Comparison of disease and economic burden between MRSA infection and MRSA colonization in a university hospital: a retrospective data integration study

Abstract Background Although there is a growing concern and policy regarding infections or colonization caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), the prognosis of MRSA infections compared to that of methicillin-susceptible Staphylococcus aureus (MSSA) infections remains controversial. Moreover, there have not been any studies comparing both the burden of disease and its impact on the healthcare economy between MRSA infection and colonization while adjusting for confounding factors. These comparisons are crucial for developing effective infection control measures and healthcare policies. We aimed to compare the disease and economic burden between MRSA and MSSA infections and between MRSA infection and colonization. Methods We retrospectively investigated data of 496 in-patients with MRSA or MSSA infections and of 1178 in-patients with MRSA infections or MRSA colonization from a university hospital in Japan from 2016 to 2021. We compared in-hospital mortality, length of stay, and hospital charges between in-patients with MRSA and MSSA infections and those with MRSA infections and MRSA colonization using multiple regressions. We combined surveillance data, including all microbiological test results, data on patients with infections, treatment histories, and clinical outcomes, to create the datasets. Results There was no statistically significant difference in in-hospital mortality rates between matched MRSA vs. MSSA infections and MRSA infection vs. colonization. On the contrary, the adjusted effects of the MRSA infection compared to those of MSSA infection on length of stay and hospital charges were 1.21-fold (95% confidence interval [CI] 1.03–1.42, P = 0.019) and 1.70-fold (95% CI 1.39–2.07, P < 0.00001), respectively. The adjusted effects of the MRSA infection compared to those of MRSA colonization on length of stay and hospital charges were 1.41-fold (95% CI 1.25–1.58, P < 0.00001) and 1.53-fold (95% CI 1.33–1.75, P < 0.00001), respectively. Regarding confounding factors, hemodialysis or hemofiltration was consistently identified and adjusted for in the multiple regression analyses comparing MRSA and MSSA infections, as well as MRSA infection and MRSA colonization. Conclusions MRSA infection was associated with longer length of stay and higher hospital charges than both MSSA infection and MRSA colonization. Furthermore, hemodialysis or hemofiltration was identified as a common underlying factor contributing to increased length of stay and hospital charges

Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach

Androgens modulate the morphological characteristics of human endometrial stromal cells decidualized in vitro

The activated androgen receptor (AR) in decidualizing human endometrial stromal cells (HESCs) regulates genes involved in cytoskeletal organization, cell motility, and cell cycle progression. Androgens also enhance the secretion of prolactin, a widely used marker of decidualized HESCs. The purpose of the present study was to investigate the direct effects of androgens on the ultrastructural changes associated with decidual transformation of HESCs. Primary HESC cultures were established and propagated, and confluent cultures were decidualized for 6 days with 8-bromoadenosine 3',5'-cyclic monophosphate (8-br-cAMP) and progesterone (P4) in the presence or absence of dihydrotestosterone (DHT). Phase-contrast image analysis demonstrated that DHT increases the shape index of decidualizing cells, which was reversed upon cotreatment with the AR antagonist flutamide. Electron microscopy demonstrated that DHT enhances many of the ultrastructural changes induced by 8-br-cAMP and P4 in HESCs. Decidualizing cells are characterized by an abundant cytoplasm, multiple cell surface projections and, unlike undifferentiated HESCs, form 2 or more cell layers. The DHT further stimulated cytoplasmic expansion, lipid droplet formation, the production of an abundant extracellular matrix, and gap junction formation in decidualized HESCs. The present study demonstrates that androgen signaling has an impact on the morphological and ultrastructural changes associated with the decidual process. Our findings show that androgens promote the development and expansion of cytoplasmic organelles and gap junctions in decidualizing HESCs. These results suggest that androgens in early pregnancy play an important role in promoting the cellular transformation associated with decidualization

Additional file 1 of Comparison of disease and economic burden between MRSA infection and MRSA colonization in a university hospital: a retrospective data integration study

Supplementary Material

Metagenomic analyses of the gut microbiota associated with colorectal adenoma.

Recent studies have suggested an association between certain members of the Fusobacterium genus, especially F. nucleatum, and the progression of advanced colorectal carcinoma (CRC). We assessed such an association of the gut microbiota in Japanese patients with colorectal adenoma (CRA) or intramucosal CRC using colonoscopy aspirates. We analyzed samples from 81 Japanese patients, including 47 CRA and 24 intramucosal CRC patients, and 10 healthy subjects. Metagenomic analysis of the V3-V4 region of the 16S ribosomal RNA gene was performed. The linear discriminant analysis (LDA) effect size (LEfSe) method was used to examine microbial dysbiosis, revealing significant differences in bacterial abundances between the healthy controls and CRA or intramucosal CRC patients. In particular, F. varium was statistically more abundant in patients with CRA and intramucosal CRC than in healthy subjects. Here, we present the metagenomic profile of CRA and intramucosal CRC and demonstrate that F. varium is at least partially involved in the pathogenesis of CRA and intramucosal CRC

Schematic model of attenuated bleomycin-induced skin fibrosis and accelerated wound healing in endothelial cell-specific endothelin 1 knockout mice.

<p>Schematic model of attenuated bleomycin-induced skin fibrosis and accelerated wound healing in endothelial cell-specific endothelin 1 knockout mice.</p

Cutaneous wound healing in WT and ET-1^f/f; Tie-2-Cre (+) mice.

<p>(A) Representative wound closure in wild-type (WT) and ET-1^f/f; Tie-2-Cre (+) (KO) mice at days 0, 5, 7, 10 post-wounding. (B) Hematoxylin-Eosin (HE) staining of wound tissues derived from wild-type (WT) and ET-1^f/f; Tie-2-Cre (+) (KO) mice at days 3, 7, 12 post-wounding. Arrow heads indicated bilateral edges of wound granulation tissue. Double-headed arrows indicated the distance between the leading edges of wounded epidermis. The one representative result is shown. Scale bar = 1000 µm. (C) Measurements of granulation tissue size (the distance between the arrow heads) in the wild-type (WT) and ET-1^f/f; Tie-2-Cre (+) (KO) mice at days 3, 7, 12 post-wounding. Data are expressed as the mean ± SD of six independent experiments. *<i>P</i><0.05 as compared with the value in WT mice. (D) Measurements of epithelial gap (the distance of double-headed arrows) in the wild-type (WT) and ET-1^f/f; Tie-2-Cre (+) (KO) mice at days 3, 7, 12 post-wounding. Data are expressed as the mean ± SD of six independent experiments. *<i>P</i><0.05 as compared with the value in WT mice.</p

Infiltrating cells in the wounding bed at day 3, 7 and 12 of the wild-type (WT) and ET-1^f/f; Tie-2-Cre (+) (KO) mice.

<p>Myeloperoxidase (A), F4/80 (B) and CD3 (C) were stained. Positive cells were counted in five random high-power fields (0.06 mm², magnification, ×400). Data were expressed as the mean ± SD of six independent counts (left panel). The representative results of immunostaining for myeloperoxidase, F4/80 and CD3 are shown (right panel).</p