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In 2012, a global outbreak of invasive Mycobacterium chimaera (M. chimaera) infection was identified in patients after cardiopulmonary bypass surgery. Investigations revealed the source to be heater-cooler unit (HCU) exhaust, with point-source contamination discovered at the LivaNova HCU manufacturing plant (London, UK). We report our experience with affected HCUs at a high-volume pediatric cardiac surgery center in the United States.A multidisciplinary task force was established for outbreak management, including removing contaminated HCUs from service. Patients identified as exposed to affected HCUs were systematically contacted. A call center was created for patient/family inquiries, and symptomatic patients were assessed using an institutional triage protocol, including laboratory/culture data and infectious diseases consultation.Cardiopulmonary bypass surgeries were performed in 4276 patients (median age: 2.1 years; range: 0-48.4 years) between October 2010 and October 2016. Call center volume was highest in the first 6 weeks after patient notification, totaling 307 calls and yielding 70 clinical patient assessments. Presenting symptoms included fatigue (60%), fever (49%), night sweats (46%), myalgias (34%), and weight loss (24%). Among the 70 assessed patients, echocardiogram (n = 30), cardiac computed tomography (n = 2), cardiac magnetic resonance imaging (n = 1), and pulmonary computed tomography (n = 1) did not reveal abnormalities suggestive of active infection. Infectious diseases consultation occurred in 23 (33%) patients. Acid-fast bacilli blood cultures were obtained in 30 patients; all were negative.Through a highly coordinated outreach effort, no patients have been found to have M. chimaera infection in the 6 years after exposure to contaminated HCUs. Ongoing vigilance for cases that may yet manifest is needed.

Purpose Nontuberculous mycobacteria (NTM) infection is an important issue after lung transplantation. However, a large-scale epidemiological study on this issue in Korea is lacking. We aimed to evaluate the epidemiology of NTM infection after lung transplant surgery in Korea. Methods Between October 2012 and December 2018, we retrospectively evaluated lung transplant recipients in a referral hospital in South Korea. A total of 215 recipients were enrolled. The median age at transplantation was 56 years (range, 17–75), and 62% were men. Bronchoscopy was performed according to the surveillance protocol and clinical indications. A diagnosis of NTM infection was defined as a positive NTM culture from a bronchial washing, bronchoalveolar lavage sample, or two separate sputum samples. We determined NTM pulmonary disease (NTM-PD) according to the American Thoracic Society/Infectious Disease Society of America 2007 guidelines. The Kaplan–Meier method and log-rank test were used for conditional survival analysis in patients with follow-up of ≥12 months. Results Fourteen patients (6.5%) were diagnosed with NTM infection at a median of 11.8 months (range, 0.3–51.4) after transplantation. Nine patients (4.2%) were diagnosed with NTM-PD, and the incidence rate was 1980/100,000 person-years. Mycobacterium abscessus was the most common species causing NTM-PD (66%), followed by M. avium complex (33%). The presence of NTM infection did not influence all-cause mortality among those who underwent follow-up for ≥12 months (N = 133, log-rank P = 0.816). Conclusion The incidence of NTM-PD was considerably high among lung-transplant recipients. M. abscessus was the most common causative species of NTM-PD after lung transplantation.

A 48-year-old woman with extensive clarithromycin-resistant Mycobacterium avium complex pulmonary disease (MAC-PD) was successfully treated by left lower lobectomy and lingulectomy following combination treatment of intravenous/inhaled amikacin plus bronchial occlusion by Endobronchial Watanabe Spigots (EWSs). A left pneumonectomy was initially indicated for removing all the lesions, but the procedure would have been barely tolerated by the patient. However, her preoperative combination treatment sufficiently reduced the lesions requiring resection to allow surgical preservation of the left upper division. This novel approach might be promising for patients with Mycobacterium avium complex lung disease whose pulmonary reserve will not allow an extensive parenchymal resection.

Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the M. avium intracellulare complex (MAC), which includes both M. avium and M. intracellulare. Typically, NTM infections affect the lungs and subsequently demonstrate a chronic course. Therefore, persistent respiratory symptoms generally indicate of the presence of pulmonary NTM diseases, and chest radiography, along with a sputum examination, are essential for its diagnosis. Because NTM are ubiquitous environmental organisms, a positive culture from a minimum of two separate expectorated sputum samples are required to make a diagnosis. The repertoire of effective drugs for treatment is considerably limited, indicating the need for long-term management with multiple drugs. Establishing a treatment regimen with high therapeutic efficacy and safety is an important issue for the future.

