Reducing antibiotic prescribing in general practice in Australia: a cluster randomised controlled trial of a multimodal intervention.

BACKGROUND: The health and economic burden of antimicrobial resistance (in Australia is significant. Interventions that help guide and improve appropriate prescribing for acute respiratory tract infections in the community represent an opportunity to slow the spread of resistant bacteria. Clinicians who work in primary care are potentially the most influential health care professionals to address the problem of antimicrobial resistance, because this is where most antibiotics are prescribed. METHODS: A cluster randomised trial was conducted comparing two parallel groups of 27 urban general practices in Queensland, Australia: 13 intervention and 14 control practices, with 56 and 54 general practitioners (GPs), respectively. This study evaluated an integrated, multifaceted evidence-based package of interventions implemented over a 6-month period. The evaluation included quantitative and qualitative components, and an economic analysis. RESULTS: A multimodal package of interventions resulted in a reduction of 3.81 prescriptions per GP per month. This equates to 1280.16 prescriptions for the 56GPs in the intervention practices over the 6-month period. The cost per prescription avoided was A$148. The qualitative feedback showed that the interventions were well received by the GPs and did not impact on consultation time. Providing GPs with a choice of tools might enhance their uptake and support for antimicrobial stewardship in the community. CONCLUSIONS: A multimodal package of interventions to enhance rational prescribing of antibiotics is effective, feasible and acceptable in general practice. Investment in antimicrobial stewardship strategies in primary care may ultimately provide the important returns for public health into the future.

Molecular identification and in vitro evaluation of probiotic functional properties of some Egyptian lactic acid bacteria and yeasts.

BACKGROUND: The health-promoting effects along with global economic importance of consuming food products supplemented with probiotic microorganisms encouraged the researchers to discover new probiotics. RESULTS: Fourteen lactic acid bacterial isolates were identified as Enterococcus mediterraneensis, Lactobacillus fermentum, and Streptococcus lutetiensis by 16S rRNA gene sequencing, and in vitro characterized for their actual probiotic potential. All E. mediterraneensis isolates were resistant to clindamycin, whereas Lb. fermentum isolates were resistant to ampicillin, clindamycin, and vancomycin. The E. mediterraneensis and Lb. fermentum isolates displayed high overall digestive survival, ranged from 1.35 ± 0.06 to 32.73 ± 0.84% and from 2.01 ± 0.01 to 23.9 ± 1.85%, respectively. All isolates displayed cell surface hydrophobicity, ranged between 15.44 ± 6.72 and 39.79 ± 2.87%. The strongest auto-aggregation capability, higher than 40%, was observed for most E. mediterraneensis and Lb. fermentum isolates. The E. mediterraneensis isolates (L2, L12, and L15), Lb. fermentum (L8, L9, and L10), and Strep. lutetiensis (L14) exhibited the greatest co-aggregation with Salmonella typhimurium, Escherichia coli O157:H7, Staphylococcus aureus, and Bacillus cereus. Fifty-seven and fourteen hundredth percent of E. mediterraneensis isolates could be considered bacteriocinogenic against E. coli O157:H7, B. cereus, and S. aureus. CONCLUSION: This study is the first one to isolate Enterococcus mediterraneensis in Egypt and to characterize it as new species of probiotics globally. According to the results, E. mediterraneensis (L2, L12, and L15), Lb. fermentum (L8, L9, and L10), and Strep. lutetiensis (L14) are the most promising in vitro probiotic candidates.

Dual Targeting of VEGFR2 and C-Met Kinases via the Design and Synthesis of Substituted 3-(Triazolo-thiadiazin-3-yl)indolin-2-one Derivatives as Angiogenesis Inhibitors.

The vascular endothelial growth factor receptor 2 (VEGFR2) and c-mesenchymal epithelial transition factor (c-Met) are members of receptor tyrosine kinases which have a crucial role in the process of angiogenesis. Isatin moiety is a versatile group that is shared in many compounds targeting both c-Met and VEGFR2 kinases. In this study, we designed and synthesized different derivatives of substituted 3-(triazolo-thiadiazin-3-yl)indolin-2-one derivatives (6a-y) as dual inhibitors for c-Met and VEGFR2 enzymes. Eight compounds 6a, 6b, 6e, 6l, 6n, 6r, 6v, and 6y were assessed for their anticancer activities against a panel of 58 cancer cell lines according to the US-NCI protocol. Compound 6b revealed the most effective antiproliferative potency (GI %), with broad-spectrum activity against different subpanels of the most NCI 58 tumor cell lines. An in vivo hen's egg-chorioallantoic membrane (HET-CAM) angiogenic study was carried out for 21 compounds 6a, b, d, f, h, i, k-o, t, and 6x to check their mortality and toxicity. At 100 µM concentration, all compounds produced 100% mortality of the chick embryos. At 40 µM concentration, 13 compounds did not exhibit any detectable mortality (nontoxic) and revealed a potent antiangiogenic effect. Seven compounds 6b, 6d, 6f, 6n, 6o, 6t, and 6x significantly decreased the number of blood vessels, and compound 6b was the most effective antiangiogenic agent comparable to dexamethasone. Molecular docking studies were conducted for compound 6b to investigate its mode of interaction within the binding site of both c-Met and VEGFR2 kinases.

Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein.

BACKGROUND: Effective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action. METHODS: Therefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3. RESULTS: Significantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups. CONCLUSION: These SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.

Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

Ion-exchange complex of famotidine: sustained release and taste masking approach of stable liquid dosage form.

A stable controlled release resinate-complex for the highly bitter taste famotidine (FAM) was developed to allow once-daily administration and improve patient compliance especially in pediatric and geriatric medicine. The drug-resinate complexes were prepared in different drug to resin (Amberlite IRP-69) ratios by weight (1:1, 1:2, 1:3, 1:4, 1:5 and 1:6). The optimized drug-resinate complex resulted from 1:6 drug to resin ratio experienced maximum drug loading and sustained release property. Hence, it was subjected to physicochemical characterizations by differential scanning colorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The optimized complex was further dispensed in the prepared syrup and the suspension was subjected to accelerated stability study, as mentioned in the International Conference on Harmonization (ICH) guidelines. Furthermore, the gustatory properties of the complex were evaluated on humans. The syrup complied successfully with ICH guidelines and sufficiently alleviated the bitterness of famotidine.