論文 - 宮崎 泰可
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Yamashita C., Takesue Y., Matsumoto K., Ikegame K., Enoki Y., Uchino M., Miyazaki T., Izumikawa K., Takada T., Okinaka K., Ueda T., Miyazaki Y., Mayumi T.
Journal of Infection and Chemotherapy 26 ( 6 ) 596 - 603 2020年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49–0.99; RR 0.48, 95% CI 0.33–0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87–1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46–0.99; RR 0.53, 95% CI 0.37–0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.
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Takazono T., Imamura Y., Kitamura M., Furugen R., Hirayama T., Tashiro M., Saijo T., Yamamoto K., Miyazaki T., Saito T., Izumikawa K., Yanagihara K., Mukae H.
Respiratory Investigation 58 ( 3 ) 212 - 215 2020年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Respiratory Investigation
Endobronchial volatile sulfur compounds in patients with lung abscess or lung cancer were measured using the Oral Chroma™ gas chromatograph. High levels of hydrogen sulfide and methyl mercaptan were observed in some patients with lung abscess but not in patients with lung cancer. Measuring endobronchial volatile sulfur compounds could be useful for the rapid diagnosis of lung abscess caused by obligate anaerobes.
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Akagi K., Miyazaki T., Oshima K., Umemura A., Shimada S., Morita K., Senju H., Tashiro M., Takazono T., Saijo T., Kurihara S., Sekino M., Yamamoto K., Imamura Y., Izumikawa K., Yanagihara K., Uda A., Morikawa S., Yoshikawa T., Kurosu T., Shimojima M., Saijo M., Mukae H.
BMC Infectious Diseases 20 ( 1 ) 2020年4月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. Case presentation: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. Conclusions: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed.
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Tashiro M., Takazono T., Saijo T., Yamamoto K., Imamura Y., Miyazaki T., Kakeya H., Ando T., Ogawa K., Kishi K., Tokimatsu I., Hayashi Y., Fujiuchi S., Yanagihara K., Miyazaki Y., Ichihara K., Mukae H., Kohno S., Izumikawa K.
Clinical Infectious Diseases 70 ( 5 ) 835 - 842 2020年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Infectious Diseases
Background. There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). Methods. We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. Results. Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.5 and OR, 5.7; 95% CI, 2.0-15.7, respectively). Conclusions. Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients. Clinical Trials Registration: UMIN000007055.
DOI： 10.1093/cid/ciz287
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Miyazaki T., Yanagihara K., Kakeya H., Izumikawa K., Mukae H., Shindo Y., Yamamoto Y., Tateda K., Tomono K., Ishida T., Hasegawa Y., Niki Y., Watanabe A., Soma K., Kohno S.
Journal of Infection and Chemotherapy 26 ( 2 ) 242 - 251 2020年2月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia. This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed. In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31–14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35–7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26–9.92) were risk factors for mortality. In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.
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Nakada-Motokawa N., Miyazaki T., Mizuta S., Tanaka Y., Hirayama T., Takazono T., Saijo T., Yamamoto K., Imamura Y., Izumikawa K., Yanagihara K., Makimura K., Takeda K., Kohno S., Mukae H.
ChemistrySelect 5 ( 3 ) 1140 - 1145 2020年1月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ChemistrySelect
Invasive fungal infections are growing causes of morbidity and mortality in immunocompromised patients. However, only one antifungal drug class has been developed in the last 30 years, extremely limiting current therapeutic options. To address unmet medical needs, we performed high-throughput screening of 9600 chemical compounds and identified an aminohydrazone derivative as a novel and potent antifungal compound. We then designed and synthesized a series of aminohydrazone derivatives, and demonstrated that 1-[(E)-[4-(3′,4′-dichlorobenxyloxy)phenyl methylidene]amino]-guanidine had the most potent inhibitory activity and exhibited a broad spectrum of antifungal activities against Candida species (including multidrug resistant C. auris), Aspergillus species, Cryptococcus neoformans, and Rhizopus oryzae. Against C. albicans, the leading cause of Candida infections, the compound had fungicidal activity for planktonic cells at 8 μg mL−1 (25 μM) and anti-biofilm activity at 34 μg mL−1 (100 μM). This study provides new insights for the development of a new drug class for the treatment of invasive fungal infections which are often refractory to conventional therapies.
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Tanaka Y., Yamamoto K., Fukuda Y., Umemura A., Yoshida M., Ideguchi S., Ashizawa N., Hirayama T., Tashiro M., Takazono T., Imamura Y., Miyazaki T., Izumikawa K., Yanagihara K., Chang B., Mukae H.
Emerging Microbes and Infections 9 ( 1 ) 2266 - 2268 2020年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Emerging Microbes and Infections
A 68-year-old Japanese man was admitted to our hospital for an acute febrile illness with shivering and impaired consciousness. He was a previous smoker and had a history of chronic obstructive pulmonary disease, for which he inhaled steroid with a long-acting bronchodilator. He had received a 23-valent pneumococcal polysaccharide vaccination 2 years previously. He was intubated and placed on a ventilator in intensive care unit because of acute respiratory failure and hypercapnia. Streptococcus pneumoniae was grown from his blood, sputum, and urine cultures, and he was diagnosed with invasive pneumococcal disease with acute renal failure. He was treated with intravenous beta-lactam and macrolide with continuous hemodiafiltration and was discharged 3 months later. The pneumococcus was identified as serotype 12F, and his serotype-specific IgG and opsonophagocytic index against serotype 12F indicating a lack of protection from IPD among PPV23 serotypes. This case highlights that some individuals may have a serotype-specific polysaccharide antibody failure that makes them susceptible to serotype 12F invasive pneumococcal disease. This case also illustrates the need for serotype-specific IgG and opsonophagocytic index titre cut-offs for each specific pneumococcal serotype in available vaccines to understand the vaccination protection for individual patients better.
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Izumikawa K., Kakeya H., Sakai F., Shibuya K., Sugita T., Takazono T., Takata T., Tashiro M., Teruya K., Nakamura S., Noguchi H., Hiruma M., Makimura K., Miyazaki T., Miyazaki Y., Yamagishi Y., Yoshida K., Watanabe A.
Medical Mycology Journal 61 ( 4 ) 61 - 89 2020年