MIC Values Research Articles

Evaluation of Antibacterial Properties of Zinc Oxide Nanoparticles Against Bacteria Isolated from Animal Wounds

Background/Objectives: This research aimed to determine the efficacy of metallic oxide nanoparticles, especially zinc oxide nanoparticles (ZnO-NPs), in inhibiting a wide range of bacteria isolated from animal wounds, indicating their potential as alternative antimicrobial therapies in veterinary medicine. Method: The disc diffusion technique, broth microdilution technique, and time-kill kinetic assay were performed to determine the antibacterial activity of the ZnO-NPs. Results: Transmission electron microscopy (TEM) and scanning electron microscopy (SEM showed that the ZnO-NPs were spherical and polygonal with sizes ranging from 50 to 100 nm, while DLS (NanoSizer) measured an average size of 512.3 to 535.7 nm with a polydispersity index (PDI) of 0.50 to 0.63 due to particle size agglomeration. The ZnO-NPs exhibited antibacterial activity against several bacterial strains isolated from animal wounds, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, with inhibition zones ranging from 10.0 to 24.5 mm, average MIC values ranging from 1.87 ± 0.36 to 3.12 ± 0.62 mg/mL, and an optimum inhibitory effect against Staphylococcus spp. The time-kill kinetic assay revealed that the Zn-ONPs eradicated Staphylococcus spp. and Klebsiella pneumoniae, as well as Escherichia coli and Pseudomonas aeruginosa (99.9% or 3-log10 reduction), within 30 min of treatment. They also demonstrated a varying degree of antibiofilm formation activity, as indicated by the percentage reduction in biofilm formation compared to the untreated biofilm-forming bacterial strains. Conclusion: ZnO-NPs effectively inhibit bacterial growth and biofilm formation in animal wound isolates.

Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity

Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.

Essential Oils From Chromolaena odorata (L.) R. M. King and H. Robinson Stem Barks and Leaves: Chemical Analysis, Biological Activity and In Silico Approach.

The current study first describes the chemical profiles of essential oils from Vietnamese Chromolaena odorata fresh stem barks and leaves. The gas chromatography-flame ionization detection/mass spectrometry (GC-FID/MS) analysis revealed that α-pinene (6.97%-38.91%), β-pinene (5.68%-11.64%), geijerene (10.60%-26.68%), germacrene D (9.33%-16.87%), and (E)-caryophyllene (5.03%-9.12%) were the major compounds. Essential oils showed strong anti-inflammation against NO (nitric oxidative) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells with IC50 values of 42.44-49.01µg/mL. Two essential oils also exhibited cytotoxicity against four cancer cell lines, K562, HeLa, HepG2, and MCF-7, antioxidant activity to capture DPPH radicals, and antidiabetics in α-glucosidase inhibition. Both samples showed varying levels in the antimicrobial experiment, especially the leaf essential oil, which showed strong antibacterial activity against the bacterium Bacillus subtilis with a MIC value of 64µg/mL. From the molecular docking investigation, geijerene had a higher affinity for cyclooxygenase-2 (COX-2) than the other main compounds, whereas germacrene D had the strongest binding affinity for two protein targets, COX-2, and B. subtilis FtsZ. It was discovered that the main factor stabilizing the bindings of these compounds to the target proteins was hydrophobic interactions.

Pharmacokinetics and Chicken Meat Residue of Tilmicosin after Administration Through Drinking Water in Broiler Chicken

Background: Tilmicosin is an antimycoplasmic drug of great utility in controlling mycoplasmosis in chicken. The drug despite its efficacy, has a high residue impact leading to a long withdrawal period. In this study, an attempt has been made to rationalize the dosage to reduce the residue burden by adopting a lower dose. Methods: The dose of tilmicosin was arrived at based on a pilot study wherein different doses were administered, and the levels were checked in plasma and meat. In the main study, tilmicosin was administered to broiler chicken as a bolus oral dose or “in drinking water” at the dose rate of 25 mg. kg-1 body weight. Blood was collected at different time points for the study. A trial to assay drug residues in tissues was also carried out. The assay of tilmicosin in chicken plasma/tissues was done using a sensitive HPLC assay. Result: In both pharmacokinetics study groups, tilmicosin concentrations could be reasonably detected only in 4 of the eight birds tested. In the birds that responded, the mean plasma concentrations remained above the MIC values of 0.05 µg.ml-1. The residue level in the lung and muscle could be detected up to day 14, and no residue from 18th day, after administration of tilmicosin through drinking water. The lung, the organ of mycoplasma infection revealed high concentrations of tilmicosin up to 14 days after the last dose. The results show that the Tilmicosin administered at a reduced rate of 25 mg.Kg-1 can be useful therapeutically, with a reduced residue burden in broiler chicken.

