What is the best treatment approach for toe web cellulitis secondary to fungal infection that is unresponsive to Keflex (cephalexin) and topical Terbinafine (terbinafine)?

Treatment of Toe Web Cellulitis Secondary to Fungal Infection Unresponsive to Keflex and Topical Terbinafine

For toe web cellulitis secondary to fungal infection that has not responded to cephalexin (Keflex) and topical terbinafine, the recommended treatment is oral fluconazole combined with clindamycin, along with aggressive local care of the toe web spaces.

Understanding the Condition

Toe web cellulitis often develops as a complication of fungal infections (tinea pedis) in the interdigital spaces. This represents a complex infection pattern:

1. Initial fungal infection creates skin fissures and maceration
2. These damaged areas allow bacterial entry (typically streptococci and sometimes staphylococci)
3. Resulting cellulitis develops that requires both antifungal and antibacterial treatment

Treatment Algorithm

Step 1: Address Both Infectious Components

• Antifungal therapy: Oral fluconazole 200mg on day 1, followed by 100mg daily for 2-4 weeks 1
• Antibacterial therapy: Clindamycin 300-450mg orally three times daily for 5-7 days 2

Step 2: Local Wound Care (Critical Component)

• Thoroughly clean and dry toe web spaces daily
• Apply antiseptic solutions (such as dilute povidone-iodine or chlorhexidine)
• Keep feet dry by:
  • Using absorbent cotton between toes
  • Changing socks frequently
  • Using moisture-wicking socks
  • Avoiding occlusive footwear

Step 3: Evaluate for Treatment Response

• Assess after 3-5 days for signs of improvement
• If no improvement, consider:
  • Obtaining wound culture to identify specific pathogens
  • Ultrasound to rule out deeper infection
  • Broadening antibiotic coverage if indicated

Rationale for Treatment Selection

The failure of initial therapy with cephalexin and topical terbinafine suggests:

1. Resistant organisms: Cephalexin primarily targets streptococci but may miss MRSA or gram-negative bacteria that can colonize macerated toe webs 2

2. Inadequate antifungal penetration: Topical terbinafine may not adequately penetrate the macerated, inflamed tissue 3

3. Mixed infection: The presence of both fungi and bacteria requires dual therapy 2

Fluconazole is preferred over terbinafine for this scenario because:

• It has better activity against Candida species that may be present in toe web infections 2, 4
• It achieves good tissue penetration in inflamed areas 1

Clindamycin is chosen because:

• It provides coverage against streptococci and staphylococci, including MRSA 2
• It has better tissue penetration in inflamed areas than cephalexin

Special Considerations

For Diabetic Patients

If the patient has diabetes, consider:

• More aggressive antibiotic therapy
• Lower threshold for imaging to rule out deeper infection
• Longer duration of therapy (10-14 days) 2
• Earlier follow-up (within 48-72 hours)

For Recurrent Infections

For patients with recurrent episodes:

• Consider prophylactic antifungal therapy (weekly fluconazole 150mg) 2
• Implement rigorous daily foot hygiene
• Address predisposing factors (obesity, hyperhidrosis, immunosuppression)
• Consider cotton toe spacers for persistent maceration 2

Common Pitfalls to Avoid

1. Treating only the bacterial component: Failure to adequately treat the underlying fungal infection will lead to recurrence 2

2. Inadequate local care: Simply prescribing medications without addressing the local environment (moisture, maceration) will result in treatment failure 2

3. Missing deeper infection: Toe web infections can extend to deeper tissues, especially in diabetic or immunocompromised patients 2

4. Assuming MRSA coverage is always needed: While clindamycin is recommended here due to treatment failure, studies show that for typical cellulitis without abscess, adding MRSA coverage (like TMP-SMX) to cephalexin does not significantly improve outcomes 5, 6

By addressing both the fungal and bacterial components while emphasizing local care, this approach offers the best chance for clinical resolution and prevention of recurrence.