1.Successful Treatment of VancomycinResistant Enterococcus species Bone and Joint Infection with Daptomycin Plus Beta Lactam Agents
Infection and Chemotherapy 2022;54(4):797-802
Bone and joint infections (BJI) caused by vancomycin-resistant Enterococcus spp. (VRE) are difficult to treat due to limited antibiotic options. Although linezolid can be used for VRE treatment, it is often discontinued due to time-dependent bone marrow suppression. Daptomycin, a lipopeptide antibiotic agent with rapid bactericidal activity, is another available therapeutic option for VRE infections. We report a case of VRE BJI successfully treated with a high dose of daptomycin plus β-lactam agents. An 84-year-old man received linezolid for the treatment of VRE BJI. After 2 weeks of therapy, the patient experienced bleeding events associated with linezolid-induced bone marrow toxicity and linezolid was discontinued. Next, high-dose daptomycin therapy combined with a β-lactam agent was selected to treat the remaining VRE BJI. During daptomycin treatment, microbiological eradication was achieved, and the patient clinically improved without evidence of adverse events. We highlight the need for daptomycin use for the treatment of VRE infections, especially in cases where linezolid is ineffective
2.Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections
Yeon Ju LA ; Hye Rim KIM ; Dong Hyun OH ; Jin Young AHN ; Yong Chan KIM
Yonsei Medical Journal 2022;63(7):611-618
Purpose:
This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI).
Materials and Methods:
We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis.
Results:
A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71– 6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis.
Conclusion
Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.
3.Regulation of B cell activating factor (BAFF) receptor expression by NF-kappaB signaling in rheumatoid arthritis B cells.
Yun Ju WOO ; Bo Young YOON ; Joo Yeon JHUN ; Hye Jwa OH ; Sewon MIN ; Mi La CHO ; Sung Hwan PARK ; Ho Youn KIM ; Jun Ki MIN
Experimental & Molecular Medicine 2011;43(6):350-357
B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-kappaB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-kappaB inhibitors. NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-kappaB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-kappaB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-kappaB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.
Arthritis, Rheumatoid/genetics/*metabolism/pathology/physiopathology
;
B-Cell Activating Factor/genetics/metabolism
;
B-Cell Activation Factor Receptor/genetics/*metabolism
;
B-Lymphocytes/*drug effects/immunology/metabolism/pathology
;
Cell Separation
;
Cells, Cultured
;
Disease Progression
;
Enzyme Inhibitors/pharmacology
;
Flow Cytometry
;
Gene Expression Regulation/immunology
;
Humans
;
Immunohistochemistry
;
NF-kappa B/*metabolism
;
Signal Transduction/immunology
;
Synovial Membrane/*pathology
;
T-Lymphocytes/drug effects/immunology/metabolism/pathology
;
Transcriptional Activation/drug effects
4.The Marginal Zone B Cells have an Increased Antibody Expression in Mice with Collagen-induced Arthritis.
Yun Ju WOO ; Jun Ki MIN ; Mi La CHO ; Young Joo KIM ; Joo Yeon JHUN ; Min Jung PARK ; Young Mi MOON ; Mi Kyung PARK ; Ho Youn KIM
The Journal of the Korean Rheumatism Association 2009;16(1):23-32
OBJECTIVE: Mature B cells in the spleen of mouse can be divide into two main subsets: the follicular (FO) B cells and the marginal zone (MZ) B cells. In this study, we investigated which subtype of B cells is involved in the production of costimulatory molecules, cytokine and antibody during the induction of autoimmune arthritis. METHODS: The MZB and FOB cells isolated from DBA/1J induced- and collagen-induced arthritis (CIA) mice were stimulated with LPS or CpG. The costimulatory molecules were measured by flow cytometry (FACs). The cytokines were measured by ELISA. Production of antibodies by the MZB cells or FOB cells was measured by ELISA and the results were observed by confocal microscopy. RESULTS: The expression of co-stimulatory molecules was stronger in the MZB cells than that in the FOB cells. The production of cytokines (IL-10, IL-6) and antibodies was higher in the MZB cells. The IgG expression of the MZB cells, which is known to be associated with the acceleration of autoimmunity, was higher in the CIA mice than that in the DBA/1J mice. CONCLUSION: We observed that the MZB cells were increased in the CIA mice. The costimulatory molecules, cytokine and auto-antibodies were increased in the MZB cells compared to that of the FOB cells. Our results suggest that MZB cells mainly produce autoantibodies, and they play a key role in development of autoimmune arthritis.
