Inhaled Antibiotics for Mycobacterial Lung Disease

Abstract

Mycobacterial lung diseases are an increasing global health concern. Tuberculosis and nontuberculous mycobacteria differ in disease severity, epidemiology, and treatment strategies, but there are also a number of similarities. Pathophysiology and disease progression appear to be relatively similar between these two clinical diagnoses, and as a result these difficult to treat pulmonary infections often require similarly extensive treatment durations of multiple systemic drugs. In an effort to improve treatment outcomes for all mycobacterial lung diseases, a significant body of research has investigated the use of inhaled antibiotics. This review discusses previous research into inhaled development programs, as well as ongoing research of inhaled therapies for both nontuberculous mycobacterial lung disease, and tuberculosis. Due to the similarities between the causative agents, this review will also discuss the potential cross-fertilization of development programs between these similar-yet-different diseases. Finally, we will discuss some of the perceived difficulties in developing a clinically utilized inhaled antibiotic for mycobacterial diseases, and potential arguments in favor of the approach.

Inhaled Liposomal Antimicrobial Delivery in Lung Infections

“…Liposomal ciprofloxacin is prepared using negatively charged liposomes (liposome surfaces coated with polyethylene glycol or PEG) and is delivered by inhalation or intravenous routes. In preclinical studies liposomal ciprofloxacin has shown great promise in the treatment of P. aeruginosa and MAC lung infections, since it was able to infiltrate established biofilms and penetrate infected macrophages [56][57][58]. The in vivo release profile after intratracheal instillation in mice confirmed that the liposomal formulation satisfied the requirement for sustained levels of ciprofloxacin in the lung for a duration of 24 h, having a lung clearance half-life after inhalation of approximately 12 h (compared with 1 h for free ciprofloxacin).…”

Emerging trends in inhaled drug delivery

“…Non-tuberculous mycobacteria, primarily caused by Mycobacterium avium complex and Mycobacterium abscessus, lung infections are found in immunocompromised and otherwise functionally compromised lungs. It is particularly serious in cystic fibrosis patients and a portion of the elderly population identified in Lady Windermere Syndrome [47][48][49]. The disease manifests as extracellular biofilms associated with bronchiectasis and intracellular disease in lung macrophages [50].…”

<p>The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults</p>

“…5 This process leads to an immune response that results in granuloma formation, a phenomenon that allows NTM strains to survive. 5,13 The consequences of tuberculosis infections (M. tuberculosis) are typically more severe and are characterized by cavitary lung disease that leads to increased mortality. It is important to note, however, that lung cavity formation is present in some rare cases of NTM infection.…”

“…It is important to note, however, that lung cavity formation is present in some rare cases of NTM infection. 5 The symptoms of NTMinduced pulmonary disease are variable, but nearly all patients present with a chronic or recurring cough. 29 Variable symptoms include fever, fatigue, increased sputum production, hemoptysis, dyspnea, chest pain, and weight loss.…”