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The effects of a rifampicin (RIF) on the evolution of Clostridioides difficile infection (CDI) have not previously been investigated and there is currently no consensus on whether RIF re-administration is feasible.This retrospective observational study included consecutive tuberculosis (TB) patients diagnosed with comorbid RIF-associated CDI (RA-CDI) using strict diagnostic criteria. We investigated the association between RA-CDI and clinical outcomes, and also examined the feasibility of re-administering RIF.Out of the 11,230 patients were admitted to TB ward at our hospital, 156 TB patients (1.4%) were diagnosed with CDI and the overall incidence of CDI was calculated as 2.1 cases per 10,000 patient-days. Of 156 patients with CDI, 86 were diagnosed with RA-CDI, of whom 28 (32.6%) were re-administered with RIF. In the re-administration group, time to initial sputum smear conversion was significantly shorter than for patients who were not re-administered with RIF (42 days [interquartile range, IQR: 35-65] vs. 55 days [IQR: 44-70], p = 0.041). Further, RIF re-administration significantly reduced length of hospital stay (69 days [IQR: 66-82] vs. 81 days [IQR: 72-89], p = 0.014). Ten patients (35.7%) had recurrent CDI after RIF re-administration. On the other hand, 15 patients (53.6%) were able to continue their TB treatment, including the RIF regimen.The present study strengthens the argument for including RIF in the list of antibiotics that can induce CDI, particularly in elderly men suffering from underlying conditions. Although careful attention must be paid to the possibility of CDI recurrence, a strategy of re-administration of RIF is feasible.

Background The fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first–third waves and the fourth wave. Methods We performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center. Results We identified 404 patients (median age: 71.0 years [interquartile range: 56.0–80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first–third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital. Conclusions Cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.

Background Antibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM. Methods We performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated. Results Antibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364–4615) days. During follow-up, 13 patients had a negative conversion of sputum culture. Conclusions AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.

Objective The incidence of pulmonary nontuberculous mycobacterial (NTM) infections has increased in recent decades. Nevertheless, NTM pleurisy is still a rare disease. The objective of the present study was to elucidate the clinical features and outcomes of NTM pleurisy. Methods A retrospective study was undertaken of consecutive patients whose pleural effusion culture yielded NTM, from 2002 to 2016 at a respiratory hospital in Japan. The clinical features, treatment, and outcomes of these patients were analyzed. Result The 12 patients with NTM pleurisy were predominantly male, with a median age of 69 years (range, 48-93 years). They included eight patients with a history of smoking and six patients with immunosuppressive comorbidities such as malignancy, diabetes mellitus, and conditions requiring steroid administration. Fibrocavitary disease was the most common radiographic feature of these patients, and Mycobacterium avium complex was the most common pathogen. Pneumothorax was complicated in 11 patients. Surgery was performed on seven patients, in addition to thoracic drainage for the treatment of pleurisy and pneumothorax. Three patients died of respiratory failure. Conclusion Pneumothorax is a frequent complication of NTM pleurisy, often making the condition difficult to treat. Surgery at an appropriate time should therefore considered for refractory cases.

Background: Among Mycobacterium abscessus complex infections, patients with M. abscessus subsp. abscessus (MAA) lung disease are difficult to treat and no standard therapy has been established. Few reports have investigated the drug susceptibility of these strains. We retrospectively investigated how in vitro drug susceptibility testing (DST) of MAA affects the induction of sputum conversion using pharmacotherapy. Methods: Patients with MAA lung disease diagnosed and treated between 2010 and 2014 at our hospital were enrolled and divided into Group A (sputum conversion without relapse within 1 year) and Group B (persistent positive cultured or negative conversion with relapse). MAA was identified in M. abscessus using sequence with genotyping, and DST of MAA was performed. Results: We assessed 23 patients (9 males and 14 females). There were 8 patients in Group A and 15 in Group B. Higher prevalence of susceptible isolates for clarithromycin (CAM) susceptibility on day 14 was noted in Group A than in Group B (P = 0.03) and no significant difference observed in the two groups for other drugs. Conclusions: In vitro DST of MAA, especially CAM susceptibility on day 14, affected the results of negative conversion. No other drugs were found to affect sputum culture negative conversion.

A 71-year-old woman with polymyositis presenting with left thigh pain and an intermittent fever was admitted to Osaka Rosai Hospital. We initially diagnosed that her pain and fever were caused by a soft tissue infection because her polymyositis was controlled. She did not respond to various antibiotic therapies. Chest computed tomography demonstrated miliary tuberculosis (TB). Ziehl-Neelsen staining of liver biopsy specimens revealed epithelioid cell granuloma and acid-fast bacilli. Therefore, we finally diagnosed the lesion as TB fasciitis that improved with anti-TB drug therapy. The atypical presentation of TB fasciitis demonstrates the clinical importance of eliminating TB infections in immunocompromised hosts.