Discovery of Novel FtsZ Inhibitors with Antimicrobial Activity by Virtual Screening and In Vitro Biological Evaluation.

The filamentous temperature-sensitive protein Z (FtsZ) plays a vital role in bacterial division, making it an important antibacterial target. The inhibitor activity targeting the cleft between the H7 helix and the C-terminal substructural domain exhibited superior binding compared to the GTP binding site. This highlights the potential of the cleft as a promising target for further inhibitor discovery. In this study, we established a virtual screening pipeline using Discovery Studio software and employed FRED for molecular docking and Functional-Class Fingerprints_6(FCFP_6)for molecular clustering, resulting in the identification of 38 potentially active compounds. These 38 compounds were then subjected to the following FtsZ inhibition assays, resulting in the four active compounds B6, B21, B26, and B31. Further experiments showed that compounds B6 and B26 exhibited antimicrobial activity with MIC values of 8 μg/mL and 32 μg/mL. Finally, molecular dynamics was used to analyze the binding modes of the protein-ligand. In addition, we predicted the physicochemical properties and toxicity of B6 and B26. In summary, our study successfully identified novel FtsZ inhibitors with antimicrobial activity through virtual screening and in vitro biological evaluation, demonstrating their potential for further investigation.

Synthesis and mechanistic studies of 4-aminoquinoline-Isatin molecular hybrids and Schiff's bases as promising antimicrobial agents.

In this investigation, to determine their potential as specific antibacterial agents, Schiff's bases (LT-SB1-23 and SB1-SB12) and novel quinoline-isatin hybrids were subjected to microbiological testing. The in-vitro screening against bacterial strains (Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhi) exhibited their antibacterial potential with many of the compounds showing inhibition range of 90-100% at 200μg/mL, against most of the tested strains. The MIC values of some of the compounds showed good antibacterial efficacy with values ranging from 32 to 128μg/mL. Their bacterial growth inhibitory potential was further supported by disk diffusion and growth curve assays. Interestingly, one of the Schiff's bases (LT-SB7) displayed strong synergistic activity against E. coli and S. typhi with 16-64 folds reduction in MIC values. Additionally, it exhibited up to 85% suppression of biofilm at ½MIC against AA209 environmental bacterial isolate and reduced the development of multidrug-resistant bacterial isolates. Promising compound LT-SB7 underwent 100 ns molecular dynamics simulations with biofilm-causing protein (PDB ID: 7C7U) to assess conformational changes and complex stability. Overall, this study identified compounds as effective antibacterial alternatives for the future.

Pharmacokinetics of difloxacin after single intravenous, oral and intramuscular administration in pigeons.

This study aimed to investigate the pharmacokinetics of difloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. Thirty pigeons were randomly divided into three groups (IM, IV, and PO; n = 10 per group). Difloxacin was administered at 10 mg/kg body weight (BW) via each route. Blood samples were collected at various intervals from 0 to 48 h, and plasma was analyzed for difloxacin concentrations using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were determined using Phoenix software and a non-compartmental analysis (NCA) approach. After PO and IM administration, peak plasma concentrations (Cmax) were observed as 1.81 ± 0.47 and 6.52 ± 1.62 μg/mL, occurring at 2.60 ± 0.97 and 0.63 ± 0.24 h, respectively. Bioavailability (F) was 38.35 % ± 10.45 % for PO and 90.25 % ± 26.14 % for IM administration. Following IV administration, difloxacin was widely distributed, with a volume of distribution (VZ) of 2.52 ± 0.65 L/kg and a steady-state volume of distribution (VSS) of 1.87 ± 0.27 L/kg. Difloxacin exhibited slow elimination, with elimination half-lives (t1/2λzs) of 1.61 ± 0.3, 2.64 ± 0.64, and 4.27 ± 1.14 h after IM, PO, and IV administration, respectively. Based on the AUC/MIC ratios calculated here, the current IM or IV administration at 10 mg/kg BW is effective against bacterial infections with MIC values ≤ 0.1 μg/mL, while the current oral dose (10 mg/kg BW) may be insufficient, particularly for infections caused by pathogens with MIC values exceeding 0.1 μg/mL.

