No abstract

Development of a regional cumulative antibiogram that targets key ESKAPE pathogens is feasible, while observed trends may help aid future antimicrobial stewardship efforts.

Synthesis, characterization, electrochemical studies and ATRA activity of copper complexes with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) ligand in the presence of ascorbic acid as a reducing agent were reported. [Cu II (TPEN')Br][Br] (TPEN' denotes tetracoordinated ligand) catalyst showed a very low activity in ATRA of CBr 4 to 1octene, methyl methacrylate, methyl acrylate and styrene in methanol, which is a typical solvent used for ATRA reactions employing ascorbic acid. On the contrary, the yields and stereoselectivity towards monoadduct formation were dramatically increased in slightly polar but aprotic acetone. Based on molecular structures of isolated [Cu II (TPEN)][BPh 4 ] and [Cu II (TPEN')Br][Br] complexes, as well as UV-Vis and cyclic voltammetry studies, an equilibrium was proposed involving inactive [Cu II (TPEN)] 2+ and ATRP active [Cu II (TPEN')Br] + cations The halidophilicity of the bromide-based deactivating complex ([Cu II (TPEN')Br][Br]) decreased approximately 750 times upon changing the solvent from acetone (K Br =3000±230) to methanol (K Br =4.1±0.1), explaining poor catalytic activity in methanol. In acetone, [Cu II (TPEN')Br][Br] complex was nearly as active in ATRA reactions employing ascorbic acid as previously reported [Cu II (TPMA)Br][Br].

Pharmacokinetic modeling was used to describe 5 (and 6)-carboxy-2',7'-dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA dosing models were based on simultaneous fitting of CDF levels in apical, basolateral, and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being 3-fold higher following basolateral dosing, thus supporting nonsaturable CDF efflux kinetics. A 3-compartment catenary model with intracellular CDFDA hydrolysis described CDF disposition. This model predicted that apical CDF efflux was not altered in the presence of MK-571, and that basolateral membrane clearance was enhanced to account for reduced intracellular CDF in the presence of this multidrug resistance-associated protein (MRP) inhibitor. Similar effects were predicted for glyceollin, while genistein exposure had no predicted effects on CDF efflux. These modulator effects are discussed in the context of model predicted intracellular CDF concentrations relative to reports of CDF affinity (measured by K) for MRP2 and MRP3. This model-based analysis confirms the complexity of efflux kinetics and suggests that other transporters may have contributed to CDF efflux.