Pulmonary Mycobacterium Avium-intracellulare Complex Disease Research Articles

Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment

BackgroundClofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD. MethodsThis prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included. ResultsThe steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study. ConclusionCFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Treatment outcomes and relapse in patients with Mycobacterium avium-intracellulare complex pulmonary disease.

The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0-483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0-483), and the 1-year relapse rate was 17%.

Detection of Mycobacterium avium-intracellulare Complex (MAC) by Bronchial Lavage and the Relationship with Titers of Anti-Glycopeptidolipid-Core IgA Antibodies to MAC in Patients with Pulmonary MAC Disease.

Higher rates of diagnosis of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease by bronchoscopy (BS) in patients who could not diagnose by sputum cultures have been suggested, but the detailed utility of BS, especially in combination with anti-glycopeptidolipid-core IgA antibodies (anti-MAC Ab), is still unclear. A total of 111 patients at our hospital with suspected MAC who underwent BS because they were sputum-negative from April 2018 to March 2022 were analyzed prospectively. These patients were also divided into two groups, anti-MAC Ab-positive and anti-MAC Ab-negative, and compared. A total of 111 patients underwent BS, though 95 (38.0%) of 250 enrolled patients were sputum smear/culture-positive. The age of the 111 patients was 69.14 (31.0-89.0) years, and 90 (81.0%) were female; 69 (62.2%) of 111 patients were either smear-positive (n = 42, 37.8%) or culture-positive (n = 27, 24.3%) by BS. Of the total 111 patients, 69 (62.2%) were anti-MAC Ab-positive and 57 (82.6%) of 69 patients were also positive by BS. In contrast, only 12 (28.6%) of the 42 anti-MAC Ab-negative patients were positive by BS. The sensitivity and specificity of anti-MAC Ab for positive by BS were 82.6% and 71.4%, respectively, and the area under the curve (AUC) on receiver-operating characteristic (ROC) curve analysis was 0.807. BS and anti-MAC Ab showed similar usefulness to confirm the diagnosis in patients who could not be diagnosed by sputum examination, but pulmonary MAC disease was strongly suspected based on chest radiography/CT findings. These two examinations were correlated, and their combination appeared to provide more accurate diagnosis and earlier therapy.

Long-Term Prognosis and Antimycobacterial Glycolipid Antibody as Biomarker in Mycobacterium avium-intracellulare Complex Pulmonary Disease.

ABSTRACTClinical characteristics and outcomes of multidrug chemotherapy have been used as the main prognostic factors for Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) over the last decade; however, no useful prognostic biomarkers have been reported. The aim is to ascertain whether the serum antibody titers could include useful prognostic predictors of MAC-PD. Ninety-four patients with MAC-PD were enrolled and regularly followed up with for more than 5 years or until death. Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses were used to identify predictors of mortality in this prospective observational study. According to treatment outcomes, 85 patients completed follow-up and were classified into four groups. Seventeen patients (20%) died during follow-up (median, 10.1 years; interquartile range, 8.1 to 12.4 years). All 11 patients with MAC-PD-specific death were included in the 14 patients of the group nonresponsive to the multidrug chemotherapy. They had significantly higher anti-Mycobacterium glycolipid (MBGL) antibody titers than those in the other groups and a significantly (P < 0.0001) poorer survival prognosis. The anti-MBGL antibody titers also served as a negative prognostic factor. A cutoff score of 7, which was calculated by clinical poor prognostic characteristics and anti-MBGL antibody titers, differentiated the nonresponse group and the other groups at baseline (sensitivity, specificity, and area under the curve: 92.9%, 81.7%, and 0.95, respectively). In conclusion, anti-MBGL antibody titers were useful to assess the refractory MAC-PD. The predictions of treatment outcome and mortality become more accurate by using anti-MBGL antibody and clinical poor prognostic characteristics together.IMPORTANCE The natural history of MAC-PD is challenging to predict in immunocompetent patients at diagnosis, and the current multidrug chemotherapy options are not strong enough to eliminate mycobacteria from the lungs. Therefore, the diagnosis of MAC-PD does not necessarily lead to the decision to start chemotherapy. We have also observed refractory patients in clinical practice, who were resistant to multiple-drug chemotherapy and showed persistent excretion of MAC bacilli and progressive worsening of chest radiographic findings until death. We have reported that the measurements of anti-MBGL antibody titers helped assess refractory MAC-PD in this study. Furthermore, the predictions of treatment outcome and mortality become more accurate by using the anti-MBGL antibody in addition to clinical poor prognostic characteristics, which were older age, lower body mass index, the positive results of a smear test for acid-fast bacteria (AFB), and presence of cavitary disease.