Structural characterization, cytotoxicity, antibiofilm activity, and synergistic potential with molecular docking analysis of ibuprofen-derived hydrazide against bacterial pathogens.

The study investigates the synthesis, characterization, and antibacterial activity of an ibuprofen-derived hydrazide (HIDZ). It was synthesized and characterized using NMR spectroscopy, DFT Calculations, and ADMET studies. Furthermore, HIDZ cytotoxicity on L929cells was evaluated using the MTT reduction assay. Antibacterial activity was assessed against Gram-positive and Gram-negative strains through the microdilution method. The combinatory potential of HIDZ was performed using the checkerboard test with β-lactam antibiotics, oxacillin (OXA), meropenem (MER), and cefepime (CPM). Antibiofilm activity was evaluated for biofilm inhibition and disruption, particularly in combination with OXA. Molecular docking analysis examined HIDZ interactions with Thymidylate kinase, DNA Gyrase B, and DNA Topoisomerase IV subunit B. The global chemical reactivity descriptors analysis revealed significant variations in the atomic centers' susceptibility, highlighting the environment's importance in determining the reactive behavior of HIDZ. Pharmacokinetic predictions indicated efficient permeability across biological membranes, suggesting favorable bioavailability. MTT experiment showed that HIDZ caused cytotoxicity on higher concentrations over L929 fibroblasts. HIDZ exhibited superior activity against Gram-positive strains compared to ibuprofen, with lower MIC and MBC values. Both compounds were ineffective against Gram-negative strains. However, HIDZ was able to inhibit the biofilm formation of the most tested strains. The combinatory effect shows an additive effect between HIDZ and β-lactams. However, the HIDZ/OXA combination improved biofilm disruption, achieving up to a 92% reduction in residual biofilm and cell viability compared to the control. Molecular docking simulations showed that HIDZ may interact with bacterial enzymes, improving antibiotic efficiency. The study suggests that HIDZ has promising potential as an antibacterial and antibiofilm agent, particularly against Gram-positive bacteria and in combination with β-lactam antibiotics.

Anti-bacterial efficacy of Boron Nanosheet against clinical isolates and its in vivo toxicity assessment using Artemiasalina.

Microbes have been increasing their potential against newly developed drugs and antibiotics daily. The increased microbial drug resistance is still a challenging societal inconvenience. 2D nanomaterials, such as graphene, fascinate researchers with their unique physical and chemical properties and have a major role in current science and technology. Nowadays, researchers have been replacing graphene with its analogous 2D material, borophene, which is a single layer of boron with a honeycomb plane. Boron nanosheets which are theoretically investigated, have been synthesized by various top-down and bottom-up approaches. Our study focuses on synthesizing boron-based material from the precursor MgB2 which possesses a honeycomb boron structure with sandwiched Mg atoms. The Mg atoms have been selectively removed using the chelating agents at alkaline pH. The synthesized boron nanosheets have been characterized by FT-IR, Raman, XRD, FESEM, EDS, and TGA. The formation of B-H-B, B-B and B-O bond is confirmed by FT-IR and Raman spectra. It is also evident from XPS spectra which possess B1s spectra at 193eV. The efficient chelation and exfoliation is confirmed by EDS and FESEM analysis which shows the presence of boron and trace amount of Mg with bark like projections. Though there are several studies on antibacterial activity of compounds, generally the studies are with laboratory cultures of bacterial strains. Clinical studies offer more valid results and are very sparse in literature. The use of clinical strains in the present study is one of the novelty. It has also been analyzed for its anti-bacterial activity against clinical strains of B. subtilis, S. aureus, E. coli, and K. pneumonia. Boron nanosheets possess an enhanced zone of inhibition (8mm, 11mm) against clinical strains of B. subtilis where the micro dilution studies show MIC and MBC values as 125μg and 62.5μg. The in vivo toxicity studies carried out using Brine Shrimp Lethality Assay reveal higher LC50 values of boron nanosheets (>1mg/ml), which in turn portrays its non-toxic nature. Thus, the synthesized boron nanosheets are toxic to multidrug-resistant B. subtilis where it is non-toxic to mammalian cells. Thus, the study could advance the applications of borophene in biomedical applications.

