Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. METHODS: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). RESULTS: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. CONCLUSION: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

Impact of prognostic nutritional index on outcomes in patients with Mycobacterium avium complex pulmonary disease.

Onodera's prognostic nutritional index (PNI) is useful in predicting prognosis of various diseases. But the usefulness of PNI in non-surgical patients has not been sufficiently proven yet. In patients with mycobacterium avium complex pulmonary disease (MAC-PD), malnutrition is an important factor that affects the quality of life and morbidity. Here, we aimed to evaluate whether PNI is related with clinical outcomes in MAC-PD patients. We examined 663 patients diagnosed with MAC-PD between May 2005 and November 2017. PNI score was calculated at the time of diagnosis and treatment initiation, and patients were divided into malnutrition and non-malnutrition groups according to a cut-off PNI score of 45. As the recommended duration of treatment for MAC-PD is 12 months following sputum conversion, treatment duration less than 12 months was defined as treatment intolerance. Survivals were compared with the log-rank test. Multivariate logistic regression and multivariate Cox proportional hazards models were used to estimate the odds ratio (OR) and hazards ratio (HR) for treatment intolerance and mortality, respectively. Of the 306 patients that received treatment, 193 received treatment longer than 12 months. In the multivariable logistic regression model, malnutrition at the time of treatment initiation was related with treatment intolerance (OR: 2.559, 95% confidence interval [CI]: 1.414-4.634, P = 0.002). Patients in the malnutrition group at the time of diagnosis exhibited lower survival (P<0.001) and malnutrition at the time of diagnosis was a significant risk for all-cause mortality (HR: 2.755, 95% CI: 1.610-4.475, P<0.001). Malnutrition, as defined by PNI, is an independent predictor for treatment intolerance and all-cause mortality in patients with MAC-PD.

Impact of Aspergillus precipitating antibody test results on clinical outcomes of patients with Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD. METHODS: We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis. RESULTS: We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P < 0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA: 9 and allergic bronchopulmonary aspergillosis: 3) and 12 APAb-negative patients (10.8%, CPA: 12) (P < 0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors. CONCLUSIONS: APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis.

DIAGNOSIS AND MANAGEMENT OF MYCOBACTERIOSIS IN A COLONY OF LITTLE PENGUINS (EUDYPTULA MINOR).

A group of zoo-housed little penguins (Eudyptula minor) was diagnosed with mycobacteriosis. While undergoing multidetector computed tomography (MDCT) imaging for an unrelated research project, pulmonary lesions were detected in multiple individuals. In general, birds appeared healthy and free of outward signs of disease. After the loss of three individuals, polyclonal mycobacterial disease due to Mycobacterium avium-intracellulare complex was confirmed. Surviving birds were treated with rifampin (45 mg/kg), ethambutol (30 mg/kg), clarithromycin (10 mg/kg), and enrofloxacin (30 mg/kg) compounded into a single capsule administered once a day in food. After 3 mo of therapy, MDCT imaging documented a decrease in nodule size and number in all remaining birds, with further improvement documented after 13 mo of treatment. MDCT imaging was invaluable for diagnosing disease, documenting disease progression over time, and assessing response to therapy. Early initiation of therapy before the development of outward signs of disease led to resolution of mycobacterial pulmonary lesions in multiple penguins. Mycobacterial disease in this group of little penguins, as well as previously published reports, suggests that the species is at increased risk for developing mycobacteriosis.

Discovery of Nosiheptide, Griseoviridin, and Etamycin as Potent Anti-Mycobacterial Agents against Mycobacterium avium Complex.

Mycobacterium avium complex (MAC) is a serious disease mainly caused by M. avium and M. intracellulare. Although the incidence of MAC infection is increasing worldwide, only a few agents are clinically used, and their therapeutic effects are limited. Therefore, new anti-MAC agents are needed. Approximately 6600 microbial samples were screened for new anti-mycobacterial agents that inhibit the growth of both M. avium and M. intracellulare, and two culture broths derived from marine actinomycete strains OPMA1245 and OPMA1730 had strong activity. Nosiheptide (1) was isolated from the culture broth of OPMA1245, and griseoviridin (2) and etamycin (viridogrisein) (3) were isolated from the culture broth of OPMA1730. They had potent anti-mycobacterial activity against M. avium and M. intracellulare with minimum inhibitory concentrations (MICs) between 0.024 and 1.56 µg/mL. In addition, a combination of 2 and 3 markedly enhanced the anti-mycobacterial activity against both M. avium and M. intracellulare. Furthermore, a combination 2 and 3 had a therapeutic effect comparable to that of ethambutol in a silkworm infection assay with M. smegmatis.

