-acquired MRSA but lacks streptococcal coverage—add clindamycin if streptococci suspected)
• Clindamycin monotherapy (covers both MRSA and streptococci)

Treatment duration: 1-2 weeks, stopping when infection signs resolve, not when wound fully heals 2, 3

Moderate Infections

First-line parenteral choice: Piperacillin-tazobactam provides broad gram-positive, gram-negative, and anaerobic coverage 2

Alternative regimens 2:

• Ertapenem 1g once daily (convenient outpatient option)
• Ampicillin-sulbactam
• Levofloxacin or ciprofloxacin PLUS clindamycin (for broader coverage without cephalosporins)

Treatment duration: 2-3 weeks, extending to 3-4 weeks if extensive infection or severe peripheral arterial disease present 2, 3

Severe Infections

First-line regimen: Vancomycin PLUS piperacillin-tazobactam or carbapenem to cover MRSA, gram-negatives, and anaerobes 2

Alternative broad-spectrum agents to combine with vancomycin 2:

• Ceftazidime or cefepime (anti-pseudomonal cephalosporins)
• Aztreonam (for beta-lactam allergic patients)
• Meropenem or imipenem-cilastatin (carbapenems)

Treatment duration: 2-4 weeks depending on adequacy of debridement, soft-tissue wound coverage, and vascularity 2

Special Pathogen Considerations

MRSA Coverage

Add empiric MRSA-targeted therapy when 2:

• Local MRSA prevalence exceeds 50% for mild infections or 30% for moderate infections
• Recent hospitalization or healthcare exposure
• Previous MRSA infection or colonization
• Recent inappropriate antibiotic use
• Chronic wounds or presence of osteomyelitis

MRSA-active agents 2:

• Vancomycin: Standard for severe infections requiring IV therapy (requires therapeutic monitoring; efficacy may be reduced with increasing MICs)
• Linezolid: Excellent oral bioavailability allowing IV-to-oral transition (increased toxicity risk with use >2 weeks; requires monitoring)
• Daptomycin: Demonstrated 89.2% clinical success in real-world MRSA diabetic foot infection cohorts (requires serial CPK monitoring)

Pseudomonas Coverage

Do NOT empirically cover Pseudomonas in temperate climates unless 2, 4:

• Previously isolated from the affected site within recent weeks
• Macerated wounds with frequent water exposure
• Patient resides in Asia, North Africa, or warm climates
• Moderate-to-severe infection with above risk factors

Anti-pseudomonal options when indicated 2:

• Piperacillin-tazobactam
• Ciprofloxacin or levofloxacin
• Ceftazidime or cefepime

Anaerobic Coverage

Consider anaerobic coverage for 1, 2:

• Chronic, previously treated infections
• Severe infections with extensive necrosis
• Foul-smelling discharge or crepitus

Agents with anaerobic activity: Piperacillin-tazobactam, ampicillin-sulbactam, ertapenem, metronidazole (as adjunct), or clindamycin 2

Critical Non-Antibiotic Management

Surgical Debridement

Urgent surgical consultation is mandatory for 2:

• Deep abscess formation requiring drainage
• Extensive necrosis or gangrene
• Necrotizing fasciitis
• Crepitus suggesting gas-forming organisms

Sharp debridement with scalpel is preferable to hydrotherapy or topical debriding agents, as it provides definitive and controllable tissue removal 1

Vascular Assessment and Revascularization

Healing is severely impaired when 1:

• Ankle pressure <50 mmHg
• Toe pressure <50 mmHg
• Transcutaneous oxygen pressure (TcPO2) <30 mmHg
• Ankle-brachial index <0.6

For severely infected ischemic feet, perform revascularization within 1-2 days rather than delaying for prolonged antibiotic therapy, as antibiotics alone are insufficient without adequate perfusion 1, 2

Pressure Offloading

For plantar ulcers, use non-removable knee-high offloading devices 1, 4:

• Total contact casting (preferable)
• Irremovable walker
• Instruct patients to limit standing and walking, using crutches or mobility aids if necessary

Metabolic Control

Optimize glycemic control to blood glucose <8 mmol/L (<140 mg/dL), using insulin if necessary, as hyperglycemia impairs both infection eradication and wound healing 1, 2

Obtaining Cultures and Definitive Therapy

Before starting antibiotics, obtain deep tissue cultures via biopsy or curettage after debridement—not superficial swabs—as swabs have poor correlation with true pathogens 2, 3

Once culture results return 2:

• Narrow antibiotics to target identified pathogens
• Focus on virulent species (S. aureus, group A/B streptococci)
• Less-virulent organisms may not require coverage if clinical response is good

Monitoring and Treatment Adjustment

Evaluate clinical response 2:

• Daily for inpatients
• Every 2-5 days initially for outpatients
• Primary indicators: resolution of local inflammation (erythema, warmth, tenderness) and systemic symptoms (fever, tachycardia)

If no improvement after 4 weeks of appropriate therapy, re-evaluate for 2:

• Undiagnosed abscess
• Osteomyelitis
• Antibiotic resistance
• Severe ischemia requiring revascularization

Common Pitfalls to Avoid

• Do NOT continue antibiotics until complete wound healing—stop when infection signs resolve, as there is no evidence supporting prolonged therapy and it increases antibiotic resistance risk 2
• Do NOT treat clinically uninfected ulcers with antibiotics for prevention or to promote healing 2, 4
• Do NOT use unnecessarily broad empiric coverage for mild infections—most can be treated with agents covering only aerobic gram-positive cocci 2
• Do NOT rely on antibiotics alone without adequate debridement and offloading—surgical source control is essential 2, 4
• Do NOT delay revascularization in ischemic limbs—early intervention (within 1-2 days) is crucial for healing 1

Adjunctive Wound Care

• Perform frequent wound debridement with scalpel to remove necrotic tissue 1
• Control exudate and maintain moist wound environment 1
• Consider negative pressure therapy for post-operative wounds 1
• Avoid footbaths—they induce skin maceration 1
• Elevate affected extremity to promote gravity drainage of edema 1
• Treat underlying predisposing conditions: tinea pedis, venous eczema, or trauma 1, 4