Mycobacterium avium complex (MAC) infection mainly causes pulmonary disease. However, in 20% to 30% of cases, it also induces various extrapulmonary diseases. Disseminated MAC infection occasionally occurs in immunocompromised patients but very rarely in immunocompetent patients. An 80-year-old immunocompetent woman presented with multiple chronic wounds on the scalp that had not improved despite prolonged treatment. A scalp abscess caused by disseminated MAC infection 4 years ago had gone through repeated cycles of improvement and aggravation despite continued use of anti-mycobacterial agents and active wound care. Enhanced brain computed tomography and magnetic resonance imaging revealed multiple skull defects and abscesses invading the dura mater. Under general anesthesia, the infected scalp skin and bone were sufficiently removed, and the bone and soft tissue defects were repaired with cranioplasty using a titanium mesh plate and local flap. As exemplified in this case, multiple chronic wounds unresponsive to treatment need to be screened for MAC infection. As chronic MAC infection in the scalp can cause skull destruction and brain infection, it needs to be treated aggressively at an early stage to prevent serious morbidity and mortality. Effective MAC infection management involves adequate medication, regular follow-up imaging, and active surgical procedure.

A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.

Background Mycobacterium marseillense is a new species of the Mycobacterium avium complex. There has been only a few human infections caused by M. marseillense worldwide. Case presentation We report a case of tenosynovitis caused by M. marseillense in an immunocompetent adult in Japan. The isolate was initially identified as M. intracellulare using commercial real time polymerase chain reaction assays and later identified as M. marseillense with sequencing of the the rpoB and hsp65 regions, and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Conclusions This is the first case reporting on M. marseillense generating a positive result with commercial real time PCR assays targeting MAC. Human infections associated by M. marseillense might be underreported due to similarities with Mycobacterium intracellulare. To accurately identify M. marseillese, MALDI-TOF MS might provide a rapid and reliable method.

Although there has been a drastic decline in the cases of Tuberculosis in the United States, the prevalence of infections caused by Mycobacterium avium Complex (MAC) has steadily increased in the past decades. Mycobacterium avium (M. avium) is one of the most abundant microorganisms in the MAC species. The mycobacterium genus is divided into two major groups: tuberculosis causing mycobacteria and non-tuberculous mycobacteria. MAC is most prominent among the non-tuberculous mycobacteria. MAC is an opportunistic pathogen that is present in soil, water, and droplets in the air. MAC infections can result in respiratory disease and can disseminate in affected patients. MAC infections are especially prevalent in patients with preexisting respiratory conditions such as Chronic Obstructive Pulmonary Disease (COPD). COPD is one of the most common lung conditions in the world with the primary cause being smoking in developed countries. COPD involves chronic inflammation of lung tissue resulting in increased susceptibility to infection. There is a lack of research regarding the pathophysiology that leads COPD patients to be susceptible to MAC infection. Our review paper therefore aims to investigate how the pathogenicity of MAC bacteria and immune decline seen in COPD patients leads to a greater susceptibility to MAC infection among COPD patients.

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the cli...

Objectives The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not sufficiently effective against nontuberculous mycobacteria (NTM) and there is a need for new drugs. This study aimed to estimate the overall in vitro activity of clofazimine (CFZ) against MAC and MABS clinical isolates. Methods We systematically searched four databases up to 1 March 2020 to identify relevant studies. Studies were included if they used the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). We assessed the pooled in vitro CFZ resistance rate in MAC and MABS clinical isolates using a random- effects model. Sources of heterogeneity were evaluated using Cochran's Q and the I2 statistic. Potential for publication bias was explored using Begg's and Egger's tests. All analyses were conducted using Stata 14.0. Results A total of 20 publications (11 reports for MAC and 15 for MABS) were included. The pooled rates of in vitro resistance to CFZ in clinical isolates of MAC and MABS were 9.0% [95% confidence interval (CI) 3.0–17.0%] and 16.0% (95% CI 4.0–34.0%), respectively. There was no evidence of publication bias. Conclusion This study reports the frequency of CFZ resistance in clinical isolates of MAC and MABS. According to the results, establishing accurate DST methods for detecting CFZ resistance, performing DST for all NTM isolates to provide effective treatment, and continuous monitoring of drug resistance are suggested for the prevention and control of CFZ-resistant NTM.

Patients with HIV-infection diagnosed at late stages usually have significant immunosuppression and demand simultaneous antiretroviral therapy and treatment of opportunistic infections. The presence of HCV coinfection makes treatment even more challenging because of possible adverse effects and drug-drug interactions. HCV cure in such clinical situations not only prevents fibrosis progression, but can also enhance virologic and/or immunologic response to antiretrovirals and thus effective treatment of opportunistic infections. Thorough consideration of all existing diseases and drug interactions of the combined therapy makes simultaneous treatment of HIV, chronic hepatitis C, and opportunistic infections not only possible but the best way to improve outcomes in a complex clinical situation.

