Mycobacterium porcinum Disseminated Infection in Non-severely Immunocompromised Host.

Mycobacterium porcinum is a nontuberculous mycobacteria (NTM) recently identified to cause human infection. Correct speciation of NTMs can be difficult and result in misdiagnosis and delayed treatment. Because of the paucity of the literature, there is a lack of awareness of the possibility of serious infections caused by M. porcinum. Although severe infections tend to occur in individuals with certain risk factors, the primary being an immunocompromised state, our case illustrates that it can also be possible in non-severely immunocompromised individuals. A 65-year-old male with a medical history of diabetes mellitus (DM), end-stage renal disease (ESRD) on hemodialysis (HD), congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD) was admitted to the emergency room due to a laceration on his right lower leg following a fall. He reported shortness of breath but denied other respiratory symptoms. On examination, he showed signs of infection and increased oxygen requirement compared to baseline. Blood culture was positive for acid-fast bacilli (AFB), initially reported as M. avium complex (MAC) and later confirmed as M. porcinum through gene sequencing and morphology analysis. Interval blood cultures taken a week later confirmed true M. porcinum bacteremia. Treatment initially involved intravenous antibiotics- imipenem and ciprofloxacin before transitioning to oral linezolid and ciprofloxacin based on sensitivities. Following 10 days of antibiotic therapy, subsequent blood cultures returned negative, and treatment with oral antibiotics was advised, with continued outpatient follow-up with infectious disease in two weeks. M. porcinum, typically considered a contaminant in healthy individuals, was identified as the causative agent of a disseminated infection in a non-severely immunocompromised patient. This case underscores the importance of accurately identifying the specific mycobacterial species, confirming true infection, and conducting antibiotic susceptibility testing due to the distinct antibiotic susceptibility profile of M. porcinum compared to other NTM like MAC.

The First Case Report of Inactive Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) in a Pneumoconiosis Patient Caused by Mycobacterium europaeum in China.

We reported a 51-year-old male electric welder with stage I pneumoconiosis, who had no significant cough, sputum, fever, chest pain, or other discomfort. However, regular physical examination at our hospital revealed bilateral pulmonary nodules with cavity formation. Blood routine, liver or kidney function, and infection-related biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT), were normal. Sputum and alveolar lavage fluid (BALF) acid-fast bacilli (AFB) smears, BALF Mycobacterium tuberculosis (TB) PCR, and T-SPOT.TB were negative. The nucleic acid sequence of Mycobacterium europaeum was detected by BALF metagenomic next-generation sequencing (mNGS), which was confirmed by the subsequent positive culture for NTM. Considering stable conditions, no significant discomfort, and no significant changes in the lung lesion, the patient was diagnosed with inactive nontuberculous mycobacterial pulmonary disease (NTM-PD).

Amikacin Liposome Inhalation Suspension in the Real-World Management of Refractory Mycobacterium avium Complex Pulmonary Disease.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Mycobacterium gordonae Infection in a Patient With Non-small Cell Lung Cancer.

Mycobacterium gordonae (MG) is one of the least pathogenic nontuberculous mycobacteria (NTM). We report an unusual case of MG infection in a patient with newly diagnosed lung cancer. A 61-year-old woman presented with shortness of breath and weight loss. Six months prior to admission, she was diagnosed with MG infection based on positive sputum cultures and bronchioalveolar lavage. Despite anti-mycobacterial therapy, her symptoms worsened and she lost approximately 100 pounds. A transbronchial biopsy obtained one week prior to admission revealed adenocarcinoma of the lung. At admission, vital signs were normal, and a physical exam revealed bilateral crackles. Computed tomography (CT) scan of the chest revealed infiltrates with ground-glass opacity. The patient was admitted to the oncology service for evaluation. Our findings suggest that symptomatic individuals with positive cultures of MG should proceed with extensive workup for possible underlying lung cancer especially if not responding to anti-mycobacterial therapy.

Targeting intracellular nontuberculous mycobacteria and M. tuberculosis with a bactericidal enzymatic cocktail.

To address intracellular mycobacterial infections, we developed a cocktail of four enzymes that catalytically attack three layers of the mycobacterial envelope. This cocktail is delivered to macrophages, through a targeted liposome presented here as ENTX_001. Endolytix Cocktail 1 (EC1) leverages mycobacteriophage lysin enzymes LysA and LysB, while also including α-amylase and isoamylase for degradation of the mycobacterial envelope from outside of the cell. The LysA family of proteins from mycobacteriophages has been shown to cleave the peptidoglycan layer, whereas LysB is an esterase that hydrolyzes the linkage between arabinogalactan and mycolic acids of the mycomembrane. The challenge of gaining access to the substrates of LysA and LysB provided exogenously was addressed by adding amylase enzymes that degrade the extracellular capsule shown to be present in Mycobacterium tuberculosis. This enzybiotic approach avoids antimicrobial resistance, specific receptor-mediated binding, and intracellular DNA surveillance pathways that limit many bacteriophage applications. We show this cocktail of enzymes is bactericidal in vitro against both rapid- and slow-growing nontuberculous mycobacteria (NTM) as well as M. tuberculosis strains. The EC1 cocktail shows superior killing activity when compared to previously characterized LysB alone. EC1 is also powerfully synergistic with standard-of-care antibiotics. In addition to in vitro killing of NTM, ENTX_001 demonstrates the rescue of infected macrophages from necrotic death by Mycobacteroides abscessus and Mycobacterium avium. Here, we demonstrate shredding of mycobacterial cells by EC1 into cellular debris as a mechanism of bactericide.IMPORTANCEThe world needs entirely new forms of antibiotics as resistance to chemical antibiotics is a critical problem facing society. We addressed this need by developing a targeted enzyme therapy for a broad range of species and strains within mycobacteria and highly related genera including nontuberculous mycobacteria such as Mycobacteroides abscessus, Mycobacterium avium, Mycobacterium intracellulare, as well as Mycobacterium tuberculosis. One advantage of this approach is the ability to drive our lytic enzymes through encapsulation into macrophage-targeted liposomes resulting in attack of mycobacteria in the cells that harbor them where they hide from the adaptive immune system and grow. Furthermore, this approach shreds mycobacteria independent of cell physiology as the drug targets the mycobacterial envelope while sidestepping the host range limitations observed with phage therapy and resistance to chemical antibiotics.

Prevalence of pulmonary artery dilation in non-cystic fibrosis bronchiectasis: a computed tomography analysis from a cohort of the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry.

Although pulmonary artery (PA) dilation is independently associated with significant morbidity and mortality in patients with pulmonary diseases irrespective of diagnosed pulmonary hypertension, its relationship with nontuberculous mycobacteria (NTM) is unknown. The Bronchiectasis and NTM Research Registry is a multicenter registry created to foster research in non-cystic fibrosis (CF) bronchiectasis and NTM lung disease. The majority of patients with non-CF bronchiectasis at Oregon Health & Science University have NTM infections. To determine the prevalence of PA dilation in these patients and its association with supplemental oxygen use, severity of bronchiectasis, tobacco use, and NTM in the sputum culture, we evaluated the chest computed tomography (CT) scans from 321 patients in a cross-sectional analysis. We measured the severity of bronchiectasis by applying modified Reiff criteria and measured the diameters of the PA and aorta (Ao), with PA dilation defined as a PA:Ao ratio >0.9. In our cohort, the mean age was 67.3 years and 83.2% were female. The mean modified Reiff score was 7.1, indicating moderate disease severity. Forty-two patients (13.1%) were found to have PA dilation. PA dilation was positively associated with the use of supplemental oxygen (P<0.001), but there was no association between PA dilation and NTM infection.

Rates and Risk Factors of Progression in Patients With Nontuberculous Mycobacterial Pulmonary Disease: Secondary Analysis of a Prospective Cohort Study.

BACKGROUND: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. RESEARCH QUESTION: What is the rate of NTM-PD progression, and what are the predictors of progression? STUDY DESIGN AND METHODS: Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. RESULTS: Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression. INTERPRETATION: About half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01616745; URL: www. CLINICALTRIALS: gov.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. METHODS: We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves. RESULTS: There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI-lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI-lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. CONCLUSION: 18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

Prevalence of Mycobacterium kansasii in clinical and environmental isolates, a systematic review and meta-analysis.

Background: Mycobacterium kansasii infection is one of the most common causes of non-tuberculosis mycobacterial (NTM) disease worldwide. However, accurate information on the global prevalence of this bacterium is lacking. Therefore, this study was conducted to investigate the prevalence of M. kansasii in clinical and environmental isolates. Methods: Databases, including PubMed, Scopus, and the Web of Science, were utilized to gather articles on the prevalence of M. kansasii in clinical and environmental isolates. The collected data were analyzed using Comprehensive Meta-Analysis software. Results: A total of 118 and 16 studies met the inclusion criteria and were used to analyze the prevalence of M. kansasii in clinical and environmental isolates, respectively. The prevalence of M. kansasii in NTM and environmental isolates were 9.4 and 5.8%, respectively. Subsequent analysis showed an increasing prevalence of M. kansasii over the years. Additionally, the results indicated a significant difference in the prevalence of this bacteria among different regions. Conclusion: The relatively high prevalence of M. kansasii among NTM isolates suggests the need for further implementation of infection control strategies. It is also important to establish appropriate diagnostic criteria and management guidelines for screening this microorganism in environmental samples in order to prevent its spread, given its high prevalence in environmental isolates.

Synthesis and in†vitro Metabolic Stability of Sterically Shielded Antimycobacterial Phenylalanine Amides.

Nα-aroyl-N-aryl-phenylalanine amides (AAPs) are RNA polymerase inhibitors with activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria. We observed that AAPs rapidly degrade in microsomal suspensions, suggesting that avoiding hepatic metabolism is critical for their effectiveness in vivo. As both amide bonds are potential metabolic weak points of the molecule, we synthesized 16 novel AAP analogs in which the amide bonds are shielded by methyl or fluoro substituents in close proximity. Some derivatives show improved microsomal stability, while being plasma-stable and non-cytotoxic. In parallel with the metabolic stability studies, the antimycobacterial activity of the AAPs against Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium avium and Mycobacterium intracellulare was determined. The stability data are discussed in relation to the antimycobacterial activity of the panel of compounds and reveal that the concept of steric shielding of the anilide groups by a fluoro substituent has the potential to improve the stability and bioavailability of AAPs.

Evaluation of nucleotide MALDI-TOF-MS for the identification of Mycobacterium species.

Background: The accurate identification of the Mycobacterium tuberculosis complex (MTBC) and different nontuberculous mycobacteria (NTM) species is crucial for the timely diagnosis of NTM infections and for reducing poor prognoses. Nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been extensively used for microbial identification with high accuracy and throughput. However, its efficacy for Mycobacterium species identification has been less studied. The objective of this study was to evaluate the performance of nucleotide MALDI-TOF-MS for Mycobacterium species identification. Methods: A total of 933 clinical Mycobacterium isolates were preliminarily identified as NTM by the MPB64 test. These isolates were identified by nucleotide MALDI-TOF-MS and Sanger sequencing. The performance of nucleotide MALDI-TOF MS for identifying various Mycobacterium species was analyzed based on Sanger sequencing as the gold standard. Results: The total correct detection rate of all 933 clinical Mycobacterium isolates using nucleotide MALDI-TOF-MS was 91.64% (855/933), and mixed infections were detected in 18.65% (174/933) of the samples. The correct detection rates for Mycobacterium intracellulare, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium avium, MTBC, Mycobacterium gordonae, and Mycobacterium massiliense were 99.32% (585/589), 100% (86/86), 98.46% (64/65), 94.59% (35/37), 100.00% (34/34), 95.65% (22/23), and 100% (19/19), respectively. For the identification of the MTBC, M. intracellulare, M. abscessus, M. kansasii, M. avium, M. gordonae, and M. massiliense, nucleotide MALDI-TOF-MS and Sanger sequencing results were in good agreement (k > 0.7). Conclusion: In conclusion, nucleotide MALDI-TOF-MS is a promising approach for identifying MTBC and the most common clinical NTM species.

Characterisation and antimicrobial susceptibility pattern of non-tuberculous mycobacteria.

Background: Non-tuberculous mycobacteria (NTM) management comprises prolonged therapy that includes macrolides. Non-tuberculous mycobacteria can cause disease in patients with predisposing conditions such as HIV and structural lung disease. Local data on NTM disease and macrolide resistance are scarce, and routine antimicrobial susceptibility testing is currently not performed for NTM in South Africa. Objectives: This study aims to characterise NTM isolated at Tshepong National Health Laboratory Service (NHLS) according to species and antimicrobial susceptibility pattern. Method: A retrospective data analysis of NTM isolates from Tshepong NHLS was performed from January to June 2020. GenoType® NTM-DR was performed on selected isolates where the assay can confirm the species and determine resistance to macrolides and aminoglycosides. Results: Of the 194 collected NTM isolates, 183 were included in the study. Patients' ages ranged from 1 day to 81 years (median 36 years). The most common specimen was sputum (84.7%), followed by gastric aspirate (6.6%). The most common NTM isolated were Mycobacterium (M.) intracellulare (67.6%), M. fortuitum (12.6%), M. species (4.3%), M. kansasii (3.9%), and M. scrofulaceum (3.9%). Macrolide resistance occurred in 2.8% of tested isolates; no aminoglycoside resistance was detected. Although most isolates were from males (62.3%), resistance was observed only in females. Conclusion: M. intracellulare predominated, with only two M. intracellulare and two M. abscessus isolates showing macrolide resistance; aminoglycoside resistance was absent. Contribution: This study highlights the need for increased awareness of NTM, regular nationwide NTM surveillance, and monitoring of resistance trends to guide future patient management and ensure good treatment outcomes.

Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Pacemaker infection at generator site by Mycobacterium mageritense: A case report and review of the literature.

We herein report an unusual case of Mycobacterium mageritense pacemaker infection at generator site in a 62-year old female with no pertinent past medical history. Pacemaker-related infections caused by nontuberculous mycobacteria are rare but can lead to significant morbidity and mortality. Mycobacterium mageritense is rarely reported in pacemaker infections and is challenging to treat due to resistance to many antimicrobial agents. In our case, the patient's pacemaker infection did not respond to standard treatment, leading to complete device removal. Our case highlights the challenges in treating Mycobacterium Mageritense, especially that our patient had a more resistant organism than those reported previously in literature. To our knowledge, such cases are infrequently reported in the literature.

Five-year species distribution and antimicrobial susceptibility of non-tuberculous mycobacteria in Malaysia, 2018-2022.

Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.

NewickTreeModifier: A simple web tool to prune and modify Newick trees.

Large-scale selection analyses of protein-coding sequences and phylogenetic tree reconstructions require suitable trees in Newick format. We developed the NewickTreeModifier (NTM), a simple web-based tool to trim and modify Newick trees for such analyses. The users can choose provided master trees or upload a tree to prune it to selected species available in FASTA, NEXUS, or PHYLIP sequence format with an internal converter, a simple species list, or directly determined from a checklist interface of the master trees. Plant, insect, and vertebrate master trees comprise the maximum number of species in an up-to-date phylogenetic order directly transferable to the pruned Newick outfile. NTM is available at https://retrogenomics.uni-muenster.de/tools/ntm.

Evaluation of the FluoroType Mycobacteria assay for identification of mycobacteria.

Accurate species identification is a prerequisite for successful management of tuberculosis and non-tuberculous mycobacterial (NTM) diseases. The novel FluoroType Mycobacteria assay combines three established GenoType DNA strip assays (CM, AS, and NTM-DR), allowing detection of Mycobacterium tuberculosis and 32 NTM species/subspecies in a single assay with automatic detection and result analysis. We evaluated the clinical performance of the FluoroType assay and its feasibility in replacing the GenoType Mycobacterium CM assay as the initial method for mycobacterial identification. A total of 191 clinical mycobacterial cultures were analyzed in this study: 180 identified for one mycobacterial species, 6 for multiple, and 5 for no mycobacterial species. Positive percent agreement (PPA) for the FluoroType assay was 87.8% (n = 158), with full agreement for 23/29 species. Weakest PPA was observed for Mycobacterium gordonae (50%, n = 9/18), Mycobacterium interjectum (40%, n = 2/5), and Mycobacterium intracellulare (42%, n = 5/12). Clinical and mixed cultures containing multiple mycobacterial species gave equally single species and genus level identifications (n = 30). No cross-reactivity with non-mycobacterial species was observed (n = 22). In a separate in silico analysis of 2016-2022 HUS area (Finland) register data (n = 2,573), the FluoroType assay was estimated to produce 18.8% (n = 471) inadequate identifications (genus/false species) if used as the primary identification method compared to 14.2% (n = 366) with the GenoType CM assay. The FluoroType assay was significantly more convenient in terms of assay workflow and result interpretation compared to the entirely manual and subjective GenoType CM assay. However, the feasibility of the assay should be critically assessed with respect to the local NTM species distribution. IMPORTANCE: This study is the first clinical evaluation report of the novel FluoroType Mycobacteria assay. The assay has the potential to replace the established GenoType NTM product family in identification of culture-enriched mycobacteria. However, our research results suggest that the assay performs suboptimally and may not be feasible for use in all clinical settings.

Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo.

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05-0.94 µg/mL, 0.88-7.22 µg/mL (M. abscessus subsp. abscessus), and 0.22-8.67 µg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13-1.18, 0.18-1.50, and 0.17-1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials. IMPORTANCE: Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000-2019. 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 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 anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

The impact of nontuberculous mycobacterial lung disease in critically ill patients: Significance for survival and ventilator use.

BACKGROUND: This study investigates the impact of nontuberculous mycobacterial lung disease (NTM-LD) on mortality and mechanical ventilation use in critically ill patients. METHODS: We enrolled patients with NTM-LD or tuberculosis (TB) in intensive care units (ICU) and analysed their association with 30-day mortality and with mechanical ventilator-free survival (VFS) at 30 days after ICU admission. RESULTS: A total of 5996 ICU-admitted patients were included, of which 541 (9.0 %) had TB and 173 (2.9 %) had NTM-LD. The overall 30-day mortality was 22.2 %. The patients with NTM-LD had an adjusted hazard ratio (aHR) of 1.49 (95 % CI, 1.06-2.05), and TB patients had an aHR of 2.33 (95 % CI, 1.68-3.24), compared to ICU patients with negative sputum mycobacterial culture by multivariable Cox proportional hazard (PH) regression. The aHR of age<65 years, obesity, idiopathic pulmonary fibrosis, end-stage kidney disease, active cancer and autoimmune disease and diagnosis of respiratory failure were also significantly positively associated with ICU 30-day mortality. In multivariable Cox PH regression for VFS at 30 days in patients requiring invasive mechanical ventilation, NTM-LD was negatively associated with VFS (aHR 0.71, 95 % CI: 0.56-0.92, p = 0.009), while TB showed no significant association. The diagnosis of respiratory failure itself predicted unfavourable outcome for 30-day mortality and a negative impact on VFS at 30 days. CONCLUSIONS: NTM-LD and TB were not uncommon in ICU and both were correlated with increasing 30-day mortality in ICU patients. NTM-LD was associated with a poorer outcome in terms of VFS at 30 days.