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Complete Genome Sequence of Mycolicibacterium sp. Strain NIID-NTM18, Isolated from Cardiac Implantable Electronic Device Infection and Most Similar to Mycolicibacterium litorale.

Hanako Fukano, Hiroshi Miyama, Seiji Takatsuki, Aki Hirabayashi, Masato Suzuki, Mitsunori Yoshida, Yoshifumi Uwamino, Naoki Hasegawa, Yoshihiko Hoshino

Microbiology resource announcements 9 （ 36 ） 2020年09月

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Clostridioides difficile感染症に対するメトロニダゾールとバンコマイシンの有効性及び安全性評価

三澤可奈, 池谷修, 榎木裕紀, 田口和明, 松元一明, 宇野俊介, 上蓑義典, 長谷川直樹

日本化学療法学会雑誌（(公社)日本化学療法学会） 68 （ Suppl.A ） 339 - 339 2020年09月

ISSN 1340-7007

Gene Xpertを用いた空気予防策解除の妥当性評価

上蓑義典, 宇野俊介, 鎌田浩史, 西村知泰, 石井誠, 長谷川直樹

結核（(一社)日本結核・非結核性抗酸菌症学会） 95 （ 5 ） 122 - 122 2020年09月

ISSN 0022-9776

Does the patient truly not have congenital anomalies of the kidney and urinary tract? Urinary tract infection caused by Gardnerella vaginalis.

Takuma Ohnishi, Shinya Asato, Ayaka Maeda, Mika Nagata, Yoshifumi Uwamino, Isamu Kamimaki

Pediatrics international : official journal of the Japan Pediatric Society 62 （ 8 ） 1009 - 1010 2020年08月

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The rough colony morphotype of Mycobacterium avium exhibits high virulence in human macrophages and mice.

Tomoyasu Nishimura, Masayuki Shimoda, Eiko Tamizu, Shunsuke Uno, Yoshifumi Uwamino, Shoko Kashimura, Ikuya Yano, Naoki Hasegawa

Journal of medical microbiology 69 （ 7 ） 1020 - 1033 2020年07月

Introduction. The incidence of Mycobacterium avium complex (MAC) pulmonary disease (MAC PD), a refractory chronic respiratory tract infection, is increasing worldwide. MAC has three predominant colony morphotypes: smooth opaque (SmO), smooth transparent (SmT) and rough (Rg).Aim. To determine whether colony morphotypes can predict the prognosis of MAC PD, we evaluated the virulence of SmO, SmT and Rg in mice and in human macrophages.Methodology. We compared the characteristics of mice and human macrophages infected with the SmO, SmT, or Rg morphotypes of M. avium subsp. hominissuis 104. C57BL/6 mice and human macrophages derived from peripheral mononuclear cells were used in these experiments.Results. In comparison to SmO- or SmT-infected mice, Rg-infected mice revealed severe pathologically confirmed pneumonia, increased lung weight and increased lung bacterial burden. Rg-infected macrophages revealed significant cytotoxicity, increased bacterial burden, secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CCL5 and CCL3), and formation of cell clusters. Rg formed larger bacterial aggregates than SmO and SmT. Cytotoxicity, bacterial burden and secretion of IL-6, CCL5 and CCL3 were induced strongly by Rg infection, and were decreased by disaggregation of the bacteria.Conclusion.M. avium Rg, which is associated with bacterial aggregation, has the highest virulence among the predominant colony morphotypes.

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Clinical utility of SARS-CoV-2 whole genome sequencing in deciphering source of infection

Takenouchi T., Iwasaki Y.W., Harada S., Ishizu H., Uwamino Y., Uno S., Osada A., Abe K., Hasegawa N., Murata M., Takebayashi T., Fukunaga K., Saya H., Kitagawa Y., Amagai M., Siomi H., Kosaki K.

