RESUMEN
Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii (sensu stricto), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii's increased virulence and drug resistance.
Asunto(s)
Genoma Bacteriano , Genómica , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Filogenia , Mycobacterium kansasii/genética , Mycobacterium kansasii/clasificación , Mycobacterium kansasii/aislamiento & purificación , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Animales , Virulencia/genéticaRESUMEN
Mycobacterium kansasii is a bacterium included in non-tuberculous mycobacteria (NTM) that can cause lung disease. It shares a significant number of antigens with Mycobacterium tuberculosis (Mtb), suggesting that it has the potential to be used as a tuberculosis (TB) vaccine. Therefore, we subcutaneously vaccinated mice with reference strain, M. kansasii-ATCC12478 [M. kansasii-American Type Culture Collection (ATCC)], and clinically isolated strain, M. kansasii-SM-1 to evaluate potential as a TB vaccine by comparing with bacille Calmette-Guerin (BCG) vaccine. Ten weeks after vaccination, we evaluated immunogenicity of M. kansasii-ATCC and M. kansasii-SM-1, and M. kansasii-SM-1 immunization induces potent Mtb antigen-specific IFN-γ-producing CD4+ T cells than M. kansasii-ATCC. Upon Mtb infection, M. kansasii-SM-1 provided better protection than M. kansasii-ATCC, which was comparable to the efficacy of BCG. These results showed that the clinical strain M. kansasii-SM-1, which exhibits an enhanced Mtb antigen-specific Th1 response, shows greater vaccine efficacy compared to M. kansasii-ATCC. In this study, we demonstrated that vaccine efficacy can vary depending on the strain of M. kansasii and that its efficacy can be comparable to BCG. This suggests that M. kansasii has the potential to be a live TB vaccine candidate.IMPORTANCEMycobacterium kansasii, a non-tuberculous mycobacteria (NTM) species causing lung disease, shares key antigens with Mycobacterium tuberculosis (Mtb), indicating its potential for TB vaccine development. Subcutaneous vaccination of mice with M. kansasii strains reference strain M. kansasii-ATCC12478 [(M. kansasii-American Type Culture Collection (ATCC)] and clinically isolated strain M. kansasii-SM-1 revealed differences in immunogenicity. M. kansasii-SM-1 induced a robust Mtb antigen-specific IFN-γ-producing CD4+ T cell response compared to M. kansasii-ATCC. Additionally, M. kansasii-SM-1 conferred better protection against Mtb infection than M. kansasii-ATCC, which is comparable to bacille Calmette-Guerin (BCG). These findings underscore the variable vaccine efficacy among M. kansasii strains, with M. kansasii-SM-1 exhibiting promising potential as a live TB vaccine candidate, suggesting its comparative effectiveness to BCG.
Asunto(s)
Vacuna BCG , Mycobacterium kansasii , Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Tuberculosis , Animales , Mycobacterium kansasii/inmunología , Mycobacterium kansasii/aislamiento & purificación , Ratones , Mycobacterium tuberculosis/inmunología , Vacunas contra la Tuberculosis/inmunología , Tuberculosis/prevención & control , Tuberculosis/microbiología , Tuberculosis/inmunología , Femenino , Vacuna BCG/inmunología , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/prevención & control , Infecciones por Mycobacterium no Tuberculosas/inmunología , Linfocitos T CD4-Positivos/inmunología , Inmunogenicidad Vacunal , Antígenos Bacterianos/inmunología , Vacunación , Interferón gamma/inmunología , Interferón gamma/metabolismo , Ratones Endogámicos C57BLRESUMEN
Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Filogeografía , Humanos , Mycobacterium kansasii/genética , Mycobacterium kansasii/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Taiwán/epidemiología , Anciano , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/epidemiología , Filogenia , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Riesgo , Secuenciación Completa del GenomaRESUMEN
This report details a rare case of surgical site infection (SSI) caused by Mycobacterium kansasii following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a 53-year-old patient with IgA-κ type multiple myeloma. After undergoing multiple chemotherapy regimens and two stem cell transplants, the patient developed an SSI 31-month post-transplantation, manifesting as an intracranial abscess at the site of a previous craniotomy. M. kansasii was isolated from the drainage fluid, marking this instance as a unique case in the literature of nontuberculous mycobacteria (NTM) infection post-allo-HSCT with such a delayed onset. The patient's treatment included targeted antimicrobial therapy based on susceptibility testing, resulting in eventual resolution of the infection, although the patient later succumbed to multiple myeloma relapse. This case underscores the critical need to consider NTM infections in the differential diagnosis of persistent fevers and SSIs in immunocompromised patients, particularly those with chronic graft-versus-host disease. It highlights the importance of early diagnostic and therapeutic interventions to manage these infections effectively. This report contributes to the limited but growing body of literature on NTM infections post-allo-HSCT and emphasizes the need for vigilance in monitoring postoperative patients, especially those with prolonged immunosuppression.
Asunto(s)
Antibacterianos , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Infección de la Herida Quirúrgica , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/etiología , Mycobacterium kansasii/aislamiento & purificación , Persona de Mediana Edad , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/etiología , Masculino , Mieloma Múltiple/terapia , Antibacterianos/uso terapéutico , Trasplante Homólogo/efectos adversos , Huésped Inmunocomprometido , Resultado FatalRESUMEN
OBJECTIVE: To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai. METHODS: A population-based retrospective study was conducted using presumptive pulmonary tuberculosis surveillance data of Shanghai between 2010 and 2019. The study described the spatial distribution of NTM-PD notification rates, employing hierarchical Bayesian mapping for high-risk areas and the Getis-Ord Gi* statistic to identify hot spots and explore associated factors. RESULTS: Of 1652 NTM-PD cases, the most common species was Mycobacterium kansasii complex (MKC) (41.9%), followed by Mycobacterium avium complex (MAC) (27.1%) and Mycobacterium abscessus complex (MABC) (16.2%). MKC-PD patients were generally younger males with a higher incidence of pulmonary cavities, while MAC-PD patients were more often farmers or had a history of tuberculosis treatment. MKC-PD hot spots were primarily located in the areas alongside the Huangpu River, while MAC-PD hot spots were mainly in the western agricultural areas. Patients with MKC-PD and MAC-PD exhibited a higher risk of spatial clustering compared to those with MABC-PD. CONCLUSIONS: Different types of NTM-PD exhibit distinct patterns of spatial clustering and are associated with various factors. These findings underscore the importance of environmental and host factors in the epidemic of NTM-PD.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , China/epidemiología , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Mycobacterium kansasii/aislamiento & purificación , Micobacterias no Tuberculosas/aislamiento & purificación , Teorema de Bayes , Incidencia , Análisis Espacial , Factores de Riesgo , Adulto Joven , Complejo Mycobacterium avium/aislamiento & purificación , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología , Mycobacterium abscessus/aislamiento & purificaciónRESUMEN
Mycobacterium kansasii, an important opportunistic pathogen of humans, causes serious pulmonary disease. Sixty M. kansasii isolates were collected for investigating the clinical characteristics of patients with M. kansasii infections as well as drug susceptibility and genotypes of M. kansasii. More than 90% of the patients infected with M. kansasii were from eastern China. According to the internal transcribed spacers (ITS), rpoB, hsp65, and tuf, all M. kansasii isolates were classified as molecular type I, irrespective of the disease manifestation. Sixty M. kansasii isolates from China were diverse and separated into four branches. Pairwise average nucleotide identity (ANI) values for M. kansasii isolates affiliated with different genotypes were more than 85%. The earliest isolate was isolated from Jiangsu in 1983. Of the isolates, 78.3% (47/60) were isolated since 1999. All isolates were sensitive to rifabutin. All but one isolate was sensitive to clarithromycin. Sensitivity rates to rifampin, amikacin, moxifloxacin, and linezolid were 80.0%, 90.0%, 88.3%, and 91.7%, respectively. A high rate of resistance was noted for ciprofloxacin (44 isolates, 73.3%) and ethambutol (46 isolates, 76.7%). Compared with M. tuberculosis H37Rv, 12 mutations of embCA were observed in all M. kansasii isolates. All these 60 M. kansasii isolates shared identical sequences of rpoB, inhA, katG, rrl, rrs, rpsL, gyrA, and gyrB. In conclusion, M. kansasii isolates are exhibiting greater genetic diversity globally. The resistance mechanism of M. kansasii is not necessarily related to gene mutation. IMPORTANCE M. kansasii type I is the main genotype spreading worldwide. The molecular history of the global spread of type I isolates remains largely unclear. We conducted a detailed analysis of genomic evolution of global M. kansasii isolates. Our results suggest that M. kansasii isolates exhibit greater genetic diversity globally.
