SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

No abstract

Candida glabrata can become resistant to fluconazole, causing persistent colonization and invasive infection during prolonged exposure to the drug. To determine the mechanism of resistance in this setting, weekly oropharyngeal cultures for C. glabrata were obtained over a 2-year period from hematopoietic stem cell transplant recipients who were receiving fluconazole prophylaxis. In 20 patients from whom at least two isolates of the same karyotype were obtained more than two weeks apart, fluconazole MICs doubled every 31 days on average. The mechanism of fluconazole resistance in isolates from the 14 of the 20 patients studied in whom MICs changed at least fourfold was studied. Cellular resistance was accompanied by increased drug efflux as measured by decreased accumulation of fluconazole and rhodamine 6G and increased abundance of transcripts from two drug transporters, CgCDR1 and PDH1. The rapidity and regularity of the rising resistance indicated that C. glabrata is able to upregulate drug efflux without losing the ability to maintain colonization.Fluconazole prophylaxis of hematopoietic stem cell transplant recipients decreased the incidence of candidemia at the Fred Hutchinson Cancer Research Center from 11% in 1980 to 1986 to 3% in 1994 to 1997 (13). The Candida species most commonly invading the bloodstream also changed. The prevalence of Candida albicans in blood cultures decreased from 64 to 3%, whereas that of Candida glabrata increased from 4 to 47%. Colonization with C. glabrata occurred in 88 of 585 (15%) patients receiving fluconazole prophylaxis. Colonization was present on admission in 43% of the patients and appeared after admission in 57% of the patients, with the median time of onset being day 36. C. glabrata sepsis occurred by posttransplant day 120 in 9.8% of colonized patients.The fluconazole MIC for C. glabrata is approximately 16 times higher than that for C. albicans (18), accounting for the selection of this species during fluconazole prophylaxis. We addressed the question whether resistance increased during fluconazole prophylaxis for stem cell recipients and, if so, whether this change was due to the acquisition of a new isolate or a change in an existing isolate. We also asked whether increased fluconazole resistance in an existing isolate might be due to increased drug efflux and increased activity of the ABC transporters CgCDR1 and PDH1, which have been associated with fluconazole resistance in prior reports (15,20).Both genes were noted to have increased transcription in isolates which were more fluconazole resistant than a patient's prior isolate. In both reports, increased resistance occurred in the same strain in the patient rather than by acquisition of a new strain. To provide an estimate of drug efflux, we measured fluconazole and rhodamine 6G accumulation in pairs of isolates that had been obtained from the same patient and had the same karyotype. Both compounds have been reported to have less accumulation in fluconazole-resistant C. glabrata due to increased drug efflux (...

This study demonstrated risk factors for perforation and delayed bleeding associated with ESD. Furthermore, it was clarified that perforation and delayed bleeding influenced post-procedure results and prognosis after ESD.

SUMMARYChronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment is limited. We conducted a randomized, multicenter, open-label trial comparing intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for the treatment of 107 inpatients with CPA to compare the efficacy and safety of both drugs as initial treatment in Japan.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children and young adults. Although MP sometimes causes self-limiting pneumonia, severe and fulminant cases with hypoxia occur, but their clinical features have rarely been reported. This study aimed to reveal the clinical manifestations, risk factors, and treatment of fulminant MP pneumonia (MPP). Using PubMed and abstracts from the proceedings of several domestic Japanese academic societies, we reviewed the Japanese and English literature for cases of fulminant or severe MPP reported in Japan. All clinical information such as sex, age, underlying diseases, clinical symptoms, clinical course, laboratory and radiological findings, and treatment was collected and analyzed. In total, 52 fulminant MPP cases were reported between September, 1979 and February, 2010. The dominant population of fulminant MPP was young adults without severe underlying diseases. Cough (97.3%), fever (100.0%), and dyspnea (83.3%) with diffuse abnormal findings in radiological examinations were noted. Antibiotics without anti-mycoplasmal activity were used in 32 cases (61.5%) as initial treatment prior to the onset of hypoxia. Anti-mycoplasmal drugs were appropriately used in 41 cases (78.8%) after onset of respiratory failure with steroids (23 cases, 45.1%) and effective. The majority of patients improved within 3-5 3 days after steroid administration. There were only 2 fatal cases. Although this small retrospective study did not reveal the apparent risk factors of fulminant MPP, initial inappropriate use of antibiotics may be a risk factor, and early administration of appropriate anti-mycoplasmal drugs with steroids as a cellular immune suppressor is required.4

A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress.