Mycobacterium Avium Complex Pulmonary Disease Research Articles

Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.

Myosteatosis as a prognostic factor of Mycobacterium avium complex pulmonary disease

Quantitative body composition affects the prognosis of patients with Mycobacterium avium complex pulmonary disease (MAC-PD). However, whether the qualitative body composition obtained indirectly through computed tomography (CT) affects their prognosis is debatable. We retrospectively analyzed patients with MAC-PD who underwent non-contrast CT at MAC-PD diagnosis. The cross-sectional area of the erector spinae muscle (ESM area), the Hounsfield unit of the erector spinae muscle (ESM HU), and the cross-sectional area of subcutaneous fat (SQF area) were measured at the level of the first lumbar vertebra. Myosteatosis were defined below the median value of ESM HU for each sex. Of 377 patients, 45 (11.9%) died during the follow-up. Patients who died were older and had a lower ratio of females (33.3%). In body compositions, SQF area and ESM HU were lower in the patients who died. In multivariable analysis, a low ESM HU was associated with increased mortality (ESM HU adjusted hazard ratio [aHR] 0.95, 95% confidence interval [CI] 0.93–0.97) through body composition. SQF area revealed protective effects in MAC-PD patients with body mass index ≥ 18.5 kg/m2 (aHR 0.98, 95% CI 0.95–1.00). In conclusion, the decrease in ESM HU, which indirectly reflects myosteatosis, is associated with mortality in patients with MAC-PD.

In vitro and intracellular activities of novel thiopeptide derivatives against macrolide-susceptible and macrolide-resistant Mycobacterium avium complex.

Unsatisfactory outcomes following long-term multidrug treatment in patients with Mycobacterium avium complex (MAC) pulmonary disease have urged us to develop novel antibiotics. Thiopeptides, a class of peptide antibiotics derived from natural products, have potential as drug candidates that target bacterial ribosomes, but drug development has been hampered due to their extremely poor solubility. Here, we evaluated three new compounds (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2 with enhanced aqueous solubility; the derivatives were generated based on structure-activity relationship analysis. We conducted in vitro drug susceptibility and intracellular antimycobacterial activity testing of the three thiopeptide derivatives against various MAC strains, including macrolide-resistant MAC clinical isolates. These compounds showed low MICs against MAC, similar to that of clarithromycin (CLR). In particular, two compounds, AJ-037 and AJ-206, had intracellular antimycobacterial activities, along with synergistic effects with CLR, and inhibited the growth of MAC inside macrophages. Moreover, these two compounds showed in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing cross-resistance with CLR. Taken together, the results of the current study suggest that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infection, including for macrolide-resistant MAC strains. IMPORTANCE Novel antibiotics for the treatment of MAC infection are urgently needed because the treatment outcomes using the standard regimen for Mycobacterium avium complex (MAC) pulmonary disease remain unsatisfactory. Here, we evaluated three novel thiopeptide derivatives (AJ-037, AJ-039, and AJ-206) derived from the thiopeptide micrococcin P2, and they were confirmed to be effective against macrolide-susceptible and macrolide-resistant MAC. Our thiopeptide derivatives have enhanced aqueous solubility through structural modifications of poorly soluble thiopeptides. The thiopeptide derivatives showed minimal inhibitory concentrations against MAC that were comparable to clarithromycin (CLR). Notably, two compounds, AJ-037 and AJ-206, exhibited intracellular antimycobacterial activities and acted synergistically with CLR to hinder the growth of MAC within macrophages. Additionally, these compounds demonstrated in vitro and intracellular anti-MAC activities against macrolide-resistant MAC strains without showing any cross-resistance with CLR. We believe that AJ-037 and AJ-206 can be promising anti-MAC agents for the treatment of MAC infections, including macrolide-resistant MAC strains.

Longitudinal changes in radiographic features of pulmonary Mycobacterium avium complex diseases

BackgroundThe radiographic features of Mycobacterium avium complex pulmonary disease (MAC-PD), a major component of nontuberculous mycobacteria, consist of a variety of lesions; however, the responsiveness of each type of radiographic factor to treatment is unclear. Thus, we evaluated the longitudinal changes of each factor in serial computed tomography (CT) images using a mixed-effects model, and investigated the radiographic transition in patients with MAC-PD whose progress could be followed. MethodsIn this retrospective study, eighty-four patients diagnosed with MAC-PD and with yearly CT records were recruited after a review of 328 medical records with culture-positive MAC in respiratory specimens. The study participants were divided into two groups: treatment (n = 43) and no-treatment (n = 41) groups. Radiographic images were scored using the nodule (N), infiltration (I), cavity (C), ectasis (E) scoring system. Longitudinal changes in each radiographic lesion factor were analyzed using a mixed-effects model in treated and untreated patients. ResultsAll factors tended to progress without treatment, and significant longitudinal changes were observed in the N, I, and E factors (N: p = 0.010, I: p = 0.004, E: p < 0.001). Although treatment tended to improve N and I in radiographic images (N: p = 0.006, I: p = 0.203), cavities and ectasis progressed, regardless of treatment (C: p = 0.057 and E: p = 0.033). ConclusionRadiographic changes of MAC-PD can be categorized into reversible (nodules and infiltrations) and irreversible (cavities and ectasis) lesions. Early treatment may prevent the accumulation of irreversible factors.

Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis.

Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. There is a characteristic cytokine profile at each clinical stage of MAC.

Prevalence of systemic and local risk factors for pulmonary non-tuberculous mycobacterial disease in Japan: a single-institution study.

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms.

Microbiological Cure at Treatment Completion Is Associated With Longer Survival in Patients With Mycobacterium avium Complex Pulmonary Disease

Morbidity and mortality from nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing. Mycobacterium avium complex (MAC) is the most common cause of NTM-PD. Microbiological outcomes are widely used as the primary end point of antimicrobial treatment, but their long-term impact on prognosis is uncertain. Do patients who achieve microbiological cure at the end of treatment have longer survival than those who do not? We retrospectively analyzed adult patients who met the diagnostic criteria for NTM-PD, were infected with MAC species, and were treated with a macrolide-based regimen for≥ 12months per guidelines between January 2008 and May 2021 at a tertiary referral center. Mycobacterial culture was performed during antimicrobial treatment to assess the microbiological outcome. Patients with three or more consecutive negative cultures collected≥ 4weeks apart and no positive cultures until treatment completion were considered to have achieved microbiological cure. To assess the impact of microbiological cure on all-cause mortality, we performed multivariable Cox proportional hazards regression analysis adjusted for age, sex, BMI, presence of cavitary lesions, erythrocyte sedimentation rate, and underlying comorbid conditions. Among 382 patients enrolled, 236 (61.8%) achieved microbiological cure at completion of treatment. These patients were younger, had lower erythrocyte sedimentation rates, were less likely to use four or more drugs, and had shorter treatment duration than those who failed to achieve microbiological cure. During a median follow-up of 3.2 (first quartile to third quartile, 1.4-5.4) years after treatment completion, 53 patients died. Microbiological cure was significantly associated with reduced mortality after adjustment for major clinical factors (adjusted hazard ratio, 0.52; 95%CI, 0.28-0.94). The association between microbiological cure and mortality was maintained in a sensitivity analysis that included all patients treated< 12months. Microbiological cure at completion of treatment is associated with longer survival in patients with MAC-PD.

Comparison of Treatment Outcomes of Cavitary Mycobacterium avium Complex Pulmonary Disease with Streptomycin or Amikacin Use.

The comparative outcomes of specific aminoglycosides in cavitary type (fibrocavitary or cavitary nodular bronchiectatic type) Mycobacterium avium complex (MAC) pulmonary disease (PD) are unelucidated. We investigated the treatment outcomes with streptomycin or amikacin inclusion in the treatment regimen. From 2006 to 2020, 168 patients with cavitary MAC-PD who received guideline-based therapy (a three-drug oral antibiotic regimen with macrolide, ethambutol, and rifampin with an injectable aminoglycoside) for ≥1 year at a tertiary referral center in South Korea were retrospectively enrolled. We compared the rates of the culture conversion achievement of patients with streptomycin or amikacin use. Of the 168 participants, 127 patients (75.6%) received streptomycin and 41 (24.4%) received amikacin (median [interquartile range] treatment duration of 17.6 [14.2 to 25.2] and 17.0 [14.0 to 19.4] weeks, respectively). The overall culture conversion rate at treatment completion was 75.6% (127/168), and the rates were similar for the streptomycin-treated and amikacin-treated groups (74.8% [95/127] and 78.0% [32/41], respectively; P = 0.674). A multivariate analysis revealed that the achievement of culture conversion did not differ significantly with streptomycin or amikacin use (adjusted odds ratio, 1.086; 95% confidence interval, 0.425 to 2.777). The rate of adverse events was similar in the two groups. In conclusion, in cavitary MAC-PD, treatment with streptomycin-containing and amikacin-containing regimens results in similar rates of culture conversion achievement. IMPORTANCE We found that among the participants with cavitary MAC-PD who received guideline-based treatment for ≥1 year, the selection of either streptomycin or amikacin in the treatment regimen led to similar rates of culture conversion at treatment completion. In addition, the adverse reaction development rate did not differ significantly for streptomycin and amikacin. These findings suggest that either streptomycin or amikacin can be selected for the treatment of MAC-PD, according to the physician's or patient's preference, such as the route of administration.

Health state utility estimation of Mycobacterium avium complex pulmonary disease using a time trade-off approach

AimsTo obtain appropriate health state utility values for cost-effectiveness analyses of new Mycobacterium avium complex pulmonary disease (MAC-PD) treatments. The impact of MAC-PD severity and symptoms on quality of life (QoL) also were quantified.MethodsA questionnaire describing four health states, MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative, was developed based on St. George’s Respiratory Questionnaire (SGRQ) Symptom and Activity scores from the CONVERT trial. The time trade-off (TTO) method with ping-pong titration procedure was used to estimate health state utilities. Regression analyses assessed the impacts of covariates.ResultsOf 319 Japanese adults (49.8% female, mean age 44.8 years), mean (95% CI) health state utility scores (MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative) were 0.252 (0.194–0.310), 0.535 (0.488–0.582), 0.816 (0.793–0.839), and 0.881 (0.866–0.896), respectively. MAC-negative state utility scores were significantly higher than MAC-positive severe (mean difference [95% CI], 0.629 [0.574–0.684]), MAC-positive moderate (0.346 [0.304–0.389]), and MAC-positive mild (0.065 [0.048–0.082]) scores (p < .001 each). Most participants would trade survival duration to avoid MAC-positive states (97.5% to avoid MAC-positive severe; 88.7% MAC-positive moderate; 61.4% MAC-positive mild). Regression analyses to investigate the impact of background characteristics showed similar utility differences between health states when not adjusted for covariates.LimitationsSome participant demographics differed from the general population; however, this did not impact utility differences among health states as regression analyses adjusting for demographics did not affect these differences. Similar investigations are needed among patients with MAC-PD and in other countries.ConclusionsThis study evaluating the impact of MAC-PD on utilities using the TTO method demonstrates that differences in utilities are dependent on the severity of respiratory symptoms and their impacts on daily activities and QoL. These results could contribute to a better quantification of the value of MAC-PD treatments and improve assessments of cost-effectiveness.

Impact of Treatment on Long-Term Survival of Patients With Mycobacterium avium Complex Pulmonary Disease.

Whether antimicrobial treatment improves long-term survival in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) is unclear. We analyzed survival in patients aged ≥18 years who were treated for MAC-PD at a tertiary referral center in South Korea between 1 January 2009 and 31 December 2020. Treatment exposure was divided into 4 time intervals: <6, ≥6 to <12, ≥12 to <18, and ≥18 months. Time-varying multivariable Cox proportional hazards models were used to calculate the all-cause mortality risk in each time interval. The model was adjusted for major clinical factors related to mortality including age, sex, body mass index, presence of cavities, erythrocyte sedimentation rate, positive acid-fast bacilli (AFB) smear, clarithromycin resistance, and comorbid conditions. A total of 486 patients treated for MAC-PD were included in the analysis. A significant inverse correlation was observed between mortality and duration of treatment (P for trend = .007). Long-term treatment (≥18 months) was significantly associated with reduced mortality (adjusted hazard ratio, 0.32 [95% confidence interval, .15-.71]). In subgroup analyses, patients with cavitary lesions (adjusted hazard ratio, 0.17 [95% confidence interval, .05-.57]) or positive AFB smears (0.13 [.02-.84]) at baseline maintained this significant inverse relationship between treatment duration and mortality. Long-term antimicrobial treatment should be actively considered in patients with progressive MAC-PD, especially in the presence of cavities or positive AFB smears indicative of high mycobacterial burden.

