Non-tuberculous Mycobacterial Infection In Patients Research Articles

Phenotypical characteristics of nontuberculous mycobacterial infection in patients with bronchiectasis

BackgroundThe global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis.MethodsA retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020. Clinical, laboratory, pulmonary function, and radiological data were compared between patients with a positive or negative NTM culture.ResultsCompared to the NTM-negative group (n=677), the NTM-positive group (n=94) was characterized (P ≤0.05 for all) by older age, greater proportion of females, and higher rates of gastroesophageal reflux disease and muco-active medication use; lower body mass index, serum albumin level, and lymphocyte and eosinophil counts; lower values of forced expiratory volume in one second, forced vital capacity, and their ratio, and lower diffusing lung capacity for carbon monoxide; higher rates of bronchiectasis in both lungs and upper lobes and higher number of involved lobes; and more exacerbations in the year prior bronchoscopy. On multivariate analysis, older age (OR 1.05, 95% CI 1.02-1.07, P=0.001), lower body mass index (OR 1.16, 95% CI 1.16-1.07, P <0.001), and increased number of involved lobes (OR 1.26, 95% CI 1.01-1.44, P=0.04) were associated with NTM infection.ConclusionsPatients with bronchiectasis and NTM pulmonary infection are more likely to be older and female with more severe clinical, laboratory, pulmonary function, and radiological parameters than those without NTM infection. This phenotype can be used for screening patients with suspected NTM disease.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study.

Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205-1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial.

Nontuberculous Mycobacterial infection in patients with bronchiectasis. A single-center study

Nontuberculous Mycobacterial infection in patients with bronchiectasis. A single-center study

Nontuberculous mycobacterial (NTM) infections in bronchiectasis patients: A retrospective US registry cohort study

RationaleLongitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease. ObjectivesTo describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR). MethodsThis was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008–2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort). ResultsBetween 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009–2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively. ConclusionsA considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.

Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation.

The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. Diagnosing mycobacterial disease among patients with hematologic disease and treatment-associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in-vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug-drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes.

Incidence and associated risk factors of nontuberculous mycobacterial infection in patients with depression.

It has been reported that the risk of mental health problems such as anxiety or depression increases in patients with nontuberculous mycobacterial (NTM) infection. However, no studies have investigated whether the incidence of NTM infection increases in patients with depression. This study aimed to investigate the incidence of NTM infection in patients with depression and evaluate the association between NTM infection and depression stratified by age and sex. Data from 2002 to 2013 were collected from patients aged ≥ 20 years in the National Health Insurance Service-National Sample Cohort database. Patients with and without depression aged over 20 years were matched with 1 to 4 by sex, age, and year of diagnosis. The incidence rate was calculated in 100,000 person-years, and a multivariable subdistribution hazard model was used to evaluate the adjusted hazard ratio (aHR) for the development of NTM infection. We included 37,554 individuals (12,752 men and 24,802 women) and 149,213 controls in the depression and non-depression groups, respectively. The cumulative incidence of NTM infection did not differ significantly between the depression and non-depression groups during the follow-up period (22.2 vs. 24.5 per 100,000 person-years, p = 0.571). The age- and sex-stratified effects on the incidence of NTM infection were not significantly higher in patients with depression than in those without depression. After adjusting for covariates including age, sex, comorbidity, income, and region, the risk of NTM infection did not significantly differ between the depression and non-depression groups (aHR 0.83, 95% confidence interval 0.58-1.17). The incidence of NTM infections in patients with depression was not significantly higher than that in patients without depression. However, due to the small number of NTM infections, we might have underestimated the differences between the two groups. Further studies are needed to identify factors associated with NTM pulmonary disease in patients with depression.

Non-tuberculous mycobacterial infections in patients with end-stage renal disease: prevalence, risk factors, and mortality

Non-tuberculous mycobacterial (NTM) disease has increased in prevalence in the USA, however, little is known on NTM in the population with end-stage renal disease (ESRD). Thus, we investigated patients with...

