Byung Woo Jhun

Mycobacterial Characteristics and Treatment Outcomes in Mycobacterium abscessus Lung Disease

Background. Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods. Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results. Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions. Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration. NCT00970801.

Clinical characteristics and treatment outcomes of chronic pulmonary aspergillosis

Chronic pulmonary aspergillosis (CPA) is a relatively uncommon disease that has been poorly characterized. This study investigated the clinical features and treatment outcomes of CPA through a retrospective review of records of patients with newly diagnosed CPA between January 2008 and January 2012. A total of 70 CPA patients, which included 51 (73%) males, had a median age of 55 years. Fifty-seven patients (81%) had a history of pulmonary tuberculosis and pulmonary disease caused by nontuberculous mycobacteria (NTM) was a primary underlying condition in 32 patients (46%). Most patients (n = 66; 99%) were treated with oral itraconazole, for a median of 6.4 months. Treatment response of 73% of patients was based on alleviation of symptoms and in 44% on computed tomography. Laboratory tests improved for more than 60% of patients and overall favorable responses were achieved in 44 patients (62%). Five of the latter (11%) had to restart antifungal therapy after a median of 9.2 months after therapy. Death occurred in 10 patients (14%). This study suggested that NTM lung disease was an important risk factor for CPA development. While treatment with oral itraconazole for approximately 6 months was moderately effective in treating CPA, a more effective treatment is required.

Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia

The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.

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.

Nodal stations and diagnostic performances of endobronchial ultrasound-guided transbronchial needle aspiration in patients with non-small cell lung cancer.

There are no accurate data on the relationship between nodal station and diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We evaluated the impact of nodal station and size on the diagnostic performance of EBUS-TBNA in patients with non-small cell lung cancer (NSCLC). Consecutive patients who underwent EBUS-TBNA of mediastinal or hilar lymph nodes for staging or diagnosis of NSCLC were included in this retrospective study. Between May 2009 and February 2010, EBUS-TBNA was performed in 373 mediastinal and hilar lymph nodes in 151 patients. The overall diagnostic sensitivity, specificity, accuracy and negative predictive value (NPV) of EBUS-TBNA were 91.6%, 98.6%, 93.8%, and 84.3%, respectively. NPV of the left side nodal group was significantly lower than those of the other groups (P = 0.047) and sensitivity of the left side nodal group tended to decrease (P = 0.096) compared with those of the other groups. Diagnostic sensitivity and NPV of 4L lymph node were 83.3% and 66.7%, respectively. However, diagnostic performances of EBUS-TBNA did not differ according to nodal size. Bronchoscopists should consider the impact of nodal stations on diagnostic performances of EBUS-TBNA.

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 implications of initial peripheral eosinophilia in acute eosinophilic pneumonia.

The initial peripheral eosinophil count (PEC) is rarely elevated but tends to increase during the clinical course of acute eosinophilic pneumonia (AEP). We evaluated whether initial peripheral eosinophilia is an indicator of mild disease in patients with AEP.

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.

Clinical implications of correlation between peripheral eosinophil count and serum levels of IL-5 and tryptase in acute eosinophilic pneumonia

BACKGROUND The peripheral eosinophil count (PEC) tends to increase during the course of acute eosinophilic pneumonia (AEP), and an initially elevated PEC is associated with milder disease. However, there is a lack of data regarding these phenomena and inflammatory process of AEP. METHODS We prospectively evaluated serial changes in serum interleukin (IL)-5 levels and the correlation between the initial level of IL-5 and the PEC to investigate whether the initial PEC indicates a resolving state of inflammation. We also evaluated serum tryptase levels to investigate the possibility of involvement of mast cell activity in AEP. RESULTS Twenty-one AEP patients were included, and all patients improved within 10 days after corticosteroid treatment. The median initial serum IL-5 level among all patients was 561.0 pg/mL, which decreased to zero at 10 days of follow-up (n = 15, P < 0.001). The median initial serum tryptase level (detectable in 20 of 21 patients) was 3.7 ng/mL and decreased to a median of 1.1 ng/mL at 10 days of follow-up (n = 15, P < 0.001). The initial serum IL-5 and C-reactive protein levels were positively correlated (P = 0.009, r = 0.556), and the initial serum IL-5 level was inversely correlated with the initial PEC (P = 0.004, r = -0.603). CONCLUSIONS Our data suggest that IL-5 is an important cytokine involved in the recruitment of eosinophils from peripheral blood into the lungs, that an initially elevated PEC is associated with a resolving state of inflammation, and that mast cells are potentially involved in the inflammatory process of AEP.