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M. abscessus Treatment
Treating NTM Lung Disease Caused by M. abscessus: An Uphill Battle

Released: October 27, 2023

Shannon Kasperbauer
Shannon Kasperbauer, MD
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Key Takeaways
  • Mycobacterium abscessus infection is one of the most difficult pulmonary infections to treat owing to the inherent resistance to antimicrobials and low cure rates.
  • Guidelines offer a framework for management, but much is unknown regarding the optimal treatment of this infection. 
  • New agents are in development that offer promise.

The management of Mycobacterium abscessus is challenging because of the inherent drug resistance and requirement of a multidrug regimen for months to years. A multisociety guideline is available to offer guidance for the management of this lung disease.

Laboratory Diagnosis Must Include Macrolide Resistance Testing

The most important characteristic of M. abscessus is its relationship to the macrolides. There are 3 subspecies of M. abscessus: abscessus, massiliense and bolettii. These organisms may be resistant to macrolides through 2 distinct mechanisms. The first is related to an erm(41) gene that most subspecies (abscessus or bolettii) possess, which confers inducible macrolide resistance. This inducible resistance presents itself through either phenotypic testing that allows for extended incubation (14 days) or molecular testing for the erm(41) gene. Fortunately, M. massiliense has a truncated and therefore dysfunctional erm(41) gene. Approximately 20% of the M. abscessus subspecies abscessus have a C-to-T substitution at position 28 in the erm gene, which renders the erm gene dysfunctional.

The second mechanism of macrolide resistance is termed “constitutive”, otherwise known as acquired resistance through a mutation in the ribosomal RNA (rrs). These isolates will have dense resistance to the macrolides at Day 3 of incubation. The reason this characteristic is so vital is related to the dramatic difference in cure between the 2 different phenotypes.

Initiation of Treatment or Watchful Waiting

The nontuberculous mycobacteria (NTM) guideline suggests that, in people who meet the diagnostic criteria for NTM lung disease, initiation of treatment rather than watchful waiting is warranted, especially when positive acid-fast bacilli sputum smears and/or cavitary lung disease are present. Studies in M. abscessus specifically have also identified that patients with bilateral lung disease or a low BMI (<18.5 kg/m2) are more likely to progress requiring treatment.

Even when antimicrobial therapy is not initiated, patients with bronchiectasis should initiate good airway clearance techniques using oscillating positive expiratory pressure valves, high-frequency chest wall oscillation, and/or hypertonic saline. In addition, exercise capacity, nutritional status, and gastroesophageal reflux should be assessed.

Antimicrobial Susceptibility Testing

Antimicrobial susceptibility testing for M. abscessus should include minimum inhibitory concentrations to clarithromycin and amikacin. As noted above, the isolate should be examined to determine if a functional erm(41) gene is present so that you know if inducible macrolide resistance is present.

Treatment of M. abscessus Lung Disease

Treatment is typically labeled “intensive” for the first phase because intravenous agents are necessary. This may last for 8 to 12 weeks before stepping down to a consolidation phase. For macrolide-susceptible M. abscessus lung disease, the guidelines strongly recommend using a macrolide as part of your multidrug regimen.

The other agents often used in the intensive phase include intravenous imipenem, cefoxitin, amikacin, and a tetracycline analogue (eg, tigecycline, omadacycline, eravacycline). It is suggested that intensive treatment comprise at least 3 active agents for macrolide-sensitive strains and up to 4 agents for macrolide-resistant strains.

After the intensive phase, it is recommended to continue 3 to 4 agents during the consolidation phase, depending on whether you are treating a macrolide-sensitive or -resistant organism. Other options to include in either phase of treatment include clofazimine, linezolid, tedizolid, inhaled amikacin, or bedaquiline.

The optimal duration of treatment is unknown. In a meta-analysis, the cure rates for macrolide-sensitive M. abscessus are 88% compared with 23% for macrolide-resistant disease (regardless of the mechanism of macrolide resistance). Surgical resection should be considered as an adjunct to drug therapy and should only occur in select cases with an experienced center.

There is a tremendous unmet need for new therapies in this NTM infection. Duration is measured in years, with substantial drug toxicity and abysmal cure rates in macrolide-resistant strains. Fortunately, multiple new agents have notable in vitro and in vivo activity against M. abscessus and we anxiously await additional data to support their utility in patients with M. abscessus. 

Goals of Therapy

As with pulmonary MAC, the goals of M. abcessus lung disease treatment are threefold. The ultimate goal is cure, defined as sustained culture conversion for at least 12 months off treatment. The second goal is symptom improvement, and the third is radiographic improvement.

Most patients with macrolide resistance will not achieve the first goal of cure, but many will feel better on therapy. Some patients may need chronic suppression of their infection if they experience relapse of symptoms off treatment.

Monitoring

Patients started on treatment should be monitored for treatment response with monthly sputum cultures. Monitoring for adverse events should be individualized based on treatment regimen, age, comorbidities, concurrent medications, overlapping medication toxicities, and resources available.

Your Thoughts?

What proportion of your patients with M. abscessus initiate treatment? What is your experience with adherence to treatment and likelihood of culture conversion? Join the conversation by posting a comment.