Comparative genomic analysis of Mycobacterium intracellulare: implications for clinical taxonomic classification in pulmonary Mycobacterium avium-intracellulare complex disease

BackgroundMycobacterium intracellulare is a representative etiological agent of emerging pulmonary M. avium-intracellulare complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary M. avium-intracellulare complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for M. avium; however, the genomic characteristics of M. intracellulare remain to be elucidated.ResultsIn this study, we performed comparative genomic analysis of 55 M. intracellulare and related strains such as M. paraintracellulare (MP), M. indicus pranii (MIP) and M. yonogonense. Based on the average nucleotide identity, the clinical M. intracellulare strains were phylogenetically grouped in two clusters: (1) the typical M. intracellulare (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., fadE3, fadE33), transporters (e.g., mce3), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. M. intracellulare was shown to be pan-genomic at the species and subspecies levels. The mce genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies.ConclusionsOur data suggest that genomic diversity among M. intracellulare, M. paraintracellulare, M. indicus pranii and M. yonogonense remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as mce genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for M. intracellulare and related strains.

A CASE OF MAC IN A PATIENT WITH CHRONIC SILICOSIS

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Our patient is a 32-year-old male with chronic silicosis who presented with one week of worsening dyspnea and cough in the setting of a 40 pound weight loss over 3 months. CASE PRESENTATION: The patient was diagnosed with silicosis in 2015 (Image 1) in the setting of prolonged work with cutting porous stone without use of PPE; he had a negative mycobacterial work-up then. He was lost to follow-up and continued to work until one week prior to this presentation. On hospital presentation he was found to be febrile, severely cachectic, using accessory muscles for respiration, and with fine bilateral inspiratory crackles diffusely. He was subsequently admitted to the ICU for hypercapnic and hypoxemic respiratory failure requiring non-invasive ventilation (NIV). CT findings suggested progressive massive fibrosis (PMF) with eggshell calcifications of mediastinal lymph nodes; however, a cavitary infectious process could not be ruled out (Image 2 and 3). He was started on empiric antibiotics for bacterial pneumonia. Laboratory testing revealed negative bacterial, fungal, and viral sputum/blood cultures. He showed marginal improvement in respiratory status after initiating NIV and completing antibiotics. Although the initial AFB sputum smears were negative, two weeks later two separate AFB cultures each grew Mycobacterium Avium Complex (MAC). He was fully weaned off NIV after starting anti-mycobacterial therapy. Given the imaging and his clinical improvement, this decompensation was thought to be secondary to PMF with MAC superinfection. DISCUSSION: Silicosis occurs following chronic occupational exposure to aerosolized silica from mining, stone cutting, or sandblasting. Patients often are asymptomatic despite abnormal x-ray findings. Imaging of chronic silicosis typically follows nodular patterns of inflammation (which was noted on our patient's initial diagnosis) and in more acute presentations ground-glass opacities and crazy paving have been described. Our patient's clinical presentation and CT findings of diffuse coalescent densities and cavitations led us to consider PMF and mycobacterial disease over simple silicosis. PMF is a rare, and in most cases irreversible, complication of silicosis defined as conglomeration of dense fibrosis preferentially involving the upper lung lobes. Eggshell calcifications of lymph nodes are often described. Mycobacterial infection is also a rare complication of silicosis, classically with mycobacterium tuberculosis (TB); however there have been many case reports with silicosis patients developing MAC infections. These mycobacterial infections present with constitutional and TB-like symptoms such as weight loss. CONCLUSIONS: Progressive massive fibrosis in silicosis is a rare complication that leads to severe structural lung disease and respiratory failure. Mycobacterial superinfection, including MAC, should be considered in decompensated patients with silicosis. Reference #1: Jiro Fujita,Takumi Kishimoto,Yuji Ohtsuki,Eriko Shigeto,Takayuki Ohnishi,Masahiro Shiode,Yasufumi Yamaji,Ichizo Suemitsu,Ichiro Yamadori,Shuji Bandoh,Kazutaka Nishimura,Toshiharu Matsushima,Toshihiko Ishida. Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis. Respir Med. 2004 Aug;98(8):721-5. DISCLOSURES: No relevant relationships by Neel Bhan, source=Web Response No relevant relationships by Nicola Hanania, source=Web Response No relevant relationships by Lauren Nicholas Herrera, source=Web Response No relevant relationships by Hal Zhang, source=Web Response

