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[Infections caused by the so-called atypical mycobacteria (author's transl)].

A number of cases of patients in whom the so-called atypical mycobacteria were identified in our institute are presented briefly in this report. Predisposing factors such as occupation and existing tissue damage, particularly in prolonged respiratory tract diseases, play a significant role in the establishment of the infection in the host organism. The bacteriological culturing, testing and typing of these organisms is an important adjunct to the clinical picture.

Adult

Isolation and identification of mycobacteria from cattle slaughtered in Pakistan.

Specimens of lung, liver and mesenteric lymph node from cows and buffaloes slaughtered in the Lahore area were cultured to investigate the type of mycobacteria involved in bovine tuberculosis. Employing the concentration method, 56 out of 530 cattle were found to be culture positive for acid-fast bacteria, 48 being Mycobacterium bovis and eight atypical mycobacteria. No M tuberculosis or M avium was isolated. Most of the isolated M bovis strains were found to be highly virulent for rabbits.

Animals

Pulmonary mycobacterial infections due to Mycobacterium intracellulare-avium complex. Clinical features and course in 100 consecutive cases.

One hundred consecutive cases of pulmonary infection due to Mycobacterium intracellulare-avium seen during a 3 1/2-year period qualified for review on the basis of a compatible chest x-ray film, repeated isolations from cultures of sputum, and follow-up of three to eight years. Infections with M intracellulare-avium represented 27 percent of all mycobacterial infections seen during this period, including those due to M tuberculosis. The cases of disease due to M intracellulare-avium were predominantly in men with preexisting pulmonary disease, with a peak incidence in the sixth decade, but nearly one-third of the cases were in younger persons free of coexisting disease. The disease was chronic and indolent in most cases, and only a few showed a progressive course. A stable course was frequently observed despite prolonged persistently positive cultures of sputum. A favorable prognosis was most often found in those with previously treated tuberculosis. Poor prognosis was often due to a serious associated disease, such as cancer, rather than to advancing mycobacterial infection itself. Age, sex, or race was unrelated to prognosis. Conversion to negative status on culture was attained in one-half of the cases. Those with extensive radiographic involvement or cavitation were more likely to have treatment fail bacteriologically. No combination of chemotherapy appeared to be particularly effective, including the use of five or more drugs in eight cases demonstrating progressive disease. Surgery, too, was ultimately disappointing in that recurrence appeared in six of 18 carefully selected cases.

Adult

A demographic study of disease due to Mycobacterium kansasii or M intracellulare-avium in Texas.

The number of patients reported th have disease due to Mycobacterium kansasii or M intracellulare-avium has increased in Texas from January 1967 to December 1976, in contrast to a decrease in tuberculosis. Presented is an analysis of 1,409 patients infected with M kansasii and 706 patients infected with M intracellulare-avium. The former group clustered in urban areas with more than twice the incidence compared to nonurban areas (P less than 0.001). The latter group was more diffusely distributed with approximately twice the incidence in nonurban areas compared to urban areas (P less than 0.001). The average age of the group infected with M kansasii was 50 years and of the group infected with M intracellulare-avium 58 years. In patients infected with M kansasii only, the average age was significantly higher for men than women. There was a male predominance in both groups, ie, 3:1 in M kansasii and 2:1 in M intracellulare-avium. Persons with Spanish surnames had a low incidence of disease due to M kansasii. No other racial or ethnic association was noted. The various factors involved in determining the atypical mycobacterial diseases are discussed.

Adolescent

Concanavalin A induced suppressor activity in human leprosy.

Peripheral blood lymphocytes from nine normal subjects and 40 patients with leprosy were pretreated in vitro with Concanavalin A (Con A). Cells from normal subjects pretreated for 24 hours showed consistent and effective generation of suppressive activity which inhibited mitogen induced transformation of autologous lymphocytes. Prolongation of Con A pretreatment to 40 hours resulted in maximal suppressive activity. Tuberculoid leprosy patients had lymphocytes in their blood which on 24 hour pretreatment with Con A exerted suppressive effects markedly greater than the maximal suppression noted with 40 hour pretreated normal lymphocytes. In contrast, untreated patients with polar lepromatous leprosy showed a decrease in suppressive activity which could not be altered by prolongation of Con A pretreatment: the loss of suppressive activity noted in this form of leprosy was restored during erythema nodosum leprosum.

