预约演示

更新于：2025-05-07

Proteobacteria infection

变形菌感染

更新于：2025-05-07

基本信息

别名-

简介-

关联

项与变形菌感染相关的药物

Walkmycin C

靶点

WalK

作用机制

Walk蛋白抑制剂

在研机构-

原研机构

Kinki University

在研适应症-

非在研适应症

变形菌感染

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与变形菌感染相关的临床试验

NCT00773799

/ Unknown statusN/A

Mastering Hospital Antimicrobial Resistance and Its Spread Into the Community

Data on occurrence of antimicrobial resistant bacteria acquisition in rehabilitation centers will be collected. After removal of patient identifiers, information regarding the patients population will be entered into electronic sheet. The phase will last twelve months in each center.

开始日期2008-10-01

申办/合作机构

Rayner Intraocular Lenses Ltd.

100 项与变形菌感染相关的临床结果

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100 项与变形菌感染相关的转化医学

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0 项与变形菌感染相关的专利（医药）

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项与变形菌感染相关的文献（医药）

2025-06-01·Fish & Shellfish Immunology

Neu1-deficient zebrafish cells exhibit reduced Edwardsiella piscicida infection due to altered lysosomal exocytosis and membrane dynamics

Article

作者: Tsurusaki, Akari ; Shiozaki, Kazuhiro ; Komatsu, Masaharu ; Ishii, Mika

Edwardsiella piscicida is a Gram-negative intracellular pathogen causing Edwardsiellosis, leading to economic losses in aquaculture. While phagocytosis is its primary infection route, alternative entry pathways remain largely unexplored. Neu1 sialidase, a lysosomal enzyme in glycoconjugate degradation, was investigated for its role in E. piscicida infection using primary cultured cells derived from Neu1-KO zebrafish fin (Neu1-KO cells). Compared to wild-type (WT) cells, Neu1-KO cells exhibited lower infection rates, which were associated with enhanced lysosomal exocytosis. Infection was restored by the intracellular calcium chelator BAPTA-AM, highlighting the role of exocytosis. Leupeptin, a cysteine/serine protease inhibitor, increased E. piscicida infection in Neu1-KO cells. Neu1-KO cells exhibited lower rab10 expression and reduced membrane ruffling, which was restored by BAPTA-AM and leupeptin. Given the role of epidermal growth factor receptor (EGFR) signaling, we assessed its phosphorylation, which was reduced in Neu1-KO cells but restored by treatment with BAPTA-AM and leupeptin. This suggests that inhibiting lysosome exocytosis or extracellular protease activity may enhance EGFR phosphorylation. These findings indicate that the decreased E. piscicida infection in Neu1-KO cells resulted from enhanced lysosomal exocytosis, leading to increased extracellular protease secretion, subsequent EGFR inactivation by extracellular protease, and reduced EGFR-regulated ruffling. This study provides novel insights into the regulatory mechanisms of bacterial infection and lysosomal exocytosis, informing potential therapeutic strategies against intracellular pathogens.

2025-05-01·Clinical Microbiology and Infection

What is the most effective antibiotic monotherapy for severe Pseudomonas aeruginosa infection? A systematic review and meta-analysis of randomized controlled trials

Review

作者: Tekes-Manuva, Dorit ; Halperin, Erez ; Leibovici, Leonard ; Avni, Tomer ; Kozlovski, Dror ; Elbaz, Michal ; Yahav, Dafna ; Babich, Tanya