High mortality in peritonitis due to Mycobacterium avium complex: retrospective study and systematic literature review.

BACKGROUND: Mycobacterium avium complex (MAC) infection is often disseminated and mainly involves lymph nodes, spleen, liver or bone marrow. Peritonitis due to MAC infection (PMAC) is a very uncommon manifestation. METHODS: In this report, after describing the case of the only PMAC infection in our 10-year retrospective study, which occurred in an AIDS patient who was non-adherent to highly active antiretroviral therapy (HAART), we performed a systematic literature review of documented bacteriological PMAC. RESULTS: Including our patient, 51 cases of PMAC have been reported. Patients were most often male (sex ratio 2.14), with a median age of 41 years (2.8-72) and an immunodeficiency in all cases, most often AIDS (57%), cirrhosis (20%) and continuous ambulatory peritoneal dialysis (CAPD) (18%). Ascites was more often chylous (54%) than exudative (46%) and, in this case, lymphocytic (60%), with an inconstantly positive acid-fast bacilli smear (54%). Non-disseminated PMAC patients were more likely to have peritoneal dialysis (39% versus 6.5%, p < .01) or cancer with immunosuppressive therapy (39% versus 0%, p < .0001), while AIDS was the leading underlying disease in disseminated-PMAC patients (83% versus 11%, p < .001). Mortality was high (50%), with no difference between disseminated and non-disseminated PMAC. CONCLUSIONS: This report highlights the need to be aware of an atypical presentation of PMAC infection, which is associated with a high rate of mortality even for non-disseminated infection.

Mycobacterium avium complex infection in patients with human immunodeficiency virus: A systematic review and meta-analysis.

BACKGROUND: Mycobacterium avium-intracellulare complex (MAC) is one of the leading causes of death among people living with human immunodeficiency virus (HIV). The current study was aimed to determine the frequency of MAC infection in patients infected with HIV. METHODS: Embase, PubMed, and Web of Science were searched for relevant studies. All statistical analyses were performed by STATA version 14. RESULTS: From 6,627 retrieved articles, 23 were included in the final analysis. A total of 18,463 patients with HIV were included in the analysis. The frequency of MAC infection in patients with HIV was found to be 10.6% (95% confidence interval, 6.9-14.2). CONCLUSION: The relatively large fractions of HIV-infected patients were coinfected with MAC, which may poses significant public health problems. Continued progress in the development of rapid diagnostic methods and preventive therapy for MAC should lead to further improvements in survival and quality of life in patients with HIV.

High mortality in patients with Mycobacterium avium complex lung disease: a systematic review.

BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) pulmonary disease caused by Mycobacterium avium complex (MAC) in apparently immune-competent people is increasing worldwide. We performed a systematic review of the published literature on five-year all-cause mortality in patients with MAC lung disease, and pooled the mortality rates to give an overall estimate of five-year mortality from these studies. METHODS: We systematically reviewed the literature up to 1st August 2017 using PubMed® and ProQuest Dialog™ to search Medline® and Embase® databases, respectively. Eligible studies contained > 10 patients with MAC, and numerical five-year mortality data or a treatment evaluation for this patient group. Mortality data were extracted and analysed to determine a pooled estimate of all-cause mortality. RESULTS: Fourteen of 1035 identified studies, comprising 17 data sets with data from a total of 9035 patients, were eligible. The pooled estimate of five-year all-cause mortality was 27% (95% CI 21.3-37.8%). A high degree of heterogeneity was observed (I2 = 96%). The mortality in the data sets varied between 10 and 48%. Studies predominantly including patients with cavitary disease or greater comorbidity reported a higher risk of death. Patients in Asian studies tended to have a lower mortality risk. Predictors of mortality consistent across studies included male sex, presence of comorbidities and advanced patient age. CONCLUSIONS: Despite high heterogeneity, most studies in patients with MAC pulmonary disease document a five-year all-cause mortality exceeding 25%, indicating poor prognosis. These findings emphasise the need for more effective management and additional prospective mortality data collection.

