Abstract Physicians often fail to suspect Clostridium difficile infection (CDI) and many microbiology laboratories use suboptimal diagnostic techniques. To estimate the extent of and reasons for ...incorrect diagnosis of CDI in Japan, we investigated toxigenic C. difficile isolated from all stool culture samples and clinical course. Over a 12-month period in 2010, all stool culture samples (n = 975) submitted from inpatients in a university hospital in Japan were cultured for C. difficile and routine microbiological testing was conducted. In total, 177 C. difficile isolates were recovered, and 127 isolates were toxigenic. Among the toxin-A-positive/toxin-B-positive isolates, 12 were also positive for the binary toxin gene. However, clinically important ribotypes, such as 027 and 078, were not identified. A total of 58 (45.7%) cases with toxigenic C. difficile had unformed stool, and the incidence CDI was 1.6 cases per 10,000 patient-days. Of these 58 cases, 40 were not diagnosed in routine testing due to a lack of clinical suspicion (24.1%, 14/58) or a negative C. difficile toxin assay result (44.8%, 26/58). A stool toxin assay was performed in 54 patients (78.2%, 54/69) who did not have unformed stool. The present study demonstrated that a significant number of CDI cases in Japan might be overlooked or misdiagnosed in clinical practice due to a lack of clinical suspicion and limitations of microbiological testing for CDI in Japan. Providing education to promote awareness of CDI among physicians is important to improve the accuracy of diagnosis in Japan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Multiple clones of Staphylococcus aureus were identified in implantable device-associated infection.•Different clones were recovered from blood cultures on the same day, including both MRSA and ...MSSA.•Antimicrobial susceptibility of a clone can change during prolonged courses of treatment of chronic infections.
The case of a patient with left ventricular assist device (LVAD)-associated endocarditis involving multiple clones of Staphylococcus aureus is presented. Different clones with distinct colony morphology were identified from blood cultures collected on the same day and showed diverse antimicrobial resistance patterns. In addition, a difference in antimicrobial susceptibility was observed even within an identical clone recovered 400 days apart due to the loss of SCCmec for methicillin and modification of the 23S rRNA target site for linezolid during a long-term treatment course.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is considerable interest in expanding B cell-targeted therapies in human autoimmune diseases. However, clinical trials in human primary biliary cholangitis (PBC) using a chimeric antibody ...against human CD20 (hCD20) have showed limited efficacy. Two potential explanations for these disappointing results are the appearance of anti-drug antibodies (ADAs) and the high frequency of patients with moderate PBC or patients who had failed ursodeoxycholic acid treatment. Here, we studied a novel humanized IgG1 antibody against hCD20 and explored its efficacy in early stage PBC using a well-defined murine model. We developed a unique murine model consisting of dnTGF-βRII mice expressing hCD20 and human Fcγ receptors (hFcγRs). Beginning at 4-6 weeks of age, equivalent to stage I/II human PBC, female mice were given weekly injections of an anti-hCD20 antibody (TKM-011) or vehicle control, and monitored for liver histology as well as a broad panel of immunological readouts. After 16 weeks' treatment, we observed a significant reduction in portal inflammation, a decrease in liver-infiltrating mononuclear cells as well as a reduction in liver CD8
T cells. Importantly, direct correlations between numbers of liver non-B cells and B cells (
= 0.7426,
= 0.0006) and between numbers of liver memory CD8
T cells and B cells (
= 0.6423,
= 0.0054) were apparent. Accompanying these changes was a dramatic reduction in anti-mitochondrial antibodies (AMAs), interleukin (IL)-12p40 and IL-5, and elevated levels of the anti-inflammatory chemokine CXCL1/KC. In mice that developed ADAs, clinical improvements were less pronounced. Sustained treatment with B cell-targeted therapies may broadly inhibit effector pathways in PBC, but may need to be administered early in the natural history of PBC.
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•HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils.•HGF inhibited the secretory process mediated by piecemeal degranulation.•In contrast, the ...inhibitory effect of HGF on ETosis-mediated cytolytic degranulation was limited.
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract We aimed to elucidate the current epidemiological features of outpatient skin and soft tissue infection (SSTI)-associated methicillin-resistant Staphylococcus aureus (MRSA) in Japan. ...Altogether, we evaluated the performance of a phage-open reading frame typing (POT) kit for genotyping these MRSA strains. We collected 57 MRSA strains from all outpatients with SSTIs attending a teaching hospital in Japan. Drug susceptibility measurement and genotyping including SCC mec typing, spa typing, multilocus sequence typing, pulsed-field gel electrophoresis, and commercial POT-kit were performed. The majority of strains (39 strains, 68 %) had the SCC mec -II element. Seventeen strains (30 %) with SCC mec -IV accounted for the second largest population. Strains with SCC mec -IV and SCC mec -V appeared multiclonal, and a predominance of Panton–Valentine leukocidin (PVL) gene-negative CC8/ spa -CC008 strains, as well as the first isolate of an ST93 strain in Japan, was observed among them. Only one USA300 strain was identified. Strains with SCC mec -IV and SCC mec -V were significantly susceptible to antimicrobials. The PVL gene was found in 5 SCC mec -IV strains and 1 SCC mec -V strain. The POT-kit successfully predicted the SCC mec type in 54 strains (95 %), and typing by POT1 scores was highly concordant with SCC mec typing and spa typing. Moreover, three PVL-positive strains fell into a particular POT type (POT scores, 106–77–113). Simpson’s index of the POT-kit was 0.977. In conclusion, the present study clarified the multiclonal nature of outpatient SSTI-associated MRSA in a teaching hospital in Japan. These data also underscore the utility of the POT-kit for non-outbreak surveillance through its simple platform consisting of two multiplex PCRs without sequencing.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPCLJ, UPUK, VKSCE, ZAGLJ
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