Background Pulmonary non-tuberculous mycobacterial disease (PNTM) is a known risk factor for chronic pulmonary aspergillosis (CPA). However, few studies have focused on the prognosis of PNTM-associated CPA. In the present investigation, we aimed to elucidate the clinical course and prognostic factors of CPA in patients with PNTM. Methods We retrospectively investigated the medical records of 62 patients with CPA and a history of PNTM who were admitted to Kinki-chuo Chest Medical Center between 2010 and 2015. Co-morbidities, causative microorganisms, radiological findings, and outcomes were evaluated. Results The patients’ median age was 69.5 years, and the median follow-up period was 4.2 years. The major underlying diseases, other than PNTM and CPA, were old pulmonary tuberculosis, chronic obstructive pulmonary disease, and interstitial pneumonia. The most common causative NTM species were Mycobacterium avium complex (MAC; 37 patients; 59.7%) and Mycobacterium kansasii (20 patients; 32.3%). Survival was 83% after 1 year and 61% after 5 years. Use of systemic corticosteroids (hazard ratio: 3.32, 95% confidence interval: 1.23–9.51; P=0.00177) and C-reactive protein levels ≥ 5.0 mg/dL (hazard ratio: 8.96, 95% confidence interval: 2.15–62.9; P=0.0014) at the time of CPA diagnosis were associated with increased over-all mortality. Conclusions CPA frequently developed in patients with MAC and M. kansasii PNTM. The treatment course of PNTM was not associated with all-cause mortality. However, systemic corticosteroid use and high CRP levels were negative prognostic factors of CPA in patients with PNTM. Since the prognosis is poor, early diagnosis and treatment of CPA are important in patients with PNTM.

Purpose: Never-smokers account for a large proportion of subjects in general population studies on nontuberculous mycobacteria lung disease (NTM-LD). However, the influence of NTM infection on the lung function of never-smokers has not yet been evaluated. The aim of this study was to determine how NTM-LD impairs the lung function in never-smokers, and whether there are an association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers with NTM-LD or not. Methods: We performed a retrospective study of patients (1) who have never smoked during their lifetime; (2) with at least two respiratory specimens from sputum, one bronchial washing sample, or one lung tissue that were culture positive for the same NTM species; and (3) who underwent at least two pulmonary function tests. We enrolled healthy never-smokers as the control group. Results: In 22 never-smokers with NTM-LD, the median forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at baseline was lower than those in 9 healthy never-smokers [1800 vs 2080 ml (p = 0.23) and 2230 vs 2620 ml (p = 0.06)], respectively. The median change in FEV1 in never-smokers with NTM-LD was lower than that in healthy never-smokers [−70 vs 20 ml per year (p = 0.07), respectively]. On univariate analysis, baseline %-predicted FEV1 in never-smokers with NTM-LD was associated with changes in FVC (p = 0.026) and FEV1 (p = 0.013). Anti-NTM treatment was administered for at least 1 year in 19 patients (86.4%). The relationship between worsening chest CT findings and rapid progressive decline in both FVC (p = 0.66) and FEV1 (p = 0.23) were not significant. Conclusion: Never-smokers with NTM-LD showed lung function decline. There was no association between successful NTM-LD treatment in radiologic outcomes and improvement in lung function of never-smokers. Keywords: Lung function, Never-smoker, Nontuberculous mycobacterial lung disease, Bronchiectasis

Background Pulmonary nocardiosis is a rare but severe infection caused by Nocardia species. This study aimed at describing the clinical characteristics and prognosis of pulmonary nocardiosis. Methods An observational, retrospective study was undertaken of patients diagnosed with pulmonary nocardiosis over a 13-year period at the Kinki-Chuo Chest Medical Center, Osaka, Japan. Results Seven patients with airway nocardial colonization and 59 patients with pulmonary nocardiosis were identified, one of whom had disseminated nocardiosis. Patients with pulmonary nocardiosis were predominantly male patients (73%), with a mean age of 66 (range, 15–88) years. New-onset cough and dyspnea were the most common manifestations (76%). Although 52 (88%) patients had at least one underlying pulmonary disease, most patients did not appear to be systemically immunocompromised. The predominant abnormality on chest computed tomography in pulmonary nocardiosis was airspace consolidation (52%), sometimes associated with cavitation. Multivariate Cox proportional-hazards analysis revealed the following significant and independent risk factors for overall mortality: age >68 years (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.6–14; p =0.05), pulmonary aspergillosis (HR, 8.8; 95% CI, 2.4–33; p =0.01), and trimethoprim/sulfamethoxazole (TMP-SMZ) resistance (HR, 4.3; 95% CI, 1.6–11; p =0.04). Conclusions Clinicians should be aware that pulmonary nocardiosis can occur even in immunocompetent patients, especially those with an underlying pulmonary disease. In pulmonary nocardiosis, older age, pulmonary aspergillosis, and TMP-SMZ resistance are associated with increased risk of mortality.

