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Frontiers in Immunology 2021Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial... (Review)
Review
Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.
Topics: Autophagy; Drug Discovery; Humans; Mycobacterium; Mycobacterium Infections; Skin Diseases, Bacterial
PubMed: 34113346
DOI: 10.3389/fimmu.2021.674241 -
BMC Infectious Diseases Apr 2023Opportunistic infection is an under-recognized complication of Cushing's syndrome, with infection due to atypical mycobacterium rarely reported. Mycobacterium szulgai... (Review)
Review
BACKGROUND
Opportunistic infection is an under-recognized complication of Cushing's syndrome, with infection due to atypical mycobacterium rarely reported. Mycobacterium szulgai commonly presents as pulmonary infection, with cutaneous infection seldom reported in the literature.
CASE PRESENTATION
48-year-old man with a newly-diagnosed Cushing's syndrome secondary to adrenal adenoma presented with a subcutaneous mass on the dorsum of his right hand, was diagnosed with cutaneous Mycobacterium szulgai infection. The most likely source of the infection was through minor unnoticed trauma and inoculation from a foreign body. The patient's Cushing's syndrome, high serum cortisol levels and secondary immune suppression facilitated mycobacterial replication and infection. The patient was successfully treated with adrenalectomy, surgical debridement of cutaneous lesion, and a combination of rifampicin, levofloxacin, clarithromycin, and ethambutol for 6 months. There were no signs of relapse one year after cessation of anti-mycobacterial treatment. A literature review on cutaneous M. szulgai infection to further characterize the clinical characteristics of this condition, identified 17 cases of cutaneous M. szulgai infection in the English literature. Cutaneous M. szulgai infections with subsequent disease dissemination are commonly reported in immunocompromised hosts (10/17, 58.8%), as well as in immunocompetent patients with a history of breached skin integrity, such as invasive medical procedures or trauma. The right upper extremity is the most commonly involved site. Cutaneous M. szulgai infection is well controlled with a combination of anti-mycobacterial therapy and surgical debridement. Disseminated infections required a longer duration of therapy than localized cutaneous infections. Surgical debridement may shorten the duration of antibiotics.
CONCLUSIONS
Cutaneous M. szulgai infection is a rare complication of adrenal Cushing's syndrome. Further studies are needed to provide evidence-based guidelines on the best combination of anti-mycobacterial and surgical therapy for managing this rare infective complication.
Topics: Male; Humans; Middle Aged; Cushing Syndrome; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium; Skin Diseases, Bacterial
PubMed: 37101119
DOI: 10.1186/s12879-023-08253-5 -
Molecules (Basel, Switzerland) Oct 2022Unlike Tuberculosis (TB), lung disease is a highly drug-resistant bacterial infection with no reliable treatment options. De novo drug discovery is urgently needed but... (Review)
Review
Unlike Tuberculosis (TB), lung disease is a highly drug-resistant bacterial infection with no reliable treatment options. De novo drug discovery is urgently needed but is hampered by the bacterium's extreme drug resistance profile, leaving the current drug pipeline underpopulated. One proposed strategy to accelerate de novo drug discovery is to prioritize screening of advanced TB-active compounds for anti- activity. This approach would take advantage of the greater chance of homologous drug targets between mycobacterial species, increasing hit rates. Furthermore, the screening of compound series with established structure-activity-relationship, pharmacokinetic, and tolerability properties should fast-track the development of in vitro anti- hits into lead compounds with in vivo efficacy. In this review, we evaluated the effectiveness of this strategy by examining the literature. We found several examples where the screening of advanced TB chemical matter resulted in the identification of anti- compounds with in vivo proof-of-concept, effectively populating the drug pipeline with promising new candidates. These reports validate the screening of advanced TB chemical matter as an effective means of fast-tracking drug discovery.
Topics: Humans; Mycobacterium abscessus; Mycobacterium; Drug Discovery; Mycobacterium Infections, Nontuberculous; Tuberculosis; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 36296540
DOI: 10.3390/molecules27206948 -
Ocular Immunology and Inflammation Jan 2022To report clinical features and outcomes of nontuberculous mycobacteria (NTM) presenting as uveitis in HIV positive patients.
PURPOSE
To report clinical features and outcomes of nontuberculous mycobacteria (NTM) presenting as uveitis in HIV positive patients.
MATERIALS AND METHODS
Retrospective study of HIV positive patients who were diagnosed as uveitis due to NTM.
RESULTS
Six eyes of four HIV positive patients with NTM were studied. Average age at presentation was 35.5 years (range 30-38). With specific PCR primers, was detected in three patients (75%) and in one patient (25%). Culture was positive in two cases. Two eyes (33.33%) each had endophthalmitis and necrotizing retinitis like picture, one eye (16.66%) each had chorioretinitis and frosted branch angitis like. Visual acuity improved in two eyes (33.33%), worsened in three eyes (50%), and remained unchanged in one eye (16.6%).
CONCLUSIONS
NTM infection is a unique entity in immunosuppressed with poor visual outcome. PCR forms a useful tool for rapid diagnosis and timely initiation of specific anti-tuberculosis therapy.
Topics: Adult; HIV Seropositivity; Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Retrospective Studies; Uveitis
PubMed: 32813606
DOI: 10.1080/09273948.2020.1788610 -
International Journal of Molecular... Jun 2020The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of... (Review)
Review
The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.
Topics: Humans; Immunity; Incidence; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prevalence
PubMed: 32570978
DOI: 10.3390/ijms21124351 -
Journal of Infection and Chemotherapy :... Sep 2022Disseminated infections of Mycolicibacter arupensis, a slowly growing nontuberculous mycobacteria (NTM) which causes synovitis, osteomyelitis, or pulmonary infections...
Disseminated Mycolicibacter arupensis and Mycobacterium avium co-infection in a patient with anti-interferon-γ neutralizing autoantibody-associated immunodeficiency syndrome.
BACKGROUND
Disseminated infections of Mycolicibacter arupensis, a slowly growing nontuberculous mycobacteria (NTM) which causes synovitis, osteomyelitis, or pulmonary infections have rarely been reported. We report a case of disseminated M. arupensis and Mycobacterium avium co-infection in a patient with anti-interferon (IFN)-γ neutralizing autoantibody-associated immunodeficiency syndrome.
CASE PRESENTATION
A 68-year-old Japanese male without human immunodeficiency virus infection was referred with complaints of persistent low-grade fever, arthralgia of the upper limbs, and weight loss of 10 kg. Cervical and mediastinal lymphadenopathies as well as a nodular opacity in the right lung were detected, and biopsy specimens of the cervical lymph node yielded M. arupensis without evidence of malignant cells. M. arupensis was also detected in sputum and peripheral blood. Computed tomography (CT) revealed deterioration of the right supraclavicular lymphadenopathy with internal necrosis and multiple low-density splenic lesions. Bone marrow and aspirates from the cervical lymph node collected at initiation of treatment yielded M. avium. The presence of anti-IFN-γ neutralizing autoantibodies was detected, leading to a diagnosis of co-infection of M. arupensis and M. avium with anti-IFN-γ neutralizing autoantibody-associated immunodeficiency syndrome. Post initiation of treatment with clarithromycin, ethambutol, and rifabutin, his fever declined, and his polyarthritis resolved. He developed disseminated varicella zoster during treatment; however, a follow-up CT scan six months after treatment revealed improvement of the lymphadenopathies, consolidation in the right lung, and splenic lesions.
CONCLUSION
This is the first report of disseminated M. arupensis and M. avium co-infection in a patient with anti-IFN-γ neutralizing autoantibody-associated immunodeficiency syndrome.
Topics: Aged; Autoantibodies; Coinfection; Humans; Immunologic Deficiency Syndromes; Interferon-gamma; Lymphadenopathy; Male; Mycobacteriaceae; Mycobacterium Infections, Nontuberculous; Mycobacterium avium; Mycobacterium avium-intracellulare Infection
PubMed: 35691862
DOI: 10.1016/j.jiac.2022.05.018 -
Indian Journal of Ophthalmology Jan 2024Atypical mycobacteria or non-tuberculous mycobacteria (NTM) are a group of acid-fast bacteria that are pathogenic to different parts of the eye. The organisms can cause... (Review)
Review
Atypical mycobacteria or non-tuberculous mycobacteria (NTM) are a group of acid-fast bacteria that are pathogenic to different parts of the eye. The organisms can cause a spectrum of ocular infections including keratitis, scleritis, uveitis, endophthalmitis and orbital cellulitis. Trauma, whether surgical or nonsurgical, has the highest correlation with development of this infection. Common surgeries after which these infections have been reported include laser in situ keratomileusis (LASIK) and scleral buckle surgery. The organism is noted to form biofilms with sequestration of the microbe at different inaccessible locations leading to high virulence. Collection of infective ocular material (corneal scraping/necrotic scleral tissue/abscess material/vitreous aspirate, etc.) and laboratory identification of the organism through microbiologic testing are vital for confirming presence of the infection and initiating treatment. In cluster infections, tracing the source of infection in the hospital setting via testing of different in-house samples is equally important to prevent further occurrences. Although the incidence of these infections is low, their presence can cause prolonged disease that may often be resistant to medical therapy alone. In this review, we describe the various types of NTM-ocular infections, their clinical presentation, laboratory diagnosis, management, and outcomes.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Eye Infections, Bacterial; Keratitis; Eye Infections; Cornea
PubMed: 38131566
DOI: 10.4103/IJO.IJO_560_23 -
BMC Infectious Diseases Oct 2023Mycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical...