Clinical significance of Aspergillus species isolated from respiratory specimens in patients with Mycobacterium avium complex lung disease.

Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). An Aspergillus-positive respiratory specimen often reflects colonization, and thus the clinical significance of Aspergillus isolation in MAC-LD patients is not well understood. The objective of this study was to investigate the clinical characteristics and outcomes of MAC-LD patients in whom Aspergillus was isolated from respiratory specimens. We performed a retrospective review of the medical records of 329 MAC-LD patients. We compared the characteristics and mortality rates between patients with Aspergillus isolation and those without. All Aspergillus species detected from respiratory specimens within the follow-up period were reviewed. Aspergillus was detected in 40 (12.2%) of the 329 patients. There were no significant differences in the clinical characteristics and mortality rates between patients with and without Aspergillus isolation. Among the 40 patients with Aspergillus isolation, 9 (22.5%) developed CPA. CPA was most often caused by A. fumigatus. In the 40 Aspergillus-positive patients, patients with A. fumigatus isolation had a significantly higher mortality rate than those without (P < 0.001). The multivariate Cox proportional hazards model showed older age (P = 0.050), presence of respiratory comorbidities (P = 0.008), hypoalbuminemia (P < 0.001), and isolation of A. fumigatus (P = 0.005) to be prognostic factors for mortality in MAC-LD patients. There was no significant difference in the mortality rates between patients with Aspergillus isolation and those without. However, isolation of A. fumigatus may be associated with poor prognosis in MAC-LD patients.

Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study.

BACKGROUND: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. METHODS: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. RESULTS: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m2, lymphocyte count <1000 cells/µL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2. CONCLUSIONS: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

Clinical features of patients with bacteraemia caused by Mycobacterium avium complex species and antimicrobial susceptibility of the isolates at a medical centre in Taiwan, 2008-2014.

Advanced molecular typing methods have greatly expanded the taxonomy of Mycobacterium avium complex (MAC) species; however, little is known about the epidemiology and clinical features of bacteraemia caused by different MAC species. In this study, the clinical characteristics of patients treated for MAC bacteraemia in a tertiary-care centre in northern Taiwan during 2008-2014 were investigated. Isolates were identified to species level by rpoB gene and 16S-23S rRNA internal transcribed spacer region sequencing. Among 30 patients with bacteraemia due to MAC, the majority (n = 26) had concomitant human immunodeficiency virus (HIV) infection. Of the 30 blood isolates obtained from patients, 24 were M. avium subsp. hominissuis, 4 were Mycobacterium colombiense and 2 were Mycobacterium intracellulare. All four M. colombiense isolates were from HIV-infected patients. Bacteraemia due to M. colombiense was associated with higher 30-day mortality than bacteraemia due to M. avium subsp. hominissuis [2/4 (50%) vs. 1/24 (4%); P = 0.045, Fisher's exact test]. All four M. colombiense isolates were susceptible to clarithromycin, moxifloxacin and linezolid. Among the five patients who received ethambutol treatment and four patients who received fluoroquinolone treatment for various durations between positive MAC cultures, two and three patients, respectively, had isolates with significantly increased (≥4-fold) ethambutol and fluoroquinolone minimum inhibitory concentrations. M. colombiense was the second leading causative pathogen of MAC bacteraemia, comprising 15% of all MAC isolates obtained from HIV-positive patients. Monitoring the susceptibility of MAC isolates to ethambutol and fluoroquinolones is warranted in patients with persistent MAC bacteraemia.

Clinical significance of the radiological severity score in Mycobacterium avium complex lung disease patients.

