Mycobacterium Research Articles

Clinical analysis and risk factors associated with poor prognosis in nontuberculous mycobacterial infection

ABSTRACT Recently, the incidence and prevalence of NTM have been increasing nationwide in many countries. This study aimed to identify risk factors associated with the prognosis and mortality of non-HIV nontuberculous mycobacterial disease patients. This retrospective study was conducted at Peking Union Medical College Hospital. The electronic medical records in the hospital’s database from January 2013 to December 2022 were retrospectively reviewed. Relevant data, including clinical characteristics, laboratory findings, microbiological tests, treatments, and outcomes were collected and subjected to statistical analyses. The search identified 745 patients diagnosed with NTM infection, of whom 147 met the inclusion criteria. NTM pulmonary disease was the most commonly observed (n = 93; 63.3%), followed by disseminated infection (n = 43; 29.3%). The most frequent NTM species was Mycobacterium avium complex (55.8%), followed by Mycobacterium abscessus (21.2%). The incidence of Aspergillus and Pseudomonas aeruginosa infection was significantly higher in the NTM pulmonary disease group than in the disseminated NTM group. Cumulative mortality in the total patients was 24.49% at 5 years. High Charlson Comorbidity Index (CCI), high neutrophil-to-lymphocyte-ratio (NLR), haematological disease, and disseminated infection were identified as independent predictors of unfavourable outcomes. The area under the curve (AUC) values for NLR and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) were 0.751 and 0.763 with optimal cut-off values of 9.50 and 3.83, respectively, for prediction of mortality in patients with NTM disease.

Mortality and causes of death in non-tuberculous mycobacterial pulmonary disease.

<sec><title>BACKGROUND</title>Mortality and causes of death in non-tuberculous mycobacterial pulmonary disease (NTM-PD) are not well-described over long follow-up periods, particularly in Europe. We investigated whether NTM-PD is associated with higher mortality rates and different causes of death than matched controls.</sec><sec><title>METHODS</title>Danish national registers were used to identify patients with NTM-PD from 2000-2017 and to match them 1:4 with controls based on age, sex, cohabitation status, and municipality.</sec><sec><title>RESULTS</title>We identified 661 patients with NTM-PD (50.4% male, median age 66 years, interquartile range [IQR] 48-84). The 5-year mortality rate for NTM-PD was 51% (95% CI 47-55) compared to 15% (95% CI 14-17) for controls. The hazard ratio (HR) of death for NTM-PD was 3.1 (95% CI 2.7-3.5; P < 0.001) compared to controls, persisting after adjusting for Charlson Comorbidity Index with an adjusted HR of 1.9 (95% CI 1.63-2.22; P < 0.001). Median age at death was 72 years (IQR 58-86) for NTM-PD patients and 81 years (IQR 69-93) for controls. Deaths due to respiratory diseases were more frequent in NTM-PD patients (45.2%) than in controls (11.6%). Mycobacterial infection directly caused death in 5.8% of NTM-PD patients.</sec><sec><title>CONCLUSION</title>NTM-PD is associated with significantly higher all-cause mortality than controls, particularly in the initial years following diagnosis. These findings highlight the need for increased attention to NTM-PD and related respiratory conditions.</sec>.

Clinically significant hemoptysis and all-cause mortality in patients with nontuberculous mycobacterial pulmonary disease.

