Non-tuberculous cutaneous mycobacterioses

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

Mycobacterium abscessus urinary tract infection: case report / Infecção urinária por Mycobacterium abscessus: relato de caso

Abstract Urinary tract infection is a serious public health issue that predominantly affects women. In men, it is more often associated with prostatic hyperplasia and bladder catheterization. Urogenital tuberculosis presents with nonspecific with nonspecific symptoms and the diagnosis can be made in the presence of sterile leukocyturia and recurrent infection with acid urine. Non-tuberculous mycobacteria or other non-tuberculosis mycobacteria are opportunistic pathogens that inhabit the soil, water or environment surfaces, and usually cause diseases in immunocompromised individuals. Mycobacterium abscessus is an agent that causes lung, skin and soft tissue hospital infections. Urinary tract infections by this pathogen are rare.

Resumo Infecção do trato urinário é um sério problema de saúde pública que acomete predominantemente as mulheres. Em homens, está mais relacionada com hiperplasia prostática e cateterismo vesical. A tuberculose urogenital cursa com sintomas inespecíficos e o diagnóstico pode ser aventado na presença de leucocitúria estéril, e infecção recorrente com urina ácida. Micobactérias não tuberculosas ou mycobacteria other than tuberculosis são patógenos oportunistas que habitam o solo, a água ou superfícies do meio ambiente, e geralmente causam doenças em imunodeprimidos. Mycobacterium abscessus é um agente que causa infecções nosocomiais, pulmonares, de pele e de tecidos moles. Infecção urinária decorrente desse patógeno é considerada rara.

Características clínicas e epidemiológicas de casos de infecção pulmonar por Mycobacterium kansasii no Rio de Janeiro, no período de 2006 a 2016 / Clinical and epidemiological characteristics of M. kansasii pulmonary infections from Rio de Janeiro, Brazil, between 2006 and 2016

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.

El costo de la belleza: Comunicación de seis casos clínicos con infección por micobacterias atípicas secundario a inyecciones intradérmicas y reacción a un dermoimplante de origen desconocido / The cost of beauty: six cosmetological clinical cases due to atypical mycobacterial infection secondary to intradermal injections plus reaction to foreign dermal implant

Resumen Comunicamos seis casos de mujeres quienes, tras la aplicación mediante mesoterapia con plasma rico en plaquetas, así como de un material de relleno intradérmico de origen desconocido, desarrollaron una infección en los sitios de inyección asociada a Mycobacterium massiliense, así como granulomas con reacción a cuerpo extraño. Aunque los cultivos fueron negativos, se logró la identificación del microorganismo por extracción de ADN de tejidos blandos obtenido por biopsia y posterior secuenciación del producto obtenido. Debido a la gran similitud en los cultivos de M. massiliense con la especie relacionada Mycobacterium abscessus, y a que tienen diferente respuesta terapéutica, las técnicas moleculares de diagnóstico son una opción real a considerar para administrar en forma precoz el tratamiento específico contra el patógeno y evitar la progresión de la infección.

We report six cases of female patients who, after the application by mesotherapy with platelet-rich plasma, as well as of an intradermal filler material of unknown origin, developed infection at the injection sites associated to Mycobacterium massiliense, as well as granuloma with reaction to foreign body. Although the cultures were negative, the identification of the microorganism was achieved by extraction of soft tissue DNA obtained by biopsy and sequencing the obtained product, with which the therapy was redirected against the particular species. Due to the great similarity in the culture between M. massiliense with the related species M. abscessus, to the required time for its growth, and to the different therapeutic response of each strain, molecular diagnostic techniques are a real option to consider to administer in an early way the appropriate treatment against the pathogen and prevent infection progression.

Clinical aspects in patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex, in the Brazilian Amazon / Aspectos clínicos em pacientes com infecção pulmonar por micobactérias do complexo Mycobacterium abscessus na Amazônia brasileira

ABSTRACT Objective: To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). Methods: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. Results: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. Conclusions: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

