What are the recent approaches to treating Mycobacterium fortuitum infections?

Recent Approaches to Treating Mycobacterium fortuitum Infections

For Mycobacterium fortuitum infections, treatment should include a minimum of 4 months of combination therapy with at least two antibiotics selected based on in vitro susceptibility testing, with surgical intervention when indicated for extensive disease or abscess formation. 1

Organism Characteristics

• M. fortuitum belongs to a group that historically included three species/taxa: M. fortuitum, M. peregrinum, and an unnamed third biovariant complex 1
• Recently, additional species have been described within this group, including M. houstonense and M. boenickei 1
• Separation of these species can only be accomplished by molecular testing 1

Clinical Presentations

• Pulmonary disease due to M. fortuitum is clinically similar to lung disease caused by M. abscessus, but is relatively rare 1
• M. fortuitum is more commonly found in patients with gastroesophageal disorders with chronic vomiting 1
• Skin, bone, and soft tissue are important sites of M. fortuitum infections 1
• Recently identified as a cause of furunculosis associated with whirlpool footbaths in nail salons 1
• Can present as surgical site infections following various procedures, including spinal surgery 2
• May rarely present as community-acquired pneumonia even in immunocompetent hosts 3

Antimicrobial Susceptibility

• M. fortuitum isolates are typically susceptible to multiple oral antimicrobial agents 1
• Susceptibility rates include: amikacin (100%), ciprofloxacin/ofloxacin (100%), sulfonamides (100%), imipenem (100%), cefoxitin (50%), clarithromycin (80%), and doxycycline (50%) 1, 4
• Drug susceptibility testing is essential for guiding effective therapy 4
• Important caution: All isolates of M. fortuitum contain an inducible erythromycin methylase erm(39) gene that confers resistance to macrolides 1, 4
• Despite "susceptible" MICs seen in 80% of isolates for clarithromycin, macrolides should be used with caution due to this inducible resistance mechanism 1, 4

Treatment Approach for M. fortuitum Infections

General Principles

• Therapy should include at least two agents with in vitro activity against the clinical isolate 1, 4
• Minimum treatment duration of 4 months for skin, bone, and soft tissue disease 1
• For bone infections specifically, 6 months of therapy is recommended 1
• For pulmonary disease, treatment should continue for at least 12 months after sputum cultures become negative 1

Initial Empiric Therapy

• While awaiting susceptibility results, initiate therapy with amikacin plus either cefoxitin or imipenem 4, 5
• Continue this initial combination for at least 2 weeks or until clinical improvement 4, 5

Definitive Therapy Based on Infection Site

Pulmonary Infections

• Combination therapy with at least two agents based on susceptibility testing 1
• Treatment should continue for at least 12 months of negative sputum cultures 1
• Drug combinations are dictated by patient tolerance and in vitro susceptibility 1

Skin, Soft Tissue, and Bone Infections

• For localized disease: Consider oral therapy with a sulfonamide or fluoroquinolone based on susceptibilities 6, 5
• For extensive disease: Initial therapy with amikacin or amikacin plus cefoxitin, followed by oral agents based on susceptibilities 6, 5
• Surgical debridement is often necessary, especially with extensive disease or abscess formation 1, 6, 5
• Removal of foreign bodies (e.g., breast implants, catheters) is essential for recovery 1

Corneal Infections

• Treatment often involves both topical and oral agents 1
• Amikacin, fluoroquinolones, clarithromycin, and azithromycin are usually drugs of choice 1
• Visual outcomes are typically poor, and many patients require corneal transplant 1

Special Considerations

• Macrolides (clarithromycin, azithromycin) should be used with caution due to inducible resistance 1, 4
• Despite this concern, macrolides have shown promising results in some cases when used as part of combination therapy 7, 5
• Surgical intervention is crucial in many cases, with 60-74% of patients requiring some form of surgical treatment 1, 6
• Response to appropriate therapy is generally good, with cultures typically becoming negative within 6 weeks of starting appropriate chemotherapy (except for sternal osteomyelitis, which may take up to 14 weeks) 6

Treatment Monitoring

• Follow cultures to document response to therapy 1, 6
• Consider susceptibility testing for patients who remain culture positive after more than 3 months of therapy 1
• Extended follow-up (12+ months) is recommended after completion of therapy to monitor for relapse 6