External Validation of the BACES Score in Canadian Patients With Nontuberculous Mycobacterial Pulmonary Disease.

BACKGROUND: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) can be variable and difficult to predict. Recently, the BACES score was developed as a tool to predict all-cause mortality in patients with NTM-PD. This score is calculated based on five patient characteristics (BMI, age, cavity, erythrocyte sedimentation rate, and sex), and higher scores portend worse prognosis. Although the BACES score has been validated in a cohort of South Korean patients, it has not yet been validated in other settings or ethnic groups. RESEARCH QUESTION: How well does the BACES mortality score perform in a cohort of Canadian patients with NTM-PD? STUDY DESIGN AND METHODS: We performed a single-center retrospective chart review. Patients who were seen between July 2003 and June 2021 were eligible for inclusion if they met guideline-based diagnostic criteria for NTM-PD and were excluded if any component of the BACES score was missing. To assess the model's discriminatory performance, we compared Kaplan-Meier curves between risk groups and calculated Harrell's C index. To assess calibration, we used a graphical calibration curve. RESULTS: The cohort included 435 patients with a median follow-up of 5.8 years. The median age was 64 years and 74% were female. Based on the BACES scores, patients were classified into three risk groups: low, moderate, or high. Survival curves showed clear separation of the risk groups. Harrell's C index was 0.733 in the study cohort, indicating moderate to good discriminatory performance, although this was lower than the value reported in the derivation cohort (0.812). The graphical calibration curve showed a tendency of the BACES model to underpredict mortality. INTERPRETATION: The BACES model was evaluated in a multicultural cohort of Canadian patients and demonstrated good discriminatory performance but suboptimal calibration, which may be due to population differences, the use of dichotomized variables in model construction, or both.

Association of indicators of extensive disease and rifampin-resistant tuberculosis treatment outcomes: an individual participant data meta-analysis.

BACKGROUND: Indicators of extensive disease-acid fast bacilli (AFB) smear positivity and lung cavitation-have been inconsistently associated with clinical rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) outcomes. We evaluated the association of these indicators with end-of-treatment outcomes. METHODS: We did an individual participant data meta-analysis of people treated for RR/MDR-TB with longer regimens with documented AFB smear and chest radiography findings. We compared people AFB smear-negative without cavities to people: (1) smear-negative with lung cavities; (2) smear-positive without lung cavities and (3) AFB smear-positive with lung cavities. Using multivariable logistic regression accounting for demographic, treatment and clinical factors, we calculated adjusted ORs (aOR) for any unfavourable outcome (death, lost to follow-up, failure/recurrence), and mortality and treatment failure/recurrence alone. RESULTS: We included 5596 participants; included participants significantly differed from excluded participants. Overall, 774 (13.8%) were AFB smear-negative without cavities, 647 (11.6%) only had cavities, 1424 (25.4%) were AFB smear-positive alone and 2751 (49.2%) were AFB smear-positive with cavities. The median age was 37 years (IQR: 28-47), 3580 (64%) were male and 686 (12.5%) had HIV. Compared with participants AFB smear-negative without cavities, aOR (95% CI) for any unfavourable outcome was 1.0 (0.8 to 1.4) for participants smear-negative with lung cavities, 1.2 (0.9 to 1.5) if smear-positive without cavities and 1.6 (1.3 to 2.0) if AFB smear-positive with lung cavities. Odds were only significantly increased for mortality (1.5, 95% CI 1.1 to 2.1) and failure/recurrence (2.2, 95% CI 1.5 to 3.3) among participants AFB smear-positive with lung cavities. CONCLUSION: Only the combination of AFB smear-positivity and lung cavitation was associated with unfavourable outcomes, suggesting they may benefit from stronger regimens.

Tolerability Outcomes of American Thoracic Society/Infectious Diseases Society of America Guideline-Recommended Multidrug Antibiotic Treatment for Mycobacterium avium Complex Pulmonary Disease in US Medicare Beneficiaries With Bronchiectasis.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. RESEARCH QUESTION: Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation? STUDY DESIGN AND METHODS: In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens. RESULTS: The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). INTERPRETATION: Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD.

