Difference in drug susceptibility distribution and clinical characteristics between Mycobacterium avium and Mycobacterium intracellulare lung diseases in Shanghai, China.

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria.Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare.Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species (Mycobacterium avium and Mycobacterium intracellulare) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions.Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M. intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions.Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml-1) than M. intracellulare (8 µg ml-1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml-1) than M. avium (≤0.25 µg ml-1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections.Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.

Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure.

BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.

Distribution and outcomes of infection of Mycobacterium avium complex species in cystic fibrosis.

BACKGROUND: The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking. METHODS: This was a single center, retrospective study. MAC isolates had species identification with MLSA of rpoB and the 16S23S ITS region. Clinical data were compared between species. RESULTS: Twenty-three people with CF and 57 MAC isolates were included. Infection with M. avium was the most common (65.2%). M. intracellulare was associated with higher rates of NTM disease, younger age, and steeper decline in lung function prior to infection. CONCLUSIONS: We observed worse clinical outcomes in people with M. intracellulare infection relative to other MAC species. Further investigation of clinical outcomes of MAC infection among CF patients is warranted to better define the utility of species-level identification of MAC isolates in CF.

Outcomes and risk factors after adjuvant surgical treatments for Mycobacterium avium complex lung disease.

BACKGROUND: Limited information is currently available on the postoperative outcomes of Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVE: To show the outcomes of pulmonary resection and identify risk factors after adjuvant surgical treatments for MAC-LD. METHODS: One hundred and eight patients underwent adjuvant lung resection for MAC-LD at two hospitals between January 2008 and July 2016. We retrospectively evaluated outcomes and risk factors. RESULTS: Postoperative complications occurred in 14 patients (13%). After lung resection, 98 out of 108 patients (91%) achieved sputum culture conversion, eight (8.2%) of whom developed microbiological recurrence during the follow-up period. As a result, the success rate of adjuvant surgical treatments for MAC-LD with drug resistance was 83%. A multivariable analysis showed that a longer period from the initial medical treatment to surgery (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p = 0.008) was independently associated with an increased risk of unfavorable outcomes after adjuvant surgery. CONCLUSIONS: Adjuvant surgical treatments for MAC-LD have acceptable outcomes. Better control of the disease may be achieved in some patients with drug resistance and indications for surgery through surgical treatments, and pulmonary resection needs to be performed earlier rather than continuing chemotherapy in these patients because it reduces unfavorable outcomes.

Quantitative assessment of erector spinae muscles in patients with Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: No reports exist regarding skeletal muscle involvement in patients with Mycobacterium avium complex lung disease (MAC-LD). The cross-sectional area of the erector spinae muscles (ESMCSA) reflects physical activity and can be assessed by computed tomography (CT). We investigated the relationship between ESMCSA and physiological parameters and prognosis in MAC-LD patients. MATERIAL AND METHODS: In this prospective observational study, the ESMCSA was measured on single-slice axial CT images. MAC-LD patients and sex- and age-matched controls (non-MAC-LD participants) were evaluated. We evaluated the relationship between the ESMCSA and physiological parameters and prognosis. RESULTS: A total of 260 patients (209 female; median age, 69 years; 190 with nodular/bronchiectatic disease; 74 with cavitary lesions) were enrolled. The ESMCSA was not different between MAC-LD patients and controls. In MAC-LD patients, the ESMCSA was significantly associated with age, body mass index (BMI), pulmonary function, CT severity, and health-related quality of life (HRQL). Multivariate Cox proportional hazards analyses revealed that an ESMCSA < -1 standard derivation (hazards ratio [HR], 2.76; P = 0.047) was significantly associated with all-cause mortality, along with BMI < 18.5 kg/m2 (HR, 3.67; P = 0.02) and presence of cavitary lesions (HR, 5.84; P = 0.001). However, the ESMCSA was not significantly associated with all-cause mortality when current treatment status, % predicted functional vital capacity, and forced expiratory volume in 1 s were added to the analyses. CONCLUSIONS: Although the prognostic impact was limited, ESMCSA was significantly associated with HRQL and prognostic physiological parameters, such as BMI and pulmonary function.

