Machine Learning-Based Differentiation of Nontuberculous Mycobacteria Lung Disease and Pulmonary Tuberculosis Using CT Images.

An increasing number of patients infected with nontuberculous mycobacteria (NTM) are observed worldwide. However, it is challenging to identify NTM lung diseases from pulmonary tuberculosis (PTB) due to considerable overlap in classic manifestations and clinical and radiographic characteristics. This study quantifies both cavitary and bronchiectasis regions in CT images and explores a machine learning approach for the differentiation of NTM lung diseases and PTB. It involves 116 patients and 103 quantitative features. After the selection of informative features, a linear support vector machine performs disease classification, and simultaneously, discriminative features are recognized. Experimental results indicate that bronchiectasis is relatively more informative, and two features are figured out due to promising prediction performance (area under the curve, 0.84 ± 0.06; accuracy, 0.85 ± 0.06; sensitivity, 0.88 ± 0.07; and specificity, 0.80 ± 0.12). This study provides insight into machine learning-based identification of NTM lung diseases from PTB, and more importantly, it makes early and quick diagnosis of NTM lung diseases possible that can facilitate lung disease management and treatment planning.

Clinical-epidemiological profile and factors related to the mortality of patients with nontuberculous mycobacteria isolated at a reference hospital in Ceará, Northeastern Brazil.

Background: There is a significant shortage of official records that enable estimating the real prevalence of nontuberculous mycobacteria (NTM) infections in Brazil. The study aims to investigate the clinical, laboratory, and epidemiological aspects of patients with NTM isolation at an infectious diseases reference hospital, and to identify factors associated with mortality. Methods: This was an observational study in which clinical, epidemiological, and laboratory aspects were evaluated in patients with NTM isolated at care in Hospital São José, located in Northeastern Brazil, from 2005 to 2016. The records of the reference laboratory for NTM isolates were searched from the culture results of patients. Afterward, the medical records of the patients were reviewed. The analytical assessment was conducted by the Mann-Whitney and Fisher's exact test. The adopted level of significance was 5%. Results: A total of 69 patients were described, with a predominance of males (73.9%). The main clinical forms identified were: pulmonary (60.9%) and disseminated (27.5%). The most frequently NTM identified were Mycobacterium avium (24.6%) and Mycobacterium fortuitum (10.1%). Forty-eight (69.6%) patients had HIV infection. The mortality was 24.6%, and the risk factors for deaths identified were: origin from outside the metropolitan region; weight loss; HIV infection; anemia; hyperbilirubinemia; increased serum glutamic-oxaloacetic transaminase, alkaline phosphatase, lactate dehydrogenase; and impaired renal function. Among the patients with HIV, the main changes related to death were: lower counts of CD4+ and CD8+ T lymphocytes. Conclusion: Maintaining constant vigilance regarding the possibility of NTM infection is required, namely in patients co-infected with HIV/AIDS.

Distribution and outcomes of infection of Mycobacterium avium complex species in cystic fibrosis.

BACKGROUND: The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking. METHODS: This was a single center, retrospective study. MAC isolates had species identification with MLSA of rpoB and the 16S23S ITS region. Clinical data were compared between species. RESULTS: Twenty-three people with CF and 57 MAC isolates were included. Infection with M. avium was the most common (65.2%). M. intracellulare was associated with higher rates of NTM disease, younger age, and steeper decline in lung function prior to infection. CONCLUSIONS: We observed worse clinical outcomes in people with M. intracellulare infection relative to other MAC species. Further investigation of clinical outcomes of MAC infection among CF patients is warranted to better define the utility of species-level identification of MAC isolates in CF.

Portuguese in vitro antibiotic susceptibilities favor current nontuberculous mycobacteria treatment guidelines.

SETTING: Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans for which effective treatment is challenging. There is, however, very little information on the prevalence of NTM drug resistance in Portugal. OBJECTIVE AND DESIGN: Our aim was to analyze the drug susceptibility testing (DST) performed in NTM at the Portuguese National Health Institute Dr. Ricardo Jorge from February 2003 to February 2016. A total of 262 DST were included in the analysis. RESULTS: Most (94%) M. avium intracellulare complex isolates showed in vitro susceptibility to clarithromycin. All M. kansasii isolates were susceptible to rifampicin and ethambutol and 97.1% were susceptible to isoniazid. The majority of rapidly-growing mycobacteria (RGM) demonstrated in vitro susceptibility to amikacin, clarithromycin and cefoxitin. However, in RGM there was a marked increase on the relative risk of having sulfamethoxazole resistance in isolates resistant to ciprofloxacin compared to susceptible isolates. CONCLUSION: Tested NTM in Portugal revealed in vitro susceptibility to most of the antimicrobials currently recommended for treatment. However, our results also suggest that sulfamethoxazole should be avoided in treatment of RGM resistant to ciprofloxacin (or vice versa). Further trials that correlate the in vitro DST results with the clinical outcome are needed in order to reach conclusions on efficient antimicrobial therapy.

Mycobacterium ahvazicum sp. nov., the nineteenth species of the Mycobacterium simiae complex.

Four slowly growing mycobacteria isolates were isolated from the respiratory tract and soft tissue biopsies collected in four unrelated patients in Iran. Conventional phenotypic tests indicated that these four isolates were identical to Mycobacterium lentiflavum while 16S rRNA gene sequencing yielded a unique sequence separated from that of M. lentiflavum. One representative strain AFP-003T was characterized as comprising a 6,121,237-bp chromosome (66.24% guanosine-cytosine content) encoding for 5,758 protein-coding genes, 50 tRNA and one complete rRNA operon. A total of 2,876 proteins were found to be associated with the mobilome, including 195 phage proteins. A total of 1,235 proteins were found to be associated with virulence and 96 with toxin/antitoxin systems. The genome of AFP-003T has the genetic potential to produce secondary metabolites, with 39 genes found to be associated with polyketide synthases and non-ribosomal peptide syntases and 11 genes encoding for bacteriocins. Two regions encoding putative prophages and three OriC regions separated by the dnaA gene were predicted. Strain AFP-003T genome exhibits 86% average nucleotide identity with Mycobacterium genavense genome. Genetic and genomic data indicate that strain AFP-003T is representative of a novel Mycobacterium species that we named Mycobacterium ahvazicum, the nineteenth species of the expanding Mycobacterium simiae complex.

Nontuberculous mycobacteria in gastrostomy fed patients with cystic fibrosis.

Multi-drug resistant Mycobacterium abscessus complex (MABSC) is a form of Nontuberculous mycobacteria (NTM) of special, international concern in Cystic Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were studied. Bacterial and fungal isolates were cultured. Mycobacterium were identified by rpoB, sodA and hsp65 gene sequencing and strain typed using variable number tandem repeat. Bacteria and/or fungi grew from all gastric juice, sputa and PEG samples. MABSC were detected in 7 patients. Five had MABSC in their sputum. Two had an identical MABSC strain in their sputum and gastric juice and one had the same strain isolated from their PEG tube and sputum. Two patients who were sputum sample negative had MABSC isolated in their gastric juice or PEG tube. MABSC were therefore identified for the first time from a gastric sample in a minority of patients. We conclude that gastric juice and PEG-tubes may be a potential source of MABSC isolates in CF patients, and these findings warrant further study.

Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease

Abstract Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p < 0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p = 0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p = 0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.

Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease.

Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p<0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p=0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p=0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.

Nontuberculous mycobacterial cervicofacial lymphadenitis--a review and proposed classification system.

OBJECTIVE: To describe a clinical staging system for nontuberculous mycobacterial (NTM) cervicofacial lymphadenitis that has both diagnostic and therapeutic implications. METHODS: A Medline database search was performed using key words "nontuberculous mycobacteria". All articles pertaining to nontuberculous mycobacterial cervicofacial lymphadenitis were reviewed for data evaluation regarding diagnosis and treatment methodologies. RESULTS: Nontuberculous cervicofacial lymphadenitis infections pass through distinctly segmented clinical phases. In Stage I, a painless mass presents with notable increase in vascularity. Stage II is characterized by liquefaction of the affected lymph node, causing the mass to appear fluctuant. Significant skin changes characterize Stage III, whereby overlying skin may develop violaceous discoloration and become notably thinner, or parchment-like, with a "shiny" appearance. During Stage IV, the lesion fistulizes to the skin surface causing a draining wound. CONCLUSIONS: While nontuberculous mycobacterial cervicofacial lymphadenitis has typically been thought of as a surgical disease, further characterization is warranted. We present a new classification system for appraising the clinical stages of nontuberculous mycobacterial cervicofacial lymphadenitis that may be used as part of a greater approach to disease management: (1) after other causes have been ruled out, the possibility of a tuberculous scrofula must be eliminated, and the degree of diagnostic suspicion must be categorized; (2) the clinical stage of the infection can be determined using the classification system described; and (3) a stage-specific treatment may be chosen based on the individual patient.

Clinical characteristics and prognosis of nontuberculous mycobacterial lung disease with different radiographic patterns.

