Search Results (171)

Background/Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) has been associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive ANCA-associated vasculitis (AAV). However, clinical factors associated with MPO-ANCA positivity in patients with NTM-PD remain unclear. This study determined the frequency of MPO-ANCA positivity among tested patients with NTM-PD and explored the clinical factors associated with MPO-ANCA positivity. Methods: This study retrospectively analyzed patients aged ≥15 years old with NTM-PD who were treated at Tokyo Shinagawa Hospital and underwent MPO-ANCA testing between April 2020 and March 2024. Clinical data, including nontuberculous mycobacterial species, serum Mycobacterium avium complex (MAC) antibody titers, radiographic findings, and nodule, infiltration/consolidation, cavity, and ectasis scores, were collected from their electronic medical records. Patients were classified into MPO-ANCA-positive and negative groups, and clinical factors were compared. Results: Among 109 patients with NTM-PD, 49 underwent testing for MPO-ANCA and proteinase 3 (PR3)-ANCA. MPO-ANCA was positive in five patients (10.2%), whereas PR3-ANCA was positive in one (2.0%). Among the five MPO-ANCA-positive patients, three had MAC antibody titers above the upper limit of measurement (>10 U/mL), and one developed AAV with biopsy-proven pauci-immune crescentic glomerulonephritis and mononeuritis multiplex. The MAC antibody titer was significantly higher in the MPO-ANCA-positive group than in the MPO-ANCA-negative group [10.0 (3.89–10.0) vs. 1.92 (0.19–6.19) U/mL, p = 0.038]. Conclusions: MPO-ANCA positivity was observed in a subset of tested patients with NTM-PD and was associated with higher MAC antibody titers. These findings suggest that chronic MAC-related antigen exposure or local pulmonary disease activity in NTM-PD may be associated with MPO-ANCA positivity. Full article

Whipple disease is a rare systemic infection caused by Tropheryma whipplei that often presents with nonspecific gastrointestinal symptoms and may mimic other disorders. We report the case of a 75-year-old woman with type 2 diabetes mellitus who presented with chronic diarrhoea and a 15 kg unintentional weight loss over 6 months despite preserved appetite. Laboratory investigations revealed iron-deficiency anaemia, hypoproteinaemia, mild inflammatory and liver function abnormalities, and peripheral eosinophilia. Extensive infectious, autoimmune, and gastrointestinal investigations were unrevealing. Abdominal computed tomography demonstrated mesenteric lymphadenopathy, raising suspicion for lymphoma. Histopathological examination of duodenal biopsies revealed numerous foamy macrophages containing periodic acid–Schiff-positive, diastase-resistant granular material, consistent with Whipple disease. Ziehl–Neelsen staining additionally demonstrated acid-fast bacilli, and subsequent investigations confirmed concomitant Mycobacterium szulgai infection. The significance of this finding remains uncertain, as it may represent either true coinfection or incidental colonisation. A potential explanation is that T. whipplei-induced macrophage dysfunction creates a permissive intracellular niche for nontuberculous mycobacteria, although supporting evidence is lacking. Following antimicrobial therapy, the patient experienced marked clinical improvement with resolution of symptoms and an 8 kg weight gain. This case highlights the diagnostic challenges of Whipple disease and the need to consider concomitant mycobacterial infection when acid-fast organisms are identified. Full article

Background/Objectives: Granulomatous inflammation in tissue biopsies presents a diagnostic challenge, particularly in differentiating between Mycobacterium tuberculosis complex (MTB) and non-tuberculous mycobacteria (NTM) in high-HIV-prevalence areas. This study evaluates the prevalence and species distribution of mycobacteria in formalin-fixed, paraffin-embedded (FFPE) tissues from patients with granulomatous inflammation and correlates these findings with demographic and clinical data. Methods: Conducted at the NHLS-Dr George Mukhari Tertiary Laboratory, the retrospective descriptive study analysed 37 FFPE samples (January 2019–December 2020) after obtaining ethical approval and collecting clinicopathological data. Histopathological assessments using H&E and Ziehl–Neelsen (ZN) stains were carried out, and mycobacterial species were identified utilising multiplex PCR with reverse hybridisation (GenoType MTBC/CM/AS assays). Results: The cohort had an average age of 38.59 years, with a predominance of females (59.5%) and a high HIV positivity rate (62.2%). The most common biopsy site was lymph nodes (32.4%). All samples exhibited necrotising granulomas, but only 8.1% displayed acid-fast bacilli (AFB) on ZN staining. Molecular testing revealed mycobacterial DNA in 75.7% of samples, identifying NTM alone in 50.0%, MTB alone in 10.7%, and both in 28.6%. M. fortuitum was the most frequently recognised species. Importantly, there was no significant association between mycobacterial detection and HIV status (p > 0.05). Conclusions: The findings demonstrate that molecular methods substantially improve mycobacterial detection rates and speciation. This underscores the diagnostic limitations of ZN staining and highlights the importance of molecular diagnostics for accurately identifying bacterial aetiology, crucial for appropriate antimicrobial therapy in immunocompromised patients. Full article

