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Re-Examining Lung Transplantation in Patients with Mycobacterium Abscessus


Alyssa A. Perez, MD, EdM
Alyssa.Perez@ucsf.edu

Steven R. Hays, MD
Steven.Hays@ucsf.edu
University of California San Francisco
San Francisco, CA, USA



A 26F with a history of cystic fibrosis (FEV1 0.89) and Mycobacterium abscessus (diagnosed in 2006) presents for pre-lung transplant evaluation at your center after being turned away from multiple programs due to M abscessus infection.

The prevalence of nontuberculous mycobacterial (NTM) pulmonary infection is increasing worldwide among patients with structural lung disease and importantly, among our pre-lung transplant population [1]. Infection with NTM poses numerous challenges to lung transplantation as the organisms are difficult to eradicate, therapies are difficult to tolerate, and infection with NTM is associated with worse outcomes if present pre or acquired post lung-transplantation [2,3]. Particularly worrisome is Mycobacterium abscessus, which is considered to be a relatively strong contraindication to lung transplantation given association with poor outcomes [4].

NTM are ubiquitous in the environment and are found in water and soil. M abscessus is the most common cause of rapidly growing mycobacterium (RGM) pulmonary infection and is considered a virulent pathogen [1,5,6]. M abscessus is becoming increasingly prevalent among patients with structural lung disease, particularly in those with cystic fibrosis and bronchiectasis [1,7]. Part of this may be due to its ubiquitous nature in the environment as well as increased rates of detection; however, there is also evidence of patient to patient transmission among the cystic fibrosis population [5]. Among patients with cystic fibrosis, chronic infection with M abscessus portends a more rapid decline in FEV1 compared to patients with non-M abscessus NTM [2].

Why is M abscessus considered a relative contraindication to lung transplantation?

These recommendations stem from case reports in literature that describe a high post-transplant mortality associated with pre-lung transplant infection with M abscessus and a high rate of recurrent and refractory infection with M abscessus post-transplant [2,8,9]. In general, post-lung transplant infection with NTM is associated with increased mortality as well as the development of chronic lung allograft dysfunction (CLAD) [9,10]. Several retrospective studies have identified M abscessus as the most common mycobacterium causing NTM disease post-transplant [3,4]. Post-transplant, extra-pulmonary M abscessus infection involving the skin and soft tissue has also been observed, and the general recommendation has been for surgical debridement [11].

There is evolving, albeit limited, data to suggest that good outcomes are possible in patients with pre-transplant infection with M abscessus. There are two case series, one from Denmark and the other from Sweden, that describe successful transplantation of patients with pre-transplant infection with M abscessus [12,13]. One recent retrospective case study from the University of North Carolina by Lobo et al, found no difference in mortality between cystic fibrosis transplant recipients with pre-lung transplant infection with M abscessus and those without M abscessus infection [14].

M abscessus is notoriously difficult to treat, however, improving treatment regimens have helped treat these infections successfully. Generally speaking, the treatment of M abscessus is undertaken in a biphasic approach beginning with an intensive phase lasting 1-4 months (until smear conversion), comprised of multiple IV and oral drugs followed by a consolidation phase usually compromised of daily oral and inhaled medications6. Drug choice is tailored to patient micro sensitivities as much as possible; however, generally includes a macrolide backbone, amikacin, cefoxitin and imipenem [15]. Tigecycline, inhaled amikacin and linezolid are other agents being used to treat M abscessus [5]. A recent study in the Journal of Cystic Fibrosis by Da Costa et al showed that treatment of M abscessus in cystic fibrosis patients significantly improved lung function at 30 and 60 days and may prevent progression of lung function decline beyond this time period [15].

Should we transplant patients with pre-transplant infection with M abscessus?

