Positive Nontuberculous Mycobacteria Culture Research Articles

1868. Epidemiology of Healthcare Facility-Associated Nontuberculous Mycobacteria at a 10-Hospital Network

Abstract Background Numerous studies have reported that rates of nontuberculous mycobacteria (NTM) infections are increasing. However, data on the epidemiology of healthcare facility-associated (HCFA) NTM are sparse. We performed a multicenter longitudinal study to analyze the epidemiology of NTM at a network of U.S. academic hospitals. Methods We retrospectively analyzed data on positive cultures for NTM obtained from 2012-2020 at a network of 10 U.S. academic hospitals and associated clinics (Table). Variables analyzed included NTM species, specimen source, and hospital admission status. A unique NTM episode was defined as a patient’s first positive culture for a particular NTM species and specimen source category (pulmonary vs. extrapulmonary). Episodes linked to isolates obtained on day 3 or later of hospitalization were considered to represent hospital-onset (HO) NTM. Seven hospitals contributed at least 12 months of baseline data prior to January 2014, and within this closed cohort, trends of NTM incidence rates were estimated with log regression. Characteristics of a 10-hospital network that performed retrospective culture-based NTM surveillance from 2012-2020. Results Across the 10-hospital network, 24,376 total NTM isolates were identified during 19,248,137 patient-days of surveillance; 12,847 (53%) isolates represented unique NTM episodes. Of these episodes, 3,044 (24%) were HO-NTM, which were most commonly caused by M. avium complex (n=1,466, 48%), M. abscessus complex (n=397, 13%), and M. chelonae-M. immunogenum (n=348, 11%). For 595 (20%) HO episodes, specimen source was extrapulmonary. Individual hospital incidence rates of HO-NTM were highly variable with a median rate of 1.1 episodes per 10,000 patient-days (range, 0.4 – 5.5 episodes) (Table). For the 7-hospital closed cohort, the HO-NTM incidence rate decreased from 2.3 to 1.4 episodes per 10,000 patient-days from 2014 to 2020 (incidence rate ratio, 0.6; 95% CI, 0.5-0.7; P < .0001) (Figure 1). Trend analysis estimated that the rate of HO-NTM decreased by 10% per year (95% CI, 8-12%; P < .0001) (Figure 2). Incidence rates of NTM episodes observed from 2014-2020 at a 7-hospital cohort. Admitted epsiodes consisted of episodes that were hospital-onset (HO) or not HO. Log regression model of hospital-onset NTM incidence rates from 2014-2020 within a 7-hospital cohort. The fit plot displays predicted values with 95% confidence limits and observed rates. Conclusion Network HO-NTM incidence rates decreased from 2014-2020, but rates varied substantially at individual hospitals. These results provide comprehensive data on HCFA-NTM isolation, including rates that can serve as external benchmarks. Given hospital variability, NTM surveillance at the individual hospital level is paramount. Disclosures Arthur W. Baker, MD, MPH, Insmed: Grant/Research Support|Medincell: Advisor/Consultant Ricardo M. La Hoz, MD, Takeda: Advisor/Consultant Melissa B. Miller, PhD, BioFire: Advisor/Consultant|BioFire: Honoraria|Cantata Bio: Grant/Research Support|Luminex Molecular Diagnostics: Advisor/Consultant|Luminex Molecular Diagnostics: Honoraria|MiraVista Diagnostics: Advisor/Consultant|MiraVista Diagnostics: Honoraria|QIAGEN: Advisor/Consultant|QIAGEN: Grant/Research Support|QIAGEN: Honoraria David J. Weber, MD, MPH, BD: Advisor/Consultant|Germitic: Advisor/Consultant|GSK: DSMB|PDI: Advisor/Consultant|Pfizer: Advisor/Consultant|Wellair: Advisor/Consultant Barbara D. Alexander, MD, F2G Pharmaceuticals: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Leadiaint: Grant/Research Support|Merck: Advisor/Consultant|Scynexis: Grant/Research Support|Thermofisher: Advisor/Consultant Jason E. Stout, MD, MHS, AN2 pharmaceuticals: Grant/Research Support

Lung infection with nontuberculous mycobacteria

ObjectiveTo describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methodsWe retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. ResultsWe included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). ConclusionThe diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

Epidemiology of non-tuberculous mycobacterial diseases in Slovakia during the years 2016–2021

Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found worldwide, primarily in the environment. They predominantly affect the lungs, especially in individuals with compromised immune systems. Recent studies suggest an increasing incidence of NTM disease; however, their actual clinical impact in Slovakia remains uncertain. In this study, we conducted a retrospective analysis using a representative collection of NTM cases in the country. We searched the national database for patients with positive NTM cultures between January 2016 and December 2021. A total of 1355 NTM-positive cultures were identified in Slovakia, with no significant increase observed during the study period. Among these, 358 cases (26.4%) were confirmed as NTM disease. The incidence of the disease was notably higher in individuals over 55 years old (p < 0.0001). Moreover, women diagnosed with NTM disease exhibited a significantly higher average age than men (p = 0.0005). The majority of NTM disease cases were attributed to Mycobacterium (M.) intracellulare (39.9%) and M. avium (38.5%). Geographically, the highest incidence of NTM disease was observed in the Bratislava region (10.69 per 100,000 population).

Coexistence of lung cancer in a patient with non-tuberculous mycobacteria

Nontuberculous mycobacteria (NTM) may mimic lung carcinoma as a solitary mass or miliary nodules, the coexistence of NTM and lung carcinoma is rare. The diagnosis may be delayed due to a high initial index of suspicion for mycobacterium tuberculosis complex rather than malignancy in an endemic country like India. We report a rare case of 47-year-old male who presented with exertional dyspnea, cough with expectoration and fever was initially treated with anti-tuberculous drugs following a mycobacterium avium complex growth in BAL cultures. Despite treatment, patient’s condition worsened, and computed tomography (CT) guided biopsy was done which showed adenocarcinoma. This case report highlights that a lung biopsy is a necessity for accurate diagnosis, and a positive NTM culture doesn't always exclude a concomitant lung carcinoma.

Rapid and Accurate Identification of Nontuberculous Mycobacteria Directly from Positive Primary MGIT Cultures by MALDI-TOF MS.

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Accurate and rapid mycobacterial species identification is needed to successfully diagnose, treat, and manage infections caused by NTM. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS, was demonstrated to effectively identify mycobacteria isolates subcultured from solid or liquid media rather than new positive cultures. The present study aims to develop a new extraction protocol to yield rapid and accurate identification of NTM from primary MGIT cultures by MALDI-TOF MS. A total of 60 positive MGIT broths were examined by the Bruker Biotyper system with Mycobacteria Library v. 2.0 (Bruker Daltonics GmbH & Co. KG., Bremen, Germany). The results were compared with those obtained by the molecular method, line probe assay GenoType Mycobacterium CM/AS/NTM-DR. All samples were concordantly identified by MALDI-TOF MS and the molecular test for all the tested mycobacteria. Fifty-seven (95%) MGIT positive cultures for NTM from clinical samples had a MALDI-TOF MS analysis score S ≥ 1.8. Although a small number of strains and a limited diversity of mycobacterial species were analysed, our results suggest that MALDI-TOF MS could represent a promising routine diagnostic tool for identifying mycobacterial species directly from primary liquid culture.

Nontuberculous Mycobacterial Lung Disease in the Patients with Cystic Fibrosis-A Challenging Diagnostic Problem.

Background: Cystic fibrosis (CF) is an autosomal, recessive genetic disorder, caused by a mutation in the cystic fibrosis transmembrane conductance receptor regulator (CFTR) gene. Dysregulated mucous production, and decreased bronchial mucociliary clearance, results in increased susceptibility to bacterial and fungal infections. Recently, nontuberculous mycobacteria (NTM) infections were identified as an emerging clinical problem in CF patients. Aim: The aim of the present study was to assess the frequency of NTM isolations in CF patients hospitalized in the pulmonary department, serving as a hospital CF center, and to describe challenges concerning the recognition of NTMLD (nontuberculous mycobacterial lung disease) in those patients. Methods: Consecutive CF patients, who were hospitalized due to pulmonary exacerbations (PEX), in a single CF center, between 2010 and 2020, were retrospectively assessed for the presence of NTM in respiratory specimens. Clinical and radiological data were retrospectively reviewed. Results: Positive respiratory specimen cultures for NTM were obtained in 11 out of 151 patients (7%), mean age—35.7 years, mean BMI—20.2 kg/m2, mean FEV1—58.6% pred. Cultures and phenotyping revealed the presence of Mycobacterium avium (M. avium)—in six patients, Mycobacterium chimaera (M. chimaera) in two, Mycobacterium kansasii (M. kansasii)—in one, Mycobacterium abscessus (M. abscessus)—in one, Mycobacterium lentifavum (M. lentiflavum)—in one. Simultaneously, respiratory cultures were positive for fungi in 91% of patients: Candida albicans (C. albicans)—in 82%, Aspergillus fumigatus (A. fumigatus)—in 45%. Clinical signs of NTMLD were non—specific, chest CT indicated NTMLD in five patients only. Conclusion: Due to non-specific clinical presentation, frequent sputum cultures for NTM and analysis of serial chest CT examinations are crucial for NTMLD recognition in CF patients. Further studies concerning the predictive role of fungal pathogens for NTMLD development in CF patients are needed.

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study.

Bronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM. This retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort. In total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score. Bronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.

NonTuberculous Mycobacteria Blood Stream Infection in Pediatric and Adult Patients: 15 Years Surveillance.

Nontuberculous Mycobacteria (NTM) are rare causes of bloodstream infection (BSI). This study addresses the management and prognosis of NTM BSI and the differences between adult and pediatric patients. We retrospectively reviewed the medical charts of patients at any age with NTM BSI, from January 1, 2005, to June 30, 2020. Data on demographics, underlying conditions, clinical manifestations, NTM species, antibiotic treatments and outcomes were retrieved. Positive blood cultures for NTM were detected in 43 patients, 30 children and 13 adults. Median age: 10.37 years (IQR 6.692-39.864). Thirty-seven (86%) patients had an active malignant disease. Fever was the chief sign in 23 (53.5%) patients and pulmonary manifestations in 14 (32.6%). Rapidly growing NTM comprised 39 (90.7%) of the isolates. Central venous catheter (CVC) was documented in 39 (90.7%) cases, 31 (79.5%) of which were removed as part of treatment. Antibiotic treatment directed against NTM was documented in 26 (60.5%) patients. CVC was removed in 7/17 patients who were not treated with antibiotics. Relapse occurred in 3 cases; no 30-days mortality was reported. Children and adults had similar clinical characteristics. However, children had a higher rate of CVC at the time of bacteremia and a higher chance to receive treatment. NTM BSI was seen mainly in oncologic patients with CVC. Children and adults had a similar disease course and outcome. Relapse was rare and NTM-related mortality was not reported.

Infección pulmonar por micobacterias no tuberculosas

ObjectiveTo describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment. Material and methodsWe retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analyzed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment. ResultsWe included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1%), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement). ConclusionThe diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.

Healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (HALT NTM) study: Rationale and study design.

BackgroundHealthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observational study to standardize the approach to NTM outbreak investigation among pwCF.MethodsThis is a parallel multi-site study of pwCF within a single Center who have respiratory NTM isolates identified as being highly-similar. Participants have a history of positive airway cultures for NTM, receive care within a single Center, and have been identified as part of a possible outbreak based on genomic analysis of NTM isolates. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of a shared healthcare-associated encounter(s) among patients in a Center and identification of environmental isolates that are genetically highly-similar to respiratory isolates recovered from pwCF. Secondary endpoints include characterization of potential transmission modes and settings, as well as incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region.DiscussionWe hypothesize that genetically highly-similar strains of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from environmental sources. This novel study design will establish a standardized, evidence-based epidemiologic investigation tool for healthcare-associated NTM outbreak investigation within CF Care Centers, will broaden the scope of independent outbreak investigations and demonstrate the frequency and nature of healthcare-associated NTM transmission in CF Care Centers nationwide. Furthermore, it will provide valuable insights into modeling risk factors associated with healthcare-associated NTM transmission and better inform future infection prevention and control guidelines. This study will systematically characterize clinically-relevant NTM isolates of CF healthcare environmental dust and water biofilms and set the stage to describe the most common environmental sources within the healthcare setting harboring clinically-relevant NTM isolates.Trial registrationClinicalTrials.gov NCT04024423. Date of registry July 18, 2019.

Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015–2020)

Background: Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. Methods: Retrospective analysis (2015–2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients’ characteristics, NTM strains, and time to culture positivity were reported. Results: Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m²). The Mycobacterium avium complex (MAC) was the most frequently identified group (37% of strains) followed by Mycobacterium gordonae (25%) and Mycobacterium xenopi (12%) among the slowly growing mycobacteria (SGM), while the Mycobacterium chelonae/abscessus group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (n = 19, 43% of cases in patients treated) followed by RGM (n = 15, 34%) and M. xenopi (n = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. Conclusions: In Western Switzerland, M. avium and M. gordonae were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

The frequency and related factors of non-tuberculosis mycobacteria infections among patients with cystic fibrosis.

Non-tuberculous mycobacteria (NTM) can cause chronic lung infection particularly in patients who have structural lung disease such as cystic fibrosis (CF). We evaluated the incidence and management of NTM infections in patients with CF in our center. A retrospective cohort study was carried out on CF patients having at least one positive NTM isolate between 2012 and 2020. Ten patients (2.1%) had at least one positive NTM culture from respiratory samples. All of them were vaccinated with Bacille Calmette-Guérin (BCG) vaccine, which is in the national vaccination program in our country. Eight patients had the Mycobacterium abscessus complex, one had Mycobacterium avium, and one had Mycobacterium szulgai growth in their respiratory samples. Three patients had transient NTM infection, two had persistent, and five had active NTM infection (NTM pulmonary disease). Patients with NTM pulmonary disease received antibiogram-directed antimycobacterial therapy. In patients with NTM pulmonary disease, the median ppFEV1 and BMI decreased by 17% and 1%, respectively, at the time of the first NTM isolation when compared with the values one year before the first NTM isolation. Culture conversion was not seen in any patient infected with Mycobacteriunm abscessus complex. The NTM infection incidence is lower in our country than in those countries where the BCG vaccine is not routinely applied. The BCG vaccine may be a protective factor for NTM infection. Further studies are needed about the prevalence of NTM infections, facilitating and protective factors, and appropriate management of NTM infections in patients with CF.

Late onset of microbial keratitis after laser in situ keratomileusis surgery: case series.

To report predisposing factors, clinical features, microbiology spectrum, antibiotic resistance, antimicrobial therapy, and outcomes of patients with a previous laser in situ keratomileusis (LASIK) surgery and diagnosed with presumed microbial keratitis. Sydney Eye Hospital, Sydney, New South Wales, Australia. Retrospective case review. Patients were identified from pathology and hospital coding data from 2012 to 2016. Inclusion criteria were all patients with a previous LASIK surgery, a presumed diagnosis of microbial keratitis, and a corneal scrape performed and aged older than 18 years. Demographics, clinical details, and outcomes were collated from the medical records. Sixteen patients were included, with median age of 41.5 years (range 22 to 85 years) and 56.2% of women. The median time between LASIK procedure and microbial keratitis presentation was 38.3 months (interquartile range 6.7 to 77.45 months). Cultures were positive for bacteria in 12 (75%) of 16 scrapes. Of the bacterial isolates, 12 (85.7%) were gram-positive and 2 (14.3%) gram-negative. Sensitivity profiles for the isolated bacteria were similar between fortified antibiotics (cefalotin and gentamicin) and commercial products (chloramphenicol and ofloxacin). Complications included the need for tectonic grafts, nonhealing epithelial defects, thinning, and neovascularization. Late onset of keratitis after LASIK can occur with no positive cultures for nontuberculous mycobacteria, no interface involvement, and no other usual features reported in case series of infectious keratitis in LASIK patients. It has a similar clinical course to non-LASIK keratitis, such that the surgery may not have been a risk factor for infection.

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

Nontuberculous mycobacterial infection after lung transplantation: A single-center experience in South Korea.

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. 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. 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). 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.

Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway

BackgroundIndividuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. MethodsUrine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. ConclusionThese findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.

The Italian registry of pulmonary nontuberculous mycobacteria - IRENE: the study protocol

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration: Clinicaltrial.gov: NCT03339063.

Lymphadenitis by non-tuberculous mycobacteria in children.

Non-tuberculous mycobacteria (NTM) constitute an important cause of cervical lymphadenitis in immunocompetent children. The aims of this study were to estimate the incidence of lymphadenitis due to NTM in children in Cyprus and to describe the characteristics, diagnostic approach, management and outcome of such infections. Children aged 1-5years old, evaluated at Archbishop Makarios III Hospital, Nicosia, Cyprus, from 1 January 2007 to 31 December 2016 for lymphadenopathy, were included in the study. All children had positive lymph node culture for NTM. A total of 22 cases of culture-positive lymphadenitis caused by NTM were reviewed. Patient age ranged from 16 to 55months. Tuberculin skin test produced an induration in 81.0% of cases (diameter, 4-17mm). Mycobacterium avium was isolated in 17 cases (77.3%), M.intracellulare in three (13.6%), M.paraffinicum in one (4.5%) and M.kansasii in one case (4.5%). All 22 patients underwent surgical excision of affected nodes. Additional anti-mycobacterial treatment was given when complete excision was not achieved or for post-surgical recurrence. Complications were few and included scar in three children and one case of transient facial nerve palsy. Surgical excision of NTM-infected lymph nodes is an effective diagnostic and therapeutic approach. When total surgical excision is not feasible, a combination of partial excision with a clarithromycin-including drug regimen appears safe, effective and causes milder and fewer complications than surgery alone.

927. Tap Water Avoidance Decreases Rates of Nontuberculous Mycobacteria in Intensive Care Units

BackgroundWe recently investigated a clonal outbreak of Mycobacterium abscessus molecularly linked to a colonized water supply at a new hospital addition. Use of sterile water instead of tap water for patient care in ICUs successfully mitigated the respiratory phase of the outbreak. We hypothesized that avoidance of tap water would also be associated with decreased respiratory isolation of other nontuberculous mycobacteria (NTM).MethodsWe analyzed all positive cultures for NTM obtained at our hospital from August 2013 through December 2015. The pre-intervention outbreak period was defined as August 2013 through May 2014; the tap water avoidance intervention period was defined as June 2014 through December 2015. NTM isolation was defined as a positive culture from a respiratory specimen obtained from an ICU patient on day 3 or later of hospitalization. We also performed AFB cultures of biofilms obtained from ICU water sources.ResultsNTM were isolated from 137 patients during 70,168 patient-days (figure). NTM isolation decreased from 41.0 patients/10,000 patient-days in the outbreak period to 9.9 patients/10,000 patient-days in the intervention period (IRR, 0.24; 95% CI, 0.17–0.34; P < .0001) (table). Incidence rates of the 4 most common NTM (M. abscessus, M. chelonae/immunogenum, M. avium complex, and M. gordonae) also markedly decreased. Biofilm cultures were positive for at least 1 NTM isolate in 25 of 33 (76%) ICU water sources, including M. abscessus (n = 11, 33%), M. chelonae/immunogenum (n = 11, 33%), and M. gordonae (n = 11, 33%).ConclusionThe use of sterile water for ICU patient care substantially decreased NTM isolation from patient respiratory specimens, presumably reducing risk of symptomatic infection. Hospitals with endemic NTM should consider tap water avoidance for high-risk patients. Table:Incidence rates of NTM isolated from the respiratory tract of ICU patients.NTMOutbreak cases/10,000 patient-daysIntervention cases/10,000 patient-daysIRR (95% CI) P-value M. abscessus 16.62.30.14 (0.07–0.27)<.0001 M. chelonae/immunogenum12.01.70.14 (0.06–0.30)<.0001 M. avium complex7.43.50.48 (0.24–0.94).03 M. gordonae 4.60.80.18 (0.06–0.57).001Other NTM0.51.73.58 (0.45–28.62).20All NTM (Total)41.09.90.24 (0.17–0.34)<.0001Disclosures All authors: No reported disclosures.

Pulmonary isolation and clinical relevance of nontuberculous mycobacteria during nationwide survey in Serbia, 2010-2015.

The rates of pulmonary colonization and disease due to nontuberculous mycobacteria (NTM) appear to be increasing globally, but diversity of species recovered as well as clinical relevance of NTM isolates differ considerably by geographic region. The first nationwide study of isolation frequency and clinical significance of NTM in Serbia included all patients with respiratory specimens yielding a positive NTM culture over the six-year period, 2010–2015. We analyzed trends in annual NTM isolation and NTM pulmonary disease (PD) incidence rates, with NTM PD cases defined in accordance with microbiological criteria established by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA). 777 pulmonary NTM isolates were collected from 565 patients, of whom 126 (22.3%) met the ATS/IDSA criteria. The annual NTM isolation and NTM PD incidence rates per 100,000 changed over 2010–2015 from 0.9 to 1.6 (p = 0.1746) and from 0.18 to 0.48 (p = f0.0040), respectively. Both isolation and disease rates increased considerably with age, while higher NTM PD rates were also associated with residence in urbanized areas. Diversity of NTM species isolated was shown to be region-specific, with M. xenopi as the most prevalent species (17.3%), and increasing isolation rates of rapid growing mycobacteria (RGM) (p = 0.0072). M. xenopi was also the most common cause of NTM PD (28.6%), followed by RGM (27.8%). With 73% clinically relevant isolates, M. abscessus was identified as the most clinically relevant NTM species. While NTM PD obviously remains a rare disease in Serbia, the overall results justify recognition of NTM as pathogens of rising importance, and require further characterization of their epidemiology in the country.