Nontuberculous Mycobacteria Infection Research Articles

1423. A Rare Case of Mycobacterium chelonae Septic Joint

Abstract Background Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic soft tissue infections and which may affect underlying joints and bone by direct extension. NTM septic joint infections are rare and literature on their management is scarce. Methods Here we describe a case of septic ankle due to M. chelonae, a rapid grower NTM, and review treatment of these infections. Results An 86-year-old man presented to our hospital with complaints of a painful left ankle. Three months prior he noticed a pimple on his left foot after tripping over a lawnmower. The lesion evolved into erythema and painful swelling of the left ankle. Magnetic resonance imaging (MRI) of the left lower extremity revealed a fracture of the distal tibial metaphysis. Turbid joint fluid was aspirated showing 211,450 white blood cells with 97% neutrophils. Patient underwent partial removal of the left tibia with insertion of a drug implant device. Culture results showed acid fast bacilli at day three and the pathology report confirmed atypical mycobacterial infection (Fig 1, 2). Empiric meropenem, linezolid, and azithromycin were initiated until the identification of M. chelonae was obtained. Based on susceptibilities meropenem was discontinued and ciprofloxacin was added. A repeat MRI showed osteomyelitis and small abscesses about the left ankle leading to repeat debridement. Cultures from debridement were negative. Tobramycin IV three times a week was added and ciprofloxacin was discontinued. Patient soon developed acute renal failure, NSTEMI, and lactic acidosis. After a goals of care discussion with patient’s family, antibiotics were discontinued. He passed away soon thereafter. The backbone of NTM treatment usually consists of a macrolide plus 2-3 other agents but susceptibilities can be misleading. Data correlating outcomes of in vitro susceptibility and clinical response is mixed. Consequently, management of NTM infections is often derived from case reports and from the tuberculosis literature. As seen in this patient, effective treatment can be elusive. Neutrophils surround vacuoles filled with acid-fast staining organisms on Fite staining H&E Stain shows pink stained organisms in vacuoles Conclusion NTM infections are often resistant to antimycobacterial therapy and require multi-drug regimens with surgical intervention. Due to this complexity, a multidisciplinary approach is vital to improve outcomes. Disclosures All Authors: No reported disclosures.

Changing Incidence and Characteristics of Nontuberculous Mycobacterial Infections in Scotland and Comparison With Mycobacterium tuberculosis Complex Incidence (2011 to 2019).

An increase in infections with nontuberculous mycobacteria (NTM) has been noted globally, and their incidence has overtaken that of Mycobacterium tuberculosis complex (MTBc) in many countries. Using data from a national reference laboratory, we aimed to determine if this trend could be observed in Scotland. We undertook a retrospective review of all NTM isolates received by the Scottish Mycobacteria Reference Laboratory (SMRL) over 9 years from 2011 to 2019 inclusive. Clinical episodes were defined as per 2017 British Thoracic Society and 2020 American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/Infectious Diseases Society of America NTM guidelines. These rates were compared with Scottish tuberculosis rates over the same period. Of 8552 NTM isolates from 4586 patients in 2011 to 2019, 7739 (90.5%) were considered clinically relevant. These represented 2409 episodes of NTM infection, with M. avium, M. intracellulare, and M. abscessus complex being most common. A total of 1953 (81.1%) were pulmonary NTM infection episodes from 1470 patients and 456 extrapulmonary episodes from 370 patients. We estimated a rise in incidence from 3.4 to 6.5 per 100 000 person-years (2011-2019 inclusive), with an increase in NTM incidence over MTBc incidence in Scotland by 2017. The incidence of NTM infection in Scotland has overtaken MTBc incidence. NTM infection leads to a costly health care burden, possibly as much as UK£1.47 million (US$ and €1.73 million) annually. We recommend standardization of isolate referral with clinical surveillance and implementation of agreed standards of care delivered through multidisciplinary teams. This would improve diagnosis and patient management as well as assessment of diagnostics and novel treatments through clinical trials.

