Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015–2020)

<b><i>Background:</i></b> Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. <b><i>Methods:</i></b> Retrospective analysis (2015–2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients’ characteristics, NTM strains, and time to culture positivity were reported. <b><i>Results:</i></b> Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m²). The <i>Mycobacterium avium</i> complex (MAC) was the most frequently identified group (37% of strains) followed by <i>Mycobacterium gordonae</i> (25%) and <i>Mycobacterium xenopi</i> (12%) among the slowly growing mycobacteria (SGM), while the <i>Mycobacterium chelonae/abscessus</i> group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (<i>n</i> = 19, 43% of cases in patients treated) followed by RGM (<i>n</i> = 15, 34%) and <i>M. xenopi</i> (<i>n</i> = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. <b><i>Conclusions:</i></b> In Western Switzerland, <i>M. avium</i> and <i>M. gordonae</i> were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

Conserved and specialized functions of Type VII secretion systems in non-tuberculous mycobacteria

Non-tuberculous mycobacteria (NTM) are a large group of micro-organisms comprising more than 200 individual species. Most NTM are saprophytic organisms and are found mainly in terrestrial and aquatic environments. In recent years, NTM have been increasingly associated with infections in both immunocompetent and immunocompromised individuals, prompting significant efforts to understand the diverse pathogenic and signalling traits of these emerging pathogens. Since the discovery of Type VII secretion systems (T7SS), there have been significant developments regarding the role of these complex systems in mycobacteria. These specialised systems, also known as Early Antigenic Secretion (ESX) systems, are employed to secrete proteins across the inner membrane. They also play an essential role in virulence, nutrient uptake and conjugation. Our understanding of T7SS in mycobacteria has significantly benefited over the last few years, from the resolution of ESX-3 structure in Mycobacterium smegmatis , to ESX-5 structures in Mycobacterium xenopi and Mycobacterium tuberculosis . In addition, ESX-4, considered until recently as a non-functional system in both pathogenic and non-pathogenic mycobacteria, has been proposed to play an important role in the virulence of Mycobacterium abscessus ; an increasingly recognized opportunistic NTM causing severe lung diseases. These major findings have led to important new insights into the functional mechanisms of these biological systems, their implication in virulence, nutrient acquisitions and cell wall shaping, and will be discussed in this review.

Complete Genome Sequence of Mycobacterium heckeshornense JCM 15655T, Closely Related to a Pathogenic Nontuberculous Mycobacterial Species, Mycobacterium xenopi

ABSTRACT Mycobacterium heckeshornense is a slow-growing mycobacterial species for which pathogenic features are unclear. Here, we report the complete genome sequence of an M. heckeshornense type strain. This sequence will provide essential information for future taxonomic and comparative genome studies of these mycobacteria.

Mycobacterium xenopi osteomyelitis of the spine: a case report

ABSTRACT BACKGROUND: Mycobacterium xenopi (M. xenopi) osteomyelitis is an uncommon infection which is found in immunosuppressed patients. It is reported to be a slow-growing, nonchromogenic or scotochromogenic nontuberculous mycobacterium. The lungs constitute the most common site for infection and extrapulmonary manifestations, and disseminated forms of the disease are rare. Only a few cases of spontaneous spinal involvement have been reported. We report a case of M. xenopi vertebral osteomyelitis of the spine PATIENT AND METHODS: A 41-year-old female patient, HIV reactive on antiretroviral therapy with a low CD4 count of 183 cells/mm3, presented with clinical and radiological features in keeping with thoracic spinal tuberculosis, complicated with thoracic myelopathy. She was managed surgically with costo-transversectomy and drainage of the paraspinal cold abscess. The Ziehl-Neelsen staining was negative for acid-fast bacilli. However, the histology result revealed a necrotising granulomatous inflammation. A delayed result of polymerase chain reaction (PCR)/line probe assay for Mycobacterium genus testing revealed the presence of M. xenopi, as the cause for the spine osteomyelitis and thoracic myelopathy. However, no M. xenopi susceptibility testing, and no specific photoreactivity techniques for strain identification, were performed. Anti-tuberculosis therapy (ATT) consisting of a two-month initiation phase using rifampicin, isoniazid, ethambutol and pyrazinamide, followed by a seven-month continuation phase using rifampicin and isoniazid, was initiated according to national guidelines. She was fitted with a thoraco-lumbar-sacral orthosis, and underwent a spinal rehabilitation programme. Upon receipt of the PCR result, and considering the good clinical and radiological response to ATT, a consensus was reached with the Infectious Disease Unit (IDU) to continue with ATT until 18 months due to the atypical nature of the pathogen. RESULTS: The patient was successfully treated with the standard TB regimen, but for a period of 18 months, and made full clinical neurological recovery, without any back pain. Furthermore, her CD4 count had also improved to 707 cells/mm3 with a viral load reported lower than 1 000 copies/ml CONCLUSION: This case report emphasises the importance of biopsy in suspected spinal tuberculosis and highlights the concerns with laboratory testing and the prognostic and therapeutic implications of a positive strain identification Level of evidence: Level 5 Keywords: Mycobacterium xenopi osteomyelitis, tuberculosis, anti-tuberculosis treatment

Review of the international clinical practice guidelines for the treatment of lung infections caused by nontuberculous mycobacteria

Non-tuberculous mycobacteria (NTM) include more than 190 species and subspecies. Some NTM species can cause human diseases of the lungs or extrapulmonary infections. The guidelines focus on pulmonary mycobacteriosis in adult patients without cystic fibrosis or HIV infection caused by the most common NTMs, such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among slow-growing NTMs and Mycobacterium abscessus complex among fast-growing species. Experts of American Thoracic Society (ATS), European Respiratory Society (ERS), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), and American Society for Infectious Diseases (IDSA) contributed to the development of the guidelines. A total of 31 evidence-based recommendations are provided for the diagnosis and treatment of NTM-induced lung infections.