[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.

Pneumonia due to Achromobacter xylosoxidans with a chronic course resembling non-tuberculous mycobacterial infection.

Achromobacter xylosoxidans is a common bacterium that rarely causes pneumonia. Determining whether A. xylosoxidans is the cause of lung infection in patients suspected of having chronic infectious lung disease is challenging because it can present with colonization. We report a case of a 56-year-old immunocompetent woman suspected of having non-tuberculous mycobacteria (NTM) infection on imaging examination and monitored for 3 years. Sputum examinations revealed A. xylosoxidans several times, and it was determined to be a colonization. A. xylosoxidans was isolated from bronchial lavage fluid and aspirated sputum, but no evidence of NTM was observed. She was diagnosed with A. xylosoxidans infection and given ceftazidime for 2 weeks. Her symptoms and imaging findings improved rapidly after treatment, without recurrences. A. xylosoxidans rarely causes chronic lower respiratory tract infections similar to NTM in immunocompetent patients. A. xylosoxidans may be a target for treatment when detected in lower respiratory tract specimens.

Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.

BACKGROUND: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. METHODS: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. RESULTS: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. CONCLUSIONS: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. TRIAL REGISTRATION: This study registered ClinicalTrials.gov NO. NCT05280886.

Air pollution and airborne infection with mycobacterial bioaerosols: a potential attribution of soot.

Atmospheric pollutants are hypothesized to enhance the viability of airborne microbes by preventing them from degradation processes, thereby enhancing their atmospheric survival. In this study, Mycobacterium smegmatis is used as a model airborne bacteria, and different amounts of soot particles are employed as model air pollutants. The toxic effects of soot on aerosolized M. smegmatis are first evaluated and excluded by introducing them separately into a chamber, being sampled on a filter, and then cultured and counted. Secondly, the bacteria-soot mixture is exposed to UV with different durations and then cultured for bacterial viability evaluations. The results show that under UV exposure, the survival rates of the low-, medium-, and high-soot groups are 1.1 (±0.8) %, 70.9 (±4.3) %, and 61.0 (±17.6) %, respectively. This evidence significantly enhanced survival rates by soot at all UV exposures, though the combinations of UV exposure and soot amounts revealed a changing pattern of survival rates. The possible influence by direct and indirect effects of UV-damaging mechanisms is proposed. This study indicates the soot-induced survival rate enhancements of M. smegmatis under UV stress conditions, representing the possible relations between air pollution and the extended pathogenic viability and, therefore, increased airborne infection probability.

Pathological humerus fracture due to anti-interferon-gamma autoantibodies: A case report.

BACKGROUND: Various etiologies contribute to pathological fractures, including bone infections. Recently, non-tuberculosis Mycobacterium-related bone infections among patients with anti-interferon-gamma autoantibody-induced adult-onset immunodeficiency has raised concerns in Southeast Asia, with the common presentations including osteomyelitis. However, it also rarely manifests as traumatic fractures, as reported in this case. CASE SUMMARY: A diabetic female fractured her humerus after a traumatic accident and received fixation surgery. Abnormal necrotic bone tissue and abscess formation were noted, and she was diagnosed with a pathological fracture due to non-tuberculosis Mycobacterium infection. Multiple bone involvement was also revealed in a bone scan. Anti-interferon-gamma autoantibodies were then checked due to an unexplained immunocompromised status and found to be positive. Her humerus fracture and multiple bone infections healed after steroid and anti-non-tuberculosis Mycobacterium medication treatment following fixation surgery. CONCLUSION: Comprehensive preoperative evaluations may help identify pathological fractures and guide the treatment course.

A first case report of nasopharyngeal Mycobacterium abscessus subspecies massiliense infection.

BACKGROUND: Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. CASE PRESENTATION: A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. CONCLUSION: It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

Severe Pulmonary Mycobacterium abscessus Cases Due to Co-Infection with Other Microorganisms Well Treated by Clarithromycin and Sitafloxacin in Japan.

BACKGROUND: Mycobacterium abscessus frequently causes severe infections, yet its pathophysiological features and treatment regimens have not been established. CASE REPORT: We present five cases of severe pneumonia due to Mycobacterium abscessus infection in Japan. All cases were diabetic patients, with possible acceleration to pneumonia due to co-infection with other microorganisms. However, following a short period of hospitalization and combination therapy with intravenous imipenem/cilastatin and amikacin, all the cases were successfully treated as outpatients with oral clarithromycin and sitafloxacin. CONCLUSION: M. abscessus infections can become severe in the presence of diabetes mellitus and co-infection with other chronic infectious organisms. Sitafloxacin might be a key drug in the treatment of M. abscessus infection in future.

