Nobuyuki Shimono

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (64)122.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In our hospital, positive blood culture rates of Helicobacter cinaedi dramatically increased after introducing the Bactec system. A simulated culture model of H. cinaedi bacteremia demonstrated no positive signals using the BacT/Alert system, despite efficient growth in bottles. Clinically suspected H. cinaedi bacteremia should be monitored more closely when using the BacT/Alert system, preferably with subcultivation after 7days of incubation. Copyright © 2015. Published by Elsevier Inc.
    Diagnostic microbiology and infectious disease 07/2015; 52. DOI:10.1016/j.diagmicrobio.2015.07.017 · 2.46 Impact Factor
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    ABSTRACT: Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is critical in the clinical setting and to define a therapeutic strategy; however, the associated factors and prognosis for S. maltophilia bacteremia have not been fully evaluated to adequately characterize these factors. We first conducted a matched case-control study to clarify these questions. A total of 30 case patients with S. maltophilia bacteremia were compared with 30 control patients with P. aeruginosa bacteremia between January 2005 and August 2014, according to matching criteria based on underlying disease, age, and gender. The 30-day mortality rate for the case patients (53.3%) was significantly higher than that of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional logistic regression analysis showed that the predisposing factors specific for the detection of S. maltophilia bacteremia were indwelling artificial products other than a central venous catheter, ICU stay, and previous use of anti-MRSA drugs. The high severity of illness was associated with mortality in both case and control patients. Interestingly, inappropriate antimicrobial treatment was an additional independent risk factor for mortality in only the case patients with S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with fluoroquinolones inactive against the S. maltophilia isolates was mainly responsible for the inappropriate treatment. These results suggest that more precise prediction and more appropriate treatment might improve the prognosis of patients with S. maltophilia bacteremia.
    PLoS ONE 07/2015; 10(7):e0133731. DOI:10.1371/journal.pone.0133731 · 3.23 Impact Factor
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    Dataset: mmc2
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    Dataset: mmc1
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    ABSTRACT: Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis. We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay. Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity. We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Transplant Infectious Disease 07/2015; DOI:10.1111/tid.12423 · 2.06 Impact Factor
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    ABSTRACT: Microflex LT (Bruker Daltonics) and VITEK MS (bioMerieux) are bacterial identification systems that are based on Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometer (MALDI-TOF MS). For VITEK MS, two identification softwares, the VITEK MS IVD software (IVD) and SARAMIS software (SARAMIS), are available. Microflex LT is equipped with the MALDI Biotyper RTC software (Biotyper). Although the identification accuracy of each instrument has been compared for various bacteria, no detailed examination has been conducted for the identification accuracy of Clostridium difficile. In this report, we compared the three identification softwares in the identification reproducibility in three ATCC C. difficile strains and the identification accuracy in 50 clinical C. difficile isolates. The results showed 100%, 91.7%, and 100% identification reproducibility accuracy of ATCC strains when examined by IVD, SARAMIS, and Biotyper software, respectively. For the identification of the clinical isolates, all three softwares exhibited satisfactory identification accuracy of C. difficile. Among the 50 clinical isolates, seven showed identical toxin genotype corresponding to the exact same ribotype. However, MALDI-TOF failed to identify them as the identical type. Based on the above results, we concluded that both the types of MALDI-TOF MS reproducibly identified C. difficile, however, they are currently not suitable for typing of C. difficile clones.
    Journal of Medical Microbiology 07/2015; DOI:10.1099/jmm.0.000136 · 2.25 Impact Factor
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    ABSTRACT: Fungus balls have been rarely implicated as a cause of urinary tract obstruction. Here, we report a case of Candida albicans fungus balls in the urinary tract after the treatment of Candida endophthalmitis that has enough periods and adequate amount of antifungal agents. The patient completely recovered from this rare complication by irrigating through single-J stent and changing antifungal agents. Here we emphasize that we should take into account not only the susceptibility test results but also the difference in excretion route and tissue distribution of antifungal agents. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Journal of Infection and Chemotherapy 05/2015; 21(9). DOI:10.1016/j.jiac.2015.04.009 · 1.49 Impact Factor
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    ABSTRACT: Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27-468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Infection and Chemotherapy 04/2015; 21(7). DOI:10.1016/j.jiac.2015.04.004 · 1.49 Impact Factor
  • Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 04/2015; 48(2):S128. DOI:10.1016/j.jmii.2015.02.452 · 2.35 Impact Factor
  • Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 04/2015; 48(2):S170. DOI:10.1016/j.jmii.2015.02.595 · 2.35 Impact Factor
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    ABSTRACT: The virulence of Stenotrophomonas maltophilia is low, but once it causes bacteremia in immunocompromised patients, the course sometimes becomes fatal. Trimethoprim-sulfamethoxazole(ST) is the standard antimicrobial agents for the treatment of S. maltophilia. In our hospital, the resistance rate of S. maltophilia against ST had been reported at around 90%.Our institution uses the broth microdilution method in antimicrobial susceptibility testing(AST) for S. maltophilia, but assessment of the result is not always easy. From April 2005 through March 2011, 22 clinical strains of S. maltophilia were isolated from bacteremia patients in Kyushu University Hospital in Japan. Using these strains, we compared the results of 4 different AST methods; the broth microdilution method(BMD) combined with visual judgment by a single medical technologist(BMD sgl) and BMD judged by two or more experienced medical technologists(BMD pi), an E test(ET) and the agar dilution method(AD). The results demonstrated the following AST resistance: 90.9% with BMD sgl, 54.5% with BMD pi, 27.3% with ET, and 31.8% with AD. From these results, it has become apparent the difficulty of visual assessment in BMD. Compared to AD, which is regarded as a standard method, we detected major errors(ME) in 4.5% with ET, 49.0% with BMD sgl and 13.7% with BMD pi. The reason why we observed more ME cases in BMD was judged to be the influence of the gross visual assessment process. With regard to the adverse effects of ME cases in BMD sgl, we studied the clinical and laboratory information by extracting digital medical records. In 13 cases with ME, in BMD sgl, ST was administered in 3 cases, and the mortality rate was 33.3%, whereas the mortality rate of the cases without administration of ST was 30%. Fortunately, there was no significant adverse difference between the groups with or without administration of ST. However, considering the difficulty in evaluating the AST results of ST against S. maltophilia with BMD, we should try ET for confirmation of the results.
