What is the recommended treatment regimen for disseminated Mycobacterium abscessus infection?

From the Guidelines

The recommended treatment regimen for disseminated Mycobacterium abscessus infection typically involves a multidrug approach with an initial intensive phase followed by a continuation phase, as outlined in the British Thoracic Society guidelines 1.

Treatment Overview

The treatment should begin with a combination of intravenous medications including amikacin (10-15 mg/kg daily), intravenous tigecycline (50 mg twice daily), and where tolerated intravenous imipenem (1 g twice daily), along with oral macrolides such as azithromycin (250-500 mg daily) or clarithromycin (500 mg twice daily) if the isolate is macrolide-susceptible 1.

Key Considerations

• The intensive phase should last for at least 1 month, with the duration influenced by the severity of infection, treatment response, and tolerance of the regimen 1.
• Following the intensive phase, patients should continue with oral medications including a macrolide plus some combination of clofazimine (50-100 mg daily), linezolid (600 mg daily), or fluoroquinolones based on susceptibility testing for at least 12 months after culture conversion 1.
• Surgical debridement of infected tissues may be necessary as an adjunct to antimicrobial therapy.
• Regular monitoring for drug toxicities is essential, including audiometry for amikacin, renal function tests, liver function tests, and complete blood counts.

Treatment Duration and Monitoring

• Treatment duration is typically prolonged, often 12-18 months total, with at least 12 months of therapy after negative cultures.
• M. abscessus is highly resistant to many antibiotics, and treatment success depends on using multiple drugs with different mechanisms of action to overcome resistance and prevent further resistance development 1. Some key points to consider in the treatment of disseminated M. abscessus infection include:
• The importance of susceptibility testing to guide antibiotic selection 1.
• The need for close monitoring of patients for signs of treatment failure or toxicity 1.
• The potential role of surgical intervention in selected cases 1.

From the Research

Disseminated Mycobacterium abscessus Treatment

The recommended treatment regimen for disseminated Mycobacterium abscessus infection is not well established, but several studies have investigated potential treatment options.

• The current treatment regimens recommended for Mycobacterium abscessus subspecies abscessus (Mab) pulmonary disease are not effective 2.
• Subspecies identification is critical for disease management, as subspecies abscessus and bolletii have an inducible macrolide resistance gene [erm(41)] that results in clinical macrolide resistance 3.
• Macrolide resistance has a profoundly negative impact on M abscessus treatment response, and preserving macrolide susceptibility with adequate companion drugs for macrolides is among the highest treatment priorities 3.
• Amikacin is regarded as the next most important drug for M abscessus treatment, although data validating that assertion are lacking 3.
• Recent guidelines suggest that treatment should be guided by in vitro susceptibilities, but aside from macrolides and amikacin, no other antibiotics have a validated minimum inhibitory concentration for M abscessus 3.
• Combination therapy with clarithromycin, amikacin, and other active antimicrobial agents may lead to clinical improvement, but the rate of treatment failure is still high 4.
• Newer drugs have become available, with encouraging in vitro activity against M abscessus, but in vivo validation of their superiority to current agents is not yet available 3.

Potential Treatment Options

Several potential treatment options have been identified, including:

• Tebipenem/avibactam, daunorubicin, omadacycline, and bedaquiline, which have shown low MICs and efficacy at clinically achievable concentrations 2.
• Amikacin, tigecycline, imipenem, and clarithromycin, which have been tested in combination against M. abscessus subsp. abscessus using the in vitro time-kill assay 5.
• Azithromycin and clarithromycin, which have been compared for their resistance patterns and gene sequences associated with resistance in M. abscessus complex isolates 6.

Considerations for Treatment

When considering treatment options for disseminated Mycobacterium abscessus infection, several factors should be taken into account, including:

• The subspecies of M. abscessus, as this can affect treatment outcomes 3.
• The presence of macrolide resistance, which can significantly impact treatment response 3.
• The use of combination therapy, which may lead to improved treatment outcomes 4, 5.
• The potential for treatment failure, which is still high despite the use of combination therapy 4.