A step forwarded on the in vitro and in vivo validation of rifabutin-loaded liposomes for the management of highly virulent MRSA infections.

Staphylococcus aureus (S. aureus) infections, especially methicillin resistant (MRSA), constitute an alarming public health issue due to its association with high mortality, morbidity, and hospitalization costs. The increasing antibiotic resistance and biofilm-associated infections of MRSA prompted the discovery of novel and more effective therapeutic strategies. Our team has been working on alternative therapies against S. aureus infections. For this, we have been repurposing an existing antibacterial drug, rifabutin (RFB), through its association to a nanotechnological platform, liposomes, aiming to promote a preferential targeting to infected sites and maximizing its potential antibacterial effect. The therapeutic potential of RFB formulations against a MRSA commercial strain (MRSA ATCC®-33592), either in planktonic or biofilm forms, was assessed. RFB displayed higher antibacterial effects towards biofilm than vancomycin (VCM), the gold standard treatment against MRSA infections, with MBIC50 values of 103 and > 800 μg/ml, respectively. Moreover, the antimicrobial effect of RFB-loaded liposomes demonstrated to be lipid composition-dependent based on MIC50 and MBIC50 values, which was also confirmed by confocal laser scanning microscopy. These studies supported that for positively charged RFB liposomes an electrostatic interaction at biofilm surface occurs without internalization. On the other hand, for RFB-loaded liposomes with neutral surface charge a high internalization within the biofilm was observed. Moreover, this RFB liposomal formulation has also demonstrated to be stable in human plasma, as more than 83 % of RFB was still associated to liposomes 24 h after incubation at 37 °C. The proof of concept of RFB formulations was assessed in MRSA systemic murine models of infection. Therapeutic effect and survival rates were evaluated for animals induced and treated with RFB in free and liposomal forms and compared with negative and positive controls. For the lower infection murine model, 100 % survival was achieved for all groups under study. However, in a higher infection model only for the group of animals treated with RFB incorporated in liposomes a 100 % survival was attained. In terms of bacterial burden, RFB formulations exhibited lower levels when compared to VCM, even using a lower therapeutic dose: 20 vs 40 mg/kg of body weight, respectively. Overall, RFB constitutes an alternative and effective therapeutic strategy towards MRSA infections, being this effect potentiated through its association to a lipid nanoplatform.

Comprehensive study of Biginelli's compounds show antibacterial activity against Vibrio parahaemolyticus of two strains: In vitro and computational approaches.

This study addresses the critical challenges faced by global aquatic industries such as overfishing, habitat destruction, pollution, climate change, and unsustainable aquaculture practices. It focuses on developing effective solutions by synthesizing potent inhibitors against Vibrio parahaemolyticus of two strains namely: MTCC-451 (A) and Vp-S14 (B). Biginelli's compounds (B1-4) were identified as promising inhibitors with confirmed antibacterial activity through in silico and in vitro studies. Then virtual screening through ADMET, best correlation with regard to QSAR studies, the docking analysis is used to determine, the ligand B1 would be more favorable comparable with others for conducting bacterial studies and DFT calculations show that the optimized structure of ligand B1 has the best FMO values, MEP values and appropriate electronic structural state. This research study is very helpful and matches for "Antibacterial analysis". A total of 99 Biginelli compounds were selected for virtual screening including 2D-QSAR, ADME/T, molecular docking, and DFT calculations. The virtual screened compounds were synthesized then for biological studies. The four highlighted compounds (B1-4) with favorable ADME properties and strong binding affinities compared to gentamicin in both ADME and docking analysis respectively. Further analysis via DFT provided structural insights and active site identification. In vitro assays against pathogenic Vp strains demonstrated significant bactericidal activity, with MIC values of 1.25mg/ml (MTCC-451) and 1mg/ml (Vp-S14).

