What is the treatment for a suspected Buruli ulcer caused by Mycobacterium ulcerans after an insect bite on the leg that has not healed for a month?

Treatment of Buruli Ulcer (Mycobacterium ulcerans Infection)

For suspected Buruli ulcer on the leg that has not healed for a month, surgical debridement combined with skin grafting is the treatment of choice, supplemented with an 8-week course of rifampin and clarithromycin to prevent relapse.

Diagnosis and Clinical Presentation

• Buruli ulcer presents as an indolent, progressive necrotic lesion of the skin with characteristic scalloped or indeterminate edges 1
• Infection typically occurs through abraded or compromised skin after contact with contaminated water or soil
• The disease commonly affects children and young adults and can result in severe scarring and deformities of the extremities if not properly treated 1
• A non-healing ulcer for one month following an insect bite in an endemic area is highly suspicious for M. ulcerans infection

Treatment Approach

Surgical Management

• Wide surgical excision with skin grafting is the primary treatment of choice for established ulcers 1
• Medical treatment alone for large established ulcers has historically been disappointing 1
• Surgical intervention is particularly important for larger lesions (>5 cm in diameter) 2

Antibiotic Therapy

• The WHO-recommended antibiotic regimen consists of:

  • Rifampin (10 mg/kg/day orally) AND
  • Clarithromycin (500 mg twice daily orally)
  • Administered daily for 8 weeks under directly observed therapy 2, 3

• This combination has demonstrated high efficacy with cure rates of 96% in clinical studies 2

• For smaller lesions (<5 cm), antibiotic therapy alone may be sufficient without surgical intervention 2

Treatment Algorithm Based on Lesion Size

1. Small lesions (<5 cm):

   • 8-week course of rifampin and clarithromycin
   • Surgery generally not required (only 17% of such cases needed surgery) 2

2. Medium lesions (5-15 cm):

   • 8-week course of rifampin and clarithromycin
   • Consider surgical intervention based on clinical response

3. Large lesions (>15 cm):

   • 8-week course of rifampin and clarithromycin
   • Surgical excision and skin grafting highly likely (73% of such cases required surgery) 2

Important Considerations

• Timing of surgery: Typically performed after 4 weeks of antibiotic therapy 4
• Post-surgical antibiotics: Continue antibiotics for the remainder of the 8-week course after surgery 4
• Monitoring: Regular follow-up is essential to assess healing and detect potential recurrence
• Recurrence rate: Very low (1-1.5%) when proper combined therapy is administered 2, 4

Risk Factors for Treatment Failure

Recent research has identified potential risk factors for antibiotic treatment failure 5:

• Weight >90 kg
• Male gender
• Immunosuppression
• Inadequate dosing of antibiotics

Emerging Treatment Options

Newer research suggests potential for shorter treatment courses:

• Combination therapy with rifapentine, clofazimine, and Q203 (telacebec) has shown promise in reducing treatment duration to 2 weeks in animal models 6
• However, these regimens are still experimental and not yet recommended for clinical use

Conclusion

Early diagnosis and prompt initiation of treatment are crucial for preventing disability. The combination of surgical debridement with skin grafting and 8 weeks of rifampin plus clarithromycin offers the best outcomes for established Buruli ulcers, with very low recurrence rates.