Pulmonary mycobacterium avium complex disease complicated by cancer: an 11-year survey at a single-center / Journal of Rural Medicine

Objective: Pulmonary mycobacterium avium complex (MAC) disease is increasing significantly worldwide. Several studies have investigated the clinical features of pulmonary MAC disease in the setting of cancer. Here, we aimed to clarify the clinical characteristics of patients with cancer with recent onset of pulmonary MAC disease and the effect of cancer on the onset of this disease.Patients and Methods: Of the 323 consecutive Japanese patients newly diagnosed with pulmonary MAC disease at Jichi Medical University Hospital between and 2006–2017, we retrospectively reviewed 79 consecutive patients with cancer.Results: Seventeen patients had lung cancer (21.0%), while 62 had non-lung cancer. Of the 17 patients with lung cancer, 16 had adenocarcinoma of which 10 had stage I to III disease; 8 of the 10 patients had not received chemotherapy. Sixteen patients with lung cancer had a MAC infection in the ipsilateral lung. Notably, 9 of the 11 lung cancer patients who did not undergo surgery had a MAC infection in the affected lobe. Of the 39 patients with the most common types of non-lung cancer (14 had gastric cancer, 13 had colorectal cancer, and 12 had breast cancer), 22 had stage I to III disease, and 18 of these 22 had not received chemotherapy.Conclusion: Lung cancer may act as a local factor contributing to the onset of pulmonary MAC disease in the ipsilateral lung. However, the underlying mechanism by which a history of cancer might affect the onset of pulmonary MAC disease remains unclear. Further investigation into this mechanism is needed.

Effect of coexisting advanced extrapulmonary solid cancer on progression of Mycobacterium avium complex lung disease / Efeito da coexistência de câncer sólido extrapulmonar avançado na progressão da doença pulmonar por complexo Mycobacterium avium

ABSTRACT Objective: Although Mycobacterium avium complex (MAC) lung disease has been shown to be associated with lung cancer and hematologic malignancies, there have been few studies of its relationships with other types of cancer. The aim of this study was to assess the effect that coexisting advanced extrapulmonary solid tumors have on the progression of MAC lung disease. Methods: This was a retrospective study of patients diagnosed with MAC lung disease, on the basis of the American Thoracic Society (ATS) criteria, between October of 2005 and March of 2019. The patients were divided into three groups: those with advanced-stage cancer (A-SC group); those with early-stage cancer (E-SC group); and those without cancer (control group). Progression of MAC lung disease was defined as exacerbation seen on imaging. Patient characteristics and the time to progression were compared among the three groups. Results: A total of 286 patients met the ATS diagnostic criteria for MAC lung disease, and 128 of those were excluded. Of the remaining 158 patients, 20 (7.0%) were in the A-SC group, 36 (12.6%) were in the E-SC group, and 102 (35.7%) were in the control group. The median time to progression in the A-SC, E-SC, and control groups was 432, 3,595, and 2,829 days, respectively (p < 0.01). A proportional hazards model showed that the significant predictors of MAC lung disease progression were advanced-stage cancer (hazard ratio [HR] = 6.096; 95% CI: 2.688-13.826; p < 0.01), cavitary lesions (HR = 2.750; 95% CI: 1.306-5.791; p < 0.01), and a high Nodule-Infiltration-Cavity-Ectasis score (HR = 1.046; 95% CI: 1.004-1.091; p = 0.033). Conclusions: A coexisting advanced extrapulmonary solid tumor could hasten the progression of MAC lung disease.