BACKGROUND
Mycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA.
CASE PRESENTATION
Two months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem-cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance.
CONCLUSIONS
Aortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective.
Topics: Male; Humans; Aged, 80 and over; Clarithromycin; Anti-Bacterial Agents; Mycobacterium abscessus; Abscess; Macrolides; Drug Resistance, Bacterial; Amikacin; Mycobacterium Infections, Nontuberculous; Cilastatin, Imipenem Drug Combination; Stents; Microbial Sensitivity Tests
PubMed: 37848843
DOI: 10.1186/s12879-023-08702-1 -
The Annals of Otology, Rhinology, and... Nov 2023To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic... (Review)
Review
OBJECTIVES
To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection.
METHODS
Case report and review of the literature.
RESULTS
A 68-year-old female with history of prior smoking, gastroesophageal reflux disease, asthma, bronchiectasis, and tracheobronchomalacia presented with a 3-month history of shortness of breath, exertional inspiratory stridor, and hoarseness. Flexible laryngoscopy demonstrated ulceration of medial aspect of right vocal fold and subglottic tissue abnormality with crusting and ulceration extending through the upper trachea. Microdirect laryngoscopy with tissue biopsies and carbon dioxide (CO2) laser ablation of disease completed, and intraoperative culture revealed positive Aspergillus and acid-fast bacilli with Mycobacterium abscessus (type of NTM). Patient began antimicrobial treatment of cefoxitin, imipenem, amikacin, azithromycin, clofazimine, and itraconazole. Fourteen months after initial presentation, patient developed subglottic stenosis with limited extension into the proximal trachea prompting CO laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis.
CONCLUSION
Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.
Topics: Female; Humans; Aged; Trachea; Constriction, Pathologic; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Larynx; Steroids
PubMed: 36951110
DOI: 10.1177/00034894231161871 -
Nontuberculous mycobacteria isolation from sputum specimens: A retrospective analysis of 1061 cases.International Journal of... 2023In recent years, with the development of laboratory methods, the frequency of nontuberculosis mycobacteria (NTM) infections has increased. The primary aim of this study...
BACKGROUND
In recent years, with the development of laboratory methods, the frequency of nontuberculosis mycobacteria (NTM) infections has increased. The primary aim of this study was to evaluate the clinical significance of therapeutic drug monitoring (TDM) growths in respiratory samples, and the secondary aim was to evaluate the treatment regimens and treatment outcomes of treatment for TDM disease.
METHODS
This study was a retrospective cohort study. Persons with NTM growth in respiratory samples admitted to the reference hospital between 2009 and 2020 were included in this study. Samples detected as NTM by the immunochromatographic rapid diagnostic test, those requested by the clinicians, species were determined by the hsp65PCRREA method. The subjects were classified into 3 groups: patients with NTM infection who received treatment (135, 12.7%), those followed up without treatment (690, 65.1%), and a last group of patients with Mycobacterium tuberculosis (TB) complex strains were isolated and received TB treatment (236, 22.2%). Initiating NTM treatment was decided in accordance with the American Thoracic Society recommendations.
RESULTS
The mean ± standard deviation age of patients was 53.8 ± 16.5 years, and 749 (70.6%) were male. In total, 278 (26.2%) out of 1061 cases had identified, and the most frequent species were MAC (81; Mycobacterium avium: 39, Mycobacterium intracellulare: 39, and MAC: 3), Mycobacterium abscessus (67), Mycobacterium kansasii (48), Mycobacterium fortuitum (23), Mycobacterium chelonae (12), Mycobacterium gordonae (11), and Mycobacterium szulgai (11). In the NTM treatment group, 116 (85.9%) of 135 patients had multiple culture positivity. Previous TB treatment history had 51 (37.8%) of 135 patients, respiratory comorbidities were evident in 37 (27.4%) of 135 patients. Thorax computed tomography imaging in 84 patients revealed nodule 38 (45.2%), consolidation 46 (54.8%), cavity 52 (61.9%), and bronchiectasis 27 (32.1%). Treatment results in the NTM treatment group were as follows: ongoing treatment 14 (10.4%), cure 64 (47.4%), default 33 (24.4%), exitus 19 (14.1%), recurrence 3 (2.2%), and refractory disease 2 (1.5%).
CONCLUSION
This is a large case series evaluating the clinical significance of NTM growths and NTM treatment in Turkey. The clinical significance of NTM growth in respiratory samples is low. Treatment success rates of NTM patients who are treated are low. Treatment defaults and mortality rates are high. New drugs and new regimens are needed.
Topics: Humans; Male; Adult; Middle Aged; Aged; Female; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Sputum; Mycobacterium; Mycobacterium chelonae
PubMed: 36926764
DOI: 10.4103/ijmy.ijmy_10_23