Treatment of the Less Common Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic evaluation follows the established criteria for all nontuberculous mycobacteria, but with certain qualifications given species-specific and regional differences in pathogenicity. Clinicians should first institute nonpharmacologic management and evaluate clinical, radiologic, and microbiologic factors in the decision regarding antimycobacterial therapy. Treatment is challenging, and evidence-based recommendations are limited for most species. Drug susceptibility testing is used to help with regimen selection; however, this approach is imperfect given the uncertain correlation between in vitro activity and clinical response for most drugs.

Inclusion of non-medical interventions in model-based economic evaluations for tuberculosis: A scoping review.

BACKGROUND: The economic evaluation of health interventions is important in priority setting. Several guidance documents exist to support the conduct of economic evaluations, however, there is limited guidance for the evaluation of non-medical interventions. For tuberculosis (TB), where equity-deserving groups are disproportionately impacted, assessing interventions aimed at addressing social risk factors is necessary to effectively reduce TB burden. OBJECTIVE: This scoping review seeks to assess the existing literature on model-based economic evaluations of TB interventions to gauge the extent to which non-medical interventions have been evaluated in low-TB-incidence jurisdictions. As a secondary objective, this review aims to characterize key features of existing economic evaluations of medical and non-medical interventions. METHODS: A literature search was conducted in the grey literature and MEDLINE, Embase, EconLit, and PsychINFO databases to September 6, 2022 following the Arksey and O'Malley framework. Eligible articles were those that used decision-analytic modeling for economic evaluation of TB interventions in low-TB-incidence jurisdictions. RESULTS: This review identified 127 studies that met the inclusion criteria; 11 focused on prevention, 73 on detection, and 43 on treatment of TB. Only three studies (2%) evaluated non-medical interventions, including smoking reduction strategies, improving housing conditions, and providing food vouchers. All three non-medical intervention evaluations incorporated TB transmission and robust uncertainty analysis into the evaluation. The remainder of the studies evaluated direct medical interventions, eight of which were focused on specific implementation components (e.g., video observed therapy) which shared similar methodological challenges as the non-medical interventions. The majority of remaining evaluated medical interventions were focused on comparing various screening programs (e.g., immigrant screening program) and treatment regimens. CONCLUSIONS: This scoping review identified a gap in literature in the evaluation of non-medical TB interventions. However, the identified articles provided useful examples of how economic modeling can be used to explore non-traditional interventions using existing economic evaluation methods.

Hepatotoxicity and tuberculosis treatment outcomes in chronic liver disease.

Background: The treatment of tuberculosis (TB) is known to cause liver injury, however, there is limited data to guide optimal treatment for patients with chronic liver disease. Methods: We undertook a retrospective case series of patients with chronic liver disease and TB disease. The primary objective was to determine if there was a difference in the incidence of drug-induced liver injury (DILI) in patients with cirrhosis versus those with chronic hepatitis. Additionally, we sought to compare TB treatment outcomes, type and duration of therapy, and incidence of adverse events. Results: We included 56 patients (chronic hepatitis 40; cirrhosis 16). There were 33 patients (58.9%) who experienced DILI requiring treatment modification, with no significant difference between groups (65% versus 43.8%, p = 0.23). Patients with chronic hepatitis were more likely to receive treatment with standard first-line intensive phase therapy that included a combination of rifampin (RIF), isoniazid, and pyrazinamide (80.8% versus 19.2%, p = 0.03) and any regimen than included isoniazid (92.5% versus 68.8%, p = 0.04). The risk of DILI was higher when more hepatotoxic TB medications were used. Overall treatment success in this cohort was low (55.4%), with no significant difference between groups (62.5% versus 37.5%, p = 0.14). Most patients with treatment success (97%) were able to tolerate a rifamycin. Conclusions: The risk of DILI is high, especially with the use of isoniazid, in patients with TB and chronic liver disease. This risk can be effectively mitigated with no difference in treatment outcomes in the presence of cirrhosis.