Hemoptysis is one of the major symptoms in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its prevalence, incidence, and impact on long-term prognosis remain uncertain. We evaluated the incidence of clinically significant hemoptysis, and determined its association with mortality in patients with NTM-PD. Patients enrolled in a prospective observational cohort (NCT01616745) between July 2011 and May 2023 were analyzed. We evaluated risk factors for clinically significant hemoptysis-defined as hemoptysis events requiring interventions such as bronchial artery embolization or surgical resection -and its association with all-cause mortality. Among 506 patients from the ongoing cohort, 43 patients (8.5%) experienced clinically significant hemoptysis during a median follow-up of 5.1 years. The overall incidence of clinically significant hemoptysis was 2.1 (95% confidence interval [CI]; 1.5-2.9) cases per 100 person-years. Identified risk factors included a history of tuberculosis (incidence rate ratio [IRR], 1.91; 95% CI, 1.02-3.60), higher c-reactive protein (CRP) (IRR, 1.20 for 1mg/dl increase; 95% CI, 1.01-1.43), and lower % predicted forced vital capacity (FVC) (IRR, 0.81 for 10% increase; 95% CI, 0.66-0.98). Clinically significant hemoptysis was independently associated with an increased risk of all-cause mortality (adjusted hazard ratio, 2.39; 95% CI, 1.31-4.36). In patients with NTM-PD, those with history of tuberculosis, higher CRP levels, and lower % predicted FVC were at a higher risk of subsequent clinically significant hemoptysis. Importantly, clinically significant hemoptysis was associated with an elevated risk of all-cause mortality. ClinicalTrials.gov; No.: NCT01616745.

Nodular-bronchiectatic pattern in pulmonary nocardiosis: Immune status and treatment outcomes in a multicenter retrospective study.

Pulmonary nocardiosis is a rare opportunistic infection, with approximately 15% of patients being immunocompetent. The isolation rate of Nocardia spp. has recently increased, indicating rising clinical concern. This study aimed to summarize computed tomography (CT) findings, evaluate treatment outcomes, and improve disease recognition. We retrospectively analyzed 12 pulmonary nocardiosis cases recorded over 10 years in three hospitals, excluding two unclear cases. All pathogens were detected on smears and isolated from respiratory specimens. The mean age was 73.0±12.9 years, with 9 men and 6 smokers. Among the included patients, 8 had underlying pulmonary diseases, 4 had non-pulmonary diseases, and 3 were on steroids. The most common species were N. cyriacigeorgica and N. nova. CT findings included cavitary, consolidation/infiltrative, and nodular-bronchiectatic (NB) patterns. The NB pattern, particularly common in immunocompetent patients, was associated with significantly better treatment outcomes than non-NB patterns (Fisher's exact test, p=0.0476). All isolates were susceptible to trimethoprim/sulfamethoxazole. Eight patients recovered with appropriate antimicrobial therapy, while two patients died. Pulmonary nocardiosis presented three CT patterns, with the NB pattern being the most frequent and showing favorable treatment outcomes, especially in immunocompetent patients. While Nocardia spp. can develop in patients with preexisting bronchiectasis, it may also independently cause bronchiectasis. Nocardia infection should be considered as a differential diagnosis in patients exhibiting the NB pattern, resembling that of nontuberculous mycobacterial pulmonary diseases.

Association of poor sleep quality with clinical variables in nontuberculous mycobacterial pulmonary disease.

The high prevalence of poor sleep quality in patients with chronic respiratory diseases makes it an important clinical topic. However, the prevalence and characteristics of poor sleep quality in those with nontuberculous mycobacterial pulmonary disease and its association with clinical variables remain unclear. This retrospective study involved patients with nontuberculous mycobacterial pulmonary disease between June 2017 and May 2022. The prevalence of poor sleep quality was measured by the Pittsburgh Sleep Quality Index was used to and its association with clinical variables including age, sex, laboratory data, pulmonary function, respiratory symptoms, mental health, health-related quality of life, and physical function was assessed. The median age of 233 participants was 65 years, with poor sleep quality present in 123 patients (52.8%) who were older, female, and unemployed with dyspnea, anxiety symptoms, low health-related quality of life, and low exercise capacity. Many reported that they "cannot get to sleep within 30min," "wake up in the middle of the night or early morning," "have to get up to use the bathroom," "cannot breathe comfortably," or "cough or snore loudly." Multivariate logistic regression analysis indicated a significant association between poor sleep quality, female sex, and low health-related quality of life. Our results suggested that for the patients in this study, a multidisciplinary management that considers poor sleep quality is required and assessment of sleep quality as a screening is needed.

NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles

Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by Mycobacterium avium complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls. A total of 2614 proteins were identified in the discovery cohort. The EV protein signature from patients with NTM-PD and TB reflected infectious diseases and inflammatory response pathways. Among the identified proteins, the expression of Na+/H+ exchanger regulatory factor 2 (NHERF2) was significantly elevated in patients with MAC-PD compared with healthy controls and patients with TB. Moreover, upregulation of NHERF2 was confirmed by immunoblotting of serum EVs and immunohistochemistry of lungs with mycobacterial infection. Our findings highlight that NHERF2 in serum EVs might be a potential biomarker for distinguishing MAC-PD from TB, possibly reflecting the pathogenesis of MAC-PD.

P-793. Long-term Outcomes of Mycobacterium avim complex Pulmonary Disease in Kyushu, Japan: A Retrospective Multicenter Study

Abstract Background Recently, the number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has increased worldwide. The most common causative organism in Japan is the Mycobacterium avium complex (MAC). The incidence of MAC pulmonary disease (MAC-PD) is higher than that in other countries, and deaths from MAC-PD are increasing. Complex cases involving radiological fibrocavitary patterns and pulmonary aspergillosis have been reported as poor prognostic factors; however, available evidence is limited. To address this gap, we initiated a retrospective, multicenter study in Kyushu, Japan, focusing on the long-term prognosis of patients five years after the diagnosis of MAC-PD. The primary objective of this study was to investigate the factors that influence the outcomes of these patients by employing data accessible at the time of their initial diagnosis. Methods This was a retrospective cohort study of patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 medical centers in Kyushu, Japan, between 2010 and 2017. Patient data were collected from medical records by respiratory experts and recorded using the EDC. Results The study enrolled 1317 patients with NTM-PD, of whom 1214 had MAC-PD. Patients with insufficient information were excluded, and 856 patients were analyzed: 546 (63.8%) with a non-cavitary nodular bronchiectatic (NB) pattern and 194 (22.7%) with a cavitary NB or fibrocavitary pattern. 107 (12.5%) died from all-cause by 5 years after diagnosis and 137 (16.0%) by 10 years; in the group that died after 5 years, the following were detected as risk factors in multivariate analysis: male sex (OR = 2.90, 95% confidential interval 1.84-4.56), age ≥ 70 (OR = 2.20, 95%CI 1.33-3.63), lobes with cavities ≥ 2 lobes (OR = 2.16, 95%CI 1.07-4.36), albumin &amp;lt; 3.5 g/dL (OR = 3.68, 95%CI 2.29-5.91), and oral corticosteroids (OR 1.97, 95%CI 1.04-3.73). Conclusion Male sex and fibrocavitary patterns have been reported to be poor prognostic factors for MAC-PD. In our study, we found that cavitary formation in more than two lobes, lower albumin levels, and oral corticosteroids were newly considered poor prognostic factors. We believe that our findings may help determine treatment induction and predict the prognosis of MAC-PD. Disclosures Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi &amp; Co., Ltd.: Advisor/Consultant|Shionogi &amp; Co., Ltd.: Grant/Research Support|Shionogi &amp; Co., Ltd.: Lecture fees

P-1072. Evaluation of the Spontaneous Mutation Frequencies of SPR719 Alone and in Combination with Other Agents Used to Treat Mycobacterium avium Complex Pulmonary Disease

Abstract Background SPR720 (fobrepodacin), a novel oral benzimidazole prodrug that inhibits the ATPase activity of mycobacterial DNA gyrase B, is being developed for treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD). SPR719, the active moiety of SPR720, has previously demonstrated antimycobacterial activity against nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), the most common causative agent of NTM-PD. Methods In this study, the spontaneous mutation frequencies (SMFs) of MAC ATCC 700898 (macrolide-susceptible) and a clinical macrolide-resistant MAC isolate (MMX 9461) were evaluated in the presence of SPR719 alone, standard-of-care antimycobacterial agents (clarithromycin, ethambutol, and rifampin) alone, and for SPR719 in combination with these agents. The minimal inhibitory concentrations (MICs) for SPR719 and comparators against the NTM were determined by agar dilution. SMFs were determined by plating a high inoculum (108-109 colony forming units) on selective agar prepared at 2-, 4-, and 8-fold the MIC for SPR719, and at 4-fold the MIC for comparator agents. SMFs were also determined for SPR719 in combination with antimycobacterial agents where SPR719 was evaluated at 2-fold the MIC and a paired agent was evaluated at 4-fold the MIC. Putative mutants were patched from selection plates onto agar containing the selection drug, and susceptibility was then evaluated by broth microdilution alongside the parent isolate. Results All concentrations of SPR719 alone and in combination with other agents prevented growth of both isolates, resulting in low SMFs for SPR719 (&amp;lt; 2.21 × 10-9 and &amp;lt; 7.14 × 10-11). In contrast, mutants were readily selected with rifampin (SMF of 2.55 × 10-8 and 1.99 × 10-8) and clarithromycin (SMF of 1.16 × 10-8), and these mutants exhibited elevated MIC values ≥ 4-fold the MIC of the parent by broth microdilution. Colonies emerged during selection with ethambutol but were unstable and did not grow when patched onto ethambutol-containing agar. Conclusion The low propensity for the development of resistance against the novel agent SPR719 alone and in combination with other agents is important because emergence of resistance is a clinical concern in the setting of prolonged combination therapy for NTM-PD. Disclosures Nicole Cotroneo, B.S., Spero: Advisor/Consultant Ian A. Critchley, PhD, Spero: Employee Kamal Hamed, MD, MPH, Spero: Employee

P-762. Prevalence and/or Recurrence of Non-Tubercular Mycobacterial Pulmonary Disease in Structural and Airway Lung Disease

Abstract Background Nontuberculous mycobacterial pulmonary disease (NTM-PD) frequently remains undetected, especially among patients with preexisting respiratory conditions who are prone to develop the disease. This study aims to explore the prevalence, species diversity, and outcomes of NTM-PD in India, an uncharted topic. Methods We conducted a prospective observational study, enrolling 69 patients with symptomatic chronic respiratory diseases or a history of Tuberculosis (TB). These patients underwent thorough clinical assessment, chest computed tomography scans, and either a single bronchoscopic sample or three sputum samples for microbiological analysis, along with relevant biochemical investigations. Diagnosis of NTM-PD followed the ATS 2020 diagnostic criteria. The growth of the organism was compared using patented indigenous media with or without p-nitrobenzoic acid. Results The prevalence of NTM-PD was 17.4%, with TB affecting 31.9% of cases. Baseline clinical symptoms and their duration showed no statistically significant differences, except NTM-PD patients with hemoptysis had significantly shorter symptom durations than other groups. Isolation rates were notably higher with the patented indigenous media compared to the mycobacterial growth indicator tube for both NTM (100% vs. 33.3%, p &amp;lt; 0.001) and Mycobacterium tuberculosis (M.Tb) (57.1% vs. 47.6%, p &amp;lt; 0.001). NTM-PD patients exhibited a significantly higher proportion of fibro-cavitary disease compared to other groups when comparing radiological findings. After monitoring NTM-PD patients following treatment, one patient (20%) experienced a recurrence of symptoms within six months, rest continue to be under follow-up. Conclusion In a high-burden TB setting, clinical suspicion and effort to look for NTM-PD is often low. Our study highlights the high prevalence of NTM-PD in individuals with chronic lung conditions/past history of TB. Patients with NTM-PD show higher rates of fibro-cavitary disease, possibly allowing the NTM to form biofilms and hence lead to relapses. Diagnosis of NTM-PD is thus important, to ensure desired treatment for the recommended duration and a thorough and prolonged post-treatment monitoring due to higher relapse risk. Disclosures All Authors: No reported disclosures

P-757. Microbiological and clinical characteristics of extrapulmonary nontuberculous mycobacterial disease in a Chinese general hospital