Asunto(s)
Antituberculosos/farmacología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/efectos de los fármacos , Mycobacterium kansasii/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , China , Farmacorresistencia Bacteriana Múltiple , Femenino , Variación Genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Mycobacterium kansasii/clasificación , Mycobacterium kansasii/genética , Adulto JovenRESUMEN
Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.
Asunto(s)
Agua Potable/microbiología , Genoma Bacteriano/genética , Enfermedades Pulmonares/epidemiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Mycobacterium kansasii/genética , Metabolismo Energético/genética , Variación Genética/genética , Genética de Población/métodos , Genómica , Humanos , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/aislamiento & purificación , Virulencia/genética , Microbiología del AguaRESUMEN
We report a case of a retired school teacher who presented with rapid cognitive and functional decline following the COVID-19 lockdown period that was diagnosed as worsening depression by referring physician. This highlights the potentially life-threatening consequences of delayed diagnosis and management of delirium, an often reversible syndrome, due to lockdown restrictions. As the pandemic outlives its initial projections, its downstream impact on an already vulnerable population continues to emerge.
Asunto(s)
COVID-19 , Diagnóstico Tardío , Delirio/etiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium kansasii/aislamiento & purificación , Anciano , Humanos , Hipercalcemia/sangre , Soledad , Pandemias , SARS-CoV-2 , Aislamiento SocialRESUMEN
Nontuberculous mycobacterial (NTM) infections in humans have increased in prevalence in recent decades. Mycobacterium kansasii is one of the most prevalent human pathogenic NTM species worldwide. Herein, we report the first isolation of M. kansasii from an indoor domestic cat in Japan. Comparative genome sequence analysis of the feline isolate showed this pathogen is genetically identical to human pathogenic M. kansasii. This finding suggests that M. kansasii has a potential risk of zoonoses and requires the "One Health" approach to control NTM infection.
Asunto(s)
Zoonosis Bacterianas/microbiología , Enfermedades de los Gatos/microbiología , Infecciones por Mycobacterium no Tuberculosas/veterinaria , Mycobacterium kansasii/aislamiento & purificación , Mascotas/microbiología , Animales , Zoonosis Bacterianas/transmisión , Gatos , Femenino , Humanos , Japón , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/transmisión , Mycobacterium kansasii/clasificación , Mycobacterium kansasii/genética , FilogeniaRESUMEN
Mycobacterium kansasii is an opportunistic pathogen that causes both intrapulmonary and extrapulmonary infections. The symptoms of the pulmonary diseases caused by M. kansasii closely resemble Mycobacterium tuberculosis. Rapid and accurate differentiation of M. kansasii from M. tuberculosis, as well as other mycobacteria, is crucial for developing effective therapeutics and disease treatment. In this study, we combined loop-mediated isothermal amplification (LAMP) with lateral flow biosensors (LFB) to detect M. kansasii, by targeting the species-specific sequence of rpoB, a gene which encodes the ß subunit of bacterial RNA polymerase. The assay was validated to ensure that it was highly selective by testing M. kansasii, M. tuberculosis, other species of respiratory bacteria, and other nontuberculous mycobacteria. The detection limit of the assay was 1 fg/µL of DNA and 50 CFU of bacilli in sputum. The M. kansasii-LAMP-LFB assay is a fast, cheap, and accurate method for detecting M. kansasii by constant temperature amplification and simple interpretation.
