Diagnosis Of Nontuberculous Mycobacteria Research Articles

Value of Metagenomic Next-Generation Sequencing in Clinical Diagnosis and Targeted Therapy of Nontuberculous Mycobacteria Infection

Abstract The purpose of this study was to assess the value of metagenomic next-generation sequencing (mNGS) for rapid diagnosis of diseases caused by nontuberculous mycobacteria (NTM). We retrospectively reviewed four NTM-infected cases diagnosed by smear microscopy, mycobacterial culture and mNGS methods. We found that the mNGS method not only had a shorter detection turnaround time (3–4 days) than Mycobacterium culture (15–20 days) but also had higher sensitivity and specificity to identify NTM compared with conventional detection methods. In addition, mNGS was able to identify coinfections by NTM and other bacteria, fungi or viruses. Overall, diagnosis of NTM by mNGS can provide timely and precise guidance for subsequent clinical treatment of NTM infections.

Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient: A case report

BACKGROUND Infections by non-tuberculous mycobacteria (NTM) have become more common in recent years. Mycobacterium canariasense (M. canariasense ) was first reported as an opportunistic pathogen in 2004, but there have been very few case reports since then. Nocardia is a genus of aerobic and Gram-positive bacilli, and these species are also opportunistic pathogens and in the Mycobacteriales order. Conventional methods for diagnosis of NTM are inefficient. Metagenomic next-generation sequencing (mNGS) can rapidly detect many pathogenic microorganisms, even rare species. Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms. There are no previous reports of infection by M. canariasense and Nocardia farcinica (N. farcinica ), especially in immunocompetent patients. This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M. canariasense , N. farcinica , and Candida parapsilosis (C. parapsilosis ) based on mNGS. CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk, and recurrent episodes of moderate-grade fever for 1 wk. She received antibiotics for 1 wk at a local hospital, and experienced defervescence, but the productive cough and chest pain persisted. We collected samples of a lung lesion and alveolar lavage fluid for mNGS. The lung tissue was positive for M. canariasense , N. farcinica , and C. parapsilosis , and the alveolar lavage fluid was positive for M. canariasense . The diagnosis was pneumonia, and application of appropriate antibiotic therapy cured the patient. CONCLUSION Etiological diagnosis is critical for patients with infectious diseases. mNGS can identify rare and novel pathogens, and does not require a priori knowledge.

The Price of Beauty: A Literature Review on Non-Tuberculous Mycobacteria Infection After Cosmetic Procedures.

Abstract Non-tuberculous mycobacteria (NTM) infection of the skin and soft tissues is a complication of cosmetic procedures. The incidence of cutaneous NTM infections has increased significantly as aesthetic operations have become more commonplace. With the rise of cosmetic tourism, the geographic expansion of NTM infections is a major concern. Due to the unique pathogenesis of NTM infections, diagnosis and treatment remain significant challenges for clinicians. Clinical management relies on a combination of antibiotic therapy with drug susceptibility testing and appropriate surgical debridement. Some new drugs, photodynamic therapy, and bacteriophage therapy have been developed in recent years, and may improve the aesthetic outcomes. This review summarizes the cosmetic procedures prone to NTM infections in recent years and their clinical features. We propose a 2-stage treatment procedure, including a hospitalization phase and a follow-up phase. We aim to increase the alertness of clinicians to NTM infections for timely detection and treatment. Level of Evidence: 3

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up

BackgroundThe epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determined the incidence and prevalence of NTM infections and focused on social risk factors. Additionally, we described persons suffering from pulmonary and extrapulmonary NTM. Research questionWhat is the incidence and prevalence of NTM and what are the characteristics of the affected patients? MethodsThis is a nationwide retrospective register-based cohort study in Denmark. Adult patients with NTM diagnosis in the Danish national registers from 2000-2017 were classified as having either pulmonary or extrapulmonary NTM disease. ResultsWe identified 1,146 adults with an NTM diagnosis. 661 patients had pulmonary NTM of which 50.4% were male, while 485 had extrapulmonary NTM of which 59.6% were male. The median age (Interquartile range), was 66 years (18) and 57 years (32), respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary and 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest in 70+ year-olds (19.3 per 100,000). Compared to pulmonary NTM patients, extrapulmonary NTM patients were more likely to be employed and had a higher educational level. InterpretationThe prevalence of NTM disease in Denmark increased between 2000 and 2017. Pulmonary and extrapulmonary NTM patients are two distinct groups that differ in age, gender, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects.

Nontuberculous mycobacteria (NTM) are ubiquitous. NTM can affect different organs and may cause disseminated diseases, but the pulmonary form is the most common form. Pulmonary NTM is commonly seen in patients with underlying diseases. Pulmonary Mycobacterium avium complex (MAC) is the most common NTM disease and M. abscessus (MAB) is the most challenging to treat. This review is prepared with the following objectives: (a) to evaluate new methods available for the diagnosis of pulmonary MAC or MAB, (b) to assess advances in developing new therapeutics and their impact on treatment of pulmonary MAC or MAB, and (c) to evaluate the prospects of preventive strategies including vaccines against pulmonary MAC or MAB. A literature search was conducted using PubMed/MEDLINE and multiple search terms. The search was restricted to the English language and human studies. The database query resulted in a total of 197 publications. After the title and abstract review, 64 articles were included in this analysis. The guidelines by the American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Infectious Diseases Society of America (IDSA) are widely applicable. The guidelines are based on expert opinion and there may be a need to broaden criteria to include those with underlying lung diseases who may not fulfill some of the criteria as 'probable cases' for better follow up and management. Some cases with only one culture-positive sputum sample or suggestive histology without a positive culture may benefit from new methods of confirming NTM infection. Amikacin liposomal inhalation suspension (ALIS), gallium containing compounds and immunotherapies will have potential in the management of pulmonary MAC and MAB. the prevalence of pulmonary NTM is increasing. The efforts to optimize diagnosis and treatment of pulmonary NTM are encouraging. There is still a need to develop new diagnostics and therapeutics.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME CAUSED BY TWO SPECIES OF NONTUBERCULOUS MYCOBACTERIA PRESENTING AS MEDIASTINAL LYMPHADENOPATHY

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME CAUSED BY TWO SPECIES OF NONTUBERCULOUS MYCOBACTERIA PRESENTING AS MEDIASTINAL LYMPHADENOPATHY

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

Electrochemical DNA Biosensor to Detect Glycopeptidolipids of Nontuberculous Mycobacteria

In many regions, nontuberculous Mycobacteria (NTM) pulmonary infections have outnumbered tuberculosis infections over the past 30 years, yet NTM infections are frequently misdiagnosed. One critical challenge is that the current “gold standard” for NTM diagnosis involves a weeks‐to‐month long microbiological culture‐based method. To provide a more efficient diagnostic method, we have developed a novel electrochemical DNA‐based (E‐DNA) biosensor to detect NTM. Our E‐DNA biosensor targets a mycobacterial glycopeptidolipid (GPL) found on the exterior cell wall of NTM, which demonstrates high exclusivity for NTM. To create the E‐DNA biosensor, we successfully generated a GPL‐specific single‐stranded DNA aptamer through a modified SELEX (systematic evolution of ligands by exponential enrichment) process followed by high throughput sequencing to quantify potential aptamer sequences. The putative aptamers were then synthesized and screened via fluorescence, with the best candidate aptamer displaying a dissociation constant in the low nanomolar range (KDapp = 0.73 nM). Computational analysis was used to predict secondary and tertiary structure of the aptamer, allowing optimization of that aptamer sequence to find the minimum binding domain and engineer in a two‐state folding mechanism. The aptamer will then be synthesized with a 5’ thiol linkage to facilitate attachment to a gold electrode along with an internal redox reporter (methylene blue). This will enable an electrochemical interrogation method wherein changes in the peak current in square wave voltametric analysis correlate to a conformational rearrangement of the aptamer upon binding to GPL. In future studies, this E‐DNA biosensor will be verified against NTM‐positive patient samples. Ultimately, this approach should provide a rapid, point‐of‐care diagnostic method that eliminates the current lengthy culturing requirements to shorten the duration between the onset of symptoms and correctly targeted treatment of patients infected with NTM.

Establishment and validation of a predictive model for nontuberculous mycobacterial infections in acid-fast bacilli smear-positive patients.

IntroductionNontuberculous mycobacteria (NTM) and pulmonary tuberculosis (PTB) are difficult to distinguish in initial acid‐fast bacilli (AFB) smear‐positive patients.ObjectivesEstablish a predictive model to identify more effectively NTM infections in initial AFB patients.MethodsConsecutive AFB smear‐positive patients in the Respiratory Department of Shanghai Pulmonary Hospital from January 2019 to February 2020 were retrospectively analysed. A multivariate regression was used to determine the independent risk factors for NTM. A receiver operating characteristic (ROC) curve was used to determine the model's predictive discrimination. The model was validated internally by a calibration curve and externally for consecutive AFB smear‐positive patients from March to June 2020 in this institution.ResultsPresenting with haemoptysis, bronchiectasis, a negative QuantiFERON tuberculosis (QFT) test and being female were characteristics significantly more common in patients with NTM (P ≤ 0.001), when compared with PTB. The involvement of right middle lobe, left lingual lobe and cystic change was more commonly seen on chest high‐resolution computed tomography (HRCT) in patients with NTM (P < 0.05), compared with PTB. Multivariate regression showed female, bronchiectasis, negative test for QFT and right middle lobe lesion were independent risk factors for NTM (P < 0.05). A ROC curve showed a sensitivity and specificity of 85.9% and 93.4%, respectively, and the area under the curve (AUC) was 0.963. Moreover, internal and external validation both confirmed the effectiveness of the model.ConclusionsThe predictive model would be useful for early differential diagnosis of NTM in initial AFB smear‐positive patients.

Increasing Trend of Nontuberculous Mycobacteria Isolation in a Referral Clinical Laboratory in South Korea.

Background and Objectives: Nontuberculous mycobacteria (NTM) infections are increasing worldwide. We evaluated the annual trends of NTM isolation on acid-fast bacillus (AFB) culture, compared to that of Mycobacterium tuberculosis, and the distribution of NTM species nationwide in South Korea. Materials and Methods: The study was conducted in a diagnostic center that is a major referral laboratory for the diagnosis of tuberculosis and NTM in South Korea. All laboratory results of AFB culture from January 2014 to December 2019 were collected. All NTM identified were definitively identified to the species level. Results: A total of 345,871 tests were performed for the diagnosis of mycobacteria. The isolation rate of NTM and M. tuberculosis was 3.7% (12,969 cases) and 4.4% (15,081 cases), respectively. The annual isolation rate of NTM increased gradually from 2.7% in 2014 to 4.8% in 2019, whereas that of M. tuberculosis decreased from 6.2% to 3.3%. There were 4988 cases of NTM identified to the species level. M. avium complex (MAC) was the most common species isolated from pulmonary sites (59.8%), followed by M. gordonae (9.2%), M. abscessus (7.0%), and M. fortuitum (5.5%). Extrapulmonary NTM were identified in 29 cases (0.6%). MAC was also the most common NTM species isolated from extrapulmonary sites (65.5%), followed by M. kansasii (10.3%), M. abscessus (6.9%), and M. fortuitum (6.9%). Conclusions: The annual isolation rate of NTM has increased gradually, whereas that of M. tuberculosis has decreased. Follow-up studies of the increases in NTM identification and NTM infections in South Korea are needed.

