Case Report of a Patient With Treatment-Refractory Nontuberculous Mycobacteria (NTM) Lung Infection Treated With Once Daily (QD) Liposomal Amikacin for Inhalation (LAI)

Abstract

Introduction: Achieving negative NTM cultures is useful in assessing treatment effectiveness, and is a clinically important endpoint in NTM lung infection.(1,2) LAI is a novel amikacin formulation evaluated in TR02112, a placebo (PBO)-controlled study in adults with NTM lung infection refractory to guideline-based therapy for >6 months. Here we present data on a patient with Mycobacterium avium complex (MAC) NTM infection who was enrolled in TR02-112, randomized to PBO in the 84-day double-blind (DB) phase, and transitioned to LAI 590 mg QD in the open-label (OL) phase for 84 more days. CASE PRESENTATION: A 53-year old female with a history of asthma, treated with an inhaled corticosteroid and an anti-IgE monoclonal antibody, was diagnosed with MAC infection in April 2010. In June 2010, due to progressive fatigue and dyspnea on exertion, she began a suboptimal multidrug regimen of daily oral clarithromycin (cla) 500 mg, ethambutol (eth) 800 mg, and rifampin (rif) 600 mg at an outside institution. Her sputum remained culture-positive when she presented to NYU 18 months later and had her regimen optimized to cla 500 mg twice daily, eth 900 mg QD, and rif 600 mg QD. Despite 9 months of optimal therapy, her sputum remained culture-positive until September 2012, when she started PBO in TR02-112. She remained culture-positive through the DB phase. Upon transitioning to LAI in the OL phase, her sputum cultures converted to negative after 1 month and remained negative through the OL phase and the 28-day follow-up. She tolerated LAI well, mainly complaining of hoarseness, which improved with reduction in LAI frequency from 7 to 5 days/week. DISCUSSION: Patients with refractory NTM lung infection have limited therapeutic options and are often treated for lengthy durations with multidrug regimens.(1,2) Adding LAI to this patient's regimen converted her sputum cultures to negative after 1 month, which has implications for shortening overall treatment durations. Conclusions: LAI was effective in achieving and maintaining negative cultures in a patient with treatment-refractory NTM lung infection. Further LAI studies are warranted.