Asunto(s)
Técnicas Biosensibles/métodos , Técnicas de Diagnóstico Molecular/métodos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium kansasii/clasificación , Mycobacterium kansasii/genética , Sensibilidad y EspecificidadAsunto(s)
Huesos/diagnóstico por imagen , Imagen Multimodal/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium kansasii/aislamiento & purificación , Adulto , Huesos/microbiología , Tos/diagnóstico , Tos/etiología , Femenino , Fiebre/diagnóstico , Fiebre/etiología , Estudios de Seguimiento , Humanos , Levofloxacino/uso terapéutico , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Imagen por Resonancia Magnética/métodos , Moxifloxacino/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Enfermedades Raras , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.
Asunto(s)
Antituberculosos/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Pulmón/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Mycobacterium kansasii/aislamiento & purificación , Brasil/epidemiología , Farmacorresistencia Microbiana , Etambutol/uso terapéutico , Femenino , Humanos , Isoniazida/uso terapéutico , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Rifampin/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Mycobacterium kansasii is one of the major non-tuberculous mycobacteria species that typically cause pulmonary diseases. M. kansasii is known to cause septic arthritis as an extrapulmonary disease in immunosuppressed patients or chronic skin disease. Herein, we present a case of M. kansasii arthritis involving the elbow of an immunocompetent patient, which was initially suspected to be a soft-tissue tumor. A 70-year-old man presented with a swollen left elbow that had progressed for 18 months with deteriorating arthralgia and limited range of motion. Magnetic resonance imaging revealed filling of the intra-articular space of the elbow and surrounding of the radial head with a soft tissue mass with mixed signal intensity. Initial incisional biopsy was performed via the lateral approach to the elbow joint, and pathological examination of the mass did not reveal any evidence of malignancy. One year after the first operation, arthroscopic surgery was performed to excise the mass following the recurrence of swelling and limited function of the elbow. Pathological examination of the resected synovium revealed epithelioid granulomas containing a multinucleated giant cell and inflammatory cell infiltration, characteristic of mycobacterial infection. M. kansasii was cultured after 2 weeks of incubation of the synovial sample. He experienced full resolution of the swelling and limited function following a combination of synovectomy and multidrug antimycobacterial treatment (rifampin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day). This case highlights the need to consider this rare infection in the differential diagnosis of intra-articular soft tissue tumor-like lesions even in immunocompetent patients.
Asunto(s)
Artritis Infecciosa/diagnóstico , Articulación del Codo/patología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium kansasii/aislamiento & purificación , Neoplasias de los Tejidos Blandos/diagnóstico , Anciano , Antibacterianos/uso terapéutico , Artritis Infecciosa/complicaciones , Artritis Infecciosa/tratamiento farmacológico , Claritromicina/uso terapéutico , Diagnóstico Diferencial , Articulación del Codo/diagnóstico por imagen , Etambutol/uso terapéutico , Humanos , Inmunocompetencia , Imagen por Resonancia Magnética , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Rifampin/uso terapéutico , Resultado del TratamientoRESUMEN
RESUMO Objetivo Avaliar características clínicas, tomográficas e microbiológicas dos pacientes com doença pulmonar causada pela M. kansasii (DPMK) atendidos em unidade ambulatorial no período 2006-2016. Métodos Estudo descritivo, em que foram analisados 38 pacientes. Foram analisadas as características demográficas, clínico-radiológicas, laboratoriais e terapêuticas. Resultados A média de idade foi 64 anos (DP=10,6; IIQ=57-72; mediana=65,0) e 22 (57,9%) eram pacientes do sexo masculino. Comorbidade pulmonar estava presente em 89,5%. A comorbidade mais frequente foi a bronquiectasia (78,9%). Tratamento anterior para tuberculose pulmonar (TBP) foi relatado em 65,9%. O esquema terapêutico mais utilizado foi rifampicina, isoniazida e etambutol (44,7%). A tomografia de tórax (TCT) mostrou bronquiectasia (94,1%), distorção arquitetural (76,5%), espessamento de septo (67,6%) e cavidades (64,7%). A doença foi bilateral em 85,2%. Houve 10,7% de resistência à rifampicina, 67,9% resistentes ao etambutol e sensibilidade à claritromicina. Conclusão Em pacientes com doença pulmonar estrutural, é importante a busca de DPMNT, principal diagnóstico diferencial com TBP. TC de tórax demonstra diferentes padrões que se sobrepõem ao de doença estrutural causada por TBP ou outras enfermidades pulmonares. Destaca-se a resistência ao etambutol, fármaco componente do esquema preconizado.
ABSTRACT Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Mycobacterium kansasii/aislamiento & purificación , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Antituberculosos/uso terapéutico , Rifampin/uso terapéutico , Brasil/epidemiología , Farmacorresistencia Microbiana , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Etambutol/uso terapéutico , Isoniazida/uso terapéutico , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnósticoRESUMEN
Disseminated nontuberculous mycobacterial (NTM) infections usually occur in severely immunosuppressed patients. These infections may also occur in previously immunocompetent patients with acquired anti-interferon-gamma antibodies (anti-IFN-γ Abs). A previously healthy 33-year-old man presented with a 3-week history of cough and fever. Chest computed tomography showed air-space consolidation in the middle lobe of the right lung and enlargement of the supraclavicular, mediastinal, and hilar lymph nodes. Tissue samples obtained via mediastinoscopy showed granuloma formation with acid-fast bacteria; cultures from the tissue revealed Mycobacterium kansasii. Accordingly, a diagnosis of disseminated M. kansasii disease was made. The positive control tested negative in the QuantiFERON-TB Gold In-tube test, suggesting the presence of anti-IFN-γ Abs. The ELISA test for anti-IFN-γ Abs demonstrated an increased titer. Antimycobacterial drug treatments were initiated after diagnosis. His symptoms improved over 2 months, and he remains well on outpatient management. Disseminated M. kansasii disease is a very rare condition suggestive of immunosuppression. Testing for anti-IFN-γ antibodies might be important in all cases of disseminated M. kansasii disease.
Asunto(s)
Autoanticuerpos/inmunología , Huésped Inmunocomprometido , Interferón gamma/inmunología , Linfadenitis/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/aislamiento & purificación , Adulto , Humanos , Linfadenitis/patología , Masculino , Infecciones por Mycobacterium no Tuberculosas/diagnósticoRESUMEN
BACKGROUND: GATA2 is a transcription factor that is a critical regulator of gene expression in hematopoietic cells. GATA2 deficiency presents with multi-lineage cytopenia, mycobacterial, fungal and viral infections. Patients with GATA2 mutation have a high risk of developing myelodysplastic syndrome or acute myeloid leukemia. CASE PRESENTATION: We described a 43 years-old white male with 20-year follow-up of autoimmune and thrombotic phenomena, hypothyroidism, disseminated refractory Mycobacterium kansasii infection and MonoMAC syndrome. GATA2 c.1061 C > T; p.T354 M mutation was identified after he progressed from myelodysplastic pancytopenia to refractory anemia with excess blasts type II. His relatives were also investigated and he underwent unsuccessful haematopoietic stem cell transplantation. We discuss the clinical features, genetic diagnosis and treatment of this immunodeficiency disorder. CONCLUSIONS: This case illustrates the challenge how a multidisciplinary disease should be handle. Once usual causes of immunodeficiency were excluded, clinicians should considerGATA2 deficiency in patients with myelodysplasia and long-standing Mycobacterium kansasii infection.
