Multiple Nontuberculous Mycobacteria Research Articles

Mixed infection of three nontuberculous mycobacteria species identified by metagenomic next-generation sequencing in a patient with peritoneal dialysis-associated peritonitis: a rare case report and literature review

BackgroundPeritonitis caused by nontuberculous mycobacteria (NTM) is an infrequent but important complication in patients undergoing peritoneal dialysis (PD). There has been no report of mixed infections with multiple NTM. Peritoneal dialysis-associated peritonitis (PDAP) caused by Mycobacterium abscessus is more common than that caused by M. smegmatis and M. goodii.Case presentationThis case concerns a patient with PDAP caused by gram-positive bacilli, which could not be identified at the species level in successive detections of initial peritoneal effluent. Later, M. smegmatis was detected with no sensitivity results in bacterial culture. However, metagenomic next-generation sequencing (mNGS) and first whole-genome sequences indicated that there were three species coexisting in the culture, including M. smegmatis (24,708 reads), M. abscessus (9224 reads), and M. goodii (8305 reads). This is the first case of PDAP with specific evidence that conventional detection methods isolated a poorly pathogenic NTM, whereas mNGS and first whole-genome sequences identified multiple NTM. Pathogenic bacteria might not be detected using conventional methods due to their lower abundance. This case report is the first description of mixed infections with more than two species of NTM during PDAP.ConclusionsPDAP caused by multiple NTM is rare, and the diagnosis is difficult. When NTM are isolated by conventional tests in patients who are suspected of infection, clinicians should be vigilant, and further tests should be performed to determine the presence of rare or even previously unknown bacteria, for which the quantity is relatively low, but the pathogenicity is high. The rare pathogen may be a primary agent in causing such complications.

Impacts of Nontuberculous Mycobacteria Isolates in Non-cystic Fibrosis Bronchiectasis: A 16-Year Cohort Study in Taiwan.

BackgroundThe prevalence of nontuberculous mycobacteria (NTM) in patients with chronic respiratory disease has increased. The implication of NTM in non-CF bronchiectasis remained controversial. This study investigated the impact of NTM in non-CF bronchiectasis in Taiwan.MethodsClinical manifestation, imaging, and microbiological data were retrieved from the Chang Gung Research Database, the largest electronic medical record-based database in Taiwan. Patients with bronchiectasis during 2001–2016 were included. Cox proportional hazard model was employed to compare outcomes between patients with negative and positive NTM isolates after 1:1 propensity score matching.ResultsA total of 19,647 non-CF bronchiectasis patients were enrolled and 11,492 patients were eligible for analysis after exclusion screening. Finally, patients with negative and positive NTM isolates—650 each—were analyzed after propensity score matching. The patients with negative NTM isolates were divided into three groups: Pseudomonas aeruginosa isolates (n = 53); fungus isolates (n = 26); and concomitant P. aeruginosa and fungus isolates (n = 8). The patients with positive NTM isolates were divided into five groups: single NTM isolate (n = 458); multiple NTM isolates (n = 60); concomitant NTM and P. aeruginosa isolates (n = 89); concomitant NTM and fungus isolates (n = 33); and concomitant NTM, P. aeruginosa, and fungus isolates (n = 10). Patients with P. aeruginosa isolates; concomitant NTM and P. aeruginosa isolates; concomitant NTM, P. aeruginosa, and fungus isolates had independently associated with respiratory failure and death. Patients with single or multiple NTM isolates were not related to ventilator use, but both were independent risk factor for mortality.ConclusionNTM, either combined with P. aeruginosa or fungus, exhibited more frequent exacerbations in non-CF bronchiectasis patients. Moreover, NTM predicted mortality in non-CF bronchiectasis patients and were also correlated to respiratory failure while concomitantly isolated with P. aeruginosa and fungus.

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria.

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.

Coinfection With Multiple Nontuberculous Mycobacteria as a Possible Exacerbating Factor in Pulmonary Nontuberculous Mycobacteriosis: Clone Library Analysis Using the 16S Ribosomal RNA Gene

Mycobacterial culture is the gold standard for the diagnosis of nontuberculous Mycobacterium (NTM) infections. However, this method is not suitable for detection of coinfection with different NTMs. The goal of this study was to determine if clone library analysis of BAL fluid (BALF) was useful for detection of NTM phylotypes, including multiple NTM phylotypes, in pulmonary NTM infections. BALF samples obtained from 120 patients with suspected pulmonary NTM infections were retrospectively evaluated by using the mycobacterial culture and clone library methods between July 2010 and August2016. In total, 55 (45.8%) patients were diagnosed as NTM positive according to results of mycobacterial culture, and 52 patients were NTM positive as determined by using the clone library method. Furthermore, 45 (86.5%) and seven (13.5%) patients exhibited a single phylotype (mono-phylotype group) and multiple phylotypes of NTM (multi-phylotype group), respectively. Compared with the mono-phylotype group, the multi-phylotype group had a significantly higher incidence of adverse chest CT findings (P= .048). In addition, 11 patients who were NTM negative according to results of BALF mycobacterial culture were determined to be NTM positive according to the clone library method. Six of these 11 patients were eventually diagnosed as NTM positive by using mycobacterial culture results within 6.2 ± 2.1months following the initial sample collection. Coinfection multiple phylotypes could be associated with adverse clinical findings. In addition, patients who test positive for NTM genes but negative for mycobacterial culture may be diagnosed with NTM lung infection within 1 year of the initial sample collection. Further follow-up of these patients may facilitate early detection of NTM species.

Profile of patients with pulmonary non-tuberculous mycobacterial disease mimicking pulmonary tuberculosis

IntroductionWith the introduction of newer molecular diagnostic tools, an increasing number of Non-tuberculous Mycobacteria (NTM) affecting the respiratory system and mimicking symptoms of pulmonary tuberculosis (PTB) are being identified. They may be misdiagnosed and treated as PTB, often categorized as treatment failures if they do not respond to treatment. This manuscript aims to characterize patients with pulmonary NTM disease. MethodsPatient characteristics of bacteriologically confirmed pulmonary NTM disease, attending the ICMR-National Institute for Research in Tuberculosis, Chennai were prospectively compiled over a two-year period (2017–2018). ResultsA total of 122 patients with recurrent chest symptoms and not responding to anti-tuberculosis treatment were screened for NTM. Thirty-nine cases (26 males and 13 females) of symptomatic pulmonary NTM were diagnosed. The mean (SD) patient age and body mass index were 48.6 ± 11 years and 16.3 ± 3. All male participants were smokers, had at least one episode of previous ATT. Mycobacterium kansasii (48.7%) was the most frequently isolated species followed by Mycobacterium intracellulare (20.5%), Mycobacterium abscessus (7.6%) followed by Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kyorinense, and Mycobacterium simiae. Infection with multiple NTMs was seen in four patients. Isoniazid resistance was identified in 20 patients. Based on species identified, treatment was initiated as per American Thoracic Society guidelines and continued up to 12 months of culture negativity. ConclusionsM. kansasii is the commonest pulmonary NTM isolated in Tamilnadu with a higher prevalence in males and elderly. Sensitization of both patients and providers is essential to avoid misdiagnosis and delay in diagnosis of pulmonary NTM disease as pulmonary TB.

Implication of species change of Nontuberculous Mycobacteria during or after treatment

BackgroundCo-existence or subsequent isolation of multiple nontuberculous mycobacteria (NTM) species in same patient has been reported. However, clinical significance of these observations is unclear. The aim of this study was to determine clinical implications of changes of NTM species during or after treatment in patients with NTM lung disease.MethodsPatients with NTM lung disease, who experienced changes of NTM species during treatment or within 2 years of treatment completion between January 1, 2009 and December 31, 2015, were included in the analysis. Demographic, clinical, microbiological, and radiographic data were reviewed and analyzed.ResultsDuring the study period, 473 patients were newly diagnosed with NTM lung disease. Treatment was started in 164 patients (34.6%). Among these 164 patients, 16 experienced changes of NTM species during or within 2 years of treatment completion. Seven showed changes from M. avium complex (MAC) to M. abscessus subspecies abscessus (MAA) and five patients displayed changes from M. abscessus subspecies massiliense (MAM) to MAC. With isolation of new NTM species, 6 out of 7 patients with change from MAC to MAA reported worsening of symptoms, whereas none of the five patients with change from MAM to MAC reported worsening of symptoms. All MAA isolated during or after treatment for MAC lung diseases showed inducible resistance to clarithromycin.ConclusionsChange of NTM species may occur during or after treatment for NTM lung disease. Especially, changes from MAC to MAA is accompanied by symptomatic and radiographic worsening as well as inducible resistance to clarithromycin.