Background Although spontaneous sputum conversion can occur in noncavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex lung disease (MAC-LD), little is known about redevelopment after spontaneous conversion. We investigated the redevelopment phenomenon after spontaneous sputum conversion in patients with NC-NB MAC-LD. Material and methods Among patients diagnosed with NC-NB MAC-LD between 2000 and 2013, 140 patients who experienced spontaneous sputum conversion, and whose follow-up duration after conversion was ≥6 months, were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. Results Of the 140 patients, 34 (24.3%) underwent redevelopment during the median follow-up period of 71.0 months (interquartile range [IQR], 58.8–87.5). Redevelopment occurred at a median interval of 25.0 months (IQR, 11.5–41.8) after spontaneous sputum conversion. The mean age of the 34 patients with redevelopment was 63.6 years, and 73.5% were women. No statistically significant differences in clinical characteristics were noted between the 34 patients with redevelopment and those with persistent conversion. Among the 34 patients with redevelopment, 6 received treatment at a median interval of 8 months (IQR, 1.5–16.8) after redevelopment. No significant differences in clinical characteristics were noted between the six treated and 28 untreated patients. Conclusion At least approximately 24% of patients with spontaneous sputum conversion in NC-NB MAC-LD had redevelopment, and a portion of them required treatment. These findings suggest that long-term follow-up is necessary for patients with NC-NB MAC-LD, even those who experience spontaneous sputum conversion.

Introduction While MAC native joint septic arthritis is historically considered a rare entity, the number of reported cases have increased in recent decades. However, no comprehensive review of this topic has been conducted. Objectives To conduct a systematic review of cases of MAC native joint septic arthritis reported in the literature and summarize the presentations, baseline characteristics, risk factors, diagnosis, treatment, and treatment outcomes. Methods A systematic review was conducted by performing an extensive literature search through Medline, Google Scholar, and Web of Science, starting from their inception. Screening of articles, assessment of eligibility, and data synthesis from eligible articles were independently performed by two reviewers with input from a third reviewer to achieve consensus. Inclusion criteria to determine eligibility included articles in English, case reports/case series, adult patients who presented with MAC/MA/MI septic arthritis of a native joint. Statistical analyses were performed using Statistical Package for the Social Sciences. Results Thirty-three cases of MAC native joint septic arthritis were reported since 1976. MAC septic arthritis affects immunocompetent and immunocompromised patients, most frequently as a monoarthritis involving the knees and wrist. MAC septic arthritis may present in the context of disseminated MAC infection and primary MAC septic arthritis. The average time to diagnosis from onset of symptoms was 20 months, where the majority of cases were initially misdiagnosed. Although arthrocentesis can be used to make the diagnosis, a synovial biopsy is necessary in many cases to confirm the diagnosis. A combination of surgery and antimycobacterial drug treatment has the highest chance of achieving complete resolution. Conclusion The diagnosis of septic arthritis of native joints due to MAC can be challenging and/or delayed. A high level of suspicion is needed in high-risk patients and also when atypical presentations occur. Therefore, understanding the presentation, risk factors, and pitfalls in diagnosing MAC septic arthritis are essential. MAC septic arthritis literature is scarce, necessitating further research of this rare condition to increase awareness, diagnostic accuracy and determine the optimal treatment strategy to improve patient outcomes.

Mycobacterium avium complex pulmonary disease (MAC-PD) can be serologically diagnosed according to the presence of anti-glycopeptidolipid (GPL)-core IgA antibodies. However, few studies have examined the association between serum anti-GPL-core IgA antibody titers and the clinical characteristics of patients with MAC-PD. From April 2014 to June 2019, we determined the level of anti-GPL-core IgA antibodies in 489 MAC-PD patients at our institute. Of them, 89 patients fulfilled the criteria of the American Thoracic Society and the Infectious Diseases Society of America statement on the diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. These patients were divided into antibody-positive (n = 59) or -negative (n = 30) groups according to their serum anti-GPL-core IgA antibody results. Additionally, the positive antibody group was further divided into a strong positive group (n = 27) and a weak positive group (n = 32), and their clinical characteristics were retrospectively compared. Disease progression requiring treatment during the 12 months following diagnosis and extensive radiological findings were significantly abundant in the strong positive group compared with the weak positive group. Our findings revealed that serum anti-GPL-core IgA antibody titers are useful not only for diagnosing MAC-PD but also for predicting the risk of exacerbation.

