Antibiotic prescribing practices of medical doctors in a resource-limited setting and the influence of individual perceptions and stewardship support: a survey in three tertiary hospitals in Vietnam.

Objectives: To understand antibiotic prescribing and influencing factors to inform antimicrobial stewardship (AMS) interventions to reduce unwanted consequences of antibiotic use in hospitals in Vietnam, a lower-middle-income country in Asia. Methods: We conducted a cross-sectional study of doctors at three tertiary hospitals using non-probability convenience sampling, through a paper-based (Hospitals 1 and 2) or electronic (Hospital 3) survey. Questions included items on perceptions regarding antibiotic resistance and AMS, prescribing practices, knowledge, demographics and training. We used principal components analysis and mixed-effects models to examine practices and identify influencing factors. Results: Among 314 surveyed participants, 61%, 57% and 59% in Hospitals 1, 2 and 3, respectively, felt certain about the appropriateness of their antibiotic prescriptions. In total, 9% reported sometimes prescribing antibiotics when not needed to meet patients' expectations, and 13% reported doing so to avoid perceived complications. Higher prescribing confidence was found among those with positive perceptions about AMS (P < 0.0001), whereas negative perceptions about colleagues' practices reduced this confidence (P < 0.0001). Individual preference for branded antibiotics was associated with more unnecessary prescribing whereas having higher prescribing confidence decreased the habits of prescribing when not needed. Conclusions: This study provides important implications for design of hospital interventions to address influencing factors on antibiotic prescribing in Vietnam and similar resource-limited settings. Specific interventions should target improving knowledge through education and training for doctors, enhancing the support from the AMS team, and promoting guidelines and policies for appropriate antibiotic use in hospital.

A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN): pilot implementation in three countries in Southeast Asia, 2019-2020.

Background: Case-based surveillance of antimicrobial resistance (AMR) provides more actionable data than isolate- or sample-based surveillance. We developed A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN) as a lightweight but comprehensive platform, in which we combine clinical data collection with diagnostic stewardship, microbiological data collection and visualisation of the linked clinical-microbiology dataset. Data are compatible with WHO GLASS surveillance and can be stratified by syndrome and other metadata. Summary metrics can be visualised and fed back directly for clinical decision-making and to inform local treatment guidelines and national policy. Methods: An ACORN pilot was implemented in three hospitals in Southeast Asia (1 paediatric, 2 general) to collect clinical and microbiological data from patients with community- or hospital-acquired pneumonia, sepsis, or meningitis. The implementation package included tools to capture site and laboratory capacity information, guidelines on diagnostic stewardship, and a web-based data visualisation and analysis platform. Results: Between December 2019 and October 2020, 2294 patients were enrolled with 2464 discrete infection episodes (1786 community-acquired, 518 healthcare-associated and 160 hospital-acquired). Overall, 28-day mortality was 8.7%. Third generation cephalosporin resistance was identified in 54.2% (39/72) of E. coli and 38.7% (12/31) of K. pneumoniae isolates . Almost a quarter of S. aureus isolates were methicillin resistant (23.0%, 14/61). 290/2464 episodes could be linked to a pathogen, highlighting the level of enrolment required to achieve an acceptable volume of isolate data. However, the combination with clinical metadata allowed for more nuanced interpretation and immediate feedback of results. Conclusions: ACORN was technically feasible to implement and acceptable at site level. With minor changes from lessons learned during the pilot ACORN is now being scaled up and implemented in 15 hospitals in 9 low- and middle-income countries to generate sufficient case-based data to determine incidence, outcomes, and susceptibility of target pathogens among patients with infectious syndromes.

Sources for isolation of extracellular polymeric substances (EPSs) producing bacterial strains which are capable of using wastewater sludge as solo substrate.

