Comparison of a silver-coated needleless connector and a standard needleless connector for the prevention of central line-associated bloodstream infections.

OBJECTIVE: To assess the impact of a novel, silver-coated needleless connectors (NCs) on central-line-associated bloodstream infection (CLABSI) rates compared with a mechanically identical NCs without a silver coating. DESIGN: Prospective longitudinal observation study SETTING Two 500-bed university hospitals PATIENTS: All hospitalized adults from November 2009 to June 2011 with non-hemodialysis central lines INTERVENTIONS: Hospital A started with silver-coated NCs and switched to standard NCs in September 2010; hospital B started with standard NCs and switched to silver-coated NCs. The primary outcome was the difference revealed by Poisson multivariate regression in CLABSI rate using standard Centers for Disease Control and Prevention surveillance definitions. The secondary outcome was a comparison of organism-specific CLABSI rates by NC type. RESULTS: Among 15,845 hospital admissions, 140,186 central-line days and 221 CLABSIs were recorded during the study period. In a multivariate model, the CLABSI rate per 1,000 central-line days was lower with silver-coated NCs than with standard NCs (1.21 vs 1.79; incidence rate ratio=0.68 [95% CI: 0.52-0.89], P=.005). A lower CLABSI rate per 1,000 central-line days for the silver-coated NCs versus the standard NCs was observed with S. aureus (0.11 vs 0.30, P=.02), enterococci (0.10 vs 0.27, P=.03), and Gram-negative organisms (0.28 vs 0.63, P=.003) but not with coagulase-negative staphylococci (0.31 vs 0.36) or Candida spp. (0.42 vs 0.40). CONCLUSIONS: The use of silver-coated NCs decreased the CLABSI rate by 32%. CLABSI reduction efforts should include efforts to minimize contamination of NCs.

Ectonucleotide triphosphate diphosphohydrolase-1 (CD39) mediates resistance to occlusive arterial thrombus formation after vascular injury in mice.

Modulation of purinergic signaling, which is critical for vascular homeostasis and the response to vascular injury, is regulated by hydrolysis of proinflammatory ATP and/or ADP by ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD-1; CD39) to AMP, which then is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine. We report here that compared with littermate controls (wild type), transgenic mice expressing human ENTPDase-1 were resistant to the formation of an occlusive thrombus after FeCl(3)-induced carotid artery injury. Treatment of mice with the nonhydrolyzable ADP analog, adenosine-5'-0-(2-thiodiphosphate) trilithium salt, Ado-5'-PP[S], negated the protection from thrombosis, consistent with a role for ADP in platelet recruitment and thrombus formation. ENTPD-1 expression decreased whole-blood aggregation after stimulation by ADP, an effect negated by adenosine-5'-0-(2-thiodiphosphate) trilithium salt, Ado-5'-PP[S] stimulation, and limited the ability to maintain the platelet fibrinogen receptor, glycoprotein α(IIb)/ß(3), in a fully activated state, which is critical for thrombus formation. In vivo treatment with a CD73 antagonist, a nonselective adenosine-receptor antagonist, or a selective A(2A) or A(2B) adenosine-receptor antagonist, negated the resistance to thrombosis in transgenic mice expressing human ENTPD-1, suggesting a role for adenosine generation and engagement of adenosine receptors in conferring in vivo resistance to occlusive thrombosis in this model. In summary, our findings identify ENTPDase-1 modulation of purinergic signaling as a key determinant of the formation of an occlusive thrombus after vascular injury.

Transgenic swine: expression of human CD39 protects against myocardial injury.

UNLABELLED: CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD-1) rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator. While expression of human CD39 in a murine model of myocardial ischemia/reperfusion (I/R) injury confers cardiac protection, the translational therapeutic potential of these findings requires further testing in a large animal model. To determine if transgenic expression of CD39 reduces infarct size in a swine model of myocardial ischemia/reperfusion injury, transgenic pigs expressing human CD39 (hCD39) were generated via somatic cell nuclear transfer and characterized. Expression of hC39 in cardiac tissue was confirmed by immunoblot and immunohistochemistry. Myocardial I/R injury was induced by intracoronary balloon inflation in the left anterior descending (LAD) artery for 60 min followed by 3 hours of reperfusion. The ischemic area was delineated by perfusion with 5% phthalo blue and the myocardial infarct size was determined by triphenyl tetrazolium chloride (TTC) staining. During ischemia, the rate-pressure product was significantly lower in control versus hCD39-Tg swine. Following reperfusion, compared to littermate control swine, hCD39-Tg animals displayed a significant reduction in infarct size (hCD39-Tg: 17.2 ± 4.3% vs. CONTROL: 44.7 ± 5.2%, P=0.0025). Our findings demonstrate for the first time that the findings in transgenic mouse models translate to large animal transgenic models and validate the potential to translate CD39 into the clinical arena to attenuate human myocardial ischemia/reperfusion injury.