RESUMO Objetivo: Embora tenha sido demonstrado que a doença pulmonar por Mycobacterium avium complex (MAC, complexo M. avium) está associada a câncer de pulmão e neoplasias hematológicas, há poucos estudos sobre sua relação com outros tipos de câncer. O objetivo deste estudo foi avaliar o efeito da coexistência de tumores sólidos extrapulmonares avançados na progressão da doença pulmonar por MAC. Métodos: Estudo retrospectivo de pacientes diagnosticados com doença pulmonar por MAC, segundo os critérios da American Thoracic Society (ATS), entre outubro de 2005 e março de 2019. Os pacientes foram divididos em três grupos: grupo câncer em estágio avançado (grupo CEA), grupo câncer em estágio inicial (grupo CEI) e grupo sem câncer (grupo controle). Progressão da doença pulmonar por MAC foi definida como exacerbação observada em exame de imagem. As características dos pacientes e o tempo para progressão foram comparados entre os três grupos. Resultados: Um total de 286 pacientes preencheu os critérios diagnósticos da ATS para doença pulmonar por MAC, sendo 128 deles excluídos. Dos 158 pacientes restantes, 20 (7,0%) eram do grupo CEA, 36 (12,6%), do grupo CEI e 102 (35,7%), do grupo controle. A mediana de tempo para progressão nos grupos CEA, CEI e controle foi de 432, 3.595 e 2.829 dias, respectivamente (p < 0,01). Um modelo de riscos proporcionais demonstrou que os preditores significativos de progressão da doença pulmonar por MAC foram câncer em estágio avançado (razão de risco [RR] = 6,096; 95%IC: 2,688-13,826; p < 0,01), lesões cavitárias (RR = 2,750; 95%IC: 1,306-5,791; p < 0,01) e pontuação alta no sistema Nódulo-Infiltração-Cavidade-Ectasia (RR = 1,046; 95%IC: 1,004-1,091; p = 0,033). Conclusões: A coexistência de tumor sólido extrapulmonar avançado poderia acelerar a progressão da doença pulmonar por MAC.

Nontuberculous mycobacterial infection in a tertiary care center in Mexico, 2001-2017

ABSTRACT Introduction: Nontuberculous mycobacteria (NTM) comprise several pathogens with a complex profile of virulence, diverse epidemiological and clinical patterns as well as host specificity. Recently, an increase in the number of NTM infections has been observed; therefore, the objective of this study was to evaluate the clinical characteristics and outcomes of these infections. Methods: We included patients with NTM infections between 2001-2017 and obtained risk factors, clinical features and outcomes; finally, we compared this data between slowly growing (SGM) and rapidly growing mycobacteria (RGM). Results: A total of 230 patients were evaluated, 158 (69%) infected and 72 (31%) colonized/pseudoinfected. The average annual incidence in the first 11 years of the study was 0.5 cases per 1000 admissions and increased to 2.0 cases per 1000 admissions later on. The distribution of NTM infections was as follows: bloodstream and disseminated disease 72 (45%), lung infection 67 (42%), skin and soft tissue infection 19 (12%). Mycobacterium avium complex was the most common isolate within SGM infections, and HIV-infected patients were the most affected. Within RGM infections, M. fortuitum was the most common isolate from patients with underlying conditions such as cancer, type-2 diabetes mellitus, presence of invasive devices, and use of immunosuppressive therapy. We did not find significant differences in deaths and persistent infections between disseminated SGM infection when compared to disseminated RGM infection (42% vs. 24%, p = 0.22). However, disseminated SGM infection required a longer duration of therapy than disseminated RGM infection (median, 210 vs. 42 days, p = 0.01). NTM lung disease showed no significant differences in outcomes among treated versus non-treated patients (p = 0.27). Conclusions: Our results show a significant increase in the number of Non-tuberculosis-mycobacteria infections in our setting. Patients with slow-growing-mycobacteria infections were mainly persons living with human immunodeficiency virus . Older patients with chronic diseases were common among those with rapidly-growing-mycobacteria infections. For non-tuberculosis-mycobacteria lung infection, antibiotic therapy should be carefully individualized.

Enfermedad pulmonar por Mycobacterium intracellulare en una paciente inmunocompetente: reporte de un caso en el Perú / Pulmonary disease by mycobacterium intracellulare in an immunocompetent patient: Report of a case in Peru

RESUMEN Presentamos una paciente inmunocompetente cuya enfermedad comenzó a los 49 años con tos, seguida de esputo purulento y hemoptoico, por lo que se diagnosticó bronquiectasias. Tres años después, luego de hemoptisis, le practicaron segmentectomía medial del lóbulo medio y quedó asintomática por meses. Al encontrarse tuberculosis en el informe de patología fue tratada con 4HREZ2R2H2. Cinco años después su BK fue 2+ recibiendo un nuevo esquema de 4HREZ2R2H2, con lo que no logro negativizar declarándose el fracaso al tratamiento. Al hallar en la genotipificación de su cultivo Mycobacterium intracellulare, la paciente recibió azitromicina, moxifloxacina y etambutol, hubo mejoría, pero abandonó el tratamiento a los ocho meses; lo reinició 18 meses después, junto con tratamiento para la depresión y el reflujo gastroesofágico. Al mes la paciente estuvo asintomática, pero hizo reacción dérmica a la moxifloxacina y se la reemplazó por amikacina. Salió de alta y al año estuvo curada, a los 64 años de edad.

ABSTRACT We present the case of an immunocompetent patient whose illness began at age 49 with a cough, followed by purulent and hemoptoic sputum; bronchiectasis was diagnosed. Three years later, after hemoptysis, she underwent medial segmentectomy of the middle lobe and was asymptomatic for months. When tuberculosis was found in the pathology report, she was treated with 4HREZ2R2H2. Five years later her BK was 2+, thus receiving a new scheme of 4HREZ2R2H2, which did not succeed in obtaining negative results and the treatment was declared as a failure. After genotyping her Mycobacterium intracellulare culture, the patient received azithromycin, moxifloxacin and ethambutol. There was improvement, but she abandoned the treatment at 8 months; she restarted it 18 months later, along with treatment for depression and gastroesophageal reflux. After one month the patient was asymptomatic, but she had a dermal reaction to moxifloxacin which was replaced with amikacin. One year later, she was cured and discharged, at the age of 64.

Molecular isolation and identification of Mycobacterium avium subsp. hominissuis in Didelphis virginiana from Hidalgo, Mexico

Objective: To isolate and identify the exact species of the genus Mycobacterium from Didelphis (D.) virginiana, and the direct implications of this bacterium to public health and veterinary medicine. Methods: Thirty-one D. virginiana were captured and necropsied in Hidalgo, Mexico. Tissue samples were collected to culture mycobacteria present and examine individual specimens' histopathology. Mycobacterium identification was obtained through the application of amplification and sequencing of 16S rDNA techniques. Results: Three strains were isolated and identified as Mycobacterium (M.) avium subsp. hominissuis by utilizing M. avium complex- specific primers. Granulomatous lesions were observed in the subpleural zone (granuloma grade Π ) and bronchial (granuloma grade I ) of the lungs of D. virginiana with positive isolation. Conclusions: Three strains of M. avium subsp. hominissuis, from lung tissue samples of D. virginiana were identified. This subspecies of M. avium has important implications in public health and veterinary medicine.

Molecular isolation and identification of Mycobacterium avium subsp. hominissuis in Didelphis virginiana from Hidalgo, Mexico

Objective: To isolate and identify the exact species of the genus Mycobacterium from Didelphis (D.) virginiana, and the direct implications of this bacterium to public health and veterinary medicine. Methods: Thirty-one D. virginiana were captured and necropsied in Hidalgo, Mexico. Tissue samples were collected to culture mycobacteria present and examine individual specimens' histopathology. Mycobacterium identification was obtained through the application of amplification and sequencing of 16S rDNA techniques. Results: Three strains were isolated and identified as Mycobacterium (M.) avium subsp. hominissuis by utilizing M. avium complex- specific primers. Granulomatous lesions were observed in the subpleural zone (granuloma grade Π ) and bronchial (granuloma grade I ) of the lungs of D. virginiana with positive isolation. Conclusions: Three strains of M. avium subsp. hominissuis, from lung tissue samples of D. virginiana were identified. This subspecies of M. avium has important implications in public health and veterinary medicine.

Treatment of Mycobacterium avium Complex Pulmonary Disease / 결핵및호흡기질환

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient / 감염과화학요법

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Mycobacterium avium Complex Infection-Related Immune Reconstitution Inflammatory Syndrome Mimicking Lymphoma in an Human Immunodeficiency Virus-Infected Patient / 감염과화학요법

In acquired immunodeficiency syndrome (AIDS) patients, immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium complex (MAC) infection is one of the most difficult IRIS types to manage. We report an unusual case of MAC-associated IRIS. At first the patient was diagnosed human immunodeficiency virus (HIV) infection after he was admitted with pneumocystis pneumonia. After starting antiretroviral therapy he presented unmasked IRIS with MAC infection. Next, he was hospitalized with continuous loose stools and new-onset fever. Investigation included computed tomography (CT), which showed homogeneous enhancement and enlargement of the lymph nodes (LN), elevation of ferritin (>1,650 ng/mL) and lactate dehydrogenase (306 IU/L) levels, and F- fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan, which showed increased FDG uptake. These findings were highly indicative of lymphoma. We performed laparoscopic biopsy of the mesenteric LN, and the biopsy culture grew MAC. So we made a diagnosis of MAC-associated. Therefore, IRIS must be considered as a possible diagnosis when AIDS patients develop new symptoms or exhibit exacerbations of existing symptoms. Furthermore the biopsies should be conducted.