SETTING: Practical methods for assessing the radiographic findings of Mycobacterium avium complex lung disease (MAC-LD) have not been established. OBJECTIVE: To identify a correlation between the radiological score and semi-quantitative culture results of respiratory samples, and to assess the prognostic impact of this radiological score in MAC-LD patients. DESIGN: We retrospectively studied 218 MAC-LD patients. Radiographic findings were classified as nodule (N), infiltration shadow (I), cavity (C) and bronchiectasis (E), scored individually according to the area occupied on six lung field divisions, and added to give the radiological severity score. RESULTS: The radiological score positively correlated with the semi-quantitative culture score (P = 0.003). In univariate analysis, the radiological score was a significant negative prognostic factor for overall survival. On multivariate analysis, factors I, C and E were independent negative prognostic factors for overall survival. We compared the prognostic value of the total score of all four factors and the three significant factors (I, C and E) using receiver operating characteristic curve analysis; the corresponding areas under the curves were respectively 0.628 and 0.763 (P < 0.001). CONCLUSIONS: The radiological score correlates with prognosis. The combined score of factors I, C and E may more accurately predict prognosis in MAC-LD patients.

Clinical Characteristics, Treatment Outcomes, and Resistance Mutations Associated with Macrolide-Resistant Mycobacterium avium Complex Lung Disease.

Macrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due to Mycobacterium avium complex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form. M. intracellulare was the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.

Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/bronchiectatic Mycobacterium avium complex lung disease.

OBJECTIVES: Some patients with nodular/bronchiectatic Mycobacterium avium complex lung disease (NB MAC-LD) deteriorate and die. The main aim of the study is to evaluate the prognostic factors and radiographic outcomes in patients with NB MAC-LD. SETTING: Retrospective single-centre review. PARTICIPANTS: 782 HIV-negative patients with NB MAC-LD treated at our institution in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and MAC-LD progression mortality rates and the prognostic factors, and radiographic deterioration rates and the prognostic factors. RESULTS: Mean age was 68.1 years, and median follow-up period was 4.3 years. Death from any cause and progression of MAC lung disease (MAC-LD) occurred in 130 (16.6%), and 19 (2.4%) patients, respectively. All-cause and MAC-LD progression 10-year mortality rates were 27.4% and 4.8%, respectively. In 536 patients with MAC-LD who were followed-up for more than 1 year, radiographic deterioration occurred in 221 (41.2%) patients and median time-to-radiographic deterioration was 9 years. A multivariate Cox proportional hazard model showed male sex, older age, body mass index <18.5 kg/m(2), absence of bloody sputum, hypoalbuminaemia and erythrocyte sedimentation rate >40 mm/h to be negative prognostic factors for all-cause mortality, and the presence of idiopathic pulmonary fibrosis, haemoglobin <11.3 mg/dL, C reactive protein >1.0 mg/dL and the presence of cavity to be negative prognostic factors for radiographic deterioration. CONCLUSIONS: Only 2.4% of patients with NB MAC-LD died from MAC-LD progression. As clinical trials testing the effectiveness of drug therapy in patients with NB MAC-LD are being designed and implemented, the primary end point could be time-to-radiographic deterioration, and trial patients need to be stratified according to these prognostic factors before randomisation.

Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.

Mycobacterium avium complex infection in non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Reliable markers of disease progression or stability to assist in management decisions are lacking in patients with non-cystic fibrosis bronchiectasis and Mycobacterium avium complex (MAC) infection. METHODS: Data from 52 adults with non-cystic fibrosis bronchiectasis and coexisting MAC infection managed at our institution over a 5-year period were retrospectively analysed. High-resolution computed tomography (HRCT) scans were scored using a scoring system that focused on findings associated with MAC infection. RESULTS: Chronic pulmonary aspergillosis was independently associated with mortality (hazard ratio (HR) = 8.916, 95% confidence interval (CI) = 1.324-60.027), as were nodules with cavitation (HR = 5.911, 95% CI = 1.095-25.911) and emphysema (HR = 1.027, 95% CI = 1.002-1.053) on HRCT. Anti-MAC chemotherapy was more likely to lead to MAC culture conversion (67% vs. 27%, P = 0.005) but did not improve survival as compared with patients managed with observation. Longitudinally, patients who had improvements in HRCT scores were younger (60.2 ± 9.19 years vs. 69.83 ± 12.43 years, P = 0.043), while the presence of cavitation within nodules predicted a deterioration in HRCT scores (0.5 (0-3) vs. 0 (0-1), P = 0.033). No significant longitudinal differences were found in lung function in the cohort as a whole or within different groups. CONCLUSIONS: Chronic pulmonary aspergillosis in patients with bronchiectasis and coexisting MAC infection is a strong predictor of mortality. Cavitation within nodules and emphysema on HRCT at presentation were independently associated with mortality.

