Extrapulmonary Nontuberculous Mycobacteria Infections Research Articles

Epidemiology of Pulmonary and Extrapulmonary Nontuberculous Mycobacteria Infections at 4 US Emerging Infections Program Sites: A 6-Month Pilot.

Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance. The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review. Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure. Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions.

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.

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).

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.