Disseminated Mycobacterium avium infection in a young woman with sickle cell disease and iatrogenic iron overload

A 29-year-old woman with known sickle cell disease (SCD) and iatrogenic iron overload presented to the emergency department with a recurrent pain crisis and fever. Blood cultures obtained at a recent prior admission for the same complaints grew M avium. Bone marrow biopsy revealed non-caseating granulomas, but stains for mycobacteria and fungi were negative. Disseminated non-tuberculous mycobacterial infections (NTMIs) occur almost exclusively in immunosuppressed patients. SCD is not considered a risk factor for the development of disseminated NTMIs, making diagnosis challenging in this population. However, a number of case reports describing disseminated NTMIs in patients with SCD have been published. This case adds to the current literature, suggesting SCD with iatrogenic iron overload is a possible risk factor for disseminated NTMIs. Potential mechanisms for this increased risk include 1) functional asplenia, 2) iatrogenic iron overload, 3) chronic indwelling central venous catheters, and 4) hydroxyurea use. Further investigation is required to describe the strength and mechanism of the relationship between SCD and disseminated NTMIs.

Association of low fat mass with nontuberculous mycobacterial infection in patients with bronchiectasis.

The incidence of pulmonary nontuberculous mycobacterial (NTM) infection is high in patients with underlying lung disease such as bronchiectasis. Although previous studies have reported many risk factors contributing to the development of NTM-lung disease (LD), only a few reports on the relationship of the characteristics of patients, such as body mass index (BMI), skeletal mass, and fat mass, with NTM-LD have been published. We aimed to investigate the association between these parameters and NTM-LD in patients with bronchiectasis.A monocentric retrospective study in a university hospital was conducted over 4 years (2013–2016). Parameters including BMI, skeletal mass, and fat mass were measured using bioelectrical impedance analysis in noncystic fibrosis bronchiectasis patients. Patients were grouped by the presence or absence of NTM-LD, and the differences in BMI, skeletal mass, and fat mass between the 2 groups were compared. In the NTM-LD group, the progression of disease was also followed.Two hundred forty-five patients with bronchiectasis were enrolled in the study. One hundred six subjects (48%) had NTM-LD. These patients with NTM-LD were predominantly female, and had a significantly lower body weight (58.20 ± 8.84 vs 54.16 ± 8.99, P < .001), BMI (22.67 ± 3.04 vs 21.20 ± 2.59 kg/m2, P < .001), fat mass (16.19 ± 6.60 vs 14.23 ± 5.79, P = .013), and fat mass index (FMI; 6.79 ± 2.70 vs 5.57 ± 2.27 kg/m2, P < .001). Multivariate regression analysis showed that both female sex and lower FMI but not skeletal muscle index were independent risk factors for NTM-LD after adjusting for age, bronchiectasis severity index, and BMI (odds ratio 3.86 (1.99–7.78); 0.72 (0.63–0.82), P < .001, respectively).Our results suggest that lower FMI may contribute to susceptibility to NTM infection in patients with bronchiectasis, independent of age or its severity.

Association between the Use of Inhaled Corticosteroids and Pulmonary Nontuberculous Mycobacterial Infection: A Systematic Review

The incidence of nontuberculous mycobacterial (NTM) pulmonary disease has increased in recent years. It seems that patients with structural lung diseases treated with inhaled corticosteroids (ICS) are at risk of pulmonary NTM infection. This systematic review investigated the articles focused on the association between the use of ICS and pulmonary NTM infection. The current study assessed four categories, namely the association between the use of ICS therapy and NTM infections, bacterial factors involved in the incidence of NTM infection in patients undergoing ICS therapy, the relationship between dosage and long-term use of ICS therapy in the incidence of NTM infection, and main risk factors of the incidence of NTM infection in patients undergoing ICS therapy. Based on the obtained results of the present study, there was an association between the use of ICS therapy and NTM infections. It seems that ICS increases the risk of NTM infection by 1.8 to 8 times. Accordingly, 40-90% of patients with NTM had a history of ICS usage. Mycobacterium avium complex was the most common bacterial factor in NTM patients undergoing ICS therapy. The relationship between a higher dosage of ICS therapy and an increased risk of NTM was confirmed in the majority of the studies. Age, gender, smoking history, and underlying diseases are the main risk factors for the incidence of NTM in patients receiving ICS therapy.

Novel therapies for treatment of resistant and refractory nontuberculous mycobacterial infections in patients with cystic fibrosis.

Respiratory infections caused by non-tuberculous mycobacteria (NTM) are a major cause of morbidity for patients living with cystic fibrosis (CF), as NTM pulmonary disease (NTM-PD) is challenging to both diagnose and eradicate. Despite the lengthy courses of the established regimens recommended by the Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) consensus guidelines, only about 50% to 60% of patients achieve culture conversion, and treatment regimens are often complicated by antibiotic resistance and toxicities. Since publication of the CFF/ECFS guidelines, several new or alternative antibiotic regimens have been described for patients with CF who have NTM-PD. These regimens offer new options for patients who do not clear NTM with standard therapies or cannot utilize the usual regimens due to toxicities or drug-drug interactions.

Diagnosis of NTM active infection in lymphadenopathy patients with anti-interferon-gamma auto-antibody using inhibitory ELISA vs. indirect ELISA

The anti-interferon-gamma (IFN-gamma) autoantibody is a known cause of opportunistic non-tuberculous mycobacterial (NTM) infection in adults. Diagnosis of those patients is difficult due to the low sensitivity of bacterial culture, and because detection of the neutralizing autoantibody needs special laboratory devices. We conducted a retrospective review of indirect and inhibitory ELISA, both used for detection of anti-IFN-gamma auto-antibody in 102 patients with lymphadenopathies. We assessed hospital records of NTM isolation and/or diagnosis of NTM infection. The review revealed the compatible sensitivity and superior specificity and predictive values for inhibitory ELISA over against indirect ELISA—the latter achieving 100% specificity and positive predictive value for diagnosis of NTM infection in patients with lymphadenopathies. The results confirm functional assays that show plasma samples from NTM-infected patients with positive results by either indirect and/or inhibitory ELISA are IFN-gamma neutralizing autoantibodies. The inhibitory titer of anti-IFN-gamma auto-antibody can be used to distinguish patients with active from inactive NTM infection. Inhibitory ELISA is thus a practical, rapid, high performance tool for routine detection of anti-IFN-gamma autoantibody and NTM infection diagnosis before confirmation, enabling a timely therapeutic strategy for active infection treatment.

Recent increase in non-tuberculous mycobacterial infection in patients with connective tissue diseases in Japan

BackgroundNon-tuberculous mycobacterial (NTM) infection is currently a growing health concern due to the increasing incidence and the need for prolonged therapy. In patients with connective tissue diseases, use of immunosuppressants may lead to an increased risk of NTM infection. However, few studies have examined the recent incidence of NTM infection among connective tissue diseases patients. This study investigated recent trends in NTM infection among connective tissue diseases patients. MethodsWe included adult patients from whose cultures NTM were isolated between January 2009 and October 2017 in our hospital. By reviewing their medical records, connective tissue diseases patients were identified. Types of connective tissue disease, NTM species, and treatment of NTM infection were extracted. ResultsNTM was isolated from 657 patients during the period. Among these, 24 patients had connective tissue diseases. The number and rate of NTM isolates from connective tissue diseases patients increased during the period, with 4 patients 2009 to 2012 (1.9%), and 20 patients from 2013 to 2017 (3.3%; P = 0.04). The proportion of Mycobacterium avium complex (MAC) to total NTM tended to be lower among connective tissue diseases patients (58.3%) than among non-connective tissue disease-patients (72.8%), but the difference was not significant (P = 0.20). Mycobacterium xenopi was significantly more frequent in connective tissue disease patients than in non-connective tissue diseases patients (P < 0.01). ConclusionThe recent increase in the incidence of NTM infections in connective tissue diseases patients was larger than that in the total population. NTM species other than MAC were isolated from connective tissue diseases patients.

