堪萨斯分枝杆菌作为无人类免疫缺陷病毒(HIV)患者非结核分枝杆菌(NTM)引起肺部感染的主要病因:来自阿根廷布宜诺斯艾利斯一个中心的经验

G. Yusti, M. Heres, Alejandra González, Mariano Fielli, A. Ceccato, A. Zapata
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Methods: A retrospective review of all the respiratory cultures positive for NTM in the Bacteriology Laboratory of Posadas Hospital between January 2010 and December 2015 was performed. 31 patients without Human Immunodeficiency Virus (HIV) from whom NTM was isolated in respiratory samples, which fulfilled diagnostic criteria for NTM disease were included. Results: The mean age was 50 years at the time of the diagnosis (SD ± 17.2); and 19 patients (61.3%) were males. Mycobacterium kansasii was the most commonly isolated NTM (68%) followed by Mycobacterium avium Complex (MAC) (19%). M. kansasii was the most common cause of pulmonary infection by NTM in these HIV-negative patients. Cultures should be performed to identify the species and to treat accordingly. 46% of the patients included in the study, there was no evidence of risk factors. Only 32% of the subjects had respiratory comorbidities, and the most common radiologic finding was cavitation (55%). Discussion: Our study indicates that M. kansasii is the primary etiology of NTM pulmonary disease in HIV-negative patients in our service area in Buenos Aires. This finding supports the consideration that patients with symptoms compatible with pulmonary tuberculosis should also be evaluated for NTM with appropriate acid-fast bacilli cultures, as treatment regimens differ vastly according to the specific pathogen isolated, although clinical and radiographic presentations may have overlapping features. The possibility of M. kansasii pulmonary disease or other NTM should be considered in patients treated empirically for TB without appropriate clinical response. 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Many epidemiological reports and reviews have shown that NTM disease have been increasing since the 1950s [1,6]. The clinical significance of NTM isolation is not always clear and it is difficult to assess the incidence or prevalence of NTM disease due to several factors, notably its difficulty in differentiation from colonization. Although the detection of NTM colonies has been increasing since the 1950s [6] it is unclear why NTM disease have been increasing in humans. There are several potential contributing factors, such as, (i) an increase of mycobacterial infection sources in the environment, (ii) an increase in susceptible individuals, such as those Human Immunodeficiency Virus (HIV) positive, (iii) improvements in detection methods and laboratory equipment sensitivities (iv) an increasing life expectancy of those with chronic structural pulmonary disease (v) an increased awareness of NTM diseases [1,7]. In many countries, especially those in high-burden areas for TB, the diagnosis of TB is mainly based on the detection of acid-fast bacilli in a sputum smear, as well as on their symptoms and the results of a chest X-ray [1]. Pulmonary diseases caused by NTM could be presumptively treated as pulmonary tuberculosis (TB) as the microbiologic smear of the sputum does not distinguish NTM from TB, and the clinical manifestations are similar. In Latin America the prevalence of NTM is estimated to be much lower than that of TB. The incidence of tuberculosis in Argentina is of 23,91/ 100,000 inhabitants with wide regional variations. In the province of Buenos Aires, it is 30,27/100,000 inhabitants. There are differences in the relative abundances of mycobacterial species that cause NTM diseases across geographic areas, the NTM distribution is most notably associated with variants in environmental factors such as, soil and water distribution systems [1,7]. 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引用次数: 1

摘要

