Enfermedad pulmonar por Mycobacterium intracellulare, un reto diagnóstico. Reporte de caso / Lung disease due to Mycobacterium intracellulare. A diagnostic challenge, Case report

La incidencia de infección por micobacterias no tuberculosas (MNT) y el número de casos han ido en aumento, especialmente en mujeres y personas mayores, teniendo en los Estados Unidos entre el 2008 y 2015 una incidencia de 4.16 a 6.69 por 100000 entre las mujeres y de 12.70 a 18.37 por 100000, entre los mayores de 65 años. "Los pacientes con compromiso estructural del parénquima pulmonar, antecedente de inmunosupresión o inmunodeficiencia tienen mayor riesgo de desarrollar infección por MNT". Sin embargo, se han presentado informes de pacientes inmunocompetentes en asociación con opacidades nodulares y bronquiectasias. Se trata de una mujer de 79 años con antecedente de tuberculosis pulmonar documentada en dos oportunidades: último proceso infeccioso en el año 2021. Recibió manejo por seis meses de esquema vigente con tetraconjugado. Actualmente acude a consulta con cuadro clínico de más de seis meses de evolución dados por pérdida de peso de más del 10 % en un año, disnea a moderados esfuerzos y tos con expectoración purulenta. Al examen físico se encontró índice de masa corporal (IMC) bajo, tórax hipoexpansible con estertores tipo crépitos en ambos hemitórax. En la tomografía de tórax se evidenciaron bronquiectasias generalizadas, algunas áreas de árbol en gemación y lesiones cavitadas. Se consideró la realización de fibrobroncoscopia con lavado broncoalveolar documentándose baciloscopias negativas, con cultivo positivo para micobacteria no tuberculosa. Se solicitó tipificación de micobacterias con coloración de Kinyoun, y pruebas bioquímicas a partir de cepas de cultivo del lavado broncoalveolar, con reporte positivo para Mycobacterium intracellulare. Se inició por lo tanto manejo con azitromicina 500 mg, rifampicina 600 mg y etambutol 975 mg diarios. Los profesionales sanitarios deben ser conscientes de la posible infección por MNT sobre todo existiendo afectación estructural pulmonar previa, basando el tratamiento en la sospecha clínica y/o las circunstancias epidemiológicas.

The incidence of non-tuberculous mycobacterial (NTM) infection and the number of cases have been increasing, especially in women and the elderly, having EE. Between 2008 and 2015 an incidence of 4.16 to 6.69 per 100,000 among women and from 12.70 to 18.37 per 100,000 among those over 65. "Patients with structural involvement of the pulmonary parenchyma, history of immunosuppression or immunodeficiency have a higher risk of developing NTM infection". However, immunocompetent patients have been reported in association with nodular opacities and bronchiectasis. This is a 79-year-old woman with a history of pulmonary tuberculosis documented on 2 occasions: the last infectious process in 2021. It received management for 6 months of the current tetraconjugate schema. He is currently in consultation with a clinical picture of more than 6 months of evolution given by weight loss of more than 10% in a year, dyspnea to moderate efforts and cough with purulent expectoration. Physical examination revealed low body mass index (BMI) and, a hypoexpandable thorax with a crescent-like sternum in both hemithorax. Chest tomography revealed widespread bronchiectasis, some groaning tree areas and cavitated lesions. Bronchoscopy fibro bronchoscopy with bronchoalveolar lavage has been reported negative bacilloscopies, positive culture for non-tuberculosis mycobacteria. Mycobacteria typing, Kinyoun coloration, and biochemical tests were requested from bronchoalveolar lavage culture strains with positive reports for Mycobacterium intracellulare. Management was therefore initiated with azithromycin 500 mg, rifampin 600 mg and ethambutol 975mg daily. Healthcare professionals should be aware of possible NTM infection especially existing prior lung structural involvement based on clinical suspicion and/or epidemiological circumstances.

