The Experts below are selected from a list of 23181 Experts worldwide ranked by ideXlab platform
Yan Q Xiong - One of the best experts on this subject based on the ideXlab platform.
-
telavancin is active against Experimental aortic valve endocarditis caused by daptomycin and methicillin resistant staphylococcus aureus strains
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Wessam Abdelhady, Yan Q Xiong, Arnold S Bayer, Rachelle GonzalesAbstract:ABSTRACT We compared the efficacy of telavancin (TLV) and daptomycin (DAP) in an Experimental Rabbit endocarditis model caused by two clinically derived daptomycin-resistant (DAP r ) methicillin-resistant Staphylococcus aureus (MRSA) strains. TLV treatment significantly reduced MRSA densities in all target tissues and increased the percentage of these organs rendered culture negative compared to those with the untreated control or DAP-treated animals. These results demonstrate that TLV has potent in vivo efficacy against DAP r MRSA isolates in this invasive endovascular infection model.
-
comparative efficacy of telavancin and daptomycin in Experimental endocarditis due to multi clonotype mrsa strains
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Yan Q Xiong, Arnold S Bayer, Wessam Abdelhady, Chieh Genna TangAbstract:BACKGROUND MRSA strains of clonal complexes (CCs) 5, 8, 30 and 45 are leading causes of complicated endovascular infections associated with suboptimal clinical outcomes. Telavancin is a novel anti-MRSA agent that both inhibits bacterial cell wall synthesis and disrupts membranes by depolarization. METHODS In this study, we compared the in vitro susceptibility and in vivo efficacy of telavancin versus daptomycin in an Experimental Rabbit infective endocarditis (IE) model caused by four MRSA strains representing each of the above CC types. RESULTS All study strains were susceptible to telavancin (MICs of ≤0.12 mg/L) and daptomycin (MICs of ≤0.5 mg/L). In vitro time-kill analyses revealed that supra-MIC levels of telavancin were effective at preventing regrowth at 24 h of incubation. In the IE animal model for all CC types, treatment with telavancin produced significantly greater reductions in MRSA counts as compared with daptomycin-treated animals in all target tissues. Moreover, telavancin-treated animals had a significantly higher percentage of sterile tissue cultures versus daptomycin-treated animals (e.g. 78%-100% versus 0% sterile vegetations and 100% versus 0%-11% sterile kidneys and spleen, in the telavancin- and daptomycin-treated animals, respectively). CONCLUSIONS These results suggest that telavancin exhibits significantly greater efficacies versus daptomycin in treating Experimental IE caused by MRSA clinical isolates across four common CC types.
-
the role of staphylococcal carotenogenesis in resistance to host defense peptides and in vivo virulence in Experimental endocarditis model
Pathogens and Disease, 2015Co-Authors: Yan Q Xiong, Soojin Yang, Steven Y C Tong, Danya N Alvarez, Nagendra N MishraAbstract:The defining hallmark of the newly described species, Staphylococcus argenteus , in comparison to its sister species, S. aureus and S. schweitzeri , is the absence of production of the carotenoid pigment, staphyloxanthin. Staphylococcus argenteus lacks the responsible genetic locus crtOPQMN. We examined the impact of carotenoid synthesis in two non-pigmented S. argenteus strains, MSHR1132 and SCC1165. Following complementation with a plasmid containing the carotenoid operon (pTX- crtOPQMN) , compared to wild type, both complemented strains showed substantial carotenoid production, with a resultant increase in cell membrane rigidity. Surprisingly, both crtOPQMN -complemented strains exhibited increased susceptibility to the host defense peptides, LL-37 and hNP-1 in vitro , and reduced virulence in an Experimental Rabbit endocarditis model.