Scubcutaneous Mycobacterium marinum infection misdiagnosed as sporotrichosis: A case report

Nontuberculous mycobacteria (NTM), are natural inhabitants of natural waters, engineered water systems, and soils. As a consequence of their ubiquitous distribution, humans are surrounded by these opportunistic pathogens. In this report, we describe a case of scubcutaneous Mycobacterium marinum infection associated with home tropical ornamental fish aquaria. A 43-years-old man reported progressively increasing nodules over his left forearm and hand for more than 7 months. Based on NTM culture, pathological examination, identification by gene sequencing and matrix assisted laser desorption ionization time of flight mass spectrometry, the diagnosis of scubcutaneous NTM infection was confirmed. The patient was treated with itraconazole for suspected sporotrichosis over 1 month. The patient was treated with oral doxycycline hydrochloride capsules (200 mg/day) for 5 months, the nodules had resolved. Home aquarium environments may serve as a possible source of mycobacteria infection in urban family.

Necroptosis-related subtypes are associated with bronchiectasis in pulmonary non-tuberculous mycobacteria-infected patients: a perspective based on transcriptomic analysis.

The aim of this study was to explore the potential mechanisms responsible for the different manifestations of bronchiectasis in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection. We found that the necroptosis level increased significantly after NTM infection. Further, the 31 pNTM-infected patients were classified into two subtypes based on necroptosis-related genes (NRGs) by unsupervised cluster analysis. After that, we compared the differences in clinical parameters, immune cell infiltration, and gene expression between the two subtypes. We observed that the high-necroptosis subtype possessed higher CT scores for bronchiectasis extent (P = 0.008) and severity (P = 0.023). And, more neutrophil infiltration in the high-necroptosis subtype was demonstrated both by the CIBERSORT algorithm and by blood neutrophil count (P = 0.001). Next, 688 differentially expressed genes (DEGs) between two subtypes were identified. To explore the portion in DEGs that might contribute to bronchiectasis, we intersected the DEGs with two gene modules. These two gene modules were identified as the most associated with CT scores for bronchiectasis extent and severity by weighted gene co-expression network analysis (WGCNA). Ninety-three intersection genes were obtained. Finally, 7 hub genes including ACSL1, ANXA3, DYSF, HK3, SLC11A1, STX11, and TLR4 were further screened out by machine learning algorithms and protein-protein interaction network analysis. These results suggested that the differential levels of necroptosis in pNTM patients might lead to differential extent and severity of bronchiectasis on radiographic imaging. This process might be associated with neutrophil infiltration and the involvement of seven hub genes.

Methods of isolation and identification of nontuberculous mycobacteria from environmental samples: A scoping review

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment. Some species of NTM are pathogenic and cause lung disease in susceptible persons. Epidemiologic studies of environmental NTM infection risk rely on both culture-dependent and culture-independent techniques for NTM isolation and identification. In this review, we summarized current methods used to isolate and identify NTM from the environment. We searched PubMed, Embase, Scopus, Web of Science: Core Collection, and Global Health (CAB Direct) for peer-reviewed studies from the last 12 years. We identified 1685 unique citations and 110 studies met our inclusion and exclusion criteria. Approximately half (55%) of the studies identified in this review used a combination of culture-independent and culture-dependent methods. The most common environmental substrate analyzed was water (n = 90). Identification of current, common methods for the isolation and identification of NTM from environmental samples may contribute to the development of standard methodological practices in the future. The choice of isolation method is based on the research question, environment, and species. A summary of common methods may contribute to the development of standard practices for isolation and identification of NTM from environmental samples, which may lead to more robust and comparable results.

Nghiên cứu tỷ lệ phân bố các loài Nontuberculous mycobacteria phân lập được tại bệnh viện 74 Trung ương bằng phương pháp giải trình tự gen hsp65

In recent years, the burden of nontuberculous mycobacteria pulmonary disease has increased worldwide. Nontuberculous mycobacteria - NTM infection is often misdiagnosed with Mycobacterium tuberculosis - MTB because of their similar clinical manifestations and preclinical manifestations. For MTB, the National Tuberculosis Program and the Ministry of Health (Vietnam) have a standard treatment regimen, while for NTM, an individualized treatment regimen based on infectious NTM species. Therefore, accurate identification of the causative NTM species can help clinicians choosing an effective treatment regimen. Among 122 suspected NTM samples collected at National Hospital 74, we successfully identified 115 strains belonging to NTM. Analytical DNA sequences, building phylogenetic trees were analyzed by Bioedit, ClustalX2, and MEGA-X software; comparing and identifying reference species from gene bank were used BLAST-NCBI. Slow-growing mycobacteria accounted for 61.7%, consists of Mycobacterium avium complex (37.4%), Mycobacterium lentiflavum (7.0%), Mycobacterium simiae (7.0%), Mycobacterium gordonae complex (5.2%) and other species less than 2.0%. The detection rate of rapid-growing mycobacteria was 38.3% including Mycobacterium abscessus complex (31.3%), and Mycobacterium fortuitum (7.0%). The most prevalent NTM species belonged to Mycobacterium avium complex and Mycobacterium abscessus complex (68.7%). The proportion of NTM infection in patients 50 years and older is 2.3 times higher than in patients under 50 years. This proportion is 5 times higher in females while there is no significant difference in males.