Synthesis, single crystal investigations, DFT studies, biological activities, DNA cytotoxicity and molecular docking studies of copper(II) complex derived from the new o-vanillin Schiff base ligand

A novel Schiff base derivative, (E)-N’-(2-hydroxy-3-methoxybenzylidene)-2-phenylacetohydrazide (HMPH, H2L), and its Cu(II) complex were synthesized through the direct condensation of o-vanillin with phenylacetichydrazide in ethanol under reflux conditions. The synthesized ligand was identified usingelemental analysis, Fourier transform infrared (FTIR) and ultraviolet–visible (UV–Vis.) spectroscopy. The structures of HMPH (C16H16N2O3)2 and its Cu(II) complex [Cu(L)(H2O)]·H2O (C16H16N2CuO4·H2O) were analysed by single crystal X-ray diffraction technique. The X-ray diffraction results showed that HMPH crystallised in an orthorhombic Pca21 space group with a Z value of 8, while [Cu(L)(H2O)]·H2O crystallised in a monoclinic C 2/c space group with the same z value. The Cu(II) ion is coordinated to the acetohydrazide ligands via hydrazone nitrogen, aceto oxygen (N(2) and O(1)) and hydroxyl O(2) atoms. In addition to the single crystal structures of HMPH and [Cu(L)(H2O)]·H2O, the optimised molecular structures, molecular electrostatic potential meps, molecular orbital energy values, and interactions between DNA bases and molecular structures are determined by DFT/B3LYP/6-311G(d, p) for HMPH and DFT/B3LYP/LanL2DZ for [Cu(L)(H2O)]·H2O. The copper complex was found to be more potent than the organic ligand in terms of antimicrobial activity, with a strong anti-biofilm effect even at low MIC values. The cytotoxicity of the synthesized compounds was investigated on MDA-MB-231 cell lines. The [Cu(L)(H2O)]·H2O complex was found to be more lethal than the HMPH ligand. Furthermore, molecular docking studies of HMPH and [Cu(L)(H2O)]·H2O with P. aeruginosa ATCC27853 (PDB ID: 6P8U) were presented to explain the observed antibacterial activity and the mechanism-of-action.

In-vitro susceptibility of cefiderocol and other comparators in carbapenem-resistant Gram-negative bacilli: A study from India.

Cefiderocol is a parenteral catechol-type siderophore cephalosporin, which has been approved for the treatment of Gram-negative bacterial infections. Its activity among the carbapenem-resistant Gram-negative bacilli (CR-GNBs) in India is largely unknown. We tested in-vitro susceptibility of cefiderocol in 84 CR-GNB [ carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP)] by broth microdilution (BMD) and disc diffusion (DD) using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and concordance of DD was compared with BMD. Cefiderocol susceptibility was evaluated based on the presence of blaNDM and blaOXA-48 genes. Following CLSI and EUCAST breakpoints, 76.2% [CRKP: 95.65% (22/23); CRPA: 80% (16/20); CREC: 65% (13/20); CRAB: 61.9% (13/21)] and 52.3% [ CRKP: 82.6% (19/23); CRPA: 50% (10/20); CREC: 20% (4/20)] of CR-GNBs were observed susceptible to cefiderocol, respectively. The susceptibility to cefiderocol was seen higher with lower MIC50 and MIC90 values for CRKP [1μg/ml; 4μg/ml ] and CRPA [2μg/ml; 8μg/ml ] in comparison to the other two groups of organisms. The categorical agreement between BMD and DD was found between 90% and 100% for all organisms. Cefiderocol susceptibility among the isolates harbouring blaNDM, blaOXA-48, and both blaNDM and blaOXA-48 genes was observed 75% (24/32); 100% (3/3); and 66.6% (4/6), respectively. Cefiderocol demonstrated high in-vitro activity against CRKP and CRPA isolates from India with lower MIC50 and MIC90 irrespective of the presence of blaNDM and blaOXA-48 genes.

Chlorella vulgaris as a producer of lipids for antibacterial, antibiofilm and antifungal properties

The aim of this study was to investigate the antibacterial, antifungal, and anti-biofilm activities of the methanolic extract of marine Chlorella vulgaris along with its lipid composition, including carotenoids. The C. vulgaris strain, isolated from the Mediterranean coast of northern Morocco, was identified morphologically and molecularly by partial sequencing of the 18S rRNA gene. The methanolic extract of C. vulgaris demonstrated significant antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria, with MIC values ranging from 3.12 to 12.5 mg mL−1. The antibiofilm activity of the extract was dose-dependent against Staphylococcus epidermidis and Pseudomonas aeruginosa. The extract demonstrated antifungal activity against four fungal strains. A. brasiliensis was shown to be the most sensitive species, whereas M. hiemalis was the least sensitive one. The identified lipid compounds mainly consisted of polar species e.g. phospholipids and carotenoids including lutein and neoxanthin, whose antimicrobial activity is generally recognised.