文献中很少描述hiv阴性患者因非结核分枝杆菌(NTM)肺部感染而引起的肺部疾病。目前,NTM由150多种组成,它们在全球自然和人为环境中普遍存在。本研究的目的是确定阿根廷布宜诺斯艾利斯市hiv阴性患者中最常见的NTM引起肺部疾病的种类。NTM引起的肺部疾病的患病率很难确定,因为NTM的分离并不一定意味着疾病。方法:回顾性分析2010年1月至2015年12月Posadas医院细菌学实验室所有NTM呼吸道培养阳性病例。本研究纳入31例呼吸道样本中分离到NTM的非HIV患者,符合NTM病诊断标准。结果:确诊时平均年龄50岁(SD±17.2);男性19例(61.3%)。最常见的NTM是堪萨斯分枝杆菌(68%),其次是鸟分枝杆菌复合体(MAC)(19%)。在这些hiv阴性患者中,堪萨斯分枝杆菌是NTM肺部感染的最常见原因。应进行培养以确定菌种并进行相应的处理。研究中46%的患者,没有危险因素的证据。只有32%的受试者有呼吸道合并症,最常见的放射学发现是空化(55%)。讨论:我们的研究表明,M. kansasii是我们在布宜诺斯艾利斯服务地区hiv阴性患者NTM肺病的主要病因。这一发现支持了这样一种观点,即症状与肺结核相一致的患者也应该通过适当的抗酸杆菌培养来评估NTM,因为根据分离的特定病原体,治疗方案有很大差异,尽管临床和放射学表现可能有重叠的特征。在经验治疗的结核病患者没有适当的临床反应时,应考虑堪萨斯分枝杆菌肺病或其他NTM的可能性。DOI: 10.18297/jri/vol2/iss1/5收件日期:2018年2月12日收件日期:2018年3月17日网站:https://ir.library.louisville.edu/jri隶属机构:1Alejandro Posadas National Hospital, Buenos Aires, Argentina©2018,作者。通讯作者:Alejandra González工作地址:Alejandro Posadas National Hospital, Buenos Aires, Argentina工作邮箱:alestork@yahoo.com.ar全球肺部疾病常见的NTM病因[5]。很难比较不同地理区域NTM疾病的发病率和流行程度。由于大多数国家不要求向公共卫生当局报告NTM疾病,因此对NTM疾病发病率和流行率的研究在不同国家开展的方式不同。为了比较关于在有限地理区域内NTM发病率和流行率随时间变化的报告,必须比较使用相同方法的报告。许多流行病学报告和综述表明,自20世纪50年代以来,NTM疾病一直在增加[1,6]。NTM分离的临床意义并不总是明确的,由于几个因素,特别是难以与定植区分,难以评估NTM病的发病率或患病率。虽然自20世纪50年代以来NTM菌落的检测一直在增加[6],但尚不清楚为什么NTM病在人类中增加。有几个潜在的促成因素,例如,(i)环境中分枝杆菌感染源的增加,(ii)易感个体的增加,例如人类免疫缺陷病毒(HIV)阳性的个体,(iii)检测方法和实验室设备灵敏度的改进,(iv)慢性结构性肺病患者的预期寿命延长,(v)对NTM疾病的认识提高[1,7]。在许多国家,特别是结核病高负担地区,结核病的诊断主要基于痰涂片中抗酸杆菌的检测,以及它们的症状和胸部x线检查结果[1]。NTM引起的肺部疾病可推定为肺结核(TB),因为痰中微生物涂片不能区分NTM与TB,且临床表现相似。在拉丁美洲,NTM的流行率估计远低于结核病。阿根廷的结核病发病率为2391 / 10万居民,区域差异很大。在布宜诺斯艾利斯省,每10万居民中就有3027人患病。 不同地理区域导致NTM疾病的分枝杆菌种类的相对丰度存在差异,NTM的分布与土壤和水分布系统等环境因素的变异最为显著[1,7]。在hiv阴性患者中,NTM引起的肺部疾病在文献中很少有报道[8]。本研究的目的是确定阿根廷布宜诺斯艾利斯市hiv阴性患者中最常见的NTM引起肺部疾病的种类。材料与方法回顾性分析2010年1月至2015年12月Posadas医院细菌学实验室所有NTM呼吸道培养阳性病例。波萨达斯医院是一家高度复杂的医院,拥有500张住院床位,服务区覆盖约440万人口。本研究已获得IRB批准。年龄大于15岁且符合ATS/IDSA对NTM所致肺部疾病诊断标准的患者纳入研究[2]。研究中的所有患者都进行了HIV筛查,我们排除了那些呈现HIV血清学阳性的患者。采用BACTEC MGIT(荧光)培养基和固体培养基(Lowenstein Jensen)进行培养。采用横向流动免疫法(LFA)对阳性培养物进行区分NTM和TB。分析以下变量:年龄、性别、NTM种类、临床和放射学特征。对于分类变量,我们使用百分比作为频率测量。根据样本分布,连续变量表示为平均值或中位数。采用计算环境R 3.4.3版软件进行统计分析[9]。
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Myobacterium kansasii as the Primary Etiology of Pulmonary Infections due to Non-Tuberculous Mycobacterium (NTM) in Patients WIthout Human Immunodeficiency Virus (HIV): Experience from a Center in Buenos Aires, Argentina
Introduction: Pulmonary diseases due to non-tuberculous mycobacterium (NTM) lung infection in HIV-negative patients are rarely described in the literature. Currently, NTM consist of more than 150 species, and they are globally ubiquitous in both natural and man-made environments.The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIVnegative patients in the city of Buenos Aires, Argentina. The prevalence of pulmonary diseases caused by NTM is difficult to determine since the isolation of NTM does not necessarily indicate disease. Methods: A retrospective review of all the respiratory cultures positive for NTM in the Bacteriology Laboratory of Posadas Hospital between January 2010 and December 2015 was performed. 31 patients without Human Immunodeficiency Virus (HIV) from whom NTM was isolated in respiratory samples, which fulfilled diagnostic criteria for NTM disease were included. Results: The mean age was 50 years at the time of the diagnosis (SD ± 17.2); and 19 patients (61.3%) were males. Mycobacterium kansasii was the most commonly isolated NTM (68%) followed by Mycobacterium avium Complex (MAC) (19%). M. kansasii was the most common cause of pulmonary infection by NTM in these HIV-negative patients. Cultures should be performed to identify the species and to treat accordingly. 46% of the patients included in the study, there was no evidence of risk factors. Only 32% of the subjects had respiratory comorbidities, and the most common radiologic finding was cavitation (55%). Discussion: Our study indicates that M. kansasii is the primary etiology of NTM pulmonary disease in HIV-negative patients in our service area in Buenos Aires. This finding supports the consideration that patients with symptoms compatible with pulmonary tuberculosis should also be evaluated for NTM with appropriate acid-fast bacilli cultures, as treatment regimens differ vastly according to the specific pathogen isolated, although clinical and radiographic presentations may have overlapping features. The possibility of M. kansasii pulmonary disease or other NTM should be considered in patients treated empirically for TB without appropriate clinical response. DOI: 10.18297/jri/vol2/iss1/5 Received Date: February 12, 2018 Accepted Date: March 17, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1Alejandro Posadas National Hospital, Buenos Aires, Argentina ©2018, The Author(s). 