Lowest Minimum Inhibitory Concentration Research Articles

Ziziphora tenuior L. Essential Oil as a Bio‐Based Antimicrobial and Plant‐Based Preservative for Increasing the Shelf Life of Mayonnaise

The food industry is seeking alternatives to chemical additives and preservatives due to the increasing consumers’ demand for healthier food products. Ziziphora tenuior L. (Z. tenuior) is an aromatic medicinal plant that exhibits various biological properties such as antibacterial, antifungal, antioxidant and anti‐inflammatory properties. The aim of this study was to assess the impact of Z. tenuior essential oil (ZTEO) incorporation (700 μg/g) into mayonnaise on its stability, as well as to investigate the potential for replacing synthetic preservatives. The results demonstrated that the ZTEO extraction yield by the Soxhlet method was 3%. The GC‐MS analysis of ZTEO showed the presence of 36 different components, with pulegone (27.5%), borneol (16.5%), 1, 8‐cineole (9.8%), camphor (8.37%), β‐pinene (5.31%), and α‐pinene (4.64%) as the major compounds. Results of antimicrobial activity showed that the highest and the lowest minimum inhibitory concentration (MIC) values were obtained for Escherichia coli (700 μg/mL) and Saccharomyces cerevisiae (10 μg/mL). Also, the inhibition zone diameter increased by increasing the level of ZTEO, and Staphylococcus aureus (33 mm) and S. cerevisiae (36 mm) had the highest inhibition zone at level of 75%. Incorporation of ZTEO into mayonnaise prevented the growth of all microorganisms (bacteria, fungi, and yeast) during three months of storage. This indicates the potential of ZTEO as a natural preservative to replace synthetic preservatives. The results indicated the potential for incorporating ZTEO into mayonnaises and demonstrated the possibility of replacing commonly used preservatives with a natural alternative, offering consumers healthier food.

Antifungal potential of multi-drug-resistant Pseudomonas aeruginosa: harnessing pyocyanin for candida growth inhibition.

Pseudomonas aeruginosa is notorious for its multidrug resistance and its involvement in hospital-acquired infections. In this study, 20 bacterial strains isolated from soil samples near the Hindan River in Ghaziabad, India, were investigated for their biochemical and morphological characteristics, with a focus on identifying strains with exceptional drug resistance and pyocyanin production. The isolated bacterial strains were subjected to biochemical and morphological analyses to characterize their properties, with a particular emphasis on exopolysaccharide production. Strain GZB16/CEES1, exhibiting remarkable drug resistance and pyocyanin production. Biochemical and molecular analyses, including sequencing of its 16S rRNA gene (accession number LN735036.1), plasmid-curing assays, and estimation of plasmid size, were conducted to elucidate its drug resistance mechanisms and further pyocynin based target the Candida albicans Strain GZB16/CEES1 demonstrated 100% resistance to various antibiotics used in the investigation, with plasmid-curing assays, suggesting plasmid-based resistance gene transmission. The plasmid in GZB16/CEES1 was estimated to be approximately 24 kb in size. The study focused on P. aeruginosa's pyocyanin production, revealing its association with anticandidal activity. The minimum inhibitory concentration (MIC) of the bacterial extract against Candida albicans was 50 μg/ml, with a slightly lower pyocyanin-based MIC of 38.5 μg/ml. Scanning electron microscopy illustrated direct interactions between P. aeruginosa strains and Candida albicans cells, leading to the destruction of the latter. These findings underscore the potential of P. aeruginosa in understanding microbial interactions and developing strategies to combat fungal infections. The study highlights the importance of investigating bacterial-fungal interactions and the role of pyocyanin in antimicrobial activity. Further research in this area could lead to the development of novel therapeutic approaches for combating multidrug-resistant infections.