Mycobacterium chimaera is a non-tuberculous mycobacterium, member of the Mycobacterium avium complex (MAC), which has become a global public health concern due to infection following cardiac surgery performed with contaminated heater-cooler units. M. chimaera infection is characterized by a long latency, non-specific signs and symptoms and high mortality rates. Thus, the diagnosis is still challenging both for forensic pathologists and for clinicians. Clinical manifestations of M. chimaera infection include endocarditis, hepatitis, nephritis, encephalitis and chorioretinitis. A constant histopathologic finding is the presence of non-caseating granulomas, with multinucleated giant cells and histiocytes. Hereby, we present two cases of fatal disseminated M. chimaera infection following aortic valve surgery reporting clinical history and post-mortem findings. Further, we provide a brief overview of the literature with a special focus on histopathological characteristics of M. chimaera infection. The aim of this article is to provide a complete synopsis of histopathological characteristics useful for forensic pathologists.

Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics.

Summary Mycobacterial infections are rare in horses, donkeys and mules. Although there are a few reports in horses, mycobacterial disease is poorly documented in the donkey. Mycobacterial infection of equine species typically affects the alimentary tract, causing granulomatous enterocolitis resulting in diarrhoea and chronic weight loss, while lymph nodes and liver may also be affected. We now document recurrent oesophageal obstruction, secondary to cranial mediastinal lymphadenitis caused by Mycobacterium avium complex (MAC). To the best of our knowledge, this is the first report of MAC infection in a donkey in the UK.

The objective of the study: monitoring the spectrum of non-tuberculous mycobacteria isolated from patients who referred for medical care to the Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology.Subjects and methods. The diagnostic procedure of ATS/IDSA was used to define if the patient suffers from mycobacteriosis. The following specimens were collected to isolate non-tuberculosis mycobacteria: sputum, bronchoalveolar lavage fluid, feces, pleural fluid, surgical and biopsy specimens, and urine. The following tests were performed: Ziehl-Nielsen microscopy, microscopy stained by auramine-O, cultures by Middlebrook 7H9 in BACTEC™ MGIT™ 960 System, Becton Dickinson, USA. Non-tuberculosis mycobateria were differentiated from mycobacterium tuberculosis complex using the sdmpt64 chromatographic test (SD Bioline TBAg MPT64 test, Korea). The non-tuberculosis species were defined by the hybridization technology of DNA* strips GenoType Mycobacterium AS/CM, version 1.0.Results. Of 14,544 patients with suspected respiratory tuberculosis, non-tuberculous mycobacteria were detected in 38 (0.26%) of them, 17 (44.7%) patients had Mycobacterium avium complex, in them there were 26 men (68.4%) and 12 (31.6%) women. Non-tuberculosis mycobacteria were isolated mainly from sputum – in 27 (71.2%) patients and urine – in 6 (15.7%) patients. In 26 (68.4%) patients, mycobacteriosis was caused by slow-growing non-tuberculosis mycobacteria, of which Mycobacterium avium complex prevailed – in 17 people as well as Mgordonae – in 8 patients. Rapidly growing non-tuberculosis mycobacteria were identified in 12 (31.6%) patients, they included M. fortuitum (5 cases) and M. chelonae (4) prevailed.

Non-tuberculous mycobacteria (NTM) include more than 190 species and subspecies. Some NTM species can cause human diseases of the lungs or extrapulmonary infections. The guidelines focus on pulmonary mycobacteriosis in adult patients without cystic fibrosis or HIV infection caused by the most common NTMs, such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among slow-growing NTMs and Mycobacterium abscessus complex among fast-growing species. Experts of American Thoracic Society (ATS), European Respiratory Society (ERS), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), and American Society for Infectious Diseases (IDSA) contributed to the development of the guidelines. A total of 31 evidence-based recommendations are provided for the diagnosis and treatment of NTM-induced lung infections.

Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable.

Background Hemoptysis is a frequent and sometimes fatal complication of non-tuberculous mycobacterial (NTM) lung disease. The risk factors for hemoptysis are not well understood. In the current study, potential risk factors for hemoptysis were investigated in patients with Mycobacterium avium complex (MAC) lung disease, which is the most common NTM in Japan. Methods Medical records from the Kinki-Chuo Chest Medical Center were reviewed. Consecutive patients with MAC lung disease diagnosed in 2014 and followed up for more than 1 year in the hospital were included in the study. Hemoptysis was confirmed between 2014 and 2016. The characteristics of patients with hemoptysis and non-hemoptysis at the time of the initial diagnosis of MAC lung disease were obtained from the medical records, and the two groups were compared. The radiological findings assessed included nodules, infiltration shadows, cavities, and bronchiectasis. Each was classified and scored individually in six lung fields, and these data were used to generate radiological scores. Results The study included 82 patients with MAC lung disease, 18 with hemoptysis and 64 without. Higher total radiological severity score at the time of the initial diagnosis of MAC was associated with an increased risk of hemoptysis. Among the radiological scores, infiltration and cavities were marginally associated with the risk of hemoptysis. Conclusions The radiological severity score at the time of initial diagnosis of MAC lung disease was associated with hemoptysis.

Non-tuberculous mycobacteria are conditional pathogens that can cause many diseases, among which pulmonary infections are the most common (65–90%). Mycobacterium avium and Mycobacterium abscessus are non-tuberculous mycobacteria most often associated with lung diseases. Mass spectrometry diagnostic techniques were not effective in Mycobacterium avium complex infection. We report a case of Mycobacterium colombiense and Mycobacterium avium complex causing severe pneumonia in an adult with HIV. Our group developed a novel molecular-based method to identify Mycobacterium species. Novel techniques such as molecular cloning which we have described here can make up for the inability of matrix-assisted laser desorption ionization-time of flight mass spectrometry to distinguish the multiple microorganisms present, and may add to the diagnostic toolkit and increase the accuracy and rapidity of diagnosis in the future.

A 62-year-old woman suffering from pulmonary Mycobacterium avium complex (MAC) disease was admitted to our hospital with fever, visual impairment, and lower limb weakness. MRI detected lesions in the optic chiasm and spinal cord extending the length of 6 vertebrae. The anti-aquaporin 4 (AQP4) antibody titer determined by ELISA was elevated to 8.3 IU/l. On the basis of these findings, the patient was diagnosed as having neuromyelitis optica (NMO), when chest CT also demonstrated exacerbation of pulmonary lesions. Methylprednisolone pulse therapy and double-filtered plasma exchange ameliorated the symptoms, and the EDSS score improved from 8.5 to 6.5. Six months later, visual impairment recurred, although ELISA showed that the anti-AQP4 antibody titer had become undetectable. Also, the CSF interleukin-6 (IL-6) level was elevated to 34.8 pg/ml. There have been few reports of NMO associated with pulmonary MAC disease. An increase of IL-6 is considered to exacerbate the clinical picture of NMO, whereas it may suppress progression of the pulmonary MAC disease. Exacerbation of the pulmonary MAC disease and the following internal counteraction with IL-6 may have resulted in a NMO relapse. The present patient was therefore administered eculizumab but not satralizumab, a humanized anti-IL-6 receptor antibody, for prevention of NMO recurrence.

Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016–2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.

Background: Nontuberculous mycobacteria are an uncommon pathogen for musculoskeletal infection and are difficult to treat because of delays in diagnosis, prolonged treatment requiring both antimycobacterial therapy and surgical debridement, and high rates of resistance to antimycobacterial therapy. Case Report: We report the case of an 88-year-old male with recurrent Mycobacterium avium complex tenosynovitis despite receiving multiple courses of pharmacologic therapy and surgical debridement. Conclusion: Nontuberculous mycobacterial musculoskeletal infections can be difficult to diagnose and equally difficult to treat. A combination of antimycobacterial therapy and surgical debridement is often required; however, the rate of treatment failure remains high, particularly with rapidly growing mycobacteria such as Mycobacterium avium.

The association between Mycobacterium avium complex pulmonary disease (MAC-PD) and pleuroparenchymal fibroelastosis (PPFE) has been reported previously, and interstitial pneumonia as a comorbidity is associated with a worse prognosis. However, no study has thoroughly reported on PPFE associated with MAC-PD. The present study investigated the prevalence, clinical characteristics, and prognostic impact of PPFE in patients with MAC-PD.A total of 224 patients, newly diagnosed with MAC-PD, were retrospectively reviewed. At the time of diagnosis, chest high-resolution computed tomography (HRCT), sputum examination, and clinical characteristics were collected. The extent of PPFE and MAC-PD was evaluated semi-quantitatively using HRCT scores. Risk factor analysis for clinical or radiological deterioration necessitating multidrug antimicrobial treatment within 3 years, and all-cause mortality within 5 years, from the initial diagnosis was performed based on the PPFE score.PPFE was observed in 59 out of 224 patients (26.3%). A higher PPFE score was a risk factor for dyspnoea, fatigue, and lower body mass index (BMI) (pPPFE is a relatively common complication and an independent poor prognostic factor of MAC-PD. This study highlights the need for further studies investigating whether the presence of PPFE can be a clinical indicator for initiating treatment of MAC-PD.