Abstract Background Data on extrapulmonary nontuberculous mycobacterial disease (ENTM) in China is lacking. We aim to explore the microbiological and clinical characteristics of ENTM in a general hospital. Methods Laboratory extrapulmonary samples positive for nontuberculous mycobacteria in Zhongshan Hospital, Fudan University between Jan. 2017 and Dec. 2021 were retrospectively searched. The respective patient data were reviewed and followed until Dec. 2022. Thirty-three confirmed ENTM cases were included. Demographic, microbiological, clinical characteristics, as well as treatment and prognosis were analyzed. Results A total of 33 confirmed ENTM cases were included. The average age was (49±16.3) years. Twenty-three cases (69.7%) were female and one third of the patients were immunocompromised. Skin and soft tissue infection, bone and joint infection, and disseminated NTM disease were the most common types (57.6%, 18.2%, and 15.6%). Healthcare-associated infections accounted for 51.5% (17/33) of the cases. Mycobacterium abscessus complex (42.4%) among rapidly growing mycobacteria (RGM) was the most common causative species. Patients received combination therapy with an average of (3.5±0.8) drugs for 6.3 (4.3,9.6) months. Most cases recovered (69.7%) or improved clinically (18.2%). Compared with RGM, infections with slowly growing mycobacteria (SGM) were seen in older individuals (60.2±15.0 vs 42.6±14.0, P&amp;lt;0.05) and were more often community-acquired (83.3% vs 28.6%, P&amp;lt;0.05). Conclusion Skin and soft tissue infection is the most common type of ENTM, with Mycobacterium abscessus complex being the most important causative species. SGM infections affect older population and are more often community-acquired. Treatment of ENTM is challenging and lacks standardized protocol, future researches are warranted. Disclosures All Authors: No reported disclosures

P-777. Assessment of Epidemiologic Case Definitions for Disseminated Nontuberculous Mycobacterial Disease in Patients Without AIDS

Abstract Background Disseminated Mycobacterium avium complex (MAC) infection rates have declined in persons with HIV; some studies report increasing numbers of disseminated nontuberculous mycobacteria (NTM) infections in other groups of immunocompromised persons. However, no consensus definition exists for disseminated NTM in these populations. We compared characteristics of disseminated NTM in persons without AIDS using different epidemiologic definitions.Table 1.Disseminated nontuberculous mycobacteria definitions.. Methods CDC’s Emerging Infections Program conducted active, laboratory- and population-based NTM surveillance in 4 states (11 counties) during 2021–2022 to identify patients with NTM in clinical specimens, excluding stool or rectal swabs. Clinical and laboratory data were collected via medical record review. Disseminated NTM definitions are shown in Table 1. We determined the numbers of patients without AIDS who met each definition. Among those meeting each definition we calculated the percentages of patients with: 1) selected immunocompromising conditions; 2) MAC infection; and 3) documented clinical diagnosis of any NTM infection (i.e., NTM not likely to represent contamination or colonization).Figure 1.Number of patients meeting each disseminated nontuberculous mycobacteria definition, Emerging Infection Program, 2021–2022 (N=59). Results Among 877 patients with NTM and without AIDS, 15 patients (1.7%) had a documented disseminated NTM clinical diagnosis (definition 1); 59 (6.7%) met ≥1 of the 3 definitions. Although more patients met definition 2 (31, 3.5%) or definition 3 (53, 6.0%) than definition 1, definition 2 only captured 10/15 (66.7%) patients with a documented disseminated NTM clinical diagnosis; definition 3 captured only 9/15 (60.0%) (Figure 1). The proportion of patients with malignancy, immunosuppressive medication, or transplant differed by definition as did the proportion infected with MAC. Seven of 31 patients meeting definition 2 (22.6%) and 14/53 (26.4%) patients meeting definition 3 did not have a clinician documented diagnosis of any NTM infection in the medical record (Figure 2).Figure 2.Proportion of patients with malignancy(a), immunosuppressive medication(b), transplant(c), isolation of M. avium complex, or clinical diagnosis of any type of nontuberculous mycobacteria infection(d), stratified by disseminated NTM definition, Emerging Infections Program, 2021–2022. Conclusion Each disseminated NTM definition identified a different group of patients, limiting their usefulness and comparability. Development of a standard epidemiologic definition for disseminated NTM in persons without AIDS will enable better understanding of disease impact in susceptible populations. Disclosures Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Mannkind: Advisor/Consultant|Mannkind: Grant/Research Support|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support

