Mycobacterium Avium Complex Biofilm in a Lung Cavity

Abstract Description. A 58 year-old lifelong non-smoker female was referred to our center for management of pulmonary Mycobacterium avium complex (MAC) disease with a left apical cavity. Her medical history was significant for locally advanced non-small cell lung cancer, stage IIIA at age 46, status post left upper lobectomy (LUL). This was treated with chemotherapy, erlotinib and radiation therapy for brain metastasis. She developed a cough, and MAC was identified on bronchoalveolar lavage of the left apex. She was treated with azithromycin, ethambutol and rifampin. Rifampin was discontinued due to drug-induced hepatitis. M. chelonae was also isolated, and oral clofazimine, intravenous imipenem and amikacin were added. Due to ear fullness and leukopenia, amikacin and imipenem were discontinued. After the ear fullness resolved, inhaled amikacin was initiated. Pulmonary function tests demonstrated FEV1 of 1.92 L (76% pred), FVC 2.79 L (87% pred) and DLCO corrected 18.6 (94% pred). Recent axial imaging showed a left apical thick-walled cavity with nodules in the basilar and lateral left lung. Due to pulmonary MAC disease refractory to medical therapy for over 18 months, we recommended resection of the cavitary lesion. Sputum collected two months pre-operatively demonstrated many acid-fast bacilli (AFB) on smear, and rough and smooth variants of M. intracellulare subspecies chimaera, susceptible to clarithromycin and amikacin. We treated her with oral azithromycin, ethambutol, clofazimine, and omadacycline; inhaled amikacin and off-label ceftazidime-avibactam IV were added for additional coverage during the perioperative period. Robotic-assisted thoracoscopic surgery was attempted, however extensive adhesions and fibrosis surrounded the cavity, so the case was converted to open thoracotomy. The patient recovered uneventfully and at 6 month follow-up was symptom-free. Pathology demonstrated extensive granulomatous inflammation with necrosis and fibrosis of the wedge resection, and non-necrotizing granulomata in the hilar and intraparenchymal lymph nodes; special stains were negative for AFB. Cultures of the resected tissue were negative. Scanning electron microscopy demonstrated bacilli within a complex matrix consistent with biofilm. PCR of the tissue confirmed only MAC. Discussion. Biofilms containing MAC have been found in multiple environments, including plumbing systems and showerheads, and MAC biofilms can be created in vitro. To our knowledge, this is the first report of MAC biofilm in a human. MAC biofilm within cavities may be a cause of disease that is refractory to medical therapy.