Pulmonary sequestration is a congenital lung malformation involving the systemic arterial blood. Infection is a common complication; however, Nocardia infection is rare. We report the case of a 55-year-old immunocompetent male with recurrent infection of a pulmonary cyst in the left lower lobe. Despite the use of empirical antibiotics, the inflammation recurred. Contrast-enhanced computed tomography confirmed pulmonary sequestration, and bronchoscopy revealed Nocardia cyriacigeorgica. Although trimethoprim-sulfamethoxazole was effective, it was discontinued because of severe drug-induced rash. Surgical resection resolved the infection without the use of long-term antibiotics. Timely consideration of surgical intervention may be important for infection control in pulmonary sequestration complicated by Nocardia, especially when antibiotic management is difficult.

OBJECTIVES:We aimed to investigate a nosocomial outbreak of Mycobacterium abscessus subspecies massiliense (MAM) and to track its transmission route via genomic analyses and environmental surveys at a hospital in Osaka, Japan. The outbreak was initially detected in two patients (M1 and M2) with severe disability in 2020 and then expanded to five other patients (M3‒M7). METHODS:The 34-month observation period was divided into three phases separated by two interventions. Mycobacterial culture screening was performed for 294 clinical and environmental samples. We confirmed that five patients (M1‒M5) had infections in phase 1 (March 2020 to July 2021) and implemented an initial intervention. In phase 2 (November 2021 to May 2022), new patients (M6 and M7) were identified, wherein an environmental survey identified MAM strains, prompting a second intervention. No patients were identified in phase 3 (September to December 2022). However, MAM was isolated from the environment during follow-up surveys. A total of 52 MAM isolates were analysed, including 11 clinical isolates (one from M1 and M2 in each phase and one each from M3-M7) and 41 environmental isolates obtained from care gloves, medical devices, and room equipment surrounding patients. We sequenced the isolate genomes and identified 15 subclone clusters with a threshold of 24.5 single-nucleotide variants (SNVs). RESULTS:The overall SNV distribution of the clinical and environmental strains was within 61 SNVs, showing near-identical genomes. Clinical strains from patient M2 with persistent positivity were classified as the same subclone, with 0-6 SNVs. The isolate from a wagon brought into patient rooms showed the lowest number of SNVs (3-8) compared with isolates from M2. This subclone cluster, involving M2 and wagon isolates, formed the hub of the intercluster connection of 11 clusters comprising other clinical and environmental strains. CONCLUSIONS:M. abscessus could persist in dry environments and might be indirectly transmitted via fomites.

BACKGROUND:Delamanid is a nitro-dihydro-imidazooxazole derivative that possesses highly potent activity against Mycobacterium tuberculosis, including strains linked to multidrug-resistant tuberculosis (MDR-TB). We conducted an all-case post-marketing surveillance to assess the real-world safety and effectiveness of delamanid in treating MDR-TB in Japan. METHODS:All patients diagnosed with MDR-TB were included if they started delamanid between September 2014 and February 2023. Case report forms were collected every 6 months during the treatment period and every 12 months during the follow-up period. Safety assessment included any adverse events that occurred during the treatment period. Effectiveness assessment included the proportion of patients with sputum-culture conversion and treatment success. RESULTS:In the safety analysis set, 61.6 % of patients (114/185) were males, and the median (interquartile range) age was 48.0 (32.0, 64.0) years. During the treatment period, 54.05 % of patients (100/185) experienced adverse drug reactions (ADRs), and 8.65 % (16/185) experienced serious ADRs. Electrocardiogram QT prolongation was reported in 8.65 % of patients (16/185) but was not associated with an increased risk of cardiovascular events. In the sputum-culture conversion analysis set, sputum-culture conversion was achieved in 86.0 % of patients (80/93). In the effectiveness analysis set, treatment success was achieved in 54.1 % of patients (99/183) by the end of the treatment period. CONCLUSIONS:This surveillance showed the effectiveness of ≥6 months of delamanid treatment among patients with MDR-TB in real-world settings in Japan, with no new safety issues identified.