Opinions differ by expertise in Mycobacterium avium complex disease.

RATIONALE: Pulmonary Mycobacterium avium complex treatment guidelines rely largely on expert opinion. The extent to which nonexperts agree with recommendations of experts in this clinical area is unknown. OBJECTIVES: We sought to compare practices and perceptions of prognosis between experts and nonexperts. METHODS: We surveyed respirologists (Ontario, Canada, "nonexperts") and experts from nontuberculous mycobacterial disease centers of excellence (Canada and United States). MEASUREMENTS AND MAIN RESULTS: Forty-six Ontario respirologists (29% of 160) and 19 experts (73% of 26) participated. There was agreement between nonexperts and experts regarding disease duration before diagnosis (2 yr), likelihood of spontaneous remission (7-15%), typical duration of treatment (18 mo), first choice of therapy (guideline regimens), a subgroup of patients for whom less-intensive regimens are favored (10% after recurrence), likelihood of recurrence (30%), and median survival (10 yr in most patients). Noted differences were that nonexperts estimated fewer patients with a positive culture had disease (30% vs. 50%, P = 0.02), used intensive guidelines therapy less often in new cases (50% vs. 79%, P = 0.02), and perceived a slightly lower success rate with guidelines therapy (65% vs. 75%, P = 0.047). Response ranges were wider for nonexperts, significantly so for selection of intensive guidelines therapy in new (P = 0.01) and recurrent (P = 0.04) cases. CONCLUSION: Experts and nonexperts agreed on many issues. However, nonexperts perceived lower rates of disease among patients with isolates, tended to use less aggressive treatment approaches, and perceived lower success rates. Significant variability was observed in responses-often wider among nonexperts. Although these results are likely biased by referral, they may identify important areas for targeted education.

Profile of cause of death assigned to adults on antiretroviral therapy in Soweto.

This retrospective cohort study describes causes of death in 305 patients (baseline median CD4 count 26/µl) from 2 943 adults on antiretroviral therapy. Acute sepsis (20%), tuberculosis (18%) and Mycobacterium avium complex (MAC) bacteraemia (14%) were the most common causes. Mortality owing to the disease was 66% for MAC bacteraemia and 23% for non-Hodgkin's lymphoma. In 37 patients dying beyond one year on ART, virological failure was present in 11 (30%), and non-HIV-related causes of death occurred in 10. The main causes were acute sepsis (6), tuberculosis (7) and chronic medical conditions (5). Initiating ART at higher CD4 counts should reduce early mortality.

Predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex disease.

SETTING: Kyoto, Japan. OBJECTIVE: To determine predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex (MAC) disease. DESIGN: Retrospective study of 164 patients diagnosed with pulmonary MAC disease between 1999 and 2005 and followed for 5 years. RESULTS: Overall 5-year mortality was 28.0%. Among 117 patients with microbiological outcomes, 54 were treated (treated MAC patients) and 24 were not treated and did not experience sputum culture conversion during follow-up (untreated chronic MAC patients); 39 patients were not treated and experienced sputum culture conversion. Five-year all-cause overall mortality among the 78 patients with definite MAC disease (including treated and untreated chronic MAC patients) was 25.6%. The mortality rate was 33.3% for untreated chronic MAC patients only vs. 22.2% for treated MAC patients (P = 0.30). After adjustment for clinical, microbiological and radiological confounders, independent factors for 5-year mortality were a high Charlson comorbidity index in cases with definite MAC disease (hazard ratio [HR] 1.76) and untreated chronic MAC (HR 3.08), and presence of cavitary lesions in cases with definite MAC disease (HR 1.82) and treated MAC patients (HR 3.91). CONCLUSION: Patients with cavitary lesions require immediate treatment for sputum culture conversion and to improve their chances of survival.