Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease.

BACKGROUND: Mycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated. RESULTS: In this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies. CONCLUSIONS: Our data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.

Successful Cord Blood Transplantation for Idiopathic CD4+ Lymphocytopenia.

Idiopathic CD4+ lymphocytopenia (ICL) is the depletion of CD4+ lymphocytes to <300 cells/mm3 without human immunodeficiency virus infection or other causes of lymphocytopenia. ICL causes fatal infections; its etiology remains unclear and it lacks consensus regarding therapeutic options. We report the first patient with ICL who had a successful clinical course following a cord blood transplant (CBT). A 45-year-old woman was diagnosed with ICL and underwent partial hepatectomy for an abscess caused by the Mycobacterium avium complex. No specific gene alterations were detected through next generation sequencing-based evaluation. Following a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, busulfan, and 4 Gy total body irradiation, a single-unit CBT was performed. Neutrophils were engrafted on day +14. CD4+ lymphocyte counts increased to over 300 cells/mm3 on day +436. After 75 months, she was alive without any sequelae. CBT with an RIC regimen could be a curable treatment option for ICL.

Mycobacterium avium paratuberculosis and Mycobacterium avium complex and related subspecies as causative agents of zoonotic and occupational diseases.

Mycobacterium avium complex (MAC) and Mycobacterium avium paratuberculosis (MAP) cause zoonotic infections transmitted by birds and livestock herds. These pathogens have remained as serious economic and health threats in most areas of the world. As zoonotic diseases, the risk of development of occupational disease and even death outcome necessitate implementation of control strategies to prevent its spread. Zoonotic MAP infections include Crohn's disease, inflammatory bowel disease, ulcerative colitis, sarcoidosis, diabetes mellitus, and immune-related diseases (such as Hashimoto's thyroiditis). Paratuberculosis has classified as type B epidemic zoonotic disease according to world health organization which is transmitted to human through consumption of dairy and meat products. In addition, MAC causes pulmonary manifestations and lymphadenitis in normal hosts and human immunodeficiency virus (HIV) progression (by serotypes 1, 4, and 8). Furthermore, other subspecies have caused respiratory abscesses, neck lymph nodes, and disseminated osteomyelitis in children and ulcers. However, the data over the occupational relatedness of these subspecies is rare. These agents can cause occupational infections in susceptible herd breeders. Several molecular methods have been recognized as proper strategies for tracking the infection. In this study, some zoonotic aspects, worldwide prevalence and control strategies regarding infections due to MAP and MAC and related subspecies has been reviewed.

Mycobacterium avium complex infection in patients with human immunodeficiency virus: A systematic review and meta-analysis.

BACKGROUND: Mycobacterium avium-intracellulare complex (MAC) is one of the leading causes of death among people living with human immunodeficiency virus (HIV). The current study was aimed to determine the frequency of MAC infection in patients infected with HIV. METHODS: Embase, PubMed, and Web of Science were searched for relevant studies. All statistical analyses were performed by STATA version 14. RESULTS: From 6,627 retrieved articles, 23 were included in the final analysis. A total of 18,463 patients with HIV were included in the analysis. The frequency of MAC infection in patients with HIV was found to be 10.6% (95% confidence interval, 6.9-14.2). CONCLUSION: The relatively large fractions of HIV-infected patients were coinfected with MAC, which may poses significant public health problems. Continued progress in the development of rapid diagnostic methods and preventive therapy for MAC should lead to further improvements in survival and quality of life in patients with HIV.

Intermittent Treatment with Azithromycin and Ethambutol for Noncavitary Mycobacterium avium Complex Pulmonary Disease.

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary Mycobacterium avium complex pulmonary disease (MAC-PD). Twenty-nine (76%) of 38 patients achieved sputum culture conversion after 12 months of treatment, and sputum smear positivity was an independent factor for failure to achieve culture conversion (adjusted odds ratio, 26.7; 95% confidence interval, 2.1 to 339.9; P = 0.011). Intermittent azithromycin and ethambutol may be an optional treatment regimen for noncavitary MAC-PD.

Species distribution and clinical features of infection and colonisation with non-tuberculous mycobacteria in a tertiary care centre, central Germany, 2006-2016.

