检索问题
在中国MAC患者发病率是多少？在非结核分枝杆菌肺病中占比多少？
根据所提供的证据，以下是对中国MAC患者发病率和其在非结核分枝杆菌肺病中占比的详细分析：
1. 中国MAC患者的发病率
直接的MAC患者发病率（incidence rate）数据在提供的证据中并未明确给出全国范围的具体百分比，但有研究表明中国NTM（非结核分枝杆菌）的感染和疾病比例呈上升趋势，并且MAC是主要的病原体之一。
- NTM总体流行趋势：
- 一项对2000-2019年中国大陆NTM趋势的系统回顾和荟萃分析显示，NTM在疑似结核病患者中的粗分离率为4.66-5.78%。
- 另一项对2013-2024年中国大陆和台湾NTM感染的系统回顾和荟萃分析发现，疑似结核病患者中NTM的合并流行率为11.27%（95% CI: 9.89-12.65%）。这项研究指出，NTM在中国大陆的流行率在过去十年持续上升，并且现在已经超过了许多全球估计值。
- NTM的隔离率在2009-2021年呈上升趋势，随后在2022-2023年有所下降。
- 在广州胸科医院2013-2016年的回顾性研究中，607例NTM病例中MAC占44.5%。
- 北京协和医学院医院2013-2022年的回顾性研究中，745名NTM感染患者中有147人符合纳入标准，其中NTM肺病最常见（63.3%），而MAC是NTM肺病中最常见的物种（55.8%）。
- 在上海2010-2019年一项基于人群的回顾性研究中，1652例NTM-PD（非结核分枝杆菌肺病）病例中，MAC占27.1%。
- 虽然没有给出全国MAC患者的明确发病率数字，但上述数据表明MAC感染在中国是普遍且呈上升趋势的公共卫生问题，尤其在疑似结核病患者中占有相当大的比例。
2. MAC在非结核分枝杆菌肺病中占比
综合多项在中国进行的研究，MAC（鸟分枝杆菌复合群）在非结核分枝杆菌（NTM）肺病中是主要的致病菌之一，其占比数据因研究地域、时间和方法不同而有所差异，但普遍显示出高流行率。
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全国及区域层面的主导地位：
- 一项对2000-2019年中国大陆NTM趋势的系统回顾和荟萃分析指出，MAC和M. abscessus complex（脓肿分枝杆菌复合群）是最常见的临床NTM物种。这项研究还提到，在研究期间，MAC曾被M. abscessus取代成为主导物种，但整体上MAC仍是重要组成部分。
- 2013-2024年中国大陆和台湾的系统回顾和荟萃分析表明，在缓慢生长分枝杆菌（占总分离株的68.07%）中，MAC（特别是鸟分枝杆菌）占主导地位。
- 在中国南方，MAC是肺部NTM疾病最主要的病原体。例如，在广州胸科医院2013-2016年的研究中，MAC在607例NTM病例中占比44.5%，是所有NTM物种中最常见的。
- 在北京协和医学院医院2013-2022年的回顾性研究中，MAC是NTM肺病组中最常见的NTM物种，占比55.8%。
- 在上海一项对2010-2019年NTM肺病（NTM-PD）病例的研究中，MAC占比27.1%，是第二常见的物种，仅次于M. kansasii complex（堪萨斯分枝杆菌复合群）（41.9%），高于M. abscessus complex（16.2%）。
- 另一项在上海肺科医院收集的393株NTM分离株的研究中，MAC分离株共173株（44.0%），其中M. intracellulare（胞内分枝杆菌）为132株（33.6%），M. avium（鸟分枝杆菌）为41株（10.4%）。这表明在上海地区，M. intracellulare在MAC中更为常见，并且MAC总体占比也较高。
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MAC在全球范围内的普遍性：
- MAC是全球范围内最常被分离出的非结核分枝杆菌呼吸道病原体。在美国，结节性支气管扩张型MAC肺病（NB MAC lung disease）是MAC肺病最常见的形式。
- 在日本，MAC也是最常见的非结核分枝杆菌病原体。
- MAC是导致NTM肺病最常见的原因，并且全球发病率呈上升趋势。
- 欧洲多国研究也显示，MAC在欧洲中部是最常见的非结核分枝杆菌，其中M. avium、M. intracellulare subsp. intracellulare和M. intracellulare subsp. chimaera在临床上最相关。
总结：
在中国，MAC是导致非结核分枝杆菌（NTM）感染和肺病的主要病原体之一。虽然没有精确的全国MAC患者发病率数字，但多项研究表明NTM的总体流行率在上升，并且MAC在其中占据显著比例。
具体而言，MAC在非结核分枝杆菌肺病中的占比在不同研究和地区有所不同，但通常在27%到56%之间：
- 在北京的一项研究中，MAC在NTM肺病患者中占比为55.8%。
- 在广州的一项研究中，MAC在NTM病例中占比44.5%。
- 在上海的两项研究中，MAC的占比分别为27.1%（针对NTM-PD病例）和44.0%（针对NTM分离株）。
这些数据充分说明，MAC在中国非结核分枝杆菌肺病中占据重要且主导的地位，因此对MAC感染的诊断、治疗和监测至关重要。
References
1Treatment of Mycobacterium avium Complex (MAC).PubMed
David E Griffith
complex (MAC) is the most commonly isolated nontuberculous mycobacterial respiratory pathogen worldwide. MAC lung disease is manifested either by fibrocavitary radiographic changes similar to pulmonary tuberculosis or by bronchiectasis with nodular and reticulonodular radiographic changes. This latter form of MAC lung disease, termed "nodular bronchiectatic (NB) MAC lung disease" is the most common form of MAC lung disease in the United States. Treatment at the time of diagnosis is always indicated