RATIONALE: The clinical characteristics and prognostic impact of radiographic patterns of patients with nontuberculous mycobacterial lung disease (NTM-LD) are rarely evaluated. DESIGN: Patients with NTM-LD from 2007 to 2009 in a single medical center in Taiwan were identified. Their radiographic patterns were reviewed and classified into cavitary, bronchiectatic, or consolidative. They were also compared to patients with cavitary pulmonary tuberculosis (TB-LD). RESULTS: Of 481 NTM-LD patients identified, 62, 134, and 56 patients were categorized into cavitary, bronchiectatic, and consolidative groups, respectively. Compared with 180 TB-LD patients, cavitary NTM-LD had male predominance and was associated with higher grades of sputum acid-fast smear (3+ or 4+), prior pulmonary TB, and poor baseline pulmonary function. NTM-LD patients with consolidative pattern were likely to have underlying comorbidity, the highest blood leukocyte count and C-reactive protein, and lowest albumin. In all NTM-LD, the consolidative pattern was independently associated with poor prognosis for 6-month survival. Patients with cavitary Mycobacterium avium complex (MAC)-LD had worse 6-month survival than those with bronchiectatic pattern. CONCLUSION: In Taiwan, NTM-LD patients with consolidative pattern have the worst prognosis while patients with cavitary pattern have worse survival than those with bronchiectasis in MAC-LD. Because varying radiographic patterns represent different prognoses, understanding the characteristics of NTM-LD patients with different radiographic patterns complements clinical practice.

What's in a name? Ulcerans disease: infections due to Mycobacterium ulcerans.

Lesions due to Mycobacterium ulcerans infection may have more synonyms and eponyms than any other disease. New diseases are named for the person who discovered them, from the place from which they were first described or some major clinical feature. 'Buruli ulcer', the name by which the disease is most frequently known, is none of these. Classically, the disease presents as extensive, undermined ulcers, first described by Searls from Bairnsdale in southeastern Australia, names that gave the disease its two eponyms. A case is made for the term 'Buruli ulcer' to be dropped from the medical literature and the disease to be known as 'ulcerans disease' or simply 'ulcerans'.

Species spectrum of nontuberculous mycobacteria isolated from clinical specimens in Kuwait.

Specific identification of mycobacteria is of clinical relevance since treatment varies according to the Mycobacterium species causing infection. All mycobacterial isolates are currently identified as M. tuberculosis (MTB) or nontuberculous mycobacteria (NTM) based on p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) test, and the species spectrum of NTM-causing infections in Kuwait remains unknown. This study identified all NTM strains isolated in Kuwait from 1 October 2003 to 31 March 2004 to the species level. The mycobacteria were cultured from various clinical specimens using the BACTEC 460 TB system and NAP test was performed to differentiate MTB from NTM strains. The INNO-LiPA MYCOBACTERIA v2 assay (LiPA) was used for species-specific identification of NTM strains and some randomly selected MTB strains. The LiPA results for selected isolates were confirmed by DNA sequencing of the 16S-23S internal transcribed spacer region. A total of 325 isolates of Mycobacterium species originating from 305 individual patients were recovered during the study period, with 307 and 18 isolates identified as MTB and NTM, respectively. The LiPA correctly identified all 18 MTB isolates analyzed. Seven different NTM species were identified among 18 NTM isolates originating from 14 patients, with M. fortuitum causing the majority of NTM infections in Kuwait. One patient was infected with two NTM species. Rapid species-specific identification of NTM may help with appropriate treatment regimens for proper patient management.

The evolving story of Mycobacterium tuberculosis clade members detected in fish.

Advances in molecular analyses have permitted documentation of an increasing spectrum of mycobacteria infecting fish. Although some of these mycobacteria are not closely related, several species belong to the Mycobacterium tuberculosis clade. One member of the clade, M. marinum, is well known as an agent of piscine mycobacteriosis. Three other clade species, M. shottsii, M. pseudoshottsii and M. 'chesapeaki', have recently been identified as predominant disease agents in a widespread, continuing epizootic in wild striped bass of the Chesapeake Bay. A fifth clade member, M. ulcerans, has recently been indirectly detected in wild, African cichlid fish. As M. ulcerans is the third most common human mycobacterial infection worldwide, even such indirect evidence of M. ulcerans in fish must be more thoroughly investigated. Complicating the differentiation of these clade members is the growing recognition of intraspecies and interspecies variation in phenotypes, genes and virulence. Thus, researchers must be aware of the variety of piscine isolates within the M. tuberculosis clade. This review summarizes the methods of detection and differentiation for this important group of mycobacteria.

A pulsed-field gel electrophoresis study of Mycobacterium fortuitum in a Caribbean setting underlines high genetic diversity of the strains and excludes nosocomial outbreaks.

Among rapidly-growing opportunistic mycobacteria, organisms of the Mycobacterium fortuitum-Mycobacterium chelonae complex (M. fortuitum, M. chelonae, M. abscessus and M. peregrinum) were isolated in significantly higher numbers during the period 1993-99 from clinical samples in Guadeloupe, Martinique and French Guiana. Based on biochemical and cultural tests and PCR-restriction fragment length polymorphism (RFLP) of the hsp65 gene, 51 isolates from 47 patients were unambiguously identified as M. fortuitum. A molecular epidemiological study by pulsed-field gel electrophoresis (PFGE) using DraI and Xbal digestions of bacterial DNA revealed two clusters designated A and B; cluster A was composed of strains showing 10 bands that were isolated from 3 patients in Martinique within a 2-months period in 1999, and the cluster B was composed of 2 strains showing 9 bands from 2 patients in Martinique, also isolated within a 2-months period in 1999. The available epidemiological and clinical information neither incriminated M. fortuitum as a cause of disease in these patients, nor showed any potential epidemiolgical links between them, except for the fact that the samples were processed in the same microbiology laboratory within a short span of time. In conclusion, isolation of M. fortuitum from non-sterile sites in patients without predisposing conditions, and in absence of repeated isolation, may be caused by contaminants or colonizers that are picked up more easily due to improvement of techniques used for mycobacterial isolation and identification.

Nontuberculous mycobacterial infections in hematopoietic stem cell transplant recipients: characteristics of respiratory and catheter-related infections.

Over a 20-year period, 40 nontuberculous mycobacteria (NTM) were isolated from 6259 hematopoietic stem cell transplant (HSCT) recipients (0.64%), of which 28 were considered to have probable or definite infection (0.44%). Only 3 of 15 lower respiratory isolates obtained by bronchoalveolar lavage (BAL) and/or biopsy; (Mycobacterium avium complex [n = 2] and M. gordonae [n = 1]) caused definite or probable lower respiratory tract disease, whereas 12 of 15 were considered to cause possible lower respiratory tract disease according to Centers for Disease Control and Prevention definitions. The median time to diagnosis was 251 days following HSCT. All 3 patients with definite NTM disease were successfully treated with 3 antimicrobials for several months. Twenty-three patients had catheter-related infections, including exit site infection (n = 5), tunnel infection (n = 7), and catheter-related bacteremia (n = 11). All were caused by rapidly growing mycobacteria. The median time to diagnosis was 61 days following HSCT. All patients with catheter-related infections were successfully treated with an average of 2 antibiotics for a median of 3 weeks for exit site infection and 6 weeks for tunnel infection and catheter-related bacteremia. Soft tissue debridement was performed in all cases with tunnel infection. The catheter was removed in 21 of 23 patients with catheter-related infections. Two additional patients were diagnosed, one with lymphadenitis and one with skin lesion, due to NTM. In conclusion, NTM infections are infrequent in HSCT recipients and carry a good clinical prognosis. In the majority of lower NTM respiratory isolates obtained by BAL, a pathogenic role could not be established. However, lower respiratory tract disease can occur late after HSCT and should be considered if patients fail to respond to the treatment of concomitant infections or if evidence of tissue infection or concomitant bacteremia is present. Therapy should be performed with 2 to 3 antimicrobials, guided by antimicrobial susceptibilities, with additional surgical debridement in patients with tunnel infection.

[Cutaneous mycobacteriosis]. / Mycobactérioses cutanées.

Tuberculosis is reappearing, due to diminished surveillance, illegal immigration, the HIV epidemic and certainly also due to emerging resistance. The clinical expression of cutaneous tuberculosis depends on the stage of development, the clinical background and the virulence of the germ. Diagnosis is predominantly clinical, but laboratory results also play a role. Treatment involves the quadruple antibiotic treatment prescribed for any tubercular infection. Atypical mycobacteria are widespread throughout the environment and are pathogenic, but also saprophytic, comensal and opportunistic, figure a favourable setting in the immunodeficient individual. Following entry by penetrance, the early lesion is papulonodulary, nodulary, keratoid, crusted, ulcerated, sporotrichoid, generally without peripheral adenopathy. Histological examination discloses a granulomatous reaction limiting the development of the infection; such development is absent in the immunodeficient patient, thus explaining the spread. The most common mycobacterial infection in France, generally in the immunocompetent individual, is "aquarium disease" which follows a benign course; the most common in tropical areas is Mycobacterium ulcerans; whereas Mycobacterium avium intracellulare, fortuitum and chelonae cause, in the immunodeficient patient, severe and extensive infection. Treatment should start as soon as diagnosis is made and the germ identified.