The patient was referred to our program in March of 2012 and initially treated with PO azithromycin, IV cefoxitin and IV amikacin for smear positive M abscessus. Inhaled amikacin was added in August of 2012. In November of 2012, due to hearing loss noted on screening audiology exam and recurrent positive smear, amikacin was stopped and linezolid and tigecycline were started. Tigecycline was held temporarily due to GI intolerance. Linezolid was transitioned to tigecycline several months later due to the development of peripheral neuropathy. The patient was actively listed for transplant when AFB smear became negative although she was intermittently culture positive leading up to transplant. The four-drug regimen of PO azithromycin, IV cefoxitin, inhaled amikacin and IV tigecycline was continued until the time of transplant on 1/16/14, and a four-drug regimen was continued for eight months post-transplant. Cultures from bronchoalveolar lavage immediately post-transplant were positive for M abscessus, but have otherwise been negative to date. She developed an incisional infection due to M abscessus approximately one month following her transplantation. This was managed medically with PO azithromycin, IV cefoxitin, inhaled amikacin and linezolid. No surgical debridement was needed and the incisional wound healed well. Currently, the patient has intact graft function with no evidence of CLAD.

While pre-transplant infection with M abscessus can pose a therapeutic challenge and potentially place the recipient at high risk for recurrent infection and CLAD, improved antibiotic regimens and emerging data suggest that M abscessus can be adequately treated pre-transplant, managed post-transplant if recurrent and may not result in increased mortality post-transplant. Further studies are needed to help standardize the approach to the treatment of M abscessus infection pre-lung transplant, ensure infection eradication post-transplant and ensure that this patient population is not uniformly excluded from lung transplantation. ■

Disclosure Statement: the authors have no conflicts of interest to disclose.


References:

  1. Diel R, Ringshausen, F, Richter, E. Microbiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease. Chest 2017;152(1):120-142.
  2. Esther CR, Esserman DA, Gilligan P. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros 2010:9:117.
  3. Huang HC, Weight S, Derhovanessian A. Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. J Heart Lung Transplant 2011;30:790-798.
  4. Weill D, Benden C, Corris PA. A consensus document for the selection of lung transplant candidates: 2014- An update from the Pulmonary Transplantation Council of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2015;34:1-15.
  5. Koh WJ, Stout JE, Yew WW. Advances in the management of pulmonary disease due to Mycobacterium abscessus complex. Int J Tuberc Lung Dis. 2014;18(10):1141-1148.
  6. Van Ingen J, Ferro BE, Hoesfloot W. Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative patients. Expert Review of Anti-Infective Therapy 2013;11(10):1065-1077.
  7. Roux AL, Catherinot E, Ripoll F. Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in France. J Clin Microbiol 2009;47:4124-4128.
  8. Taylor JL, Palmer SM. Mycobacterium abscessus Chest Wall and Pulmonary Infection in a Cystic Fibrosis Lung Transplant Recipient. J Heart Lung Transplant 2006; 25:985-8.
  9. Huang HC, Weight S, Derhovanessian A. Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. J Heart Lung Transplant 2011;30:790-798.
  10. Shah SK, McAnally KJ, Seoanne L. Analysis of pulmonary non-tuberculous mycobacterial infections after lung transplantation. Transpl Infect Dis 2016:18:585-591.
  11. Chernenko, SM, MN, Humar A. Mycobacterium abscessus Infections in Lung Transplant Recipients: The International Experience. J Heart Lung Transplant 2006; 25:1447-55.
  12. Qvist T, Pressler T, Thomsen VO. Nontuberculous Mycobacterial Disease is Not a Contraindication to Lung Transplantation in Patients with Cystic Fibrosis: a retrospective analysis in a Danish Population. Transplantation Proceedings, 2013:45:342-345.
  13. Gilljam M, Schersten H, Silverborn M. Lung transplantation in patients with cystic fibrosis and Mycobacterium abscessus infection. J of Cyst Fibrosis 2010:9:272-276.
  14. Lobo, LJ, Chang LC, Esther CR. Lung transplant outcomes in cystic fibrosis patients with pre-operative Mycobacterium abscessus respiratory infections. Clin Transplant 2013:27:523-529.
  15. DaCosta A, Jordan CL, Giddings O. Outcomes associated with antibiotic regimens for treatment of Mycobacterium abscessus in cystic fibrosis patients. J of Cyst Fibros 2017:16:483-487.



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