for fibrocavitary MAC lung disease because it is always progressive and associated with increased morbidity and mortality compared with NB MAC lung disease. In contrast, the NB form of MAC lung disease is more indolent and frequently does not require antimycobacterial therapy. For patients with NB MAC lung disease, the priorities are typically to treat the underlying bronchiectasis and determine the course and impact of the MAC infection over time. Guidelines-based MAC therapy with multidrug regimens including macrolides is usually effective, but far from as predictably effective and durable as therapy for tuberculosis. It is imperative that clinicians are familiar with MAC drug resistance mechanisms and the pitfalls of inappropriate dependence on in vitro drug susceptibility testing which can predispose patients to the development of macrolide resistance with its attendant high mortality. It is now more than 20 years since the emergence of macrolides for MAC therapy with no new comparably effective agents introduced in that time, although one new inhaled amikacin therapy under study offers promise.
2Clinical analysis and risk factors associated with poor prognosis in nontuberculous mycobacterial infection.PubMed
Jinjing Chai, Sujie Zhang, Chong Ma, et al.
Recently, the incidence and prevalence of NTM have been increasing nationwide in many countries. This study aimed to identify risk factors associated with the prognosis and mortality of non-HIV nontuberculous mycobacterial disease patients. This retrospective study was conducted at Peking Union Medical College Hospital. The electronic medical records in the hospital's database from January 2013 to December 2022 were retrospectively reviewed. Relevant data, including clinical characteristics, laboratory findings, microbiological tests, treatments, and outcomes were collected and subjected to statistical analyses. The search identified 745 patients diagnosed with NTM infection, of whom 147 met the inclusion criteria. NTM pulmonary disease was the most commonly observed ( = 93; 63.3%), followed by disseminated infection ( = 43; 29.3%). The most frequent NTM species was complex (55.8%), followed by (21.2%). The incidence of and infection was significantly higher in the NTM pulmonary disease group than in the disseminated NTM group. Cumulative mortality in the total patients was 24.49% at 5 years. High Charlson Comorbidity Index (CCI), high neutrophil-to-lymphocyte-ratio (NLR), haematological disease, and disseminated infection were identified as independent predictors of unfavourable outcomes. The area under the curve (AUC) values for NLR and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) were 0.751 and 0.763 with optimal cut-off values of 9.50 and 3.83, respectively, for prediction of mortality in patients with NTM disease.
3Identification and Phylogenetic Analysis of subsp. Strain Isolated from Cow.PubMed
Yanhong Bao, Tianze Yang, Hanxue Zhang, et al.
subsp. (MAA) is the main tuberculosis pathogen of poultry and wild birds. MAA can also infect mammals such as pigs, cattle, and horses and can pose a threat to people with low immunity. Here, we describe the first identification of MAA strain HJW isolated from a cow in Jilin Province, China. The isolate was completely sequenced and a phylogenetic analysis of its relationship to members of the complex (MAC) was performed. The results revealed that strain HJW was type MAA based on the analysis of insertion sequence amplification and whole genome sequencing. The HJW genome size was 4,961,843 bp with a GC content of 69.28%. The strain was genetically most closely related to the subsp. strain DSM 44156. This study suggests that MAA may pose an infection risk to cattle and provides data support for the phylogeny of .
4Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.PubMed
Charles L Daley, Jonathan M Iaccarino, Christoph Lange, et al.
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
5[Nontuberculous mycobacteria].PubMed
Yuji Shiraishi
Mycobacterium avium complex (MAC) is the most common nontuberculous mycobacterial pathogen in Japan. There are 2 major types of clinical manifestations of MAC disease, including fibrocavitary disease and nodular bronchiectatic disease. Primary treatment of MAC disease is medical treatment. Standard multidrug regimens employ clarithromycin, rifampicin, and ethambutol. Aminoglycoside (streptomycin or kanamycin) is added if necessary. Patients whose disease is predominantly localized to 1 lung and who can tolerate resectional surgery may be considered for surgery under the following circumstances; poor response to drug therapy, the development of macrolide-resistant MAC disease, or the presence of hemoptysis. Surgery for MAC lung disease can achieve favorable treatment outcome. However, surgery is associated with significant morbidity, especially when pneumonectomy is performed. When surgical intervention is considered necessary for MAC patients, pulmonary resection should be performed before MAC lung disease has progressed too extensively to avoid pneumonectomy.
6Epidemiology of pulmonary disease due to nontuberculous mycobacteria in Southern China, 2013-2016.PubMed
Yaoju Tan, Biyi Su, Wei Shu, et al.
BACKGROUND: Pulmonary nontuberculous mycobacteria (NTM) disease is of increasing public health concern in China. Information is limited regarding risk factors associated with this disease in China. The objective of this study was to describe the epidemiology of pulmonary disease due to NTM in Southern China. METHODS: We retrospectively reviewed the medical records of pulmonary NTM patients registered in the Guangzhou Chest Hospital with positive mycobacterial cultures during 2013-2016. We described sex, age, residence, treatment history, laboratory examination results and comorbidities of pulmonary NTM patients. RESULTS: Among the 607 NTM cases, the most prevalent species were Mycobacterium avium complex (44.5%), Mycobacterium abscessus complex (40.5%), Mycobacterium kansasii (10.0%) and Mycobacterium fortuitum (2.8%). The male:female ratio was significantly lower among patients infected with rapidly growing mycobacteria (RGM) than among those with slowly growing mycobacteria (SGM). The risk of developing SGM disease significantly increased with advancing age. In addition, pulmonary RGM diseases were more common in migrant population than resident population. Notably, patients with pulmonary RGM diseases were significantly more likely to have bronchiectasis underlying noted than those with SGM diseases. No significant difference was observed in in vitro drug susceptibility among NTM species. CONCLUSION: Our data illustrate that the M. avium complex is the most predominant causative agent of pulmonary NTM disease in Southern China. Female, migrant population, the presence of bronchiectasis are independent risk factors for pulmonary diseases due to RGM. In addition, the prevalence of SGM increases significantly with advancing age.
7Trends in the Prevalence and Antibiotic Resistance of Non-tuberculous Mycobacteria in Mainland China, 2000-2019: Systematic Review and Meta-Analysis.PubMed
Lei Zhou, Da Xu, Hancan Liu, et al.