Introduction: Hairy cell leukemia is a rare, indolent chronic B cell lymphoproliferative disorder characterized by cytopenia, splenomegaly and profound immune dysfunction, predisposing affected individuals to opportunistic infections including non-tuberculous mycobacteria. Concurrent presentation with disseminated mycobacterial infection is un-common and may pose significant diagnostic challenges. Case Presentation: We report the case of a 68-year-old Caucasian man with a history of splenectomy who presented with fever, lymphadenopathy, leukopenia and a generalized rash. Initial investigations including infectious, hematological and vasculitis workups were inconclusive. Lymph node histology demonstrated necrotizing lymphadenitis, which in the context of an otherwise negative investigations was initially suggestive of Kikuchi–Fujimoto disease. Subsequently, cultures from lymph node tissue and blood yielded Mycobacterium avium complex, establishing a diagnosis of disseminated infection. Further bone marrow evaluation with flow cytometry ultimately confirmed underlying hairy cell leukemia. Conclusions: This case highlights how an impaired immune milieu may obscure classic clinical and histopathological features, contributing to diagnostic delay and potentially inappropriate immunosuppressive treatment. Clinicians should maintain a high index of suspicion for underlying hematological malignancy in patients presenting with unexplained cytopenia in association with atypical infections. Early consideration of bone marrow evaluation can be crucial. Full article

(1) Background: Indonesia faces the dual challenge of a high tuberculosis (TB) burden and increasing drug resistance. Conventional molecular diagnostics frequently fail to detect isoniazid resistance and nontuberculous mycobacteria (NTM). This study evaluates a domestic multiplex Open PCR system in Medan, Indonesia. (2) Methods: From July to November 2025, 1569 sputum specimens from suspected TB patients were analysed using the Indigen MTB/NTM/DR-TB Real-time PCR Kit Gen 2. (3) Results: Mycobacterial DNA was detected in 421 specimens (26.8%). Among these, 396 (94.1%) were drug-susceptible TB, while 16 (3.8%) showed resistance, predominantly INH mono-resistance (n = 14; 0.89% of total). Additionally, 9 cases (2.1%) involved NTM or TB-NTM co-infections. Tertiary hospitals showed significantly higher positivity rates (33.5%) than primary care (18.9%; p < 0.001). TB status was significantly associated with male (p = 0.0052) and older age (p = 0.006), whereas resistance profiles and NTM distribution were consistent across all demographic groups (p > 0.80). (4) Conclusions: This study describes the implementation and diagnostic yield of a domestic multiplex Open PCR system in Medan, Indonesia. By bridging diagnostic gaps across a decentralized referral network, this facilitates rapid and targeted therapy. Integrating multiplex domestic innovations into national diagnostic algorithms is essential for achieving Indonesia’s TB elimination targets. Full article