Association between six-minute walk test parameters and the health-related quality of life in patients with pulmonary Mycobacterium avium complex disease.

BACKGROUND: Pulmonary Mycobacterium avium complex (pMAC) disease is a chronic, slowly progressive disease. The aim of the present study was to determine the association of six-minute walk test (6MWT) parameters with pulmonary function and the health-related quality of life (HRQL) in patients with pMAC disease. METHODS: This cross-sectional study included adult patients with pMAC and was conducted at Keio University Hospital. We investigated the relationship of 6MWT parameters with clinical parameters, including pulmonary function, and HRQL, which was assessed using the 36-Item Short Form Health Survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ). RESULTS: In total, 103 consecutive patients with pMAC participated in 6MWT (median age, 64 years; 80 women) and completed SF-36 and SGRQ. The six-minute walk distance (6MWD) showed significant negative and positive correlations with all SGRQ domain scores [ρ = (- 0.54)-(- 0.32)] and the physical component summary (PCS) score (ρ = 0.39) in SF-36, respectively; the opposite was observed for the final Borg scale (FBS) score (all SGRQ scores, ρ = 0.34-0.58; PCS score, ρ = - 0.50). The distance-saturation product showed significant negative and positive correlations with all SGRQ scores [ρ = (- 0.29)-(- 0.55)] and the PCS score (ρ = 0.40), respectively. Multivariate analysis revealed that 6MWD and the FBS score were significant predictors of HRQL. CONCLUSIONS: Our findings suggest that 6MWD and the FBS score are useful parameters for evaluating HRQL in patients with pMAC. Further studies should investigate the impact of 6WMT parameters on disease progression, treatment responses, and prognosis.

Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: A cross-sectional study.

RATIONALE: Little is known about the role of Aspergillus precipitating antibody (APAb) in patients with Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVES: We investigated the clinical characteristics of patients with MAC-LD positive for APAb. METHODS: We conducted a cross-sectional study targeting patients with MAC-LD. APAb was checked in all participants. Clinical variables included laboratory data, pulmonary function, high-resolution computed tomography findings, and health-related quality of life. RESULTS: We analyzed 109 consecutive patients. Their median age was 68 years, and the median duration of MAC-LD was 4.8 years. Twenty (18.3%) patients tested positive for APAb. APAb-positive patients had significantly longer duration of MAC-LD (9.4 vs. 4.0 years, P = 0.017), more severe bronchiectasis evaluated by modified Reiff score (6.5 vs. 4, P = 0.0049), and lower forced expiratory volume in 1 s (%FEV1) (75.1% vs. 86.2%, P = 0.013) than APAb-negative patients. Analysis of covariance adjusted for background factors and underlying pulmonary disease revealed that %FEV1 was also significantly lower in patients with APAb (P = 0.045). Ten patients were newly diagnosed with chronic pulmonary aspergillosis (N = 5) or allergic bronchopulmonary aspergillosis (N = 5). CONCLUSIONS: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions.

In Defense of Lady Windermere Syndrome.

Defense of Lady Windermere Syndrome (LWS) provides a critical analysis of its proposed pathogenesis, evidence supporting a causal role of volitional cough suppression, pathogenesis of M. avium complex (MAC) superimposition, a defense of the eponym, and cites a possible contribution of LWS to the bronchiectasis population.

Nontuberculous mycobacterial empyema in an immunocompetent child.

Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium Tuberculosis complex and Mycobacterium leprae. There are very few reports of NTM in immunocompetent children causing empyema. In this article, we report a 9-year-old immunocompetent girl who presented with Mycobacterium avium-intracellulare empyema.

Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease.

BACKGROUND: In bronchiectasis patients, chronic Pseudomonas aeruginosa (PA) infection has been associated with worse health-related quality of life (HRQL), but little is known about Mycobacterium avium complex lung disease (MACLD) patients in this context. This study aimed to evaluate HRQL and investigate the impact of chronic PA infection in MACLD patients. METHODS: This cross-sectional study was conducted using the Registry of Prospective Cohort Study including MACLD patients. The 36-item Short-Form health survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ) were administered to assess clinical outcomes. Clinical variables included treatment and sputum culture status, pulmonary function tests, cavitary lesions, and modified Reiff scores on high-resolution computed tomography. RESULTS: The study included 244 MACLD patients (median age, 68 years; 196 women), 19 of whom had chronic PA infection. Modified Reiff score was higher in patients with chronic infection than in those without (P = 0.028). Regarding SF-36 scores, physical functioning subscale scores were significantly lower in patients with chronic infection (P = 0.029). Additionally, SGRQ symptoms, impact, and total scores were significantly higher in patients with chronic infection. During analysis of covariance comparisons, SGRQ symptoms and impact scores were significantly higher for patients with chronic infection (P = 0.043 and 0.021, respectively). CONCLUSIONS: MACLD patients with chronic PA infection exhibited significantly higher SGRQ scores, indicating impaired HRQL. Chronic PA infection was significantly associated with the severity of bronchiectasis.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course.

Little is known about the long-term natural history of Mycobacterium avium complex lung disease (MAC-LD) in untreated patients with stable course.The aim of this study was to investigate the natural course of untreated stable MAC-LD, with a focus on factors associated with clinical deterioration, spontaneous sputum conversion and prognosis.Of 488 patients diagnosed with MAC-LD between 1998 and 2011, 305 patients (62.5%) showed progressive MAC-LD resulting in treatment initiation within 3 years of diagnosis and 115 patients (23.6%) exhibited stable MAC-LD for at least 3 years with a median follow-up duration of 5.6 years. Patients with stable MAC-LD were more likely to have higher body mass index and less systemic symptoms at initial diagnosis compared with patients with progressive MAC-LD, while positive sputum acid-fast bacilli smear, fibrocavitary type and more extensive disease in radiological findings were more associated with progressive MAC-LD. Of the untreated patients with stable MAC-LD, 51.6% underwent spontaneous sputum conversion, with younger age, higher body mass index and negative sputum acid-fast bacilli smear at initial diagnosis found to be predictors of this occurrence.Advanced age, fibrocavitary type and abnormal pulmonary function were negative prognostic factors for survival in patients with stable MAC-LD.

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.

Proton Magnetic Resonance Imaging for Initial Assessment of Isolated Mycobacterium avium Complex Pneumonia.

RATIONALE: Computed tomographic (CT) radiography is the reference standard for imaging Mycobacterium avium complex (MAC) lung infection. Magnetic resonance imaging (MRI) has been shown to be comparable to CT for characterizing other pulmonary inflammatory conditions, but has not been rigorously tested for imaging MAC pneumonia. OBJECTIVES: To determine the feasibility of pulmonary MRI for imaging MAC pneumonia and to assess the degree of agreement between MRI and CT for assessing the anatomic features and lobar extent of MAC lung infections. METHODS: Twenty-five subjects with culture-confirmed MAC pneumonia and no identified coinfecting organisms were evaluated by thoracic MRI and then by chest CT imaging performed up to 1 week later. After deidentification, first the MRI and then the CT scans were scored 2 weeks apart by two chest radiologists working independently of one another. Discrepancies were resolved by a third chest radiologist. The scans were scored for bronchiectasis, consolidation or atelectasis, abscess or sacculation, nodules, and mucus plugging using a three-point lobar scale (absent, <50% of lobe, and >50% of lobe). Agreement analyses and ordinary least products regressions were performed. MEASUREMENTS AND MAIN RESULTS: A fixed bias was found between total CT and MRI scores, with CT scoring higher on average (median difference: 4 on a scale of 48; interquartile range: 3, 6). Fixed biases were found for bronchiectasis and consolidation or atelectasis subscale scores. Both fixed and proportional biases were found between CT and MRI mucus plugging scores. No bias was found between CT and MRI nodule scores. There was nearly perfect lobar percent agreement for more conspicuous findings such as consolidation or atelectasis and abscess or sacculation. CONCLUSIONS: In this exploratory study of 25 adult patients with culture-proven MAC lung infection, we found moderate agreement between MRI and CT for assessing the anatomic features and lobar extent of disease. Given the feasibility of chest MRI for this condition, future work is warranted to assess the clinical impact of MRI compared with CT in assessing progression of untreated MAC infection and response to treatment over time.