China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the prevention, control, and management of tuberculosis (TB) and posing a significant threat to human health. However, there is a lack of an organized monitoring system for NTM such as that used for tuberculosis. Comprehensive data on patient susceptibility, dominant species, and drug resistance profiles are needed to improve the treatment protocols and the management of NTM. Primary research reports of NTM clinical specimens from mainland China published between January 1, 2000 and May 31, 2019 were retrieved from four online resources (BIOSIS, Embase, PubMed, and Web of Science) and three Chinese medical literature databases (CNKI, Wanfang, and Vip) as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In total, 339 publications were included in the systematic review, 129 were used in the drug susceptibility analysis, and 95 were used in the meta-analysis. Traditional culture using Lowenstein-Jensen slants combined with P-nitrobenzene acid and thiophene-2-carboxylic acid hydrazine differential medium and proportional method was most commonly used for the isolation, identification, and drug susceptibility testing of NTM in China. The crude isolation rate for NTM among TB suspected cases was 4.66-5.78%, while the proportion of NTM among isolates was 11.57%. and complex were the most common clinical NTM species. NTM only showed general sensitivity to ethambutol, linezolid, clofazimine, amikacin, tobramycin, and clarithromycin. The prevalence of NTM in China has shown a decreasing trend. was replaced as the dominant species by over the course of the study. The geographic diversity of different species showed the effects of environmental and economic factors on the distribution of NTM and indicated that there were important factors still not identified. While there were only a limited number of antibiotics to which NTM showed any sensitivity, the drug resistance profiles of the isolates were highly variable and thus more caution should be taken when empirically treating NTM infection.
8Nontuberculous Mycobacteria.PubMed
Shera Tan, Shannon Kasperbauer
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and 193 species of NTM have been discovered thus far. NTM species vary in virulence from benign environmental organisms to difficult-to-treat human pathogens. Pulmonary infections remain the most common manifestation of NTM disease in humans and bronchiectasis continues to be a major risk factor for NTM pulmonary disease (NTM PD). This article will provide a useful introduction and framework for clinicians involved in the management of bronchiectasis and NTM. It includes an overview of the epidemiology, pathogenesis, diagnosis, and management of NTM PD. We will address the challenges faced in the diagnosis of NTM PD and the importance of subspeciation in guiding treatment and follow-up, especially in infections. The treatment of both complex and , the two most common NTM species known to cause disease, will be discussed in detail. Elements of the recent ATS/ERS/ESCMID/IDSA NTM guidelines published in 2020 will also be reviewed.
9Serum Cell-Free DNA-based Detection of Complex Infection.PubMed
Lin Li, Emily Henkle, Brady M Youngquist, et al.
complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) pulmonary disease (PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A clustered regularly interspaced short palindromic repeats (CRISPR)-based assay that measures MAC cell-free DNA (cfDNA) concentrations in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment. To develop and optimize a CRISPR MAC assay for MAC infection detection and to evaluate its diagnostic and prognostic performance in two MAC disease cohorts. MAC cfDNA serum concentrations were measured in individuals with diagnoses of MAC disease or who had bronchiectasis or chronic obstructive pulmonary disease diagnoses without histories of NTM PD or NTM-positive sputum cultures. Diagnostic performance was analyzed using pretreatment serum from two cohorts. Serum MAC cfDNA changes during MAC PD treatment were evaluated in a subset of patients with MAC PD who received macrolide-based multidrug regimens. The CRISPR MAC assay detected MAC cfDNA in MAC PD with 97.6% (91.6-99.7%) sensitivity and 97.6% (91.5-99.7%) specificity overall. Serum MAC cfDNA concentrations markedly decreased after MAC-directed treatment initiation in patients with MAC PD who demonstrated MAC culture conversion. This study provides preliminary evidence for the utility of a serum-based CRISPR MAC assay to rapidly detect MAC infection and monitor the response to treatment.
10Spatial Heterogeneity of Nontuberculous Mycobacterial Pulmonary Disease in Shanghai: Insights from a Ten-Year Population-Based Study.PubMed
Yangyi Zhang, Ruoyao Sun, Chenlei Yu, et al.
OBJECTIVE: To investigate the spatial heterogeneity of nontuberculous mycobacterial pulmonary disease (NTM-PD) in Shanghai. METHODS: A population-based retrospective study was conducted using presumptive pulmonary tuberculosis surveillance data of Shanghai between 2010 and 2019. The study described the spatial distribution of NTM-PD notification rates, employing hierarchical Bayesian mapping for high-risk areas and the Getis-Ord Gi* statistic to identify hot spots and explore associated factors. RESULTS: Of 1652 NTM-PD cases, the most common species was Mycobacterium kansasii complex (MKC) (41.9%), followed by Mycobacterium avium complex (MAC) (27.1%) and Mycobacterium abscessus complex (MABC) (16.2%). MKC-PD patients were generally younger males with a higher incidence of pulmonary cavities, while MAC-PD patients were more often farmers or had a history of tuberculosis treatment. MKC-PD hot spots were primarily located in the areas alongside the Huangpu River, while MAC-PD hot spots were mainly in the western agricultural areas. Patients with MKC-PD and MAC-PD exhibited a higher risk of spatial clustering compared to those with MABC-PD. CONCLUSIONS: Different types of NTM-PD exhibit distinct patterns of spatial clustering and are associated with various factors. These findings underscore the importance of environmental and host factors in the epidemic of NTM-PD.