Immunogenicity of Whole / 生物医学与环境科学（英文）

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Vacuum sealing drainage: A novel treatment method for primary cutaneous Mycobacterium intracellulare infection

The incidence of primary cutaneous Mycobacterium intracellulare infection is very low. We report a case of primary cutaneous M. intracellulare infection which presented as painful erythematous swelling of the right upper limb without systemic involvement. A novel technique of vacuum sealing drainage was successfully implemented after antimycobacterial treatment proved ineffective at the end of 3 months. Our technique also revealed some additional practical advantages.

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.

Comparison of clinical features of pulmonary infections with Mycobacterium intracellulare and Mycobacterium abscessus in tuberculosis intensive care unit / 中华临床感染病杂志

Objective To compare the clinical features of pulmonary infections with Mycobacterium intracellulare and Mycobacterium abscessus in the tuberculosis intensive care unit (ICU).Methods Clinical data of 74 patients with non-tuberculous mycobacterial pulmonary infection (NTM) admitted in tuberculosis ICU of Hangzhou Red Cross Hospital from January 2012 to May 2017 were retrospectively analyzed.There were 54 patients infected with Mycobacterial abscesses, 16 patients with Mycobacterial intracellular, 2 patients with Mycobacterium avium and 2 patients with Mycobacterium kansasii.The clinical features, imaging manifestations, treatment and prognosis of patients with Mycobacterial intracellular and Mycobacterial abscesses lung infections were compared.SPSS 21.0 software was used for statistical analysis.Survival curve analysis was performed using GraphPad Prism V 5.01.Results Among 74 patients with NTM lung disease , the infection rate of Mycobacterium abscessus was 72.87%(54/74), and the infection rate of Mycobacterium intracellular was 21.62%( 16/74 ).The age of patients with Mycobacterium intracellularis pulmonary disease was younger and the length of ICU stay was shorter than those of patients with Mycobacterium abscessus (t＝－2.729 and －6.150, P＜0.05 or ＜0.01).There was no significant difference in the gender distribution and APACHE Ⅱ scores between the two groups ( both P＞0.05).The proportion of patients with chronic obstructive pulmonary disease ( COPD) in Mycobacterium intracellularis group was significantly lower and the proportion of patients with bronchiectasis was significantly higher than those in Mycobacterial abscesses group (χ2＝3.902, P＜0.05; χ2＝23.888, P＜0.01).The proportion of patients complicated with stroke sequelae , Parkinson's disease and other central nervous system diseases ( χ2＝14.872, P＜0.01) and diabetes (χ2＝3.902, P＜0.05) in Mycobacterial abscess group was significantly higher, and that of hemoptysis was significantly lower (χ2＝9.717, P＜0.01) than those in Mycobacterium intracellularis group.Respiratory failure (93.75%) and septic shock (6.25%) were the main reasons of ICU admission for patients with Mycobacterium intracellularis lung disease; while respiratory failure (90.74%), heart failure (11.11%) and renal failure (1.85%) were main reasons of ICU admission for patients with Mycobacterial abscesses; there were no significant differences in the causes of ICU admission between the two groups ( all P＞0.05).The proportion of NTM isolated from patients with Mycobacterial intracellular lung disease, prior to mechanical ventilation was significantly higher than that of patients with Mycobacterial abscess ( χ2＝30.366, P ＜0.01 ).In imaging, the proportion of bronchiectasis in Mycobacterium intracellularis lung disease group was significantly higher than that in Mycobacterial abscesses lung disease group (χ2＝23.888, P＜0.01).There was no significant difference in the 28-day mortality rate between the two groups (χ2＝3.244, P＞0.05), while the survival rate in patients with Mycobacterium intracellularis lung disease within 120 days was significantly higher than that in patients with Mycobacterial abscesses lung disease (χ2＝12.780, P＜0.01).Conclusion When critically ill patients are positive for acid-fast staining, the ICU physician should consider the possibility of NTM lung disease.For severe patients with long-term mechanical ventilation , Mycobacterium abscessus infection should be considered first.

Recovery Rates of Non-Tuberculous Mycobacteria from Clinical Specimens Are Increasing in Korean Tertiary-Care Hospitals

Non-tuberculous mycobacteria (NTM) are being recognized increasingly as the causative agents of opportunistic infections in humans. This study investigated the epidemiologic trends of NTM recovery from various clinical specimens in 2 Korean tertiary-care hospitals. We reviewed the laboratory records of patient samples cultured for mycobacteria between 2009 and 2015 at 2 tertiary-care hospitals in Korea. The medical records for patients with positive NTM samples were also reviewed. During the study period, 144,540 specimens were cultured for mycobacteria. The proportion of NTM-positive samples increased from 23.3% in 2009 to 48.2% in 2015. The 2 most frequently isolated NTM were Mycobacterium intracellulare (38.3%) and M. avium (23.1%). The number of clinically significant diseases caused by NTM in inpatients and outpatients increased from 6.8 to 12.9 per 100,000 patients over the same period. The rates of recovery of NTM from clinical specimens and the number of patients with NTM infections increased significantly (P < 0.001, testing for trend) between 2009 and 2015.

Cutaneous Mixed Infection of Mycobacterium fortuitum and Mycobacterium intracellulare after a Fat Graft / 대한피부과학회지

Atypical mycobacteria, widely distributed in nature, are opportunistic infection strain, rare pathogen in immunocompetent patients. Recently, the increase of invasive cosmetic treatment and surgery has increased the infection of atypical mycobacteria. We report a case of cutaneous infection by Mycobacterium fortuitum and Mycobacterium intracellulare that occurred after a fat graft. A 62-year-old female patient presented painful, erythematous nodules and purulent discharge on her face after a fat graft. A skin biopsy and culture were performed. Polymerase chain reaction-hybridization to identify mycobacterium other than tuberculosis revealed M. fortuitum and M. intracellulare. The patient was treated with clarithromycin, rifampicin, and ethambutol for 1 month after excision and drainage of pus, after which the skin lesions improved. In cases of refractory cutaneous infection after an invasive cosmetic procedure, atypical mycobacterial infection should be suspected.

Micobacterias atípicas en cinco pacientes adultos sin evidencias de inmunosupresión: Construyendo una experiencia / Atypical mycobacterial infections in five adult patients without evidence of immunosuppression: Making an experience

We aim to communicate the experience gathered during the management of infections by atypical mycobacteria in immunocompetent patients in a general practice. Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections were identified: 2 with cutaneous involvement and 3 with lung infection. None of them had evidence of immunosuppression. A patient with elbow bursitis by M. chelonae presented with a high mononuclear count in fluid analysis with mycobacterial growth at the fifth day of culture. He evolved satisfactorily with clarithromycin. A case with M. fortuitum skin infection had a delayed initial diagnosis with progression to local draining lymph nodes; the culture when requested was positive after 13 days of incubation. Patients with pulmonary infection presented with prolonged cough and sputum and had in common to be postmenopausal women displaying small nodules and bronchiectases at lung images, a classical pattern. Time elapsed between respiratory sampling and a definitive inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non-immunosuppresed patients can generate diagnostic and therapeutic challenges. Delay in identification contributes to this problem.

El objetivo de este trabajo es reportar la experiencia acumulada sobre infecciones por micobacterias atípicas en pacientes sin inmunosupresión. Entre el año 2008 y 2013 se observaron cinco pacientes con infección por micobacterias atípicas: dos con infección cutánea y tres con infección pulmonar. Ninguno de estos pacientes tenía evidencias de inmunosupresión. Un paciente con bursitis de codo por M. chelonae tuvo un estudio citoquímico con aumento de celularidad de predominio mononuclear y desarrollo de bacterias al quinto día; respondió favorablemente a claritromicina. Un caso con infección cutánea por M. fortuitum evolucionó en forma prolongada con supuración ganglionar antes del diagnóstico y el cultivo solicitado a los 13 días fue positivo. Los tres pacientes con aislados pulmonares presentaron tos y expectoración y tenían en común ser mujeres en edad post-menopáusica y presentar pequeños infiltrados nodulares asociados a bronquiectasias en el estudio de imágenes pulmonares, un patrón descrito en la literatura científica. En estos tres casos, la latencia entre la toma de muestra y el informe definitivo tuvo un rango de 40 a 89 días. El aislamiento de micobacterias atípicas en muestras de expectoración en pacientes sin inmunosupresión se da en un contexto típico pero plantea dificultades diagnósticas y terapéuticas. El lento crecimiento de estos microorganismos en el laboratorio contribuye a este problema.

A Case of Mycobacterium abscessus Lung Disease in a Patient with Cystic Fibrosis / 대한내과학회지

Although cystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians, it is very rare in the Korean population. Patients with CF are at particularly high risk for developing lung disease caused by nontuberculous mycobacteria such as the Mycobacterium avium-intracellulare complex or Mycobacterium abscessus. Here, we report a successfully treated case of M. abscessus lung disease in a Korean patient with CF.

A Case of Vertebral Osteomyelitis With Epidural Abscess Caused by Mycobacterium intracellulare in a Rheumatoid Arthritis Patient

Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial lung diseases, but vertebral osteomyelitis caused by MAC is rare. We experienced a case of vertebral osteomyelitis with epidural abscess in a rheumatoid arthritis patient who received immunosuppressive agents. Initial assessment was tuberculous vertebral osteomyelitis, and then treated with antituberculous drugs. Fifty-six days later, Mycobacterium intracellulare was identified from abscess culture and drugs were altered to clarithromycin, rifabutin, and ethambutol. After 3 months of M. intracellulare treatment, the radiological findings showed increases of epidural abscess. According to the suseptibility, the patient received intravenous amikacin for four weeks, and then, oral ciprofloxacin in addition to clarithromycin, rifabutin, and ethambutol. The patient is being treated with the medication for 13 months and currently showing slow improvements.

A Case of Arthritis due to Mycobacterium Intracellulare in a Immunocompetent Patient

Nontuberculous mycobacteria (NTM) are widely distributed in nature and are usually of low pathogenic potential. NTM rarely has been recognized as a cause of musculoskeletal infections that involve joints, bone and soft tissue in immunocompetent patients. The risk factors of its infection are local traumas caused by surgery, injury, or injection. A fifty five-year-old immunocompetent patient visted to hospital due to right wrist mass and pain. Excisional biopsy was done. Histologically granulomatous inflammation was identified and Mycobacterium intracellulare was cultured. Although very rare, NTM should be suspected at least once as a causative pathogen of chronic arthritis when the cause is uncertain.

An Unusual Case of Post-Operative Spondylitis Caused by Mycobacterium Intracellulare in an Immunosuppressed Patient

There are few reported cases of post-operative spondylitis caused by Mycobacterium intracellulare. A 75-year-old female presented to our hospital with low back pain and paraparesis after a fall. The radiologic examination revealed compression fractures of L1, L3 and L4 and an epidural hematoma compressing the spinal cord. The dark-red epidural hematoma was urgently evacuated. Four weeks post-operatively, neurologic deficits recurred with fever. On magnetic resonance image, an epidural abscess and osteomyelitis were detected in the previous operative site. Five weeks post-operatively, revision was performed with multiple biopsies. The specimen were positive for acid-fast bacilli and traditional anti-tuberculous medications were started. Because the Polymerase Chain Reaction for non-tuberculous mycobacterium (NTM) was positive, the anti-tuberculous medications were changed to anti-NTM drugs. However, the neurologic deficits did not improve and persistent elevation of erythrocyte sedimentation rate and C-reactive protein were noted. Eight weeks after the revision, Mycobacterium intracellulare was detected in the specimen cultures. Despite supportive care with medication, the patient died due to multiple organ failure.