Comparison Between Moxifloxacin and Chloramphenicol for the Treatment of Bacterial Eye Infections

Background: Moxifloxacin is a bactericidal methoxyquinolone used for the treatment of conjunctivitis and prophylactic therapy in cataract and refractive surgeries. Chloramphenicol is a bacteriostatic organochlorine introduced into clinical practice in 1948 and used mainly in topical preparations because of its known toxicity. Objectives: The study aimed to evaluate the in vitro antibacterial effect and the ocular cytotoxicity of these broad-spectrum antibiotics. Methods: Antimicrobic activity was tested on four bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis), and determined through calculation of Minimum Inhibitory Concentration (MIC) and IC50 for each microorganism. Antibacterial activity was determined by microdilution method after 24 hours incubation with 2-fold serial dilutions (2.5 mg/ml to 4.883 µg/ml) of moxifloxacin and chloramphenicol. Disk diffusion test were performed according to EUCAST methodology. Biofilm formation inhibition (BIC) and biofilm Eradication Concentration (BEC) assay were conducted for P. aeruginosa and S. epidermidis using the microdilution method. Cytotoxicity of antibiotics was evaluated by MTT colorimetric assay on human corneal cell (HCE-2). Results: Cytotoxicity of antibiotics was evaluated on human epithelial corneal cells after 4 hours treatment by viability assay. Results showed that corneal cell viability was significantly higher after moxifloxacin treatment compared to Chloramphenicol (p<0.01). Moxifloxacin is characterized by a significantly lower MIC and IC50 values and a larger inhibition zone for all the strain tested, with high performance in controlling gram-negative growth, compared to Chloramphenicol. Moreover, Moxifloxacin showed higher activity compared to Chloramphenicol in the inhibition of biofilm formation and in the disruption of biofilm, especially against S. epidermidis biofilm. Conclusions: The lower corneal cell toxicity and the broader spectrum of antibacterial activity observed with Moxifloxacin suggests its use in ophthalmic solution for the treatment of bacterial eye infections.

Molecular Characterization and Antibacterial Potential of Endophytic Fungal Isolates from Selected Mangroves along the Coastline of Kenya.

The increasing emergence and re-emergence of resistant pathogenic microbes causes a health threat to the human population. Scientists have been striving to find novel bioactive compounds and drugs to overcome these obstacles. This study aimed to characterize mangrove endophytic fungi and evaluate their antibacterial activity. Heritiera littoralis, Rhizophora mucronata, Bruguiera gymnorrhiza, Avicennia marina, and Xylocarpus granatum species were collected from Tudor Creek, Mida Creek, and Gazi Bay. A total of 30 fungal isolates were subjected to molecular identification based on analysis of their ITS gene region. The isolates in the inferred phylogenetic trees were affiliated with the genus Aspergillus. Ethyl acetate and butanol crude extracts of 38.2% of the 76 isolated fungal endophytes and eight mycelia samples were screened for antibacterial activity against Staphylococcus aureus (ATCC 27853), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 25923) using the disc diffusion method. A. marina and R. mucronata harbored the most fungal endophytes that showed the highest antibacterial activity. Seven fungal broth extracts exhibited higher antibacterial activities against the tested microorganisms than the positive control. The minimum inhibitory concentration (MIC) activity for the isolates demonstrated that the ethyl acetate extract of a root endophytic fungal isolate (RC6) (3.31 ± 0.01) of A. marina is a strong inhibitor since it showed significantly lower MIC activity compared to the positive control (3.84 ± 0.00) against Pseudomonas aeruginosa (P < 0.05). Therefore, this study confirms that mangrove species harbor fungal isolates that have antibacterial activity and hence could serve as a novel source of antibiotics. It is recommended that the pure compounds from these extracts be isolated for further bioactivity tests and structural elucidation for consideration as lead molecules in drug discovery. In addition, the genes responsible for the enhanced bioactivity in these isolates can be characterized and bioengineered for pharmaceutical application.

Limonene synergistically augments fluconazole susceptibility in clinical Candida isolates from cleft lip and palate patients.

Cleft lip and palate (CLP) patients are prone to Candida infections (oral thrush) mainly due to poor oral hygiene, repetitive surgeries, and orthodontic procedures. This study was undertaken to evaluate the antifungal efficacy of limonene against clinical Candida isolates from CLP patients. The antifungal efficacy of limonene was studied alone and in combination with fluconazole (FLC) against six standards, twenty nine FLC sensitive, and three FLC resistant clinical strains using broth dilution, checkerboard microdilution, agar disk diffusion, growth curves, and spot assays. This nontoxic monoterpene gave low minimum inhibitory concentration (MIC) values of 300-375 µg/mL and 500-520 µg/mL for FLC susceptible and FLC resistant strains, respectively. It showed synergistic interaction with FLC in all clinical and standard Candida strains (fractional inhibitory concentration (FIC) index ≤0.5). Significant chemosensitization of FLC was observed even against resistant clinical isolates. Complete suppression of fungal growth was observed when using combinations. Negligible toxicity, easy availability, and potent antifungal properties suggest that limonene and FLC combinations in appropriate doses can make excellent antifungal mouthwashes during CLP treatment pre and post surgery. Impending in vivo studies are needed to validate the present data.

