Mycobacterium abscessus Complex – a Particular Challenge in the Setting of Lung Transplantation

ABSTRACT

Mycobacterium abscessus complex is an emerging pathogen in lung transplant candidates and recipients. M. abscessus complex is widespread in the environment and can cause pulmonary, skin and soft tissue, and disseminated infection, particularly in lung transplant recipients. It is innately resistant to many antibiotics making it difficult to treat. Herein we describe the epidemiology, clinical manifestations, diagnosis and treatment of M. abscessus with an emphasis on lung transplant candidates and recipients. We also outline the areas where data are lacking and the areas where further research is urgently needed.

KEYWORDS:

• Mycobacterium abscessus complex
• Non tuberculous mycobacterium
• lung transplantation
• infection
• diagnosis
• treatment
• Macrolides

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Using 16S ribosomal RNA gene sequencing M. abscessus has recently been identified to consist of three subspecies, namely, M. abscessus subsp. abscessus, M. abscessus subsp. Bolletii, and M. abscessus subsp. massiliense. M. abscessus subsp. massiliense appears to have greater susceptibility to clarithromycin and better outcomes with shorter courses of treatment.

• The prevalence of non-tuberculous mycobacterium (NTM) including M. abscessus complex has been increasing both in the general and lung transplant populations. Prevalence rates of 460–2300 cases of NTM per 100,000 patients have been reported in lung transplant recipients. This is much higher than in the general population and other transplant populations.

• Pre-transplantation infection with M. abscessus complex is predominantly confined to the lungs while post-lung transplantation infection is more commonly extra-pulmonary at sites including skin and soft tissue infections, surgical site infections, joint, and bone. Disseminated disease rarely occurs pre-transplantation.

• The diagnosis of M. abscessus complex infection post-lung transplantation is based on the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) published diagnostic criteria for NTM, including M. abscessus complex.

• Multiple small retrospective cohorts have indicated that outcomes for patients with pre-transplant NTM who are transplanted are no worse than those who were transplanted without NTM suggesting that pre-transplant isolation of M. abscessus complex may not be a complete contraindication to transplant as had previously been thought. In isolated cases, lung transplantation has resulted in prolonged periods of sputum culture negativity post-procedure. This is most often achieved in those with low microbial burden, proven culture conversion preoperatively, and prolonged presurgical antimicrobial therapy. Patients who remain smear positive at the time of transplantation appear to be more predisposed to infection of the lung allograft.

• It is generally recommended that induction therapy is composed of oral clarithromycin (500 mg twice daily) or azithromycin (500 mg daily) plus IV cefoxitin (up to 12 g in 3–4 divided doses), and amikacin (15 mg/kg daily). Azithromycin may be more effective than clarithromycin specifically for M. abscessus complex as the former induces erm(41) gene expression to a lesser degree than the latter. Maintenance therapy is usually with a combination of oral and inhaled antibiotics based on susceptibility testing results.

• Newer agents including tedizolid and bedaquiline are showing promise against M. abscessus complex but further study is required to establish their efficacy and safety profiles in transplant recipients.