Different clinical features of patients with pulmonary disease caused by various Mycobacterium avium–intracellulare complex subspecies and antimicrobial susceptibility

ObjectivesCharacteristics of the Mycobacterium avium–intracellulare complex pulmonary disease (MAC-PD) caused by distinct subspecies remain uncertain. MethodsThis study was conducted from 2013–2015 in three hospitals in Taiwan. ResultsAmong the 144 patients with MAC-PD, 57 (39.6%), 37 (25.7%), 37 (25.7%), and 13 (9.0%) were infected with Mycobacterium intracellulare subspecies intracellulare (MIsI), Mycobacterium avium subspecies hominissuis (MAsH), Mycobacterium intracellulare subspecies chimaera (MIsC), and others, respectively. Patients with MAsH-PD were younger (p = 0.010) with higher human immunodeficiency virus infection rates (27.0%, 0.0%, 0.0%, and 7.7% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p < 0.001). Twenty-two (15.3%) patients reported spontaneous culture-negative conversion, but 15 (10.4%) and 33 (22.9%) patients developed radiographic progression and unfavorable outcomes, especially MAsH-PD. The susceptibility rates to clarithromycin and inhaled amikacin were both 98.6%. MAsH demonstrated the lowest rate of resistance to moxifloxacin (66.7%, 97.3%, 89.1%, and 92.3% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.001) and MIsI isolates had the highest rate of resistance to intravenous amikacin (25%, 13.5%, 38.2%, and 15.4% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.024). ConclusionsPulmonary disease caused by distinct MAC subspecies had different outcomes and drug susceptibility. The local prevalence of species needs to be monitored.

Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex disease.

To perform a systematic review and meta-analysis of the level of funding support and the sputum culture conversion rates in pulmonary Mycobacterium avium-intracellulare complex (P-MAC) disease in adult patients without cystic fibrosis or HIV infection, treated with recommended antibiotic regimens. We performed a literature search to identify clinical trials, prospective studies and registries that reported outcomes in P-MAC patients. Studies that reported P-MAC diagnosis and treatments based on established guidelines met the inclusion criteria and were examined for bias and quality. We modified existing quality scales and came up with a 10 star quality score. Outcomes meta-analysed were sputum conversion incidence ratios (IR) and their 95% CI, weighted for study quality. Twenty-one studies that examined 28 regimens, including 2534 patients in intent-to-treat analyses and 1968 in per-protocol analyses, were identified. The study quality mean ± SD scores were 5.4 ± 2.2 out of 10 stars. Only two (9.5%) studies received public funding. There was significant heterogeneity of microbial effect among treatment regimens (I2 > 40%; P > 0.001). The pooled IR for sustained sputum conversion was 0.54 (95% CI 0.45-0.63) for macrolide-containing regimens versus 0.38 (0.25-0.52) with macrolide-free regimens. Prolonging therapy duration beyond 12 months was associated with an average decline in sputum conversion to 22% (95% CI 1%-44%). Researchers working on P-MAC therapy have received very little public funding support. As a result, the evidence base for treatment guidelines is based on studies of relatively small numbers of patients in low-quality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.

A 'shock and awe' thioridazine and moxifloxacin combination-based regimen for pulmonary Mycobacterium avium-intracellulare complex disease.

To develop a thioridazine/moxifloxacin-based combination regimen for treatment of pulmonary infection due to Mycobacterium avium-intracellulare complex (MAC) that kills bacteria faster than the standard treatment regimen. Monocytes were infected with MAC and inoculated into the hollow-fibre system model for pulmonary MAC disease (HFS-MAC). We co-administered ethambutol plus azithromycin daily for 28 days, to achieve the same human concentration-time profiles that result from standard doses, in three HFS-MAC systems. Two experimental regimens consisted of thioridazine at an exposure associated with optimal kill, given intermittently on days 0, 3, 7 and 10. Regimen A consisted of thioridazine in combination with standard dose azithromycin for the entire study duration. Regimen B was thioridazine plus moxifloxacin at concentration-time profiles achieved by the standard daily dose administered for 14 days, followed by daily azithromycin. Each HFS-MAC was sampled for bacterial burden every 7 days. The bacteria in the non-treated HFS-MAC grew at a rate of 0.11 ± 0.01 log10 cfu/mL/day. The azithromycin/ethambutol regimen decreased bacterial burden by 1.21 ± 0.74 log10 cfu/mL below baseline during the first 7 days, after which it failed. Regimen A killed 3.28 ± 0.32 log10 cfu/mL below baseline up to day 14, after which regrowth occurred once thioridazine treatment stopped. Regimen B killed bacteria to below the limits of detection in 7 days (≥5.0 log10 cfu/mL kill), with rebound in the azithromycin continuation phase. The thioridazine/moxifloxacin regimen demonstrated that rapid microbial kill could be achieved within 7 days. This is a proof of principle that short-course chemotherapy for pulmonary MAC is possible.