RESUMO Objetivo: Descrever as manifestações clínicas de pacientes com infecção pulmonar por micobactérias do complexo Mycobacterium abscessus (CMA) e compará-las com as daqueles infectados com outras micobactérias não tuberculosas (MNT). Métodos: Estudo de coorte retrospectivo envolvendo 43 pacientes divididos em dois grupos: grupo CMA, com pacientes com infecção pulmonar por CMA (n = 17); e grupo MNT, com pacientes com infecção pulmonar por MNT que não CMA (n = 26). Os pacientes foram previamente tratados com o esquema rifampicina, isoniazida, pirazinamida e etambutol antes de o diagnóstico de MNT ser confirmado com culturas positivas em duas amostras de escarro diferentes. As sequências nucleotídicas dos genes hsp65, RNAr 16S e/ou rpoB foram analisadas para a identificação das micobactérias. Foram coletadas características demográficas, clínicas e radiológicas, assim como respostas terapêuticas e desfechos. Resultados: A única manifestação clínica significativamente mais frequente no grupo CMA que no grupo MNT foi hiporexia (p = 0,0306). A chance de haver a necessidade de utilização de um segundo esquema terapêutico foi quase 12 vezes maior no grupo CMA que no grupo MNT. O sucesso terapêutico foi significativamente maior no grupo MNT que no grupo CMA (83,2% vs. 17,6%; p < 0,0001). A chance de recidiva no grupo CMA foi aproximadamente 37 vezes maior que no grupo MNT. Conclusões: Na amostra estudada, a resposta terapêutica da doença pulmonar causada por CMA evoluiu de forma menos favorável do que naquela causada pelas demais MNT.

Cuando la baciloscopía positiva no es tuberculosis. A propósito de un caso y breve review de la literatura / When smear positive is not tuberculosis. About a case and brief review of the literature

El método gold standar para el diagnóstico de la tuberculosis (TB) es el cultivo en medio sólido de Lowenstein-Jensen. Dado el alto costo y los requerimientos de infraestructura y personal entrenado que exige este método, tanto el programa nacional, como las recomendaciones de la Organización Mundial de la Salud (OMS), establecen que una baciloscopía positiva (BAAR +) confirma el diagnóstico de TB. Si bien el cultivo amplía la sensibilidad diagnóstica, tipifica los bacilos, y permite realizar pruebas de sensibilidad, no es un requisito operativo para la definición de confirmación bacteriológica de TB. En Argentina, el 1% de las BAAR (+) corresponden a otras etiologías3. Presentamos un caso comprendido en ese 1%, en el cual mostramos los problemas a los que se enfrenta un paciente (fundamentalmente demora diagnóstica y exposición innecesaria a drogas potencialmente tóxicas) cuando tiene un diagnóstico de TB de acuerdo con los stándares nacionales e internacionales y sin embargo no es TB.

The method gold standard for the diagnosis of tuberculosis (TB) is the culture in Lowenstein-Jensen’s solid way. In view of the high cost and the requirements of infrastructure and trained personnel that demands this method, both the national program, and the recommendations of the World Health Organization (WHO), they establish that a smear-positive confirms TB’s diagnosis. In addition, the culture increases the diagnostic sensitivity, typifies the bacillus and allows the sensitivity tests to be performed, but it is not an operative requirement for the definition of TB’s bacteriological confirmation. In Argentina, 1% of the BAAR (+) are due to other etiologies3. We present a case included in that 1%, in which we show the problems that a patient faces (basically diagnostic delay and unnecessary exposure to potentially toxic drugs) when it has TB’s diagnosis of agreement to the national and international standards and nevertheless it is not TB.

Neutropenia grave secundaria al tratamiento médico de una adenitis por micobacterias no tuberculosas / Severe neutropenia as side effect of medical treatment in nontuberculous mycobacterial adenitis

Non-tuberculous mycobacterial adenitis is getting more common in our environment. Epidemiologic studies and clinical trials published nowadays are limited. We present a 2-years-old boy diagnosed of Mycobacterium intracellulare adenitis and severe neutropenia as side effect of combined treatment with oral azythromycin and rifabutin, which recovers after suspending the second one. Liver metabolism of macrolide seems to increase other drugs toxicity, in this case, rifabutin. The patient eventually needed surgery due to persistence of the adenitis despite treatment with antibiotics.

Las adenopatías por micobacterias no tuberculosas (AMNT) son cada vez más frecuentes en nuestro medio. Los estudios epidemiológicos y ensayos clínicos controlados publicados hasta la fecha son escasos. Presentamos el caso de un niño de 2 años con el diagnóstico de una adenitis por Mycobacterium intracellulare que desarrolló una neutropenia grave secundaria a la terapia combinada de azitromicina y rifabutina oral. La metabolización hepática de los macrólidos parece aumentar la toxicidad de otros fármacos, en este caso, la rifabutina. Finalmente, al paciente se le realizó una exéresis quirúrgica por persistencia de la adenitis a pesar de la antibioterapia.

Treatment of Mycobacterium marinum with lymecycline: new therapeutic alternative?

Skin infections by Mycobacterium marinum are quite rare in our environment and, therefore, little studied. The majority of the lesions appear three weeks after traumas in aquariums, beaches and fish tanks. Lymph node drainage and systematization of the disease are rare and most lesions disappear in about three years. This case aims to show the effectiveness of the treatment used (lymecycline 150 mg/orally/day). This medication may be a new therapeutic option for the treatment of Mycobacterium marinum.

Mycobacterium chelonae cutaneous infection in a patient with mixed connective tissue disease

Around 50 mycobacteria species cause human disease. Immunosuppressive states predispose to non-tuberculous mycobaterium infection, such as Mycobacterium chelonae: AFB, non-tuberculous, fast growth of low virulence and uncommon as a human pathogen. It may compromise the skin and soft tissues, lungs, lymph nodes and there is also a disseminated presentation. The diagnosis involves AFB identification and culture on Agar and Lowenstein-Jensen medium base. A 41-year-old female with MCTD (LES predominance) is reported, presenting painless nodules in the right forearm. She denied local trauma. Immunosuppressed with prednisone and cyclophosphamide for 24 months. Lesion biopsy has demonstrated positive bacilloscopy (Ziehl-Neelsen stain) and M.chelonae in culture (Lowenstein-Jensen medium base), therefore clarithromycin treatment has been started (best therapy choice in the literature).

Abscess resulting from Mycobacterium kansasii in the left thigh of AIDS patient

A case of abscess resulting from Mycobacterium kansasii, in the left thigh of a 53-year-old woman infected with the Human Immunodeficiency virus, is reported. Curiously, there was no pulmonary or systemic involvement as is usual with these Mycobacterium infections. The patient had CD4 T lymphocyte count of 257 cells/µL and a viral load of 60,154 copies. Despite presenting a relatively preserved immunity, the patient also presented Criptococcic meningoencephalitis and Esophageal candidiasis. The patient responded satisfactorily to treatment for infections and after 51 days was discharged.

Mycobacterium Szulgai Pulmonary Infection: Case Report of an Uncommon Pathogen in Korea

Mycobacterium szulgai (M. szulgai) is an unusual pathogen in a human non-tuberculous mycobacterial infection. Pulmonary infection due to M. szulgai may be clinically and radiologically confused with active pulmonary tuberculosis. In contrast to other non-tuberculous mycobacteria, M. szulgai infection is well controlled by combination antimycobacterial therapy. Most of the previously reported cases of M. szulgai pulmonary infection showed cavitary upper lobe infiltrates. We herein describe a case of pulmonary M. szulgai infection that shows clinical and radiological presentations similar to active pulmonary tuberculosis.

Post-operative sinus formation due to Mycobacterium abscessus: A case report.

Summary: Mycobacterium abscessus is ubiquitously found rapidly growing mycobacteria. Although it is an uncommon pathogen, it has been known to cause cutaneous infection following inoculation, minor trauma or surgery. This communication reports an immuno-competent patient developing multiple sinuses due to Mycobacterium abscessus in the post- operative period.

Surgical resection of a cutaneous nodule in the left foot caused by mycobacteria / Exérese cirúrgica de nódulo cutâneo no pé esquerdo causado por uma micobactéria

Nontuberculous mycobacteria are etiologic agents of opportunistic human infections. Although they usually affect superficial tissues, infections in bones and joints have been described. The contamination is associated with increased environmental exposure. With appropriate therapy, the cases usually progress to complete recovery of the patient. This study reports the case of a patient who developed a cutaneous nodule in her left foot acquired when her skin was punctured by a fish. The anatomopathological examination revealed chronic central suppurative granulomatous dermo-hypodermal inflammation. Furthermore, the screening for resistant acid-fast bacilli was positive.

Micobactérias não tuberculosas são agentes causadores de infecções oportunistas no homem. Embora, geralmente, afetem tecidos superficiais, infecções em ossos e articulações têm sido descritas. O contágio está associado ao aumento da exposição do homem ao meio ambiente. Diante da terapêutica adequada, os casos normalmente evoluem com recuperação total do indivíduo. Este estudo descreve o caso clínico de um paciente que apresentou nódulo cutâneo no pé esquerdo após traumatismo com um peixe. O exame anatomopatológico revelou inflamação crônica granulomatosa centralmente supurativa dermo-hipodérmica e a pesquisa de bacilos álcool-ácido resistentes (BAAR) foi positiva.

Disease caused by non-tuberculous mycobacteria: diagnostic procedures and treatment evaluation in the North of Buenos Aires Province

Non-tuberculous mycobacteria (NTM) have emerged as pathogens frequently associated to HIV co-infection. The aims of this study were to describe the clinical importance of NTM in patients from the North of Buenos Aires Province and the drug-susceptibility patterns in relation with the therapy used. A total of 23,624 clinical specimens were investigated during the period 2004-2010. Ziehl-Neelsen stain and cultures were used for diagnosis. Molecular and biochemical tests were performed to identify the mycobacteria. TB and mycobacterioses cases were 2 118 and 108 respectively. Sixteen NTM species were found: Mycobacterium avium and Mycobacterium intracellulare as the main causative agents. Infections produced by more than one species at the same time were confirmed (4 cases). Macrolides and fluoroquinolones were the most active in vitro drugs. Treatment evaluation showed that 68.0 % of the cases completed the therapy, 20 % died; and 12 % were relapses. The cases in which the treatment outcome was evaluated received an individual tailor-made therapeutic scheme including those drugs showing in vitro activity and presumed in vivo usefulness. More than a quarter of the patients had HIV co-infection and the majority of the deaths were associated with this co-infection.

Enfermedad causada por micobacterias no tuberculosas: diagnóstico y evaluación del tratamiento en el norte del Gran Buenos Aires. Las micobacterias no tuberculosas (MNT) emergieron como patógenos frecuentemente asociados a la co-infección con el HIV. EL objetivo del estudio fue describir la importancia clínica de las MNT en pacientes de la región norte de la provincia de Buenos Aires y los patrones de drogo-sensibilidad en relación con la terapia empleada. Se investigó un total de 23.624 especímenes clínicos durante, el período 2004-2010. La tinción de Ziehl-Neelsen y los cultivos se utilizaron para diagnóstico. Las micobacterias fueron identificadas mediante pruebas bioquímicas y moleculares. Los casos de tuberculosis y micobacteriosis fueron 2 118 y 108, respectivamente. Se encontraron 16 especies de MNT, siendo las principales, Mycobacterium avium y Mycobacterium intracellulare. En 4 casos se confirmaron infecciones producidas por más de una especie al mismo tiempo. Los macrólidos y las fluoroquinolonas tuvieron mayor actividad in vitro. La evaluación del tratamiento confirmó que el 68 % de los casos completó la terapia; 20 % murió y el 12 % recayó. Los casos en los que se evaluó el tratamiento recibieron un esquema terapéutico individual incluyendo aquellas drogas que mostraron actividad in vitro. Más de un cuarto de los pacientes tuvieron co-infeccion con el HIV y la mayoría de las muertes estuvieron asociadas con esta co-infección.

Pulmonary disease due to mycobacterium massiliense.

We report a case of a patient suffering from multidrug-resistant pulmonary tuberculosis (MDR-PTB) who later developed an invasive infection of the respiratory tract with a rapidly growing non-tuberculous mycobacteria (NTM), recently identified as Mycobacterium massiliense, closely related to M. abscessus. To the best of our knowledge, this is the first case of M. massiliense infection being reported from India.

Cutaneous infection with Mycobacterium fortuitum: an unusual presentation.

Cutaneous infection with rapidly growing mycobacteria is uncommon and its diagnosis can be missed unless there is strong clinical suspicion coupled with microbiological confirmation. We report a case of localized recurrent soft tissue swelling of the foot by Mycobacterium fortuitum in a healthy adult male. The case is being reported for its uncommon clinical presentation and the associated etiological agent. The patient recovered completely following therapy with amikacin and clarithromycin.

Identification of Mycobacteria Species by HPLC and Species Distribution during Five Years at Ulsan University Hospital / 대한진단검사의학회지

BACKGROUND: Infections caused by mycobacteria have been significantly increasing. Due to the difficulty of making a decision about the pathogenicity of mycobacteria, species-level identification is very important for patients' diagnosis and treatment. The purpose of this study was to identify mycobacteria species using a high performance liquid chromatography (HPLC) method and to provide an initial database for the distribution of mycobacteria in Korea. METHODS: Acid fast bacteria isolated from 3,107 clinical specimens were identified by mycolic acid analysis using HPLC. The HPLC patterns were compared with those of standard mycobacteria species. RESULTS: The HPLC patterns were divided into single, double, and triple cluster groups, each group comprising 9, 20, and 4 species, respectively. Mycobacteria and non-tuberculous mycobacteria (NTM) were identifies by HPLC at the rates of 99.5% and 95.6%, respectively. NTM was isolated in 12.4% of the mycobacteria positive specimens. This study also found that there were 20 different NTM species with the distribution of each species ranging from 0.3% to 15.9% of the total NTM. While the rate of NTM has been increasing in Korea, M. avium-intracellulare, M. fortuitum, and M. chelonae are relatively decreasing, and M. kansasii and M. gordonae are relatively increasing. CONCLUSIONS: HPLC method was highly discriminative for the identification of NTM in clinical specimens.