Historique: Il est bien connu que le traitement de la tuberculose (TB) provoque des lésions hépatiques, mais les données sont limitées pour orienter le traitement des patients atteints d'une hépatopathie chronique. Méthodologie: Les chercheurs ont étudié une série rétrospective de cas de patients atteints d'une hépathopathie chronique et d'une TB. Ils s'étaient donné comme objectif primaire de déterminer s'il y avait une différence entre l'incidence de lésion hépatique d'origine médicamenteuse (LHOM) chez les patients atteints d'une cirrhose et ceux atteints d'une hépatite chronique. De plus, ils ont comparé les résultats des traitements de la TB, le type et la durée du traitement et l'incidence d'événements indésirables. Résultats: Les chercheurs ont inclus 56 patients (hépatite chronique : 40; cirrhose : 16). De ce nombre, 33 (58,9 %) avaient présenté une LHOM ayant suscité une modification au traitement, sans différence notable entre les groupes : 65 % par rapport à 43,8 %, p = 0,23. Les patients atteints d'hépatite chronique étaient plus susceptibles de recevoir un traitement intensif standard en première ligne qui incluait une combinaison de rifampine (RIF), d'isoniazide et de pyrazinamide (80,8 % par rapport à 19,2 %, p = 0,03) ou une posologie qui comprenait de l'isoniazide (92,5 % par rapport à 68,8 %, p = 0,04). Le risque de LHOM était plus élevé lors de l'utilisation de médicaments contre la TB plus hépatotoxiques. La réussite globale du traitement était faible au sein de cette cohorte (55,4 %) et n'entraînait pas de différence significative entre les groupes (62,5 % par rapport à 37,5 %, p = 0,14). La plupart des patients dont le traitement était efficace (97 %) toléraient la rifamycine. Conclusions: Le risque de LHOM est élevé chez les patients atteints de TB et d'hépatopathie chronique, particulièrement lors de l'utilisation d'isoniazide. En présence de cirrhose, il est possible de l'atténuer avec efficacité sans modifier l'issue du traitement.

Evaluation of Mycobacterium Avium Complex Pulmonary Disease Treatment Completion and Adherence to ATS/IDSA Guidelines.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. METHODS: We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. RESULTS: We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. CONCLUSIONS: Overall, nearly half of new MAC therapy users were prescribed a non-guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources.

The Other Nontuberculous Mycobacteria: Clinical Aspects of Lung Disease Caused by Less Common Slowly Growing Nontuberculous Mycobacteria Species.

Slowly growing nontuberculous mycobacteria (NTM) comprise a diverse group of environmental organisms, many of which are important human pathogens. The most common and well-known member of this group is Mycobacterium avium, the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) globally. This review focuses on the less common, but notable, species of slowly growing NTM with respect to lung disease. To prepare this article, literature searches were performed using each species name as the key word. Society guidelines were consulted, and relevant articles also were identified through the reference lists of key articles. The specific organisms highlighted include Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Although these organisms are closely related, they have distinct epidemiologic features and behavior as pathogens. Therefore, the diagnosis and management of NTM-PD require a nuanced approach that takes into consideration the unique characteristics of each species. There is limited evidence to inform the optimal treatment of NTM-PD. Antimicrobial therapy is often challenging because of the presence of drug resistance and few antibiotic options. Regimen selection should generally be guided by drug susceptibility testing, although the correlation between clinical outcomes and in vitro susceptibility thresholds has not been defined for most species.

Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.

We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.

Increasing and More Commonly Refractory Mycobacterium avium Pulmonary Disease, Toronto, Ontario, Canada.

In mid-2014, Public Health Ontario Laboratories identified coincident increasing Mycobacterium avium isolation and falling M. xenopi isolation in the Toronto, Ontario, Canada, area. We performed a retrospective cohort of all patients in a Toronto clinic who began treatment for either M. avium or M. xenopi pulmonary disease during 2009-2012 (early period) or 2015-2018 (late period), studying their relative proportions and sputum culture conversion. We conducted a subgroup analysis among patients who lived in the Toronto-York region. The proportion of patients with M. avium was higher in the late period (138/146 [94.5%] vs. 82/106 [77.4%]; p<0.001). Among M. avium patients, conversion was lower in the late period (26.1% vs. 39.0%; p = 0.05). The increase in the proportion of patients with M. avium pulmonary disease and the reduction in the frequency of sputum culture conversion is unexplained but could suggest an increase in environmental M. avium exposure.

Impact of COVID-19 on Tuberculosis Prevention and Treatment in Canada: A Multicenter Analysis of 10 833 Patients.