21 ULJRI Vol 2, (1) 2018 ORIGINAL RESEARCH *Correspondence To: Alejandra González Work Address: Alejandro Posadas National Hospital, Buenos Aires, Argentina, Work Email: alestork@yahoo.com.ar common NTM cause of pulmonary disease worldwide [5]. It is difficult to compare the incidence and prevalence of NTM diseases across geographic areas. Because reporting NTM disease to public health authorities is not required in most countries, studies of the incidence and prevalence of NTM disease are performed differently in different countries. To compare reports regarding changes in the incidence and prevalence of NTM disease over time in a limited geographic area, one must compare reports that used the same methods. Many epidemiological reports and reviews have shown that NTM disease have been increasing since the 1950s [1,6]. The clinical significance of NTM isolation is not always clear and it is difficult to assess the incidence or prevalence of NTM disease due to several factors, notably its difficulty in differentiation from colonization. Although the detection of NTM colonies has been increasing since the 1950s [6] it is unclear why NTM disease have been increasing in humans. There are several potential contributing factors, such as, (i) an increase of mycobacterial infection sources in the environment, (ii) an increase in susceptible individuals, such as those Human Immunodeficiency Virus (HIV) positive, (iii) improvements in detection methods and laboratory equipment sensitivities (iv) an increasing life expectancy of those with chronic structural pulmonary disease (v) an increased awareness of NTM diseases [1,7]. In many countries, especially those in high-burden areas for TB, the diagnosis of TB is mainly based on the detection of acid-fast bacilli in a sputum smear, as well as on their symptoms and the results of a chest X-ray [1]. Pulmonary diseases caused by NTM could be presumptively treated as pulmonary tuberculosis (TB) as the microbiologic smear of the sputum does not distinguish NTM from TB, and the clinical manifestations are similar. In Latin America the prevalence of NTM is estimated to be much lower than that of TB. The incidence of tuberculosis in Argentina is of 23,91/ 100,000 inhabitants with wide regional variations. In the province of Buenos Aires, it is 30,27/100,000 inhabitants. There are differences in the relative abundances of mycobacterial species that cause NTM diseases across geographic areas, the NTM distribution is most notably associated with variants in environmental factors such as, soil and water distribution systems [1,7]. Pulmonary diseases due to NTM in HIV-negative patients are rarely described in the literature [8]. The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIV-negative patients in the city of Buenos Aires, Argentina. Materials and Methods A retrospective review of all the respiratory cultures positive for NTM in the Bacteriology Laboratory of Posadas Hospital between January 2010 and December 2015 was performed. Posadas Hospital is a high complexity hospital with 500 admission beds and a service area covering a population of approximately 4,400,000. IRB approval was obtained for this study. Patients older than 15 years old that fulfilled the ATS/IDSA diagnostic criteria for pulmonary disease due to NTM were included in the study [2]. All patients in the study were screened for HIV and we excluded those who presented with positive HIV serology. The method utilized to perform the cultures was the BACTEC MGIT (fluorescence) in addition to solid culture media (Lowenstein Jensen). Lateral flow immunoassay (LFA) were performed on positive cultures to differentiate NTM from TB. The following variables were analyzed: age, sex, NTM species, and clinical and radiological characteristics. For the categorical variables, we used percentages as frequency measurements. The continuous variables were expressed as mean or median depending on the sample distribution. Statistical analysis was performed using the computing environment R version 3.4.3 software [9].
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