Investigation of the influence of dry extracts of bupleurum aureum and Salsola collina L. on the antimicrobial effect of co-trimoxazole

Scientific data on the pharmacodynamics of dry extracts of Bupleurum aureum and Salsola collina L. based on the results of studying the antimicrobial effect and the similar effect of co-trimoxazole when they are used together have been supplemented. The investigated phytoextracts do not show antimicrobial properties, but they do not change the antimicrobial effect of co-trimoxazole when they are used in combination. The aim of the study was to experimentally investigate the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establish the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when used together. Materials and methods. The research was conducted in May 2016. Screening of the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establishing of the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when they are used together was carried out in the laboratory of the Department of Microbiology of the National Pharmaceutical University, which has a certificate of attestation 045/14 dated 28.10.2014. For determination of antimicrobial activity, the agar diffusion method ("well" method), which is based on the ability of medicinal substances to penetrate the agar layer, was used. A set of reference strains of microorganisms was used: S. aureus ATCC 6538, E. coli ATCC 8739, P. aeruginosa ATCC 9027, B. subtilis ATCC 6633, C. albicans ATCC 10231. Petri dishes were filled with two layers of solid nutrient medium. The lower layer - 10 ml of melted "cold" AGV agar (medium No. 3), the upper layer - nutrient medium for the corresponding test strain. After cooling the lower layer of agar, three thin-walled steel cylinders (inner diameter - 6.0±0.1 mm, height - 10.0±0.1 mm) were placed on it at an equal distance from each other and from the edge of the cup. The top layer was poured around the cylinders - 13.5 ml of agar, melted and cooled to 45-48°С, mixed with the seed dose of the test microorganism (1.5 ml of microbial suspension, the concentration corresponding to the type of microorganism). After cooling the upper layer of agar, the cylinders were removed with sterile tweezers and 0.25-0.3 ml of the studied drug was added to the resulting wells. The results were recorded after 24 h by measuring the zone of growth inhibition, including the diameter of the wells. Measurements were made with an accuracy of 1 mm, while focusing on the complete absence of visible growth. The obtained data were analyzed using the methods of variational statistics. The significance level is p<0.05. The studied plant extracts of Bupleurum aureum (aqueous and alcoholic) and Salsola collina L. (aqueous and alcoholic) were used in doses of 0.005 mg/ml and 0.01 mg/ml, which corresponded to doses of 5 mg/kg and 10 mg/kg. Experimental data were also processed by parametric (Newman-Keuls) and non-parametric (Mann-Whitney) methods of variational statistics, using the Statistica 6.0 statistical software package; differences were considered statistically significant at p<0.05. Results. At the final stage, the determination of the antimicrobial effect of water and alcohol extracts of Bupleurum aureum and Salsola collina L. at doses of 1 mg/ml and 5 mg/ml was carried out, and the effect of BAS of these extracts on the antimicrobial effect of co-trimoxazole when used together was determined. In the course of the study, it has been established, that the addition of the above-mentioned extracts to the co-trimoxazole formulation does not affect its initial antimicrobial properties. Conclusion. Today, drug-induced liver injury remains one of the most important problems of hepatology and pediatrics, pharmacological science pays a lot of attention to the search for new effective and harmless drugs with a hepatoprotective effect, and the improvement of existing drugs is primarily aimed at increasing their specificity and reducing side effects related to the pharmacological properties of the drug. Currently, there is increasing interest in medicinal plants as a source of various biologically active substances (BAS), which provide a wide spectrum of pharmacological action of the agent, which allows to immediately affect various links of the pathogenesis of liver diseases. The analysis of scientific sources made it possible to establish that medicinal products of plant origin, thanks to BAS, possess polymodality of effects and reveal a versatile complex effect on the course of pathological processes in the body. Most drugs are characterized by good tolerability, absence of withdrawal syndrome and toxicity to parenchymal organs. Medicinal plants are used not only as monopreparations, but also in combination with synthetic drugs and as raw materials for obtaining BA

<i>Klebsiella pneumoniae</i> Susceptibility to Carbapenem/Relebactam Combinations: Influence of Inoculum Density and Carbapenem-to-Inhibitor Concentration Ratio

The inoculum effect (IE) is a well-known phenomenon with beta-lactams. At the same time, the IE has not been extensively studied with carbapenem/carbapenemase inhibitor combinations. The antibiotic-to-inhibitor concentration ratio used in susceptibility testing can influence the in vitro activity of the combination. To explore the role of these factors, imipenem/relebactam and doripenem/relebactam MICs were estimated against six Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae strains at standard inocula (SI) and high inocula (HI) by two methods: with a fixed relebactam concentration and with a fixed, pharmacokinetic-based carbapenem-to-relebactam concentration ratio. The combination MICs at HI, compared to SI, increased with most of the tested strains. However, the IE occurred with only two K. pneumoniae strains regardless of the MIC testing method. The relationship between the MICs at SI and the respective inoculum-induced MIC changes was observed when the MICs were estimated at pharmacokinetic-based carbapenem-to-relebactam concentration ratios. Thus, (1) IE was observed with both carbapenem/relebactam combinations regardless of the MIC testing method; however, IE was not observed frequently among tested K. pneumoniae strains. (2) At HI, carbapenem/relebactam combination MICs increased to levels associated with carbapenem resistance. (3) Combination MICs determined at pharmacokinetic-based carbapenem-to-inhibitor concentration ratios predict susceptibility elevations at HI in KPC-producing K. pneumoniae

Natural Nanoclay-Based Silver-Phosphomolybdic Acid Composite with a Dual Antimicrobial Effect

[Image: see text] The problem of microbial growth on various surfaces has increased concern in society in the context of antibiotic misuse and the spreading of hospital infections. Thus, the development of new, antibiotic-free antibacterial strategies is required to combat bacteria resistant to usual antibiotic treatments. This work reports a new method for producing an antibiotic-free antibacterial halloysite-based nanocomposite with silver nanoparticles and phosphomolybdic acid as biocides, which can be used as components of smart antimicrobial coatings. The composite was characterized by using energy-dispersive X-ray fluorescence spectroscopy and transmission electron microscopy. The release of phosphomolybdic acid from the nanocomposite was studied by using UV–vis spectroscopy. It was shown that the antibiotic-free nanocomposite consisting of halloysite nanotubes decorated with silver nanoparticles loaded with phosphomolybdic acid and treated with calcium chloride possesses broad antibacterial properties, including the complete growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa bacteria at a 0.5 g × L(–1) concentration and Acinetobacter baumannii at a 0.25 g × L(–1) concentration