What is the best course of treatment for a patient with worsening leg swelling and redness, despite initial treatment with Lasix (furosemide) and zinc oxide, and a history of recent hospitalization for infection, including a urinary tract infection (UTI) with E. coli?

Worsening Leg Swelling and Redness Despite Initial Treatment

This patient requires urgent reassessment for cellulitis or deep vein thrombosis (DVT), not simply continued diuretic therapy. Despite a negative Doppler previously, the worsening redness, swelling, and tenderness with failure to respond to Lasix strongly suggests an infectious or thrombotic process rather than simple volume overload.

Immediate Diagnostic Workup

Obtain a repeat venous duplex ultrasound immediately to exclude DVT, as the clinical presentation has changed since the initial negative study 1. Approximately 25% of patients with superficial thrombophlebitis have underlying DVT that may not have been apparent on initial imaging 2.

Assess for cellulitis by examining for:

• Spreading erythema with defined borders
• Warmth extending beyond the area of swelling
• Systemic signs including fever, tachycardia, or confusion 1
• Presence of skin breakdown, ulceration, or portal of entry 1

Order baseline laboratory studies:

• Complete blood count with differential to assess for leukocytosis 1
• Blood cultures if fever or systemic symptoms present 1
• Renal function and electrolytes given recent diuretic use 1
• C-reactive protein or erythrocyte sedimentation rate if infection suspected 1

Treatment Algorithm Based on Findings

If DVT is Confirmed on Repeat Ultrasound

Initiate therapeutic anticoagulation immediately with low-molecular-weight heparin (LMWH), fondaparinux, or unfractionated heparin 1. The American College of Chest Physicians recommends LMWH or fondaparinux over IV unfractionated heparin for acute DVT 1.

• Start warfarin on the same day as parenteral therapy and continue parenteral anticoagulation for minimum 5 days until INR ≥2.0 for at least 24 hours 1
• Continue anticoagulation for at least 3 months for provoked DVT 1
• Encourage early ambulation rather than bed rest to reduce complications 1, 2

If Cellulitis is Diagnosed

Classify infection severity to guide antibiotic selection 1:

For mild cellulitis (erythema ≤2 cm around affected area, no systemic symptoms):

• Oral dicloxacillin, cephalexin, or clindamycin for gram-positive coverage 1
• Consider trimethoprim-sulfamethoxazole or doxycycline if MRSA risk factors present (recent hospitalization, healthcare exposure) 1

For moderate cellulitis (erythema >2 cm, lymphangitic streaking, or recent hospitalization with E. coli bacteremia):

• Oral or IV amoxicillin-clavulanate, levofloxacin, or ceftriaxone for broader coverage including gram-negatives 1
• Given this patient's recent E. coli infection, levofloxacin 750 mg daily or ceftriaxone 1-2g daily provides appropriate coverage 1

For severe cellulitis (systemic toxicity, fever, hypotension, confusion):

• Hospitalize and initiate IV piperacillin-tazobactam or vancomycin plus ceftazidime 1
• Consider vancomycin plus ertapenem if recent hospitalization increases MRSA and resistant gram-negative risk 1

If Superficial Thrombophlebitis is Found

For superficial vein thrombosis ≥5 cm in length:

• Fondaparinux 2.5 mg subcutaneously daily for 45 days reduces progression to DVT from 1.3% to 0.2% 2, 3
• Alternative: Rivaroxaban 10 mg orally daily for 45 days 2

If thrombus is within 3 cm of saphenofemoral junction:

• Treat as DVT-equivalent with therapeutic-dose anticoagulation for at least 3 months 2, 3

Critical Pitfalls to Avoid

Do not continue diuretics without identifying the underlying cause of worsening symptoms 4. Lasix failure with progressive symptoms indicates the wrong diagnosis or treatment approach.

Do not assume the previous negative Doppler excludes current DVT, as thrombosis can develop or extend after initial imaging 1, 2. Serial imaging is essential when clinical suspicion remains high 1.

Do not delay anticoagulation if DVT is strongly suspected clinically while awaiting ultrasound results, particularly given recent hospitalization and immobility 1. The American College of Chest Physicians recommends empiric anticoagulation for high clinical suspicion cases 1.

Do not prescribe fluoroquinolones empirically without considering recent antibiotic exposure, as this patient's recent E. coli UTI treatment may have selected for resistant organisms 5, 6, 7. Resistance rates to ciprofloxacin in recently hospitalized patients can exceed 10% 6.

Adjunctive Measures

Elevate the affected limb and apply warm compresses if infection or superficial thrombophlebitis is present 2, 3.

Use NSAIDs for pain control unless contraindicated by renal function or bleeding risk 2, 3.

Discontinue zinc oxide as it provides no therapeutic benefit for cellulitis or thrombosis and may delay appropriate treatment 4.

Monitor for extension or worsening with repeat examination in 24-48 hours if outpatient management is chosen 1, 2.