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Global Transmission of the penA Allele 60.001–Containing High-Level Ceftriaxone-Resistant Gonococcal FC428 Clone and Antimicrobial Therapy of Associated Cases:A Review

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Infectious Microbes & Diseases 2023年第1期5卷 13-20页

作者： stijn van der Veen Department of Microbiology and Department of Dermatology of Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouPeople’s Republic of China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouPeople’s Republic of China Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering HangzhouPeople’s Republic of China

Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line ***,ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported,commonly as a result of sporadic high-level ceftriaxone-resistant *** recent years,*** strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant,penA allele 60.001,have shown global transmission,resulting in ceftriaxone treatment failure in a number of *** FC428 clone was first encountered in Japan in 2015 and subsequently in China,Europe,Australia,North America and Southeast Asia *** associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5-1 mg/***,where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect,penA allele 60.001 does not seem to affect in vitro *** limited impact of penA allele 60.001 on biological fitness might be associated with its successful global *** the FC428 clone displays high-level ceftriaxone resistance,most gonorrhea cases associatedwith this clone were still successfully curedwith ceftriaxonewhen intramuscular or intravenous doses of 500mg to 2 g were used.A successful alternative therapy seems to be ertapenem given at 1-g doses,although further clinical studies are required to validate *** review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.

关键词： Neisseria gonorrhoeae FC428 penA 60.001 ceftriaxone biological fitness antimicrobial resistance

Role of Outer Membrane Vesicles in Bacterial Physiology and Host Cell Interactions

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Infectious Microbes & Diseases 2020年第1期2卷 3-9页

作者： Lingyu Gao stijn van der Veen Department of Microbiology and Parasitology School of MedicineZhejiang UniversityHangzhouChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Dermatology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina.

Outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules may occur,and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic *** the detailed mechanisms of OMV biogenesis are not fully illuminated yet,several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated *** secretion offers a way for both intra-and inter-species bacterial communication and for interaction or modulation of the bacterial ***,OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host *** the host,OMVs are internalized via host cell endocytosis pathways,allowing them to subsequently trigger a variety of cellular *** this review,we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.

关键词： endocytosis OMP OMV outer membrane vesicles secretion system virulence factors

Determination of Fusidic Acid Susceptibility of Multidrug-resistant Gonococcal Isolates from China

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Infectious Microbes & Diseases 2019年第2期1卷 70-74页

作者： Fan Yang stijn van der Veen Department of Microbiology and Parasitology School of MedicineZhejiang UniversityHangzhouChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Dermatology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina

The currently recommended gonococcal therapies are rapidly losing efficacy and;therefore,novel options for treatment are urgently required to ensure future treatment remains *** we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic *** isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin,antimicrobials that are currently recommended as a first-line dual *** official susceptibility breakpoints have not been established,all gonococcal isolates appeared to be susceptible to fusidic acid,with the majority of isolates displaying a minimal inhibitory concentration(MIC)of 0.25 or 0.5mg/***,the MIC90 was 0.5mg/L,with a MIC range of 0.08-2mg/***,no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was *** analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations(4MIC).In conclusion,fusidic acid displayed consistent antimicrobial activity against *** and,given the absence of cross-resistance with ceftriaxone and azithromycin,might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.

关键词： fusidic acid multidrug-resistance Neisseria gonorrhoeae

Antibiotic Resistance and Treatment Options for Multidrug-Resistant Gonorrhea

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Infectious Microbes & Diseases 2020年第2期2卷 67-76页

作者： Fan Yang Jing Yan stijn van der Veen Department of Microbiology and Parasitology School of MedicineZhejiang UniversityHangzhouChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Dermatology Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina

Gonorrhea is a sexually transmitted disease with a high global *** causative agent,Neisseria gonorrhoeae,has shown a remarkable flexibility to adapt and become resistant to all antimicrobials introduced over the past century for gonococcal *** currently last available first-line therapy that is recommended in most countries is ***,resistance levels against ceftriaxone are rising globally and incidences of confirmed treatment failure are increasingly encountered,particularly with the global spreading of the ceftriaxone-resistant FC428 clone in recent *** against most antimicrobials has been the result of adaptive genomic mutations that reduce affinity of the antimicrobial to its target protein or rRNA,although most multidrug-resistant strains also appear to have an upregulated multidrug efflux *** ensure gonococcal treatment remains available in the future,alternative therapies are urgently ***,both alternative clinically approved antimicrobials and novel antimicrobials have been intensely studied both in gonococcal susceptibility analyses and clinical efficacy *** there have been some limited successes,all studied alternative therapies that reached clinical trials have displayed some shortcomings in their efficacy against pharyngeal infections and/or overlapping resistance determinants with previously or currently used *** review summarizes the development of gonococcal antimicrobial resistance over the past century,describes the mechanisms involved in antimicrobial resistance,and provides an overview of the alternative therapies that have been under investigation this past decade.

关键词： Neisseria gonorrhoeae antimicrobial resistance AMR ceftriaxone alternative therapy

Double balloon endoscopy associated pancreatitis:A description of six cases

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World Journal of Gastroenterology 2008年第5期14卷 720-724页

作者： Soeresh VA Jarbandhan stijn JB van Weyenberg Willem M van der Veer Dimitri GN Heine Chris JJ Mulder Maarten AJM Jacobs Small Bowel Unit Department of Gastroenterology VU University Medical Center Amsterdam The Netherlands

AIM:To perform a single-center analysis of all double balloon endoscopy (DBE) related cases of pancreatitis identified prospectively from a recorded DBE-complication database. METHODS:From November 2003 until January 2007, 603 DBE procedures were performed on 412 patients, with data on complications recorded in a database. The setting was a tertiary care center offering DBE. DBE was performed from the antegrade or retrograde route. Out-come measurements included age, gender, medication, indication, DBE-endoscope type, insertion depth, proce-dure duration, findings, interventions, post-procedural abdominal pain, and post-procedural hospitalization. RESULTS:This is the largest single-center study report-ing on post-DBE pancreatitis prospectively. Six patients (1.0%) developed post-DBE pancreatitis, all after antegrade DBE. There was no association with gender, duration of the procedure or type of endoscope. The mean age was 51.9 years (range 25-78). Four patients had severe pancreatitis. Of these, two had inflammatory signs in the body-tail region, one had pancreatitis in the tail region, and the total pancreas was involved in one. CONCLUSION:The incidence of post-DBE pancreatitis in our series is higher than previously reported. We found no relation with DBE-endoscope type. The inflammatory changes occurred in the body-tail region of the pancreas, suggesting that post-DBE pancreatitis is caused by repetitive mechanical strain on the pancreas.

关键词： Double balloon endoscopy Small intestine Adverse events Complications Pancreatitis Enteroscopy

Systematic review of cystic duct closure techniques in relation to prevention of bile duct leakage after laparoscopic cholecystectomy

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World Journal of Gastrointestinal Surgery 2018年第6期10卷 57-69页

作者： Aafke H van Dijk stijn van Roessel Philip R de Reuver Djamila Boerma Marja A Boermeester Sandra C Donkervoort Departement of Surgery Amsterdam University Medical Centre Department of Surgery Radboud University Medical Center Department of Surgery St. Antonius Hospital Department of Surgery Onze Lieve Vrouw Gasthuis

AIM To study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy(LC) for biliary *** A systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic duct leakage(CDL) was the primary outcome. Risk of bias was evaluated. Odds ratios were analyzed for comparison of techniques and pooled event rates for non-comparative analyses. Pooled event rates were compared for each of included *** Out of 1491 articles, 38 studies were included. A total of 47491 patients were included, of which 38683(81.5%)underwent cystic duct closure with non-locking(metal)clips. All studies were of low-moderate methodological quality. Only two studies reported separate data on uncomplicated and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4(95%CI: 0.06-2.48)was found for harmonic energy vs clip closure and an odds ratio of 0.17(95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL rate was around 1% for harmonic energy and metal clips, and 0% for locking clips and ligatures. CONCLUSION Based on available evidence it is not possible to either recommend or discourage any of the techniques for cystic duct closure during LC with respects to CDL,although data point out a slight preference for locking clips and ligatures vs other techniques. No separate recommendation can be made for complicated gallbladder disease.