Disseminated nontuberculous mycobacterial infection with cryptic immunodeficiency mimicking malignancy: a case report

BackgroundNontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab.Case presentationA middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up.ConclusionWe reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

Whole genome sequencing and prediction of antimicrobial susceptibilities in non-tuberculous mycobacteria.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens commonly causing chronic, pulmonary disease which is notoriously hard to treat. Current treatment for NTM infections involves at least three active drugs (including one macrolide: clarithromycin or azithromycin) over 12 months or longer. At present there are limited phenotypic in vitro drug susceptibility testing options for NTM which are standardised globally. As seen with tuberculosis, whole genome sequencing has the potential to transform drug susceptibility testing in NTM, by utilising a genotypic approach. The Comprehensive Resistance Prediction for Tuberculosis is a database used to predict Mycobacterium tuberculosis resistance: at present there are no similar databases available to accurately predict NTM resistance. Recent studies have shown concordance between phenotypic and genotypic NTM resistance results. To benefit from the advantages of whole genome sequencing, further advances in resistance prediction need to take place, as well as there being better information on novel drug mutations and an understanding of the impact of whole genome sequencing on NTM treatment outcomes.

Use of Statistical Process Control Methods for Early Detection of Healthcare Facility-Associated Nontuberculous Mycobacteria Outbreaks: A Single-Center Pilot Study.

Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly implicated in healthcare facility-associated (HCFA) infections and outbreaks. We analyzed the performance of statistical process control (SPC) methods in detecting HCFA NTM outbreaks. We retrospectively analyzed 3 NTM outbreaks that occurred from 2013 to 2016 at a tertiary care hospital. The outbreaks consisted of pulmonary Mycobacterium abscessus complex (MABC) acquisition, cardiac surgery-associated extrapulmonary MABC infection, and a bronchoscopy-associated pseudo-outbreak of Mycobacterium avium complex (MAC). We analyzed monthly case rates of unique patients who had positive respiratory cultures for MABC, non-respiratory cultures for MABC, and bronchoalveolar lavage cultures for MAC, respectively. For each outbreak, we used these rates to construct a pilot moving average (MA) SPC chart with a rolling baseline window. We also explored the performance of numerous alternative control charts, including exponentially weighted MA, Shewhart, and cumulative sum charts. The pilot MA chart detected each outbreak within 2 months of outbreak onset, preceding actual outbreak detection by an average of 6 months. Over a combined 117 months of pre-outbreak and post-outbreak surveillance, no false-positive SPC signals occurred (specificity, 100%). Prospective use of this chart for NTM surveillance could have prevented an estimated 108 cases of NTM. Six high-performing alternative charts detected all outbreaks during the month of onset, with specificities ranging from 85.7% to 94.9%. SPC methods have potential to substantially improve HCFA NTM surveillance, promoting early outbreak detection and prevention of NTM infections. Additional study is needed to determine the best application of SPC for prospective HCFA NTM surveillance in other settings.

Pulmonary Non-tuberculous Mycobacterial Infections in Category II Failures from National Tuberculosis Programme

Pulmonary infections due to non-tuberculous mycobacteria (NTM) are increasingly being reported. These can mimic drug-resitant tubercuolosis. A diagnosis of NTM infections needs a high degree of clinical suspicion and repeated isolation of the organism on culture. NTM infections occur commonly in immunocompromised individuals and in people with lung abnormalities. Currently there are no guidelines on drug combinations and the duration of treatment is not adequately defined. Two cases of pulmonary infection with NTM in immune-competent individuals are described in the present report. Although the bacteriological, radiological and clinical response to treatment was good; early discontinuation of treatment resulted in recurrence and change in drug susceptibility pattern, suggesting the need for prolonged treatment for achieving cure.