11Non-tuberculous mycobacterial infections in mainland China and Taiwan: a systematic review and meta-analysis of epidemiology, species distribution, and drug resistance (2013-2024).PubMed
Xinru Xu, Yanyi Lei, Li Zheng
INTRODUCTION: Non-tuberculous mycobacteria (NTM) represent an emerging public health threat in China. Despite evidence of rising NTM prevalence and significant regional variation, comprehensive and up-to-date nationwide data on epidemiology, species distribution, and drug resistance patterns have been lacking. This study aimed to systematically evaluate the prevalence, geographical and temporal trends, species composition, and antimicrobial resistance of NTM in mainland China and Taiwan from 2013 to 2024. METHODS: Adhering to PRISMA guidelines, this systematic review and meta-analysis (PROSPERO: CRD42024540102) included 43 studies (2013-2024) encompassing 17,959 NTM isolates from 225,733 suspected TB patients. Stata software was used for meta-analysis with a random-effects model; publication bias was assessed via Egger's test and funnel plots. RESULTS: The pooled NTM prevalence among suspected tuberculosis patients was 11.27% (95% CI: 9.89-12.65%), with marked geographic variation: highest in northeast (24.18%) and southeast coastal regions (12.83%), and lowest in southwest (2.30%). Slowly growing mycobacteria accounted for 68.07% of isolates, dominated by complex (especially ); rapidly growing mycobacteria (26.57%) were more prevalent in southern provinces, with predominant. An overall upward trend in NTM isolation was observed from 2009-2021, followed by a decline in 2022-2023. Widespread resistance to first-line antituberculosis drugs was universal, whereas clarithromycin, amikacin, linezolid, and clofazimine retained good activity. CONCLUSION: NTM prevalence in China has continued to rise over the past decade and now exceeds many global estimates, with pronounced coastal-southern predominance. The persistently high resistance to standard antituberculosis drugs underscores the urgent need for standardized diagnostic protocols, mandatory NTM reporting, enhanced surveillance networks, and region-tailored treatment guidelines. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024540102.
12Mycobacterium avium Complex Disease.PubMed
Charles L Daley
Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient. Successful treatment requires a multipronged approach that includes antibiotics, aggressive pulmonary hygiene, and sometimes resection of the diseased lung. A combination of azithromycin, rifampin, and ethambutol administered three times weekly is recommend for nodular bronchiectatic disease, whereas the same regimen may be used for cavitary disease but administered daily and often with inclusion of a parenteral aminoglycoside. Disseminated MAC (DMAC) is almost exclusively seen in patients with late-stage AIDS and can be treated with a macrolide in combination with ethambutol, with or without rifabutin: the most important intervention in this setting is to gain HIV control with the use of potent antiretroviral therapy. Treatment outcomes for many patients with MAC disease remain suboptimal, so new drugs and treatment regimens are greatly needed. Given the high rate of reinfection after cure, one of the greatest needs is a better understanding of where infection occurs and how this can be prevented.
13Correlation of drug exposure and bacterial susceptibility with treatment response for lung disease: protocol for a prospective observational cohort study.PubMed
Xubin Zheng, Li Wang, Lina Davies Forsman, et al.
