Seong Mi Moon

Clinical Significance of Mycobacterium kansasii Isolates from Respiratory Specimens

The clinical significance of Mycobacterium kansasii respiratory isolates is uncertain. The aims of this study were to determine the clinical relevance of M. kansasii isolates and to identify the clinical features and outcomes of M. kansasii lung disease. We reviewed the medical records of 104 patients from whom at least one respiratory M. kansasii isolate was obtained from January 2003 to July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%) met the diagnostic criteria for nontuberculous mycobacterial lung disease; among them, 41 (76%) patients received antibiotic treatment for a median time of 15.0 months (interquartile range [IQR], 7.0–18.0 months). The remaining 13 (24%) without overt disease progression were observed for a median period of 24.0 months (IQR, 5.0–34.5 months). Patients with M. kansasii lung disease exhibited various radiographic findings of lung disease, including the fibrocavitary form (n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in patients who received treatment (n = 23, 56%), while the nodular bronchiectatic form was more common in patients with M. kansasii lung disease who did not receive treatment (n = 9, 70%). None of the patients with a single sputum isolate (n = 18) developed M. kansasii disease over a median follow-up period of 12.0 months (IQR, 4.0–26.5 months). In total, 52% of all patients with M. kansasii respiratory isolates exhibited clinically significant disease. Moreover, patients with M. kansasii lung disease displayed diverse radiographic findings in addition to the fibrocavitary form. The nodular bronchiectatic form was more common in patients with M. kansasii lung disease with an indolent clinical course. Thus, since the clinical significance of a single M. kansasii respiratory isolate is not definite, strict adherence to recommended diagnostic criteria is advised.

Complete remission in CD30-positive refractory extranodal NK/T-cell lymphoma with brentuximab vedotin

TO THE EDITOR: [Abstract] The treatment outcome of relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKL) is poor. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has recently been approved for the treatment of relapsed Hodgkins lymphoma and anaplastic large-cell lymphoma (ALCL). We report on a case of a 63-year-old man who presented with multiple skin lesions, and was diagnosed with ENKL. Since the disease was refractory to most chemotherapy drugs, we performed an analysis of the skin biopsy to evaluate marker CD30. The patients lymphoma cells demonstrated CD30-positivity, and treatment with single-agent brentuximab vedotin was commenced as of December 2013. Following 4 cycles of single-agent brentuximab vedotin treatment, all of the skin lesions had cleared, and a [18F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan demonstrated complete remission (CR) of the disease. This study suggests that single-agent brentuximab vedotin could be effective in the treatment of CD30-positive non-Hodgkin lymphomas other than ALCL. Extranodal natural killer (NK)/T-cell lymphoma (ENKL) is an aggressive, non-Hodgkin lymphoma for which a standard therapy has not yet been established. The treatment outcomes of advanced relapsed or refractory ENKL, with conventional chemotherapy, are extremely poor [1]. Brentuximab vedotin (Seattle Genetics Inc., Bothell, WA, USA) is an anti-CD30 antibody-drug conjugate that is covalently linked, via a protease-cleavable linker, to the microtubule-disrupting agent, monomethyl auristatin E. In a phase 1 clinical trial of 45 patients with relapsed or refractory CD30-positive lymphomas, treatment with single-agent brentuximab vedotin resulted in an overall response rate (ORR) of 67% [2]. In a phase 2 clinical trial for relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL), single-agent brentuximab vedotin treatment resulted in an ORR of 86%, and a complete remission (CR) rate of 57% [3]. Based on these results, brentuximab vedotin was approved by the United States Food and Drug Administration, in August 2011, for the treatment of relapsed Hodgkins lymphoma and ALCL. In a recent phase 2 clinical trial for relapsed T-cell lymphoma, treatment with single-agent brentuximab vedotin resulted in an ORR of 41% in relapsed T-cell lymphoma and 54% in angioimmunoblastic T-cell lymphoma patients, respectively [4]. Therefore, these studies demonstrate that single-agent brentuximab vedotin treatment in non-Hodgkin lymphoma patients with tumors expressing CD30 can induce objective responses. Here, we report on a case of a 63-year-old man with refractory CD30-positive ENKL in which CR was achieved with single-agent brentuximab vedotin treatment.

Clofazimine-Containing Regimen for the Treatment of Mycobacterium abscessus Lung Disease.