Patient-Reported Symptom and Health-Related Quality-of-Life Validation and Responsiveness During the First 6 Months of Treatment for Mycobacterium avium Complex Pulmonary Disease

Nontuberculous mycobacteria (NTM), predominately Mycobacterium avium complex (MAC), cause chronic pulmonary disease. Improvements in symptoms and health-related quality of life (HRQoL) are important treatment outcomes, but no validated patient-reported outcome (PRO) measure exists. What are the validity and responsiveness of the Quality of Life-Bronchiectasis (QOL-B) questionnaire respiratory symptoms scale and key HRQoL measures during the first 6months of MAC pulmonary disease (MAC-PD) treatment? Comparison of Two- vs Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease (MAC2v3) is an ongoing randomized, multisite pragmatic clinical trial. Patients with MAC-PD were randomized to azithromycin-based two-drug or three-drug therapy; treatment groups were combined for this analysis. PROs were measured at baseline, 3months, and 6months. The QOL-B respiratory symptoms, vitality, physical functioning, health perceptions, and NTM symptom domain scores (on a scale of 0-100, with 100 being best) were analyzed separately. We performed psychometric and descriptive analyses in the population enrolled as of the time of analysis and calculated the minimal important difference (MID) using distribution-based methods. Finally, we evaluated responsiveness using paired t tests and latent growth curve analysis in the subset with longitudinal surveys completed by the time of analysis. The baseline population included 228 patients, of whom 144 had completed longitudinal surveys. Patients predominately were female (82%) and had bronchiectasis (88%); 50%were 70 years of age or older. The respiratory symptoms domain showed good psychometric properties (no floor or ceiling effects; Cronbach's α, 0.85) and an MID of 6.4 to 6.9. Vitality and health perceptions domain scores performed similarly. Respiratory symptoms domain scores improved by 7.8 points (P< .0001) and 7.5 points (P< .0001), and the physical functioning domain score improved by 4.6 points (P< .003) and 4.2 points (P= .01) at 3 and 6months, respectively. Latent growth curve analysis confirmed a nonlinear, statistically significant improvement in respiratory symptoms and physical functioning domain scores by 3months. The QOL-B respiratory symptoms and physical functioning scales exhibited good psychometric properties in patients with MAC-PD. Respiratory symptoms scores improved beyond the MID by 3months after treatment initiation. ClinicalTrials.gov; No.: NCT03672630; URL: www. gov.

Efficacy of three sputum specimens for the diagnosis of Mycobacterium avium complex pulmonary disease

BackgroundIn Mycobacterium avium complex pulmonary disease (MAC-PD), diagnosis requires a positive culture from at least two separate expectorated sputum specimens. The optimal number of sputum examinations remains unclear.ObjectiveThis study sought to elucidate the diagnostic yield of acid-fast bacilli in MAC-PD using 3 sputum specimens and to clarify the clinical characteristics of patients with MAC-PD diagnosed using 3 sputum specimens. Furthermore, we investigated the correlation between increased number of sputum specimens and diagnostic yield.MethodsWe reviewed the medical records of 139 patients with MAC-PD diagnosed at Toho University Omori Medical Center for whom at least three sputum specimens were examined before treatment from November 2014 through June 2021. Patients were classified into the 3-sputum diagnosed and the non-3 sputum diagnosed groups based on diagnostic procedure; clinical and radiological characteristics were compared. We also assessed diagnostic yield with the increased number of sputum specimens.ResultsDiagnostic yield with 3 sputum specimens was 16.5% (23/139). The 3-sputum diagnosed group had a lower body mass index [18.6(17–19.5) vs. 19.5(18–21.5); p = 0.014], and higher chest CT score [9(6.5–13) vs. 6(4–9); p = 0.011] including cavitary lesions (39.1% vs. 19%; p = 0.037) compared with the non-3 sputum diagnosed group. When the number of sputum specimens was increased to 6, the diagnostic yield increased to 23.7% (33/139).ConclusionDiagnostic yield with 3 sputum specimens was 16.5%. Patients diagnosed using 3 sputum specimens had more severe chest CT findings including cavitary lesions. Increasing the number of sputum specimens to 6 improved diagnostic yield by 7.2%.

Radiologic Subtypes and Treatment Outcome of Unclassifiable Type Mycobacterium avium Complex Pulmonary Disease.

Although the "unclassifiable type" is categorized as one of the radiologic classifications in Mycobacterium avium complex (MAC) pulmonary disease (PD), there have been few studies of this type thus far. We aimed to investigate the radiologic subtypes and treatment outcome of unclassifiable type MAC-PD. Ninety-six patients with unclassifiable type MAC-PD who initiated a macrolide-containing regimen from 2001 to 2020 were identified at a tertiary referral center in South Korea. Among these 96 patients, 1-year culture conversion rate was analyzed for 48 patients who received standard treatment (three-drug oral-antibiotic combination with or without an injectable agent) for ≥ 1 year. The mean age of the 96 patients was 65.4 ± 10.8 years, and 72.9% of them were male. These patients were classified into four major radiologic subtypes; the most common subtype was the focal cavity subtype (n = 31, 32.3%), followed by the focal mass or nodule (n = 23, 24.0%), consolidation upon emphysema (n = 21, 21.9%), and bronchiolitis (n = 21, 21.9%) subtypes. For the 48 patients who received standard treatment for ≥ 1 year, the overall rate of culture conversion at 1-year was 93.8%. All patients in the focal cavity subtype and focal mass or nodule subtype categories achieved 1-year culture conversion. Additionally, 1-year culture conversion rate was 92.9% in consolidation upon emphysema subtype and 75.0% in bronchiolitis subtype. Unclassifiable type MAC-PD can be radiologically further categorized into four major radiologic subtypes. The treatment outcome of all of these subtypes seems to be favorable.

Lady Windermere Syndrome: Historical Perspective and Report of a Rare Case

Abstract Introduction/Objective Lady Windermere syndrome refers to Mycobacterium avium complex (MAC) pulmonary disease with an isolated lingular or middle lobe pattern of involvement. This is thought to be due to habitual suppression of the cough voluntarily. Typical demographics are that of elderly female patient. Although the etiology remains unclear high prevalence of pectus excavatum, scoliosis and mitral valve prolapse has also been noted in these patients. The purpose of this report this to describe a case of this syndrome. Methods/Case Report A 64-year-old female with a history of breast carcinoma status post bilateral mastectomies, and thyroid papillary microcarcinoma, status post thyroidectomy, presented with hemoptysis. Clinically and radiological findings were consistent with pneumonia which improved but did not completely resolve following antibiotic treatment. Computerized tomography (CT) revealed progressive infiltrates and bronchoscopy cultures grew Mycobacterium avium complex (MAC). Repeat antibiotic therapy resulted in only marginal improvement. Repeat CT showed diffuse bronchiectatic changes with scattered nodularity and tree-in-bud opacities, with majority of involvement in the right middle lobe and lingula. Multiple interventions were employed to ameliorate the patient’s condition including a positive expiratory pressure device, gastroesophageal reflux disease (GERD) precautions and combinations of 2 drug therapies without significant improvement in her condition. It was ultimately decided that she may benefit from a right middle lobectomy. Histologic sections from the lobectomy specimen showed necrotizing and non-necrotizing granulomatous inflammation and bronchiolectasis. Rare acid-fast microorganisms were identified on AFB special satin. Lady Windermere syndrome was suggested in the diagnostic comment after expert consultation. Patient’s symptoms improved after surgery and additional samples show no growth of MAC. Results (if a Case Study enter NA) NA Conclusion Although rendering a definite diagnosis is challenging in such cases, the constellation of clinical, radiologic, and histologic finding can be used to raise the possibility of Lady Windermere syndrome.

Clinical Outcome with Standard Regimen plus Clofazimine or Moxifloxacin in Cavitary Mycobacterium avium Complex Pulmonary Disease.

In this retrospective analysis including 173 patients in a tertiary referral center in South Korea, compared with the standard therapeutic regimen, clofazimine or moxifloxacin plus standard treatment regimen potentially did not induce a higher 1-year culture conversion rate in patients with Mycobacterium avium complex pulmonary disease who present with cavitary lesions (fibrocavitary or cavitary nodular bronchiectatic type).

Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculosis or MAC pulmonary disease, in a subject with type 2 diabetes mellitus: case report

BackgroundAddison’s disease is primary adrenal dysfunction and is characterized by decrease of cortisol level and increase of adrenocorticotropic hormone (ACTH) level. It is known that infection is one of main causes of Addison’s disease. Among various infections, tuberculous infection accounts for the majority of them. Recently the number of subjects with non-tuberculous mycobacterial infection has been increased, and the infection can also bring about Addison’s disease. Mycobacterium avium complex (MAC) pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection.Case presentationAn 83-year-old female was suspected of having adrenal failure in our outpatient care and hospitalized in our institution. There was pigmentation in her face, hands and legs, especially in auricle and nail beds in her hands and legs. In rapid ACTH load test (0.25 mg of 1–24 ACTH), cortisol level was not increased at all. An abdominal computed tomography (CT) showed swelling of both adrenal glands accompanied by calcification. QuantiFERON test was negative and mycobacterium tuberculosis complex was negative in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of adrenal tuberculosis. It is known that MAC pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. In this subject, however, anti-MAC antibody was negative and MAC-related bacteria were not detected in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of MAC pulmonary disease. Mycobacterium abscessus (Mab) was positive in bronchial lung lavage fluid culture. Based on these data, we diagnosed this subject with Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculous or MAC pulmonary disease. Decreased sodium level and increased eosinophil number were normalized and appetite loss was markedly mitigated after starting hydrocortisone therapy. A chest CT which was taken about 6 months later showed drastic reduction of consolidation in the upper lobe of the left lung although calcification in the adrenal gland was still observed.ConclusionsWe should bear in mind the possibility of Addison’s disease triggered by another type of infection rather than adrenal tuberculosis or MAC pulmonary disease.

Use of Anti-Glycopeptidolipid-Core Antibodies Serology for Diagnosis and Monitoring of Mycobacterium avium Complex Pulmonary Disease in the United States.

There is an unmet need for rapid, accurate, and noninvasive assays for diagnosis and monitoring of Mycobacterium avium complex pulmonary disease (MAC-PD). We evaluated the diagnostic accuracy of an anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody test in a US cohort of MAC patients, and we described serial serology changes during antimicrobial therapy. We identified serum samples from MAC patients starting treatment at enrollment and control subjects with or without bronchiectasis within OHSU's NTM Biobank. We conducted diagnostic test accuracy. Changes in mean levels of anti-GPL-core IgA antibodies between 0 and 3, 6, or 12 months after treatment start were assessed using the Student's paired t test. Pearson's correlation coefficient was calculated for IgA antibody levels and Student paired t test measures. We included 25 MAC patients and 18 controls. At baseline, IgA antibody concentrations in MAC patients (3.40 ± 6.77 U/mL) were significantly higher than in controls without bronchiectasis (0.14 ± 0.03 U/mL, P = .02). Sensitivity and specificity for MAC-PD in this population was 48% and 89% (cutoff point 0.7 U/mL), respectively. Among MAC patients starting antimicrobial therapy, mean IgA levels decreased 0.3202 U/mL (P = .86) at month 3, 0.8678 U/mL (P = .47) at month 6, and 1.9816 U/mL (P = .41) at 1 year. Quality of Life-Bronchiectasis Respiratory Symptom Scale improvement correlated with decreasing IgA titers after 12 months of treatment in MAC patients (r = -0.50, P = .06). Anti-GPL-core IgA antibody levels are relatively specific for MAC-PD and decrease with treatment. Larger studies are warranted to evaluate the role of IgA serology in monitoring treatment response or for disease relapse/reinfection.

CLINICAL CHARACTERISTICS OF PATIENTS TREATED WITH ANTIMYCOBACTERIALS VS NO ANTIMYCOBACTERIALS IN NONCAVITARY MYCOBACTERIUM AVIUM COMPLEX PULMONARY DISEASE

CLINICAL CHARACTERISTICS OF PATIENTS TREATED WITH ANTIMYCOBACTERIALS VS NO ANTIMYCOBACTERIALS IN NONCAVITARY MYCOBACTERIUM AVIUM COMPLEX PULMONARY DISEASE

ATYPICAL PRESENTATION OF MYCOBACTERIUM CHIMAERA PNEUMONIA FOLLOWING TRANSESOPHAGEAL ECHOCARDIOGRAPHY

ATYPICAL PRESENTATION OF MYCOBACTERIUM CHIMAERA PNEUMONIA FOLLOWING TRANSESOPHAGEAL ECHOCARDIOGRAPHY

Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease.

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25-45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied. Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance. Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.