Ohmyungsamycin promotes M1-like inflammatory responses to enhance host defence against Mycobacteroides abscessus infections

ABSTRACT Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against Mycobacterium tuberculosis. However, its role in nontuberculous mycobacteria (NTMs) infections has not been clarified. Mycobacteroides abscessus (Mabc) is a rapidly growing NTM that has emerged as a human pathogen in both immunocompetent and immunosuppressed individuals. In this study, we demonstrated that OMS had significant antimicrobial effects against Mabc infection in both immunocompetent and immunodeficient mice, and in macrophages. OMS treatment amplified Mabc-induced expression of M1-related proinflammatory cytokines and inducible nitric oxide synthase, and significantly downregulated arginase-1 expression in murine macrophages. In addition, OMS augmented Mabc-mediated production of mitochondrial reactive oxygen species (mtROS), which promoted M1-like proinflammatory responses in Mabc-infected macrophages. OMS-induced production of mtROS and nitric oxide was critical for OMS-mediated antimicrobial responses during Mabc infections. Notably, the combination of OMS and rifabutin had a synergistic effect on the antimicrobial responses against Mabc infections in vitro, in murine macrophages, and in zebrafish models in vivo. Collectively, these data strongly suggest that OMS may be an effective M1-like adjunctive therapeutic against Mabc infections, either alone or in combination with antibiotics.

Synthesis and Biological Characterization of Fluorescent Cyclipostins and Cyclophostin Analogues: New Insights for the Diagnosis of Mycobacterial-Related Diseases.

Patients with cystic fibrosis (CF) have a significantly higher risk of acquiring nontuberculous mycobacteria infections, predominantly due to Mycobacterium abscessus, than the healthy population. Because M. abscessus infections are a major cause of clinical decline and morbidity in CF patients, improving treatment and the detection of this mycobacterium in the context of a polymicrobial culture represents a critical component to better manage patient care. We report here the synthesis of fluorescent Dansyl derivatives of four active cyclipostins and cyclophostin analogues (CyCs) and provide new insights regarding the CyC's lack of activity against Gram-negative and Gram-positive bacteria, and above all into their mode of action against intramacrophagic M. abscessus cells. Our results pointed out that the intracellularly active CyC accumulate in acidic compartments within macrophage cells, that this accumulation appears to be essential for their delivery to mycobacteria-containing phagosomes, and consequently, for their antimicrobial effect against intracellular replicating M. abscessus, and that modification of such intracellular localization via disruption of endolysosomal pH strongly affects the CyC accumulation and efficacy. Moreover, we discovered that these fluorescent compounds could become efficient probes to specifically label mycobacterial species with high sensitivity, including M. abscessus in the presence several other pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. Collectively, all present and previous data emphasized the therapeutic potential of unlabeled CyCs and the attractiveness of the fluorescent CyC as a potential new efficient diagnostic tool to be exploited in future diagnostic developments against mycobacterial-related infections, especially against M. abscessus.

Profile of patients with post-tuberculosis bronchiectasis in a tertiary care hospital in Brazil

Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.

Epidemiology and management of nontuberculous mycobacterial disease in people with cystic fibrosis, the Netherlands

BackgroundNontuberculous mycobacteria (NTM) are opportunistic, difficult to treat pathogens. With increasing prevalence of NTM infections in people with cystic fibrosis (pwCF) and the improved life expectancy, the burden is expected to grow. MethodsWe assessed the epidemiology and management of NTM isolation and disease in pwCF in the Netherlands using a survey and retrospective, case-controlled data from the Dutch CF Registry. We determined the isolation prevalence, treatment and outcomes from 2013-2019. ResultsNTM isolation prevalence increased from 1.0% to 3.6% (2013-2019). This was a single NTM isolation in 53.7% of the adults and 60.0% of the children. M. abscessus and M. avium complex (MAC) were most frequent (47.1 and 30.9%). Of the treated pwCF, 48.5% attained culture conversion of M. abscessus; 54.5% for MAC. Children with an NTM isolation showed more infections with S. maltophilia and/or A. fumigatus (p < 0.001) compared to controls. In the year prior to NTM isolation, children in the NTM group had a lower mean FEV1% predicted (81.5 ± 16.7 vs. 88.6 ± 15.3, p = 0.024), while adults in the NTM group had more IV antibiotic days compared to controls (60 vs. 17, p = 0.047). In the following years, FEV1% predicted declined faster in pwCF with NTM than the control group (children: -3.8% vs. -1.6%, p = 0.023; adults: -0.7% and 0.4%, ns). ConclusionsThe isolation prevalence of 3.6%, poor treatment outcomes and associated lung function decline emphasize that NTM pulmonary disease (NTM-PD) is a significant health issue among pwCF in the Netherlands. Its prevention and treatment require increased attention.

