What is the best course of treatment for a patient presenting with bilateral lower limb pain, fever, and leukocytosis?

Management of Bilateral Lower Limb Pain with High Fever and Leukocytosis

This presentation demands immediate hospitalization, blood cultures before antibiotics, urgent imaging to identify the infection source, and empiric broad-spectrum IV antibiotics covering both gram-positive and gram-negative organisms, as bilateral leg involvement with systemic signs indicates severe infection requiring aggressive treatment to prevent mortality and limb loss.

Immediate Diagnostic Actions

Blood Work and Cultures

• Obtain blood cultures immediately before initiating antibiotics, but do not delay antibiotic administration while waiting for results 1
• Blood cultures are positive in 5-15% of cellulitis cases and guide subsequent therapy 1
• Measure C-reactive protein (CRP) and complete blood count with differential, as CRP ≥5 mg/dL has high specificity for serious bacterial infection 2, 3
• Leukocytosis with fever strongly suggests bacterial infection requiring immediate antimicrobial therapy 4

Imaging Strategy

• Plain radiographs are appropriate as initial imaging but should not delay antibiotic therapy in obvious cellulitis 1
• If the diagnosis is unclear or deep infection is suspected, obtain CT of the lower extremities with IV contrast to identify abscesses, necrotizing fasciitis, or osteomyelitis 2, 3
• Ultrasound can identify fluid collections requiring drainage 3

Critical Differential Diagnoses to Exclude

Life-Threatening Conditions

• Bilateral cellulitis with systemic toxicity: The most likely diagnosis given fever, leukocytosis, and bilateral leg pain, requiring immediate IV antibiotics 1
• Necrotizing soft tissue infection: Rapidly expanding erythema, severe pain out of proportion to examination, or skin changes (bullae, crepitus) mandate emergent surgical consultation 1
• Deep venous thrombosis: Assess for unilateral versus bilateral swelling, calf tenderness, and risk factors, though bilateral presentation is less typical 1

Special Population Considerations

• In diabetic patients, consider diabetic foot infection with systemic spread, which may present with fever and leukocytosis even without obvious foot wounds 5
• Diabetic patients and elderly may not mount typical inflammatory responses, so absence of high fever does not rule out serious infection 1
• In immunocompromised patients, lower the threshold for admission and aggressive treatment 1, 2

Hospitalization Criteria

This patient requires immediate hospitalization based on the following:

• Systemic signs of infection (fever >38°C, leukocytosis) indicate severe infection 1, 2
• Bilateral involvement suggests extensive disease that is potentially limb-threatening 5
• Patients with fever, tachycardia, or hypotension require inpatient management 1, 2

Empiric Antibiotic Regimen

Initial IV Therapy

• Start broad-spectrum IV antibiotics immediately after obtaining blood cultures 1, 2
• For bilateral cellulitis without purulent drainage: Cefazolin 2g IV every 8 hours OR ceftriaxone 1-2g IV daily 1, 2
• If MRSA risk factors present (prior MRSA infection, injection drug use, purulent drainage): Add vancomycin 15-20 mg/kg IV every 8-12 hours 1
• If necrotizing infection suspected: Use piperacillin-tazobactam 4.5g IV every 6 hours PLUS vancomycin, and obtain immediate surgical consultation 2

Antibiotic Selection Rationale

• Third-generation cephalosporins (ceftriaxone) provide excellent coverage for streptococci and gram-negative organisms 2, 6, 7
• Cefazolin is preferred for uncomplicated cellulitis without MRSA risk 1
• Do not use oral antibiotics initially in patients with systemic signs of severe infection 1, 7

Common Pitfalls to Avoid

Diagnostic Errors

• Do not assume this is venous eczema or stasis dermatitis: Bilateral red legs without fever or leukocytosis may be non-infectious, but the presence of systemic signs mandates treating as infection 1
• Do not delay antibiotics waiting for imaging results: Expanding cellulitis requires immediate treatment to prevent systemic sepsis and tissue necrosis 1
• Do not dismiss the severity because of bilateral presentation: While unilateral cellulitis is more common, bilateral involvement with systemic signs indicates severe, potentially life-threatening infection 1

Treatment Errors

• Do not use outpatient oral therapy: Patients with fever and leukocytosis require IV antibiotics and hospitalization 1, 7
• Do not assume absence of purulence rules out abscess: Obtain imaging if clinical improvement does not occur within 48-72 hours 2, 3
• Do not continue empiric broad-spectrum antibiotics indefinitely: Reassess at 3-5 days and narrow therapy based on culture results and clinical response 2, 8

Monitoring and Reassessment

Clinical Response Indicators

• Expect clinical improvement within 48-72 hours of appropriate antibiotic therapy 2
• Monitor temperature, heart rate, white blood cell count, and CRP daily 2, 3
• If no improvement by day 3-5, repeat imaging to assess for abscess, osteomyelitis, or alternative diagnosis 2, 3

Discharge Criteria

• Discharge when systemic inflammatory response has resolved (afebrile >24 hours, normalizing WBC, clinically stable) 5
• Transition to oral antibiotics only after documented clinical improvement and ability to tolerate oral intake 5
• Ensure close outpatient follow-up within 48-72 hours of discharge 5

Duration of Therapy

• Total antibiotic duration typically 5-14 days depending on severity and clinical response 2
• Five days may be adequate for uncomplicated cellulitis with rapid response 2
• Extend to 10-14 days for slow responders or complicated infections 5