Changes in skin discoloration according to clofazimine dosage in nontuberculous mycobacterial pulmonary disease.

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.

Efficacy of an oscillating positive expiratory pressure device in patients with Mycobacterium avium complex pulmonary disease.

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.

The feasibility of rifampicin Re-administration in patients with tuberculosis and Clostridioides difficile infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effective treatment for clarithromycin-resistant Mycobacterium avium complex lung disease.

Clinical management of macrolide-resistant Mycobacterium avium complex (MR-MAC) lung disease is difficult. To date, there only exist a limited number of reports on the treatment of clarithromycin-resistant MAC (CR-MAC) lung disease. This study aimed to evaluate prognostic factors and identify effective treatments in CR-MAC lung disease. We retrospectively collected clinical data of patients newly diagnosed with CR-MAC lung disease at the Kinki-Chuo Chest Medical Center between August 2010 and June 2018. Altogether, 37 patients with CR-MAC lung disease were enrolled. The median age was 69 years; 30, 22, and 21 patients received clarithromycin, ethambutol, and rifampicin, respectively, on their own or in drug combination. The observed sputum culture conversion rate was 29.7% (11/37 patients). In univariate analysis, ethambutol significantly increased the rate of sputum culture conversion (p = 0.027, odds ratio (OR) 10; 95% confidence interval (CI) 1.11-89.77). Multivariate analysis confirmed that ethambutol increased sputum culture conversion rate (p = 0.026; OR 21.8; 95% CI 1.45-329) while the existence of lung cavities decreased it (p = 0.04; OR 0.088; 95% CI 0.009-0.887). The combined use of ethambutol with other drugs may improve sputum culture conversion rate in CR-MAC lung disease.

A Case of Lymphangioleiomyomatosis Showing the Development of Mycobacterium abscessus subsp. massiliense Infection During Sirolimus Therapy.

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.

COVID-19 in Patients with Pre-Existing Interstitial Lung Disease: Potential Value of a Steroid-Based Treatment Strategy.

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.

[A case of miliary tuberculosis complicated by disseminated intravascular coagulation and acute respiratory distress syndrome successfully treated with recombinant human soluble thrombomodulin].

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.

Delirium in Patients with COVID-19 in Japan.

Objective The incidence and clinical importance of delirium in coronavirus disease 2019 (COVID-19) have not yet been fully investigated. The present study reported the prevalence of delirium in patients with COVID-19 and identified the factors associated with delirium and mortality. Methods We performed an observational, retrospective study of patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center. Univariate and multivariate logistic regression analyses were used to explore delirium risk factors. Patients All consecutive patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center. Results We identified 600 patients [median age: 61.0 (interquartile range: 49.0-77.0) years old], of whom 61 (10.2%) developed delirium during their stay. Compared with patients without delirium, these patients were older (median age 84.0 vs. 56.0 years old, p<0.01) and had more comorbidities. Based on a multivariate analysis, age, dementia, severe disease, and lactate dehydrogenase (LDH) levels were independent risk factors for developing delirium. For every 1-year increase in age and 10-IU/L increase in LDH, the delirium risk increased by 10.8-12.0% and 4.6-5.7%, respectively. There were 15 (24.6%) in-hospital deaths in the group with delirium and 8 (1.6%) in the group without delirium (p<0.01). Delirium was associated with an increased mortality. Conclusion Delirium in patients with COVID-19 is prevalent and associated with poor clinical outcomes in Japan. Despite difficulties with COVID-19 patient care during the pandemic, physicians should be aware of the risk of delirium and be trained in its optimal management.

[A case of cryptococcal empyema successfully treated by debridement by medical thoracoscopy with local anesthesia].

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.

Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen.

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.

Clinical characteristics of COVID-19 in Osaka, Japan: Comparison of the first-third waves with the fourth wave.

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.

Serum immunoglobulin a antibodies to glycopeptidolipid core antigen for Mycobacteroides abscessus complex lung disease.

Background: Mycobacteroides abscessus complex (MABC) exhibits smooth morphotypes, expressing glycopeptidolipid (GPL), and rough morphotypes, expressing diminished GPL, on the MABC cell wall. Few reports have focused on the relationship between anti-GPL-core immunoglobulin A (IgA) antibody and colony morphology in MABC lung disease. Methods: This study aimed to test GPL core antigen in patients with MABC lung disease to investigate the relationship between coinfection/contamination in other nontuberculous mycobacteria species and colony morphology variant in MABC isolates. Patients with MABC lung disease and contamination diagnosed between 2012 and 2017 at our hospital were enrolled retrospectively. Results: Of the assessed patients, 43 patients with MABC lung disease and 13 with MABC contamination were included. There was a significant difference in anti-GPL-core IgA antibody levels between them (P = 0.02). Forty-three patients with MABC lung disease were divided into two groups as positive and negative antibodies groups. A significant increase in the positive anti-GPL-core IgA antibody was observed in coexistence with both Mycobacterium avium complex (MAC) (P = 0.02) and the isolate of the smooth variant (P = 0.03) in MABC. Conclusions: Anti-GPL-core IgA antibodies in patients with MABC are greatly influenced by MAC coexistence, and colony morphology variant of the MABC isolate.

Change in lung function in never-smokers with nontuberculous mycobacterial lung disease: A retrospective study.

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.

Mycobacterium abscessus subsp. abscessus Lung Disease: Drug Susceptibility Testing in Sputum Culture Negative Conversion.

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.