Formation of an intraluminal microbial biofilm is noted to play a significant role in the development of catheter-related infections (CRIs). Recently, it has been demonstrated that trisodium citrate (TSC) has superior antimicrobial effects over heparin for catheter locking. In this randomized controlled trial, we compared the influence of catheter locking with heparin and TSC on the in vivo intraluminal biofilm formation in haemodialysis catheters.
Six patients were studied from the time of catheter insertion for haemodialysis treatment. They were randomly assigned to TSC 30% or heparin 5000 U/ml for catheter locking for the duration of 1 month. After elective guidewire exchange of the catheter, the locking solution was also changed. After removal, catheters were dissected in three segments and examined by standardized scanning electron microscopy (SEM) to assess quantitative biofilm formation. Furthermore, standardized cultures of all segments were performed to identify any microorganisms.
In catheters filled with TSC, the average coverage by biofilm was 16% versus 63% in the heparin group (P < 0.001). A total of eight subsegments were associated with local catheter infection in the patients who were randomized to heparin locking versus three subsegments who were assigned to TSC (P < 0.05).
Our study demonstrates that using TSC 30% for catheter locking reduces the formation of microbial biofilm in haemodialysis catheters and culture-positive colonization. It is likely that this is the explanation for the observed prevention of CRIs by TSC locking.
"PMEM were treated with LTA at 10–30 µg/ml, because preliminary dose-response studies indicate these doses consistently induce a permeability increase. This range of LTA doses are biologically relevant concentrations that can be achieved in the dead space of an intravascular catheter with biofilm (107 to 109 CFU) present , . In addition to LTA, PMEM were treated with the synthetic bacterial lipoprotein and TLR2-TLR1 ligand positive control, N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine (PAM(3)CSK(4) [PAM]) (InvivoGen), at 10–30 µg/ml . "
[Show abstract][Hide abstract] ABSTRACT: Tunneled central venous catheters (TCVCs) are used for dialysis access in 82% of new hemodialysis patients and are rapidly colonized with Gram-positive organism (e.g. Staphylococcus aureus) biofilm, a source of recurrent infections and chronic inflammation. Lipoteichoic acid (LTA), a cell wall ribitol polymer from Gram-positive organisms, mediates inflammation through the Toll-like receptor 2 (TLR2). The effect of LTA on lung endothelial permeability is not known. We tested the hypothesis that LTA from Staphylococcus aureus induces alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM) that result from activation of TLR2 and are mediated by reactive oxygen/nitrogen species (RONS). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin, the activation of the TLR2 pathway was assessed by Western blot, and the generation of RONS was measured by the fluorescence of oxidized dihydroethidium and a dichlorofluorescein derivative. Treatment with LTA or the TLR2 agonist Pam((3))CSK((4)) induced significant increases in albumin permeability, IκBα phosphorylation, IRAK1 degradation, RONS generation, and endothelial nitric oxide synthase (eNOS) activation (as measured by the p-eNOS(ser1177):p-eNOS(thr495) ratio). The effects on permeability and RONS were effectively prevented by co-administration of the superoxide scavenger Tiron, the peroxynitrite scavenger Urate, or the eNOS inhibitor L-NAME and these effects as well as eNOS activation were reduced or prevented by pretreatment with an IRAK1/4 inhibitor. The results indicate that the activation of TLR2 and the generation of ROS/RNS mediates LTA-induced barrier dysfunction in PMEM.
PLoS ONE 11/2012; 7(11):e49209. DOI:10.1371/journal.pone.0049209 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: L’infection liée aux cathéters veineux centraux, événement grave en grande partie évitable, est la principale cause de bactériémie nosocomiale. Les bactériémies associées aux cathéters et liées aux cathéters doivent être bien distinguées. En l’absence de signes locaux patents, de sepsis sévère, d’immunodépression ou de matériel prothétique en place, la réalisation d’hémocultures qualitatives comparatives par le cathéter et en périphérie peut faire le diagnostic d’implication du cathéter sans obliger à son ablation.
Des taux de bactériémies liées aux cathéters (définition du consensus français) supérieurs à 1 pour 1000 journéescathéters doivent être considérés comme inacceptables. La mise en place d’un programme de prévention en réanimation est réalisable et le plus souvent efficace pour faire diminuer les taux d’infections, motiver et restructurer les équipes de soins. Si les taux d’infections sont élevés, la mise en place de mesures simples (renforcement de l’hygiène des mains, asepsie chirurgicale à la pose, solutions antiseptiques contenant de l’alcool, voie sous-clavière préférentielle, procédure d’entretien des cathéters et des lignes de perfusion, réfection immédiate des pansements souillés ou décollés, ablation des cathéters inutiles) et adaptées au mode de fonctionnement du service sont efficaces. Une gouvernance claire et une rétroinformation sont indispensables au succès de ces programmes d’amélioration de la qualité des soins. Si les taux restent élevés, ou si l’on veut aller plus loin, les pansements imprégnés de chlorhexidine permettent de diminuer encore le risque d’infection. L’utilisation des cathéters imprégnés d’agents antimicrobiens doit être limitée aux situations d’échec de la politique globale de prévention.
[Show abstract][Hide abstract] ABSTRACT: Bioassays involve multi-stage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Using microfluidic technology to integrate and automate all these steps in a single chip device is highly desirable in many practical applications such as clinical diagnostic and in-field environmental testing. We have developed self-contained and fully integrated biochip systems for immunoassay and DNA analysis. These microfluidic biochip devices can perform detection of multiple bioagents (including antigens and DNA) using electrochemical detection methods. Microfluidic mixer, valves, pumps, channels, chambers, and Combimatrix microelectrode array are integrated to perform parallel immunoassays to detect infectious particles (viruses and bacteria) from complex biological samples in a single, fully automated biochip device. All microfluidic components use very simple and inexpensive approaches in order to reduce chip complexity. Back-end detection is accomplished using an enzyme-based electrochemical detection method that has many advantages including high sensitivity ( approximately fM) and simple apparatus. The sensor is a miniaturized array of individually addressable microelectrodes controlled by active CMOS circuitry. Pathogenic bacteria and DNA detections are both demonstrated. The devices with capabilities of on-chip sample processing and detection provide a cost-effective solution to direct sample-to-answer biological analysis for point-of-care genetic analysis, disease diagnosis, and in-field bio-threat detection.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2004; 7:5394. DOI:10.1109/IEMBS.2004.1404507
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