-
efficacy of nz2114 a novel plectasin derived cationic antimicrobial peptide antibiotic in Experimental endocarditis due to methicillin resistant staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2011Co-Authors: Hans-henrik Kristensen, Yan Q Xiong, Wessam Abdel Hady, Antoine Deslandes, Astrid Rey, Laurent Fraisse, Michael R Yeaman, Arnold S BayerAbstract:Cationic antimicrobial peptides (CAPs) play important roles in host immune defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent activity against Gram-positive bacteria. In this study, we investigated (i) the in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics of NZ2114 and (ii) the in vivo efficacy of NZ2114 in comparison with those of two conventional antibiotics, vancomycin or daptomycin, in an Experimental Rabbit infective endocarditis (IE) model due to a methicillin-resistant Staphylococcus aureus (MRSA) strain (ATCC 33591). All NZ2114 regimens (5, 10, and 20 mg/kg of body weight, intravenously [i.v.], twice daily for 3 days) significantly decreased MRSA densities in cardiac vegetations, kidneys, and spleen versus those in untreated controls, except in one scenario (5 mg/kg, splenic MRSA counts). The efficacy of NZ2114 was clearly dose dependent in all target tissues. At 20 mg/kg, NZ2114 showed a significantly greater efficacy than vancomycin (P MIC) (%T(>MIC) is the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions), as analyzed by a sigmoid maximum-effect (E(max)) model (R(2) > 0.69). The superior efficacy of NZ2114 in this MRSA IE model suggests the potential for further development of this compound for treating serious MRSA infections.
Arnold S Bayer - One of the best experts on this subject based on the ideXlab platform.
-
telavancin is active against Experimental aortic valve endocarditis caused by daptomycin and methicillin resistant staphylococcus aureus strains
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Wessam Abdelhady, Yan Q Xiong, Arnold S Bayer, Rachelle GonzalesAbstract:ABSTRACT We compared the efficacy of telavancin (TLV) and daptomycin (DAP) in an Experimental Rabbit endocarditis model caused by two clinically derived daptomycin-resistant (DAP r ) methicillin-resistant Staphylococcus aureus (MRSA) strains. TLV treatment significantly reduced MRSA densities in all target tissues and increased the percentage of these organs rendered culture negative compared to those with the untreated control or DAP-treated animals. These results demonstrate that TLV has potent in vivo efficacy against DAP r MRSA isolates in this invasive endovascular infection model.
-
comparative efficacy of telavancin and daptomycin in Experimental endocarditis due to multi clonotype mrsa strains
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Yan Q Xiong, Arnold S Bayer, Wessam Abdelhady, Chieh Genna TangAbstract:BACKGROUND MRSA strains of clonal complexes (CCs) 5, 8, 30 and 45 are leading causes of complicated endovascular infections associated with suboptimal clinical outcomes. Telavancin is a novel anti-MRSA agent that both inhibits bacterial cell wall synthesis and disrupts membranes by depolarization. METHODS In this study, we compared the in vitro susceptibility and in vivo efficacy of telavancin versus daptomycin in an Experimental Rabbit infective endocarditis (IE) model caused by four MRSA strains representing each of the above CC types. RESULTS All study strains were susceptible to telavancin (MICs of ≤0.12 mg/L) and daptomycin (MICs of ≤0.5 mg/L). In vitro time-kill analyses revealed that supra-MIC levels of telavancin were effective at preventing regrowth at 24 h of incubation. In the IE animal model for all CC types, treatment with telavancin produced significantly greater reductions in MRSA counts as compared with daptomycin-treated animals in all target tissues. Moreover, telavancin-treated animals had a significantly higher percentage of sterile tissue cultures versus daptomycin-treated animals (e.g. 78%-100% versus 0% sterile vegetations and 100% versus 0%-11% sterile kidneys and spleen, in the telavancin- and daptomycin-treated animals, respectively). CONCLUSIONS These results suggest that telavancin exhibits significantly greater efficacies versus daptomycin in treating Experimental IE caused by MRSA clinical isolates across four common CC types.