1355. Efficacy and Tolerability of Linezolid Adjunctive Treatment for Nontuberculous Mycobacterial Infection in Patients with Acquired Anti-Interferon-Gamma Autoantibody

BackgroundDespite a long duration of combined oral antimycobacterial drugs, relapse/ reinfection of nontuberculous mycobacteria (NTM) is common among patients with anti-interferon gamma autoantibodies (anti-IFN-γ auto-Abs).MethodsWe reported here, an interim analysis of the prospective study of 25 patients with anti-IFN-γ auto-Abs, who received oral linezolid (LZD) adjunctive treatment for their NTM infections, at Siriraj Hospital, Bangkok, Thailand, between December 2017 and April 2019.Results8 patients (32%) were male, with a median age of 52.5 years. NTM identified among them included Mycobacterium abscessus (n = 19), M. avium complex (MAC) (n = 2), M. fortuitum (n = 2), M. kansasii (n = 1), and both M. abscessus and MAC (n = 1). The median duration of follow-up was 11 months (range 1.6–15 months). LZD 600 mg/day was given until clinical remission, then reduced to 300 mg/day for a total duration of at least 9 months. Other patient’s managements, including choice and duration of other antimycobacterial therapy were determined by the attending physician. Clinical remission was achieved, and LZD was discontinued at 9 months in 10 patients. NTM infection remained active and LZD was continued to 12 months in 4 patients. Two patients only completed 6 months of LZD. Culture proven relapse of M. abscessus occurred in 3 patients during LZD treatment, and 1 patient developed M. haemophilum infection after discontinuation of all drugs for 3 months. One patient was retreated with intravenous antimycobacterial drugs based on clinical suspicious of relapse NTM infection. LZD-related serious adverse events leading to discontinue of LZD occurred in 5 patients; severe myelosuppression (n = 1), peripheral neuropathy (n = 2), exfoliative dermatitis (n = 1), and idiopathic increased intracranial pressure (n = 1). Anemia occurred in 3 patients during the 600 mg LZD once-daily treatment period. No patient developed anemia after LZD was adjusted to 300 mg twice daily. The rate of peripheral neuropathy was similar throughout the study period.ConclusionLZD might reduce the rate of relapsed/ reinfection of NTM infection in these patients. LZD 300 mg twice daily was less toxicity and more tolerable than 600 mg once daily. Long-term study with this modified regimen is now on-going.Disclosures All authors: No reported disclosures.

Development and exacerbation of pulmonary nontuberculous mycobacterial infection in patients with systemic autoimmune rheumatic diseases

Objectives: To examine the development and exacerbation of pulmonary nontuberculous mycobacterial (NTM) infection in patients with systemic autoimmune rheumatic diseases (SARD).Methods: We conducted a case–control study. Seventeen of 7013 patients with SARD fulfilling the criteria for pulmonary NTM infection were enrolled in the NTM group. The control group was matched for age, sex, and SARD at a ratio of 2:1.Results: Eight patients with rheumatoid arthritis, four with systemic vasculitis, three with Sjögren’s syndrome, and one each with dermatomyositis and systemic lupus erythematosus were included in the NTM group. Mycobacterium avium was detected in 12 (71%) patients, M. chelonae in 2, and M. intracellulare, M. abscessus, and M. kansasii in 1 patient each. Preexisting lung disease was more common in the NTM group than in the control group (88% versus 38%, p = .0009), particularly bronchiectasis (65% versus 29%, p = .033). The body mass index and serum albumin level were significantly lower in the NTM group than in the control group. Six patients (35%) experienced NTM exacerbation during observation. Clinical immune status at the time of NTM diagnosis, as indicated by the peripheral blood leukocyte/lymphocyte count and serum immunoglobulin G level, was unremarkable and comparable between patients with and without exacerbation, as were the treatments for SARD.Conclusions: In patients with SARD, pulmonary NTM infection may develop and exacerbate without clinically apparent immunosuppression.

Tap water: A possible source of nontuberculous mycobacterial infection in patients with T cell deficiency

Five patients, all with severe T cell dysfunction, had invasive non-tuberculous mycobacteria (NTM) infections diagnosed over a 16 month period, with four meeting Centers for Disease Control and Prevention criteria for hospital-acquired infections. Testing of the hospitals tap water confirmed the presence of NTM. NTM are naturally present in water systems and present a threat to patients with lymphopenia; steps should be taken to avoid NTM exposure when caring for this patient population.