Impact of non-tuberculous mycobacteria on pulmonary function decline in chronic obstructive pulmonary disease

Although chronic obstructive pulmonary disease (COPD) is a common form of structural lung disease associated with pulmonary non-tuberculous mycobacteria (NTM) infection, no longitudinal studies have investigated the role of NTM in COPD disease progression. From 2000 to 2008, spirometry-confirmed COPD patients with sputum specimens sent for mycobacterial cultures were included. Analysis of clinical, microbiological and pulmonary function data was performed. The 251 patients were divided into three groups according to the number of NTM isolates: multiple (n = 47), single (n = 63), and no (n = 141) isolates. Mycobacterium avium complex was the most common species in multiple isolates (36.2%) and single isolate (28.6%) groups. Overall, 24.7% of COPD patients had been admitted for exacerbations at least once a year, and patients with multiple and single NTM isolates were more than twice as likely as those with no isolate to experience such exacerbations (38.3% vs. 31.7% vs. 17.0%). After controlling for confounders, patients with multiple NTM isolates had a greater decline in forced expiratory volume in one second than those with single or no isolates (-79.4 ± 32.8 ml vs. -61.6 ± 31.9 ml and -56.2 ± 31.5 ml). This study suggests that NTM may play a role in disease progression and deterioration of pulmonary function in COPD patients.

Isolation of multiple nontuberculous mycobacteria species in the same patients

During the observation of many patients with nontuberculous mycobacteria (NTM) infections, we have often isolated different NTM species in the same patient. In this study we elucidated the patterns of multiple NTM species isolation. The analysis included all patients from whom more than one species of mycobacteria were cultured from a respiratory specimen at Seoul National University Hospital, a tertiary referral hospital in South Korea, between January 2002 and December 2008. The demographic characteristics and clinical and radiographic findings were reviewed retrospectively. Multiple NTM species were isolated from 37 patients. Four patients with Mycobacterium gordonae, Mycobacterium terrae, or Mycobacterium lentiflavum were excluded due to the possibility of contamination. Transition to another NTM species was observed in 23 patients (69.7%), while alternating isolation of two or three NTM species was seen in nine patients. Two species were isolated simultaneously from different sputum samples collected from one patient on the same day. Different NTM species were isolated from the same patients.

Clinical significance of isolation of nontuberculous mycobacteria in pulmonary tuberculosis patients

Clinical significance of isolation of nontuberculous mycobacteria (NTM) from respiratory specimens in patients with pulmonary tuberculosis is unknown. This study aimed to investigate the prevalence and clinical impact of NTM in pulmonary tuberculosis patients. We retrospectively reviewed data of patients with culture-confirmed pulmonary tuberculosis from 2000 to 2006. Those in whom NTM were isolated from respiratory specimens collected within two months before and nine months after the index culture of tuberculosis was plated were compared with those without NTM. Patients were followed for one year after initiation of anti-tuberculous treatment. Among 2133 patients with pulmonary tuberculosis, 48 (2.3%) with multiple and 106 (5.0%) with one isolate(s) of NTM were identified. Another 144 without NTM were selected and compared. The one-year mortality rates were similar among three groups. Patients with multiple NTM isolates were more likely to be symptomatic, sought medical help earlier, had smear-positive respiratory specimens, and received anti-tuberculous treatment later than those with single/no isolate(s). Cavities were more commonly visualized radiographically in patients with multiple/single NTM isolate(s) than those without NTM isolates. The mean duration of anti-tuberculous treatment was 8.8 months for patients with multiple NTM isolates, significantly longer than that in patients with single (7.6 months) and no NTM isolate(s) (7.5 months). NTM were present in the respiratory tract of 7.3% of patients with pulmonary tuberculosis. Although the outcomes were similar, the presence of NTM was associated with different clinical manifestations and had a significant impact on the treatment of tuberculosis.

INFECTION WITH MULTIPLE NONTUBERCULOUS MYCOBACTERIA IN A PATIENT WITH MOUNIER-KUHN SYNDROME: A CASE REPORT

INTRODUCTION: Mounier-Kuhn syndrome (MKS) is a rare disorder of the central airways with less than 100 reported cases. We report a patient with MKS infected with multiple nontuberculous mycobacteria.