What is the appropriate work‑up and management for a 67‑year‑old woman with Streptococcus mitis bacteremia, a complicated left‑foot skin and soft‑tissue infection, and a white blood cell count of 38,000 with a left shift (elevated segmented neutrophils)?

Management of Streptococcus mitis Bacteremia with Complicated Foot Infection

Initiate high-dose intravenous penicillin G (30 million units daily in divided doses) immediately, combined with vancomycin 15–20 mg/kg IV every 8–12 hours plus piperacillin-tazobactam 3.375–4.5 g IV every 6 hours, and obtain emergent surgical consultation for the complicated foot infection within 12 hours of admission. 1, 2

Immediate Diagnostic Work-Up

Blood Culture and Source Control Assessment

• Obtain at least two sets of blood cultures from separate sites before initiating antibiotics, as S. mitis bacteremia in the setting of severe neutropenia or complicated skin/soft-tissue infection requires pathogen confirmation and susceptibility testing 2, 3.
• Assess the foot infection for necrotizing fasciitis using the "Finger test": make a 2-cm incision down to the deep fascia under local anesthesia; minimal tissue resistance to finger dissection, absence of bleeding, necrotic tissue, or murky "dishwater" fluid all suggest necrotizing infection requiring emergent debridement 2.
• Perform bedside ultrasound of the foot to detect diffuse subcutaneous thickening with fluid accumulation >4 mm along the deep fascial layer, which has 88.2% sensitivity and 93.3% specificity for necrotizing fasciitis 2.
• Obtain plain radiographs of the foot to rule out gas in soft tissue or osteomyelitis; if clinical suspicion for deep infection remains high despite negative X-rays, proceed to MRI 2.

Laboratory Assessment

• Document the absolute neutrophil count (ANC) from the differential; a WBC of 38,000 with elevated segmenters suggests a robust inflammatory response, but verify whether this represents true neutrophilia or a left shift with immature forms 3.
• Measure C-reactive protein (CRP) and procalcitonin to gauge systemic inflammatory burden; CRP elevation occurs in 65.9% of S. mitis bacteremia cases, while procalcitonin elevation is less common (9.4%) 3.
• Check renal function (creatinine, BUN) and hepatic function (AST, ALT) to guide antibiotic dosing and detect early organ dysfunction 4.
• Obtain a baseline echocardiogram (transthoracic or transesophageal) to exclude infective endocarditis, although S. mitis rarely causes IE even in bacteremic patients; among 210 neutropenic patients with S. mitis BSI, none developed IE 5.

Assessment for Predisposing Factors

• Examine the oral cavity for mucositis, ulceration, or dental disease, as oral mucosal damage is present in 40% of S. mitis bacteremia cases and represents a portal of entry 3.
• Inspect the foot for penetrating trauma, foreign bodies, or chronic wounds (diabetic ulcer, venous stasis ulcer) that may have introduced S. mitis from skin or environmental flora 2, 6.
• Document any recent chemotherapy, immunosuppressive therapy, or hematologic malignancy, as 97.7% of pediatric S. mitis bacteremia occurs during neutropenia, and 84.7% of cases are in acute myeloid leukemia patients 3.
• Check for central venous catheter presence, as six of eight neutropenic patients with S. mitis septicemia in one series had central lines 1.

Antibiotic Management Algorithm

Empiric Broad-Spectrum Therapy (First 24–48 Hours)

The combination of vancomycin plus piperacillin-tazobactam is mandatory for complicated foot infections with systemic toxicity until culture results return. 2, 4

• Vancomycin 15–20 mg/kg IV every 8–12 hours (target trough 15–20 mg/L) provides MRSA coverage, which is essential for complicated skin/soft-tissue infections with purulent drainage or systemic signs 2, 6.
• Piperacillin-tazobactam 3.375–4.5 g IV every 6 hours covers polymicrobial flora (aerobic and anaerobic gram-negatives, streptococci, anaerobes) commonly present in diabetic foot infections and necrotizing soft-tissue infections 2, 4.
• Add high-dose penicillin G 30 million units daily (5 million units IV every 4 hours) immediately upon suspicion of S. mitis bacteremia, as this regimen is life-saving and dramatically superior to standard empiric regimens that lack adequate streptococcal coverage 1.