Bacterial placentitis in horses commonly results in abortion, premature birth or compromised neonatal foal health. Although mycobacterial infections are generally uncommon in horses, 10 equine abortion cases caused by Mycobacterium avium subsp. hominissuis (MAH) infections occurred between 2018 and 2019 in Japan. They occurred on seven Thoroughbred horse farms in the Hidaka district of Hokkaido, but direct contact among the mares on different farms was not recorded. Most cases were characterized by extensive pathological lesions of the placenta, which are not typical in cases of common pathogenic bacteria such as Streptococcus zooepidemicus and Escherichia coli. All abortions featured white–yellow exudates on the surface of the placenta. Mycobacterial granuloma formations were histologically found in the placenta and fetal organs, and acid‐fast bacteria were isolated from the placenta, fetal samples (heart, lung, liver, kidney, spleen and stomach contents) or uterine lavage fluid. The greatest number of bacteria was isolated from necrotic lesions on the placenta, which could be an important site for bacterial isolation in mycobacterial equine abortions. The isolates were identified as MAH based on internal genome sequences. In variable number tandem repeat analysis, all patterns of the strains were identical. Single nucleotide polymorphism analysis of the core genome grouped all strains in the II‐a/SC3 subcluster. Both results reveal that these strains share the same genetic background, suggesting that the horses had been infected by the same unknown contagious source., This article reports 10 equine abortions cases caused by Mycobacterial avium subsp. hominissuis infections. We confirmed the isolated strains shared the same genetic background, suggesting that the horses had been infected by the same contagious source.

Mycobacterium avium complex (MAC) is a non-tuberculous mycobacteria (NTM) that causes subacute or chronic nodular bronchiectasis, cavitary or fibro-cavitary pneumonia in patients with chronic structural lung pathology including emphysema, chronic bronchitis, and bronchiectasis. It is also known to cause pulmonary and extrapulmonary infections in patients with impaired cell mediated immunity such as transplant recipients, (Acquired Immune Deficiency Syndrome) AIDS where it can cause disseminated infections. Empyema from MAC has been reported in immunocompromised patients and is a rare phenomenon. Here we report a patient who presented with chronic left pleural effusion and a left lower lobe lung mass that went undiagnosed for 2 years, despite extensive work-up. Later in his course, he presented with a large effusion complicated by a bronchopleural fistula and was diagnosed as MAC empyema. To our knowledge, this is the first case of MAC empyema, that presented as a chronic lung mass, complicated by a bronchopleural fistula. In this article, we present the clinical, laboratory, and radiological features, with emphasis on a combined medical and surgical approach in the management of MAC empyema. We also provide a brief overview of cases of MAC associated pleurisy and empyema that have been reported in literature.

Background Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections. Methods We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity. Results Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures. Conclusions These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.

RATIONALE: Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria, and some pathogenic species cause lung disease. Environmental factors contribute to increased NTM abundance, with higher potential for exposure and infection. OBJECTIVES: To identify water-quality constituents that influence the risk of NTM infection in Oregon. METHODS: We conducted a population-based cohort study using patient incidence data from the Oregon statewide NTM laboratory data collected as part of a public health surveillance project from 2007 through 2012. To estimate the risk of NTM pulmonary infection (PI) from exposure to water constituents, we extracted water-quality data from the Water Quality Portal and associated these data with corresponding patient county of residence. Using generalized linear models, we modeled two outcomes: Mycobacterium avium complex species PI and Mycobacterium abscessus group species PI. RESULTS: For every 1-unit increase in the log concentration of vanadium in surface water, infection risk increased by 49% among persons with Mycobacterium avium complex PI. Among those with Mycobacterium abscessus PI, we observed that for every 1-unit increase in the log concentration of molybdenum in surface water, infection risk increased by 41%. The highest risk of infection due to Mycobacterium abscessus group infection was concentrated in counties within the Northwestern region of Oregon. High infection risk associated with Mycobacterium avium complex species did not show any geographic pattern. CONCLUSIONS: Concentrations of the trace metals molybdenum and vanadium in surface water sources were associated with NTM infection in Oregon. These findings may help identify regions at higher risk of NTM infection to guide risk reduction strategies.

TheMAC bacterial infections occur both in immunocompetent people and those with functional predispositions and compromised immunity, particularly during HIV infection or immunosuppressive treatment. The incidence of MAC infections in humans is growing, with the most common form of infection being pulmonary disease (MTC-PD); however, there are conflicting reports on the role ofAlthough new antibiotics are being created to inhibit the growth and division of

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria—which include clinical, radiological, and microbiologic criteria—should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens.