Survey of Drug Prescription Patterns Among Patients with Nontuberculous Mycobacterial Disease Using the Database of Health Insurance Claims / 薬剤疫学

In recent years, the number of patients with non-tuberculosis mycobacteria (NTM) has rapidly increasing.According to the nationwide survey conducted in 2014, the number of patients with NTM was reported to increase 9.7 times compared to the survey in 1980. Among them, the patients with Mycobacterium avium complex (MAC) account for about 88.8% of them. It is the main cause of the rapid increase of NTM patients mainly in middle-aged and elderly woman. To treat patients with MAC, it is common to do chemotherapy over one year after the bacteria becomes negative. Among experts of NTM, it is recommended to do chemotherapy preventing generation of resistant bacteria by using clarithromycin (CAM) and rifampicin and ethambutol (EB) in combination. Meanwhile, a monotherapy of CAM and high-dose EB administration over a long period are not currently recommended due to side effects. However, it has not been clarified so far how many such drug prescriptions had existed. Therefore, in this study, we investigated the actual drug prescription of 571 patients who were presumed to be NTM in health insurance data collected from 2015 to 2016. As a result, about 5.1% (29 cases) of CAM monotherapy and 4.4% (15 cases) of EB high-dose prescription over 3 months were observed. In general, because NTM is a case where a long-term antibiotic treatment is required, it increases the possibility of any disadvantages exerting on patients. Hence, we consider it is an important and urgent matter to inform the correct information widely to clinical workers and sites.

Changing Epidemiology of Nontuberculous Mycobacterial Lung Diseases in a Tertiary Referral Hospital in Korea between 2001 and 2015

This study investigated the changes in the major etiologic organisms and clinical phenotypes of nontuberculous mycobacterial lung disease (NTM-LD) over a recent 15-year period in Korea. The increase of number of patients with NTM-LD was primarily due to an increase of Mycobacterium avium complex (MAC) lung disease (LD). Among MAC cases, the proportion of M. avium increased compared with M. intracellulare, whereas the incidence of M. abscessus complex and M. kansasii LD remained relatively stable. The proportion of cases of the nodular bronchiectatic form increased compared with the fibrocavitary form of NTM-LD.

Nasal swab real-time PCR is not suitable for in vivo diagnosis of bovine tuberculosis / A PCR em tempo real de swab nasal não é adequada para o diagnóstico in vivo de tuberculose bovina

Bovine tuberculosis (bTB) is a zoonosis causing economic losses and public health risks in many countries. The disease diagnosis in live animals is performed by intradermal tuberculin test, which is based on delayed hypersensitivity reactions. As tuberculosis has complex immune response, this test has limitations in sensitivity and specificity. This study sought to test an alternative approach for in vivo diagnosis of bovine tuberculosis, based on real-time polymerase chain reaction (PCR). DNA samples, extracted from nasal swabs of live cows, were used for SYBR® Green real-time PCR, which is able to differentiate between Mycobacterium tuberculosis and Mycobacterium avium complexes. Statistical analysis was performed to compare the results of tuberculin test, the in vivo gold standard bTB diagnosis method, with real-time PCR, thereby determining the specificity and sensitivity of molecular method. Cervical comparative test (CCT) was performed in 238 animals, of which 193 had suitable DNA from nasal swabs for molecular analysis, as indicated by amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, and were included in the study. In total, 25 (10.5%) of the animals were CCT reactive, of which none was positive in the molecular test. Of the 168 CCT negative animals, four were positive for M. tuberculosis complex at real time PCR from nasal swabs. The comparison of these results generated values of sensitivity and specificity of 0% and 97.6%, respectively; moreover, low coefficients of agreement and correlation (-0.029 and -0.049, respectively) between the results obtained with both tests were also observed. This study showed that real-time PCR from nasal swabs is not suitable for in vivo diagnosis of bovine tuberculosis; thus tuberculin skin test is still the best option for this purpose.(AU)

A tuberculose bovina (bTB) é uma zoonose que causa perdas econômicas e riscos à saúde pública em muitos países. O diagnóstico da doença em animais vivos é realizado pelo teste intradérmico da tuberculina, que é baseado em reações de hipersensibilidade tardia. Como a tuberculose tem resposta imunológica complexa, este teste tem limitações em termos de sensibilidade e especificidade. Este estudo procurou desenvolver uma abordagem alternativa para o diagnóstico in vivo da tuberculose bovina, com base na reação em cadeia da polimerase (PCR) em tempo real. As amostras de DNA, extraídas de suabes nasais de vacas vivas, foram usadas para PCR em tempo real com SYBR® Green, capaz de diferenciar os complexos Mycobacterium tuberculosis e Mycobacterium avium. A análise estatística foi realizada para comparar os resultados de teste de tuberculina, padrão ouro para o diagnóstico in vivo da bTB, com PCR em tempo real, determinando-se assim a especificidade e sensibilidade do método molecular. O teste cervical comparativo (TCC) foi realizado em 238 animais, dos quais 193 tiveram DNA dos suabes nasais adequados para análise molecular, como indicado pela amplificação do gene gliceraldeído-3-fosfato-desidrogenase (GAPDH), e foram incluídos no estudo. No total, 25 (10,5%) animais foram reativos no TCC, dos quais nenhum foi positivo no teste molecular. Dos 168 animais negativos no TCC, quatro foram positivos para o complexo M. tuberculosis na PCR em tempo real a partir dos suabes nasais. A comparação destes resultados gerou valores de sensibilidade e especificidade de 0% e 97,6%, respectivamente; além disso, baixos coeficientes de concordância e correlação (-0,029 e -0,049, respectivamente) entre os resultados obtidos com ambos os testes também foram observados. Este estudo mostrou que a PCR em tempo real a partir de suabes nasais não é adequada para o diagnóstico in vivo da tuberculose bovina; portanto, o teste da tuberculina ainda é a melhor opção para este fim.(AU)

Infección por el complejo Mycobacterium avium-intracellulare en pacientes con VIH/SIDA en un hospital peruano: Una serie de casos / Infection by the Mycobacterium avium-intracellulare complex in patients with HIV/AIDS in a Peruvian hospital: A series of cases

RESUMEN Existe poca información sobre la presencia del complejo Mycobacterium avium-intracellulare (MAC) en el Perú. Se describen cinco casos de infección por MAC en pacientes con VIH/SIDA del Hospital Nacional Dos de Mayo, Lima-Perú. Los pacientes presentaron, principalmente, fiebre persistente, diarrea crónica, síndrome consuntivo, pancitopenia y citofagocitosis. En todos ellos se identificó bacilos acido-alcohol resistentes en heces, por lo que recibieron tratamiento antituberculoso. El cultivo de heces fue negativo para Mycobacterium tuberculosis y, posteriormente, en todos se identificó a MAC mediante una prueba molecular (Genotype) en el cultivo de heces. Tres pacientes recibieron tratamiento para MAC luego de la identificación; sin embargo, todos fallecieron. Ante presentaciones similares a lo reportado, se sugiere el uso de métodos de mayor rendimiento (hemocultivo, mielocultivo, pruebas moleculares), así como asociar tempranamente drogas con actividad para MAC al esquema antituberculoso con la intención de mejorar el pronóstico de este grupo de pacientes.

ABSTRACT There is little information on the presence of the Mycobacterium avium-Intracellulare (MAC) complex in Peru. Five cases of MAC infection are described in patients with HIV/AIDS at the National Hospital Dos de Mayo, Lima - Peru. The patients presented, mainly, persistent fever, chronic diarrhea, consumptive syndrome, pancytopenia and citofagocitosis. In all of them, resistant acid-alcohol bacilli were identified in feces, so they received antituberculous treatment. The culture of feces was negative for Mycobacterium tuberculosis and, later, in all cases MAC was identified using a molecular test (genotype) in the culture of feces. Three patients received treatment for MAC right after identification; however, they all died. Before presentations similar to the reported, we suggest the use of higher performance methods (blood culture, myeloculture, molecular tests), as well as early associating drugs with activity for MAC to antitubercular scheme with the intention of improving the prognosis of this group of patients.

Enfermedad pulmonar causada por complejo Mycobacterium avium y M. abscessus / Pulmonary disease caused by Mycobacterium avium complex and M. abscessus

Resumen Introducción: después del complejo Mycobacterium tuberculosis, las principales especies de micobacterias causando enfermedad pulmonar son el complejo Mycobacterium avium (MAC) y Mycobacterium abscessus, el tratamiento es prolongado, presentan un amplio perfil de resistencia y algunas veces es necesaria la resección quirúrgica del tejido, dificultando la curación de algunos casos. Objetivo: realizar un análisis de los casos a los que se les aisló de muestras pulmonares MAC y M. abscessus en el periodo de 2012-2014 en el Laboratorio Nacional de Referencia de Colombia. Material y métodos: se realizó un estudio de serie de casos de 42 personas a las que se les aisló de muestras pulmonares MAC y M. abscessus, los cuales fueron identificados mediante pruebas fenotípicas y genotípicas. La fuente de información fue el Formato Único de Vigilancia de las Micobacterias que se recibe con cada uno de los aislados que llegan al INS. Se analizaron las variables edad, sexo, tipo de muestra y presencia de factores de riesgo. Resultados: en 32 de los casos se identificó MAC y en 10 M. abscessus como agente etiológico causante de enfermedad pulmonar, 26 (61.9%) de los casos tenían entre 51 y 86 años. Los principales factores de riesgo fueron: antecedente de tratamiento antituberculosis 16 (38.1%) y persona con VIH 7 (16.7%) y sin factor de riesgo 9 (21.2%) casos. Discusión: este trabajo reporta como agente etiológico MAC y M. abscessus en personas mayores de 50 años sin factores de riesgo, con antecedentes de tuberculosis, indicando que se debe fortalecer la realización de cultivo e identificación de especie en éstas para que tengan un adecuado diagnóstico y tratamiento.

Abstract Introduction: after the Mycobacterium tuberculosis complex, the main species of mycobacteria causing lung disease are Mycobacterium avium complex and Mycobacterium abscessus. The treatment is prolonged; they present a broad resistance profile and sometimes the surgical resection of the tissue is necessary, making healing difficult in some cases. Objective: to perform an analysis of the cases to which MAC and M. abscessus were isolated from pulmonary samples in the period from 2012 to 2014 in the National Reference Laboratory of Colombia. Materials and Methods: a case series study of 42 individuals to whom Mac and M. abcessus were isolated from pulmonary samples that were identified by phenotypic and genotypic tests, was carried out. The source of information was the unique format of surveillance of mycobacteria that is received with each of the isolates that come to the National Health Institute. The variables age, sex, type of sample and presence of risk factors were analyzed. Results: in 32 patients MAC was identified as etiological agent causing pulmonary disease and in 10 cases, M. abscessus was the agent. 26 (61.9%) of the patients were between 51 and 86 years of age. The main risk factors were: antecedent of anti-tuberculosis treatment in16 (38.1%),7 with HIV (16.7%) and without risk factor 9 cases (21.2%).

Simultaneous Diagnosis of Pneumococcal Sepsis and Disseminated Mycobacterium avium Complex Infection in a Patient with Acquired Immunodeficiency Syndrome / 대한내과학회지

The incidence of bacteremia in human immunodeficiency virus (HIV)-infected patients is significantly decreased by highly active antiretroviral therapy (HAART). However, bacteremia remains a major cause of morbidity and mortality in HIV-infected patients. A 43-year-old male who had fever and cough for 1 week presented to the emergency room. He was diagnosed with acquired immunodeficiency syndrome combined with atypical pneumonia and started on antibiotics plus HAART. After 3 days, Streptococcus pneumoniae was grown in blood cultures. Three weeks later, acid-fast bacilli cultures of blood and bronchoalveolar lavage fluid grew Mycobacterium avium complex (MAC); hence, the patient was treated with antimycobacterial drugs. HIV-infected patients with persistent fever despite administration of appropriate antibiotics should be examined for simultaneous infection by other organisms, such as nontuberculous mycobacteria. We report a case of simultaneous detection of MAC and S. pneumoniae in the blood of a treatment-naïve HIV-infected patient.

Pathogenic spectrum, clinical features and drug resistance of pneumonia caused by nontuberculous mycobacteria in acquined immunodeficiency syndrome patients / 中华传染病杂志

Objective To explore the pathogen spectrum, drug resistance rate and clinical characteristics of pneumonia caused by non-tuberculous mycobacteria (NTM) in acquined immuno-deficiency syndrome (AIDS) patients.Methods The clinical data of 31 hospitalized AIDS patients with bronchoalceolar lavage flind (BALF) culture confirmed NTM pulmonary disease in Guangzhou No.8 People′s Hospital from January,2008 to February,2015 were retrospectively analyzed, including pathogen spectrum, drug resistance rate and clinical characteristics.The clinical characteristics and drug resistance were compared between Mycobacterium avmm-intracellulare complex (MAC) pneumonia and the non-MAC pneumonia, and t test and chi-square test were used.Results Of the 31 AIDS patients,28 were male and 3 were female, with the mean age of 40.9 years old.The 31 NTM strains were consisted of 14 MAC strains and 17 non-MAC strains (including 4 M.kansasii strains,3 M.lentiflavumstrains, 2 M.szulgai strains, 2 M.yongonense strains etc).There was no significant difference between two groups in sex ratio, mean age, clinical manifestations, laboratory tests and treatment outcome (all P>0.05).The major clinical manifestations included fever, productive cough, weight loss, anemia and low CD4+ count (<50/μL).Most patients showed thoracic lymphadenectasis and patchy shadows in lungs, and few patients had millet shadows and pericardial effusion.Compared with non-MAC strains, MAC strains had higher drug resistant rate of moxifloxacin (10/14 vs 4/17), levofloxacin (14/14 vs 8/17), and clarithromycin (11/14 vs 7/17).More extensively drug resistance strains were seen in non-MAC strains compared with MAC strains (11/14 vs 7/17).Conclusions MAC is the most common pathogen of NTM pulmonary disease in AIDS patients.The clinical features of pneumonia caused by MAC and non-MAC are similar, but drug resistance of MAC strains are more severe.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives / 결핵및호흡기질환

Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

Multiple Cavitary Pulmonary Nodules Caused by Mycobacterium intracellulare / 가정의학회지

Nontuberculous mycobacteria (NTM) have been increasingly recognized as an important cause of chronic pulmonary infections. The Mycobacterium avium complex (MAC), which is composed of two species, Mycobacterium avium and Mycobacterium intracelluare, is the most commonly encountered pathogen associated with NTM lung disease. MAC pulmonary infection typically presents in a fibrocavitary form or a nodular bronchiectatic form. However, there have been atypical presentations of MAC pulmonary infections, including solitary pulmonary nodules (SPN). There have been several previous reports of SPN due to MAC infection in the United States, Japan, and Korea. In 2009, Sekine and colleagues reported a case of MAC pulmonary infection presenting with multiple nodules. To date, however, there have been no cases of NTM lung infection with multiple cavitary pulmonary nodules, and neither a fibrotic change nor nodular bronchiectasis. The present case showed a multiple cavitating nodular lung infection due to MAC, which is very rare and different from the typical presentation of MAC pulmonary infections. We also showed that percutaneous transthoracic needle aspiration can be a useful diagnostic tool to evaluate a case of multiple cavitary nodules.

Mycobacterium avium Complex Peritonitis in an Acquired Immune Deficiency Syndrome Patient / 대한내과학회지

Mycobacterium avium complex (MAC) is an opportunistic bacterium that primarily infects acquired immune deficiency syndrome (AIDS) patients with low CD4+ T cell counts; however, peritonitis caused by MAC in AIDS patients is rare. Here, we report the first case of peritonitis caused by MAC in AIDS patients in Korea. A 41-year-old female with poor adherence to antiretroviral therapy was admitted to hospital with nonspecific symptoms; an abdominal computed tomography (CT) scan revealed substantial ascites, splenomegaly, and lymphadenopathy. Based on the CT scan and ascitic fluid cultures, MAC peritonitis was diagnosed. In addition to antiretroviral therapy, clarithromycin, rifabutin, and ethambutol were administered to treat the MAC infection, and the patient's symptoms improved.