What is the recommended treatment for Mycobacterium abscessus infections?

Treatment of Mycobacterium abscessus Infections

The recommended treatment for Mycobacterium abscessus infections requires a multidrug regimen that includes at least three active drugs guided by in vitro susceptibility testing, with an initial intensive phase followed by a continuation phase. 1

Initial Phase Treatment (≥4 weeks)

The initial phase should consist of:

• Intravenous amikacin (15 mg/kg daily or 3× per week)
• Intravenous tigecycline (50 mg twice daily)
• Intravenous imipenem (1 g twice daily, where tolerated)
• Oral macrolide (clarithromycin 500 mg twice daily or azithromycin 250-500 mg daily)

Important considerations for initial phase:

• Duration should be at least 4 weeks but may be extended based on disease severity, treatment response, and medication tolerance 1
• Antiemetic medication (ondansetron and/or aprepitant) should be prescribed to reduce nausea/vomiting with tigecycline and imipenem 1
• Monotherapy with a macrolide should NEVER be used due to risk of developing resistance 1
• Cefoxitin (up to 12 g/day IV in divided doses) can be used as an alternative to imipenem, but has higher rates of adverse effects (neutropenia in 51%, thrombocytopenia in 6%) 1, 2

Continuation Phase Treatment

After the initial phase, treatment should transition to:

• Nebulized amikacin
• Oral macrolide (clarithromycin 500 mg twice daily or azithromycin 250-500 mg daily)
• 2-4 additional oral antibiotics based on susceptibility and tolerance from:
  • Clofazimine
  • Linezolid
  • Minocycline/doxycycline
  • Moxifloxacin/ciprofloxacin
  • Co-trimoxazole

Important considerations for continuation phase:

• Treatment should continue for a minimum of 12 months after culture conversion 1
• For patients who fail to culture-convert, long-term suppressive antibiotic therapy may be beneficial 1
• If the isolate has constitutive macrolide resistance, the macrolide should not be counted as an active drug 1
• In cases of amikacin resistance (MIC >64 mg/L or 16S rRNA gene mutation), substitute amikacin with an alternative antibiotic 1

Treatment Outcomes and Prognosis

Treatment outcomes vary significantly based on the M. abscessus subspecies:

• M. abscessus subsp. massiliense: 88-91% culture conversion rate 1, 3
• M. abscessus subsp. abscessus: 25-31% culture conversion rate 1, 3

This difference is due to the presence of a functional erm(41) gene in M. abscessus subsp. abscessus that confers inducible macrolide resistance 1.

Special Considerations

1. Surgical resection: For patients with focal disease who can tolerate surgery, surgical resection combined with multidrug therapy offers the best chance for cure 1

2. Macrolide selection: Azithromycin may be preferred over clarithromycin as it is a weaker inducer of erm(41) gene expression 1

3. Inhaled amikacin: Recent evidence suggests favorable outcomes with inhaled amikacin in the continuation phase, particularly for M. abscessus subsp. massiliense 3

4. Expert consultation: Management should involve a physician experienced in treating NTM pulmonary disease 1

5. Drug toxicity monitoring: Regular monitoring for adverse effects is essential, particularly:

   • Aminoglycosides: hearing loss, vestibular toxicity, nephrotoxicity
   • Cefoxitin: neutropenia, thrombocytopenia
   • Linezolid: peripheral neuropathy, optic neuritis, anemia
   • Tigecycline: nausea, vomiting

Common Pitfalls to Avoid

• Inadequate drug combinations: Using fewer than three active drugs increases risk of treatment failure and resistance development
• Inappropriate treatment duration: Treating for less than 12 months after culture conversion
• Failure to identify subspecies: Not distinguishing between M. abscessus subspecies abscessus and massiliense, which have different treatment outcomes
• Monotherapy with macrolides: This approach will lead to resistance and treatment failure 1
• Overlooking surgical options: Not considering surgical resection for localized disease
• Insufficient monitoring: Not regularly assessing for drug toxicities and treatment response

M. abscessus remains one of the most difficult-to-treat mycobacterial infections, with overall cure rates of approximately 58% despite aggressive therapy 2. Treatment decisions should be guided by antimicrobial susceptibility testing, and regimens may need adjustment based on clinical response and tolerability.