Influences of NaCl and Na2SO4 on the Micellization Behavior of the Mixture of Cetylpyridinium Chloride + Polyvinyl Pyrrolidone at Several Temperatures

Herein, the conductivity measurement technique is used to determine the interactions that may occur between polyvinyl pyrrolidone (PVP) polymer and cetylpyridinium chloride (CPC) surfactant in the presence of NaCl and Na2SO4 of fixed concentration at variable temperatures (298.15–323.15 K) with an interval of 5 K. In the absence or presence of salts, we observed three critical micelle concentrations (CMC) for the CPC + PVP mixture. In all situations, CMC1 values of CPC + PVP system were found to be higher in water than in attendance of salts (NaCl and Na2SO4). Temperature and additives have the tendency to affect counterion binding values. Various physico-chemical parameters were analyzed and demonstrated smoothly, including free energy (ΔG0m), enthalpy (ΔH0m) and entropy change (ΔS0m). The micellization process is achieved to be spontaneous based on the obtained negative ΔG0m values. The linearity of the ΔHmo and ΔSmo values is excellent. The intrinsic enthalpy gain (ΔH0*m) and compensation temperature (Tc) were calculated and discussed with logical points. Interactions of polymer hydrophobic chains or the polymer + surfactant associated with amphiphilic surface-active drugs can employ a strong impact on the behavior of the gels.

Insights Into the Inhibition of MOX-1 β-Lactamase by S02030, a Boronic Acid Transition State Inhibitor

The rise of multidrug resistant (MDR) Gram-negative bacteria has accelerated the development of novel inhibitors of class A and C β-lactamases. Presently, the search for novel compounds with new mechanisms of action is a clinical and scientific priority. To this end, we determined the 2.13-Å resolution crystal structure of S02030, a boronic acid transition state inhibitor (BATSI), bound to MOX-1 β-lactamase, a plasmid-borne, expanded-spectrum AmpC β-lactamase (ESAC) and compared this to the previously reported aztreonam (ATM)-bound MOX-1 structure. Superposition of these two complexes shows that S02030 binds in the active-site cavity more deeply than ATM. In contrast, the SO3 interactions and the positional change of the β-strand amino acids from Lys315 to Asn320 were more prominent in the ATM-bound structure. MICs were performed using a fixed concentration of S02030 (4 μg/ml) as a proof of principle. Microbiological evaluation against a laboratory strain of Escherichia coli expressing MOX-1 revealed that MICs against ceftazidime are reduced from 2.0 to 0.12 μg/ml when S02030 is added at a concentration of 4 μg/ml. The IC50 and Ki of S02030 vs. MOX-1 were 1.25 ± 0.34 and 0.56 ± 0.03 μM, respectively. Monobactams such as ATM can serve as informative templates for design of mechanism-based inhibitors such as S02030 against ESAC β-lactamases.

Thermal And Kinetic Study of Electrochemical Deposition of Lead On FTO Substrate

We report the electrochemical deposition of lead (Pb) onto fluorine-doped tin oxide (FTO) electrodes in a sodium nitrate bath (0.4M NaNO3) at constant potential conditions. The kinetics electrodeposition processes have been in situ monitored for advanced nucleation stages by chronoamperometry for various temperature at fixed concentration of Pb2+, that is 0.1M. The microstructure and morphological characteristics of the deposit layers were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-Ray EDX techniques. The results show that the current density as well as the deposits density strongly depend on the temperature. The correlation between the experimental results and the theoretical process of the lead deposits was discussed and verified.

789. Susceptibility of Phenotypic Subsets of Pseudomonas aeruginosa Isolates to Cefiderocol and Comparator Agents from SIDERO-WT 2014-2019