Drastically Progressive Ethambutol-induced Optic Neuropathy after Withdrawal of Ethambutol: A Case Report and Literature Review.

Ethambutol-induced optic neuropathy (EON) is a well-known complication, although low-dose ethambutol seldom causes EON. An 85-year-old man with non-tuberculous mycobacterial lung disease was taking antibiotics, including low-dose ethambutol. On day 85 of treatment, the diagnosis of EON was made. Despite prior discontinuation, his best corrected visual acuity drastically deteriorated from 20/17 (right eye) and 20/20 (left eye) to 20/330 (right eye) and 20/1,000 (left eye) within 3 weeks, and this symptom did not resolve. To our knowledge, there have been no reported cases with drastically progressing and irreversible EON even after the withdrawal of low-dose and short-term ethambutol.

Non-tuberculosis Mycobacterium Tenosynovitis with Rice Bodies in a Patient with Systemic Lupus Erythematosus.

Infectious disease with various presentations in systemic lupus erythematosus often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic synovitis with epithelioid granuloma. A mycobacterial culture confirmed invasive mycobacterial tenosynovitis due to Mycobacterium chelonae. The patient was treated with moxifloxacin and clarithromycin and completely recovered.

Whole genome sequencing of Nontuberculous Mycobacterium (NTM) isolates from sputum specimens of co-habiting patients with NTM pulmonary disease and NTM isolates from their environment.

BACKGROUND: Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. RESULTS: We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients' NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources. CONCLUSIONS: In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.

Successful treatment of an AIDS patient with prolonged Mycobacterium avium bacteremia, high HIV RNA, HBV infection, Kaposi's sarcoma and cytomegalovirus retinitis.

We report an AIDS patient with a high HIV RNA copy number in the plasma who was successfully treated for prolonged Mycobacterium avium bacteremia and other complications. An HIV-infected patient with high fever, anemia, high alkaline phosphatase, cystic lung lesions, hepatitis B virus infection and Kaposi's sarcoma was referred to our hospital. PCR of the blood revealed Mycobacterium avium bacteremia and the time to blood culture positivity was 8 days. The HIV-1 RNA copy number in the plasma was more than ten million copies/ml and the CD4-positive T cell count was 21 cells/µL. Although the high fever resolved five days after therapy for Mycobacterium avium was started, the fever recurred just before starting anti-retroviral therapy (ART) including dolutegravir. The patient experienced repeated but self-limiting bouts of severe inflammation. Mycobacteremia was intermittently detected up to 79 days, suggesting that the recurrent episodes of inflammation were due to the intermittent dissemination of mycobacteria, and that persistent treatment is needed. Five months after the beginning of ART, the HIV-1 RNA copy number in the plasma was still 28,000 copies/ml. An HIV drug-resistance test revealed sensitivity to all anti-retroviral drugs. Eleven months after the initiation of ART, the HIV RNA copy number in the plasma decreased to 45 copies/mL and the CD4-positive T cell count recovered to 205 cells/µL. Our case also suggests that dolutegravir can be effective in cases with prolonged high levels of HIV RNA. Our findings emphasize that prompt diagnosis and persistent therapy for mycobacterial infection are important for successful treatment.

The mycma_1113 Gene from Mycobacterium abscessus subsp. massiliense is Related to Siderophore Synthesis.

Iron (Fe) homeostasis control is important for both pathogen and the host. During infection, the host reduces the access of microorganisms to iron, however, studies have shown that virulent pathogens are capable to sequester Fe from host proteins, and establish the infection. M. abscessus subsp. massiliense (Mycma), that is resistant to most drugs used against tuberculosis, was responsible for outbreaks around the world showing increased virulence when compared to other rapidly growing mycobacteria. The goal of this study was to determine whether Mycma produce siderophores and if the mycma_1113 gene expression, a putative homolog of M. tuberculosis mbtB gene located in the mbt gene cluster, is related to the synthesis of these molecules. For that, the effect of different iron concentrations on the growth of Mycma, the expression of mycma_1113 gene, and the production of siderophores was evaluated in vitro and in vivo. It is shown that Mycma produce siderophores under iron deprivation conditions and mycma_1113 gene expression was influenced by iron availability. The mycma_1113 gene expression was also increased after macrophage or in vivo infection indicating that mycobactin synthesis by Mycma could participate in the Fe sequestration from the host during infection. In conclusion, we show that Mycma produces siderophores under iron deprivation conditions and that the mycma_1113 gene is involved in this process, furthermore, this gene expression is induced during infection.