Journal of Hospital Infection （Journal of Hospital Infection） 107 40 - 4 2020年05月

ISSN 01956701

Coronavirus disease 2019 (COVID-19) caused by human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide problem. From the standpoint of hospital infection control, determining the source of infection is critical. We conducted the present study to evaluate the efficacy of using whole genome sequencing to determine the source of infection in hospitalized patients who do not have a clear infectious contact history. Recently, we encountered two seemingly separate COVID-19 clusters in a tertiary hospital. Whole viral genome sequencing distinguished the two clusters according to the viral haplotype. However, the source of infection was unclear in 14 patients with COVID-19 who were clinically unlinked to clusters 1 or 2. These patients, who had no clear history of infectious contact within the hospital (‘undetermined source of infection’), had haplotypes similar to those in cluster 2 but did not have two of the mutations used to characterize cluster 2, suggesting that these 14 cases of ‘undetermined source of infection’ were not derived from cluster 2. Whole viral genome sequencing can be useful for confirming that sporadic COVID-19 cases with an undetermined source of infection are indeed not part of clusters at the institutional level.

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Effect of refrigeration of blood samples in lithium-heparin tubes on QuantiFERON TB Gold Plus test result

Uwamino Y., Sakai A., Nishimura T., Noguchi M., Uno S., Fujiwara H., Mori M., Wakui M., Murata M., Hasegawa N.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 26 （ 3 ） 312 - 314 2020年03月

ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The QuantiFERON TB Gold Plus (QFT-Plus) test is a newly approved interferon-gamma releasing assay test for detecting latent tuberculosis. Although blood samples for QFT test can be refrigerated for 48 h in lithium-heparin tubes according to package inserts, no published data are available on the effects of sample refrigeration on the test results. We conducted a clinical study that aimed to elucidate whether sample refrigeration for 48 h affects QFT-Plus test results. We collected 2 blood samples each from 40 participants for QFT-Plus; one sample was refrigerated before incubation for QFT-Plus assay, while the other sample was incubated soon after collection and treated as control. After comparing QFT-Plus test results of refrigerated samples and control samples, the concordance rate and kappa coefficient between them were 95% and 0.90, respectively. Thus, blood samples for QFT-Plus test can be refrigerated for 48 h in lithium-heparin tubes without influencing the test results.

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Showering is associated with Mycobacterium avium complex lung disease: An observational study in Japanese women

Uwamino Y., Nishimura T., Sato Y., Tamizu E., Uno S., Mori M., Fujiwara H., Kawabe H., Murata M., Hasegawa N.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 26 （ 3 ） 211 - 214 2020年03月

ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Mycobacterium avium complex refers to a group of environmental bacteria which inhabit water and soil. Although Mycobacterium avium complex is capable of causing refractory lung infections, the risk factors for Mycobacterium avium complex lung disease are still unclear. This study aimed to determine the associations between Mycobacterium avium complex lung disease and soil or water exposure. Using questionnaires along with clinical data, we compared soil exposure, along with bathtub bathing and showering habits between 172 women with Mycobacterium avium complex lung disease and 339 women without Mycobacterium avium complex infection as controls. Showering was found to be independently associated with the presence of Mycobacterium avium complex lung disease (adjusted odds ratio 5.72, 95%, confidence interval 1.99 to 16.46). Although the mean age of the groups was different, an age-matched sub-analysis yielded similar results. These results indicate that showering may be a risk factor for Mycobacterium avium complex lung disease.

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Clostridioides difficile感染症治療薬の有効性と安全性に関する検討

三澤可奈, 池谷修, 榎木裕紀, 田口和明, 松元一明, 宇野俊介, 上蓑義典, 長谷川直樹

日本化学療法学会雑誌（(公社)日本化学療法学会） 68 （ 2 ） 274 - 274 2020年03月

ISSN 1340-7007

バンコマイシンの周術期投与におけるレッドネック症候群発症リスクに関する検討

池谷修, 宇野俊介, 上蓑義典, 尾原秀明, 栗原智宏, 早川智久, 石川春樹, 高野八百子, 松元一明, 長谷川直樹, 新庄正宜, 森毅彦

日本化学療法学会雑誌（(公社)日本化学療法学会） 68 （ 2 ） 291 - 291 2020年03月

ISSN 1340-7007

The annual risk of tuberculosis infection in newly hired researchers and healthcare workers using interferon-gamma release assay in Japan

Nishimura T., Ota M., Mori M., Takano Y., Fujiwara H., Uwamino Y., Uno S., Hasegawa N.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 26 （ 8 ） 818 - 822 2020年