Green synthesis of Ag/V2O5 and Ag/V2O5-curdlan nanocomposites from Sargassum latifolium extract for enhanced antimicrobial and antioxidant activities.

The emergence of clinic-isolated bacteria and their ability to develop resistance mechanisms against conventional antimicrobials highlights the urgent need for novel, sustainable antimicrobial agents. This study explores the synthesis of Ag/V2O5 nanocomposites (NCs) using Sargassum latifolium extract, which is incorporated into a curdlan biocompatible matrix. The developed nanocomposites are evaluated for their antioxidant and antimicrobial activities, with a particular focus on their effectiveness against pathogenic bacteria. The applied method in this work combines green synthesis with the process of uniform distribution of nanoparticles to a biocompatible polymer, which is a way forward towards the design of efficient biocompatible antimicrobial systems. The Ag/V2O5 nanoparticles prepared with green synthesis were characterized by UV-Vis absorption, FTIR, XRD, SEM, EDX, zeta potential, DLS, and TEM. It has also been established that the antimicrobial property of the curdlan matrix has been enhanced with the addition of Ag/V2O5 nanoparticles in the incorporated curdlan composites. Ag/V2O5-curdlan also showed significantly enhanced antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria thus implying enhanced antimicrobial action of the prepared nanocomposite by increasing the size of the bacterial zone of inhibition from 14.0 to 18.0 mm. Besides, the curdlan NC in the presence of Ag/V2O5 demonstrated an even lower value of MIC against Rhizoctonia solani (140.156 μg/mL) in comparison with Ag/V2O5 NC (226.413 μg/mL) thus predicting Augmented antifungal activity. Through performing TEM analysis, we have observed significant morphological changes in R. solani strain when the Ag/V2O5-curdlan NC was used. However, the Ag/V2O5-curdlan NC had a notably high antioxidant activity with IC50 of 0.302 mg/mL to DPPH radical scavenging assay. These results reaffirm the enhancement in antimicrobial properties when Ag/V2O5 and curdlan work together and agree with the objective of this work to propose novel and worthwhile nanomaterials for potentially applicable areas like food packaging or agriculture with insignificant harm to the environment.

Phytochemicals of Biologically Active Fractions from Silene conoidea Leaves and Stems.

Silene conoidea, a member of the Caryophyllaceae family, is a rare edible weed in Iran. It possesses various medicinal properties, including insecticidal, antimicrobial, antibacterial, and allelopathic effects. This study represents the investigation into the phytochemical contents, compounds, and biological activities of six different fractions [petroleum ether, chloroform, dichloromethane, ethyl acetate, methanol, and water] obtained from the leaves and stems of this species, with the aim of developing new natural drugs. The methanol fractions of both the leaves and stems exhibited the highest levels of total phenolic and flavonoid contents and demonstrated strong antioxidant activity in the DPPH free radical scavenging method, with IC50 values of 5.1± 1.34 and 9.67 ± 0.02 μg/mL, respectively, surpassing the activity of BHT. Additionally, the chloroform and methanol fractions showed moderate antimicrobial activity against bacterial strains, with MIC values ranging from 0.0625 to 0.5 mg/ml when compared to gentamicin. The more active fractions [chloroform and methanol] were further analyzed to identify bioactive compounds. GC-MS analysis detected forty and forty-five compounds, representing 97.97% and 99.22% of the total composition, in the chloroform fractions of the leaves and stems, respectively. The main constituents of the leaves were fatty acid derivatives [54.66%] and terpene derivatives [21.94%], whereas the stems contained terpene derivatives [40.46%] and hydrocarbon derivatives [31.41%]. LC-ESI-MS analysis of the methanol fractions revealed the presence of common groups, including flavonoids, steroids, and triterpenoid saponins. Several bioactive compounds have been identified, including rutin, kaempferol-neohesperidoside derivative, diosmin, sileneoside, hesperidin, luteolin-di-O-glucoside, orientin-O-glucoside, vitexin- O-rhamnoside, and swertisin-O-glucoside. Heatmap analysis was conducted to visualize the differences in metabolite profiles among the samples. The analyzed fractions contained compounds with potential pharmacological activities.

Metabolomics-Guided Discovery of Bipolarolides H-O, New Ophiobolin-Type Sesterterpenes with Antibacterial Activity from the Marine-Derived Fungus Uzbekistanica storfjordensis sp. nov.