    Japanese Journal of Chemotherapy 01/2015; 63(1):1-6.
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    ABSTRACT: The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae “putative serotype 6E” isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as “putative serotype 6E,” followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that CC90, including ST90 and its variants, was the most prevalent clonal group of “putative serotype 6E” isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the “putative serotype 6E” isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that “putative serotype 6E” is prevalent in Asian countries. The clonal dissemination of “putative serotype 6E” isolates was also identified.
    Diagnostic Microbiology and Infectious Disease 12/2014; 80(4). DOI:10.1016/j.diagmicrobio.2014.08.017 · 2.46 Impact Factor
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    ABSTRACT: Zygomycosis is a lethal and invasive mold infection that is often associated with hematological malignancies. The keys for successful treatment include making a rapid diagnosis and appropriately administering antifungal agents. We herein report the early diagnosis of a case of zygomycosis in a patient with acute myeloid leukemia using a deoxyribonucleic acid sequence analysis. We successfully performed allogeneic hematopoietic stem cell transplantation with the use of high-dose liposomal amphotericin B and granulocyte transfusion.
    Internal Medicine 05/2014; 53(10):1087-91. DOI:10.2169/internalmedicine.53.1366 · 0.90 Impact Factor
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    ABSTRACT: A 73-year-old woman with breast cancer and metastasis under chemotherapy suffered from fever, pleural effusion and pericardial effusion. Despite the administration of treatment with cefozopran and prednisolone, the patient's fever relapsed. An electrocardiogram identified a new complete atrioventricular block and an echocardiogram revealed vegetation with an unusual pseudotumoral mass in the right atrium. Blood cultures grew Listeria monocytogenes. The patient was eventually diagnosed with right-sided infective endocarditis, which improved following the six-week administration of ampicillin and gentamicin. Homemade yoghurt was suspected to be the cause of infection in this case. Listeria endocarditis is rare; however, physicians should pay more attention to preventing this fatal disease in immunocompromised patients.
    Internal Medicine 05/2014; 53(9):1029-1032. DOI:10.2169/internalmedicine.53.1925 · 0.90 Impact Factor
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    ABSTRACT: A methicillin-resistant Staphylococcus aureus (MRSA) strain with additional β-lactam-inducible aminoglycoside-resistance was previously reported by a group at the Kitasato University in Japan. In addition to gentamicin, the 'Kitasato strain' was resistant to arbekacin (ABK), which is primarily used as an anti-MRSA aminoglycoside. No following studies regarding the spread of MRSA strains with the newly identified resistance mechanism have been reported to date. To obtain epidemiologic data on MRSA strains with the antagonistic resistance and to analyze their genetic features, we longitudinally examined the emergence of β-lactam-inducible ABK-resistant MRSA strains at our university hospital. Among the 396 isolates, 35 (8.8%) were found to be ABK-resistant MRSA strains (the resistance being induced by β-lactams). Moreover, based on the pulsed field gel electrophoresis profiles, the clonality of those MRSA strains changed at different periods. In the Kitasato strain, the antagonistic mechanism was clearly demonstrated by the integration of transposable elements; a Tn4001-IS257 hybrid structure that contained an aminoglycoside resistance gene cointegrated into a region downstream of the β-lactamase gene. In most of the MRSA strains detected in our study, the antagonistic interaction was explained by the same mechanism as that found in the Kitasato strain. Interestingly, sequence analysis showed that all of our strains carried IS257 insertion sites different from those of the Kitasato strain. This study shows that MRSA strains with the additional antagonistic resistance are not uncommon and have been increasingly disseminating in clinical settings.
