Use of ionic liquid based chitosan as sorbent for preconcentration of fluoroquinolones in milk,egg, fish,bovine, and chicken meat samples by solid phase extraction prior to HPLC determination

The possibility of using ionic liquid based chitosan sorbent for the separation and preconcentration of fluoroquinolone antibiotics (marbofloxacin, enoxacin, ofloxacin, ciprofloxacin, and enrofloxacin) has been studied. For this reason, different ionic liquids were prepared and coated on the chitosan sorbent. The conditions of the preconcentration of fluoroquinolones on a microcolumn have been optimized and the extraction efficiencies of the prepared sorbents have been compared. The compounds were eluted with 5 mL of 20% NH₃ (v/v, MeOH) solution and determined by HPLC with diode array and fluorescence detector. The limits of detection were found as 4.23 µ g L^?1 for marbofloxacin, and 1.09 µg L^?1 for enoxacin; 3.23 × 10^?3 µg L^?1 for ofloxacin; 8.39 × 10^?3 µg L^?1 for ciprofloxacin; and 19.50 × 10^?3 µg L^?1 for enrofloxacin. The developed method was applied for the analysis of fluoroquinolone in milk, egg, fish, bovine, and chicken samples and the recoveries were obtained in the range 70–100%.     

A New Sensor Method for Studying the Effect of Gentamicin and Cefotaxime Combination Against Escherichia coli

Abstract

A new sensor method based on a multi-channel series piezoelectric quartz crystal (MSPQC) was proposed for studying the effect of gentamicin and cefotaxime combination against Escherichia coli ATCC 25922. The frequency curves under different combination regimens were obtained and compared with each other. When antibiotic had an inhibitory effect to the growth of bacteria, frequency detection time (FDT) would be prolonged. The FDT was used to assess the effect of an antibiotic combination. By using the proposed method, simultaneous administration, different order, and time interval of nonsimultaneous administration were investigated in detail. The MSPQC method can provide the process information in real time. It is simple, rapid, and easy to perform.     

Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors

Antibiotics are key drugs in modern healthcare, especially in hospitals, where multiresistant bacteria resides and is a potential threat to human health. In the present work, a new series of adjuvants working synergistically with the carbapenem meropenem, in which a selective zinc-chelating agent was covalently linked to the small bacterial peptide D-Ala-D-Ala, was synthesized and tested against VIM-2 and NDM-1 metallo-β-lactamases (MBLs). The nature of the linker was modified in a structure-activity relationship study. Compound 1i, having an ethyl piperidine linker, lowered the MIC of meropenem from 32 to 64?mg/L to 2 and 1–2?mg/L against VIM-2- and NDM-1-producing clinical isolates, respectively. The IC₅₀ value of 1i against VIM-2 was 9.8 and 2.2?μM after 5 and 20?min, respectively. Compound 1i also showed intrinsic toxicity against three eukaryotic human tumoral cell lines between 50 and 120?μM.     

Ultrasound-engineered synthesis of WS2@CeO2 heterostructure for sonocatalytic degradation of tylosin

The main aim of the present investigation was the intercalation of WS₂ nanosheets in the structure of ceria (CeO₂) to be used for the efficient catalytic destruction of tylosin (TYL) as a macrolide antibiotic in water. As-synthesized heterostructured catalyst was placed in a sono-reactor (40 kHz and 300 W) in order to degrade TYL through the sonocatalysis. 15 wt% WS₂/CeO₂ was chosen for performing the systematic experiments. Decreasing the concentration of TYL, along with increasing the WS₂/CeO₂ dosage led to reduced degradation efficiency. The water hardness was demonstrated to be a suppressive agent on the sonocatalysis of the target pollutant. As-generated holes, OH, and also O₂⁻ were responsible for the degradation of TYL. Increasing the ultrasound power and operating temperature enhanced the degradation efficiency. The degradation rate boosted up when the temperature was raised from 10 °C (0.0107 1/min) to 40 °C (0.0165 1/min). Moreover, the lowest activation energy (E_a) for sonocatalytic degradation was obtained as 10.81 kJ/mol. The sonocatalytic activity of WS₂/CeO₂ in the sono-reactor encountered insignificant change within five consecutive operational runs (~15% reduction). The mechanism and pathways of the sonocatalytic decomposition of TYL are also proposed.     

A new antibiotic produced by the cyanobacterium-symbiotic fungus Simplicillium lanosoniveum

The culture broth of the cyanobacterium-symbiotic fungus Simplicillium lanosoniveum var. Tianjinienss Q. L. Dong exhibited unanticipated antibacterial activities against the Gram-positive bacteria, particularly the pathogenic bacterium Staphylococcus aureus, indicating the secretion of antibiotic-like metabolite, for which the modified Sabouraud medium was the suitable medium. The antibiotic-like metabolite was separated with macroporous resins CT-12 (absorption) and 95% ethanol (desorption), purified by ion-exchange resins D301T and displayed a characteristic absorption peak at 228 nm, suggesting the presence of nitrogen. The negative biuret and ninhydrin tests confirmed the absence of –NH₂ and –COOH groups. Further, HPLC and mass spectrometry analyses showed that the retention time and molecular weight of the antibiotic-like metabolite were 4.1031 min and 163.0182 (Δ ± 2.3 ppm), respectively. Taking together, we speculated that the antibiotic-like metabolite was a new antibiotic structurally similar to alkaloid, which was the first one isolated from the species of Simplicillium genus.     

Modulation of antibiotic activity by the hydroalcoholic extract from leaves of Caryocar coriaceum WITTM

The aim of this study was to identify the presence of tannins, phenols and flavonoids on the hydroalcoholic extract of Caryocar coriaceum leaves (HECCL) and to determine the antioxidant and antibacterial activity of this extract. The extract was tested alone (1024–1 μg/mL) or associated (MIC/8) with several antibiotics in order to identify any antibacterial activity against multiresistant bacterial strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa). The existence of tannins, total phenols (901.31 mg/g) and flavonoids (89.68 mg/g) was confirmed in the HECCL. The presence of rutin and quercetin were confirmed by Thin-layer chromatography (TLC). Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, the antioxidant activity of the extract (9 μg/mL) was determined. Moreover, the Minimum Inhibitory Concentration (MIC) value found for HECCL was 1024 μg/mL and the association between HECCL (MIC/8) with benzylpenicillin significantly changed its minimum inhibitory concentration from 2500 to 625 μg/mL against E. coli.     

Synthesis of spermidinylcholestanol and spermidinylcholesterol, squalamine analogues

Several novel squalamine-related polyaminosterols are reported. The synthesis of 7α-N-[3N-(4-aminobutyl)aminopropyl]aminocholestanol I, 6α-N-[3N-(4-aminobutyl)aminopropyl]aminocholestanol II, 7α and 7β-N-[3N-(4-aminobutyl)aminopropyl]aminocholesterol (III and IV), was accomplished from cholesterol, they provide the first examples in which spermidine is introduced in the B steroidal ring. These molecules showed comparable antibacteria and fungi activities to squalamine, and were cytotoxic on a human non-small cell bronchopulmonary carcinoma line (NSCLC-N6). Therefore, these molecules with antibiotic and cytotoxic activities are promising for immune-compromised patients in cancer chemotherapy.     

The efficacy of sono-electro-Fenton process for removal of Cefixime antibiotic from aqueous solutions by response surface methodology (RSM) and evaluation of toxicity of effluent by microorganisms

The increasing use of antibiotics by humans and their persistence in the environment leads to the development of drug resistance, which is nowadays considered as an environmental problem. The aim of this study was to determine the efficacy of sono-electro-Fenton process for removal of Cefixime antibiotic from aqueous solutions by Response Surface Methodology (RSM) and to evaluate the toxicity of effluent by microorganisms. In the present study, the degradation of synthetic wastewater containing Cefixime was investigated in a reactor (with a useful volume of 1 L) located in the chamber of the ultrasonic device. The effects of pH, hydrogen peroxide concentration, voltage, initial antibiotic concentration, and electrolysis time were investigated using the Box-Behnken model, and the optimal conditions for elimination were obtained by analyzing the variance. The performance of the electro-Fenton and ultrasonic process was evaluated separately and in combination under optimal conditions. Toxicity of inlet and outlet was tested by Escherichia coli and Staphylococcus aureus, and growth inhibition percentage was calculated. The intermediates were determined by LC-MS with the lowest molecular mass. The results showed that the sono-electro-Fenton process under optimum conditions, including pH of 3.07, hydrogen peroxide concentration of 0.85 mL/L, voltage 15 V, initial antibiotic concentration 10.4 mg/L and electrolysis time of 81.5 min has a percentage of removal of 97.5%. Under optimum conditions, the percentage of removal by electro-Fenton and ultrasonic separately were 81.7% and 9%, respectively, and in the hybrid process of sono-electro-Fenton, the percentage of removal increased to 97.5%. The results also showed that the biological toxicity of the outlet effluent from the sono-electro-Fenton process, compared to the inlet solution, was significantly reduced. So, we conclude that the Sono-electro-Fenton process has a significant effect on the removal of Cefixime from aqueous solutions and can also significantly reduce the biological toxicity of the effluent.     

聚(ε-己内酯)-多肽共聚物胶束增强抗生素的抗菌活性

Bacterial infection is a major threat to human health, and can cause several diseases including gastroenteritis, influenza, tetanus, and tuberculosis. As conventional antibiotic treatment may cause various undesirable effects such as stomach disorder and bacterial resistance, it is necessary to improve the antibacterial efficiency of antibiotics. Here, we synthesized a peptide-based copolymer, poly(ε-caprolactone)-block-poly(glutamic acid)-block-poly(lysine-stat-phenylalanine)[PCL₃₄-b-PGA₃₀-b-P(Lys₁₆-stat-Phe₁₂)] by ring-opening polymerization (ROP) of ε-caprolactone and amino acid N-carboxyanhydride (NCA). Successful synthesis of the copolymer was verified by proton nuclear magnetic resonance and size exclusion chromatography. This copolymer can self-assemble into negatively charged micelles (-26.7 mV) under alkaline conditions by solvent switch method. The micelle structure was confirmed by transmission electron microscopy and dynamic light scattering, and revealed to have a diameter of ~42 nm. Antibiotics were loaded into micelles during the self-assembly process, and cell viability assay was conducted to evaluate its cytotoxicity with and without tobramycin. No obvious cytotoxicity was observed for both micelles when the concentration was lower than 300 μg·mL^-1. The antibiotic-loaded micelles demonstrated very low minimum inhibitory concentrations (MICs) against both Gram-negative Escherichia coli (E. coli) (7.8 μg·mL^-1) and Gram-positive Staphylococcus aureus (S. aureus) (18.2 μg·mL^-1), while the MICs of free tobramycin were 3.9 and 1.0 μg·mL^-1, respectively. The drug-loading content and efficiency of the micelles were 5.2% and 24.3%, respectively. Therefore, the MICs of the loaded tobramycin against E. coli and S. aureus were 0.4 and 0.9 μg·mL^-1, respectively, suggesting that the micelle could enhance the antibacterial activity of antibiotics. Tobramycin-loaded micelles demonstrated a sustained release characteristic, with 85% of the antibiotics released after 8 h. In bacteria-induced acidic microenvironment, the coil conformation of PGA blocks transforms and PGA blocks shrink toward the micelle core. Concomitantly, the carboxyl side chains are protonated in an acidic environment, increasing the hydrophobicity of this micelle. Antibiotics will be captured when reaching the outer core to slow down the releasing process. Furthermore, the poly(lysine-stat-phenylalanine) [P(Lys-stat-Phe)] coronas with broad spectrum intrinsic antibacterial activity can penetrate the bacterial cell membrane, leading to leakage of the cellular contents of the bacteria and ultimately their death. Due to the sustained release property of micelle and the intrinsic activity of the antibacterial peptide segments, this micelle can greatly enhance the antibacterial activity of antibiotics. Overall, this antibiotic-loaded micelle provides a novel approach for significantly reducing the antibiotics dosage and avoiding the associated health risks.     

Application of synergistic β-lactamase inhibitors and antibiotics in the treatment of wounds infected by superbugs

Amoxicillin appears to be clinically drug-resistant due to the presence of β-lactamase in bacteria. Here, we designed and prepared a hollow Prussian Blue (HPB)-based therapeutic nanoplatform that was constructed by encapsulating amoxicillin into polyethyleneimine with β-lactamase inhibitor 4-carboxyphenylboronic acid (4-Cpba) decorated HPB nanoparticles (CPA NPs). The antibacterial effect of the CPA NPs on drug-resistant bacteria was observed by in vitro colony-forming unit, minimum inhibitory concentration, scanning electron microscopy, and fluorescence tests. The results show that amoxicillin effectively inhibited Escherichia coli and Staphylococcus aureus-resistant bacteria in the presence of 4-Cpba. The in vivo experimental results show that the CPA NPs exhibited a synergistic anti-infective effect in vivo, which inhibited the inflammatory response and apoptosis induced by the drug-resistant bacterial infection, and promoted wound healing in mice. The hematoxylin and eosin staining and blood biochemical experiments revealed that the acute toxicity of the material was negligible and it had good biocompatibility. Our results verify our design that CPA NPs can restore the antibacterial activity of amoxicillin.