A marine-derived Pleosporales fungus, Uzbekistanica storfjordensis, was isolated from driftwood and described as a new species. The fungus was cultivated in liquid media and a molecular networking-driven approach was used to identify potential new secondary metabolites. The targeted compounds were isolated using preparative HPLC-MS, and through extensive spectroscopic analysis, eight new ophiobolin-type sesterterpenes, bipolarolides H-O (1-8), were identified. The absolute configurations of the compounds were determined by ECD assessment. Bipolarolide L (5), M (6), and O (8) exhibited inhibitory activity against Streptococcus agalactiae with MIC values of 86, 66, and 64 μM, respectively.

P-304. Vancomycin Resistant Enterococcus faecium Minimum Inhibitory Concentration Trends from 2019-2024: Have We Killed Daptomycin?

Abstract Background Vancomycin resistant Enterococcus faecium (VRE) has been categorized as a bacterium with serious antibiotic resistance threats in the United States, where daptomycin (DAP) has been a drug of choice. In 2019, the Clinical and Laboratory Standard Institute M100S 29th edition revised DAP breakpoints for VRE to susceptible dose dependent with a minimum inhibitory concentration (MIC) of ≤ 4 mcg/mL. Higher MICs are associated with resistant mechanisms and increased microbiological failure is seen with MICs of 3-4 mcg/L. Linezolid (LZD) is an VRE treatment option that has favorable clinical outcomes and microbiological eradication with less emerging resistance, but LZD use can be controversial due to outdated dogma of using a bacteriostatic agent. The purpose of this study was to evaluate MIC trends for DAP and LZD in patients with VRE bloodstream infections (BSI) at a large academic medical center. Bloodstream Infection VRE Comment within the Electronic Health Record: Current and Proposed Methods IRB-exempt, cross-sectional study of adult patients with VRE BSI and a healthcare encounter from 2019-2024 at a 5-hospital health-system in southeast Michigan. Patients were identified using Microsoft SQL Server queries based on microbiology results. The primary outcome was the proportion of patients with a DAP MIC > 1 mcg/mL with corresponding LZD MICs. Our health-system currently recommends DAP or LZD for VRE BSI until susceptibilities are available via blood culture comment (Figure 1). Measured MICs of daptomycin and linezolid, 2019-2024 *Daptomycin MIC Breakpoints: Susceptible Dose Dependent = ≤ 4 mcg/mL, Resistant = ≥8 mcg/mL. Linezolid MIC Breakpoints: Susceptible = ≤4 mcg/mL, Intermediate = 4 mcg/L, Resistant ≥8 mcg/L Results 555 LZD and 491 DAP unique MICs from VRE BSI were evaluated. Figure 2 represents the average MICs by month and year for DAP and LZD from 2019-2024. The majority of DAP MICs were measured at 2 (30%), 3 (56%), and 4 (18%) mcg/mL. DAP MIC50 and MIC90 values were calculated at 3 mcg/mL and 4 mcg/mL, respectively. 98.7% of LZD MICs were measured at ≤2 mcg/mL (Table 1). LZD MIC50 and MIC90 values were calculated at 2 mcg/mL. Average daptomycin and linezolid MIC per month and year, 2019-2024 Conclusion While the VRE MICs for DAP are increasing, LZD has remained stable over the past 5 years. A possible stewardship opportunity is to modify the health-system's current blood culture comment could suggest LZD as the VRE drug of choice and high-dose DAP as an alternative in patients until susceptibilities are available (Figure 1). Disclosures Rachel M. Kenney, PharmD, BCIDP, Medtronic Inc: Spouse is an employee, stockholder

P-1517. Assessing the novel combinations against Carbapenem resistant Acinetobacter baunmannii (CRAB): ceftazidime-avibactam and ampicillin-sulbactam