-
efficacy of nz2114 a novel plectasin derived cationic antimicrobial peptide antibiotic in Experimental endocarditis due to methicillin resistant staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2011Co-Authors: Hans-henrik Kristensen, Yan Q Xiong, Wessam Abdel Hady, Antoine Deslandes, Astrid Rey, Laurent Fraisse, Michael R Yeaman, Arnold S BayerAbstract:Cationic antimicrobial peptides (CAPs) play important roles in host immune defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent activity against Gram-positive bacteria. In this study, we investigated (i) the in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics of NZ2114 and (ii) the in vivo efficacy of NZ2114 in comparison with those of two conventional antibiotics, vancomycin or daptomycin, in an Experimental Rabbit infective endocarditis (IE) model due to a methicillin-resistant Staphylococcus aureus (MRSA) strain (ATCC 33591). All NZ2114 regimens (5, 10, and 20 mg/kg of body weight, intravenously [i.v.], twice daily for 3 days) significantly decreased MRSA densities in cardiac vegetations, kidneys, and spleen versus those in untreated controls, except in one scenario (5 mg/kg, splenic MRSA counts). The efficacy of NZ2114 was clearly dose dependent in all target tissues. At 20 mg/kg, NZ2114 showed a significantly greater efficacy than vancomycin (P MIC) (%T(>MIC) is the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions), as analyzed by a sigmoid maximum-effect (E(max)) model (R(2) > 0.69). The superior efficacy of NZ2114 in this MRSA IE model suggests the potential for further development of this compound for treating serious MRSA infections.
Takeo Itoh - One of the best experts on this subject based on the ideXlab platform.
-
chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in Experimental Rabbit vein grafts
Journal of Vascular Surgery, 2009Co-Authors: Akio Kodama, Kimihiro Komori, Junko Kajikuri, Takeo ItohAbstract:Objective It has been suggested that 5-hydroxytryptamine (5-HT) plays a role in the pathogenesis of vein graft spasms. It is suggested that smooth muscle 5-HT 2A and 5-HT 1B receptors contribute to 5-HT-induced contraction, while endothelial 5-HT 1B receptors contribute to the 5-HT-induced endothelium-mediated relaxation. We recently found that chronic administration of the selective 5-HT 2A receptor antagonist sarpogrelate hydrochloride (SH) enhances the function of endothelium-derived nitric oxide (NO) in Rabbit vein grafts. However, it is unknown if such treatment modulates 5-HT-induced vasospasm in vein grafts, and if so, what the underlying mechanisms are. Methods Male Rabbits were divided into two groups: a control group and an SH-treated group. The jugular vein was interposed in the carotid artery in reversed fashion. Isometric tension was examined using vein grafts after 4 weeks. 5-HT (10 −8 -10 −6 M)-induced contraction was obtained in each group in the absence or presence of the NO synthase inhibitor l-N G -nitroarginine (l-NNA). The expression of 5-HT 2A and 5-HT 1B receptors was examined immunohistochemically. Results The 5-HT induced a concentration-dependent contractions in both groups. l-NNA did not significantly modify the 5-HT-induced contraction in the control group but enhanced it in the SH group. The 5-HT 1B receptor antagonist GR55562 inhibited the 5-HT-induced contraction in the control group, while it increased the sensitivity of contraction to 5-HT in the SH-treated group in the absence (but not in the presence) of l-NNA. Positive immunoreactivities against 5-HT 1B and 5-HT 2A receptors were identified in endothelial and medial regions of vein grafts in both groups, and the expression of 5-HT 2A receptors (but not 5-HT 1B receptors) was significantly less in the SH-treated group than in the control group. Conclusion Chronically administered SH to Rabbits upregulates the autoinhibitory mechanism by 5-HT through a release of NO from endothelium via an activation of endothelial 5-HT 1B receptors, thus attenuating its own contraction in vein grafts. Furthermore, such SH treatment downregulates the expression of smooth muscle 5-HT 2A receptors, thus further attenuating the 5-HT-induced contraction. These novel findings further support the clinical usefulness of SH in vein graft spasm after bypass grafting.
Akio Kodama - One of the best experts on this subject based on the ideXlab platform.