Clinical features of mesotherapy-associated non-tuberculous mycobacterial infections: A systematic review

Background: Cutaneous infections from non-tuberculous mycobacteria (NTM) are a well-documented but poorly characterized adverse event following mesotherapy injections. Objective: This study aims to consolidate the available literature to characterize demographic and clinical features of mesotherapy-associated NTM infections. Methods: Using PRISMA guidelines, a systematic review of PubMed, Scopus, and Embase databases was undertaken for articles reporting cases of NTM skin infections following mesotherapy. Data were analyzed using Microsoft Excel. Results: Of 1966 search results, 30 articles (N = 423 patients) met inclusion criteria. Studies were largely from South America, and patients were mostly women aged 16-55 with NTM infections arising in the abdomen, buttocks, or thighs. Nearly all patients developed multiple, well-localized lesions without systemic symptoms. Effect summary by meta-analysis revealed most infections resolved after antibiotic therapy, though many patients required multiple antibiotic courses and/or agents to resolve infection. Infections often took weeks to resolve and were complicated by post-treatment scarring. Limitations: The main limitation of this study was the heterogeneity and lack of consistency between case reports. Conclusion: Cutaneous NTM infections associated with mesotherapy generally occur in women of childbearing age, arise from injections contaminated by the environment, and are often complicated by scarring/poor cosmesis and prolonged treatment course.

Nontuberculous mycobacteria infections of the pleura: A systematic review

BackgroundNontuberculous mycobacterial (NTM) pleuritis is an uncommon manifestation of NTM infection. Case reports and small case series have shown a variable clinical course and high mortality rates. ObjectiveTo describe patients' characteristics, clinical presentation and outcomes of NTM pleural infections. MethodsA systematic review of cases of NTM pleural infections published in PubMed-indexed journals from 1980 to 2021. ResultsA total of 206 cases of NTM pleural infections were found and analyzed. Fifty-eight percent of cases were males. The mean age was 57.5 yrs (range 9–87 yrs). Forty-three percent of patients were immunosuppressed, and 43% had a chronic lung disease; thirty-two percent had neither risk factor. In addition to the pleural infection, 67% of cases had a concurrent pulmonary NTM infection, and in 18 cases there was another extrapulmonary site of NTM infection. In 29% of cases the pleural infection was the sole manifestation of NTM disease. The most common isolated mycobacterium was Mycobacterium avium complex (65%). Fifty-three percent and 26% of patients required pleural effusion drainage and a surgical intervention, respectively, to treat the infection, in addition to anti-NTM chemotherapy. Forty percent of patients developed pneumothorax, 16% suffered from empyema, and 16.5% had broncho-pleural fistula. The reported mortality rate was 24%. ConclusionNTM pleural infections may arise in immunocompetent and immunosuppressed patients, with or without chronic lung disease or concurrent NTM pulmonary infection. These infections carry a poor prognosis and a high risk of complications requiring surgical interventions in addition to anti-NTM chemotherapy.

A Case Report of Nontuberculous Mycobacterium Infection of the Hand and Treatment with a Second Dorsal Metacarpal Artery Flap

Nontuberculous mycobacterium (NTM) are emerging as an important pathogen that merit close attention from clinicians around the world. Musculoskeletal NTM infections are most commonly found on the hand. In spite of appropriate clinical care including surgery and administration of antibiotics, recurrence of NTM infection of the hand is frequent and multiple operations may be required. Consequently, repeated surgeries can cause soft tissue defects that require reconstruction. This report suggests that when NTM infection of the hand requires not only antibiotic treatment and simple surgery but also reconstruction, the dorsal metacarpal artery flap can be considered for proximal palmar and entire dorsal surface coverage of fingers.

Chronic cavitary pulmonary aspergillosis: Serial clinical and CT findings correlated with antifungal treatment and patient response.

