Treatment Approaches to Mycobacterium abscessus Pulmonary Disease.

Mycobacterium abscessus pulmonary disease is highly antibiotic-resistant, and the current armamentarium of antibiotics yields poor treatment outcomes with significant drug toxicity. Macrolide susceptibility is a key prognostic factor. Optimal drug combinations, duration of therapy, and management of refractory disease are unknown. Surgical resection, performed at centers with experience in surgical management of nontuberculous mycobacterial pulmonary disease, may produce favorable outcomes in select patients. Multiple emerging therapeutic candidates hold promise for more efficacious and tolerable treatment options.

Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by Mycobacterium avium complex (MAC) and Mycobactereoides abscessus complex (MABS). We show that active MAC infection is characterized by elevated T cell immunoglobulin and mucin-domain containing-3 expression across multiple T cell subsets. In contrast, active MABS infection was characterized by increased expression of cytotoxic T-lymphocyte-associated protein 4. Patients who failed therapy closely mirrored the healthy individual immune phenotype, with circulating immune network appearing to 'ignore' infection in the lung. Interestingly, immune biosignatures were identified that could inform disease stage and infecting species with high accuracy. Additionally, programmed cell death protein 1 blockade rescued antigen-specific IFN-γ secretion in all disease stages except persistent infection, suggesting the potential to redeploy checkpoint blockade inhibitors for NTM-PD. Collectively, our results provide new insight into species-specific 'immune chatter' occurring during NTM-PD and provide new targets, processes and pathways for diagnostics, prognostics, and treatments needed for this emerging and difficult to treat disease.

Management of Extrapulmonary Nontuberculous Mycobacterial Infections.

Extrapulmonary disease occurs in a minority of nontuberculous mycobacterial (NTM) infections. The pattern of disease tends to be multifocal in immunocompromised individuals and localized in the immunocompetent. There is increasing recognition of disseminated Mycobacterium chimaera infection, as a complication of cardiac surgery, and focal infections due to rapidly growing mycobacteria. Microbiologic diagnosis requires detection of NTM in blood or tissue samples by microscopy, culture, or molecular methods. Management of extrapulmonary NTM infection requires prolonged, targeted multiple-drug therapy and, in some cases, aggressive surgical intervention. The optimal treatment approach is often unknown. Despite combined medical and surgical therapy, outcomes may be poor. A high degree of clinical suspicion and early diagnosis are required to maximize chances of a positive outcome.

Radiology of Chronic Cavitary Infections.

Chronic cavitary lung disease is an uncommon manifestation of pulmonary infection, and is a pattern which worldwide is most commonly caused by reactivation tuberculosis. Other organisms, however, can cause similar radiologic patterns. Endemic fungi have long been recognized as potential causes of this pattern in North and South America, but the frequency with which these diseases present with chronic cavities in North America is relatively small. Nontuberculous mycobacteria and chronic aspergillus infections are recognized with increasing frequency as causes of this pattern. Melioidosis, a bacterial infection that can also cause chronic lung cavities, was previously understood to be relevant primarily in Southeast Asia, but is now understood to have a wider geographic range. While cultures, serologies, and other laboratory methods are key to identifying the infectious causes of chronic lung cavities, radiologic evaluation can contribute to the diagnosis. Differentiating the radiologic patterns of these diseases from reactivation tuberculosis depends on subtle differences in imaging findings and, in some cases, appreciation of underlying lung disease.

Chronic Cavitary Infections Other than Tuberculosis: Clinical Aspects.

Lung cavitation may be due to infectious or noninfectious pathologic processes. The latter category includes nonmalignant conditions, such as granulomatosis with polyangiitis, and malignant conditions, such as squamous cell carcinoma of the lung. Infectious etiologies that produce lung cavitation usually cause chronic illness, although some, particularly pyogenic bacteria, may produce acute cavitary disease. Tuberculosis is the most common cause of chronic pulmonary infection with cavitation. The goal of this review was to highlight a selection of the better-known infectious agents, other than tuberculosis, that can cause chronic lung disease with cavitation. Emphasis is placed on the following organisms: nontuberculous mycobacteria, Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, Aspergillus, Burkholderia pseudomallei, Paragonimus westermani, and Rhodococcus equi. These organisms generally produce clinical features and radiologic findings that overlap or mimic those of tuberculosis. In a companion article, we have further emphasized aspects of the same conditions that are more pertinent to radiologists.