Targeted Therapy After Culture Confirmation (48–72 Hours)

Once S. mitis is confirmed and susceptibilities return, narrow to penicillin-based therapy while maintaining coverage for the polymicrobial foot infection. 1, 3

• Continue high-dose penicillin G 30 million units daily for documented S. mitis bacteremia; all S. mitis isolates in recent pediatric series showed 0% resistance to penicillin, and only 10.6% resistance in one large cohort 3.
• If penicillin MIC >0.1 mcg/mL or tolerance is documented, switch to vancomycin 15–20 mg/kg IV every 8–12 hours or linezolid 600 mg IV twice daily, as 0% resistance to these agents has been reported 3, 7.
• Maintain piperacillin-tazobactam or transition to ceftriaxone 2 g IV daily plus metronidazole 500 mg IV every 8 hours to cover the polymicrobial foot infection until surgical source control is achieved 2, 4.
• Add clindamycin 600 mg IV every 8 hours if group A streptococcal co-infection is suspected (rare but possible in necrotizing fasciitis), as clindamycin suppresses toxin production 4, 8, 9.

Duration of Therapy

• Continue IV antibiotics until no further surgical debridement is necessary, clinical improvement is documented, and the patient has been afebrile for 48–72 hours 4, 8.
• For uncomplicated S. mitis bacteremia without endocarditis or deep-seated infection, 7–14 days of therapy is typical; however, complicated foot infections may require 14–21 days depending on extent of tissue involvement 2.
• Transition to oral antibiotics (amoxicillin 875 mg three times daily or cephalexin 500 mg four times daily) once clinically stable, typically after 4–5 days of IV therapy and documented blood culture clearance 6, 3.

Surgical Source Control

Timing and Indications

Surgical debridement must occur within 12 hours of admission if necrotizing fasciitis is suspected; delay beyond 12 hours significantly increases mortality (38% vs. 4.2%). 2

• Emergent surgical consultation is mandatory for any of the following: severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissues, gas in tissue, bullous changes, or systemic toxicity 2, 6.
• Incision and drainage is the primary treatment for any abscess or purulent collection; antibiotics play only a subsidiary role when drainage is inadequate 2, 6.
• Serial debridements are often required; patients with delayed surgery (>12 hours) averaged 7.4 debridements vs. 2.3 in those treated early 2.

Intraoperative Considerations

• Obtain tissue specimens (not swabs) for aerobic, anaerobic, and fungal cultures to guide antibiotic de-escalation 2.
• Perform frozen-section biopsy if clinical or radiographic findings are equivocal, although this should not delay debridement if necrotizing infection is strongly suspected 2.
• Debride all necrotic tissue completely in the first operation; incomplete debridement is associated with 38% mortality vs. 4.2% with adequate initial surgery 2.

Critical Pitfalls to Avoid

• Do not rely on standard empiric regimens (e.g., cefepime, meropenem alone) for S. mitis bacteremia; these were "clearly ineffective" in neutropenic patients, and three of eight patients died before penicillin G was added 1.
• Do not delay surgical consultation beyond 12 hours if any warning signs of necrotizing infection are present; mortality increases dramatically with delayed source control 2.
• Do not assume S. mitis is a contaminant in the setting of complicated skin/soft-tissue infection and systemic toxicity; 25% of S. mitis isolates represent true infection requiring surgical intervention 7.
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for this patient, as they lack reliable activity against S. mitis and other streptococci 6, 8.
• Do not discontinue antibiotics at 5 days as you would for uncomplicated cellulitis; complicated infections with bacteremia require 7–14 days minimum, guided by clinical response and source control 2, 4.

Adjunctive Measures

• Elevate the affected foot above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory mediators 6.
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat with topical antifungals to eradicate colonization and reduce recurrence risk 2, 6.
• Optimize glycemic control if diabetic, as hyperglycemia impairs infection clearance and wound healing 2.
• Avoid systemic corticosteroids despite the elevated WBC, as steroids are contraindicated in diabetic patients with cellulitis and may worsen outcomes in necrotizing infections 6.

Monitoring and Reassessment

• Repeat blood cultures 48–72 hours after initiating antibiotics to document clearance; persistent bacteremia suggests inadequate source control or endocarditis 2, 5.
• Reassess the foot infection daily for expanding erythema, new purulent drainage, or worsening pain, any of which mandate repeat surgical evaluation 2.
• Monitor vancomycin trough levels to maintain 15–20 mg/L for serious infections; adjust dosing based on renal function 2, 4.
• Obtain repeat echocardiography if bacteremia persists beyond 72 hours or new cardiac symptoms develop, although IE risk with S. mitis is very low 5.