关键词： Biliary surgery Cholecystectomy Outcomes Cystic duct leakage Prevention

Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery

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World Journal of Gastroenterology 2008年第45期14卷 6960-6969页

作者： Mireille FM van stijn Gerdien C Ligthart-Melis Petra G Boelens Peter G Scheffer Tom Teerlink Jos WR Twisk Alexander PJ Houdijk Paul AM van Leeuwen Department of Surgery VU University Medical Center Amsterdam Amsterdam and Medical Center Alkmaar Department of Surgery VU University Medical Center Amsterdam Department of Surgery Catharina Hospital Department of Clinical Chemistry VU University Medical Center Amsterdam Department of Epidemiology and Biostatistics VU University Medical Center Amsterdam Department of Surgery Medical Center Alkmaar

AIM: To investigate the effects of an enteral supple-ment containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal ***: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplementedwith antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied. RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after ***: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.

关键词： Antioxidants Critical illness Enteral nutrition Oxidative stress Surgery Upper gastrointestinal tract

Infectious Microbes&Diseases Contributing to COVID-19 Prevention and Control

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Infectious Microbes & Diseases 2023年第1期5卷 1-2页

作者： Qiong Zhang Yueyue He Xiang Li Shimiao Shao stijn van der Veen State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhouZhejiangChina Department of Microbiology and Department of Dermatology of Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering HangzhouChina

Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and *** to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on *** research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.

关键词： fir COV incomplete

Intracellular Delivery of mRNA in Adherent and Suspension Cells by Vapor Nanobubble Photoporation

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Nano-Micro Letters 2020年第12期12卷 404-420页

作者： Laurens Raes Stephan Stremersch Juan CFraire Toon Brans Glenn Goetgeluk stijn De Munter Lien van Hoecke Rein Verbeke Jelter van Hoeck Ranhua Xiong Xavier Saelens Bart vandekerckhove Stefaan De Smedt Koen Raemdonck Kevin Braeckmans Laboratory of General Biochemistry&Physical Pharmacy Ghent University9000 GhentBelgium Cancer Research Institute Ghent(CRIG) 9000 GhentBelgium Department of Diagnostic Sciences Ghent University9000 GhentBelgium VIB-UGent Center for Medical Biotechnology 9052 GhentBelgium Department of Biomedical Molecular Biology Ghent University9000 GhentBelgium Department of Biochemistry and Microbiology Ghent University9000 GhentBelgium

Efficient and safe cell engineering by transfection of nucleic acids remains one of the long-standing hurdles for fundamental biomedical research and many new therapeutic applications,such as CAR T cell-based *** has recently gained increasing attention as a more safe and versatile alternative tool over viral-or DNA transposon-based approaches for the generation of adoptive T ***,limitations associated with existing nonviral mRNA delivery approaches hamper progress on genetic engineering of these hard-to-transfect immune *** this study,we demonstrate that gold nanoparticle-mediated vapor nanobubble(VNB)photoporation is a promising upcoming physical transfection method capable of delivering mRNA in both adherent and suspension *** transfection experiments on HeLa cells showed the importance of transfection buffer and cargo concentration,while the technology was furthermore shown to be effective for mRNA delivery in Jurkat T cells with transfection efficiencies up to 45%.Importantly,compared to electroporation,which is the reference technology for nonviral transfection of T cells,a fivefold increase in the number of transfected viable Jurkat T cells was ***,our results point toward the use of VNB photoporation as a more gentle and efficient technology for intracellular mRNA delivery in adherent and suspension cells,with promising potential for the future engineering of cells in therapeutic and fundamental research applications.

关键词： Transfection mRNA Photoporation Optoporation Gold nanoparticles Vapor nanobubbles