Introduction The role of non-tuberculous mycobacteria (NTM) among cystic fibrosis (CF) patients, on occasion, remains unknown. The aim of our study is to evaluate the prevalence and clinical/microbiological characteristics of CF adult patients colonized by NTM, highlighting Mycobacterium abscessus (M. abscessus). Methods A retrospective study was conducted with 92 CF adult patients: including a control group of 64 patients, not colonized by NTM, and a study group of 28 patients, colonized by NTM. We have analyzed variables such as age, F508del mutation, lung function, pancreatic involvement, auramine staining and co-colonizations between both groups. Results The prevalence of NTM found was 30.4%. The most prevalent was Mycobacterium avium complex followed by M. abscessus. For M. abscessus, in the comparative study with patients colonized by other NTM, significant results were obtained for variables age. Discussion We have found a high prevalence of NTM among adult patients with CF, and we associated the presence of M. asbcessus with ages less than 30 years and F508del. Due to the pathogenic role of NTM, especially M. asbcessus, multicenter studies are required within the population suffering from CF.

The Mycobacterium avium complex (MAC) includes ubiquitous bacteria that typically cause infection in immunocompromised patients. This paper reviews the presentation, diagnosis, pathogenesis, and treatment of extrapulmonary MAC infections in immunocompetent patients by compiling information from case reports identified by a PubMed search. Mycobacterium avium complex infections in immunocompetent patients can present primarily with extrapulmonary symptoms, and this makes the diagnosis of MAC infection in these patients more difficult. The American Thoracic Society has not established criteria for the diagnosis of extrapulmonary MAC infections; testing for MAC should be based on clinical suspicion or after the exclusion of all other causative agents. Methods of testing should include molecular and biochemical tests, since these tests provide more definitive identification than routine cultures. Extrapulmonary presentations usually respond well to macrolide based multi-drug regimens started as soon as a MAC infection is identified. Key words: Mycobacterium avium, infection, diagnosis, treatment

Mycobacterium avium (Mav) causes chronic infections in immunocompromised patients that require long-term antibiotic treatment. We have previously shown that Mav takes residence in host Mϕs and establishes a compartment (MavC) in which it is hidden from host defenses. Failure to establish the MavC traps Mav in Lamp1+ phagolysosomes where growth is prevented, and inflammatory signaling activated through TLRs 7/8. To elucidate how antibiotic treatment affects mycobacterial trafficking and host defenses, we infected human primary Mϕs with Mav for 4 days prior to treatment with a macrolide, aminoglycoside, and ethambutol. We show that Mav is killed and the MavC fuses with Lamp1+ lysosomes following antibiotic treatment. However, this does not result in nuclear translocation of NF-κB or production of inflammatory cytokines, suggesting different Lamp1+ lysosomal compartments can form that differ in their innate signaling capabilities. Thus, we show that upon antibiotic treatment of a chronic infection, Mav is quietly disposed of by Mϕs.

Nontuberculous mycobacteria (NTM) are critical emerging global infectious pathogens. Though NTM can be mere colonizers when isolated from human specimens, NTM are also responsible for diverse human infections. NTM-lung disease (NTM-LD) is the most common human disease entity. The present review aims to provide general insight into NTM-LD epidemiology in Taiwan. In reviewing NTM epidemiology in Taiwan, we discovered three distinguishing features. First, NTM disease incidence has increased in Taiwan over the past decade. Second, the distribution of NTM varies geographically in Taiwan. Mycobacterium avium-intracellulare complex (MAC) is the dominant species in northern Taiwan, whereas Mycobacterium abscessus complex and MAC may be equally dominant in southern Taiwan. Third, researchers in Taiwan have published valuable research investigating NTM among special patient populations, including patients in intensive care units, with ventilator dependency, with pulmonary tuberculosis, and who are infected with specific NTM species. The largest obstacle to clarifying NTM epidemiology in Taiwan may be the lack of routine NTM species identification in laboratories. Increased awareness of NTM diseases and acknowledgment that NTM species identification is crucial and guides clinical management are essential steps for facilitating the identification of NTM species in laboratories.

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

Invasive tracheobronchial aspergillosis (ITBA) complicated by nontuberculous mycobacteria (NTM) is rare. An 88-year-old man was admitted for hemoptysis. Bronchoscopy revealed bronchial ulcers, and a tissue biopsy showed Aspergillus fumigatus. He was diagnosed with ITBA, which improved with voriconazole. During treatment, infiltrative shadows appeared in his lungs, and bronchoscopy was performed once again. A non-necrotic epithelioid granuloma and Mycobacterium intracellulare were detected in the biopsy specimen. He was diagnosed with NTM disease. It is important to note that tracheobronchial ulcers may cause hemoptysis and to identify the etiology and treat it appropriately when multiple bacteria are found.

Background Mycobacterium chimaera, one of the Mycobacterium avium complex (MAC) members, was recently identified using modern gene sequencing analysis. Unlike M. avium and M. intracellulare, little is known about the clinical features, antimicrobial susceptibilities, and treatment outcomes of M. chimaera lung disease. Methods This study was conducted in a medical center from December 2012 to July 2015. Patients who fulfilled the 2007 ATS/IDSA diagnostic criteria for nontuberculous mycobacterial lung disease were enrolled. M. chimaera isolates were identified based on the findings of sequencing of rpoB gene, the internal transcribed spacer (ITS) region of the 16S–23S rRNA gene, and the heat-shock protein 65 gene (hsp65). Minimum inhibitory concentrations (MICs) of 13 antimicrobial agents were determined. Results During the study period, 247 patients with MAC lung disease were identified, and 11.3% (28/247) of the patients had lung disease caused by M. chimaera. Among these patients, 17 (60.7%) were female, and their median age was 72.5 (40–100) years. All M. chimaera isolates were susceptible to clarithromycin and rifabutin. All the isolates were resistant to moxifloxacin and only 10 (35.7%) and 2 (7.1%) were susceptible to amikacin and linezolid, respectively. Of the nine patients who received macrolide-based regimens, more achieved radiographic resolution than those treated with non-macrolide-based regimens (66.7% vs. 15.8%, P = 0.013), and they tended to have better survival (P = 0.10). Conclusions A substantial portion (11.3%) of MAC lung disease cases were caused by M. chimaera, and treatment with macrolide-based regimens resulted in better clinical outcomes for patients with M. chimaera lung disease.

Background The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. Methods We conducted a 10-year (2005–2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus–negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Results Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0–10.4; P Conclusions Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

The marine actinomycete strain OPMA02852, identified as the genus Streptomyces, was found to produce anti-mycobacterial compounds against Mycobacterium avium complex (MAC). One new compound, designated as steffimycin E (1), was isolated together with three known steffimycins (steffimycin (2), 10-dihydrosteffimycin (3), and 8-demethoxysteffimycin (4)) from the culture broth of this producing microorganism by solvent extraction, ODS column chromatography, and preparative HPLC. Compound 1 has a tetracyclic quinone structure with a sugar moiety. Compound 1 exhibited anti-mycobacterial activity against M. intracellulare, M. bovis BCG, and M. smegmatis.

BACKGROUND: The recommended treatment duration for non-cavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex (MAC) lung disease (LD) is at least 12 months after culture conversion, but evidence supporting this is limited. This study investigated whether treatment for less than 12 months after culture conversion is acceptable in terms of recurrence rate. METHODS: The study enrolled the patients diagnosed with NC-NB MAC LD between 2001 and 2014 at a tertiary referral center in South Korea who received the standard treatment for at least 9 months after culture conversion up to October 2018. The patients were divided into a shorter treatment group (9–11 months after culture conversion) and a standard treatment group (≥12 months). RESULTS: Of the 228 patients enrolled, 59 (25.9%) were treated for 9–11 months after culture conversion and 169 (74.1%) for ≥12 months. The mean treatment durations after culture conversion in the shorter and standard treatment groups were 11.1 and 13.8 months, respectively (P

Mycobacterium avium complex refers to a group of environmental bacteria which inhabit water and soil. Although Mycobacterium avium complex is capable of causing refractory lung infections, the risk factors for Mycobacterium avium complex lung disease are still unclear. This study aimed to determine the associations between Mycobacterium avium complex lung disease and soil or water exposure. Using questionnaires along with clinical data, we compared soil exposure, along with bathtub bathing and showering habits between 172 women with Mycobacterium avium complex lung disease and 339 women without Mycobacterium avium complex infection as controls. Showering was found to be independently associated with the presence of Mycobacterium avium complex lung disease (adjusted odds ratio 5.72, 95%, confidence interval 1.99 to 16.46). Although the mean age of the groups was different, an age-matched sub-analysis yielded similar results. These results indicate that showering may be a risk factor for Mycobacterium avium complex lung disease.

Objectives : In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. Methods : Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. Results : Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). Conclusions : Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Rationale: Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), are emerging pathogens that can opportunistically cause debilitating pulmonary disease in susceptible huma...

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

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