INTRODUCTION: The burden of (MAC) lung disease is increasing globally and treatment outcome is in general poor. Therapeutic drug monitoring has the potential to improve treatment outcome by ensuring adequate drug exposure. However, very limited population-based studies exist for MAC lung disease. This study aims to describe the distribution of drug exposure for key antimycobacterial drugs at population level, and to analyse them in relationship to treatment outcome in patients with MAC lung disease. METHODS AND ANALYSIS: A prospective cohort aiming to include 100 adult patients diagnosed with and treated for MAC lung disease will be conducted in Shanghai Pulmonary Hospital, China. Blood samples will be collected after 1 month MAC treatment for measurement of macrolides, rifamycin, ethambutol, amikacin and/or fluoroquinolones, using a validated liquid-chromatography tandem mass spectrometry method. Respiratory samples will be collected at inclusion and once every 3 months for mycobacterial culture until treatment completion. Minimum inhibitory concentration (MIC) determination will be performed using a commercial broth microdilution plate. In addition to mycobacterial culture, disease severity and clinical improvement will be assessed from the perspective of lung function, radiological presentation and self-reported quality of life. Whole genome sequencing will be performed for any longitudinal isolates with significant change of MIC to explore the emergence of drug resistance-conferring mutations. The relationship between drug exposure and treatment outcome will be analysed and potential confounders will be considered for adjustment in multivariable models. Meanwhile, the associations between drug exposure in relation to MIC and markers of treatment response will be explored using Cox proportional hazards or binary logistic regression models, as appropriate. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of Shanghai Pulmonary Hospital (No. K22-149Z). Written and oral informed consent will be obtained from all participants. The study results will be submitted to a peer-reviewed journal. TRIAL REGISTERATION NUMBER: NCT05824988.
14Nontuberculous mycobacteria.PubMed
D E Griffith
The nontuberculous mycobacteria (NTM), especially Mycobacterium avium complex, are being recognized with increasing frequency as clinical pathogens, not only as a cause of disseminated disease in patients with AIDS but also as a cause of chronic lung disease in patients without AIDS. These infections have traditionally been difficult and frustrating to treat; however, the introduction of new agents, such as clarithromycin, azithromycin, and rifabutin, has significantly improved outcome for patients with some NTM infections. The new therapeutic regimens can be associated with severe toxicities and drug interactions that dictate the need for careful monitoring of patients undergoing treatment for M. avium complex disease. Clinicians will be called on with increasing frequency to determine the significance of NTM isolated from their patients. This determination will require knowledge about the pathogenicity and the appropriate therapy of a variety of NTM species.
15Comparing the Genotype and Drug Susceptibilities between Mycobacterium avium and Mycobacterium intracellulare in China.PubMed
Hui Wen Zheng, Yu Pang, Guang Xue He, et al.
OBJECTIVE: Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M. intracellulare) are the major causative agents of nontuberculous mycobacteria (NTM)-related pulmonary infections. However, little is known about the differences in drug susceptibility profiles between these two species. METHODS: A total of 393 NTM isolates were collected from Shanghai Pulmonary Disease Hospital. Sequencing of partial genes was performed to identify the strains at species level. The minimum inhibitory concentration (MIC) was used to evaluate the drug susceptibility against 20 antimicrobial agents. Variable number of tandem repeat (VNTR) typing was conducted to genotype these two species. RESULTS: A total of 173 (44.0%) M. avium complex (MAC) isolates were identified, including 41 (10.4%) M. avium isolates and 132 (33.6%) M. intracellulare isolates. Clarithromycin and amikacin were the two most effective agents against MAC isolates. The Hunter-Gaston Discriminatory Index (HGDI) values for VNTR typing of M. avium and M. intracellulare isolates were 0.993 and 0.995, respectively. Levofloxacin resistance was more common among the unclustered strains than among the clustered strains of M. intracellulare. CONCLUSION: M. intracellulare was the most common NTM species in China. Clarithromycin and amikacin had high antimicrobial activities against MAC. VNTR typing of MAC isolates revealed a high discriminatory power. Levofloxacin resistance was associated with unclustered strains of M. intracellulare.
16Mycobacterium avium: an overview.PubMed
Caroline Busatto, Júlia Silveira Vianna, Lande Vieira da Silva, et al.
Mycobacterium avium is an environmental microorganism found in soil and water sources worldwide. It is the most prevalent species of nontuberculous mycobacteria that causes infectious diseases, especially in immunocompromised individuals. This review discusses and highlights key topics about M. avium, such as epidemiology, pathogenicity, glycopeptidolipids, laboratory identification, genotyping, antimicrobial therapy and antimicrobial resistance. Additionally, the main comorbidities associated with M. avium infection are discussed.
17Clinical and genomic features of Mycobacterium avium complex: a multi-national European study.PubMed
Nils Wetzstein, Margo Diricks, Thomas B Anton, et al.
BACKGROUND: The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. METHODS: Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. RESULTS: Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). CONCLUSIONS: This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.