Extrapulmonary Nontuberculous Mycobacteria Research Articles

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up

BackgroundThe epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determined the incidence and prevalence of NTM infections and focused on social risk factors. Additionally, we described persons suffering from pulmonary and extrapulmonary NTM. Research questionWhat is the incidence and prevalence of NTM and what are the characteristics of the affected patients? MethodsThis is a nationwide retrospective register-based cohort study in Denmark. Adult patients with NTM diagnosis in the Danish national registers from 2000-2017 were classified as having either pulmonary or extrapulmonary NTM disease. ResultsWe identified 1,146 adults with an NTM diagnosis. 661 patients had pulmonary NTM of which 50.4% were male, while 485 had extrapulmonary NTM of which 59.6% were male. The median age (Interquartile range), was 66 years (18) and 57 years (32), respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary and 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest in 70+ year-olds (19.3 per 100,000). Compared to pulmonary NTM patients, extrapulmonary NTM patients were more likely to be employed and had a higher educational level. InterpretationThe prevalence of NTM disease in Denmark increased between 2000 and 2017. Pulmonary and extrapulmonary NTM patients are two distinct groups that differ in age, gender, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

1900. Disseminated and Extrapulmonary Nontuberculous Mycobacteria (NTM): Disease Management, Adverse Treatment Reactions, and Outcomes

Abstract Background Guidelines for the management of pulmonary nontuberculous mycobacterial (NTM) infections are well defined; however, similar guidelines for the treatment of disseminated or extrapulmonary NTM infections are lacking. This study aimed to describe our institutional experience in the treatment of disseminated and extrapulmonary NTM infections, and to better characterize the disease course, management, and outcomes in this patient population. Methods This single-center retrospective study was conducted at The Ohio State University Wexner Medical Center in patients who were diagnosed with disseminated or extrapulmonary NTM infection from November 1, 2011 to November 1, 2021. Only index cases were included in patients with a documented culture positive for an NTM, and patients with a positive pulmonary culture were only included if they had a documented extra-pulmonary site as well. Results 58 patients met inclusion criteria and 54 were started on antibiotic therapy. 41.4% (N=24) and 31.0% (N=18) were started on two and three antibiotics as initial therapy, respectively. 32 (59.3%) patients required changes to their initial regimen, of which 31.3% (N=10) were changed due to intolerance or adverse event. The mean time to onset of antibiotic intolerance or adverse drug events was 129.4 days (6-404 days). 67.2% (N=39) of patients had documented resolution of their infections, with 7 patients currently on antibiotic therapy at the end of the study period (38.9%). The most common antibiotic classes used included macrolides (64.8%), carbapenems (35.2%), ethambutol (25.9%), and aminoglycosides (22.2%). The antibiotic classes with most frequent intolerances were linezolid (42%), aminoglycosides (31.6%) and clarithromycin (21.0%) at a mean duration of 39.3, 72.2, and 32 days, respectively. Table 1. NTM infection characteristics, including infection site, species breakdown, and disease outcome. Table 2. NTM treatment regimen details and reasons for changing and/or not completing planned antibiotic regimen for all study patients. Table 3. Breakdown of antibiotic classes used in initial treatment regimens for dNTM-infected patients, along with antibiotics that caused patient intolerances. For each antibiotic class that caused intolerance, average time to develop intolerance listed. Conclusion Treatment of disseminated and extrapulmonary NTM infections typically requires a complicated treatment course due to prolonged durations of multiple antibiotics, patient intolerances to antibiotic classes, and difficulty with determining appropriate end of therapy timing. Additional studies are needed to better outline the ideal antibiotic regimens and duration for disseminated and extrapulmonary NTM infections. Disclosures All Authors: No reported disclosures

Clinical characteristics of extrapulmonary nontuberculous mycobacteria infections in comparison with pulmonary infections: A single-center, retrospective study in Japan

IntroductionThe prevalence of nontuberculous mycobacteria (NTM) infections is increasing worldwide. Although NTM can affect extrapulmonary organs, studies on the clinical characteristics of extrapulmonary NTM are rare. MethodsWe retrospectively analyzed patients who were newly diagnosed with NTM infections at Hiroshima University Hospital between 2001 and 2021 to investigate species distribution, infected sites, and risk factors of extrapulmonary NTM compared to pulmonary NTM. ResultsOf the 261 NTM infections, 9.6% and 90.4% had extrapulmonary and pulmonary NTM, respectively. The mean ages of patients with extrapulmonary and pulmonary NTM were 53.4 and 69.3 years, 64.0% and 42.8% were male, 36.0% and 9.3% received corticosteroids, 20.0% and 0% had acquired immune deficiency syndrome (AIDS), and 56.0% and 16.1% had any immunosuppressive conditions, respectively. Younger age, corticosteroid use, and AIDS were associated with extrapulmonary NTM. In pulmonary NTM, Mycobacterium avium complex (MAC) accounted for 86.4% of NTM species, followed by M. abscessus complex (4.2%), whereas in extrapulmonary NTM, M. abscessus complex, MAC, M. chelonae, and M. fortuitum accounted for 36.0%, 28.0%, 12.0%, and 8.0%, respectively. Compared to pulmonary NTM, extrapulmonary NTM were significantly more likely to be rapid-growing mycobacteria (RGM) (56.0% vs. 5.5%). The most common sites of infection were the skin and soft tissues (44.0%), followed by the blood (20.0%), tenosynovium, and lymph nodes (12.0%). ConclusionYounger age and immunosuppressive conditions are associated with extrapulmonary NTM, with a higher prevalence of RGM in extrapulmonary NTM than in pulmonary NTM. These results provide a better understanding of extrapulmonary NTM.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

Nontuberculous mycobacteria otomastoiditis with facial palsy.