A Case of Rapid Exacerbation of Pulmonary Mycobacterium Avium Complex Infection Mimicking Pulmonary Aspergillosis.

We herein report a case of pulmonary Mycobacterium avium complex (MAC) infection with pulmonary multiple nodules and the "halo sign" on chest computed tomography (CT) in which the patient showed rapid exacerbation seven years after undergoing bone marrow transplantation (BMT). A 68-year-old Japanese female visited our hospital due to a productive cough and dyspnea. She had undergone allogeneic BMT for acute myelocytic leukemia and received both prednisolone (2 mg/day) and cyclosporine (30 mg/day). Chest CT demonstrated no abnormal findings on admission; however, multiple pulmonary nodules and the "halo sign" were detected three weeks later. Although a fungal infection was initially suspected, a bronchoscopic examination revealed pulmonary MAC infection. In the present case, pulmonary MAC infection exhibited rapid progression with unique CT findings. Physicians should consider MAC infection in the differential diagnosis in patients who receive BMT and/or immunosuppressive agents, even if the clinical and radiological findings are atypical of the disease.

A unique case of hot tub lung worsening during the winter.

Summer-type hypersensitivity pneumonitis includes a spectrum of granulomatous lung diseases that result from the inhalation of Trichosporon species in the summer. Hot tub lung is a granulomatous lung disease caused by the inhalation of water aerosols containing non-tuberculous mycobacteria. We herein describe a case of hot tub lung that deteriorated during the winter season. Every winter, the patient's symptoms, laboratory findings and chest images worsened. Genetically identical Mycobacterium avium strains were detected in his sputum and bathtub. The circulation of bathtub water during the winter months only exacerbated his symptoms in the winter.

Risk factors for deterioration of nodular bronchiectatic Mycobacterium avium complex lung disease.

UNLABELLED: SETTING The long-term natural course of Mycobacterium avium complex (MAC) disease with nodular bronchiectasis, the most common pulmonary non-tuberculous mycobacterial disease, is not well described. OBJECTIVE: To identify risk factors for the deterioration of nodular bronchiectatic MAC lung disease over a 5-year follow-up period. DESIGN: Clinical and laboratory data of 67 patients with nodular bronchiectatic MAC lung disease were collected. Chest computerised tomographic images were used to count the number of lung segments involved at diagnosis and measure subcutaneous fat thickness during follow-up. RESULTS: The 34 patients who showed deterioration had significantly lower body mass index (BMI) (P = 0.004) and % predicted forced vital capacity (P = 0.032), higher numbers of lung segments involved (P < 0.001) and MAC-positive sputum cultures (P = 0.028), and thinner chest subcutaneous fat during follow-up (P < 0.001) than patients without deterioration. In particular, patients with both BMI <21.0 kg/m(2) and more than four lung segments involved had a 240-fold increased risk of deterioration (P < 0.001). CONCLUSION: Patients with poor nutritional status and extensive lung involvement tend to experience deterioration of nodular bronchiectatic MAC lung disease.