Acceleration
;
Animals
;
Antibodies
;
Arthritis
;
Arthritis, Experimental
;
Autoantibodies
;
Autoimmunity
;
B-Lymphocytes
;
Cytokines
;
Enzyme-Linked Immunosorbent Assay
;
Flow Cytometry
;
Immunoglobulin G
;
Mice
;
Microscopy, Confocal
;
Spleen
5.Expression of CCR2A, an isoform of MCP-1 receptor, is increased by MCP-1, CD40 ligand and TGF-beta in fibroblast like synoviocytes of patients with RA.
Mi La CHO ; Bo Young YOON ; Ji Hyeon JU ; Young Ok JUNG ; Joo Yeon JHUN ; Mi Kyung PARK ; Sung Hwan PARK ; Chul Soo CHO ; Ho Youn KIM
Experimental & Molecular Medicine 2007;39(4):499-507
Cytokine and chemokine receptors play a key role in inflammation caused by rheumatoid arthritis (RA). Two isoforms of human CC chemokine receptor R2 (CCR2), the receptor of monocyte chemoattractant protein 1 (MCP-1), have been identified but their relative expression in fibroblast-like synoviocytes (FLS) and their contribution to inflammatory responses mediated by MCP-1 or inflammatory cytokines in patients with RA remain uncertain. We examined the pattern of expression of two CCR2 isoforms upon stimulation by proinflammatory cytokines and CD40 ligation. FLS were prepared from the synovial tissues of RA patients and cultured in the presence of MCP-1, soluble CD40 ligand (sCD40L), TGF-beta, IL-1beta, IL-18, IL-15, and LPS. CCR2A and CCR2B expression was examined by immunohistochemistry, RT-PCR and western blot analysis. IL-15, TNF-alpha and MCP-1 production was determined by ELISA. Immunohistochemistry showed that CCR2A is highly expressed in RA synovium compared with OA synovium. Transcripts of both CCR2A and CCR2B were detected in FLS. Exogenous MCP-1, CD40L, TGF-beta, and IL-15 significantly increased the expression of CCR2A but not CCR2B. Exposure of FLS to sCD40L caused strong upregulation of CCR2A but not of CCR2B protein expression. MCP-1 increased the proliferation of FLS and the production of IL-15, TNF-alpha, and IL-18. Because CCR2A is the main target of regulation by cytokines and CD40 ligation, the relatively higher expression of CCR2A on the cell surface suggests that this isoform of MCP-1 receptor functions as the principal mediator of inflammatory signals in RA FLS.
Arthritis, Rheumatoid/*metabolism
;
CD40 Ligand/*pharmacology
;
Cells, Cultured
;
Chemokine CCL2/*pharmacology
;
Chemokines/biosynthesis
;
Fibroblasts/*metabolism
;
Humans
;
Protein Isoforms
;
Receptors, CCR2/*biosynthesis
;
Synovial Membrane/*pathology
;
Transforming Growth Factor beta/*pharmacology
6.Measurement of Interleukin-33 (IL-33) and IL-33 Receptors (sST2 and ST2L) in Patients with Rheumatoid Arthritis.
Yeon Sik HONG ; Su Jin MOON ; Young Bin JOO ; Chan Hong JEON ; Mi La CHO ; Ji Hyeon JU ; Hye Jwa OH ; Yu Jung HEO ; Sung Hwan PARK ; Ho Youn KIM ; Jun Ki MIN
Journal of Korean Medical Science 2011;26(9):1132-1139
The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 +/- 464.0 pg/mL) than in healthy controls (96.0 +/- 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1beta (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.
Adult
;
Aged
;
Antirheumatic Agents/therapeutic use
;
Arthritis, Rheumatoid/blood/drug therapy/*pathology
;
C-Reactive Protein/analysis
;
Female
;
Humans
;
Interleukin-1beta/analysis/blood
;
Interleukin-6/analysis/blood
;
Interleukins/*analysis/blood
;
Male
;
Middle Aged
;
Osteoarthritis/blood/pathology
;
Receptors, Cell Surface/*analysis/blood
;
Synovial Fluid/metabolism