The characteristics of patients with pulmonary Mycobacterium avium-intracellulare complex disease diagnosed by bronchial lavage culture compared to those diagnosed by sputum culture.

The utility of bronchoscopy for the diagnosis of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease has been reported; however, which patients require bronchoscopy remains unclear. Our objective was to identify the characteristics of the patients in whom bronchoscopy is needed for the diagnosis of MAC disease. Fifty-four patients with pulmonary MAC disease were divided into two groups according to established diagnostic criteria: 39 patients were diagnosed by sputum culture and 15 patients were diagnosed by bronchial lavage culture. We analysed the differences in demographic and clinical characteristics as well as microbiological and radiological data between the two groups. There were no significant differences in age, sex, smoking status, MAC species, underlying diseases, or steroid use. Significantly more patients diagnosed by sputum culture than bronchial lavage culture had a positive sputum smear for acid-fast bacilli (79.5% vs. 0.0%, respectively; p<0.001) and any symptoms (75.3% vs. 46.2%, respectively; p=0.0059). No significant differences were found in the prevalence of each computed tomography finding, including nodules, air-space disease, bronchiectasis, and cavities. However, more patients diagnosed by sputum culture than bronchial lavage culture had abnormalities in the left upper division (48.7% vs. 13.3%, respectively; p=0.017) and higher numbers of affected lobes (4.3±1.4 vs. 3.3±1.6, respectively; p=0.034). If patients suspected of having pulmonary MAC disease have a negative sputum smear, no symptoms, no abnormal findings in the left upper division, or fewer affected lobes on computed tomography, bronchoscopy might be needed for the diagnosis.

気管支型の肺Mycobacterium avium-intracellulare complex症診断における気管支鏡検査の有用性

気管支型の肺Mycobacterium avium-intracellulare complex症診断における気管支鏡検査の有用性

Thoracic imaging manifestations of mycobacterium avium-intracellulare complex infection in patients with acquired immunodeficiency syndrome

Objective To study the chest imaging manifestations of mycobacterium avium-intracellulare complex (MAC) infection in patients with acquired immunodeficiency syndrome(AIDS). Methods Thirty-one cases of proven AIDS and MAC infection were included in the study. Imaging findings and clinical data of the patients were retrospectively analyzed. Results All 31 patients underwent chest X-ray and/or chest CT examination, three patients were normal, 28 patients showed findings of lung infection. The chest CT imaging findings of MAC lung infection in AIDS patients were similar with pulmonary TB, including air space consolidation (21 cases) with three cases of large consolidation, bronchiectasis (18 cases), nodules (18 cases), miliary nodules (10 cases), cavities (10 cases), pleural effusion (10 cases), predominantly moderately enlarged mediastinal lymph nodes (15 cases), and enlarged hilus lymph nodes (7 cases). Conclusions The imaging manifestations of MAC infection in AIDS patients were varied and atypical. Air space consolidation,small nodules and bronchiectasis were the main CT manifestations of MAC pulmonary disease. Key words: Acquired immunodefieieney syndrome; Mycobacterium infections; Tomography, X-ray computed

Genetic relatedness of Mycobacterium avium-intracellulare complex isolates from patients with pulmonary MAC disease and their residential soils

Mycobacterium avium-intracellulare complex (MAC) strains were recovered from 48.9% of residential soil samples (agricultural farms (n = 7), residential yards (n = 79), and planting pots (n = 49)) of 100 pulmonary MAC patients and 35 non-infected control patients. The frequency of MAC recovery did not differ among soil types or among patients regardless of the presence of pulmonary MAC disease, infecting MAC species or period of soil exposure. Variable numbers of tandem repeats (VNTR) analysis for MAC clinical and soil isolates revealed 78 different patterns in 47 M. avium clinical isolates and 41 soil isolates, and 53 different patterns in 18 M. intracellulare clinical isolates and 37 soil isolates. Six clinical and corresponding soil isolate pairs with an identical VNTR genotype were from case patients with high soil exposure (≥2 h per week, 37.5% (6/16) with high exposure compared with 0.0% (0/19) with low or no exposure, p <0.01), suggesting that residential soils are a likely source of pulmonary MAC infection.