Concanavalin A

Comparative evaluation of molecular technologies for the identification of prevalent non-tuberculous mycobacteria in pulmonary infections: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of non-tuberculous mycobacteria pulmonary disease (NTM PD) is a burden to public health. Successful management of NTM PD critically depends on accurate species identification and reliable drug susceptibility testing to guide appropriate antibiotic therapy. Emerging molecular technologies offer rapid diagnostic solutions compared to conventional methods, but their performance varies. This study aims to provide a comprehensive evaluation of current molecular techniques for NTM identification and to present a global antibiotic resistance profile. METHODS: A systematic literature search was conducted in PubMed and Web of Science for studies published between 2005 and 2024. Studies applying molecular methods for NTM identification and resistance detection in humans were included. Data on study characteristics, diagnostic methods, sample types, sample sizes, identification sensitivity, and drug susceptibility results were extracted. Meta-analysis was performed using R with the meta4diag package. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: The analysis included 49 studies on NTM identification and 33 studies on antibiotic resistance. For species identification, all evaluated molecular technologies (MALDI-TOF MS, PCR-based methods, Sequencing, DNA chip, and DNA strip) demonstrated high pooled sensitivities (>0.92). Subgroup analysis revealed that sample type significantly affected performance for MALDI-TOF MS. Preliminary analysis of antibiotic resistance rates revealed varying patterns. For slowly growing mycobacteria, a significantly high Ethambutol resistance rate was observed in M. avium (69.20%). Among rapidly growing mycobacteria, resistance to Imipenem was notable (54.22%), and Clarithromycin resistance varied significantly within the Mycobacterium abscessus complex. CONCLUSION: Emerging molecular technologies have revolutionized the methodology for NTM identification with excellent performance. However, their performance can be influenced by sample type, particularly for MALDI-TOF MS. The alarming and heterogeneous antibiotic resistance patterns also highlight the critical need for rapid and accurate species identification and drug susceptibility testing to inform effective therapeutic strategies. Key messagesMolecular technologies demonstrate high accuracy for NTM identification.Antibiotic resistance is a serious concern with variations among NTM species and subspecies.Rapid and accurate species identification and drug susceptibility testing are crucial for guiding effective clinical management of NTM PD.

Humans

Investigation of a Mycobacterium fortuitum prosthetic joint infection outbreak at two ambulatory surgery centers in Tennessee.

OBJECTIVE: This study outlines the investigation into an outbreak of Mycobacterium fortuitum infections involving 17 cases undergoing hip or knee surgeries at two ambulatory surgery centers (ASCs) in Tennessee from January 2023 to November 2024. Notably, the outbreak could not be attributed to contaminated water sources, which are typically associated with non-tuberculous mycobacteria (NTM) outbreaks, presenting a unique challenge. METHODS: Outbreak investigation steps included Infection Prevention (IP) assessments, case-control study, environmental sampling, whole genome sequencing, and a healthcare personnel (HCP) exposure questionnaire. RESULTS: IP assessment highlighted several concerns, including no formal facility water management program (WMP), a lack of dedicated IP personnel and certified sterile processing staff, the absence of a formalized system for tracking surgical site infections, and a notable gap in understanding the requirements for reporting diseases. The case-control findings revealed a significant association between the presence of a surgical technologist in the operating room during the procedures and the occurrence of NTM infections, indicated by an odds ratio of 55.77 (95% CI [3.16-985.44]; P = 0.0097). Thirteen clinical isolates collected at one ASC and three additional isolates collected at a second ASC were highly related by whole genome sequencing. CONCLUSION: The study further elucidates valuable insights gained from the outbreak response, including the gaps in surveillance within the ambulatory surgical setting and systematic collection of cultures from environmental sources. It emphasizes the importance of thorough vetting, onboarding, continuing education, and practice monitoring for HCP.

Humans

Species distribution of nontuberculous mycobacteria isolated from respiratory specimens at a tertiary care hospital in South Korea, 2017-2022.

The clinical relevance and drug resistance patterns of nontuberculous mycobacteria (NTM) vary by species. This study investigated the species distribution of NTM isolated from respiratory specimens at a tertiary care hospital in South Korea from 2017 to 2022. A retrospective analysis was conducted on laboratory data from respiratory specimens submitted for acid-fast bacilli culture. NTM isolates were identified using a line probe assay, and those unidentifiable at the species or complex level underwent multigene sequencing of the 16S rRNA, rpoB, and hsp65 genes. Among all mycobacterial isolates, the proportion of NTM showed an increasing trend, rising from 87.4% in 2017 to 93.3% in 2022. The eight most common species were M. avium complex (61.9%), M. abscessus (14.2%), M. fortuitum complex (8.4%), M. gordonae (5.3%), M. simiae complex (3.4%), M. kansasii complex (1.9%), M. terrae complex (1.5%), and M. chelonae (1.2%), accounting for 97.7% of all NTM isolates. Among the remaining isolates (2.3%, n = 169), 161 were classified into 24 species and groups, the majority with proportions below 0.1%. Two of the eight isolates that could not be identified at the species or group level despite multigene sequencing underwent whole-genome sequencing, which suggested they likely represent novel Mycobacterium species. This study provides valuable insights into the distribution of NTM species, particularly rarely encountered species, isolated from respiratory specimens in South Korea. These findings may aid in optimizing diagnostic strategies and selecting appropriate treatment options.IMPORTANCEGiven the significant variations in clinical relevance and drug resistance patterns among nontuberculous mycobacteria (NTM) species, understanding their geographic distribution is essential for selecting appropriate treatment options and improving patient outcomes. This study investigated the distribution of NTM species isolated from respiratory specimens at a tertiary care hospital in South Korea from 2017 to 2022. Our findings revealed an increasing proportion of NTM, with M. avium complex and M. abscessus remaining predominant. Additionally, we identified 24 rarely encountered species and groups, along with two strains that likely represent novel Mycobacterium species. Our study advances the understanding of the evolving NTM epidemiology in South Korea, contributing to the optimization of diagnostic strategies and improvement of patient management.