Endobronchial Non-Tuberculosis Mycobacterium Infection Presenting in a Healthy Child.

OBJECTIVES: To describe a safe and effective treatment for endobronchial Mycobacterium avium complex. METHODS: Case report and literature review. RESULTS: We present a case of endobronchial M. avium complex in a healthy child treated with serial carbon-dioxide laser excisions and antibiotic triple therapy using azithromycin, rifampin, and ethambutol. No current guideline for the treatment of these lesions in the pediatric population exists. CONCLUSIONS: In patients with airway impingement, serial endoscopic surgical resection combined with antibiotics can provide safe and effective management.

[Identification and drug susceptibility testing of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis].

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4% NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA, hsp65, ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non-tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis. The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions:Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.

Mycobacterium mageritense Parotitis in an Immunocompetent Adult.

Mycobacterium mageritense, a rapidly growing mycobacterium, is a rare clinical pathogen. Furthermore, parotitis due to non-tuberculosis mycobacterium is very rare in adults. Herein, we report the first case of M. mageritense parotitis in an immunocompetent adult. A 40-year-old man presented with swelling in a left parotid lesion. He was diagnosed with parotitis. The culture from the parotid abscess grew M. mageritense. He was unsuccessfully treated with levofloxacin monotherapy. Trimethoprim-sulfamethoxazole was added, leading to some clinical response; however, the erythema persisted despite 14 months of antibiotic therapy. Subsequently, the skin lesion was surgically removed. The antibiotic treatment was ceased a week after surgery as the postoperative course was uneventful and the lesion had improved. No recurrence was noted at 7 months after surgery. Although extremely rare, M. mageritense can cause parotitis in immunocompetent adults, and may not be sufficiently treated with antibiotics alone.

Takayasu arteritis presented with acute heart failure: case report and review of literature.

Acute heart failure due to myocarditis is not common in Takayasu arteritis, let alone in combination with thrombosis affecting both ventricles and pulmonary arteries. The concomitant infection of non-tuberculosis mycobacterium further complicates the clinical scenario and poses challenges for implementation of tailored treatments. This case report describes a teenage girl with a history of intermittent claudication and Erythema Nodosum who developed acute heart failure. Detailed clinical investigations and imaging techniques confirmed the diagnosis.

First Report in China on the Identification and Drug Sensitivity of Mycobacterium elephantis Isolated from the Milk of a Cow with Mastitis.

OBJECTIVE: In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. METHODS: Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. RESULTS: Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacterium elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. CONCLUSION: To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.

The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a channel that normally transports anions across epithelial cell membranes. The most common manifestation of CF is buildup of mucus in the airways and bacterial colonization of the lower respiratory tract, accompanied by chronic inflammation. Antibiotics are used to control CF-associated opportunistic infections, but lengthy antibiotic treatment risks the emergence of multiple-drug resistant (MDR) strains. New antimicrobial strategies are needed to prevent and treat infections in these high-risk individuals. Autophagy contributes to the control of a variety of microbial infections. For this reason, the recent discovery of functional impairment of autophagy in CF provides a new basis for understanding susceptibility to severe infections. Here, we review the role of autophagy in host defense against CF-associated bacterial and fungal pathogens, and survey pharmacologic approaches to restore normal autophagy function in these individuals. Autophagy restoration therapy may improve pathogen clearance and mitigate lung inflammation in CF airways.

Sarcoidosis: Role of non-tuberculosis mycobacteria and Mycobacterium tuberculosis.

Sarcoidosis is a granulomatous inflammatory disease that is induced by unknown antigen(s) in a genetically susceptible host. Although the direct link between Mycobacterium tuberculosis (MTB) infection and sarcoidosis can be excluded on the basis of current knowledge, non-infectious mechanisms may explain the causative role of mycobacterial antigens. Ever since sarcoidosis was first described, its relationship with tuberculosis (TB) has been under-investigated. Whereas some researchers consider sarcoidosis and TB as two examples of the same disease process, others have rejected mycobacteria as playing any causative role in sarcoidosis. Whether they are linked causally or not, clinical evidence makes a differential diagnosis between the two conditions very challenging, particularly in countries with high burden of TB. The present study analyzes the relationship between sarcoidosis and TB and its implications in clinical practice. The coincidence of TB and sarcoidosis and the higher incidence of mycobacterial DNA in biological samples of sarcoid patients have been reported by many authors. In addition, new evidence of a similarity in MTB phenotype in sarcoidosis is provided. Overall, these observations suggest that TB and sarcoidosis may not only share the same etiology, but may even be different aspects of one disease.