High-resolution computed tomography and health-related quality of life in Mycobacterium avium complex disease

Kyoto, Japan. To validate the St George's Respiratory Questionnaire (SGRQ) in pulmonary Mycobacterium avium-intracellulare complex disease and to analyse the significance of high-resolution computed tomography (HRCT) findings as determinants of health-related quality of life (HRQoL) after adjusting for clinical and physiological parameters. Eighty-five patients completed the SGRQ, pulmonary function tests and other patient-reported measurements. HRCT findings were assessed using an established computed tomography (CT) scoring method. The SGRQ was validated with good internal consistency, test-retest reliability and significant correlations with most physiological variables and other patient-reported measurements. White blood cell counts, C-reactive protein levels, sputum culture results, treatment history, total CT scores, and consolidation, cavity and lobar volume-decrease CT component scores were significantly correlated with the SGRQ total and component scores. Stepwise multiple regression analyses revealed that the consolidation, cavity and lobar volume-decrease component scores were correlated with the SGRQ total and/or component scores. The total CT scores had the strongest relationships with the SGRQ total scores among the various clinical parameters tested, including microbiological, radiological, physiological and laboratory findings (32.8% of variance). HRCT findings, particularly consolidation, cavity and lobar volume-decreases, were the most significant clinical parameters related to patient HRQoL.

Predictors of 5-year mortality in pulmonary &lt;I&gt;Mycobacterium avium-intracellulare&lt;/I&gt; complex disease

Kyoto, Japan. To determine predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex (MAC) disease. Retrospective study of 164 patients diagnosed with pulmonary MAC disease between 1999 and 2005 and followed for 5 years. 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). Patients with cavitary lesions require immediate treatment for sputum culture conversion and to improve their chances of survival.

Environmental Risk Factors for Pulmonary Mycobacterium avium-intracellulare Complex Disease

Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous pathogen found in soil and water. Environmental exposure is the primary route for MAC infection. However, specific environmental risk factors have been poorly determined in immunocompetent patients with pulmonary MAC disease. A case-control study was performed with 106 patients with pulmonary MAC disease (men [women], 23 [83]; age, 64.3 ± 9.2 years) and 53 age-matched control patients with bronchiectasis but not pulmonary MAC infection (men [women], 7[46]; age, 63.0 ± 11.0 years). All participants completed a standardized questionnaire that included questions about medical history, smoking history, alcohol usage, age at menopause, and environment exposures. Environment exposures included soil exposure from farming or gardening; water exposure from bathing, showering, hot tub use, dishwashing, swimming, and drinking water; and pet exposure. No differences were identified in the patient characteristics and underlying diseases. More case patients experienced high soil exposure (≥ 2 per week) than control patients (23.6% vs 9.4%, P = .032); this remained significant after multivariate analysis (OR, 5.9; 95% CI, 1.4-24.7; P = .015). There were no significant differences in other environmental exposures. Case patients with high soil exposure were significantly older than those with low soil exposure (67.3 ± 7.3 years vs 64.3 ± 9.5 years, P = .037). Other characteristics, underlying diseases, and mycobacterial species did not differ between the two groups. Patients with pulmonary MAC disease had significantly more soil exposure than noninfected control patients, which suggests that environmental soil exposure is a likely risk factor for the development of pulmonary MAC disease.