PURPOSE: NTM are ubiquitous bacteria that can cause colonisation and infection in immunocompetent and compromised hosts. The aim of this study was to elucidate the epidemiology of infection or colonisation with NTM for the metropolitan region of Frankfurt, Germany. METHODS: All patients from whom NTM were isolated within the period from 2006 to 2016 were included in this retrospective analysis. Patient data were retrieved using the local patient data management system. Different groups were formed according to clinical manifestations, underlying diseases and mycobacterial species. They were compared in regard to mortality, duration of infection/colonisation and their geographical origins. RESULTS: A total of 297 patients with a median of 28 new patients each year were included. Most patients suffered from lung infection or colonisation (72.7%, n = 216), followed by disseminated mycobacteriosis (12.5%, n = 37). The majority were HIV-positive, suffering from malignoma or cystic fibrosis (29.3%, n = 87, 16.2%, n = 48, and 13.8%, n = 41, respectively). 17.2% of patients showed no predisposing condition (n = 51). Mycobacterium avium complex (MAC) species were most frequently isolated (40.7%, n = 121). Infection/colonisation was longest in CF patients (median of 1094 days). The mortality was highest in malignoma patients (52.4%), while CF patients had the lowest overall mortality rate (5.3%). But mortality analysis showed non-significant results within different mycobacterial species and clinical manifestations. CONCLUSION: NTM remain rare but underestimated pathogens in lung and disseminated disease. MAC were the species most frequently isolated. Depending on species and underlying predispositions, the duration of infection/colonisation can be unexpectedly long.

Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmonary disease in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease. METHODS: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD. RESULTS: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m2 and lymphocyte count <1500/µl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD. CONCLUSION: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.

Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with Mycobacterium avium Complex and Mycobacterium abscessus Complex.

Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus (25% [3/12]) than in patients infected with MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.

High mortality in patients with Mycobacterium avium complex lung disease: a systematic review.

BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) pulmonary disease caused by Mycobacterium avium complex (MAC) in apparently immune-competent people is increasing worldwide. We performed a systematic review of the published literature on five-year all-cause mortality in patients with MAC lung disease, and pooled the mortality rates to give an overall estimate of five-year mortality from these studies. METHODS: We systematically reviewed the literature up to 1st August 2017 using PubMed® and ProQuest Dialog™ to search Medline® and Embase® databases, respectively. Eligible studies contained > 10 patients with MAC, and numerical five-year mortality data or a treatment evaluation for this patient group. Mortality data were extracted and analysed to determine a pooled estimate of all-cause mortality. RESULTS: Fourteen of 1035 identified studies, comprising 17 data sets with data from a total of 9035 patients, were eligible. The pooled estimate of five-year all-cause mortality was 27% (95% CI 21.3-37.8%). A high degree of heterogeneity was observed (I2 = 96%). The mortality in the data sets varied between 10 and 48%. Studies predominantly including patients with cavitary disease or greater comorbidity reported a higher risk of death. Patients in Asian studies tended to have a lower mortality risk. Predictors of mortality consistent across studies included male sex, presence of comorbidities and advanced patient age. CONCLUSIONS: Despite high heterogeneity, most studies in patients with MAC pulmonary disease document a five-year all-cause mortality exceeding 25%, indicating poor prognosis. These findings emphasise the need for more effective management and additional prospective mortality data collection.

A case report of fatal disseminated Mycobacterium colombiense infection in a renal transplant recipient.

We report the first case of disseminated Mycobacterium colombiense infection in a solid organ transplant recipient. Co-infection with Cryptococcus neoformans led to fatal multisystem organ failure. We review the pathogen and host factors contributing to these opportunistic infections.

In Defense of Lady Windermere Syndrome.

Defense of Lady Windermere Syndrome (LWS) provides a critical analysis of its proposed pathogenesis, evidence supporting a causal role of volitional cough suppression, pathogenesis of M. avium complex (MAC) superimposition, a defense of the eponym, and cites a possible contribution of LWS to the bronchiectasis population.

Clinical Characteristics and Treatment Outcomes of Patients with Macrolide-Resistant Mycobacterium massiliense Lung Disease.

Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.

Infectious Causes of Right Middle Lobe Syndrome.

Right middle lobe (RML) syndrome is defined as recurrent or chronic obstruction or infection of the middle lobe of the right lung. Nonobstructive causes of middle lobe syndrome include inflammatory processes and defects in the bronchial anatomy and collateral ventilation. We report on 2 case patients with RML syndrome, one due to infection with Mycobacterium avium complex followed by M asiaticum infection and the other due to allergic bronchopulmonary aspergillosis. A history of atopy, asthma, or chronic obstructive pulmonary disease has been reported in up to one-half of those with RML. The diagnosis can be made by plain radiography, computed tomography, and bronchoscopy. Medical treatment consists of bronchodilators, mucolytics, and antimicrobials. Patients whose disease is unresponsive to treatment and those with obstructive RML syndrome can be offered surgical treatment.

Nontuberculosis mycobacterial infections at a specialized tuberculosis treatment centre in the Republic of Korea.

BACKGROUND: The incidence of nontuberculous mycobacteria (NTM) infections is increasing worldwide, however formal evaluations of the epidemiology of NTM infections are limited. Understanding the trends and true prevalence of NTM is a major priority for optimizing infection control programmes and resources. The purpose of this study was to investigate the epidemiology, clinical manifestations, and radiologic findings in NTM-infected patients at specialized Tuberculosis (Tb) treatment centre in South Korea, which is endemic to Tb, and find solutions to control NTM infections. METHODS: A retrospective descriptive study was conducted among patients who were diagnosed with NTM from November 2011 to January 2016 at Seoul Metropolitan Government Seobuk hospital, Korea, using medical records and chest radiography results. Prevalence of NTM using national health insurance data was compared to the prevalence and incidence of Tb using National statistics data. RESULTS: The age- and sex- adjusted prevalence of NTM infection per 100,000 population increased between 2009 (9.4) and 2016 (36.1). However, the prevalence and incidence of Tb per 100,000 population decreased from 106.5 to 74.4, and 81.2 to 61.8, respectively. In total, 64 patients (37 [57.8%] men) were enrolled in the study. Among 33 (51.6%) patients with slowly growing nontuberculous mycobacteria (SGM) infection, 29 were detected with Mycobacterium avium complex (n = 13, M. avium; n = 16, M. intracellulare), and 4 with M. kansasii. Among 31 (48.4%) patients with rapidly growing nontuberculous mycobacteria (RGM) infection, 27 and 4 patients were detected with M. abscessus complex and M. fortuitum complex, respectively. RGM patients were more likely to have current Tb (P = 0.041), cough (P < 0.05), and sputum (P < 0.01) than SGM patients in the univariate analysis, but not in the multivariate analysis. CONCLUSION: Given the increasing prevalence of NTM infections, precise epidemiological and surveillance data should be obtained by reporting NTM infections to public health authorities. Introducing nucleic acid amplification tests to differentiate between Tb and NTM in smear-positive specimens should be considered.

Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study.

BACKGROUND: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. METHODS: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. RESULTS: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m2, lymphocyte count <1000 cells/µL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2. CONCLUSIONS: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases.

BACKGROUND: In multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review. METHODS: The study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients. RESULTS: All 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3 months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2 µg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy. CONCLUSIONS: Inhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.

A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease.

In this study, we sought to develop a nonhuman primate model of pulmonary Mycobacterium avium complex (MAC) disease. Blood and bronchoalveolar lavage fluid were collected from three female rhesus macaques infected intrabronchially with escalating doses of M. avium subsp. hominissuis. Immunity was determined by measuring cytokine levels, lymphocyte proliferation, and antigen-specific responses. Disease progression was monitored clinically and microbiologically with serial thoracic radiographs, computed tomography scans, and quantitative mycobacterial cultures. The animal subjected to the highest inoculum showed evidence of chronic pulmonary MAC disease. Therefore, rhesus macaques could provide a robust model in which to investigate host-pathogen interactions during MAC infection.

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007-2012.

BACKGROUND: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. METHODS: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. RESULTS: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old. CONCLUSION: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required.

Comparison of Clinical Features, Virulence, and Relapse among Mycobacterium avium Complex Species.

RATIONALE: Traditionally, Mycobacterium avium complex (MAC) has been composed of M. avium and M. intracellulare; however, advances in genetic sequencing have allowed discovery of several novel species. With these discoveries, investigation of differences in risk factors, virulence, and clinical outcomes have emerged. OBJECTIVES: We conducted a retrospective cohort study evaluating all MAC isolates obtained from pulmonary specimens at our institution from 2000 to 2012 and investigated the clinical courses associated with distinct MAC species. METHODS: To classify isolates into distinct species, a multilocus sequence analysis using rpoB and internal transcribed spacer (ITS) as targets was performed. We reviewed patient medical records to analyze clinical characteristics and outcomes for the cohort. MEASUREMENTS AND MAIN RESULTS: Of the isolates from the 448 included patients, 54% were M. avium, 18% were M. intracellulare, and 28% were M. chimaera. Using American Thoracic Society/Infectious Diseases Society of America criteria, patients whose isolates were identified as M. avium (adjusted odds ratio [AOR], 2.14; 95% confidence interval [CI], 1.33-3.44) or M. intracellulare (AOR, 3.12; 95% CI, 1.62-5.99) were more likely to meet criteria for infection than patients with M. chimaera. Patients infected with M. chimaera were more likely to be prescribed an immunosuppressant compared with all other patients (AOR, 2.75; 95% CI, 1.17-6.40). Patients treated for infections with M. avium (AOR, 5.64; 95% CI, 1.51-21.10) and M. chimaera (AOR, 4.47; 95% CI, 1.08-18.53) were more likely to have a clinical relapse/reinfection than those with M. intracellulare. CONCLUSIONS: Our findings suggest that specific MAC species have varying degrees of virulence and classifying MAC isolates into distinct species aids in identifying which patients are at higher risk of clinical relapse/reinfection.