BACKGROUND AND OBJECTIVESSevere infections caused by Pseudomonas aeruginosa are associated with significant morbidity and mortality, particularly in hospitalized and immunocompromised patients. Determining the optimal definitive monotherapy for these infections is critical. The main objective was to compile the evidence of subgroups of patients with Pseudomonas aeruginosa infection from randomized control trials (RCTs) evaluating different definite antipseudomonal monotherapies for severe P. aeruginosa infection.METHODSSystematic review and meta-analysis of RCTs that assessed monotherapy with an antipseudomonal drug versus another antipseudomonal for definite treatment, and reported on the subgroup of patients with P. aeruginosa infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS and the reference lists of included trials. Eligibility criteria included RCTs enrolling hospitalized adults (≥18 years) with microbiologically confirmed severe P. aeruginosa infections. Studies were excluded if they included >20% of patients receiving combination therapy or if patients had resistant P. aeruginosa strains at recruitment. Antipseudomonal drugs evaluated included cephalosporins, carbapenems, penicillins, quinolones and aztreonam. The primary outcome was 30-day mortality. Risk of bias was assessed using the Cochrane tool. Results were pooled using fixed-effects and random-effects models as appropriate. Relative risk (RR) and 95% CIs were calculated. Sensitivity analyses and subgroup analyses were performed when data were available.RESULTSA total of 76 RCTs and 1681 patients with pseudomonal infection were included. Due to the low number of studies which reported our outcomes of interest, all subgroup analyses were underpowered. No difference in all-cause mortality was found for any direct antibiotic comparison. Higher clinical failure rates of carbapenems versus piperacillin-tazobactam were observed for pneumonia in two RCTs (RR, 2.55; 95% CI, 1.29-5.03; I² = 0%, n = 2), and higher microbiological failure rates with carbapenems versus other comparators (RR, 1.24; 95% CI, 1.02-1.51; I² = 0%, n = 23). Patients treated with imipenem were more likely to develop resistance to the study drug versus comparators (RR, 2.33; 95% CI, 1.61-3.38; I² = 0%, n = 7).CONCLUSIONSIn this systematic review and meta-analysis of definite antipseudomonal monotherapy for P. aeruginosa infection, we found no evidence of clinical benefit differences among direct antibiotic comparisons, but all subgroup analyses were underpowered to detect significant differences.

2024-03-01·Journal of Cystic Fibrosis

Global disparities in cystic fibrosis outcomes prior to CFTR modulators: A CF registries cohort study in South Africa and Canada

Article

作者: Verstraete, Janine ; Stewart, Cheryl ; Morrow, Brenda ; Pepper, Michael S ; Zampoli, Marco ; Sykes, Jenna ; Zar, Heather J ; Cheng, Stephanie Y ; Stephenson, Anne L

BACKGROUNDOutcomes of cystic fibrosis (CF) differ between low-middle income and high-income countries, but comparative data are lacking. We compared South African (SA) and Canadian CF outcomes to explore what disparities existed prior to access of CFTR modulators in Canada.METHODSA cross-sectional study of SA and Canadian CF registries data for period 1 January to 31 December 2018. CF registry data were harmonised between countries to compare lung function and nutrition outcomes. Poor nutrition was defined as BMIz-score < -1 in children and < 18.5 kg/m² in adults. Standardised mean difference (SMD) >10 was considered significant.RESULTSAfter excluding Canadians on CFTR modulators and lung transplant recipients, data on 4049 Canadian and 446 SA people was analysed. Compared to Canada, people in SA were younger (median age 15.8 years vs. 24.1 years: SMD 52) with fewer males (47.8% vs 54.2%; SMD 12.5) and White (70.9% vs. 93.3%; SMD 61.3). Class I-III CFTR mutation frequency was similar in SA (n = 384, 86.1%) and Canada (n = 3426, 84.9%). After adjusting for age, gender, diagnosis age, genotype, P.aeruginosa infection and pulmonary treatments, FEV1pp was 8.9% lower (95% CI 6.3% to 11.4%) and poor nutrition 1.7-fold more common (OR 1.70; 95% CI 1.19-2.41) in SA compared to Canada.CONCLUSIONLung function and nutrition was significantly lower in SA compared to Canada. Global disparities in CF outcomes between high and low-middle income countries are likely to widen as CFTR modulators are rapidly scaled up in only high-income countries.

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