Background/Objectives: Nanopore sequencing is increasingly used in mycobacterial diagnostics, where clinical microbiologists and diagnostic laboratories must decide when broad metagenomic next-generation sequencing (mNGS) or focused targeted next-generation sequencing (tNGS) is most appropriate. This review examined reported clinical and laboratory roles of nanopore mNGS and tNGS in tuberculosis (TB) and nontuberculous mycobacterial (NTM) settings. Methods: Targeted searches of PubMed/MEDLINE, Embase, Web of Science Core Collection, and Scopus were refreshed on 4 April 2026. Thirty-five records spanning original clinical studies, evidence syntheses, and guideline-context documents were included. Results: Nanopore mNGS is most useful for broad organism detection and diagnostic rescue in unresolved pulmonary and extrapulmonary presentations, particularly when first-line testing is negative, discordant, low-yield, or when mixed infection is suspected. Nanopore tNGS appears better aligned with predefined TB confirmation and resistance-focused workflows because targeted regions allow more standardized interpretation. Agreement is strongest for rifampicin- and isoniazid-related resistance targets. In NTM settings, evidence is stronger for detection and species identification than for disease-level diagnosis. Common implementation constraints include pre-analytical variation, contamination control, host-background interference, inconsistent bioinformatics, and limited workforce capacity. Conclusions: A practical tiered approach is supported in which mNGS is positioned mainly for diagnostic rescue and discovery, whereas tNGS is considered for predefined workflows requiring standardized target interrogation and resistance-associated mutation reporting under local validation and quality systems. Full article

Differential diagnosis of tuberculosis (TB) and non-tuberculous mycobacteria (NTM) is extremely challenging, especially in a high TB burden setting like India. A definitive diagnosis of NTM, along with additional speciation, is warranted to improve NTM management. Beyond the diagnosis of NTM and its speciation, clinical correlation is vital for differentiating NTM colonisation or contamination from disease. In this cross-sectional, retrospective analysis, both pulmonary and extrapulmonary samples from 1121 presumptive NTM patients from Tuberculosis Units across the country and from other private hospitals were included. Composite diagnosis were performed using X-rays, nucleic acid amplification tests, smear microscopy, and mycobacterial growth indicator tube cultures, with speciation of NTM isolates confirmed by line probe assay. Of the 1121 presumptive NTM patients, 66.0% were smear-negative, 44.7% had X-ray changes, and 98.0% were M. tuberculosis-negative according to the nucleic acid amplification test. Cultures identified 310 patients as NTM-positive, including 22 extrapulmonary cases. Speciation was performed for 135 NTM-positive isolates, where M. abscessus was identified as the predominant species in 30.4%, followed by M. kansasii in 25.1%. Our study demonstrated that although the composite diagnosis of NTM holds promise for identifying pulmonary and extrapulmonary NTM, culture (mean confirmation rate of 30–40% over 5 years) remains the gold standard, with NTM speciation by line probe assay completing the diagnosis. Full article

Obstructive jaundice is a common digestive disorder with multiple etiologies. Non-tuberculous mycobacterial (NTM) infection is an opportunistic disease that may present with localized pulmonary involvement or disseminated multi-organ manifestations. However, biliary involvement in disseminated NTM infection is rare, and its characteristics and progression remain poorly understood. We report a patient with progressive jaundice who was eventually considered to have probable biliary NTM infection after comprehensive evaluation, exclusion of alternative etiologies, and a favorable therapeutic response despite negative microbiological testing. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to relieve biliary obstruction, but the patient developed recurrent and refractory ampullary bleeding requiring repeated endoscopic interventions. Clinical improvement was achieved following combined antimycobacterial therapy and immunomodulatory treatment. Biliary NTM infection is a rare cause of obstructive jaundice, and ERCP remains necessary for biliary decompression, while post-ERCP bleeding risk should be carefully monitored. Full article

Mycobacterium chelonae is a rapidly growing nontuberculous mycobacterium (NTM) that can infect both immunocompetent and immunocompromised hosts. Cutaneous and soft tissue infections are the most common manifestations and occur more frequently in individuals with underlying immune dysfunction. Patients with chronic lymphocytic leukemia (CLL), particularly those receiving targeted therapies such as ibrutinib, may be at increased risk of opportunistic infections. The diagnostic workup, microbiological findings, antimicrobial susceptibility testing, and therapeutic approach adopted for a cutaneous M. chelonae infection arising in a CLL patient four months after the introduction of ibrutinib were described. Clinical course and surgical management are also reported. A 60-year-old beekeeper with B-cell CLL developed a progressive cutaneous lesion on the left lower limb within four months of starting ibrutinib. Culture of a skin biopsy identified M. chelonae. Antimicrobial therapy was initiated based on in vitro susceptibility testing, resulting in partial clinical improvement. Complete resolution required surgical excision of the infected tissue followed by skin grafting. The patient’s underlying hematologic disease, ongoing immunosuppression, and recent exposure to ibrutinib likely contributed to susceptibility and persistence of infection. This case highlights the increasing recognition of nontuberculous mycobacterial infections in immunocompromised individuals and underscores the importance of early diagnosis and susceptibility- guided therapy. Clinical response may be incomplete, and combined medical and surgical approaches may be required in selected cases. NTM infections should be considered in patients receiving Bruton’s tyrosine kinase inhibitors who present with persistent, atypical, or non-healing cutaneous lesions. However, the association between ibrutinib therapy and susceptibility to infection remains uncertain, as multiple predisposing factors may coexist. Increased awareness of this possible association, together with careful clinical evaluation, may facilitate earlier diagnosis and improved management. Full article

