A systematic review and narrative synthesis of pharmacist-led education-based antimicrobial stewardship interventions and their effect on antimicrobial use in hospital inpatients

Acknowledgements The authors would like to thank Dr Peerawat Jinathongthai and Dr Sisira Donsamak (Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Thailand) who advised and contributed in the literature search. Funding TM has received the Royal Thai Government Scholarship for his doctoral study (scholarship number ST G5397) at The University of Bath, Bath, UK. None of the other authors were funded by a specific grant for this research from any funding agency in the public, commercial, or non-for-profit sectors.Peer reviewedPostprin

What influences the implementation and sustainability of antibiotic stewardship programmes in hospitals? A qualitative study of antibiotic pharmacists' perspectives across South West England

Objectives Antibiotic stewardship programmes (ASPs) are needed at every hospital as they can improve antibiotic use and address antibiotic resistance. Pharmacists are key agents and specialists in these programmes. This study explored antibiotic pharmacists' perceptions of factors that influence the implementation and sustainability of hospital-based ASPs. Methods Semistructured interviews were conducted with hospital antibiotic pharmacists face-to-face or by telephone. NVivo V.12 software was used to collate and organise the data grouped within codes. Thematic analysis was undertaken using inductive and deductive approaches to produce overarching themes. Results Thirteen pharmacists from 13 hospitals were interviewed. Four main themes were identified: (1) 'organisational culture' which highlighted the importance of strong local clinical leadership to help achieve organisational buy-in and address resistance among physicians or clinical hierarchies; (2) 'national influences' including networks, guidance and incentive schemes which were considered to be a driver to bring about changes across organisation; (3) 'continuous monitoring with feedback ASP data, preferably through direct communication' to demonstrate the impact of the programmes which then facilitated ongoing support from local leadership and improved engagement across organisation; and (4) 'resources' which indicated the need of information technology and dedicated personnel with protected time to support ASP activities. Conclusions Interventions and strategies should operate at different levels—individual, team, organisational and national—to help implement and sustain ASPs in hospital. This is also the first study to identify and highlight the importance of national initiatives in contributing to the implementation and sustainability of hospital-based ASPs

Assessment of Mechanical/Chemical Properties and Cytotoxicity of Resin-Modified Glass Ionomer Cements Containing Sr/F-Bioactive Glass Nanoparticles and Methacrylate Functionalized Polyacids

This study prepared low-toxicity, elemental-releasing resin-modified glass ionomer cements (RMGICs). The effect of 2-hydroxyethyl methacrylate (HEMA, 0 or 5 wt%) and Sr/F-bioactive glass nanoparticles (Sr/F-BGNPs, 5 or 10 wt%) on chemical/mechanical properties and cytotoxicity were examined. Commercial RMGIC (Vitrebond, VB) and calcium silicate cement (Theracal LC, TC) were used as comparisons. Adding HEMA and increasing Sr/F-BGNPs concentration decreased monomer conversion and enhanced elemental release but without significant effect on cytotoxicity. Rising Sr/F-BGNPs reduced the strength of the materials. The degree of monomer conversion of VB (96%) was much higher than that of the experimental RMGICs (21–51%) and TC (28%). The highest biaxial flexural strength of experimental materials (31 MPa) was significantly lower than VB (46 MPa) (p < 0.01) but higher than TC (24 MPa). The RMGICs with 5 wt% HEMA showed higher cumulative fluoride release (137 ppm) than VB (88 ppm) (p < 0.01). Unlike VB, all experimental RMGICs showed Ca, P, and Sr release. Cell viability in the presence of extracts from experimental RMGICs (89–98%) and TC (93%) was significantly higher than for VB (4%). Experimental RMGICs showed desirable physical/mechanical properties with lower toxicity than the commercial material

Nano-Hydroxyapatite and Nano-Hydroxyapatite/Zinc Oxide Scaffold for Bone Tissue Engineering Application

This research aims to evaluate the mechanical properties, biocompatibility, and degradation behavior of scaffolds made of pure hydroxyapatite (HA) and HA‐modified by ZnO for bone tissue engineering applications. HA and ZnO were developed using sol‐gel and precipitation methods respectively. The scaffolds properties were characterized using X‐ray diffraction (XRD), Fourier transform spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), atomic absorption (AA), and atomic force microscopy (AFM). The interaction of scaffold with cells was assessed using in vitro cell proliferation and alkaline phosphatase (ALP) assays. The obtained results indicate that the HA/ZnO scaffolds possess higher compressive strength, fracture toughness, and density—but lower hardness—when compared to the pure HA scaffolds. After immersing the scaffold in the SBF solution, more deposited apatite appeared on the HA/ZnO, which results in the rougher surface on this scaffold compared to the pure HA scaffold. Finally, the in vitro biological analysis using human osteoblast cells reveals that scaffolds are biocompatible with adequate ALP activity

Evaluation Of Mechanical and Biocompatibility Properties of Hydroxyapatite/Manganese Dioxide Nanocomposite Scaffolds for Bone Tissue Engineering Application

The aim of this research was to evaluate the mechanical properties, biocompatibility, and degradation behavior of scaffolds made of pure hydroxyapatite (HA) and HA‐modified by MnO2 for bone tissue engineering applications. HA and MnO2 were developed using sol‐gel and precipitation methods, respectively. The scaffolds properties were characterized using X‐ray diffraction (XRD), Fourier transform spectroscopy (FTIR), scanning electron microcopy (SEM), energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM). The interaction of scaffold with cells was assessed using in vitro cell proliferation and alkaline phosphatase (ALP) assays. The obtained results indicate that the HA/ MnO2 scaffolds possess higher compressive strength, toughness, hardness, and density when compared to the pure HA scaffolds. After immersing the scaffold in the SBF solution, more deposited apatite appeared on the HA/MnO2, which results in the rougher surface on this scaffold compared to the pure HA scaffold. Finally, the in vitro biological analysis using human osteoblast cells reveals that scaffolds are biocompatible with adequate ALP activit

Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach

© 2020 Elsevier B.V. The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing the size of HIV reservoirs within the mesenteric lymphatic system