ISSN 1341321X

© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The tuberculosis (TB) notification rate in Japan is gradually decreasing but has not yet achieved “pre-elimination,” defined by the World Health Organization. To effectively tackle, control, and eliminate TB, estimating and monitoring the annual risk of TB infection (ARI) using tuberculin skin testing (TST) to understand the dynamics of TB epidemiology are significantly important. However, studies estimating ARIs using TST are few considering that Bacillus Calmette-Guérin vaccination coverage is high in Japan. This was a single-center, cross-sectional study conducted between January 2011 and December 2018 in Tokyo area where interferon-gamma release assays (IGRAs) were performed in newly hired researchers of Keio University School of Medicine and healthcare workers of Keio University Hospital to determine TB infection. We estimated the prevalence of TB infection and ARI based on their IGRA results. Among the 3908 subjects, 83 (2.124%) had positive IGRA results. Multiple logistic regression analysis revealed that age was a significant risk factor for positive IGRA result (adjusted odds ratio, 1.046). The ARIs were 0.049%–0.156% between 1986 and 2004, midyears of TB infection, but have not significantly decreased over approximately two decades. To decrease the risk of TB infection, advanced strategies to control and eliminate TB in Tokyo area are significantly required.

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5.非重症例に対するClostridioides difficile感染症治療薬の有効性に関する検討

池谷修, 三澤可奈, 宇野俊介, 上蓑義典, 内田翔, 高野八百子, 松元一明, 長谷川直樹

日本臨床腸内微生物学会誌（日本臨床腸内微生物学会） 22 （ 1 ） 34 - 34 2020年

Low serum estradiol levels are related to Mycobacterium avium complex lung disease: A cross-sectional study

Uwamino Y., Nishimura T., Sato Y., Tamizu E., Asakura T., Uno S., Mori M., Fujiwara H., Ishii M., Kawabe H., Murata M., Hasegawa N.

BMC Infectious Diseases （BMC Infectious Diseases） 19 （ 1 ） 1055 - 1055 2019年12月

© 2019 The Author(s). Background: The risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women. Methods: This cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age-and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD. Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age-and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE). Results: Forty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 μg/dL vs. 114.0 μg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02-199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899-0.995). Even the age-and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001). Conclusions: Low serum E2 levels were strongly related to MAC-LD in postmenopausal women.

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Moraxella catarrhalisを含む複数菌種が検出された頸椎化膿性脊椎炎の1例

荒美幸, 宇野俊介, 上蓑義典, 永田美香, 池谷修, 長谷川直樹

日本臨床微生物学会雑誌（(一社)日本臨床微生物学会） 30 （ Suppl.1 ） 307 - 307 2019年12月

ISSN 2434-866X

QuantiFERON TBゴールドプラスの検体のヘパリン管採血と,その冷蔵保存による検査結果への影響

酒井昭子, 上蓑義典, 西村知泰, 森正明, 宇野俊介, 藤原宏, 村田満, 長谷川直樹

日本臨床微生物学会雑誌（(一社)日本臨床微生物学会） 30 （ Suppl.1 ） 295 - 295 2019年12月

ISSN 2434-866X

Recovery of FRI-5 carbapenemase at a Japanese hospital where FRI-4 carbapenemase was discovered.

Yoshifumi Uwamino, Hiroaki Kubota, Takashi Sasaki, Asami Kosaka, Mie Furuhashi, Shunsuke Uno, Jun Kudoh, Mitsuru Murata, Naoki Hasegawa

The Journal of antimicrobial chemotherapy 74 （ 11 ） 3390 - 3392 2019年11月

ISSN 1460-2091

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Evaluation for optimal dosing of vancomycin in patients with different physical types

Hashimoto M., Iketani O., Ichinose N., Enoki Y., Taguchi K., Uno S., Uwamino Y., Hasegawa N., Matsumoto K.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 25 （ 9 ） 735 - 737 2019年09月