In this report, we describe systemic granulomatous mycobacteriosis in an orbiculate batfish from an aquarium in South Korea. Gross examination of the deceased fish showed multifocal nodular lesions in multiple internal organs including the gills, spleen, and kidney. Histopathological analysis demonstrated severe chronic systemic granulomatous inflammation, and Ziehl–Neelsen staining highlighted abundant intralesional acid-fast bacilli. Molecular analysis based on partial sequencing of the 16S ribosomal RNA (rRNA) and heat shock protein 65 (hsp65) genes showed that the detected organism was most closely related to Mycobacterium marinum. Because the molecular analysis was performed using partial sequences obtained from formalin-fixed, paraffin-embedded tissues, definitive species-level identification was not possible. This case represents systemic granulomatous mycobacteriosis associated with a Mycobacterium marinum-like organism in orbiculate batfish in an aquarium in South Korea and emphasizes the need for continuous disease surveillance and improved diagnostic awareness of non-tuberculous mycobacterial infections in ornamental and public aquarium fish. Full article

Background: Nontuberculous mycobacteria (NTM) skin infections pose significant diagnostic challenges in clinical practice, due to nonspecific clinical/histopathological features and limitations of conventional pathogenic detection methods. Metagenomic next-generation sequencing (mNGS) offers a promising approach but requires further evaluation. Methods: A prospective pilot study at Peking Union Medical College Hospital enrolled 20 patients with cutaneous NTM infection, confirmed by positive skin culture or mNGS. All patients underwent thorough clinical assessment, skin biopsy for histopathology and culture, and mNGS testing of skin tissue. Treatment was based on identified species and disease extent. Treatment outcomes were tracked. Results: Among 20 patients (median age 45.5 years), fingers were the most common site affected (n = 10), followed by forearms (n = 7), hands (n = 4), and face (n = 4). Mycobacterium marinum was the predominant pathogen (n = 12), associated with fish bone puncture, followed by M. abscessus (n = 4). mNGS demonstrated a substantially higher positivity rate than culture (95% [19/20] vs. 30% [6/20]) and delivered results faster. Histopathology revealed granulomatous inflammation in all cases. Nineteen patients presented with non-disseminated disease; one immunocompromised patient (GATA2 deficiency) had disseminated M. abscessus infection. Treatment success was achieved in 17 patients (85%) with tailored antibiotic regimens. Adverse drug effects occurred in seven patients. Conclusions: In this pilot study of cutaneous NTM infections, mNGS enabled more rapid diagnosis relative to conventional culture. Clinical presentation and exposure history correlate with specific NTM species. Integrating mNGS with clinical assessment significantly improves diagnosis and management. Full article