Control of Mycobacterium fortuitum and Mycobacterium intracellulare infections with respect to distinct granuloma formations in livers of BALB/c mice

Mycobacterium fortuitum is a rapidly growing nontuberculous Mycobacterium that can cause a range of diseases in humans. Complications from M. fortuitum infection have been associated with numerous surgical procedures. A protective immune response against pathogenic mycobacterial infections is dependent on the granuloma formation. Within the granuloma, the macrophage effector response can inhibit bacterial replication and mediate the intracellular killing of bacteria. The granulomatous responses of BALB/c mice to rapidly and slowly growing mycobacteria were assessed in vivo and the bacterial loads in spleens and livers from M. fortuitum and Mycobacterium intracellulare-infected mice, as well as the number and size of granulomas in liver sections, were quantified. Bacterial loads were found to be approximately two times lower in M. fortuitum-infected mice than in M. intracellulare-infected mice and M. fortuitum-infected mice presented fewer granulomas compared to M. intracellulare-infected mice. These granulomas were characterized by the presence of Mac-1+ and CD4+ cells. Additionally, IFN-γmRNA expression was higher in the livers of M. fortuitum-infected mice than in those of M. intracellulare-infected mice. These data clearly show that mice are more capable of controlling an infection with M. fortuitum than M. intracellulare. This capacity is likely related to distinct granuloma formations in mice infected with M. fortuitum but not with M. intracellulare.

Identification of two clinical isolates of Mycobacterium intracellulare / 中国人兽共患病学报

To identify the species of Mycobacterium clinical isolates by molecular biology techniques,six clinical isolates which were preliminarily recognized as Mycobacterium tuberculosis by the TCH and PNB culture methods were selected in this study.PCR was applied to amplify the oxyR-ahpC interval resistant-zone(intergenic region) and the length of PCR product in four strains was the same as that of H37Rv,while the length in the other two strains was different from that of H37Rv but same as Mycobacterium intracellulare 95002.With sequencing and on-line homology comparison with H37Rv,U18263 and U71061,the DNA sequence of oxyR-ahpC intergenic region displayed a 99% homology with Mycobacterium intracellulare U71061 and an 84% homology with Mycobacterium tuberculosis H37Rv.In addition,the results of hsp65 PCR-restriction fragment length polymorphism analysis and multi-locus PCR amplification in the two strains were identical with those of Mycobacterium intracellulare 95002.These two clinical isolates which were preliminarily recognized as Mycobacterium tuberculosis by PNB and TCH culture methods were finally identified as Mycobacterium intracellulare.Results predicted that the application associated with various techniques of molecular biology would provide a faster,easier and more correct way for the species identification of Mycobacterium.

A Case of Vertebral Osteomyelitis due to Mycobacterium intracellulare / 감염과화학요법

We report a case of vertebral osteomyelitis due to Mycobacterium intracellulare in a 60-year-old man without predisposing conditions. He was successfully treated with surgical excision of the inflamed tissue and combined antimycobacterial therapy consisting of clarithromycin, ethambutol, and rifampin. In this case, polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) based on the rpo B gene of cultured isolates allowed rapid identification of M. intracellulare. Although very rare, nontuberculous mycobacteria (NTM) should be suspected as a causative pathogen of vertebral osteomyelitis. To the best of our knowledge, this is the first case of vertebral osteomyelitis caused by NTM reported in the Korean literature.

A Case of Vertebral Osteomyelitis due to Mycobacterium intracellulare / 감염과화학요법

We report a case of vertebral osteomyelitis due to Mycobacterium intracellulare in a 60-year-old man without predisposing conditions. He was successfully treated with surgical excision of the inflamed tissue and combined antimycobacterial therapy consisting of clarithromycin, ethambutol, and rifampin. In this case, polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) based on the rpo B gene of cultured isolates allowed rapid identification of M. intracellulare. Although very rare, nontuberculous mycobacteria (NTM) should be suspected as a causative pathogen of vertebral osteomyelitis. To the best of our knowledge, this is the first case of vertebral osteomyelitis caused by NTM reported in the Korean literature.