Shifting Paradigms Regarding the Role of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis Advanced Lung Disease

Abstract

Nontuberculous mycobacteria (NTM) are challenging pathogens in cystic fibrosis (CF). The best approach is unknown, in particular, in patients in need of a lung transplant (LTX). NTM sputum-positive patients were identified from all CF patients treated at the University Hospital of Zurich Adult CF Center. Course of disease and resistance to macrolide therapy was recorded. Of 6 patients who received a LTX, NTM patients were compared with patients without NTM for survival and development of chronic lung allograft dysfunction (CLAD). Of 111 CF patients, 43 (38.7%) patients grew at least one NTM culture of which 28 (25.2%) reached the stringent criteria for NTM positivity defined by three NTM positive cultures. With 32 (74.4%) isolates, M. abcessus spp. (MABSC) were the most frequent and acquired at an earlier age as compared to other NTM species (20 y [17-8] vs. 27 y [24-33]). NTM patients tended to be male and homozygous for PheF508del mutation, in particular, patients with MABSC, and more likely to require a LTX than patients without NTM (14.3% vs. 2.4%, p = 0.035). Of 28 MABSC patients with susceptibility testing, only three out of 16 (18.8%.) patients receiving treatment achieved long-term culture negativity. Treated patients were more likely to develop clarithromycin resistance than patients without treatment (68.8% vs. 16.7%, p = 0.019) with no difference in developing advanced lung disease (ALD), receiving a LTPL or death. 2 of the 6 patients undergoing LTX suffered from infection with MABSC, both of them being NTM positive before LTX. No difference in long-term survival nor in developing CLAD was observed. Two patients developed pulmonary and one extra-pulmonary infection. NTM patients are at greater risk of ALD and requiring LTX, with MABSC infection acquired at an earlier age and being more common in patients with PheF508del homozygous genotype. It is unclear whether this reflects a more rapid underlying course of CF. In MABSC patients, response to chemotherapy was poor and development of resistance common. NTM infection after LTX did not result in increased mortality or development of CLAD and BOS, but was associated with infection. Our experience supports that NTM infection should not generally be regarded as an absolute contraindication for LTX, but NTM eradication prior to LTX should be attempted.