The oral pathogen Porphyromonas gingivalis gains tolerance to the antimicrobial peptide DGL13K by synonymous mutations in hagA.

Porphyromonas gingivalis is a keystone pathogen for periodontal disease. The bacteria are black-pigmented and require heme for growth. P. gingivalis exhibit resistance to many antimicrobial peptides, which contributes to their success in the oral cavity. P. gingivalis W50 was resistant to the antimicrobial peptide LGL13K but susceptible to the all-D-amino acid stereoisomer, DGL13K. Upon prolonged exposure to DGL13K, a novel non-pigmented mutant was isolated. Exposure to the L-isomer, LGL13K, did not produce a non-pigmented mutant. The goal of this study was to characterize the genomic and cellular changes that led to the non-pigmented phenotype upon treatment with DGL13K. The non-pigmented mutant showed a low minimum inhibitory concentration and two-fold extended minimum duration for killing by DGL13K, consistent with tolerance to this peptide. The DGL13K-tolerant bacteria exhibited synonymous mutations in the hagA gene. The mutations did not prevent mRNA expression but were predicted to alter mRNA structure. The non-pigmented bacteria were deficient in hemagglutination and hemoglobin binding, suggesting that the HagA protein was not expressed. This was supported by whole cell enzyme-linked immunosorbent assay and gingipain activity assays, which suggested the absence of HagA but not of two closely related gingipains. In vivo virulence was similar for wild type and non-pigmented bacteria in the Galleria mellonella model. The results suggest that, unlike LGL13K, DGL13K can defeat multiple bacterial resistance mechanisms but bacteria can gain tolerance to DGL13K through mutations in the hagA gene.

Graphene oxide-modified polythiophene nanohybrids: antibacterial properties and sonophotocatalytic degradation of dyes under visible-light irradiation

The present work highlights the synthesis of graphene oxide (GO) modified polythiophene (PTh) for its application as an antibacterial agent as well as a visible light active photocatalyst. PTh was synthesized via the interfacial polymerization method using FeCl3 as initiator and then formulated as nanohybrids by mixing it in different weight ratios with graphene oxide (GO) i.e., 1 wt.%,3 wt.% and 5 wt. %. PTh and GO/PTh nanohybrids were characterized using FTIR, UV-visible, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) techniques. The polymerization of PTh as well as modification of PTh with GO was confirmed by IR studies, while the shifting of electronic transitions of PTH upon modification with GO were confirmed by the UV-visible studies. The degradation of dyes, Alizarin Yellow (AY), Basic Blue (BB) and Congo Red (CR) was carried out via sonophotocatalysis under visible light using PTh and GO/PTh as catalysts for a period of 60 min. The GO/PTh revealed higher degradation efficiency as compared to PTh. To evaluate its effectiveness as an antibacterial agent against Bacillus subtilis, disk diffusion inhibitory assay was carried out under dark and light conditions. The results showed that PTh and GO/PTh nanohybrids had bactericidal properties, regardless of light exposure. The results of the minimal inhibitory concentration (MIC) assay indicated the nanohybrid of 3-GO/PTh had the lowest MIC, followed by 1-GO/PTh and 5-GO/PTh.

Phyto-fabrication of Cobalt Oxide Nanoparticles from Ocimum Gratissimum L. Leaf and Flower Extracts and their Antimicrobial Activities