Elevated Serum Adiponectin Level in Patients with Mycobacterium avium-intracellulare Complex Pulmonary Disease

Background: Patients with Mycobacterium avium-intracellulare complex (MAC) pulmonary disease often suffer from weight loss. Adipokines are factors secreted by adipocytes, including leptin and adiponectin, as well as some inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Body mass index (BMI) is known to be inversely correlated with adiponectin and positively with leptin, TNF-α, and IL-6. Objective: We aimed to evaluate the levels of serum adipokines, including adiponectin, leptin, TNF-α, and IL-6 in patients with MAC pulmonary disease. Methods: Forty consecutive patients with MAC pulmonary disease (8 males; median age 62 years; median BMI 18.1) were examined. Serum levels of adiponectin, leptin, TNF-α, and IL-6 were measured with ELISA. Age-, sex- and BMI-matched healthy subjects served as controls. Results: Serum adiponectin was significantly elevated in patients with MAC pulmonary disease compared with the controls (p < 0.01). In both the patients and controls, serum adiponectin levels were inversely correlated with BMI (p < 0.05). No significant correlation was observed between serum adiponectin levels and C-reactive protein or lung function. Serum leptin levels, which were positively correlated with BMI, did not differ between patients and controls. Serum levels of TNF-α and IL-6 were significantly greater in patients with MAC pulmonary disease than in controls. The levels of TNF-α and IL-6 were not correlated with BMI and other adipokines examined. Conclusion: The results of the present study indicate that, in patients with MAC pulmonary disease, adiponectin is inappropriately secreted and may play a role in the pathophysiology of the disease.

High-Resolution CT Findings of Mycobacterium avium-intracellulare Complex Pulmonary Disease: Correlation with Pulmonary Function Test Results

High-Resolution CT Findings of Mycobacterium avium-intracellulare Complex Pulmonary Disease: Correlation with Pulmonary Function Test Results

High-Resolution CT Findings of Mycobacterium avium-intracellulare Complex Pulmonary Disease: Correlation with Pulmonary Function Test Results

The purpose of our study was to analyze the high-resolution CT findings of the nodular bronchiectatic form of Mycobacterium avium-intracellulare complex (MAC) pulmonary disease and to correlate the extent of high-resolution CT findings with pulmonary function test (PFT) results. From January 2005 through December 2005, we identified 47 patients (mean age, 58 +/- 13 years; age range, 24-72 years; male-female ratio, 11:36) with the nodular bronchiectatic form of MAC pulmonary disease who underwent both high-resolution CT and PFTs. High-resolution CT findings were reviewed retrospectively in terms of the presence and extent of bronchiectasis, cellular or inflammatory bronchiolitis (centrilobular small nodules and tree-in-bud signs), cavity, nodule, and other findings. The extent of the abnormalities seen on high-resolution CT was scored by modifying the cystic fibrosis scoring system proposed by Helbich and coworkers. The scores were correlated with PFT results using Spearman's correlation coefficient. On high-resolution CT, the three most frequently observed patterns of parenchymal abnormalities were, in decreasing order of frequency, cellular bronchiolitis (n = 47, 100%), bronchiectasis (n = 46, 98%), and consolidation (n = 27, 57%). The total CT score showed a significant correlation with the residual volume-total lung capacity (RV/TLC) ratio (r = 0.572, p < 0.001), forced expiratory volume in 1 second (FEV(1)) value (r = -0.426, p = 0.003), forced vital capacity (FVC) value (r = -0.360, p = 0.013), peak expiratory flow value (r = -0.352, p = 0.015), and peak expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75%)) (r = -0.289, p = 0.049). CT scoring of pulmonary abnormalities correlates with measures of functional impairment in patients with MAC pulmonary disease.

Antibacterial activity and clinical efficacy of sparfloxacin in Mycobacterium avium-intracellulare complex infection.

In Japan the incidence of atypical mycobacteriosis has steadily increased, with Mycobacterium avium-intracellulare complex (MAC) the most common infecting organism. A standard chemotherapy regimen for MAC infection has not been established because of significant resistance to anti-mycobacterial drugs. Sparfloxacin has good antimicrobial activity against several acid-fast bacteria and is expected to be an effective drug for treating mycobacteriosis. We examined the effects of adding sparfloxacin to anti-tuberculotic combination therapy in six patients with MAC pulmonary disease. Drug susceptibility was also assessed using the agar dilution method. The minimum inhibitory concentrations (MICs) for sparfloxacin, levofloxacin, isoniazid, rifampicin, streptomycin, ethambutol and clarithromycin was measured in clinical isolates from all patients; sparfloxacin showed the lowest MIC. Bacteriological and clinical improvements were observed in the four patients who completed the study. Dosing was discontinued in two patients because of pruritic skin eruptions. Sparfloxacin shows promise as an anti-mycobacterial agent for treating MAC pulmonary disease.