Epidemiology of human pulmonary infection with mycobacteria nontuberculous

To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai.

A population-based retrospective study was conducted using presumptive pulmonary tuberculosis surveillance data of Shanghai between 2010 and 2019. The study described the spatial distribution of NTM-PD notification rates, employing hierarchical Bayesian mapping for high-risk areas and the Getis-Ord Gi* statistic to identify hot spots and explore associated factors.

Of 1652 NTM-PD cases, the most common species was Mycobacterium kansasii complex (MKC) (41.9%), followed by Mycobacterium avium complex (MAC) (27.1%) and Mycobacterium abscessus complex (MABC) (16.2%). MKC-PD patients were generally younger males with a higher incidence of pulmonary cavities, while MAC-PD patients were more often farmers or had a history of tuberculosis treatment. MKC-PD hot spots were primarily located in the areas alongside the Huangpu River, while MAC-PD hot spots were mainly in the western agricultural areas. Patients with MKC-PD and MAC-PD exhibited a higher risk of spatial clustering compared to those with MABC-PD.

Different types of NTM-PD exhibit distinct patterns of spatial clustering and are associated with various factors. These findings underscore the importance of environmental and host factors in the epidemic of NTM-PD.

Members of the Mycobacterium avium complex (MAC), including M. avium and M. chimaera, are representatives of over 200 species of nontuberculous mycobacteria (NTMs) that are opportunistic pathogens whose source for human infection is the environment. NTMs are normal inhabitants of soils, natural waters, drinking water distribution systems, and household plumbing. NTMs cause both community- and healthcare-associated infections, including pulmonary, dermal, lymph node, and disseminated infections. Risk factors for NTM disease include preexisting lung damage, cystic fibrosis, and immunodeficiency. In addition, taller, slender, older women are at risk for NTM pulmonary disease. The prevalence of NTM disease is increasing at a rate of 5% per year, currently at 15/100,000 individuals in the United States. Much of the ecology and epidemiology of the MAC and other NTMs can be explained by the ramifications of their lipid-rich outer membrane, including disinfectant-, antibiotic-, and desiccation resistance to disinfectants and commonly used antibiotics. Antibiotic treatment is of long duration and requires multidrug regimens. Fortunately, guidelines for the diagnosis and treatment of NTM infection are available.

The benzothiazole amide CRS0393 demonstrated excellent in vitro activity against nontuberculous mycobacteria (NTM), including M. abscessus isolates from cystic fibrosis (CF) patients, with minimum inhibitory concentrations (MICs) of ≤0.03–0.5 μg/mL. The essential transport protein MmpL3 was confirmed as the target via analysis of spontaneous resistant mutants and further biological profiling. In mouse pharmacokinetic studies, intratracheal instillation of a single dose of CRS0393 resulted in high concentrations of drug in epithelial lining fluid (ELF) and lung tissue, which remained above the M. abscessus MIC for at least 9 hours post-dose. This exposure resulted in a penetration ratio of 261 for ELF and 54 for lung tissue relative to plasma. CRS0393 showed good oral bioavailability, particularly when formulated in kolliphor oil, with a lung-to-plasma penetration ratio ranging from 0.5 to 4. CRS0393 demonstrated concentration-dependent reduction of intracellular M. abscessus in a THP-1 macrophage infection model. CRS0393 was well tolerated following intranasal administration (8 mg/kg) or oral dosing (25 mg/kg) once daily for 28 days in dexamethasone-treated C3HeB/FeJ mice. Efficacy against M. abscessus strain 103 was achieved via the intranasal route, while oral dosing will need further optimization. CRS0393 holds promise for development as a novel agent with broad antimycobacterial activity.

The diseases caused by Non-tuberculous mycobacteria (NTM) has increased steadily in the last two decades. Increase in incidence of NTM infections are being reported in elderly people as they are more susceptible and often experiencing high morbidity. There is prediction that NTM infections will further rise because of expected increase in elderly population by 2050. Given the importance of NTM infection in the elderly, the interest in studying NTM characteristics in the aged population is increasing. In this review, we summarize the characteristics of NTM infection among elderly patients. We focus on epidemiology, clinical presentation, and treatment options of NTM in this age group. We highlight the differences in the diagnosis and treatment between rapid and slow growing mycobacterial infections. The current recommendations for treatment of NTM have been discussed. Finally, we have reviewed the prognosis of NTM disease in elderly patients.

Increasing evidence indicates that microbiota dysbiosis in the human body may play vital roles in carcinogenesis. However, the relationship between microbiome and lung cancer remains unclear. In this study, we aimed to characterize the microbiome in early stage of lung adenocarcinoma (LUAD), which presented as subsolid nodules (SSN) or solid nodules (SN).

We performed 16S rRNA sequencing of 35 pairs (10 SSN and 25 SN) of LUAD tumor tissues and paired adjacent normal tissues. Machine learning was used to identify microbial signatures and construct predictive models.

SSN has higher microbiome richness and diversity compared with SN (richness p = 0.017, Shannon index p = 0.17), and the microbiome composition of SSN is distinct from that of SN (Bray-Curtis p = 0.013, unweighted unifrac p = 0.001). Phylum Chloroflexi (p = 0.009), Gemmatimonadetes (p = 0.018) and genus including Cloacibacterium (p = 0.003), Subdoligranulum (p = 0.002), and Mycobacterium (p = 0.034) were significantly increased in SSN. Tumor and normal tissues had similar richness and diversity, as well as overall microbiome composition. Probiotics with anti-cancer potential, like Lactobacillus, showed elevated levels in normal tissues (p = 0.018). A random forest model with 20 genera-based biomarkers achieved high accuracy for LUAD prediction (area under curve, AUC = 0.879). Meanwhile, a five genera-based signature can accurately discriminate SSN between SN (AUC = 0.950). Cross-validation of these two models also showed high predictive performance (LUAD AUC = 0.813, SSN AUC = 0.933).

This study demonstrates, for the first time, the tumor bacterial microbiome composition of LUAD manifested as SSN is distinct from that presented as SN, which adds new knowledge to SSN in the perspective of microbiome. Furthermore, microbiome signatures showed good performance to predict LUAD or SSN.

Opportunistic premise plumbing pathogens (OPPPs) are environmental, waterborne opportunistic pathogens that are present in drinking water. They include Legionella pneumophila, Pseudomonas aeruginosa, Burkholderia cepacia, Mycobacterium avium complex (MAC), Mycobacterium abscessus complex (MAA), Stenotrophomonas maltophilia, Acinetobacter baumannii, Sphingomonas paucimobilis, Segniliparus spp., Methylobacterium spp., Cupriavidus spp., and the free-living amoebae (e.g., Acanthamoeba and Vermamoeba spp.). As OPPPs are in drinking water, humans continually come in contact with them and become infected. The OPPPs are adapted to premise plumbing; the plumbing in homes, apartments, and hospitals. The presence of OPPP in plumbing is due to a number of shared characteristics, including disinfectant resistance, growth at low organic content, adherence to pipe surfaces, biofilm formation, growth at low oxygen content, and high temperature- and desiccation-tolerance. The presence of OPPPs in drinking water systems challenge current methods for monitoring and ensuring safe drinking water.