Asunto(s)
Deficiencia GATA2/genética , Factor de Transcripción GATA2/genética , Mutación , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium kansasii/aislamiento & purificación , Síndromes Mielodisplásicos/genética , Adulto , Antibacterianos/uso terapéutico , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVES: The incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, while that of tuberculosis (TB) is decreasing in many industrialized countries, including Japan. However, the long-term evaluation of clinico-epidemiological features of NTM-PD in relation to TB are limited. We aimed to clarify the long-term changes in the epidemiology and clinical features of NTM-PD in relation to those of TB at a nationally-designated TB center in Japan. METHODS: We reviewed all mycobacterial examination records at Fukujuji Hospital between 2006 and 2016. Cases of NTM-PD were defined according to the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. The current characteristics of Mycobacterium avium complex pulmonary disease (MAC-PD) were compared with those in the 1980s and circa 2000. RESULTS: We identified a total of 3,546 pulmonary TB cases and 2,155 NTM-PD cases. While the annual number of incident pulmonary TB cases remained stable over the study period (Pâ¯=â¯0.59), that of NTM-PD cases increased significantly from 165 to 278 (Pâ¯<â¯0.01). The mean age of pulmonary TB cases increased from 59.7⯱â¯16.3 to 66.2⯱â¯21.7 years, whereas that of NTM-PD cases remained unchanged. Regarding the age distribution, the greatest increases were observed in patients over 75 years for TB and in patients 50-74 years for NTM. The most common causative organism for NTM was Mycobacterium avium complex (87.3%), M. abscessus complex (5.5%) and M. kansasii (3.9%). Among patients with MAC-PD, the proportion of the nodular bronchiectatic (NB) form increased significantly from 60.0% to 84.4% between circa 2000 and 2016 (Pâ¯<â¯0.01). Significant increases in the NB form were observed in both males (33.3%-70.7%, Pâ¯<â¯0.01) and females (71.3%-89.2%, Pâ¯<â¯0.01). CONCLUSIONS: The annual number of incident NTM-PD cases increased markedly. In contrast to patients with TB, the mean age of new NTM-PD patients did not increase in the last 10 years. Among MAC-PD patients, the proportions accounted for by the NB form increased significantly in both sexes.
Asunto(s)
Enfermedades Pulmonares/epidemiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infección por Mycobacterium avium-intracellulare/epidemiología , Tuberculosis Pulmonar/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Bronquiectasia/patología , Femenino , Humanos , Incidencia , Japón/epidemiología , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/patología , Mycobacterium abscessus/aislamiento & purificación , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/microbiología , Infección por Mycobacterium avium-intracellulare/patología , Mycobacterium kansasii/aislamiento & purificación , Micobacterias no Tuberculosas/aislamiento & purificación , Derivación y Consulta , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patologíaRESUMEN
BACKGROUND: Mycobacterium kansasii is a major pathogen associated with nontuberculous mycobacterial pulmonary disease. For treatment of M. kansasii pulmonary disease, daily therapy with isoniazid, rifampin, and ethambutol is traditionally recommended. Although a regimen containing a macrolide, instead of isoniazid, has been recently recommended, supporting data are limited. We compared the treatment outcomes of a macrolide-containing regimen (macrolide group) and an isoniazid-containing regimen (isoniazid group) on patients with M. kansasii pulmonary disease. METHODS: A total of 49 patients were identified between January 2002 and December 2016. Treatment outcomes for the isoniazid group (nâ¯=â¯24) and the macrolide group (nâ¯=â¯25) were compared. RESULTS: Baseline characteristics of the isoniazid and macrolide groups were similar. Favorable outcomes did not differ between the isoniazid group (79%, nâ¯=â¯19) and macrolide group (88%, nâ¯=â¯22, Pâ¯=â¯0.463). Total treatment duration (median 17.9 months vs. 15.4 months; Pâ¯=â¯0.712) and time to culture conversion (median 2.0 months vs. 1.2 months; Pâ¯=â¯0.838) were also similar between the isoniazid and macrolide groups. Five patients who completed three-times-weekly intermittent treatment containing a macrolide for non-cavitary M. kansasii pulmonary disease achieved negative sputum culture conversion within 12 months of treatment. Only one patient experienced recurrence of M. kansasii pulmonary disease in the isoniazid group. CONCLUSIONS: A macrolide-containing regimen appears to be as effective as an isoniazid-containing regimen for treatment of M. kansasii pulmonary disease. Additionally, intermittent therapy containing a macrolide could be an alternative treatment option for non-cavitary M. kansasii pulmonary disease.