    Journal of Medical Microbiology 02/2014; 63(Pt_5). DOI:10.1099/jmm.0.065276-0 · 2.25 Impact Factor
  • Masako Kadowaki · Nobuyuki Shimono
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    ABSTRACT: Candida catheter-related bloodstream infection (CRBSI) is a biofilm-related disease, which is usually refractory because antifungals show limited effect. With medical development and increase in number of compromised hosts, CRBSI became more frequent. Candida, which is one of the opportunistic pathogens, ranks the fourth causative organism of bacteremia. The onset of bacteremia is greatly associated with the presence of catheter. Repeated blood cultures and the central venous catheter (CVC) tip culture are done for the definitive diagnosis of Candida CRBSI. Additionally serological examinations such as (1 --> 3)-beta-D-glucan and mannan antigen are also useful for early diagnosis. It is important for the appropriate treatment to remove CVC, which is an artificial contaminated material, and administer antifungals promptly. As to the choice of antifungals, we should also take into account the ability of antibiofilm effect of antifungals as well as immunological state of host including neutropenia, prior administration of azoles, isolated or estimated Candida species, sensitivity against antifungals, administration route, pharmacokinetics (bioavailability, metabolic and excretion pathway, distribution) and drug interaction. As to complication of Candida bacteremia, first we should check endophthalmitis, which occurs frequently and leads to the loss of eyesight, as well as infective endocarditis, arthritis, metastatic infections such as embolic pneumonia and suppurative thrombotic phlebitis of catheter insertion site. Lastly we emphasize that the appropriate treatment based on the character of Candida bacteremia and biofilm leads to favorable prognosis.
    The Japanese journal of antibiotics 02/2014; 67(1):1-14.
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    ABSTRACT: Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.
    PLoS ONE 01/2014; 9(1):e85210. DOI:10.1371/journal.pone.0085210 · 3.23 Impact Factor
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    ABSTRACT: Peripheral mycotic aneurysm is a rare complication of infective endocarditis. We herein report the case of a 61-year-old man with a mycotic aneurysm in the left brachial artery, that appeared during treatment with antibiotics against infective endocarditis caused by Streptococcus sanguinis. After confirming the collateral blood flow on arteriography, we resected the aneurysm and performed valvuloplasty, annuloplasty and coronary artery bypass grafting. The patient has been in good condition without complications, such as motor dysfunction or neuropathy.
    Internal Medicine 10/2013; 52(20):2361-2365. DOI:10.2169/internalmedicine.52.0747 · 0.90 Impact Factor
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    ABSTRACT: We recently demonstrated that expression of α-defensins, the major antimicrobial peptides produced by Paneth cells was severely suppressed in mice with graft-versus-host disease (GVHD). In this study, we found that antibacterial lectin, regenerating islet-derived IIIγ (RegIIIγ) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIIIγ was mediated by a mechanism independent upon radiation-induced intestinal tract damage. MyD88-mediated signaling in intestinal epithelium was required for RegIIIγ upregulation in GVHD and antibiotic therapy downregulated RegIIIγ expression. These results suggest that MyD88-mediated sensing of the intestinal microbes disregulated in GVHD induces RegIIIγ upregulation in GVHD and argue a role for RegIIIγ in the pathogenesis of GVHD.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2013; 19(10). DOI:10.1016/j.bbmt.2013.07.027 · 3.40 Impact Factor
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    ABSTRACT: There is increasing interest in the role of T cell exhaustion and it is well known that the natural history of chronic hepatitis C virus infection (HCV) is modulated by CD8(+) T cell immunobiology. There are many pathways that alter the presence of exhaustive T cells and, in particular, they are functionally impaired by inhibitory receptors, such as programmed death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). We obtained spleen, liver, and peripheral blood (before and after splenectomy) lymphoid cells from 25 patients with HCV-related cirrhosis undergoing liver transplantation for end-stage disease or splenectomy for portal hypertension. In all samples we performed an extensive phenotypic study of exhaustion markers (PD-1, Tim-3, IFNγ) and their ligands (PD-L1, PD-L2, galectin-9) in CD8(+) T cell subpopulations (both total and HCV-specific) and in antigen-presenting cells (APC; monocytes and dendritic cells). In the spleen, total and HCV-specific CD8(+) T cells demonstrated enhanced markers of exhaustion, predominantly in the effector memory subpopulation. Similarly, splenic APC overexpressed inhibitory receptor ligands when compared to peripheral blood. Finally, when peripheral blood CD8(+) T cells were compared before and after splenectomy, markers of exhaustion were reduced in splenic CD8(+) T cells and APC. Our data in HCV related cirrhosis suggest that CD8(+) T cells in the spleen manifest a significantly higher exhaustion compared to peripheral blood and may thus contribute to the failure to control HCV. Counteracting this process may contribute to inducing an effective immune response to HCV.
    Clinical & Experimental Immunology 06/2013; 174(1). DOI:10.1111/cei.12158 · 3.04 Impact Factor

Publication Stats

310 Citations
122.65 Total Impact Points


  • 1991–2015
    • Kyushu University
      • • Division of Internal Medicine
      • • Department of Clinical Chemistry and Laboratory Medicine
      • • Graduate School of Medical Sciences
      Hukuoka, Fukuoka, Japan
  • 2012
    • University of Colombo
      Columbo, Western, Sri Lanka
  • 2008–2010
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan