[A case of silicosis complicated with non-tuberculous mycobacterium pulmonary disease].

Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.

Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Why do we use 100†mg of clofazimine in TB and NTM treatment?

Current tuberculosis and non-tuberculous mycobacterial disease guidelines recommend the use of clofazimine in a 100 mg once-daily dose. The rationale behind this exact dose is not provided. I performed a literature review to determine the reasoning behind the current dosing regimen. The current 100 mg once-daily dose of clofazimine stems from a deliberate attempt to find the minimum effective daily dose in leprosy treatment, driven by efficacy, economical and toxicity considerations. While this dose is safe, economical and practical, a higher dose with a loading phase may add relevant efficacy and treatment-shortening potential to both tuberculosis and non-tuberculous mycobacterial disease treatment. We need to revisit dose-response and maximum tolerated dose studies to get the best out of this drug, while continuing efforts to generate more active r-iminophenazine molecules that accumulate less in skin and intestinal tissues and have pharmacokinetic properties that do not require loading doses.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.

Nontuberculous Mycobacterial Infections in Cystic Fibrosis.

Nontuberculous mycobacteria (NTM) are important pathogens, with a longitudinal prevalence of up to 20% within the cystic fibrosis (CF) population. Diagnosis of NTM pulmonary disease in people with CF (pwCF) is challenging, as a majority have NTM infection that is transient or indolent, without evidence of clinical consequence. In addition, the radiographic and clinical manifestations of chronic coinfections with typical CF pathogens can overlap those of NTM, making diagnosis difficult. Comprehensive care of pwCF must be optimized to assess the true clinical impact of NTM and to improve response to treatment. Treatment requires prolonged, multidrug therapy that varies depending on NTM species, resistance pattern, and extent of disease. With a widespread use of highly effective modulator therapy (HEMT), clinical signs and symptoms of NTM disease may be less apparent, and sensitivity of sputum cultures further reduced. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in pwCF is a research priority, as a lifelong strategy is needed for this high-risk population.

Epidemiology of infection by pulmonary non-tuberculous mycobacteria in French Guiana 2008-2018.

INTRODUCTION: Unlike diseases caused by Mycobacterium tuberculosis, M. leprae and M. ulcerans, the epidemiology of pulmonary non-tuberculous mycobacteria (PNTM) has not received due attention in French Guiana. The main objective of the current study was to define the incidence of these PNTM infections: NTM pulmonary diseases (NTM-PD) and casual PNTM isolation (responsible of latent infection or simple colonization). The secondary objectives were to determine species diversity and geographic distribution of these atypical mycobacteria. METHODS: A retrospective observational study (2008-2018) of French Guiana patients with at least one PNTM positive respiratory sample in culture was conducted. Patients were then classified into two groups: casual PNTM isolation or pulmonary disease (NTM-PD), according to clinical, radiological and microbiological criteria defined by the American Thoracic Society / Infectious Disease Society of America (ATS / IDSA) in 2007. RESULTS: 178 patients were included, out of which 147 had casual PNTM isolation and 31 had NTM-PD. Estimated annual incidence rate of respiratory isolates was 6.17 / 100,000 inhabitants per year while that of NTM-PD was 1.07 / 100,000 inhabitants per year. Among the 178 patients, M. avium complex (MAC) was the most frequently isolated pathogen (38%), followed by M. fortuitum then M. abscessus (19% and 6% of cases respectively), the latter two mycobacteria being mainly found in the coastal center region. Concerning NTM-PD, two species were mainly involved: MAC (81%) and M. abscessus (16%). DISCUSSION/CONCLUSION: This is the first study on the epidemiology of PNTM infections in French Guiana. PNTM's incidence looks similar to other contries and metropolitan France and NTM-PD is mostly due to MAC and M.abscessus. Although French Guiana is the French territory with the highest tuberculosis incidence, NTM should not be overlooked.

Photoinactivation of non-tuberculous mycobacteria using Zn-phthalocyanine loaded into liposomes.

Non-tuberculous mycobacteria are a heterogeneous group of environmental bacteria and other than the well-known Mycobacterium tuberculosis complex and Mycobacterium leprae. They could cause localized or disseminated infections. Mycobacterium chelonae and Mycobacterium fortuitum are among the most clinically relevant non-tuberculous mycobacteria species. The infections treatment is complex since they are resistant to antituberculosis drugs and the biofilm formation makes them impermeable to several antibiotics. Antimicrobial photodynamic therapy (aPDT) constitutes an alternative to eliminate pathogens, principally those antimicrobials resistant. Among explored photosensitizers, phthalocyanines are considered excellent, but with a disadvantage: a lack solubility in aqueous media. Consequently, several nanocarriers have been studied in the last years. In this work, a Zn-phthalocyanine into liposomes was evaluated to photoinactivate M. fortuitum and M. chelonae. The results show a higher photodynamic activity of ZnPc into liposomes respect to solution. Furthermore, M. fortuitum was more sensible to aPDT than M. chelonae.

Pulmonary mycobacteriosis of sitatunga antelope caused by M. avium ssp. hominissuis.

INTRODUCTION AND OBJECTIVE: Mycobacteriosis are diseases caused by acid-fast mycobacteria other than M. leprae and tuberculous mycobacteria. Animal mycobacteriosis is often caused by M. avium ssp. hominissuis. Many species of animals are susceptible to infection with this bacterium, even those kept in Zoological Gardens. The aim of the study was to determine the species of bacterium responsible for causing the disease in the tested animals. MATERIAL AND METHODS: Tissue samples of two male sitatunga antelopes (Tragelaphus spekii) were analyzed. Lymph node and lung samples were subjected to anatomical examination and Ziehl-Neelsen staining. Real-time PCR was performed to confirm or rule out tuberculosis mycobacteria infection. In order to isolate the bacterial strain, tissue samples were inoculated on both solid and liquid media. HainLifescience CM tests, mass spectrometry and New Generation Sequencing were used to determine the mycobacterial species. RESULTS: Results showed that atypical mycobacteria are responsible for the antelope disease. The results of the HainLifescience CM test and mass spectrometry indicated that the mycobacterium responsible for causing mycobacteriosis was M. avium. New Generation Sequencing helped to identified a subspecies that was M. avium ssp. hominissuis. CONCLUSIONS: The sitatunga antelope is an animal susceptible to infection by M. avium ssp. hominissuis. Considering the wide range of hosts and the easiness of interspecies transmission of the pathogen, as well as its zoonotic nature, the mycobacteriosis induced by this microorganism should not be underestimated.

Nontuberculous Mycobacterial Infections.

Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae constitute nontuberculous mycobacteria (NTM). NTM infections are on the rise, particularly in the Western world. They cause a wide range of pulmonary and systemic manifestations. The 2 most common types are as follows: classical cavitary type, seen with preexisting lung disease, and the nonclassical bronchiectatic type, seen in elderly women without preexisting lung disease. Disseminated infections by the hematogenous route are common in immunocompromised patients including those with HIV. Imaging plays a key role in the diagnosis and monitoring of NTM infection.

Skin infection by Mycobacterium marinum - diagnostic and therapeutic challenge.

The number of skin infections caused by atypical mycobacteria has increased in recent decades. They usually appear after contact with wounds and interruptions in the integrity of the skin. The present report describes a case of cutaneous infection by Mycobacterium marinum, in a young, immunocompetent patient, with a prolonged evolution, diagnosed through a skin lesion culture (from a spindle biopsy of the skin). The patient was treated with multidrug therapy, including clarithromycin, doxycycline, and rifampicin, due to the lesion extent, with satisfactory results. A brief review of the literature is also provided.

Mycobacterial skin infection.

PURPOSE OF REVIEW: The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021. RECENT FINDINGS: Mycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned. SUMMARY: Mycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.

Non-tuberculous cutaneous mycobacterioses

Abstract Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.

Non-tuberculous cutaneous mycobacterioses.

Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.

Mycobacteria: Selection of Transplant Candidates and Post-lung Transplant Outcomes.

Mycobacterium is a large, clinically relevant bacterial genus made up of the agents of tuberculosis and leprosy and hundreds of species of saprophytic nontuberculous mycobacteria (NTM). Pathogenicity, clinical presentation, epidemiology, and antimicrobial susceptibilities are exceptionally diverse between species. Patients with end-stage lung disease and recipients of lung transplants are at a higher risk of developing NTM colonization and disease and of severe manifestations and outcomes of tuberculosis. Data from the past three decades have increased our knowledge of these infections in lung transplant recipients. Still, there are knowledge gaps to be addressed to further our understanding of risk factors and optimal treatments for mycobacterial infections in this population.

Arthroscopic treatment of Mycobacterium massiliense septic arthritis outbreak after intra-articular injection: A case-series report and literature review.

ABSTRACT: Non-tuberculous mycobacteria (NTM) comprise mycobacteria, with the exceptions of Mycobacterium (M.) leprae and the M. tuberculosis complex. Septic arthritis caused by NTM is so rare that there is no standardized treatment.Between April and September 2012, 27 patients were infected with M. massiliense in a single clinic following injection of steroid in the knee joint. Clinical data of 9 patients who received arthroscopic treatment in Seoul Hospital of Soonchunhyang University were analyzed retrospectively.Arthroscopic irrigation and debridement were performed average 2.6 times (1-3 times). As 6 out of 9 cases (67%) had joint contracture of the knee joint, arthroscopic adhesiolysis, and brisement were performed. After surgical procedures, Hospital for Special Surgery and Lysholm knee score showed improvement compared before the surgery, but a radiographic result evaluated by Kellgren-Lawrence revealed that 6 cases got deteriorated to stage 4 in the 4-year follow-up.NTM septic arthritis had a higher recurrence and a higher contracture incidence than septic arthritis caused by tuberculous mycobacteria or other bacteria. Treatment was possible with repeated arthroscopic debridement and intravenous antibiotics.

Clofazimine in Mycobacterium abscessus peritonitis: A pediatric case report.

Peritonitis- and catheter-related infections due to nontuberculous mycobacteria (NTM) including Mycobacterium abscessus have been reported among adults on peritoneal dialysis (PD). There is no recommended antimicrobial regimen for the treatment of M. abscessus peritonitis. Clofazimine has emerged as an important adjuvant antimicrobial treatment of M. abscessus lung infection. We report, to our knowledge, the first case of M. abscessus PD peritonitis in a child treated successfully using clofazimine as a novel adjuvant therapy to amikacin and clarithromycin. Her clinical features were similar to those of bacterial peritonitis, but she had persistence of symptoms and high inflammatory markers despite empirical therapy for peritonitis. Bacterial culture of PD effluent became positive for M. abscessus after 5 days. There was complete symptom resolution after 6 days of multidrug therapy. Due to ototoxicity, amikacin was discontinued after 6 weeks, while clarithromycin and clofazimine were continued for 9 months to ensure complete pathogen eradication before a planned renal transplant. A high index of suspicion in refractory or culture-negative cases is important for the diagnosis of NTM peritonitis. Multidrug therapy is recommended for M. abscessus infections. Clofazimine was chosen as a novel adjunct antimicrobial because of its pharmacokinetics, ease of administration, cost-effectiveness, and lack of serious adverse events.