P-782. Nontuberculous Mycobacterial Infections among Lung Transplant Recipients: A Nine-Year Cohort Study

Abstract Background The epidemiology, microbiology, and clinical course of nontuberculous mycobacterial (NTM) infection among lung transplant recipients vary considerably by geographic location. Their data is still scarce. Methods This single-center retrospective study was conducted at one of the major transplant centers in Japan. Medical records and microbiological test results of all the lung transplant recipients who underwent lung transplants between 2015 to 2023 were reviewed through December 31, 2023. Per institutional protocol, tracheal aspirates or sputum have been sent for mycobacterial cultures at the time of transplant and when clinically indicated thereafter. The definition of pulmonary NTM disease was based on the ATS/ERS/ESCMID/IDSA guidelines. Results In total, 175 lung transplants were performed during the study period (Table 1). Before transplant, 7 recipients had NTM isolation from the sputum and 5 of these 7 recipients had received bilateral lung transplants. While only 2 of these 7 recipients met the diagnosis of NTM pulmonary disease, 6 recipients received antimycobacterial treatment for a median duration of 25 months before transplant and only one case had NTM isolation after transplant (Figure 1). At the time of lung transplant, 169/175 (97%) recipient’s sputum were collected. Six species of NTM were isolated in 18 patients (10%, 18/175) at various times; at the time of transplant, between 0-1 month, 1-6 months, 6-12 months, and after 12 months in 2, 7, 3, 2, and 5 recipients, respectively (Figure 1, 2). Twenty-two isolates were recovered at the time of and after transplant, slowly growing mycobacteria accounted for 86% (19/22), including M. avium complex (N = 12) and M. gordonae (N = 4), whereas rapidly growing mycobacteria, M. fortuitum (N = 2) and M. chelonae (N = 1), accounted for the rest. Although 2 of 18 recipients with NTM isolation died, one recipient died directly from NTM infection complicated by Aspergillus coinfection. Conclusion NTM were isolated in 10% of recipients at the time of and after lung transplant. NTM, isolated before and at the time of transplant, rarely required treatment after transplant. Disclosures All Authors: No reported disclosures

Effective killing of Mycobacterium abscessus biofilm by nanoemulsion delivery of plant phytochemicals.

Mycobacterium abscessus is among the opportunistic bacterial pathogens that cause nontuberculous mycobacterial diseases. The infection caused by M. abscessus is difficult to treat because the bacterium is resistant to many of the currently available antibiotics, limiting chemotherapeutic strategies. Furthermore, it forms biofilms in clinically relevant settings, making the infection difficult to treat. Many phytochemicals have potent antimicrobial activities, but their hydrophobicity limits clinical applications. In this study, we tested a new drug delivery strategy where hydrophobic plant phytochemicals were emulsified with a biodegradable nanosponge. We show that the emulsification makes phytochemicals such as carvacrol and eugenol more effective against M. abscessus biofilms. We further demonstrate that nanoemulsified phytochemicals can kill hypoxia-induced dormant M. abscessus and effectively improve skin wound infection in mice. Our data pave the way to use phytochemical nanosponge as a platform to create synergy by combining other antimycobacterial drugs.

Disseminated nontuberculous mycobacteriosis due to Mycobacterium avium subsp. hominissuis infection in a reindeer from a zoo.