-
chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in Experimental Rabbit vein grafts
Journal of Vascular Surgery, 2009Co-Authors: Akio Kodama, Kimihiro Komori, Junko Kajikuri, Takeo ItohAbstract:Objective It has been suggested that 5-hydroxytryptamine (5-HT) plays a role in the pathogenesis of vein graft spasms. It is suggested that smooth muscle 5-HT 2A and 5-HT 1B receptors contribute to 5-HT-induced contraction, while endothelial 5-HT 1B receptors contribute to the 5-HT-induced endothelium-mediated relaxation. We recently found that chronic administration of the selective 5-HT 2A receptor antagonist sarpogrelate hydrochloride (SH) enhances the function of endothelium-derived nitric oxide (NO) in Rabbit vein grafts. However, it is unknown if such treatment modulates 5-HT-induced vasospasm in vein grafts, and if so, what the underlying mechanisms are. Methods Male Rabbits were divided into two groups: a control group and an SH-treated group. The jugular vein was interposed in the carotid artery in reversed fashion. Isometric tension was examined using vein grafts after 4 weeks. 5-HT (10 −8 -10 −6 M)-induced contraction was obtained in each group in the absence or presence of the NO synthase inhibitor l-N G -nitroarginine (l-NNA). The expression of 5-HT 2A and 5-HT 1B receptors was examined immunohistochemically. Results The 5-HT induced a concentration-dependent contractions in both groups. l-NNA did not significantly modify the 5-HT-induced contraction in the control group but enhanced it in the SH group. The 5-HT 1B receptor antagonist GR55562 inhibited the 5-HT-induced contraction in the control group, while it increased the sensitivity of contraction to 5-HT in the SH-treated group in the absence (but not in the presence) of l-NNA. Positive immunoreactivities against 5-HT 1B and 5-HT 2A receptors were identified in endothelial and medial regions of vein grafts in both groups, and the expression of 5-HT 2A receptors (but not 5-HT 1B receptors) was significantly less in the SH-treated group than in the control group. Conclusion Chronically administered SH to Rabbits upregulates the autoinhibitory mechanism by 5-HT through a release of NO from endothelium via an activation of endothelial 5-HT 1B receptors, thus attenuating its own contraction in vein grafts. Furthermore, such SH treatment downregulates the expression of smooth muscle 5-HT 2A receptors, thus further attenuating the 5-HT-induced contraction. These novel findings further support the clinical usefulness of SH in vein graft spasm after bypass grafting.
Junko Kajikuri - One of the best experts on this subject based on the ideXlab platform.
-
chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in Experimental Rabbit vein grafts
Journal of Vascular Surgery, 2009Co-Authors: Akio Kodama, Kimihiro Komori, Junko Kajikuri, Takeo ItohAbstract:Objective It has been suggested that 5-hydroxytryptamine (5-HT) plays a role in the pathogenesis of vein graft spasms. It is suggested that smooth muscle 5-HT 2A and 5-HT 1B receptors contribute to 5-HT-induced contraction, while endothelial 5-HT 1B receptors contribute to the 5-HT-induced endothelium-mediated relaxation. We recently found that chronic administration of the selective 5-HT 2A receptor antagonist sarpogrelate hydrochloride (SH) enhances the function of endothelium-derived nitric oxide (NO) in Rabbit vein grafts. However, it is unknown if such treatment modulates 5-HT-induced vasospasm in vein grafts, and if so, what the underlying mechanisms are. Methods Male Rabbits were divided into two groups: a control group and an SH-treated group. The jugular vein was interposed in the carotid artery in reversed fashion. Isometric tension was examined using vein grafts after 4 weeks. 5-HT (10 −8 -10 −6 M)-induced contraction was obtained in each group in the absence or presence of the NO synthase inhibitor l-N G -nitroarginine (l-NNA). The expression of 5-HT 2A and 5-HT 1B receptors was examined immunohistochemically. Results The 5-HT induced a concentration-dependent contractions in both groups. l-NNA did not significantly modify the 5-HT-induced contraction in the control group but enhanced it in the SH group. The 5-HT 1B receptor antagonist GR55562 inhibited the 5-HT-induced contraction in the control group, while it increased the sensitivity of contraction to 5-HT in the SH-treated group in the absence (but not in the presence) of l-NNA. Positive immunoreactivities against 5-HT 1B and 5-HT 2A receptors were identified in endothelial and medial regions of vein grafts in both groups, and the expression of 5-HT 2A receptors (but not 5-HT 1B receptors) was significantly less in the SH-treated group than in the control group. Conclusion Chronically administered SH to Rabbits upregulates the autoinhibitory mechanism by 5-HT through a release of NO from endothelium via an activation of endothelial 5-HT 1B receptors, thus attenuating its own contraction in vein grafts. Furthermore, such SH treatment downregulates the expression of smooth muscle 5-HT 2A receptors, thus further attenuating the 5-HT-induced contraction. These novel findings further support the clinical usefulness of SH in vein graft spasm after bypass grafting.