Asunto(s)
Enfermedades Pulmonares/tratamiento farmacológico , Macrólidos/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium kansasii/aislamiento & purificación , Anciano , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Quimioterapia Combinada , Etambutol/administración & dosificación , Etambutol/uso terapéutico , Femenino , Humanos , Incidencia , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiología , Macrólidos/administración & dosificación , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas , República de Corea/epidemiología , Estudios Retrospectivos , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: The objective of this study was to conduct a multicentre evaluation of the performance of the biochip assay in the rapid identification of mycobacteria in smear-positive sputum specimens. METHODS: A total of 1751 sputum specimens were obtained from 7 cities in Zhejiang, China. All of the specimens were used for the discrimination of Mycobacterium species using the biochip assay, and the results were compared to the golden standard method of culture, hsp65, 16S rRNA and rpoB sequence analysis. RESULTS: In the 1751 sputum specimens, 1685 samples were cultured successfully; among these samples, 1361 were Mycobacterium tuberculosis, 323 were NTM and 1 was Nocadia farcinica. Of the 323 NTM, most of them were Mycobacterium intracellulare(52.5%) followed by Mycobacterium abscessus (20.7%), Mycobacterium avium (11.7%), Mycobacterium kansasii (9.6%) and Mycobacterium fortuitum (1.9%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the biochip assay to differentiate TB and NTM from AFB positive specimens were 99.8%, 99.7%, 99.9%, 99.1%, 98.8%, 1, 1, and 99.7%, respectively. The concordance between the biochip assay and mycobacterial culture for the identification of NTM species was 95.4%. CONCLUSIONS: The biochip assay is a reliable tool for the rapid identification of most mycobacteria in clinical sputum specimens. This assay can be helpful for physicians in the early diagnosis and treatment of mycobacterium infections.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Esputo/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium avium/aislamiento & purificación , Mycobacterium kansasii/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , ARN Ribosómico 16S/genética , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Good outcomes with kidney and liver transplantation in HIV-positive patients have led clinicians to recommend lung transplantation in HIV-positive patients based on extrapolated data. Pre-transplant mycobacterial infection is associated with an increased risk of developing new infection or aggravating existing infection, though it does not contraindicate transplantation in non-HIV-infected patients. However, no data exists regarding the outcome of HIV-positive patients with pre-transplant mycobacterial infection. We report a case of double lung transplantation in a 50-year-old HIV-positive patient with alpha-1 antitrypsin deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one sputum culture and the patient was considered merely colonized as no clinical evidence of pulmonary or disseminated disease was present. The patient successfully underwent a double lung transplantation. Nontuberculous mycobacterial infection was diagnosed histologically on examination of native lungs. Surveillance and watchful waiting were chosen over treatment of the infection. HIV remained under control post-transplantation with no AIDS-defining illnesses throughout the follow-up. A minimal acute rejection that responded to increased corticosteroids was reported. At 12 months post-transplant, a bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence of isolation nor recurrence of nontuberculous mycobacteria was reported post-transplantation. At 15 months post-transplant, the patient remained stable with an FEV1 of 30%. The presence of pre-transplant nontuberculous mycobacterial infection did not translate into recurrence of nontuberculous mycobacterial infection post-transplant. Whether it contributed to bronchiolitis obliterans syndrome remains unknown.