Chronic cavitary pulmonary aspergillosis (CCPA) is the most common form of chronic pulmonary aspergillosis. We hypothesise that by observing serial clinical and CT findings of CCPA patients with antifungal therapy, factors helping predict responses to antifungal therapy could be withdrawn. A total of 31 patients with CCPA who received antifungal therapy for greater than six months and who had serial CT studies were included. Clinical finding analyses were performed at initial and last follow-up CT acquisition dates. Clinical characteristics and CT features were compared between clinically improving or stable and deteriorating groups. With antifungal therapy, neutrophil-to-lymphocyte ratio (2.66 vs. 5.12, p= .038) and serum albumin (4.40 vs. 3.85 g/dl, p= .013) and CRP (1.10 vs. 42.80 mg/L, p= .007) were different between two groups. With antifungal therapy, meaningful CT change, regardless of clinical response grouping, was decrease in cavity wall thickness (from 13.70 mm to 8.28 mm, p< .001). But baseline (p= .668) and follow-up (p= .278) cavity wall thickness was not different between two groups. In univariate analysis, initial maximum diameter of cavity (p= .028; HR [0.983], 95% CI [0.967-0.998]) and concurrent NTM infection (p= .030; HR [0.20], 95% CI [0.05-0.86]) were related factors for poor clinical response. With antifungal therapy, cavities demonstrate wall thinning. Of all clinical and radiological findings and their changes, initial large cavity size and concurrent presence of NTM infection are related factors to poor response to antifungal therapy.

In Vitro Activity of the Sudapyridine (WX-081) against Non-Tuberculous Mycobacteria Isolated in Beijing, China.

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows an anti-tuberculosis activity but, unlike BDQ, did not prolong QT interval (QT) in animal model studies. This study evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM). Fifty reference strains of different mycobacterial species, and 132 NTM clinical isolates from four commonly isolated NTM species were recruited. The microplate alamarBlue assay was performed to determine the MIC of WX-081 and BDQ. Cytotoxicity assay was performed for both drugs using the THP-1 cells, and the minimum bactericidal concentrations (MBCs) of both drugs against the reference strains of five selected NTM species were also determined. All the tested reference strains had MICs lower than 0.5 μg/mL, with the majority having MICs far below 0.1 μg/mL for WX-081. The epidemiological cut-offs of WX-081 ranged from 0.0156 μg/mL to 0.25 μg/mL against commonly isolated NTM, and this value was comparable with that of BDQ. The MBC/MIC ratios suggest a bacteriostatic activity for both drugs against the five selected NTM species. Cytotoxicity assays indicated that THP-1 cells had nearly 100% viability when exposed to WX-081 for 24 h below 4 μg/mL, 200- to 300-fold the MICs of Mycobacterium intracellulare, Mycobacterium avium, and Mycobacterium kansasii. WX-081 has a strong antimicrobial activity against different NTM species with low cytotoxicity and therefore has the potential to be used for treating NTM infections. IMPORTANCE Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. Over 200 species or subspecies of NTM have been reported, whereas pulmonary diseases in humans are caused mainly by M. avium complex (MAC), M. kansasii, and M. abscessus. Treatment of NTM infection is often challenging as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant-tuberculosis (MDR-TB) may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the antituberculosis efficacy but eliminate the severe side effect of BDQ. This study initially evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM).

Clinical outcomes and prognostic factors of bronchiectasis rheumatoid overlap syndrome: A multi-institution cohort study.

The information regarding bronchiectasis with RA (BROS) is limited in Asia. The objective of this study was to investigate the clinical characteristics and outcomes of BROS in Taiwan. This multi-institute cohort study included patients with BROS from January 2006 to December 2017. The clinical, functional and microbiological data of these patients were retrieved from the Chang Gung Research Database. Respiratory failure and mortality were the primary outcomes. Severe exacerbation was defined as bronchiectasis- related hospitalizations or emergency department visits. A total of 343 patients with BROS were identified. One hundred and eight patients had severe exacerbation and exhibited significantly more previous exacerbations, a lower FEV1 and higher BACI score (11.1 vs. 7.5) than patients without severe exacerbation. The most prevalent species in sputum were Non-tuberculous mycobacteria (NTM) (14.8 %), Pseudomonas aeruginosa (14.2 %), and fungus (5.9%). 68.8% of BROS patients used disease modifying antirheumatic drugs (DMARD), 7.9% used biological DMARD. NTM and tuberculosis infection rates were higher in bDMARD group compared with nbDMARD group and others. Overall, the 3-year respiratory failure rate and mortality rate were 14.6 and 25.7% respectively. Patients with RA diagnosed before bronchiectasis had a significantly higher cumulative incidence of mortality in a 3-year follow-up than those with RA diagnosed after bronchiectasis. In Cox regression, age, higher RF value and systemic steroid use were independent risk factors for mortality in BROS. BROS patients with severe exacerbation had a high mortality rate in Taiwan. bDMARD is associated with a trend of increased risk of NTM and TB infections.