Isolation of extracellular polymeric substances (EPSs) producing bacterial strains capable of using sludge as low-cost growth substrate was carried out in this study. A total of 110 EPS-producing strains were isolated from different sources, which include sludge of beer and winery wastewater treatment plant (WWTP); young, 2-month-old and 10-year-old leachate. Thirty-seven isolated strains showed good growth in sludge medium with cell count varying from 106 to 1010 most probable number (MPN)/mL and total EPS concentration from 2737 to 6639 mg/L. Twenty-one strains produced EPS with high flocculation activity (FAmax varied from 72.0% to 80.2%). The highest FAmax (80.2%) was observed with EPS produced by strain BES 19, which was isolated from sludge of beer WWTP. Sludge of beer WWTP, young leachate and 10-year-old leachate were good sources for isolation of EPS-producing bacteria.

Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage.

Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood-retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders.

Structure-Activity Relationship of Indole-Tethered Pyrimidine Derivatives that Concurrently Inhibit Epidermal Growth Factor Receptor and Other Angiokinases.

Antiangiogenic agents have been widely investigated in combination with standard chemotherapy or targeted cancer agents for better management of advanced cancers. Therapeutic agents that concurrently inhibit epidermal growth factor receptor and other angiokinases could be useful alternatives to combination therapies for epidermal growth factor receptor-dependent cancers. Here, we report the synthesis of an indole derivative of pazopanib using a bioisosteric replacement strategy, which was designated MKP101. MKP101 inhibited not only the epidermal growth factor receptor with an IC50 value of 43 nM but also inhibited angiokinases as potently as pazopanib. In addition, MKP101 effectively inhibited vascular endothelial growth factor-induced endothelial proliferation, tube formation, migration of human umbilical vein endothelial cells and proliferation of HCC827, an epidermal growth factor receptor-addicted cancer cell line. A docking model of MKP101 and the kinase domain of the epidermal growth factor receptor was generated to predict its binding mode, and validated by synthesizing and evaluating MKP101 derivatives. Additionally, a study of structure-activity relationships of indolylamino or indolyloxy pyrimidine analogues derived from MKP101 demonstrated that selectivity for epidermal growth factor receptor and other angiokinases, especially vascular endothelial growth factor receptor 2 depends on the position of substituents on pyrimidine and the type of link between pyrimidine and the indole moiety. We believe that this study could provide a basis for developing angiokinase inhibitors having high affinity for the epidermal growth factor receptor, from the pyrimidine scaffold.

Commercial product exploitation from marine microbial biodiversity: some legal and IP issues.

The biodiversity found in the marine environment is remarkable and yet largely unknown compared with the terrestrial one. The associated genetic resource, also wide and unrevealed, has raised a strong interest from the scientific and industrial community. However, despite this growing interest, the discovery of new compounds extracted from marine organisms, more precisely from microorganisms, is ruled by a complex legislation. The access and transfer of genetic resource are ruled by the Convention on Biological Diversity. One of the three core objectives of this convention is to ensure the fair and equitable sharing of benefits generated by the use of genetic resources and to split these benefits between the different stakeholders. From the discovery of a microorganism to the commercialization of a product, three main stakeholders are involved: providers of microorganisms, e.g. academic institutes, the scientists who will perform R&D on biodiversity, and the industrial companies which will commercialize the final product arising from the R&D results. This article describes how difficult and complex it might be to ensure a fair distribution of benefits of this research between the parties.

Adsorption and removal of arsenic from water by iron ore mining waste.

There is a global need to develop low-cost technologies to remove arsenic from water for individual household water supply. In this study, a purified and enriched waste material (treated magnetite waste, TMW) from the Trai Cau's iron ore mine in the Thai Nguyen Province in Vietnam was examined for its capacity to remove arsenic. The treatment system was packed with TMW that consisted of 75% of ferrous-ferric oxide (Fe(3)O(4)) and had a large surface area of 89.7 m(2)/g. The experiments were conducted at a filtration rate of 0.05 m/h to treat groundwater with an arsenic concentration of 380 microg/L and iron, manganese and phosphate concentrations of 2.07 mg/L, 0.093 mg/L and 1.6 mg/L respectively. The batch experimental results show that this new material was able to absorb up to 0.74 mg arsenic/g. The results also indicated that the treatment system removed more than 90% arsenic giving an effluent with an arsenic concentration of less than 30 microg/L while achieving a removal efficiency of about 80% for Mn(2 + ) and PO(4) (3-). This could be a promising and cost-effective new material for capturing arsenic as well as other metals from groundwater.