Background Multidrug-resistant (MDR) phenotypes are frequently observed among P. aeruginosa (PsA) isolated from hospitalized patients. This study describes the in vitro activities of cefiderocol (CFDC) and comparator agents against various non-susceptible (NS) phenotypic subsets of MDR PsA isolates from the SIDERO-WT multi-national surveillance program. Methods Clinical PsA isolates were collected from North America (NA) and Europe in 2014-2019 and tested for susceptibility at a central laboratory. MICs (μg/ml) were determined for CFDC, ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), colistin, cefepime, meropenem (MEM), and ciprofloxacin by broth microdilution according to CLSI guidelines. Aztreonam-avibactam (avibactam fixed concentration of 4 µg/ml) and imipenem/relebactam (I/R) were only tested during SIDERO-WT Year 5 (i.e. 2019). Susceptibility was interpreted according to current FDA and 2021 CLSI breakpoints. Results The different phenotypic subsets and susceptibility of tested compounds are shown in the table. Among 7700 PsA isolates, 47.7% and 23% were from respiratory and gastrointestinal sources of infection. CFDC inhibited 97.5% and 99.9% of all PsA at its FDA-S and CLSI-S MIC breakpoint of ≤1 and ≤4, respectively. CFDC had the lowest MIC90 of all tested agents and >99% S at an MIC ≤4 for all phenotypic subsets. At a MIC ≤1, CFDC displayed high susceptibility rates against all subsets including ≥88% S against CZA-NS, C/T-NS, I/R-NS, and MEM+I/R-NS isolates. Against MDR subsets, comparator agents consistently demonstrated lower activity than CFDC; 88% of MEM+C/T-NS and MEM+CZA-NS isolates had a CFDC MIC≤1 while 15.6% and 20.3% were S to I/R, respectively. 86% of MEM+CZA+C/T-NS and 80.4% CZA+C/T+I/R-NS isolates were S to CFDC. CFDC inhibited 98.1% and 99.4% of PsA isolates from NA (n = 3548) at a MIC of ≤1 and ≤4, respectively. In NA isolates that were MEM+C/T-NS; 85.7% of PsA isolates had a MIC ≤1 to CFDC and 33.3% and 28.6% were S to CZA and I/R, respectively. MEM: Meropenem; NS: Non-susceptible; CZA: Ceftazidime/avibactam; C/T: Ceftolozane/tazobactam; I/R: Imipenem/relebactam Conclusion CFDC demonstrated potent in vitro activity against a variety of phenotypic subsets of MDR P. aeruginosa isolates as compared to agents that are commonly used to treat MDR PsA infections including strains NS to other agents. These data support the use of CFDC as an important treatment option for MDR PsA. Disclosures Sean Nguyen, PharmD, Shionogi Inc (Employee) David Fam, PharmD, Shionogi (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Roger Echols, MD, Shionogi (Consultant) Yoshinori Yamano, PhD, Shionogi (Employee)

Assessment of Electrochemical Activity of some Amino acids on the Modified Carbon Electrode Surface

The present work analyzed the electrochemical activity of certain amino acids on the modified carbon electrode as-prepared, such as glycine, threonine and aspartic acid. The electrochemical methods used to investigate surface electrode behavior through amino acid molecules at a fixed concentration and temperature of 298.15 K in the perchloric acid electrolyte solution. The findings showed that the surface electrode was ideal for the analysis of glycine, threonine, and aspartic acid molecules. Aspartic acid showed electrochemical activity by voltage and polarization resistance to 0.533 mV and 9.557 ohms, respectively. In addition, the FE-SEM images showed the thin film layer on the surface electrode from the amino acid molecules in different shapes and dense aggregations, more with aspartic acid under optimum experimental conditions.

In vitro synergistic activity of aztreonam (AZT) plus novel and old β-lactamase inhibitor combinations against metallo-β-lactamase-producing AZT-resistant Enterobacterales

The emergence of metallo-β-lactamase (MBL)-producing Enterobacterales , mainly New Delhi metallo-β-lactamase (NDM), represents a clinical threat due to the limited therapeutic alternatives. Aztreonam (AZT) is stable to MBLs, but most MBL-producing Enterobacterales isolates usually co-harbour other β-lactamases that confer resistance to AZT and, consequently, its use is restricted in these isolates. We compared the ability of sulbactam (SUL), tazobactam (TAZ), clavulanic acid (CLA) and avibactam (AVI) to restore the AZT activity in MBL-producing AZT-resistant Enterobacterales isolates. A collection of 64 NDM-producing AZT-resistant Enterobacterales from five hospitals in Buenos Aires city, Argentina, were studied during the period July–December 2020. MICs were determined using the agar dilution method with Mueller–Hinton agar according to Clinical and Laboratory Standards Institute (CLSI) recommendations. AVI, SUL and TAZ were used at a fixed concentration of 4 mg l−1, whereas CLA was used at a fixed concentration of 2 mg l−1. A screening method based on disc diffusion to evaluate this synergy was also conducted. Detection of bla KPC, bla OXA, bla NDM, bla VIM, bla CTXM-1, bla PER-2 and bla CIT was performed by PCR. The AZT-AVI combination restored the AZT activity in 98.4 % of AZT-resistant strains, whereas CLA, TAZ and SUL did so in 70.3, 15.6 and 12.5 %, respectively, in isolates co-harbouring extended-spectrum β-lactamases, but were inactive in isolates harbouring AmpC-type enzymes and/or KPC. The synergy screening test showed an excellent negative predictive value to confirm the absence of synergy, but positive results should be confirmed by a quantitative method. The excellent in vitro performance of the AZT-CLA combination represents a much more economical alternative to AZT-AVI, which could be of use in the treatment of MBL-producing, AZT-resistant Enterobacterales .