The risk of nontuberculous mycobacterial infection in patients with Sj\xf6gren\u2019s syndrome: a nationwide, population-based cohort study

BackgroundNontuberculous mycobacterial (NTM) infection in immunocompromized patients is currently a growing health concern, and we aimed to examine the relative risk of NTM infection in patients with Sjögren’s syndrome (SS) compared with that in non-SS individuals.MethodsWe used the 2003–2012 Taiwanese National Health Insurance Research Database to identify 6554 incident SS cases during 2007–2012 and selected 98,310 non-SS controls matched (1:15) for age, gender, and the year of first SS diagnosis date after excluding those who had rheumatoid arthritis or systemic lupus erythematosus.ResultsWe identified four NTM-infected patients in the SS group (three in the first year) and nine in the non-SS group (three in the first year). SS patients had a higher incidence rate of NTM infection than that in non-SS individuals (IRR, 7.56; 95% CI, 2.33–24.55), especially during the first year (IRR, 16.05; 95% CI, 3.24–79.51). After adjusting for potential confounders, the risk of NTM infection was not increased in SS patients during the entire follow-up period or during the first year, but the risk increased in SS patients treated with immunosuppressants during the entire follow-up period (HR, 17.77; 95% CI, 4.53–69.61), especially during the first year (HR, 33.33; 95% CI, 4.37–254.23).ConclusionAn increased risk of NTM infection was found in SS patients treated with immunosuppressants during the first year after SS diagnosis.

Application of a stochastic modeling to assess the evolution of tuberculous and non-tuberculous mycobacterial infection in patients treated with tumor necrosis factor inhibitors.

In this manuscript we apply stochastic modeling to investigate the risk of reactivation of latent mycobacterial infections in patients undergoing treatment with tumor necrosis factor inhibitors. First, we review the perspective proposed by one of the authors in a previous work and which consists in predicting the occurrence of reactivation of latent tuberculosis infection or newly acquired tuberculosis during treatment; this is based on variational procedures on a simple set of parameters (e.g. rate of reactivation of a latent infection). Then, we develop a full analytical study of this approach through a Markov chain analysis and we find an exact solution for the temporal evolution of the number of cases of tuberculosis infection (re)activation. The analytical solution is compared with Monte Carlo simulations and with experimental data, showing overall excellent agreement. The generality of this theoretical framework allows to investigate also the case of non-tuberculous mycobacteria infections; in particular, we show that reactivation in that context plays a minor role. This may suggest that, while the screening for tuberculous is necessary prior to initiating biologics, when considering non-tuberculous mycobacteria only a watchful monitoring during the treatment is recommended. The framework outlined in this paper is quite general and could be extremely promising in further researches on drug-related adverse events.

Nontuberculous mycobacterial infections in cancer patients in a medical center in Taiwan, 2005–2008

Data on the nontuberculous mycobacterial (NTM) species that cause infection and the characteristics of disease caused by these pathogens in cancer patients are limited, so we perform this study to investigate the species distribution of NTM isolates from various clinical specimens and to elucidate the epidemiologic trends in NTM isolates and diseases among cancer patients. From 2005 through 2008, cancer patients with NTM infections as defined by the American Thoracic Society/Infectious Diseases Society of America criteria were identified at the National Taiwan University Hospital. The medical records of all patients were reviewed. During the study period, a total of 219 cancer patients with NTM infections were identified. Among them, 133 (60.7%) patients were older than 65 years, most of whom were men. Lung cancer was the most common type of cancer, followed by hematologic cancer and gastrointestinal tract cancer. Pulmonary NTM infection was the most common type of infection in 205 (93.6%) patients, followed by skin and soft tissue infections ( n = 7, 3.2%), disseminated infections ( n = 4, 1.8%), and genitourinary tract infection ( n = 3, 1.4%). Disseminated infections occurred exclusively in patients with hematologic cancer. Mycobacterium avium complex (MAC) caused the majority of pulmonary NTM infections in cancer patients; in contrast, M. abscessus was the most common causative pathogen of extrapulmonary NTM diseases, followed by MAC. In conclusion, physicians need to be aware of the possibility of co-existing pulmonary NTM infection in patients with lung cancer. In addition, disseminated NTM infection should be considered in patients with hematologic cancer.