We assessed the COVID-19 pandemic's impact on treatment of latent tuberculosis, and of active tuberculosis, at 3 centers in Montreal and Toronto, using data from 10 833 patients (8685 with latent tuberculosis infection, 2148 with active tuberculosis). Observation periods prior to declarations of COVID-19 public health emergencies ranged from 219 to 744 weeks, and after declarations, from 28 to 33 weeks. In the latter period, reductions in latent tuberculosis infection treatment initiation rates ranged from 30% to 66%. At 2 centers, active tuberculosis treatment rates fell by 16% and 29%. In Canada, cornerstone measures for tuberculosis elimination weakened during the COVID-19 pandemic.

Time to Positive Culture Detection Predicts Mycobacterium avium Pulmonary Disease Severity and Treatment Initiation.

Rationale: Additional biomarkers are needed to guide initiation of treatment for Mycobacterium avium pulmonary disease (Mav-PD). Time to positive sputum culture detection (TTP) may offer potential prognostic and monitoring value. Objectives: To determine whether TTP is associated with infection severity and early treatment response in Mav-PD. Methods: We undertook a retrospective cohort study of patients with two or more sputum cultures positive for M. avium, an "index" sputum M. avium isolate during 2015-2019, a computed tomographic scan within 6 months, and no treatment for at least 6 months before index sputum. TTP was estimated from the date of laboratory receipt of the specimen to the date of culture positivity confirmation. TTP was tested for association with markers of infection severity (Mav-PD, bronchiectasis, cavitary disease, treatment initiation by 3 and 6 months, and acid fast bacilli [AFB] smear) and treatment response using Mann-Whitney U, Spearman's correlation coefficient, and Wilcoxon signed-rank tests. We explored a threshold TTP that could identify significant M. avium disease. Results: We included 125 patients with mean (standard deviation) age 68.5 (12.5) years and 65% fulfilled disease criteria. Median TTP was 12 (interquartile range 10-15; range 6-44) days. TTP and AFB smear grade were negatively correlated (ρ -0.58; P < 0.001). TTP was associated with nontuberculous mycobacteria (NTM) disease (P = 0.03), AFB smear positivity (P < 0.001), and treatment initiation by 3 (P = 0.01) and 6 (P = 0.03) months. A threshold TTP of 10 days or less was associated with Mav-PD (80.6% vs. 58.4%; ð [95% confidence interval (CI)] 22.1% [5.6-38.6%]; P = 0.02), AFB smear positivity (83.3% vs. 20.2%, ð [95% CI] 63.1% [48.3-77.9%]; P < 0.001), treatment by 3 (38.9% vs. 13.5%; ð [95% CI] 25.4% [8.0-42.8%]; P = 0.003) and 6 (47.2% vs. 19.1%; ð [95% CI] 28.1% [9.9-46.4%]; P = 0.003) months. After 3 and 6 months of treatment, the median (interquartile range) change in TTP was 8 (1 undefined; P < 0.001) and 7 (0 undefined; P = 0.001) days, respectively. Conclusions: TTP is associated with bacterial burden and infection severity and increases in response to treatment. A threshold of 10 days or less may be useful in predicting significant Mav-PD. As a readily available biomarker, further exploration of TTP is imperative.

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients.

BACKGROUND: Lung transplant (LTX) recipients are at risk miscellaneous infections, among whom the clinical significance of nontuberculous mycobacteria (NTM) is increasingly recognized. Despite anti-mycobacterial therapy becoming standardized worldwide, there is a lack of data on treatment outcomes in LTX recipients who develop NTM-pulmonary disease (PD). We aimed to review the treatment outcomes of NTM-PD among LTX recipients in our center. METHODS: Patients who underwent LTX from January 2013 to December 2014 were consecutively enrolled in the retrospective cohort, with follow-up of data retrieved to December 2017. Clinical and radiological improvement and culture conversion after anti-mycobacterial therapy were reviewed in those who developed post-transplant NTM-PD. RESULTS: Sixteen of 230 LTX recipients developed post-transplant NTM-PD. Ten of 16 patients with post-transplant NTM-PD were treated with macrolide-containing anti-mycobacterial therapy, leading to clinical improvement in 5/10 (50%), radiological improvement in 5/10 (50%) and culture conversion in 6/10 (60%) patients. CONCLUSION: Anti-mycobacterial therapy may relieve pulmonary symptoms and reduce microbial load among individuals with post-transplant NTM-PD.

Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB).

BACKGROUND: The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. METHODS: Patients with MDR-TB treated at our institution receive amikacin at 8-10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. RESULTS: Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6-24.8%); 22.2% had subjective hearing loss (95% CI 11.2-37.1%) and 31.9% subjective tinnitus (95% CI 19.1-47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8-38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84-99%). CONCLUSIONS: Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.

Aspergillus isolation in nontuberculous mycobacterial pulmonary disease: Associated with antimycobacterial treatment initiation but not response.

PURPOSE: Chronic pulmonary aspergillosis is a serious complication of nontuberculous mycobacterial pulmonary disease (NTM-PD), and diagnosis remains challenging. The present study examined associations between the respiratory isolation of Aspergillus and the clinical characteristics and treatment outcomes of patients with NTM-PD. METHODS: All patients meeting NTM-PD criteria as defined by the ATS/IDSA statement, with at least one respiratory sample cultured for fungi, were included in this retrospective cohort analysis. Patients with at least one respiratory sample isolating Aspergillus were compared to patients who did not isolate Aspergillus. The primary outcomes were culture conversion and radiologic evolution 12 months after NTM-PD treatment initiation. RESULTS: During a 12 year period, 497 patients meeting the inclusion criteria were seen in our tertiary care center, of whom 130 grew Aspergillus. Median follow up after NTM-PD diagnosis was 46 months. Inhaled corticosteroid use, a nodular-bronchiectatic CT pattern and NTM-PD treatment initiation were more frequent in patients who isolated Aspergillus compared to those who did not (p-value respectively 0.01, 0.03 and < 0.001). Rates of culture conversion (63.0% vs. 62.2%, respectively; p-value 1) and radiologic evolution (improvement or stability in 69.7% vs. 77.2%, respectively; p-value 0.25) were not significantly different between treatment groups. Likewise, culture reversion rate and 5-year mortality were not significantly different. Additionally, A. fumigatus and repeated detection of Aspergillus were not associated with treatment outcomes. CONCLUSION: There was no association between respiratory isolation of Aspergillus and NTM-PD treatment outcomes in this cohort. However, treatment for NTM-PD was initiated more frequently in patients who isolated Aspergillus.

Costs Associated with Nontuberculous Mycobacteria Infection, Ontario, Canada, 2001-2012.

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001-2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.

Clinical outcomes in Mycobacterium xenopi versus Mycobacterium avium complex pulmonary disease: A retrospective matched cohort study.

Mycobacterium xenopi is associated with the highest mortality among pulmonary nontuberculous mycobacterial (NTM) infections, but whether this is due to the infection or other factors is unclear. There is little information regarding outcomes among patients infected with M. xenopi versus other NTM species. We conducted a retrospective matched cohort study comparing M. xenopi pulmonary disease (Mx-PD) to M. avium complex (MAC)-PD. Patients were matched by sex, age, radiologic subtype, and presence of cavitation. Baseline clinical characteristics, treatment, and outcomes were compared using matched analyses. We identified 70 Mx-PD cases: 29 fibrocavitary-type, 28 nodular-bronchiectatic-type, and 13 unclassifiable-type CT patterns, mean (SD) age 63 (13) years, and 54.3% (n = 38) female. Median follow-up duration was longer in the Mx-PD cohort (1552 days versus 1035 days, p = 0.01). Symptoms, radiologic phenotype, and pulmonary function were similar between groups although the Charlson Comorbidity Index was numerically higher in Mx-PD patients (3.6 versus 3.2, p = 0.08). Rifamycins were used less frequently in Mx-PD (59.5% versus 85.7%, p = 0.02). Although combined clinical and radiologic improvement was similar between the groups, successful treatment was more common with Mx-PD (40.5% versus 16.7%, p = 0.02) owing to superior culture conversion (70.8% versus 33.3%, p = 0.0001). Mortality 24 months after initiation of treatment was numerically but not statistically greater in the Mx-PD cohort (20.4% versus 10.3%, p = 0.32). Among matched Mx-PD and MAC-PD patients, standard anti-mycobacterial treatment was significantly more likely to achieve culture conversion and successful treatment for Mx-PD patients. Mortality among Mx-PD patients was numerically, but not statistically higher, possibly explained by increased comorbidity burden.