Effects of a BMI1008 mixture on postoperative pain in a rat model of incisional pain

Background The purpose of this study was to evaluate the analgesic effect of BMI1008 (a new drug containing lidocaine, methylene blue, dexamethasone and vitamin B complex) and to investigate the analgesic effect of lidocaine and BMI-L (other components of BMI1008 except lidocaine) at different concentrations in a rat model of incisional pain. Methods Male Sprague-Dawley rats (250–300 g) were used for the incisional pain model simulating postoperative pain. After the operation, normal saline, various concentrations of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine were injected at the incision site. The preventive analgesic effect was evaluated using BMI1008 administered 30 min before and immediately after the operation. In addition, BMI1008 was compared with positive controls using intraperitoneal ketorolac 30 mg/kg and fentanyl 0.5 μg/kg. The mechanical withdrawal threshold was measured with a von Frey filament. Results The analgesic effect according to the concentration of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine showed a concentration-dependent response and statistically significant difference among the groups (P <0.001, P <0.001, and P <0.001, respectively). The analgesic effect according to the time point of administration (before and after the operation) showed no evidence of a statistically significant difference between the groups (P = 0.170). Compared with the positive control groups, the results showed a statistically significant difference between the groups (P = 0.024). Conclusion BMI1008 showed its analgesic effect in a rat model of incisional pain in a concentration-dependent manner. Moreover, BMI-L showed an additive effect on the analgesic effect of lidocaine.

Sigmoid E max Modelling to Define the Fixed Concentration of Enmetazobactam for MIC Testing in Combination with Cefepime

Use of carbapenem antibiotics to treat infections caused by Enterobacterales expressing increasingly aggressive extended-spectrum β-lactamases (ESBL) has contributed to the emergence of carbapenem resistance. Enmetazobactam is a novel ESBL inhibitor being developed in combination with cefepime as a carbapenem-sparing option for infections caused by ESBL-producing Enterobacterales . Cefepime-enmetazobactam checkerboard minimum inhibitory concentration (MIC) profiles were obtained for a challenge panel of cefepime-resistant ESBL-producing clinical isolates of Klebsiella pneumoniae . Sigmoid E max modelling described cefepime MIC as a function of enmetazobactam concentration with no bias. A concentration of 8 μg/ml enmetazobactam proved sufficient to restore >95% of cefepime antibacterial activity in vitro against >95% of isolates tested. These results support a fixed concentration of 8 μg/ml of enmetazobactam for MIC testing.

Characterization of Glucomannan Extracted from Fresh Porang Tubers Using Ethanol Technical Grade

Glucomannan is a polysaccharide consisting of β-1.4-linked D-mannose and D-glucose monomers, which have many benefits especially in the food and pharmaceutical industry. It has been widely reported that one of the main sources of glucomannan is porang tuber (Amorphophallus muelleri Blume). Generally, glucomannan extracted or purified from porang flour. However, the drying process causes other compounds than glucomannan stick strongly, resulting low levels of glucomannan. This study was to obtain glucomannan extract in an easy, effective, and inexpensive method, by direct extraction from fresh porang tubers using ethanol technical grade. We performed two extraction methods. The first is a fixed concentration method, the sample was repeatedly extracted using 50% ethanol (FC50) and 96% ethanol (FC96) 3 times, respectively. The second is a multilevel concentration method, the sample was repeatedly extracted using ethanol 60% (first step), 80% (second step), and 96% (third step), one replication each step. The highest glucomannan content (66.56%) was obtained by a multilevel concentration method. Moisture, lipid, protein, crude fiber, calcium oxalate level significantly reduce to 13.58%, 0.07%, 4.03%, 4.95%, 0.56% respectively. FTIR spectra confirmed the presence of functional groups (O-H, C=O, C-O, C-H), that compose the glucomannan compound. SEM image showed that the granules form of glucomannan were round and oval, began to change its phase from amorphous to crystalline, related to XRD data. The results showed that the direct extraction from fresh porang tuber using ethanol technical grade with a multilevel concentration method was an effective method to extract the glucomannan

Investigating sustainable management of desalination brine through concentration using forward osmosis

A fertilizer drawn forward osmosis (FDFO) process was tested for the concentration of synthetic brine using an industrial-grade fertilizer ammonium sulfate (NH4)2SO4 as the draw solution (DS), NaCl-based synthetic brine as the feed solution (FS), and a commercial forward osmosis (FO) membrane. A bench-scale investigation and a pilot-scale investigation were carried out. By using the highest possible concentration of the DS with a fixed concentration of the FS, the brine generated by reverse osmosis (RO) desalination plants was simulated. The aim of this investigation, performed in batch mode, was to assess the feasibility of using the FDFO process with the tested DS to concentrate the brine by extracting water to dilute the DS. While the main aim of the investigated process was achieving the maximum possible volume reduction of the brine, the resulting DS was further diluted to reduce the nutrients’ concentration in the diluted DS to the acceptable levels producing fertilized water that can be used for fertigation. The investigation showed that the proposed process using the tested fertilizer resulted in an average water flux of 8.01 l/h/m2, and a volume reduction of the brine of around 12%.