Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences.

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.

Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study.

BACKGROUND: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD. METHODS: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed. RESULTS: The median age [interquartile range] of the patients was 67 [63-74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361-470] m and 1 [0-2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS. CONCLUSIONS: The decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient's condition and tailor their healthcare environment.

Nasopharyngeal Mycobacterium abscessus Infection: A Case Report and Literature Review.

Background: Mycobacterium abscessus (M. abscessus) is a rapidly growing bacterium (RGM) that causes refractory pulmonary and extrapulmonary infections. However, studies investigating pharyngeal and laryngeal M. abscessus infections are limited. Case Presentation: A 41-year-old immunocompetent woman complaining of bloody sputum was referred to our hospital. Although her sputum culture tested positive for M. abscessus subsp. abscessus, radiological findings were not indicative of pulmonary infection or sinusitis. Further diagnostic workup, including laryngeal endoscopy and positron emission tomography/computed tomography (PET/CT), confirmed the presence of nasopharyngeal M. abscessus infection. The patient was initially treated with intravenous amikacin, imipenem/cilastatin, azithromycin, and clofazimine for 28 days, after which the patient was provided with amikacin, azithromycin, clofazimine, and sitafloxacin for four months. After the completion of antibiotic therapy, the patient showed negative results on sputum smear and culture and normal findings on PET/CT and laryngeal endoscopy. Whole-genome sequencing of this strain revealed that it belonged to the ABS-GL4 cluster, which has a functional erythromycin ribosomal methylase gene, although it is not a major lineage in non-cystic fibrosis (CF) patients in Japan and Taiwan and in CF patients in European countries. We conducted a literature review and identified seven patients who developed pharyngeal/laryngeal non-tuberculous mycobacterium (NTM) infection. Four of the eight patients had a history of immunosuppressant use, including steroids. Seven of the eight patients responded well to their treatment regimens. Conclusion: Patients whose sputum culture tests are positive for NTM and who meet the diagnostic criteria for NTM infection but do not have intrapulmonary lesions should be evaluated for otorhinolaryngological infections. Our case series revealed that immunosuppressant use is a risk factor for pharyngeal/laryngeal NTM infection and that patients with pharyngeal/laryngeal NTM infections respond relatively well to antibiotic therapy.

Heart Failure With Reduced Ejection Fraction Caused by Osimertinib in a Patient With Lung Cancer: A Case Report and Literature Review.

Osimertinib is widely used for the treatment of advanced lung cancers harboring epidermal growth factor receptor (EGFR) mutations. Because of its inhibitory activity on the human epidermal growth factor receptor 2 pathway, osimertinib-induced cardiotoxicity is concerning. Large-scale international clinical studies revealed a subclinical decline in the left ventricular ejection fraction (LVEF) with osimertinib, which allowed a continuation of the drug. Only a few studies have reported symptomatic heart failure with reduced ejection fraction (HFrEF) with osimertinib, and its clinical impact in real-world settings remains unclear. A 91-year-old man was diagnosed with lung adenocarcinoma harboring an EGFR L858R mutation and was started on osimertinib. The treatment conferred substantial tumor regression; however, the patient presented with symptomatic HFrEF six weeks after osimertinib initiation. Transthoracic echocardiography demonstrated diffuse hypokinesis of the left ventricular walls with a significantly reduced ejection fraction from the baseline. Initial evaluation showed no causative cause of heart failure, and we suspected osimertinib-associated cardiomyopathy. Discontinuation of the drug along with the cardioprotective approach improved cardiac symptoms and restored the LVEF to baseline within a week. Here, we comprehensively review the literature and discuss the clinical features of HFrEF following osimertinib administration. Physicians should be aware of rare complications associated with osimertinib therapy.

Pulmonary Mycobacterium kyorinense infection secondary to cavitary pulmonary tuberculosis.

Mycobacterium kyorinense (M. kyorinense) was first reported in patients with pulmonary infection or lymphadenitis in 2009. To date, fewer than 20 cases of pulmonary or extra-pulmonary infections have been reported with the bacterium, and the clinical features remain unclear. We report a case of pulmonary M. kyorinense infection in a 45-year-old man who had a history of cavitary pulmonary tuberculosis seven years ago. The patient visited a hospital due to hemosputum and a prolonged productive cough. Chest computed tomography revealed large and thick-walled cavities, with surrounding parenchymal infiltration in the right upper and lower lung lobes. The microbiological diagnosis of M. kyorinense was based on positive culture results from multiple respiratory tract specimens. The patient's treatment started with antimycobacterial medicines, clarithromycin, moxifloxacin, and intravenous amikacin, in accordance with the drug susceptibility profile and previous case reports. The treatment stabilized the patient's symptoms and improved the thoracic imaging. In addition, the sputum culture was negative after the treatment. We reviewed the literature and summarized the clinical features of M. kyorinense infection in 18 patients. All patients with extrapulmonary infections were immunocompromised. In contrast, pulmonary infection occurred in immunocompetent patients who often had a predisposing lung disease. Cavitary lesions were observed at diagnosis only in patients with prior cystic or cavitary lung disease, including pulmonary tuberculosis. This study contributes to the body of case knowledge of M. kyorinense infection and summarizes the clinical features in the literature.

Eosinophilic annular erythema showing eosinophil cytolytic ETosis successfully treated with benralizumab.

A 56-year-old woman presented with repeated swelling of the lips and face. She had a history of childhood asthma; she had a recurrence of asthma when she was 54 years old and was taking inhaled corticosteroids, and other antiasthma drugs. The swelling of her lips and face improved temporarily with oral corticosteroids (OCS), but recurred soon after discontinuing OCS. Her peripheral blood eosinophil count was 632/µL (9.3%), and her serum was negative for myeloperoxidase-anti-neutrophil cytoplasmic antibody and serine proteinase3-anti-neutrophil cytoplasmic antibody. Hematoxylin and eosin staining of her back skin revealed abundant eosinophilic infiltrate around the vascular area of the shallow dermis layer, but no evidence of vasculitis and we diagnosed her as eosinophilic annular erythema (EAE). Punctate staining of galectin-10, chromatolytic eosinophils, and net-like DNA was also evident in close proximity to the free granules, indicating extracellular vesicles and eosinophil extracellular traps (ETosis). We started daily OCS to control her asthma and skin eruption/oedema. Three months after administering daily OCS, benralizumab was initiated for withdrawal from OCS dependence and treatment of severe asthma. After initiation of benralizumab, her skin and subcutaneous tissue symptoms promptly improved. OCS was discontinued, and no edematous erythema has been observed since then. Bronchial asthma has also been well-controlled. This is the first report on the evidence of eosinophil ETosis in the dermis of EAE patients and the efficacy of benralizumab in a patient with EAE. Benralizumab may be a useful drug for treating refractory EAE with severe eosinophilic asthma.