ABSTRACT Patients with lung disease caused by Mycobacterium abscessus subsp. abscessus (here M. abscessus) typically have poor treatment outcomes. Although clofazimine (CFZ) has been increasingly used in the treatment of M. abscessus lung disease in clinical practice, there are no reported data on its effectiveness for this disease. This study sought to evaluate the clinical efficacy of a CFZ-containing regimen for the treatment of M. abscessus lung disease. We performed a retrospective review of the medical records of 42 patients with M. abscessus lung disease who were treated with CFZ-containing regimens between November 2013 and January 2015. CFZ was administered in combination with other antibiotics as an initial antibiotic regimen in 15 (36%) patients (initial treatment group), and it was added to an existing antibiotic regimen for refractory M. abscessus lung disease in 27 (64%) patients (salvage treatment group). Overall, there was an 81% treatment response rate based on symptoms and a 31% response rate based on radiographic findings. Conversion to culture-negative sputum samples was achieved in 10 (24%) patients after CFZ-containing antibiotic treatment, and during treatment, there were significant decreases in the positivity of semiquantitative sputum cultures for acid-fast bacilli in both the initial (P = 0.018) and salvage (P = 0.001) treatment groups. Our study suggests that CFZ-containing regimens may improve treatment outcomes in patients with M. abscessus lung disease and that a prospective evaluation of CFZ in M. abscessus lung disease is warranted.

Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype

The effect of the clinical phenotype of Mycobacterium avium complex (MAC) lung disease on treatment outcome and redevelopment of nontuberculous mycobacterial (NTM) lung disease after treatment completion has not been studied systematically. We evaluated 481 treatment-naïve patients with MAC lung disease who underwent antibiotic treatment for ≥12 months between January 2002 and December 2013. Out of 481 patients, 278 (58%) had noncavitary nodular bronchiectatic (NB) disease, 80 (17%) had cavitary NB disease and 123 (25%) had fibrocavitary disease. Favourable outcome was higher in patients with noncavitary disease (88%) than in patients with cavitary disease (76% for fibrocavitary and 78% for cavitary NB disease; p<0.05). Cavitary disease was independently associated with unfavourable outcomes (p<0.05). Out of 402 patients with favourable outcomes, 118 (29%) experienced redevelopment of NTM lung disease, with the same MAC species recurring in 65 (55%) patients. The NB form was an independent risk factor for redevelopment of NTM lung disease (p<0.05). In patients with recurrent MAC lung disease due to the same species, bacterial genotyping revealed that 74% of cases were attributable to reinfection and 26% to relapse. Treatment outcomes and redevelopment of NTM lung disease after treatment completion differed by clinical phenotype of MAC lung disease. Treatment outcomes differ according to clinical phenotype in patients with Mycobacterium avium complex lung disease http://ow.ly/g4WU30dbLHQ

Clinical characteristics and treatment outcomes of pulmonary disease caused by Mycobacterium chimaera

Mycobacterium chimaera is a recently described species distinct from M. intracellulare. M. chimaera is regarded as less virulent than M. intracellulare. Using multi-locus sequence-based identification, M. chimaera lung disease was diagnosed in 11 patients. Clinical characteristics and outcomes of M. chimaera lung disease were comparable to M. intracellulare lung disease.

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

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

Comorbidity as a contributor to frequent severe acute exacerbation in COPD patients.

Background Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD. Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear. Methods A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE. We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations. Results Out of 77 patients, 61 patients (79.2%) had at least one comorbidity. During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission. Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids. In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30–12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60–55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01–1.19, P=0.036) were associated with frequent severe AEs. In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04–0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs. Conclusion Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients.

Effect of Rifampin and Rifabutin on Serum Itraconazole Levels in Patients with Chronic Pulmonary Aspergillosis and Coexisting Nontuberculous Mycobacterial Infection

ABSTRACT We investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 μg/ml; P < 0.001) or rifabutin (median, 0.34 μg/ml; P < 0.001) than those receiving itraconazole alone (median, 5.92 μg/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

ABSTRACT Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax. When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.)

Prolonged Maintenance of VV ECMO for 104 Days with Native Lung Recovery in Acute Respiratory Failure.

Recently, extracorporeal membrane oxygenation (ECMO) support has been increasingly applied in acute respiratory failure. The ECMO brings some advantages for enhancing the capacity of lung regeneration. Thus, the timing of determining irreversibility of the injured lung could be delayed. In this study, we experienced a case of prolonged maintenance of veno-venous ECMO for 104 days that resulted in native lung recovery. In this case, the initial empirical treatment showed no response within 4 weeks with ECMO support but the patient did not want a lung transplantation. With prolonged maintenance of the ECMO, related ethical issues arose, such as how long should the applied ECMO be maintained. Hence, there was a discussion that was centered on the timing of determining futility and ethical issues, while applying the ECMO in acute respiratory failure.