Republic of Korea

Comparison of culture and culture-free methods for comprehensive identification of mycobacteria: a single-center prospective study.

The genus Mycobacterium, including Mycobacterium tuberculosis and over 200 nontuberculous mycobacteria (NTM), shows wide variability in clinical outcomes and drug susceptibility. Although culture-based identification remains the gold standard, slow mycobacterial growth delays diagnosis and treatment. In this study, we evaluated a novel culture-free method for subspecies-level identification directly from sputum. In this single-center prospective cohort study at Osaka Toneyama Medical Center, we analyzed 125 sputum samples from 115 patients with NTM pulmonary disease and 10 with non-NTM respiratory conditions. Samples were decontaminated using N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) or succinic acid. We compared the reference culture method (mycobacterial culture plus whole-genome sequencing) and a culture-free direct target capture sequencing method. Core genome multi-locus sequence typing identified subspecies in both workflows, covering 186 mycobacterial species, including M. tuberculosis. The 115 NTM cohort specimens yielded 57 smear-positive and 93 culture-positive results. The identified subspecies included 48 Mycobacterium avium subsp. hominissuis, 22 Mycobacterium intracellulare subsp. intracellulare, 5 subsp. chimaera, 7 Mycobacterium abscessus subsp. abscessus, 5 subsp. massiliense, 1 M. tuberculosis, and 5 other NTM species. The culture-free method showed a high identification rate for smear-positive specimens (75.4%) but a low identification rate for smear-negative specimens (13.9%). NALC-NaOH pretreatment resulted in higher accuracy (90.5%) than did succinic acid pretreatment (66.7%). Thus, our culture-free subspecies-level identification method achieved high accuracy, especially in alkaline-treated smear-positive sputum samples, achieving rates above 90%. This method is recommended in clinical practice for patients who require rapid diagnosis and timely initiation of appropriate treatment, bypassing time-consuming culture steps.IMPORTANCEAccurate identification of Mycobacterium species and subspecies is crucial for effective treatment, as drug susceptibility and clinical outcomes vary significantly among them. However, conventional diagnosis relies on culture-based methods that can take several weeks, critically delaying appropriate therapy. This study validates a novel culture-free method using target capture sequencing for the comprehensive, subspecies-level identification of over 186 mycobacterial species directly from sputum specimens. Our findings revealed the high accuracy of this approach for smear-positive specimens, especially with alkaline pretreatment. This rapid method is applicable in clinical settings and enables timely and precise treatment decisions, greatly benefiting patients who require urgent intervention.

Humans

Genomic population structure, antimicrobial susceptibility, and clinical features of Mycobacterium xenopi isolates, Frankfurt, Germany, 1995-2020.

Mycobacterium xenopi causes non-tuberculous mycobacterial pulmonary disease (NTM-PD) that is difficult to treat. However, data on the genomic population structure, antimicrobial susceptibility, and the clinical significance of this pathogen remain scarce. We analyzed 76 clinical M. xenopi isolates from 70 patients collected between 1995 and 2020 in Frankfurt am Main, Germany. All isolates underwent phenotypic drug susceptibility testing and whole-genome sequencing. Cluster analysis, including isolates from this study and all hitherto available high-quality M. xenopi genome data sets in the Sequence Read Archive (n = 11), was performed by core genome multilocus sequence typing. In our cohort, only 26.5% of patients met criteria for clinically relevant NTM-PD. Phylogenetic analysis identified three large hospital-associated clusters (≤10 allelic difference), each involving between 7 and 20 patients and persisting for over 18 years, suggesting prolonged transmission chains or a common environmental source. We also defined three major clades (≤50 allelic difference), two of which contained isolates from the United Kingdom. Clofazimine and guideline-recommended antimycobacterial agents showed good in vitro efficacy, except rifampicin, with 23.6% resistance. This study represents a major expansion of M. xenopi genomic resources and provides insights into the genomic population structure, phenotypic susceptibility, and clinical characteristics of M. xenopi. Guideline-recommended antimycobacterials show good in vitro activity, while clofazimine may be a valuable addition to M. xenopi therapy. The identified clusters underscore the need for further investigation into transmission dynamics and globally successful clones.IMPORTANCEMycobacterium xenopi is an increasingly recognized opportunistic lung pathogen that is difficult to treat. Infections often occur in patients with pre-existing health conditions and can present substantial diagnostic and therapeutic challenges. A deeper understanding of its genetic diversity and resistance mechanisms is essential for optimal patient management and for clarifying potential transmission routes. By analyzing 76 whole-genome sequences together with detailed clinical information and phenotypic drug-susceptibility data, this study substantially expands the available genomic repertoire for M. xenopi. While clinical relevance was limited in our cohort, most guideline-recommended antimicrobial agents showed good efficacy in vitro. The detection of closely related strains might point toward a common environmental source of infection. These findings highlight the need for continued surveillance and provide a comprehensive foundation that supports more accurate monitoring, improved understanding of disease behavior, and future investigations into M. xenopi pathogenicity.

Humans