Accurate subspecies identification and drug susceptibility testing (DST) are essential for appropriate clinical management, particularly in patients infected with Mycobacterium abscessus species (MABS). We developed a novel software, mlstverse, which uses multi-locus sequence typing to identify non-tuberculous mycobacteria (NTM) species, demonstrating rapid and accurate diagnostic performance. However, these studies included only a limited number of MABS samples. In this study, we focused on MABS and evaluated the diagnostic accuracy of the system for subspecies identification and drug resistance prediction for clarithromycin (CAM) and amikacin (AMK). A total of 56 clinical isolates, previously identified as MABS by conventional methods, were analyzed. The mlstverse identified two isolates as M. intracellulare and 54 isolates as MABS, with 28 identified as M. abscessus subsp. abscessus (MAB) and 26 as M. abscessus subsp. massiliense (MMA). All results obtained through mlstverse were fully consistent with the species/subspecies exhibiting the highest average nucleotide identity (ANI) values. In contrast to the identification by ANI values, the mlstverse system clearly distinguished between MABS subspecies, with the mean differences between the highest and second-highest MLST scores of 0.16 for MAB and 0.33 for MMA, respectively. The system predicted drug susceptibility to CAM and AMK with high concordance to phenotypic DST (CAM: 98.1%, AMK: 100%). These results suggest that mlstverse provides a reliable method for accurate subspecies identification and drug resistance prediction in MABS, supporting the potential of integrating portable next-generation sequencing technologies with real-time software analysis for improved diagnostic accuracy and treatment strategies in patients with NTM infections. IMPORTANCE:Accurate subspecies identification and drug susceptibility testing (DST) are essential for appropriate clinical management of Mycobacterium abscessus species (MABS) infections. We previously developed mlstverse, a novel software utilizing multi-locus sequence typing to identify non-tuberculous mycobacteria (NTM species, demonstrating rapid and accurate diagnostic performance. However, these studies included only a limited number of MABS samples. In this study, we focused on MABS and evaluated the diagnostic accuracy of the system for subspecies identification and drug resistance prediction for clarithromycin (CAM) and amikacin (AMK). We showed that mlstverse can clearly distinguish MAB subspecies compared to ANI values and predicted drug susceptibility to CAM and AMK with high concordance to phenotypic DST. The mlstverse system provides a reliable method for accurate subspecies identification and drug resistance prediction in MABS, supporting the potential of integrating portable next-generation sequencing technologies with real-time software analysis for improved diagnostic accuracy and treatment strategies in patients with NTM infections.

Background: The prognosis of patients with coronavirus disease 2019 (COVID-19) was poor although its survival rate has been improved after the occurrence of the Omicron strain. Autoimmune pulmonary alveolar proteinosis (APAP), a lung disease caused by macrophage dysfunction induced by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing autoantibodies, is characterized by the deposition of proteinaceous material in the alveolar spaces. The clinical course of COVID-19 in patients with APAP remains unclear and this study aimed to clarify it. Methods: The data of 23 patients with APAP, who were diagnosed with COVID-19 between January 2020 and May 2023 and collected through a nationwide questionnaire surveillance system, were retrospectively reviewed. Results: Based on the epidemiological frequency at disease onset, suspected strains of severe acute respiratory syndrome coronavirus 2 were Omicron (n = 18) and non-Omicron (n = 5). Fifteen patients were vaccinated. Six and three patients received anti-viral drugs and corticosteroids, respectively. One patient in the third trimester of pregnancy died despite treatment in the intensive care unit. Six patients were complicated by pneumonia and/or required supplemental oxygen. These patients were suspected to have non-Omicron strains (p = 0.087). Vaccination status showed a significant association with suspected Omicron strains. The radiological findings in four patients and shortness of breath improved in two of the four patients after COVID-19. Conclusions: The severity and prognosis of the patients were not worse than those predicted based on the results of a previous study. The transition from a non-Omicron strain to an Omicron strain and the vaccination status may have affected these results.

Negative pressure wound therapy (NPWT) after open window thoracostomy effectively reduces empyema cavity volume, but fistula control remains challenging in cases of bronchopleural/alveolopleural fistula. We report the successful treatment of chronic tuberculous empyema with bronchopleural and/or alveolopleural fistulas through primary closure during thoracostomy, combined with simultaneous NPWT. A woman in her 90s, with a history of left upper lobectomy (60 years prior), developed chronic tuberculous empyema with a cutaneous fistula. Chest computed tomography (CT) showed an air-containing empyema cavity with surrounding pneumonia. Despite spontaneous cutaneous fistula closure, thoracic drainage confirmed an air leak, and Mycobacterium tuberculosis was isolated. Open window thoracostomy was performed with fourth-ninth rib resection (20 cm incision), alveolopleural fistula coverage using a pedicled serratus anterior flap, and cavity volume reduction with latissimus dorsi and serratus anterior flaps. NPWT commenced on postoperative day 3, continuing for six weeks after negative foam cultures. The empyema cavity decreased by 88.8%, from 118.2 cm³ to 13.2 cm³, facilitating gauze-based wound care and enabling patient transfer on day 65. Primary fistula closure during open window thoracostomy enables early implementation of NPWT, facilitating marked cavity reduction in chronic tuberculous empyema with fistula and representing a novel therapeutic strategy.

Rationale: Patients with noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex pulmonary disease (MAC-PD) are treated intermittently three times per week, although no randomized controlled trials have been conducted comparing three times weekly with daily therapy. Objectives: To assess the tolerability, safety, and efficacy of intermittent versus daily treatment in patients with previously untreated noncavitary NB MAC-PD. Methods: In an open-label study, patients were randomly assigned to the intermittent therapy group receiving clarithromycin 1,000 mg, rifampicin 600 mg, and ethambutol 25 mg/kg (maximum 1,000 mg) three days per week or the daily therapy group receiving clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 15 mg/kg (maximum 750 mg) daily for 1 year. The primary endpoint was the proportion of patients requiring modification of the initial treatment regimen. Results: Twenty-one Japanese hospitals participated in the study, enrolling 141 patients between May 2019 and December 2021. The full analysis set included 138 participants (intermittent therapy = 70; daily therapy = 68). There were no significant differences between the intermittent and daily therapy groups in terms of the regimen modification rate (20.0% [14 of 70] vs. 33.8% [23 of 68]; adjusted odds ratio, 0.48; 95% confidence interval, 0.22 to 1.05; P = 0.06) or culture conversion (70.3% vs. 80.0%; P = 0.53), time to culture conversion (28.0 vs. 28.5 d; P = 0.89), improvement in chest CT findings (60.9% vs. 71.0%; P = 0.30), or clarithromycin resistance development (1.4% vs. 0%; P = 1.00). Elevated aspartate aminotransferase (16.9% vs. 41.2%; P = 0.003) and alanine aminotransferase (18.3% vs. 44.1%; P = 0.002) were more common in the daily treatment group, whereas elevated bilirubin (11.3% vs. 1.5%; P = 0.04) and dysgeusia (14.1% vs. 1.5%; P = 0.01) were more common in the intermittent treatment group. The daily treatment group exhibited a greater absolute change in the 36-Item Short Form Health Survey physical aspect score (-2.5 points) than the intermittent treatment group (2.1 points) (P = 0.01). Conclusions: Intermittent treatment was not significantly better tolerated than daily treatment for noncavitary NB MAC-PD. However, further studies with larger numbers of patients are needed. Clinical trial registered with https://jrct.mhlw.go.jp/en-top (jRCTs031190008).

Background:Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear. Methods:We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance. Results:We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66-70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations. Conclusions:Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.

AbstractBackgroundAdvances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment.MethodsBetween January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment.ResultsA total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37–21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS.ConclusionsThis study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large‐scale studies are needed to identify the effect of CPA in patients with LC.

A 75-year-old immunocompetent man presented to the hospital with a 4-year history of hemoptysis.Although he had no underlying disease, his body mass index at admission was 16.9 kg/m 2 .Chest X-ray (Picture 1) and computed tomography (Picture 2a, b) revealed cavity in the left upper lobe and irregular pleural thickening in the right thoracic cavity.After one day of incubation, the sputum fungal culture grew white, cotton candy-like colonies on Sabouraud dextrose agar (Picture 3).Based on the morphological characteristics (Picture 4) and sequences of both the internal transcribed spacer and 28S rDNA, the fungus was confirmed

Background: CONVERT, a randomized, active -controlled, global, Phase 3 trial demonstrated that patients with treatment -refractory Mycobacterium avium complex (MAC) pulmonary disease were more likely to achieve culture conversion with amikacin liposome inhalation suspension (ALIS) plus guideline -based therapy (GBT) versus those continuing on GBT alone. This subgroup analysis reports the efficacy and safety of ALIS in Japanese patients enrolled in CONVERT. Methods: Japanese patients aged >= 20 years with treatment -refractory MAC pulmonary disease from Japanese sites were included. Patients were randomized to receive once -daily 590 mg ALIS + GBT or GBT alone; patients converting by Month 6 remained in the study to complete 12 -month treatment followed by a 12 -month offtreatment period. Nonconverters exited the study at Month 8. The primary endpoint was the proportion of patients achieving culture conversion by Month 6. Results: Of the 59 Japanese patients screened, 48 were randomized to receive ALIS + GBT (n = 34) or GBT alone (n = 14), and 41/48 (85.4 %) were women. The mean (standard deviation) age of patients was 64.5 (8.6) years, and 83.3 % of patients had bronchiectasis at baseline. By Month 6, sputum culture conversion was cumulatively achieved in 9/34 (26.5 %) patients receiving ALIS + GBT versus none receiving GBT alone. Treatment -emergent adverse events were reported in 94.1 % and 100.0 % of patients receiving ALIS + GBT and GBT alone, respectively. No deaths were reported. Conclusions: The efficacy observed in the Japanese subpopulation was largely consistent with that in the overall CONVERT study population, with more patients achieving culture conversion with ALIS + GBT versus GBT alone. Safety profiles were similar between the overall population and the Japanese subpopulation. Clinical trial registration: NCT02344004.

Patients with Mycobacterium avium complex pulmonary disease (MAC-PD) often suffer from chronic symptoms such as sputum production, which reduces quality of life. Oscillatory positive expiratory pressure (OPEP) devices are used in physiotherapy to promote the clearance of respiratory secretions. We report two cases of improved lung function and improved scores on the Leicester Cough Questionnaire (LCQ) and the Breathlessness, Cough and Sputum Scale (BCSS) after the use of OPEP in patients with MAC-PD where treatment with guideline-based therapy, including amikacin liposome inhalation suspension, had proved ineffective for symptoms. Use of OPEP might maximize the efficacy of therapy and thereby improves outcomes in patients with MAC-PD. It is important to use both guideline-based therapy and OPEP, especially in patients whose health-related quality of life is affected by sputum symptoms. Further prospective studies are warranted to assess the benefit of adding OPEP to guidelines concerning therapy for patients with MAC-PD and sputum symptoms.

BACKGROUND:Treatment outcomes for Mycobacterium abscessus species-related pulmonary disease (MABS-PD) are generally poor because of inducible clarithromycin resistance (IR). The clinical management of patients with MABS with different genotypic and phenotypic susceptibility results is also not definitive. Here, we aimed to reassess the characteristics of patients with variant MABS and their association with diagnosis, treatment intervention, and sputum culture conversion. METHODS:We retrospectively analyzed 119 patients with MABS infection. Clinical characteristics and medical history were obtained via medical chart review. Isolates were tested for clarithromycin susceptibility and classified into erm(41) sequevars. RESULTS:In the IR, non-IR, and acquired resistance groups, the sputum culture conversion rates were 22% (5/23), 80% (40/50), and 8% (1/12), respectively. In contrast, in MAB, MAB T28, MAB C28, and M. abscessus subsp. massiliense (MAM), sputum culture conversion rates were 33% (12/36), 29% (22/31), 60% (3/5), and 70.8% (34/48), respectively. The proportion of patients with non-IR MAB T28 diagnosed and treated for MABS-PD was lower than those of patients with IR or acquired resistant T28 [35.7% (5/14), 80.7% (21/26), 100% (5/5); P < 0.05], whereas the sputum culture conversion rate was high in patients with non-IR MAB T28 [80.0%(4/5), 23.8%(5/21), 0%(0/5); P < 0.01)]. The sputum culture conversion rate in treated patients with MABS-PD with IR MAB C28 or acquired resistant MAM was low [0.0% (0/1) and 14.3% (1/7)]. CONCLUSIONS:Patients with MABS-PD and non-IR were likely to have sputum culture conversion. Our results indicated that phenotypical properties were associated with MABS-PD diagnosis and treatment.

Among nontuberculous mycobacterial pulmonary diseases (NTM-PDs), Mycobacterium abscessus species pulmonary disease (MABS-PD) is one of the most severe and intractable infections. We herein report a 45-year-old woman with advanced lymphangioleiomyomatosis (LAM) who developed MABS-PD while undergoing sirolimus therapy. MABS-PD was immediately controlled using antibiotic therapy, although the patient's lung transplant registration was significantly delayed. To our knowledge, this is the first case report on the development of NTM-PD in a patient with LAM before lung transplantation. This case suggests that the early diagnosis and optimal treatment of NTM-PD are crucial in patients with advanced LAM.

Although clofazimine is currently one of the standard regimens for Mycobacterium abscessus, it frequently causes skin discoloration, posing esthetic concerns for patients. We studied thirteen Asian patients with pulmonary nontuberculous mycobacterial disease treated with clofazimine at the NHO Kinki Chuo Chest Medical Center. In three patients (two women and one man) whose dosing regimens were altered owing to skin discoloration, we continuously measured luminance (L*), red-green (a*), and yellow-blue (b*) values (using a colorimeter) in both sun-exposed and sun-unexposed skin areas at each visit. Compared to baseline L* and a* values, the ΔL* values were negative (decreased brightness) and Δa* values were positive (increased redness) while patients received daily clofazimine. After switching to intermittent or reduced dosing, these changes gradually diminished. If such a dose reduction does not affect the therapeutic outcome, an even lower clofazimine dose may be attempted to minimize skin adverse effects.

Background:When performing bronchial artery embolization (BAE), identifying the side of bleeding and thereby deciding the side of embolization is crucial for an effective and safe procedure. However, there is little evidence regarding the utility of bronchoscopy for determining the side of embolization prior to BAE in nonintubated patients with hemoptysis admitted to general wards. Research Question:Is bronchoscopy necessary prior to BAE in nonintubated patients with hemoptysis following bronchiectasis and chronic pulmonary infection? Study Design and Methods:Data from 93 consecutive nonintubated general ward patients with bronchiectasis and chronic pulmonary infection (nontuberculous mycobacteriosis, aspergillosis, and TB) who underwent de novo BAE from September 2017 to August 2023 were retrospectively reviewed. The contribution of bronchoscopy in deciding the side of embolization was evaluated. Results:All patients underwent CT imaging and 27 also underwent bronchoscopy. Bronchoscopy identified the sides of bleeding in 9 patients, but these sides could be correctly estimated in 8 of them from the CT information alone. Bronchoscopy did not reveal the side of bleeding in 18 patients, whose sides of embolization were decided using CT imaging and angiographic information. Of 66 patients without bronchoscopy, the sides of embolization were decided in 63 patients using CT imaging and angiographic information, but the priority of the embolization side could not be decided in the remaining 3 patients. Overall, 96% (89 of 93) of patients did not require bronchoscopy as part of their embolization plan. The 90-day overall survival and hemoptysis-free survival rates were 98.9% (95% CI, 92.5-99.8) and 92.3% (95% CI, 84.6-96.3), respectively. Interpretation:This study showed that bronchoscopy contributed little to the planning of BAE in nonintubated patients with hemoptysis following bronchiectasis and chronic pulmonary infection. Our findings do not support the routine use of bronchoscopy prior to BAE in this population.

The prognosis of patients with coronavirus disease 2019 (COVID-19) and pre-existing interstitial lung disease (preILD) is poor, and no effective treatment strategy has been determined. The aim of this study was to assess the effectiveness of a steroid-based treatment strategy for patients with COVID-19 and preILD. We retrospectively reviewed the medical records of 610 consecutive patients with COVID-19 treated at our institution between 1 March 2020 and 30 October 2021 and identified 7 patients with preILD, all of whom were treated with corticosteroids and remdesivir. All the patients were men with a median age of 63 years. Three of four patients with severe disease required invasive positive-pressure ventilation (n = 2) or nasal high-flow therapy (n = 1). All three patients could be weaned from respiratory support; however, one died in hospital. The remaining patient with severe COVID-19 had a do-not-resuscitate order in place and died while hospitalized. All three patients with moderate COVID-19 were discharged. The 30-day mortality was 0%, and the mortality rate during the entire observation period was 28.5%. The prognosis of our patients with COVID-19 and preILD has been better than in previous reports. Our management strategy using corticosteroids may have improved these patients' prognosis.

Abstract This study assessed the characteristics of inducible clarithromycin resistance (IR) in Mycobacterium abscessus subsp. abscessus (MAB) associated with diagnosis, treatment intervention, and sputum culture conversion in patients with M. abscessus species pulmonary disease (MABS-PD). The proportion of patients with non-IR MAB T28 diagnosed with MABS-PDand treatment intervention rateswere lower than those of patients with IR or acquired resistant T28 (P < 0.05), whereas the sputum culture conversion rate was higher in patients with non-IR MAB T28 (P < 0.01). Among the 6 patients with C28, 4 (66.7%) of 5 patients with non-IR showed favourable microbiological outcomes.