ISSN 1341321X

© 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases The sufficient dose to obtain an optimal trough concentration of vancomycin (VCM) in patients with non-standard physical types remains controversial. In this study, we examined the relationship between the dose and physical type in patients in whom an optimal trough concentration was obtained among VCM-treated patients. We retrospectively investigated the dose of VCM and physical type in patients treated with VCM between January 2012 and January 2017 at two medical institutions (n = 272). The physical type was classified using the body mass index (BMI). Patients with a BMI of <18.5 kg/m2 were assigned to the lean group, those with a BMI of 18.5–24.9 kg/m2 were assigned to the standard group, and those with a BMI of ≥25 kg/m2 were assigned to the obesity group. The mean doses of VCM per time (mg/kg) to achieve the target trough concentration of VCM, 15–20 μg/mL, were 19.8 ± 4.3, 16.5 ± 3.7, and 13.7 ± 2.7 mg/kg in the lean, standard, and obesity groups, respectively. The dose per time to achieve the target trough concentration decreased significantly in association with an increase of BMI. The upper limit of the recommended dose (15–20 mg/kg) or higher in lean patients, and the lower dose in obese patients than the recommended dose might be appropriate to achieve the target trough concentration when we calculated the dose per time based on actual body weight.

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Disseminated histoplasmosis from a calcified lung nodule after long-term corticosteroid therapy in an elderly Japanese patient: A case report

Kobayashi K., Asakura T., Kawada I., Hasegawa H., Chubachi S., Ohara K., Kuramoto J., Sugiura H., Fujishima S., Iwata S., Umeyama T., Katano H., Uwamino Y., Miyazaki Y., Kamei K., Hasegawa N., Betsuyaku T.

Medicine （Medicine） 98 （ 17 ） e15264 2019年04月

ISSN 0025-7974

RATIONALE: Histoplasmosis occurs most commonly in Northern and Central America and Southeast Asia. Increased international travel in Japan has led to a few annual reports of imported histoplasmosis. Healed sites of histoplasmosis lung infection may remain as nodules and are often accompanied by calcification. Previous studies in endemic areas supported the hypothesis that new infection/reinfection, rather than reactivation, is the main etiology of symptomatic histoplasmosis. No previous reports have presented clinical evidence of reactivation. PATIENT CONCERNS: An 83-year-old Japanese man was hospitalized with general fatigue and high fever. He had been treated with prednisolone at 13 mg/d for 7 years because of an eczematous skin disease. He had a history of travel to Los Angeles, Egypt, and Malaysia 10 to 15 years prior to admission. Five years earlier, computed tomography (CT) identified a solitary calcified nodule in the left lingual lung segment. The nodule size remained unchanged throughout a 5-year observation period. Upon admission, his respiratory condition remained stable while breathing room air. CT revealed small, randomly distributed nodular shadows in the bilateral lungs, in addition to the solitary nodule. DIAGNOSIS: Disseminated histoplasmosis, based on fungal staining and cultures of autopsy specimens. INTERVENTIONS: The patient's fever continued despite several days of treatment with meropenem, minocycline, and micafungin. Although he refused bone marrow aspiration, isoniazid, rifampicin, ethambutol, and prednisolone were administered for a tentative diagnosis of miliary tuberculosis. OUTCOMES: His fever persisted, and a laboratory examination indicated severe thrombocytopenia with disseminated intravascular coagulation. He died on day 43 postadmission. During autopsy, the fungal burden was noted to be higher in the calcified nodule than in the disseminated nodules of the lung, suggesting a pathogenesis involving endogenous reactivation of the nodule and subsequent hematogenous and lymphatic spread. LESSONS: Physicians should consider histoplasmosis in patients with calcified nodules because the infection may reactivate during long-term corticosteroid therapy.

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Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease

Asakura T., Suzuki S., Fukano H., Okamori S., Kusumoto T., Uwamino Y., Ogawa T., So M., Uno S., Namkoong H., Yoshida M., Kamata H., Ishii M., Nishimura T., Hoshino Y., Hasegawa N.

Open Forum Infectious Diseases （Open Forum Infectious Diseases） 6 （ 4 ） ofz108 2019年04月

© The Author(s) 2019. Background. Sitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD. Methods. We retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFXcontaining regimen for ≥4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy. Results. Clarithromycin resistance (minimum inhibitory concentration [MIC] ≥32 μg/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (≤1 μg/mL), and macrolide resistance were significant predictors of negative sputum culture conversion. Conclusions. Our results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD.

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リネゾリドにより低ナトリウム血症から痙攣を発症した患者

山本冴華, 田口和明, 榎木裕紀, 松元一明, 池谷修, 宇野俊介, 上蓑義典, 長谷川直樹

日本薬学会年会要旨集（(公社)日本薬学会） 139年会（ 4 ） 131 - 131 2019年03月

ISSN 0918-9823

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