Nontuberculous Mycobacteria Cultures Research Articles

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: A nationwide register-based cohort study from 1991 through 2021

BackgroundThere is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. MethodNationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. Results433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3–4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9–1.2), possible disease 1.0 (95%CI 0.8–1.2), and isolation 1.7 (95%CI 1.4–1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9–2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0–3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9–5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9–1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (−0.8 %/year, p = 0.133). ConclusionsMigrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants.

Beyond the Needle: Unmasking Atypical Mycobacteria in Postvaccination Abscesses in Children.

Atypical or nontuberculous mycobacteria (NTM) are an environmental organism responsible for opportunistic infection. Rapid-growing NTM are more commonly associated with hospital-acquired infections. Many of the organisms responsible for diseases in immunocompromised patients and hospital-acquired infections originate from tap water, such as Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium simiae, Mycobacterium mucogenicum, Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus. NTM is a rare organism responsible for the injection abscess. Considering low incidents, not much clinical data are available for this condition. Here, we discuss such cases which can be helpful to spread awareness and provide data for future policy makers. This was a retrospective study. Data on patients with injection abscess were collected from the last 6 years. Detailed history and clinical examination findings were analyzed. Children with injection abscess were operated and their further management and outcome were studied. A total of 13 cases with confirmed culture of NTM were treated over 6 years. The age ranged from 2½ months to 5¾ years with male:female ratio of 7:6. All patients hailed from the same geographical area. All children were healthy with no history of any long-term or chronic illness, without additional symptoms and had received Bacillus Calmette-Guérin vaccination at birth. The total duration of illness varied from 1 to 5 months, with a mean of 3 months. All patients had a history of intramuscular age-appropriate vaccination as per the national immunization schedule. All patients were followed up to 6 months after intervention and none of our patients developed relapse. Patient who does not respond with optimum treatment should have a high suspicion of such opportunistic infection, which is crucial to their management. Hospital-acquired NTM infections often result from contaminated instruments or fluids. Adherence to strict aseptic precautions, hand hygiene and environmental precautions are the key to preventing these infections. In case of skin and soft tissue infections / abscesses, surgical intervention plays a significant role for managing the patient.

Diagnostic performance of two commercial MPT64 assays for the identification of Mycobacterium tuberculosis complex from liquid culture

BackgroundTuberculosis (TB) is a chronic infectious disease caused by bacteria of the Mycobacterium tuberculosis complex (MTBC). Early diagnosis of TB is the most essential component to control TB. In this study, we evaluated the diagnostic performance of SD Bioline TB Ag MPT64 (SD Bioline) and BD MGIT TBc Identification (BD TBc ID) kits for the detection of MTBC from MGIT (Mycobacteria Growth Indicator Tube) 960 culture tube, positive for acid-fast bacilli (AFB). MethodsA total of 198 AFB positive MGIT cultures [MTBC, 150 and non-tuberculous mycobacteria (NTM), 48] were collected during the study period (April 2021 to March 2023) and subjected to SD Bioline and BD TBc ID assays, respectively. All the 150 MTBC positive cultures were confirmed by multiplex PCR targeting MPB64, protein B and IS6110 genes, and the 48 NTM cultures were speciated by using line probe assays technique- Genotype Mycobacterium CM assay. ResultsSD Bioline and BD TBc ID kits detected all 150 MTBC strains correctly from MGIT positive cultures and no false negative was observed. However, there was one false positive for M. abscessus by SD Bioline and two false positive results for M. abscessus and M. intracellulare each by BD TBc ID. Overall, the sensitivity of both SD Bioline and BD TBc ID tests was 100 % and specificity was 97.9 % and 95.8 %, respectively. ConclusionOur results highlighted that SD Bioline and BD TBc ID assays played a promising role in the earlier identification of MTBC present in liquid culture and may act as a potential alternative to biochemical and expensive molecular techniques.

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 &amp;lt; .0001) (Figure 1). Trend analysis estimated that the rate of HO-NTM decreased by 10% per year (95% CI, 8-12%; P &amp;lt; .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

Assessing the Impacts of Lead Corrosion Control on the Microbial Ecology and Abundance of Drinking-Water-Associated Pathogens in a Full-Scale Drinking Water Distribution System.

Increases in phosphate availability in drinking water distribution systems (DWDSs) from the use of phosphate-based corrosion control strategies may result in nutrient and microbial community composition shifts in the DWDS. This study assessed the year-long impacts of full-scale DWDS orthophosphate addition on both the microbial ecology and density of drinking-water-associated pathogens that infect the immunocompromised (DWPIs). Using 16S rRNA gene amplicon sequencing and droplet digital PCR, drinking water microbial community composition and DWPI density were examined. Microbial community composition analysis suggested significant compositional changes after the orthophosphate addition. Significant increases in total bacterial density were observed after orthophosphate addition, likely driven by a 2 log 10 increase in nontuberculous mycobacteria (NTM). Linear effect models confirmed the importance of phosphate addition with phosphorus concentration explaining 17% and 12% of the variance in NTM and L. pneumophila density, respectively. To elucidate the impact of phosphate on NTM aggregation, a comparison of planktonic and aggregate fractions of NTM cultures grown at varying phosphate concentrations was conducted. Aggregation assay results suggested that higher phosphate concentrations cause more disaggregation, and the interaction between phosphate and NTM is species specific. This work reveals new insight into the consequences of orthophosphate application on the DWDS microbiome and highlights the importance of proactively monitoring the DWDS for DWPIs.

Evaluation of the Use of Distilled Water as a Sodium Hydroxide Wash in Antimicrobial Cultures

Background: Respiratory specimens subjected to mycobacterial detection were initially pretreated with N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) to remove the mucus and normal flora.Next, they were washed and neutralized with a phosphate-buffered solution (PBS). The effectiveness of distilled water (DW) compared to PBS as a washing neutralizer during the identification of mycobacteria was evaluated in this study. Methods: We analyzed the results of the mycobacterial test conducted at a general hospital in Gwangju from October 2016 to September 2018. PBS and DW were used as a respiratory sample-washing agent for one year each. Results:The positive culture rate for the culture of mycobacteria was 12.7% (1,843/14,532) and 14.7% (2,095/14,291), when PBS and DW were used, respectively. The recovery rate of the mycobacteria growth indicator tubes (MGIT) and the separation rates of the Mycobacterium tuberculosis complex and nontuberculous mycobacteria (NTM) showed no significant change. However, in the 2% Ogawa medium, as the NTM culture increased from 47.4% (399/841) to 56.1% (630/1,122),the recovery rate increased from 45.6% (841/1,843) to 53.6% (1,122/2,095). The MGIT contamination rate decreased from 6.5% to 4.1%. Conclusion: DW as a washing agent for NALC-NaOH increased the recovery rate of Ogawa medium and reduced the contamination rate of MGIT. Therefore, the use of DW instead of PBS as a washing neutralizer during the identification of mycobacteria might be useful.

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.

ЭТИОЛОГИЧЕСКАЯ ВЕРИФИКАЦИЯ МИКОБАКТЕРИОЗА ЛЕГКИХ ПРИ ИССЛЕДОВАНИИ ОПЕРАЦИОННОГО МАТЕРИАЛА У ПАЦИЕНТОВ С ДИАГНОЗОМ А16.0 – РЕАЛЬНАЯ ПРАКТИКА

Objective: to evaluate effectiveness of etiological verification of pulmonary mycobacteriosis (PM) in patients with diagnosed “pulmonary TB without bacteriological or histological confirmation” (А16.0) as per ICD-10 and species diversity of nontuberculous mycobacteria (NTM) in resection samples from the studied cohort. Materials and methods.We analyzed test results from 28 patients with initially diagnosed “pulmonary TB without bacteriological or histological confirmation” (А16.0) as per ICD-10 and verified PM according to resection sample studies. The microbiological study (at least two sputum samples, one bronchobiopsy sample, and one resection sample) included luminescent microscopy (LUM), extraction of M. tuberculosis DNA or NTM DNA by polymerase chain reaction (PCR), culture growth on liquid media in the ВАСТЕС MGIT 960 system, identification of mycobacteria by molecular genetic methods: real-time PCR for M. tuberculosis DNA detection (Syntol, Russia) and DNA-strip technology (GenoType Mycobacterium CM/AS Hain Lifescience). Results. The analysis of referral diagnoses established that in more than half of patients with diagnosed “pulmonary TB without bacteriological or histological confirmation” (А16.0) changes in the lungs had been referred to tuberculoma (64.3%) or infiltrative TB (21.4%); 28.6% of patients had received TB treatment as per chemotherapy regimen no. 3, and 17.8% of patients – broad-spectrum antibiotics. TB treatment duration varied from 4 to 28 months. Atypical lung resections were performed in most cases (75%). NTM DNA detection in resection samples was the most informative method of etiological verification of PMB (100% of cases). NTM culture growth was observed in 17.9% of cases. Only slowly-growing NTM were represented in the studied cohort as etiologically significant. Conclusion. The diagnosis verification is based on data obtained by microbiological and/or histological, cytological studies. Studies of resection samples from TB suspects significantly improve diagnostic effectiveness.

