What is the best course of treatment for a patient presenting with fever and leg pain, suspected to be caused by a bacterial infection or deep vein thrombosis (DVT)?

Management of Fever and Leg Pain

For a patient presenting with fever and leg pain, immediately assess for life-threatening necrotizing soft tissue infection or limb-threatening diabetic foot infection requiring urgent surgical consultation within 24 hours, while simultaneously initiating empiric anticoagulation if deep vein thrombosis (DVT) is clinically suspected and diagnostic testing will be delayed. 1

Immediate Triage and Risk Stratification

Assess for Limb-Threatening or Life-Threatening Infection

Urgent surgical consultation is required within 24 hours if any of the following are present: 1

• Pain out of proportion to clinical findings 1
• Rapid progression of infection or extensive necrosis 1
• Crepitus on examination or gas on imaging 1
• Bullae, especially hemorrhagic 1
• Extensive ecchymoses or petechiae 1
• New onset wound anesthesia or recent loss of neurologic function 1
• Evidence of systemic inflammatory response (fever, tachycardia, marked leukocytosis) 1
• Critical limb ischemia 1

Common pitfall: The absence of fever or leukocytosis should NOT dissuade you from considering surgical exploration, particularly in diabetic patients with foot infections. 1

Evaluate for Deep Vein Thrombosis

Assess pre-test probability using clinical decision rules to stratify DVT as "unlikely" or "likely": 2

• If DVT is "likely" based on clinical assessment: Refer immediately for compression ultrasound 2
• If DVT is "unlikely": Obtain D-dimer testing first; if elevated, proceed to compression ultrasound 2

For high clinical suspicion of DVT, initiate parenteral anticoagulation while awaiting diagnostic testing if results will be delayed >4 hours. 1

Diagnostic Workup

Essential Initial Tests

• Complete blood count with differential 3
• Blood cultures (positive in 5-30% of deep infections) 1
• Compression ultrasound of affected leg 2
• Plain radiographs to assess for gas in tissues or bone destruction 1
• Assess for diabetes and check glucose level (hyperglycemia at presentation may suggest rapidly progressive necrotizing infection) 1

Advanced Imaging When Indicated

• CT or MRI if deep-space infection or abscess suspected 1
• Evaluate for compartmental involvement, especially plantar surface infections with dorsal erythema 1

Key clinical pearl: A plantar wound with dorsal erythema or fluctuance indicates infection has passed through fascial compartments and requires surgical intervention. 1

Treatment Algorithm

For Confirmed or Suspected Necrotizing Soft Tissue Infection

Immediate management (within 24 hours): 1

• Urgent surgical debridement and drainage 1
• High-dose IV antibiotics: Broad-spectrum coverage including anaerobes and gram-positive organisms 1
• For clostridial myonecrosis (gas gangrene): High-dose penicillin or ampicillin 1
• Assess vascular status: If limb appears ischemic, obtain vascular surgery consultation for possible revascularization 1

For Confirmed DVT

Initiate anticoagulation immediately upon diagnosis: 1, 4

Preferred initial therapy - Direct Oral Anticoagulants (DOACs): 1, 4

• Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily 4
• Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 4
• Dabigatran or edoxaban: Require 5-10 days of initial parenteral anticoagulation (LMWH or fondaparinux) before starting oral therapy 4

Alternative therapy - Warfarin with parenteral bridging: 5

• Start warfarin early with LMWH or fondaparinux bridging 4
• Continue parenteral anticoagulation minimum 5 days and until INR ≥2.0 for at least 24 hours 4
• Target INR 2.5 (range 2.0-3.0) 5

Duration of anticoagulation: 1, 4

• DVT provoked by surgery or transient risk factor: 3 months 1, 4
• Unprovoked DVT: Minimum 3 months, consider extended therapy indefinitely 1, 4
• Cancer-associated DVT: Continue as long as cancer or treatment is ongoing 4

For Non-Necrotizing Diabetic Foot Infection

Mild to moderate infection without systemic signs: 1

• Oral or IV antibiotics based on severity 1
• Wound care and offloading 1
• Assess for ischemia and consider vascular intervention if ankle-brachial index 0.4-0.9 or lower 1

Severe infection with systemic signs but no immediate limb threat: 1

• Evaluation by infectious disease specialist within 24 hours 1
• IV broad-spectrum antibiotics 1
• Consider delayed surgical intervention to allow demarcation of viable tissue 1

Special Considerations

Pediatric Patients

DVT in infants or children without central venous catheters indicates underlying hypercoagulable state or serious infection (including bacteremia). 6

• Obtain blood cultures 6
• Evaluate for malignancy if no clear infectious source 3

Common pitfall: Leg pain and fever in children may represent acute lymphoblastic leukemia rather than osteomyelitis. 3

Cancer Patients with DVT

For cancer-associated thrombosis, oral factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) are preferred over LMWH. 4

• Caution: Higher risk of gastrointestinal bleeding with DOACs in patients with GI malignancies 2

Patients with Renal Insufficiency

DOACs may require dose reduction or should be avoided in moderate to severe renal dysfunction. 4

• Consider warfarin or LMWH as alternatives 4

Outpatient vs. Inpatient Management

For uncomplicated DVT with adequate home circumstances, outpatient treatment is preferred. 4

Admit for inpatient management if: 1

• Evidence of necrotizing infection or limb-threatening infection 1
• Hemodynamic instability or systemic toxicity 1
• Inadequate home support or inability to access medications 4
• PE with hypotension 1