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a serious threat to public health, as treatment options are becoming limited. IDSA Guidance has advocated combination therapies to combat CRAB. Sulbactam (SUL), a β-lactamase inhibitor with inherent antibacterial activity against CRAB, is recognized as an important component of combination therapy. Pairing avibactam (AVI) inhibitor with ceftazidime (CAZ), has also been successful in restoring its antibiotic efficacy against many Gram-negative pathogens but has not proven effective against CRAB when used alone. In vitro assays combining SUL and AVI have shown promise against CRAB with different genetic backgrounds. Our aim is to assess the in vitro efficacy of combining ampicillin-SUL (AMS) and CAZ-AVI (CZA) against CRAB. Figure 1 Methods Three different methodological strategies were used. 89 strains underwent MIC evaluation (agar dilution) against SUL plus AVI, AMS (2:1) plus AVI, and AMS plus CZA, with a constant concentration of AVI (4 mg/L) and CAZ (8 mg/L). Additionally, 30 CRAB strains with different genetic backgrounds were used to assess AMS/CZA (14 μg and 50 μg) synergy by the disk stacking method and MTS synergy. Results AVI reduced SUL MIC values to < =4 mg/L in 96.8% of the tested isolates, excluding NDM producers. For MBLs producers, SUL-AVI MIC values less < =4 mg/L were tested in 14.3% strains (Fig. 1A). The inclusion of AMP or CAZ in the SUL-AVI combination did not result in any alterations in MIC values (98% of strains with identical values). Using stacking assay, 59% of isolates showed >3 mm increase in halo diameter for AMS with both CZA disks (Fig. 1B). Additionally, we calculated the FICI by using gradient strips (MTS) obtaining a synergistic or additive effect in 69% and 2% of strains, respectively. Antagonism was only seen in two tested NDM-1 positive isolates. Conclusion Our results demonstrated synergy between AMS and CZA in geographically diverse CRAB, including extensively drug-resistant isolates, such as those producing widespread oxacillinases. Some methods, mainly disk-based, may underestimate the true extent of AMS-CZA synergy. These findings could facilitate the implementation AMS/CZA in clinical settings and provide a potential alternative in regions where the latest approved drugs are not accessible. Disclosures David Paterson, Infectious Diseases Physician, AMR Action Fund: Board Member|Aurobac: Advisor/Consultant|bioMerieux: Grant/Research Support|bioMerieux: Honoraria|CARB-X: Advisor/Consultant|Entasis: Expert Testimony|Menarini: Honoraria|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Shionogi: Honoraria

P-1060. In vitro Activity of Gepotidacin Tested Against Molecularly Characterized Escherichia coli Isolates Responsible for Urinary Tract Infections in the US (2019-2022)

Abstract Background Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that inhibits bacterial DNA replication by a unique mechanism of action, distinct binding site and provides well-balanced inhibition (for most uncomplicated urinary tract infections [uUTI] uropathogens and Neisseria gonorrhoeae) of two different type II topoisomerase enzymes GEP completed two phase 3 trials for treatment of uUTI This study reports the activity of GEP and other oral antibacterials against E. coli (EC), including molecularly characterized isolates carrying ESBL and carbapenemase genes collected from UTI patients in the US. Methods 3,995 EC collected from 52 US sites as part of the gepotidacin uropathogen global surveillance study were included (2019-2022). CLSI methods were used for susceptibility (S) testing and MIC interpretations. Isolates with aztreonam, ceftazidime, ceftriaxone or meropenem MIC of ≥2 mg/L were subjected to genome sequencing, and screening of β-lactamase genes and epidemiology typing (MLST, O:H, and fimH). Results A total of 86.2% (3,444/3,995) of EC did not meet the MIC criteria for molecular characterization (Table) and had GEP MIC50 and MIC90 values of 2 mg/L and 4 mg/L, respectively. Cefazolin (97.0%S), fosfomycin (FOS) (99.7%S), and nitrofurantoin (NIT) (98.7%S) had activity among oral comparator agents tested against this group. A total of 13.8% (551/3,995) of EC were screened for β-lactamase genes, and this group had GEP MIC50 and MIC90 values of 2 mg/L and 4 mg/L respectively. Other oral agents had limited activity, except for FOS (98.0%S) and NIT (92.7%S). In general, GEP retained activity with MIC50 and MIC90 values of 2 mg/L and 4 mg/L, respectively, against isolates carrying ESBL, AmpC and carbapenemase genes, and against clonal complex (CC) 131 and the resistant subset O25b:H4. Conclusion GEP showed generally consistent activity against UTI-causing EC in the US, including against isolates carrying ESBL, AmpC and/or carbapenemase genes. In addition, GEP had activity against the CC131 high-risk EC clone. These data support further clinical development of GEP as a potential treatment option for uUTI caused by EC including when other oral treatment options are limited due to drug resistance. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company)