Background/Objectives: Nontuberculous mycobacterial (NTM) pulmonary infection may present with diverse radiologic manifestations that mimic lung malignancy. Furthermore, in patients with newly detected or progressively enlarging pulmonary lesions, distinguishing benign NTM-related lesions from coexisting malignancy is often challenging. When imaging findings are indeterminate, percutaneous core needle biopsy (PCNB) may be required for diagnostic clarification. This study aimed to evaluate the pathologic results, clinical characteristics, and CT features of pulmonary lesions in patients with NTM infection who underwent PCNB and to identify factors associated with malignancy. Methods: This retrospective study included 38 patients with NTM infection who underwent CT-guided PCNB for lung lesions between 2015 and 2025. Two blinded radiologists reviewed chest CT scans obtained within six weeks prior to the biopsies. Clinical variables and CT features were compared between malignant and benign lesions. Univariable and multivariable logistic regression analyses were performed to explore factors associated with malignancy. Results: Of the 38 patients, 9 (23.7%) were diagnosed with malignancy and 29 (76.3%) had benign lesions. Malignant lesions more frequently demonstrated a lobulated irregular morphology compared to benign lesions (88.9% vs. 37.9%). Emphysema was also more common in the malignancy group (88.9% vs. 24.1%, p < 0.001). In the multivariable logistic regression analysis, lobulated irregular morphology (odds ratio [OR], 19.856; 95% CI, 1.516–260.089; p = 0.023) and emphysema (OR, 35.531; 95% CI, 2.857–441.824; p = 0.005) were associated with malignancy. However, the wide confidence intervals indicate substantial uncertainty due to the limited number of malignant cases. Conclusions: In patients with NTM infection who underwent PCNB for suspicious lung lesions, a lobulated irregular morphology and the presence of emphysema were associated with malignancy in this exploratory cohort. These findings may provide useful information to support clinical decision-making regarding biopsy in patients with NTM infection and indeterminate pulmonary lesions. Full article

Pulmonary disease caused by nontuberculous mycobacteria represents an important diagnostic challenge, particularly in immunocompromised patients, in whom clinical and radiologic findings may mimic malignancy. We report the case of a 70-year-old woman with myelofibrosis treated with ruxolitinib who developed a tumor-like lesion in the left upper lobe on computed tomography, highly suggestive of lung cancer. Despite broad-spectrum antibiotic therapy, the lesion persisted; bronchoscopy did not yield diagnostic findings, and CT-guided transthoracic biopsy demonstrated necrotizing granulomatous inflammation without evidence of malignancy. Microbiological analysis subsequently identified Mycobacterium avium, and targeted antimycobacterial therapy led to clinical and radiologic improvement. This case highlights that pulmonary nontuberculous mycobacterial infection may present as a pseudotumoral lesion and should be considered in the differential diagnosis of mass-like pulmonary opacities, particularly in patients receiving Janus kinase inhibitor therapy. Full article

Mycobacteria isolated only once in repeated sputum cultures are deemed colonizers that are not normally present in the lungs despite their ubiquitous presence in the environment. We have developed a sensitive and specific PCR assay to detect slow-growing mycobacteria in culture negative sputum and have found them in 30% of the samples obtained from individuals with clinical suspicion of tuberculosis or mycobacteriosis (n = 50) and in 45% of the samples from individuals with no suspicion (n = 49). As a negative control we have analyzed infections from an extra-pulmonary location, the urinary tract (n = 21), in which mycobacterioses are rare, and did not detect them. The load of bacteria in the lungs is kept low by the defense mechanisms of the host, and mycobacteria are not normally detected in sputum cultures. Their incidental isolation would not be a consequence of a new exposure to the microorganism but a sign of susceptibility to mycobacteriosis. Full article

Background/Objectives: Prosthetic valve endocarditis caused by non-tuberculous mycobacteria is a rare but serious condition and is often associated with delayed diagnosis due to initially negative routine blood cultures with late positivity after prolonged incubation. Mycobacterium fortuitum, a rapidly growing mycobacterium, is an uncommon cause of endocarditis but may result in significant morbidity if not promptly identified. Methods: We report a 67-year-old man with prior cardiac surgery who presented 18 months later with recurrent fever, weight loss, and renal dysfunction. Initial blood cultures, echocardiography, and standard imaging were non-diagnostic. Ongoing clinical suspicion prompted extended mycobacterial cultures with prolonged incubation and molecular identification performed at a reference laboratory, which revealed M. fortuitum. Results: Antimicrobial susceptibility testing demonstrated susceptibility to amikacin, ciprofloxacin, and clarithromycin, and treatment was initiated with an amikacin-based combination regimen. The patient showed marked clinical and laboratory improvement, including resolution of fever and stabilization of renal function. Conclusions: This case highlights the diagnostic and therapeutic challenges of M. fortuitum prosthetic valve endocarditis and underscores the limitations of routine diagnostic methods in culture-negative endocarditis. It also emphasizes the importance of prolonged incubation and targeted microbiological workflows in suspected cases. Full article