Scubcutaneous Mycobacterium marinum infection misdiagnosed as sporotrichosis: A case report

Nontuberculous mycobacteria (NTM), are natural inhabitants of natural waters, engineered water systems, and soils. As a consequence of their ubiquitous distribution, humans are surrounded by these opportunistic pathogens. In this report, we describe a case of scubcutaneous Mycobacterium marinum infection associated with home tropical ornamental fish aquaria. A 43-years-old man reported progressively increasing nodules over his left forearm and hand for more than 7 months. Based on NTM culture, pathological examination, identification by gene sequencing and matrix assisted laser desorption ionization time of flight mass spectrometry, the diagnosis of scubcutaneous NTM infection was confirmed. The patient was treated with itraconazole for suspected sporotrichosis over 1 month. The patient was treated with oral doxycycline hydrochloride capsules (200 mg/day) for 5 months, the nodules had resolved. Home aquarium environments may serve as a possible source of mycobacteria infection in urban family.

Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease.

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.

Identification of nontuberculous mycobacteria isolated from household showerheads of patients with nontuberculous mycobacteria

This study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.

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.

CFTR modulator use and risk of nontuberculous mycobacteria positivity in cystic fibrosis, 2011-2018.

BackgroundPeople with cystic fibrosis are at increased risk of pulmonary nontuberculous mycobacteria (NTM) disease. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with reduced lung infection with pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. This association has not been studied with NTM.MethodsUsing encounter-level data from the US Cystic Fibrosis Foundation Patient Registry from 2011 to 2018, we identified individuals aged >12 years with one or more NTM-negative sputum culture and information on receipt of ivacaftor therapy. We used a Cox proportional hazards model to assess the relationship between CFTR modulator usage (any and monotherapy versus combination therapy) and NTM sputum culture positivity, controlling for sex, least severe class of CFTR mutation, receipt of chronic macrolides, age, body mass index and percentage predicted forced expiratory volume.ResultsOut of 25 987 unique individuals, 17 403 individuals met inclusion criteria. During follow-up, 42% of individuals received CFTR modulator therapy, and 23% had incident NTM. The median (interquartile range) time to event was 6.1 (4.0–7.3) years for those ever receiving CFTR modulators compared to 4.0 (1.6–6.5) years in those never receiving CFTR modulators. CFTR modulator use was associated with a significantly reduced hazard of NTM culture positivity (hazard ratio (HR) 0.88, 95% CI 0.79–0.97); there was no significant difference in the hazard between those receiving ivacaftor monotherapy versus combination therapy (combination HR 1.01, 95% CI 0.79–1.23).ConclusionsCFTR modulator therapy is associated with a decreased risk of NTM positivity in individuals with cystic fibrosis.

The Value of Sputum Polymerase Chain Reaction for Detection of Nontuberculous Mycobacteria in Cystic Fibrosis Patients with Negative Nontuberculous Mycobacteria Sputum Culture.

Background: Cystic Fibrosis (CF) is a life-threatening autosomal recessive disease. The purpose of this study was to evaluate the value of Polymerase Chain Reaction (PCR) in CF patients with Nontuberculous Mycobacteria (NTM) negative sputum culture. Methods: This is a descriptive cross-sectional study. The population included all children with CF, aged between 5 - 18 years old, with an NTM negative sputum culture. The patient's sputum samples were sent for smear and culture of NTM, RFLP PCR, and PCR sequence. Results: In total, 57 CF patients with negative NTM sputum culture were enrolled. Nine patients (15.78%) had positive sputum PCR for NTM. Among these strains, Mycobacterium simiae was the most common one with 5 cases (8.77% of total positive cases). Conclusion: PCR can be used as an alternative diagnostic method for NTM in CF patients with negative NTM sputum culture, always under clinical suspicion of the disease.

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.

Environmental predictors of pulmonary nontuberculous mycobacteria (NTM) sputum positivity among persons with cystic fibrosis in the state of Florida.

Nontuberculous mycobacteria (NTM) are opportunistic human pathogens that are commonly found in soil and water, and exposure to these organisms may cause pulmonary nontuberculous mycobacterial disease. Persons with cystic fibrosis (CF) are at high risk for developing pulmonary NTM infections, and studies have shown that prolonged exposure to certain environments can increase the risk of pulmonary NTM. It is therefore important to determine the risk associated with different geographic areas. Using annualized registry data obtained from the Cystic Fibrosis Foundation Patient Registry for 2010 through 2017, we conducted a geospatial analysis of NTM infections among persons with CF in Florida. A Bernoulli model in SaTScan was used to identify clustering of ZIP codes with higher than expected numbers of NTM culture positive individuals. Generalized linear mixed models with a binomial distribution were used to test the association of environmental variables and NTM culture positivity. We identified a significant cluster of M. abscessus and predictors of NTM sputum positivity, including annual precipitation and soil mineral levels.