Bacteria in the Mycobacterium tuberculosis complex and nontuberculous mycobacteria may affect a variety of animal species under human care and pose public health risks as zoonotic pathogens. A case of sudden onset of lethargy and increased respiratory effort in a 5-y-old, intact female reindeer (Rangifer tarandus) under managed care had progressed to severe dyspnea despite aggressive treatment. The animal was euthanized due to poor prognosis. Postmortem findings included: disseminated miliary nodules in the lungs, pleura, small intestine, liver, and spleen; enlarged mesenteric lymph nodes; dilated mesenteric and serosal lymphatic vessels; and renal infarcts. Histologically, granulomatous lymphadenitis and lymphangitis with intrahistiocytic acid-fast bacilli were observed. Mycobacterium sp. DNA was detected in lung via real-time PCR. Mycobacterial culture and sequencing identified Mycobacterium avium subsp. hominissuis (MAH) within pulmonary lesions. Infection with MAH has been reported in humans and many animal species; this nontuberculous mycobacterial infection may be an emerging concern in animals under managed care. To our knowledge, MAH infection has not been reported previously in reindeer.

Population-Based Analysis of the Risk of Mycobacterial Infections Associated With Immune Checkpoint Inhibitors.

In this population-based study, we examined the risk of nontuberculous mycobacterial disease associated with immune checkpoint inhibitors among people with cancer. Using a nested case-control design, we identified 184 cases and 714 matched controls; there was no significant association on conditional logistic regression (adjusted odds ratio, 0.51 [95% confidence interval, .17-1.50]; P = .22).

A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic progressive lung disease that is increasing in incidence. Host genetic factors are associated with NTM-PD susceptibility. However, the heritability of NTM-PD is not well understood. Here, we perform a two-stage genome-wide association study (GWAS) and discover a susceptibility locus at 16p21 associated with NTM-PD, especially with pulmonary Mycobacterium avium complex (MAC) disease. As the lead variant, rs194800 C allele augments protein kinase C beta (PRKCB) gene expression and associates with severer NTM-PD. The functional studies show that PRKCB exacerbates M.avium infection and promotes intracellular survival of M.avium in macrophages by inhibiting phagosomal acidification. Mechanistically, PRKCB interacts with subunit G of the vacuolar-H+-ATPase (V-ATPase) and vacuolar protein sorting-associated protein 16 homolog (VPS16), blocking the fusion between lysosomes and mycobacterial phagosomes. PRKCB inhibitor has therapeutic potential against M.avium infection. These findings provide insights into the genetic etiology of NTM-PD and highlight PRKCB as an attractive target for host-directed therapy of MAC disease.

Draft genome sequence of Mycobacterium sp. SA01 isolated from Sporobolus alterniflorus seedlings collected in Cape Cod (USA).

A draft genome was generated for a strain of Mycobacterium closely related to Mycobacterium sp. ENV421 isolated in vitro from plants of smooth cordgrass germinated in vitro from seeds collected in a salt marsh in Cape Cod (USA). Genomic DNA was sequenced using paired-end Illumina technologies. Here, we report the classification and genome statistics of Mycobacterium sp. SA01. A strain of Mycobacterium was isolated from seedlings of Sporobolus alterniflorus germinated under in vitro conditions after surface sterilization. The seeds were collected in Little Swippewisett Marsh, Barnstable, MA, USA.

Intervention strategy for Rapid Grower Mycobacteria outbreak among post-laparoscopic surgical site infection patients in a tertiary care hospital.

Background & objectives The emergence of Rapid Grower Mycobacteria (RGM) infections recently produced a great challenge among surgeons following laparoscopic surgical site infection. Infections caused by atypical mycobacteria may be overlooked due to limitations of proper diagnostic infrastructure and unawareness in the resource-limited set-up. In this study, we proposed an intervention strategy for RGM infection among patients having post-laparoscopic surgical site infections in our hospital. Methods Five hundred sixty-five samples were collected within one year (April 2018- March 2019) from the surgery outpatient department (OPD), suspecting atypical mycobacteria infection following surgery. Samples were processed in the microbiology department by conventional staining and culture. RGM was diagnosed up to the species level by both conventional and molecular methods [line probe assay (LPA)]. The antibiogram was performed by the microbroth dilution method on the RAPMYCOI kit as per Clinical and Laboratory Standard Institute (CLSI) guidelines. Simultaneous source identification was carried out. Results A biofilm-producing Mycobacterium abscessus strain was detected from the plastic disinfection tray of the surgical operation theatre (OT), which may be the continuous source of iatrogenic post-surgical infection. RGM prevalence among suspected patients was 19.47 per cent, and around 92 per cent of them were from laparoscopic surgery. Antibiotic sensitivity, as per CLSI guidelines, showed most of them (88.8%) were resistant to commonly given antibiotic clarithromycin. Most sensitivity was to antibiotics amikacin, tobramycin, moxifloxacin, and doxycycline. The game-changing intervention related to this outbreak scenario was the introduction of gas-plasma sterilization and maintaining strict asepsis in surgical operation theatre. Interpretation & conclusions Based on the analysed data, we proposed an intervention strategy in our hospital for treating and preventing RGM infection. Such an approach will help arrest the RGM-outbreaks in future.

Risk Factors and Prognostic Effects of Aspergillosis as a Complication of Nontuberculous Mycobacterial Pulmonary Disease: A Nested Case-Control Study.

The global prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) has been steadily increasing. A few small retrospective studies have reported a poor prognosis associated with chronic pulmonary aspergillosis (CPA) as a complication of NTM-PD. Furthermore, the prognostic impact of CPA may have been inadequately assessed due to differences in background factors. This study aimed to identify the risk factors for CPA in NTM-PD and compare the risk of in-hospital mortality between patients with and without aspergillosis. Data were obtained from a large-scale claims database. Patients with NTM-PD who met the inclusion criteria and those who developed CPA after the NTM diagnosis were identified. The incidence of CPA was evaluated, and risk factors were identified using multiple logistic analyses. Mortality rates were evaluated and compared between patients with and without aspergillosis after adjusting for background CPA risk factors. The incidence of CPA was 2.29% (265/11,587). The identified risk factors included male sex, chronic respiratory failure, asthma, interstitial pneumonia, pulmonary tuberculosis sequelae and systemic corticosteroid use. A total of 219 patients with CPA were matched with control cases using propensity scores based on age and identified risk factors for CPA. The adjusted hazard ratio for in-hospital mortality was 2.6 (95% CI: 1.8-3.9). CPA as a complication of NTM-PD is associated with significantly higher mortality rates. Clinicians should consider the necessity of promptly diagnosing CPA in patients with NTM-PD and the associated risk factors.

Cough and sputum symptoms reduce physical activity in patients with NTM pulmonary disease.

<sec><title>BACKGROUND</title>Although physical activity is an important outcome in patients with chronic respiratory disease, it has not been characterised in those with non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study aimed to evaluate physical activity and its associated factors in patients with NTM-PD.</sec><sec><title>METHODS</title>This prospective observational study measured daily step counts using an accelerometer to assess physical activity (steps per day). We investigated serum C-reactive protein (CRP), incremental shuttle walk test distance (ISWD), Leicester Cough Questionnaire (LCQ), modified Medical Research Council (mMRC) dyspnoea scale, and chronic cough and sputum symptoms (CCS). Patients were divided into two groups based on the presence or absence of CCS, and their physical activity were compared. The association between physical activity and these variables was examined using multivariate analysis.</sec><sec><title>RESULTS</title>We included 131 patients, with a median daily step count of 3,960. Patients with CCS had significantly lower daily step counts than those without CCS (3,426 vs 4,567). Daily step count significantly correlated with age, mMRC dyspnoea grade, CRP level, ISWD, and LCQ. Multiple regression analysis showed that the daily step count was significantly associated with ISWD and CCS.</sec><sec><title>CONCLUSIONS</title>These results suggest that CCS should be considered when assessing physical activity in patients with NTM-PD.</sec>.