Nontuberculous mycobacterium: An emerging pathogen: Indian perspective.

Nontuberculous mycobacteria (NTM), considered as mere contaminants, are off late, being reported as potential pathogens through various studies. The infections due to NTM range from pulmonary to extra pulmonary including skin and soft-tissue infections, traumatic and surgical wound infections, and catheter and implant-associated infections. Although extrapulmonary infections are extensively explored, pulmonary infections are scarcely reported due to their misdiagnosis as tuberculosis caused by M. tuberculosis (MTB). Appropriate detection methods are essential in order to facilitate the differential diagnosis of NTM from MTB infections. We aimed to collate the data available on NTM diagnosis and its epidemiology in India in this review. While diagnosis of MTB itself is more challenging in India, for appropriate treatment of NTM, special training and attention is needed for differential diagnosis of the former from latter. Currently, in India, in addition to the available techniques for identification of NTM, line probe assay (Hains life sciences) is proving to be a promising tool for the detection of NTM (common mycobacteria/additional species kit) and their antimicrobial resistance (Genotype NTM-DR VER 1.0). In future, with the price of sequencing steadily coming down, with proper monitoring, whole-genome sequencing could be the test of choice to predict the species, drug resistance, outbreaks in hospitals, and transmission dynamics.

Nucleic acid amplification techniques for rapid diagnosis of nontuberculous mycobacteria: A protocol of systematic review and meta-analysis.

BackgroundNontuberculous mycobacteria (NTM) infection is similar to Mycobacterium tuberculosis (MTB) infection. Early clinical identification and differentiation of NTM and MTB infections continues to be a major challenge. Nucleic acid amplification tests (NAATs) have the ability to efficiently and rapidly detect pathogens and are widely used in mycobacterial infections. The objective of this study is to estimate the diagnostic accuracy of NAATs for NTM.MethodsWe will search candidate studies that assessing the accuracy of NAATs for diagnosis of NTM through PubMed, Embase and the Cochrane Library until May 2021. Studies with full text that meet the inclusion criteria will be included. Following a revised tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), two researchers will independently evaluate the study quality. The STATA software (version 15.0) will be used to carry out meta-analyses. When heterogeneity is observed, subgroup analyses and meta-regression analyses will be used to explore sources of heterogeneity. Sensitivity analyses will be used to check the robustness of analyses.ConclusionWe hope that this study will provide meaningful evidence for the early and rapid diagnosis of NAATs for NTM, which will help to guide the treatment of NTM and improve the prognosis of patients.

Comprehensive Determination of Mycobacterium tuberculosis and Nontuberculous Mycobacteria From Targeted Capture Sequencing.

Infection of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) challenges effective pulmonary infectious disease control. Current phenotypic and molecular assays could not comprehensively and accurately diagnose MTB, NTM, and drug resistance. Next-generation sequencing allows an “all-in-one” approach providing results on expected drug susceptibility testing (DST) and the genotype of NTM strains. In this study, targeted capture sequencing was used to analyze the genetic backgrounds of 4 MTB strains and 32 NTM pathogenic strains in 30 clinical samples, including 14 sputum specimens and 16 bronchoalveolar lavage fluid samples. Through comparing with other TB diagnostic tests, we proved that targeted capture sequencing could be used as a highly sensitive (91.3%) and accurate (83.3%) method to diagnose TB, as well as MGIT 960. Also, we identified 7 NTM strains in 11 patients; among them, seven patients were MTB/NTM co-affected, which indicated that it was a meaningful tool for the diagnosis and treatment of NTM infection diseases in clinic. However, based on a drug-resistant mutation library (1,325 drug resistance loci), only 9 drug resistance strains and 22 drug resistance loci were discovered, having considerable discordance with the drug-resistant results of MGIT 960. Our finding indicated that targeted capture sequencing approach was applicable for the comprehensive and accurate diagnosis of MTB and NTM. However, from data presented here, the DST results identified by next-generation sequencing (NGS) showed a relatively low consistency with MGIT 960, especially in sputum samples. Further work should be done to explore the reasons for low drug-resistance detection rate of NGS.

Laboratório Central de Saúde Pública do Piauí: frequência de espécies de micobactérias e aspectos epidemiológicos, 2014-2015

Background and Objectives: Knowledge about species diversity of non-tuberculous mycobacteria (NTM) and the frequency of tuberculosis (TB) is an important issue in rural-urban regions such as Piauí (northeast of Brazil), of low incidence rate of TB , can help to improve diagnosis and prevention strategies. The aim of this study is to examine some epidemiological aspects and the frequency of Mycobacterium tuberculosis (Mtb) and NTM isolated at the central public health reference laboratory, Dr. Costa Alvarenga, Piauí (LACEN-PI). Methods: Data records of all mycobacterosis and tuberculosis cases from January 2014 to March 2015 were analyzed. Results : Of the 20% (142/706) positive growths, 70% (99) were Mtb and 10% NTM. The remainde was of inadequate clinical samples, not allowing the identification of even the suspected NTM. The most frequent clinical form was pulmonary with TB patients younger than those infected with NTM (p = 0.001), the majority living in Teresina (52%). NTMs identified were M. abscessus (36%), M. avium, M. intracellulare, Mycobacterium sp. (14% each) and M. asiaticum, M. szulgai, M. kansasii 7% (each). Mtb drug resistance (7.8%) and TB co-infection with the human immunodeficiency virus (HIV-TB) found to be high (49%, 19/39) . Conclusion: The frequencies of Mtb infection, drug resistance and HIV-TB co-infection are still underestimated and failures in the identification of NTM may decrease the actual frequency of these infections. Therefore, there is a need for improvements in TB control and in the diagnosis of NTMs in Piauí.

Outcomes of HIV-positive patients with non-tuberculous mycobacteria positive culture who received anti-tuberculous treatment in Botswana: Implications of using diagnostic algorithms without non-tuberculous mycobacteria.

BackgroundPatients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert® MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures.MethodsPLHIV attending one of the 22 participating HIV clinics, who screened positive for ≥1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment.ResultsAmong 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated ‘no MTB’. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher’s exact test p = 1.00.ConclusionsWhile the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential.

Nontuberculous mycobacteria infections of peritoneal dialysis patients: A multicenter study.

Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients. All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed. Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52-76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD. Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Nontuberculous mycobacteria: A report of eighteen cases from a tertiary care center in India.

Context:Nontuberculous mycobacteria (NTM) are ubiquitous mycobacteria present in environment and generally affect patients with either structural lung disease or immunosuppression and commonly involve lungs, lymph node, or skin.Materials and Methods:Between July 2016 and February 2019, 18 cases of NTM were diagnosed and their relevant clinical, diagnostic, and treatment details were recorded after taking informed consent.Results:We report 18 cases of NTM involving lungs (n = 11), skin and soft tissue (n = 3), joint (n = 2), genitourinary (n = 1), and central nervous system (n = 1). History of immunosuppression was present in two patients, whereas history of some form of intervention was seen in six patients. Mycobacterium fortuitum group (n = 5) was the most commonly isolated organism, followed by Mycobacterium avium complex (n = 4), Mycobacterium abscessus (n = 3), Mycobacterium kansasii (n = 2), and Mycobacterium chelonae (n = 1). In two patients, M. chelonae and M. abscessus were isolated in succession. Of these 18 patients, clinical response was present in 15 of the patients. Diagnosis and treatment of NTM in resource limited settings is extremely challenging.Conclusion:Most of the patients with NTM are misdiagnosed and are treated as tuberculosis in India, sometimes with a multidrug resistance regimen, which results in significant morbidity and mortality. We present these cases to shed some light on the epidemiology of NTM in this part of India.