A 28-year-old woman was referred to our hospital for treatment of tuberculous lymphadenitis, after presenting with fever, left cervical lymphadenopathy, and a positive interferon-gamma release assay (QuantiFERON®-TB Gold In-Tube; QFT) result. Surprisingly, biopsy specimens of the cervical lymph nodes showed necrotic lesions with prominent nuclear debris and a proliferation of histiocytes, consistent with Kikuchi-Fujimoto disease (KFD). A diagnosis was made of KFD complicated by latent tuberculosis infection (LTBI), and all symptoms had resolved completely two months post-diagnosis. KFD may be misdiagnosed as tuberculous lymphadenitis, and antibiotics unnecessarily prescribed. Careful attention should therefore be paid when diagnosing cervical lymphadenopathy.

A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD) and silicosis was referred to our hospital for an evaluation of dyspnea. A progressively enlarging cavity found in the patient's left lower lung was associated with a worsening respiratory status. One year after the initial referral, the patient was diagnosed with nontuberculous mycobacterial (NTM) infection. We herein report the case of a patient with a mixed infection of M. kansasii, M. avium complex and M. abscessus, the various organisms having been isolated in succession. Recognizing a diagnosis of mixed pulmonary NTM infection is therefore crucial in patients with underlying diseases.

A 67-year-old woman was referred to our hospital for persistent fever and dyspnea. Chest X-ray revealed diffuse reticulonodular shadows and high-resolution computed tomography showed randomly distributed small nodules. Examination of sputum and urine revealed acid-fast bacilli, which were later confirmed as Mycobacterium tuberculosis sensitive to all drugs. Laboratory tests revealed thrombocytopenia, an elevated concentration of fibrin degradation products, and severe hypoxemia. We therefore diagnosed her with miliary tuberculosis complicated by acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). After admission, her status rapidly worsened and she required mechanical ventilation. Treatment with recombinant human soluble thrombomodulin (rTM) and high-dose methylprednisolone was started in addition to the antituberculosis chemotherapy. The patient's condition gradually improved and she was weaned from ventilation on day 30. She was discharged on day 92. It is generally thought that prognosis of miliary tuberculosis complicated by DIC and ARDS is very poor. A recent report suggested that rTM is effective for DIC and ARDS secondary to sepsis. This is the first report of miliary tuberculosis complicated by DIC and ARDS successfully treated with rTM.

Cryptococcal empyema is a rare disease which usually occurs in immunocompromised patients. We describe a 57-year-old man with diabetes mellitus with a mass-like shadow in the right middle lung field. Transbronchial lung biopsy of the right lung revealed numerous yeast-like fungi in fibrotic and necrotic lesions. These findings, together with positive serum cryptococcal antigen yielded a diagnosis of pulmonary cryptococcosis secondary to diabetes mellitus. Despite treatment with several anti-fungal drugs, and dyspnea and pleural effusion developed. He was referred to our hospital for further examination and therapy. The presence of positive cryptococcal antigen and numerous yeast-like fungi were confirmed cytologically in the pleural effusion. Therefore, we suspected that pulmonary cryptococcosis had perforated into the thoracic space and empyema had developed. Because antifungal drugs were ineffective, debridement of the fibrinopurulent material by medical thoracoscopy and chest drainage were performed. The clinical symptoms of this patient improved with antifungal treatment for 1 year, and we successfully treated the cryptococcal empyema without recurrence. Debridement by medical thoracoscopy and chest drainage were useful for this case of cryptococcal empyema.

Introduction The proportion of small-cell lung cancer (SCLC) has steadily decreased in the United States and Japan as the smoking rate has declined, currently representing approximately 13% to 20% of all ung cancers. Although the cause of the disease is closely associated with smoking, there are a small number of SCLC patients reported who never smoked. Non–small-cell lung cancer (NSCLC) in nevr-smokers has been studied intensively to date, and almost 80% of ncogenic mutations have been demonstrated in the molecular bioarkers which include epidermal growth factor receptor (EGFR)