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1.
Int J Tuberc Lung Dis ; 25(5): 340-349, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33977901

RESUMO

Diseases due to pathogenic mycobacteria cause significant health and economic impact on humans worldwide. Although mycobacterial diseases primarily affect the lungs, the involvement of extrapulmonary organs has also gained ground, particularly among individuals with co-existing medical conditions. Besides Mycobacterium tuberculosis complex organisms, non-tuberculous mycobacteria (NTM) are also known to cause pulmonary and extrapulmonary diseases. Primary and disseminated extrapulmonary mycobacterial infections affect the brain, eye, mouth, tongue, lymph nodes of the neck, spine, bones, muscles, skin, pleura, pericardium, gastro-intestinal, peritoneum and genito-urinary system. The clinical presentation of extrapulmonary mycobacterial diseases, including systemic symptoms, of M. tuberculosis-infected cases and NTM-infected cases is similar. Moreover, extrapulmonary mycobacterial diseases are complicated by the involvement of diverse bacterial species as aetiological agents. Culture and molecular techniques are used to differentiate NTM from Mycobacterium tuberculosis and to classify sub-species of the pathogens. As sub-speciation and drug susceptibility profiling are critical factors in treating extrapulmonary NTM diseases, there are often significant delays in initiating treatment and customising the therapeutic regimen. Here, we summarise the clinical symptoms of NTM diseases in various extrapulmonary organs, and discuss the recent trends in diagnosing and treating these diseases. We also highlight the complications associated with the management of extrapulmonary NTM disease.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Testes Diagnósticos de Rotina , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas
2.
BMJ Case Rep ; 14(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980549

RESUMO

A 72-year-old man presented with tenosynovitis of the left hand's extensor tendons that had been present for several months. He was initially treated with corticosteroids, first by local injection then systemically, but with no effect. When re-evaluated, the patient had developed a rash, and the symptoms had spread locally to surrounding structures. At this point, the patient added to the medical history that he had been stung by a sculpin a month before the debut of symptoms. Based on this, the patient's involved area was biopsied, and subsequent microbiology findings proved consistent with Mycobacterium marinum infection. By the time of diagnosis, the patient had soft tissue involvement, arthritis and osteomyelitis with an overlying rash. This case emphasises the need for reassessment when treatment is not effective and for further investigations of the medical history to establish the correct diagnosis and treatment.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium marinum , Osteomielite , Tenossinovite , Idoso , Biópsia , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Tenossinovite/diagnóstico , Tenossinovite/terapia
6.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653829

RESUMO

A 69-year-old man renal transplant recipient for 4 years, presented with 4-day history of cough and dyspnoea. He was diagnosed with community-acquired pneumonia and treated accordingly. He deteriorated requiring intensive care unit admission and intubation. Mycobacterial culture from bronchoalveolar lavage grew colonies within 7 days of incubation while Mycobacterium tuberculosis PCR was negative. The antibiotic regimen was adjusted to cover for rapidly growing mycobacteria with imipenem, amikacin and clarithromycin. The final culture reported Mycobacterium cosmeticum He improved on the antibiotic regimen given which the organism turned to be sensitive to. We reported the second case with M. cosmeticum that fulfilled the diagnostic criteria for non-tuberculous mycobacterial lung infection. Improvement of patient's lung infection on appropriate antibiotics points to a causal relationship.


Assuntos
Transplante de Rim , Infecções por Mycobacterium não Tuberculosas , Idoso , Amicacina , Claritromicina/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Masculino , Mycobacteriaceae , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico
7.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33570485

RESUMO

Introduction. Mycobacterium abscessus complex (MABC) is an infectious agent associated with macrolide resistance and treatment failure.Hypothesis/Gap Statement. Despite drug-susceptibility testing for MABC isolates including clarithromycin (CAM), long-term treatment with azithromycin (AZM) for MABC disease is recommended.Aim. We compared phenotypic and genotypic resistance to AZM and CAM in clinical isolates and evaluated the accumulation of intrinsic macrolide resistance (AIM) and morphological changes by macrolides exposure.Methodology. Forty-nine isolates were characterized regarding erm(41) sequevars. Sequencing data were compared to the nucleotide sequence of rrl and whiB7. The AIM MIC was performed in three reference strains and 15 isolates were randomized [each set of five isolates with M. abscessus subsp. abscessus (MAA) T28, MAA C28 and subsp. massiliense (MAM)].Results. The 49 isolates were distributed as 24 MAA T28, 5 MAA C28 and 20 MAM. The MIC50 values to CAM at day 3 in MAA T28, C28 and MAM were 1, 0.12 and 0.12 µg ml-1, while those at day 14 were 32, 0.5 and 0.12 µg ml-1, respectively. The AZM-MIC50 values at day 3 of the above isolates were 4, 0.25 and 0.5 µg ml-1, while those at day 14 were >64, 0.5 and 0.5 µg ml-1, respectively. Neither mutations in rrl of MAA T28 with acquired resistance nor deletions in whiB7 of MAA T28 without inducible resistance were observed . For AIM MIC, MAA T28 showed that the time-to-detection of AZM resistance was significantly faster over that of CAM (P<0.05). Morphological changes were not determined in all isolates.Conclusion. Our findings did not support the suggestion for the preferential use of AZM for, at least, MAA T28 disease due to the high-level MIC value and the increased AIM. The long duration of AZM-based treatment eventually may favour the emergence of isolates with a high-level of intrinsic resistance.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Mycobacterium abscessus/isolamento & purificação , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Proteínas de Bactérias/genética , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/genética , Fenótipo
9.
Carbohydr Polym ; 258: 117686, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593559

RESUMO

In this study, curdlan sulphate - chitosan nanoparticles were prepared through polyelectrolyte complexing at a mass ratio of 2:1 respectively. The curdlan was produced by fermentation with Agrobacterium sp. ATCC 31750, which was then sulphated to form the polyanionic polymer. A first-line tuberculosis drug, Rifampicin and a phytochemical, DdPinitol, were encapsulated into Curdlan Sulphate (CS) - Chitosan Nanoparticles (C) (CSC NPs) of size 205.41 ± 7.24 nm. The drug release kinetics followed a Weibull model with initial burst release (48 % Rifampicin and 27 % d-Pinitol within 6 h), followed by a sustained release. The prepared CSC: d-PIN + RIF NPs was cytocompatible and entered the M.smegmatis infected macrophages through multiple endocytic pathways including clathrin, caveolae and macropinocytosis. They showed superior bactericidal activity (2.4-2.7 fold) within 4 h when compared to free drug Rifampicin (1.6 fold). The drug encapsulated CSC: RIF suppressed the pro-inflammatory gene (TNF-α by 3.66 ± 0.19 fold) and CSC: d-PIN + RIF increased expression of the anti-inflammatory gene (IL-10 by 13.09 ± 0.47 fold). Expression of TGF- ß1 gene also increased when treated with CSC: d-PIN + RIF (13.00 ± 0.19 fold) which provided the immunomodulatory activity of the encapsulated CSC NPs. Thus, curdlan sulphate - chitosan polyelectrolyte complex can be a potential nanocarrier matrix for intracellular delivery of multiple drugs.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Macrófagos/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium smegmatis/efeitos dos fármacos , beta-Glucanas/química , Animais , Sobrevivência Celular , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose , Concentração de Íons de Hidrogênio , Inflamação , Cinética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Nanopartículas/química , Polieletrólitos/química , Polímeros/química , Células RAW 264.7 , Rifampina/farmacologia
10.
J Paediatr Child Health ; 57(1): 15-18, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404128

RESUMO

Nontuberculous mycobacteria (NTM) are ubiquitous organisms in our surrounding environment. Four distinct clinical syndromes associated with NTM infection have been described: skin and soft tissue disease, lymphadenitis, disseminated disease and pulmonary disease. In children, lymphadenitis is the most common NTM clinical entity, particularly affecting those aged 1-5 years who have no known risk factors for disease. Optimal management of NTM lymphadenitis is not entirely clear, although surgical intervention is likely a definitive therapy. Disseminated NTM disease is uncommon and only seen in the setting of immunocompromise. In previously well children, this presentation should always lead to consideration of an underlying immune defect, such as Mendelian susceptibility to mycobacterial disease. Identification of the underlying cause enables more targeted therapy and better prognostic understanding. Pulmonary NTM disease is fundamentally different to the other clinical syndromes, presenting in different hosts, who have different comorbidities, and follow a different clinical course.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Criança , Pré-Escolar , Humanos , Lactente , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Pneumopatias/terapia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas , Prognóstico , Fatores de Risco
13.
Artigo em Inglês | MEDLINE | ID: mdl-33358987

RESUMO

OBJECTIVE: Chronic cervicofacial lymphadenitis in children is often caused by nontuberculous mycobacteria (NTM). Children with NTM infection who were not surgically treated were evaluated for long-term outcome with a follow-up of at least 10 years. RESULTS: Among the 117 nonsurgically treated children, the median age was 46 months (range, 9-155 months), 56 were male (47.9%), and 61 were female (52.1%). Of the overall group, 75 received antibiotic therapy consisting of clarithromycin and rifabutin (64.1%), and for 54, observation (a wait-and-see approach) was chosen (46.2%). In 100 patients, treatment was considered successful (85%), with a median resolution of 24 (range, 11-134) weeks in the antibiotic group compared to 44.5 (range, 18-130) weeks in the wait-and-see group (P < .05). After 6 months, 58 patients in the antibiotic group were successfully treated (77%), whereas 42 patients of the wait-and-see group demonstrated complete resolution after a median observation time of 44.5 weeks (100%). In 10 patients who experienced complete resolution of the lymphadenitis, infection recurrence developed years later (10%). CONCLUSION: Nonsurgical treatment of NTM infection can be considered an alternative in advanced and surgically challenging cases. However, healing will take months to years, and late recurrences are possible.


Assuntos
Linfadenite , Infecções por Mycobacterium não Tuberculosas , Tuberculose , Antibacterianos/uso terapêutico , Criança , Claritromicina/uso terapêutico , Feminino , Humanos , Lactente , Linfadenite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Resultado do Tratamento
14.
J Formos Med Assoc ; 120(1 Pt 2): 524-532, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32631707

RESUMO

BACKGROUND/PURPOSE: Mycobacterium gordonae is a ubiquitous environmental mycobacteria and has been long considered an opportunistic pathogen, causing infections only in immunocompromised hosts. Cases of M. gordonae related infections in immunocompetent host have rarely been reported, and the pathogenicity of M. gordonae remained uncertain. METHODS: From January 2016 to December 2018, seven cases of M. gordonae infection were diagnosed and treated at National Taiwan University Hospital. RESULTS: Six cases had at least one underlying disease affecting immune status, while one case had no identifiable underlying disease. The sites of infection were lung (n = 3), skin and soft tissue (n = 3), and one had disseminated disease involving the lung and bone marrow. All patients were cured after anti-mycobacterial treatment, except one patient died of refractory leukemia. CONCLUSION: Compatible with the literature reports, we demonstrate that M. gordonae could be pathogenic and causing infection not only in the immunocompromised host, but also in the otherwise healthy population. Multi-antimicrobial combination and adequate source control could have good therapeutic effect for patients with M. gordonae infections.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Antibacterianos/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Taiwan
16.
BMJ Case Rep ; 13(12)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33318281

RESUMO

Mycobacterium marinum is a slow-growing, acid-fast bacillus in the category of non-tuberculous mycobacteria which most commonly cause skin and soft tissue infections in patients, particularly those with aquatic exposure. Classically, M. marinum skin and soft tissue infections clinically manifest with formation of nodular or sporotrichoid extremity lesions, or deeper space infections such as tenosynovitis and osteomyelitis. Disseminated disease may occur in immunocompromised hosts. M. marinum is a slow-growing organism that is challenging to culture, as it typically requires 5-14 days (yet may take up to several weeks) with low temperatures of approximately 30°C to yield growth. In terms of treatment, further data are needed to elucidate the optimal regimen and duration for M. marinum infections. Combination therapy with clarithromycin and ethambutol is recommended for treatment of skin and soft tissue infections, with addition of rifampicin for deeper space infections. Surgery may be needed in addition to medical management.


Assuntos
Traumatismos dos Dedos/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium marinum/isolamento & purificação , Dermatopatias Bacterianas/diagnóstico , Infecções dos Tecidos Moles/diagnóstico , Antibacterianos/uso terapêutico , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Radiografia , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/etiologia , Dermatopatias Bacterianas/patologia , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/etiologia , Infecções dos Tecidos Moles/patologia , Resultado do Tratamento
18.
BMC Infect Dis ; 20(1): 708, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993546

RESUMO

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.


Assuntos
Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle
19.
PLoS One ; 15(9): e0239146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976521

RESUMO

The first objective of this study was to determine the GenoType NTM-DR assay performance for subspecies identification in Mycobacterium abscessus complex isolates. The second objective was to evaluate the GenoType NTM-DR assay ability to detect clarithromycin and amikacin resistance in M. abscessus complex isolates compared with drug susceptibility testing (DST) and PCR sequencing of the erm(41), rrl and rrs genes. The concordance between the GenoType NTM-DR and MLST results concerning subspecies identification was 100%. The wild type and mutated alleles of the rrl and rrs genes were detected by the GenoType NTM-DR assay and PCR sequencing with 100% (115/115) agreement. Similarly, 100% concordance between GenoType NTM-DR and DST was observed for clarithromycin and amikacin testing. Sensitivity for the detection of clarithromycin and amikacin resistance was 100%. The GenoType NTM-DR assay provides a robust and complementary tool to the gold standard methods (MLST and broth microdilution) for subspecies identification and drug resistance detection.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Técnicas de Genotipagem/instrumentação , Testes de Sensibilidade Microbiana/instrumentação , Mycobacterium abscessus/genética , Kit de Reagentes para Diagnóstico , Amicacina/farmacologia , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Análise Mutacional de DNA/instrumentação , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Genes Bacterianos/genética , Humanos , Tipagem de Sequências Multilocus , Mutação , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/isolamento & purificação , Reação em Cadeia da Polimerase
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