What is the treatment for Mycobacterium fortuitum infections?

Treatment of Mycobacterium fortuitum Infections

Treat M. fortuitum infections with at least two antibiotics based on susceptibility testing for a minimum of 4 months for skin/soft tissue disease, 6 months for bone infections, and 12 months after culture conversion for pulmonary disease, combined with surgical debridement when indicated. 1

Antimicrobial Susceptibility Profile

M. fortuitum is typically susceptible to multiple oral and parenteral agents, making it one of the more treatable rapidly growing mycobacteria:

• 100% susceptibility: amikacin, ciprofloxacin/ofloxacin, sulfonamides, and imipenem 1
• 50% susceptibility: cefoxitin and doxycycline 1
• 80% apparent susceptibility to clarithromycin - but this is misleading (see critical caveat below) 1

Drug susceptibility testing is essential before finalizing therapy, as resistance patterns can vary and guide effective treatment 1, 2

Critical Macrolide Caveat

Avoid using macrolides (clarithromycin, azithromycin) as primary agents despite "susceptible" in vitro results. All M. fortuitum isolates contain an inducible erythromycin methylase erm(39) gene that confers macrolide resistance through variable expression 3, 1. This means clarithromycin may appear susceptible on testing but fail clinically due to inducible resistance 1. If macrolides are used, they must be combined with other active agents and never used as monotherapy 1.

Treatment Algorithm by Site of Infection

Skin and Soft Tissue Infections

Localized disease (cellulitis, single abscess):

• Surgical debridement plus single oral agent (typically sulfonamide) for mean duration of 10.6 weeks 4
• Alternative single agents: ciprofloxacin or doxycycline based on susceptibility 1, 4

Extensive disease (multiple sites, deep tissue involvement):

• Initial parenteral therapy: amikacin ± cefoxitin or imipenem for 2-4 weeks until clinical improvement 1, 2, 4
• Transition to oral therapy with two susceptible agents (e.g., sulfonamide + ciprofloxacin) for total duration of 4 months 1, 4
• Surgical debridement is crucial - 60-74% of patients require surgical intervention 1

Bone and Joint Infections

• Surgical debridement plus combination therapy for minimum 6 months 1
• Initial regimen: amikacin ± cefoxitin/imipenem for 4 weeks, followed by oral agents (sulfonamide-based) for remainder of treatment 4
• Cultures typically convert within 6 weeks for most sites, but sternal osteomyelitis may require up to 14 weeks 4

Pulmonary Disease

• Treatment duration: 12 months after sputum culture conversion 1
• Combination therapy with at least two susceptible agents throughout treatment 1
• Preferred regimens based on susceptibility: amikacin + ciprofloxacin, or sulfonamide + ciprofloxacin 1, 5
• Monitor sputum cultures monthly; expect conversion within 6 weeks of appropriate therapy 1, 4
• Consider susceptibility testing if cultures remain positive after 3 months of therapy 3

Peritonitis (Dialysis-Related)

• Catheter removal is mandatory 2
• Empiric therapy: amikacin plus cefoxitin or imipenem for at least 2 weeks pending susceptibilities 2
• Continue combination therapy based on susceptibility results for minimum 4 months 2

Recommended Antibiotic Combinations

Based on 100% susceptibility rates and clinical experience:

First-line combinations:

• Amikacin + ciprofloxacin 1, 5
• Amikacin + sulfonamide 1, 4
• Ciprofloxacin + sulfonamide (for oral-only regimens) 1

Alternative combinations for resistant isolates:

• Amikacin + imipenem 1, 2
• Doxycycline + ciprofloxacin (if susceptible) 4, 6

Monitoring and Follow-Up

• Obtain follow-up cultures to document response - expect conversion within 6 weeks for most infections 1, 4
• Monitor for clinical improvement (resolution of fever, decreased drainage, healing of lesions) 4, 6
• Follow patients for mean of 12 months after treatment completion to detect rare relapses 4
• Consider repeat susceptibility testing if cultures remain positive beyond 3 months 3, 1

Special Considerations

Fluoroquinolone resistance is emerging - documented cases show gyrA gene mutations conferring resistance 7. This reinforces the importance of susceptibility testing and using combination therapy 7.

Immunocompromised patients (post-gastrectomy, rheumatoid arthritis on immunosuppressants, chronic vomiting disorders) are at higher risk for M. fortuitum infection and may require more aggressive therapy 1, 7.

Observation without antibiotics may be appropriate for stable pulmonary disease - approximately two-thirds of patients with M. fortuitum pulmonary disease remain stable without antibiotic treatment 8. However, close monitoring is essential as some progress to aggressive disease requiring treatment 3, 8.

Surgical intervention is critical - 60-74% of patients require some form of surgical debridement or excision for cure 1, 4. Do not rely on antibiotics alone for localized abscesses or extensive disease 1.