A 5-year-old male patient, receiving bilateral ventilation tube insertions 8 months ago, suffered from persisting left otorrhea and hearing loss for 3 months recently, accompanied by left post-auricular mass for 2 weeks. The examination revealed a grade IV left peripheral facial palsy (House-Brackmann grading system). High-resolution computed tomography (HRCT) (Fig. 1A and supplementary video) demonstrated opacification of the left tympanic cavity, epitympanum, mastoid antrum, and air cells. Bony erosion of the tympanic segment of the facial nerve was noticed. In contrast, HRCT demonstrated normal right external auditory canal structures and middle ear with normal pneumatization (Fig. 1B). Contrast-enhanced axial CT (Fig. 2) showed a 4-cm peripheral enhanced subperiosteal postaural abscess. He had poor empirical antibiotic therapy and topical treatment response. Left mastoidectomy was performed. Furthermore, microscopic examination of tissue samples found granulomas. Smears detected no acid-fast bacillus (AFB). Three weeks later, tissue culture was proven as Mycobacteria abscessus complex. Facial palsy improved significantly after surgical intervention as the facial nerve was relieved from inflammation and edema. The patient was treated with antimycobacterial agents for 9 months. However, his left eardrum remained perforated.Figure 2Contrast-enhanced axial computed tomography revealed a peripheral enhanced abscess over the postauricular area (arrowhead). The heterogeneously enhanced middle ear and external auditory canal soft tissue density were detected (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Nontuberculous mycobacteria (NTM) otomastoiditis was first described in 1976.1Austin W.K. Lockey M.W. Mycobacterium fortuitum mastoiditis.Arch Otolaryngol. 1976; 102: 558-560Crossref PubMed Scopus (29) Google Scholar NTM otomastoiditis is a rare type of extrapulmonary NTM that mostly affects children and may present with nonspecific symptoms, including persisting painless otorrhea, tympanic membrane perforation, middle ear granulation, and hearing loss. The incidence of facial nerve weakness in NTM otomastoiditis was approximately 12%, much higher compared to typical bacterial otomastoiditis.2Lundman L. Edvardsson H. Ängeby K. Otomastoiditis caused by non-tuberculous mycobacteria: report of 16 cases, 3 with infection intracranially.J Laryngol Otol. 2015; 129: 644-655Crossref PubMed Scopus (9) Google Scholar Facial nerve weakness in NTM otomastoiditis was mostly transient. Eardrum defect with either ventilation tube or perforation is a major risk factor for NTM otomastoiditis in children. Previous reports showed that approximately 90% of the children had a history of ventilation tubes or eardrum perforations.2Lundman L. Edvardsson H. Ängeby K. Otomastoiditis caused by non-tuberculous mycobacteria: report of 16 cases, 3 with infection intracranially.J Laryngol Otol. 2015; 129: 644-655Crossref PubMed Scopus (9) Google Scholar Differentiation between NTM and tuberculosis (TB) infection can be difficult. Clinical findings of NTM and TB otomastoiditis often overlap, causing diagnostic difficulties.3Doan H.T.H. Hoang P.T. Tran T.P.C. Tuberculous otitis media in Vietnam: clinical features and diagnostic difficulties.Eur Ann Otorhinolaryngol Head Neck Dis. 2021; 138: 467-469Crossref Scopus (2) Google Scholar AFB staining would identify mycobacteria; however, it does not discriminate NTM from TB. Hence, the growth and identification of NTM from the clinical specimens are necessary. The culture of mycobacteria is the gold standard for NTM infection diagnoses.4Gopalaswamy R. Shanmugam S. Mondal R. Subbian S. Of tuberculosis and non-tuberculous mycobacterial infections - a comparative analysis of epidemiology, diagnosis and treatment.J Biomed Sci. 2020; 27: 74Crossref PubMed Scopus (56) Google Scholar Culture is the first step in species identification. It evaluates clinical significance and antimicrobial resistance. Other diagnostic modalities can be applied only after identifying the growth of the culture media. If patients with NTM otomastoiditis did not respond to antibiotics, they could further receive mastoidectomy to reduce local bacterial load.2Lundman L. Edvardsson H. Ängeby K. Otomastoiditis caused by non-tuberculous mycobacteria: report of 16 cases, 3 with infection intracranially.J Laryngol Otol. 2015; 129: 644-655Crossref PubMed Scopus (9) Google Scholar HRCT is the image of choice to evaluate temporal bone structures. The middle ear and mastoid cavity opacification with possible fluid levels are found on HRCT. Moreover, trabeculae and cortical bone destruction can be occasionally noted in coalescent mastoiditis. If the disease inflammatory process continues, subsequent lateral mastoid cortex penetration would result in subperiosteal abscess formation. Chronic epithelial infection may result in basement membrane disruption; hence, the formation of granulation tissue. The soft tissue expanding facial nerve, with or without surrounding bony destruction, may occasionally be noticed in cases with facial palsy.5Ho M.L. Juliano A. Eisenberg R.L. Moonis G. Anatomy and pathology of the facial nerve.AJR Am J Roentgenol. 2015; 204: W612-W619Crossref PubMed Scopus (21) Google Scholar The radiological differential diagnoses of NTM otomastoiditis should include other infectious processes, cholesteatoma, cholesterol granuloma, and Langerhans’ cell histiocytosis in children.6Lo A.C.C. Nemec S.F. Opacification of the middle ear and mastoid: imaging findings and clues to differential diagnosis.Clin Radiol. 2015; 70: e1-e13Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Possibilities of NTM otomastoiditis should always be considered in patients presenting with facial palsy with extensive disease and poor treatment response for common bacterial otomastoiditis. The authors declare no conflict of interest. The following is the Supplementary data to this article.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjYWM5YjE1YmNmMWUzMGNhODlmZWQ4OGFjYTYzOTcyNyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc2MTQ2OTI5fQ.kDovTztnzM-zDpwRPhetcuw6Ou0My3ZN3nYX2SMt5PwUcfL7L9cbyhBznzHBs7n0p__GI7Zbh-golLjGr1jtPpXFLj-K2VUsGr3OYtMO4omqKBjwd2FTod6cad11owP647_j857HCXtEwpZzHy3PL2IAYxzSNYsogLPh1AxyIuJCwNk8zvzEHYOrkuiVtVxd9L2LaTRcGT8tYF-q5801fpRLq9VF7XETFH7uS5oAVMV9bvs8IXWIRDT5gYM2cxvILyl6Dy3aIhofv83wzwYsdW701QdGXU6b_KXobjrFllVqFUd5Rk3q8Jfu29vQcy8KzMfwXfciME-43LCiEUSY-Q Download .mp4 (1.4 MB) Help with .mp4 files Supplementary VideoAxial and coronal high-resolution computed tomography with the blue and yellow arrows tracing the course of the left facial nerve, showing bony erosion of the tympanic segment of the facial nerve.

Increasing Trend of Nontuberculous Mycobacteria Isolation in a Referral Clinical Laboratory in South Korea.

Background and Objectives: Nontuberculous mycobacteria (NTM) infections are increasing worldwide. We evaluated the annual trends of NTM isolation on acid-fast bacillus (AFB) culture, compared to that of Mycobacterium tuberculosis, and the distribution of NTM species nationwide in South Korea. Materials and Methods: The study was conducted in a diagnostic center that is a major referral laboratory for the diagnosis of tuberculosis and NTM in South Korea. All laboratory results of AFB culture from January 2014 to December 2019 were collected. All NTM identified were definitively identified to the species level. Results: A total of 345,871 tests were performed for the diagnosis of mycobacteria. The isolation rate of NTM and M. tuberculosis was 3.7% (12,969 cases) and 4.4% (15,081 cases), respectively. The annual isolation rate of NTM increased gradually from 2.7% in 2014 to 4.8% in 2019, whereas that of M. tuberculosis decreased from 6.2% to 3.3%. There were 4988 cases of NTM identified to the species level. M. avium complex (MAC) was the most common species isolated from pulmonary sites (59.8%), followed by M. gordonae (9.2%), M. abscessus (7.0%), and M. fortuitum (5.5%). Extrapulmonary NTM were identified in 29 cases (0.6%). MAC was also the most common NTM species isolated from extrapulmonary sites (65.5%), followed by M. kansasii (10.3%), M. abscessus (6.9%), and M. fortuitum (6.9%). Conclusions: The annual isolation rate of NTM has increased gradually, whereas that of M. tuberculosis has decreased. Follow-up studies of the increases in NTM identification and NTM infections in South Korea are needed.

Recent developments in the diagnosis and treatment of extrapulmonary non-tuberculous mycobacterial diseases.

Diseases due to pathogenic mycobacteria cause significant health and economic impact on humans worldwide. Although mycobacterial diseases primarily affect the lungs, the involvement of extrapulmonary organs has also gained ground, particularly among individuals with co-existing medical conditions. Besides Mycobacterium tuberculosis complex organisms, non-tuberculous mycobacteria (NTM) are also known to cause pulmonary and extrapulmonary diseases. Primary and disseminated extrapulmonary mycobacterial infections affect the brain, eye, mouth, tongue, lymph nodes of the neck, spine, bones, muscles, skin, pleura, pericardium, gastro-intestinal, peritoneum and genito-urinary system. The clinical presentation of extrapulmonary mycobacterial diseases, including systemic symptoms, of M. tuberculosis-infected cases and NTM-infected cases is similar. Moreover, extrapulmonary mycobacterial diseases are complicated by the involvement of diverse bacterial species as aetiological agents. Culture and molecular techniques are used to differentiate NTM from Mycobacterium tuberculosis and to classify sub-species of the pathogens. As sub-speciation and drug susceptibility profiling are critical factors in treating extrapulmonary NTM diseases, there are often significant delays in initiating treatment and customising the therapeutic regimen. Here, we summarise the clinical symptoms of NTM diseases in various extrapulmonary organs, and discuss the recent trends in diagnosing and treating these diseases. We also highlight the complications associated with the management of extrapulmonary NTM disease.

Extrapulmonary Nontuberculous Mycobacteria Infections in Hospitalized Patients, United States, 2009-2014.

Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections in susceptible persons. To characterize the epidemiology of skin and soft tissue (SST) and disseminated extrapulmonary infections caused by NTM in the United States, we used a large electronic health record database to examine clinical, demographic, and laboratory data for hospitalized patients with NTM isolated from extrapulmonary sources during 2009–2014. Using all unique inpatients as the denominator, we estimated prevalence and summarized cases by key characteristics. Of 9,196,147 inpatients, 831 had confirmed extrapulmonary NTM. The 6-year prevalence was 11 cases/100,000 inpatients; source-specific prevalence was 4.4 SST infections/100,000 inpatients and 3.7 disseminated infections/100,000 inpatients. NTM species varied across geographic region; rapidly growing NTM were most prevalent in southern states. Infection with Mycobacterium avium complex was more common among patients with concurrent HIV and fungal infection, a relevant finding because treatment is more effective for M. avium complex than for other NTM infections.

Varying clinical presentations of nontuberculous mycobacterial disease : Similar to but different from tuberculosis.

The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD are different from those of pulmonary tuberculosis (TB), confusion about these mycobacterial diseases leads to a diagnostic pitfall. Diagnostic challenges include the coexistence of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), false positives for NTM in MTB nucleic acid amplification tests, microbial substitution, and abnormal radiological manifestations caused by NTM. Features of extrapulmonary NTM diseases, such as pleurisy, vertebral osteomyelitis, and disseminated disease, are different from the corresponding tuberculous diseases. Moreover, the immunological background of the patient (status of human immunodeficiency virus infection with or without antiviral therapy, continuation or discontinuation of immunosuppressive therapy, use of immune checkpoint inhibitor, pregnancy and delivery, etc.) influences the pathophysiology of mycobacterial diseases. This review describes the varying clinical presentations of NTM disease with emphasis on the differences from TB. J. Med. Invest. 68 : 220-227, August, 2021.

Profiles of Extrapulmonary Nontuberculous Mycobacteria Infections and Predictors for Species: A Multicenter Retrospective Study.

Extrapulmonary nontuberculous mycobacteria (NTM) infections contribute to morbidity and mortality worldwide. However, studies about extrapulmonary NTM infections have been limited. Therefore, we aim to describe the diversity of extrapulmonary NTM infections and identify predictors for species. Information regarding diversity of NTM isolates, antimicrobial susceptibility testing, treatment regimens, and outcomes were collected from four tertiary care centers in South Korea. Comparisons were made between patients with rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM) infections. A total of 117 patients (46 males vs. 71 females) were included. Skin and soft tissue infections (SSTIs) predominated (34.2%), followed by bone and joint infections (28.2%). In SSTIs, RGM species were predominantly identified (26/28, 92.9%), whereas SGM species were mainly identified in bone and joint infections (18/26, 69.2%), and the difference of isolated sites was verified by a post hoc test (p < 0.001). Multivariable regression analysis revealed that male sex (vs. female sex; OR 5.30, CI 1.35–24.26, p = 0.020) and bone and joint infections (vs. SSTIs; OR 18.10, CI 3.28–157.07, p = 0.002) were predictors of SGM infections, whereas the opposite was observed for RGM infections. Bone and joint infections and male sex were predictors for SGM infections, whereas SSTIs and female sex were predictors for RGM infections.

Characteristics of Nontuberculous Mycobacterial Infections at a Midwestern Tertiary Hospital: A Retrospective Study of 365 Patients.

BackgroundThe prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease.MethodsWe conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections.ResultsWe identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185 of 365; 50.7%), followed by skin/soft tissue (56 of 365; 15.3%), disseminated (40 of 365; 11%), and lymphatic (28 of 365; 7.7%) disease. Mycobacterium avium complex was the most common species (184 of 365; 50.4%). Individuals aged >50 years were most affected (207 of 365; 56.7%). Common comorbidities included structural lung disease (116 of 365; 31.8%), use of immunosuppressive medications (78 of 365; 21.4%), malignancy (59 of 365; 16.2%), and human immunodeficiency virus (42 of 365; 11.5%).ConclusionsThis large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.

The Epidemiology of Extrapulmonary Non-tuberculous Mycobacterial Infection in a Pediatric Population.

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and a well-known cause of lymphadenitis, skin and soft tissue infections. The aim of this study was to evaluate the epidemiology of extrapulmonary pediatric NTM infections occurring from 2000 to 2017 in Queensland, Australia. All cases of NTM and TB are notifiable under the Queensland Public Health Act (2005) and associated regulations (2005). Data from 2000 to 2017 inclusive was collected from the Notifiable Conditions Database, a laboratory based notification system that covers private and public laboratory systems. Pediatric population demographic data were obtained from the Australian Bureau of Statistics by researching the number of children 0-14 years of age in Queensland from 2000 to 2017; both annual and averaged population was determined. The statistical software SPSS and Tableau was used for analysis. The mean age of diagnosis was 2.5 years with a majority of the cohort being women. Mycobacterium avium was the most commonly diagnosed pathogen. Geographic regions with the highest numbers of cases were predominantly tropical and coastal areas. M. haemophilum emerged as a more common pathogen from 2011 following a period of major flooding. Characteristics of the cohort of children susceptible to NTM disease appears consistent with previous reports. However, changes in the epidemiology of NTM infection (such as incidence, species, and geographic distribution) in children may be linked to environmental and weather factors.

2260. Clofazimine Safety and Efficacy for Treatment of Multidrug-Resistant Non-Tuberculous Mycobacteria (NTM)

BackgroundNontuberculous mycobacteria (NTM) are increasingly detected and challenging to cure given complex drug-resistance patterns and need to use often intolerable drug multidrug regimens over months to years of duration. As such, NTM infection can be associated with significant mortality and morbidity. Clofazimine is a repurposed drug used in the treatment of leprosy worldwide and increasingly in multidrug-resistant (MDR) tuberculosis. Some centers in the United States have incorporated clofazimine in the treatment of NTM but experience is limited and procurement restrictions have hampered its more widespread useMethodsA prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection among those treated with clofazimine from a single center serving referrals from across the state of Virginia under an investigational new drug protocol. Data were collected through the center’s electronic medical record and included both pretreatment and follow-up host characteristics, radiological, microbiological and pathology data. Outcomes were assessed, radiological resolution, symptom improvement, and change in pulmonary function test (among patients with cystic fibrosis).ResultsThirty-seven patients received clofazimine. NTM species for which the treatment was indicated were M. abscessus in 21 (58%), M. avium complex in 17 (45%) and 3 with M. chelonae. The most common companion drugs for M. abscessus included imipenem, tigecycline, linezolid or tedizolid, amikacin (IV induction followed by inhaled continuation phase) and azithromycin. For other basic patient characteristics refer to Table 1. Survival rate was 97%, while 73.5% had documented improvement in symptoms and only 2.9% had worsening of symptoms. Radiological resolution or partially improving were documented in 38% of the patients. there were no severe adverse events from clofazimine.ConclusionAdding clofazimine to multi-class antibiotic regimens for drug-resistant NTM treatment, including pulmonary M. abscessus disease, was well tolerated and led to clinical improvement in the majority of those treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within and otherwise optimized regimen. Disclosures All authors: No reported disclosures.

Extrapulmonary Nontuberculous Mycobacterial Disease Surveillance - Oregon, 2014-2016.

Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect immunocompromised persons. However, even healthy persons are susceptible to infection through percutaneous inoculation. Although 77% of NTM diseases manifest as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the lymphatic system, and soft tissue. NTM infections can have incubation periods that exceed 5 years (2), often require prolonged treatment, and can lead to sepsis and death. Extrapulmonary NTM outbreaks have been reported in association with contaminated surgical gentian violet (3), nail salon pedicures (4), and tattoos received at tattoo parlors (5), although few surveillance data have been available for estimating the public health burden of NTM.* On January 1, 2014, the Oregon Health Authority designated extrapulmonary NTM disease a reportable condition. To characterize extrapulmonary NTM infection, estimate resources required for surveillance, and assess the usefulness of surveillance in outbreak detection and investigation, 2014–2016 extrapulmonary NTM surveillance data were reviewed, and interviews with stakeholders were conducted. During 2014–2016, 134 extrapulmonary NTM cases (11 per 1 million persons per year) were reported in Oregon. The age distribution was bimodal, with highest incidence among persons aged <10 years (20 per 1 million persons per year) and persons aged 60–69 years (18 per 1 million persons per year). The most frequently reported predisposing factors (occurring within 14–70 days of symptom onset) were soil exposure (41/98; 42%), immunocompromised condition (42/124; 34%), and surgery (32/120; 27%). Overall, 43 (33%) patients were hospitalized, 18 (15%) developed sepsis, and one (0.7%) died. Surveillance detected or helped to control two outbreaks at low cost. Jurisdictions interested in implementing extrapulmonary NTM surveillance can use the Council of State and Territorial Epidemiologists (CSTE) standardized case definition (6) for extrapulmonary NTM reporting or investigative guidelines maintained by the Oregon Health Authority (7).

Clinical features of infection caused by non-tuberculous mycobacteria: 7years' experience.

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms associated with various infections. The aim of the study was to determine the most relevant clinical characteristics of NTM during the 7-year period. A retrospective study of NTM infections was conducted between January 2009 and December 2016. The American Thoracic Society/Infectious Disease Society of America criteria were used to define cases of pulmonary or an extrapulmonary site. A total of 85 patients were included in the study. Pulmonary cases predominated 83/85 (98%), while extrapulmonary NTM were present in 2/95 (2%) patients. Overall, ten different NTM species were isolated. The most common organisms were slow-growing mycobacteria (SGM) presented in 70/85 (82.35%) patients. Isolated SGM strains were Mycobacterium avium complex (MAC) in 25/85 (29.41%) patients, M. xenopi in 20/85 (23.53%) patients, M. kansasii in 15/85 (17.65%) patients and M. peregrinum and M. gordonae in 5/85 (5.88%) patients each. Isolated rapid-growing mycobacteria (RGM) strains were M. abscessus in 8/85 (9.41%) patients, M. fortuitum in 4/85 (4.71%) patients and M. chelonae in 3/85 (3.53%) patients. Almost all patients (98%; 83/85) had comorbidities. Among 75 (88.24%) patients who completed follow-up, 59 (69.41%), 10 (11.76%) and 6 (7%), were cured, experienced relapse and died, respectively. In the present study, pulmonary NTM infections were more frequent compared to extrapulmonary disease forms. SGM were most common isolates with MAC pulmonary disease the most frequently found. Comorbidities have an important role in NTM occurrence. Further investigation should focus on an NTM drug susceptibility testing.

Surveillance of Extrapulmonary Nontuberculous Mycobacteria Infections, Oregon, USA, 2007-2012.

Limited data are available describing extrapulmonary nontuberculous mycobacteria (NTM) infections in the general population. We describe results from statewide population-based laboratory surveillance in Oregon, USA, during 2007–2012. We defined a case of extrapulmonary NTM infection as >1 isolate from skin/soft tissue, disseminated sites, lymph node, joint, or other sites. The annual incidence of extrapulmonary NTM infection (other than Mycobacterium gordonae) was stable, averaging 1.5 cases/100,000 population. Median age of the 334 patients was 51 years, and 53% of patients were female. Half of cases were caused by M. avium complex, but rapid-growing NTM species accounted for one third of cases. Most extrapulmonary NTM infections are skin/soft tissue. Compared with pulmonary NTM infection, more extrapulmonary infections are caused by rapid-growing NTM species. the designation of NTM as a reportable disease in Oregon in 2014 will result in better detection of changes in the incidence and patterns of disease in the future.

Safety and Effectiveness of Clofazimine for Primary and Refractory Nontuberculous Mycobacterial Infection

Clofazimine is an antimicrobial agent that has activity invitro against mycobacteria. Increasingly, it has been used for the treatment of nontuberculous mycobacteria (NTM), despite limited data supporting its use in this setting. The objective of this study was to evaluate the safety, tolerability, and clinical outcomes associated with clofazimine in patients with NTM infection. This observational-cohort study assessed clofazimine as used for pediatric and adult cystic fibrosis (CF) and non-CF patients with pulmonary and extrapulmonary NTM infection as part of a multidrug regimen from 2006 to 2014. Treatment regimens and adverse drug reactions (ADRs) were captured. A total of 112 patients were included (median age, 62 years); 24 patients (21%) had CF. Eighty-seven (78%) had refractory disease with failure of previous therapy. Fifty-four patients (48%) had Mycobacterium abscessus complex, 41 (37%) had Mycobacterium avium complex, and 16 (14%) had two NTM species. The median duration of clofazimine use was 383days (range, 3-2,419days). Sixteen patients (14%) stopped clofazimine due to an ADR after a median of 101days (95%CI, 63-119). Forty-one of 82 patients (50%) with pulmonary disease converted to negative NTM cultures within 12months. Clofazimine was a safe, reasonably tolerated, and active oral drug for NTM infection in our heterogeneous population of pediatric and adult CF and non-CF patients. It should be considered as an alternative drug for treatment of NTM disease.

Nontuberculous mycobacterial infection of the musculoskeletal system in immunocompetent hosts.

Background:Nontuberculous mycobacteria (NTM) were considered saprophytic organisms for many years but now are recognized as human pathogens. Although humans are routinely exposed to NTM, the rate of clinical infection is low. Such infections usually occur in the elderly and in patients who are immunocompromised. However, there has been an increasing incidence in recent years of infections in immunocompetent hosts. NTM infections in immunocompetent individuals are secondary to direct inoculation either contamination from surgical procedures or penetrating injuries rather than hematogenous dissemination. Clinically and on histopathology, musculoskeletal infections caused by NTM resemble those caused by Mycobacterium tuberculosis but are mostly resistant to routine antituberculosis medicines.Materials and Methods:Six cases of NTM infection in immunocompetent hosts presenting to the department from 2004 to 2015 were included in study. Of which two cases (one patella and one humerus) of infection were following an open wound due to trauma while two cases (one hip and one shoulder) of infection were by inoculation following an intraarticular injection for arthrogram of the joint, one case was infection following arthroscopy of knee joint and one case (calcaneum) was infection following local injection for the treatment of plantar fasciitis. All patients underwent inaging and tissue diagnosis with samples being sent for culture, staining, and histopathology.Results:Clinical suspicion of NTM inoculation led to the correct diagnosis (four cases with culture positive and two cases with histopathological diagnosis). There treatment protocol for extrapulmonary NTM infection was radical surgical debridement and medical management based on drug sensitivity testing in culture positive cases. At a mean follow up of 3 years (range1–9 years) all patients had total remission and excellent results.Conclusions:Whenever a case of chronic granulomatous infection is encountered that does not respond to standard anti-tuberculous treatment, with a history of open trauma, surgical intervention, or injection as shown in this study, a possible NTM infection should be considered and managed appropriately.

Nontuberculous Mycobacterial Infections in a French Hospital: A 12-Year Retrospective Study.

BackgroundNontuberculous mycobacteria (NTM) are environmental organisms associated with a range of infections. Reports of NTM epidemiology are mainly focused on pulmonary infections and isolations, and extrapulmonary infections are less frequently described.MethodsWe conducted a retrospective study of NTM infections at the Bordeaux University Hospital, France, between January 2002 and December 2013. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease.ResultsIn our setting, 170 patients were included. Pulmonary cases predominated (54.1%), followed by skin and soft tissue infections (22.9%), disseminated cases (10.6%), lymphadenitis (7.7%), bone and joint infections (2.9%) and the remaining 1.8% catheter-related infections. Overall, 16 NTM species were isolated. Mycobacterium avium (31.8%) and M. intracellulare (20%) were the most common species identified, followed by M. marinum (13.5%), M. kansasii (10.6%), M. xenopi (9.4%), rapidly growing mycobacteria (9.4%) and other slowly growing mycobacteria (5.3%). In general, NTM isolates were largely prevalent in people older than 50 (62.4%); patients aged 1–10 year-old exclusively yielded M. avium from lymph nodes, almost cases having being diagnosed after 2007. Among the 121 patients with complete follow-up, 78 (64.5%), 24 (19.8%), and 19 (15.7%) were cured, experienced relapse, or died, respectively.ConclusionIn our study, extrapulmonary NTM infections represented almost half of cases, consisting mainly in skin and soft tissue infections. The increase lymphadenitis cases in children after 2007 could be linked to the cessation of mandatory BCG vaccination in France. We observed similar cure rates (64%) between pulmonary and extrapulmonary infections.

Prevalence and species spectrum of both pulmonary and extrapulmonary nontuberculous mycobacteria isolates at a tertiary care center

Objective/background: Nontuberculous mycobacteria (NTM) infection associated with pulmonary and extrapulmonary disease has been increasing globally. Despite an increase in incidence rate of NTM infection, its prevalence, species diversity, and circulation pattern in India is largely unknown. This study sought to investigate the overall burden and diversity of NTM among both pulmonary and extrapulmonary clinical isolates from a Northern Indian population. Methods: The study was conducted in the Department of Microbiology, from January 2013 to December 2015. A total of 4620 clinical samples were collected from patients suspected to have pulmonary and extrapulmonary tuberculosis. Preliminary diagnosis was performed using Ziehl–Neelsen staining followed by liquid culture in BacT/ALERT three-dimensional system. A total of 906 positive cultures obtained were differentiated as either NTM or Mycobacterium tuberculosis complex using a biochemical and MPT64 antigen test. Further identification of NTM species was confirmed with a line probe assay. Results: Out of 906 cultures isolates, 263 (29.0%) were confirmed as NTM and 643 (71.0%) were identified as Mycobacterium tuberculosis complex. A total of 79.4% of the NTM were recovered from pulmonary and 18.2% from extrapulmonary specimens. The diversity of NTM species was high (13 species) and predominated by Mycobacterium abscessus (31.3%) followed by Mycobacterium fortuitum (22%), Mycobacterium intracellulare (13.6%), Mycobacterium chelonae (9.1%), however, M. abscessus and M. fortuitum were the predominant species in both types of clinical isolates. Men (60.4%) and older patients aged greater than 55years were the predominated risk group for NTM infection. Conclusion: The high prevalence and species diversity of NTM suggests the need for immediate and accurate characterization of NTM for proper treatment and management of patients.