Background: Phyto-fabrication of nanoparticles has gained attention in recent times owing to its simple mode, cost-effective and eco-friendly nature. Objective: Hence, the present study aimed to synthesize cobalt oxide nanoparticles from methanol extracts of Ocimum gratissimum flower and leaf and to evaluate their antimicrobial action towards pathogenic bacteria and fungi. Methods: Phyto-fabrication of Cobalt nanoparticles (CoONPs) was achieved using cobalt chloride hydrate solution as a precursor. Characterization of fabricated CoONPs was performed using Ultra Violet-Visible spectrometry (UV-Vis), X-ray diffractometer (XRD), and Fourier Transform-Infrared spectroscopy (FTIR). The antimicrobial property was tested against two bacteria (Staphylococcus aureus and Escherichia coli) and two fungi (Cryptococcus albidus and Candida globasa) by agar disc diffusion technique and by measurement of Minimum Inhibitory Concentration (MIC). Results: Initial confirmation of CoONPs synthesis was observed by the colour change from light pink to reddish pink. Further, the UV-Vis spectrophotometry validated the CoONPs synthesis with a peak at 509 nm. The XRD authenticated the crystal nature of CoONPs synthesized using flower extract at 2θ angles with an average size of 54.9 nm and CoONPs fabricated using leaf extract at 2θ angles with an average size of 55.02 nm. The FTIR spectroscopy confirmed the functional groups present in plant extracts, which are believed to reduce and stabilize CoONPs. The findings of antibacterial activity showed that CoONPs synthesized using leaf showed a higher inhibition zone against E. coli (20.00 ± 2.00 mm) than S. aureus. Relating to fungi, the CoONPs fabricated using flower extract displayed significantly the highest activity against C. albidus (28.67±0.57 mm) and C. globasa (25.0 ± 0.00 mm). The lowest MIC was observed against S. aureus (MIC 7.5 µg/ml). For fungi, the smallest MIC was found against C. albidus (MIC 2.5 μg/ml). Conclusion: The current research established the efficacy of the phytochemical constituents of leaf and flower extracts of O. gratissimum for the enhancement of the effectiveness of CoONPs against both the tested bacteria and fungi.

Antimicrobial flavonoid: in silico targeting Escherichia coli DNA gyrase adeptly

A phytochemical investigation of Leucas aspera involved the isolation of flavones and steroids, along with triterpenoids. The identified chemical constituents were characterized as baicalein, baicalein-7-O-β-D-glucuronide, lup-20(29)-ene-3α,23-diol, β-sitosterol, and stigmasterol. Notably, baicalein (4) and baicalein-7-O-β-D-glucuronide (5) demonstrated significant antimicrobial activity at a low minimum inhibitory concentration against Staphylococcus aureus, Pseudomonas fluorescens, and Escherichia coli. Meanwhile, lup-20(29)-ene-3α,23-diol, β-sitosterol, and stigmasterol displayed moderate antimicrobial activity against all the screened microorganisms. Further analysis showed that baicalein-7-O-β-D-glucuronide had a strong docking score of −5.78 kcal/mol, indicating its robust interaction with E. coli DNA gyrase, which aligns with the in vitro findings. Additionally, baicalein-7-O-β-D-glucuronide exhibited in silico ADME (absorption, distribution, metabolites, and excretion) properties similar to those of tetracycline.

In vitro activity of delafloxacin against anaerobic bacteria compared with other antimicrobials

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 μg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.

Comparative Effect of Honey and Antibiotics against Multi Drug Resistant Bacteria Isolated from Surgical Site Infection

Patients undergoing surgery are predominantly exposed to surgical site infections (SSI) resulting in serious consequences. A cross-sectional study comprising 100 samples, was collected from various surgical sites of admitted and non-admitted patients in Lady Reading Hospital, Peshawar. 87 samples were tested positive for bacterial growth. After isolation and identification, the highest prevalence was recorded among isolates of Staphylococcus aureus 38 (43.6%) followed by Pseudomonas sp. 25 (28.7%), Streptococcus pyogenes 13 (14.9%) and E. coli 11 (12.6%). Antibiogram pattern was determined which showed high sensitivity of all bacterial isolates toward Clindamycin, Clarithromycin, and Piperacillin, followed by Erythromycin, Doxycycline, Co-amoxiclav, while maximum number of isolates showed resistance against Vancomycin, Ciprofloxacin, Amikacin. According to quantitative analysis, Ziziphus and Acacia honey inhibited E. coli at different Minimum Inhibitory Concentration (MIC). The results revealed that Ziziphus honey inhibited E.coli, at 100 µl concentration on the lowest MIC at 0.25 µl while Acacia honey inhibited E.coli at 75 µl concentration on lowest MIC at 0.5 µl. Ziziphus honey inhibited Pseudomonas sp. at 100 µl concentration on lowest MIC at 0.25 µl while Acacia honey inhibited Pseudomonas at 100 and 75 µl concentration on lowest MIC at 1 µl. Ziziphus honey also inhibited Staphylococcus aureus at 100 and 75 µl concentration on lowest MIC at 0.25 µl, while Acacia honey inhibited S. aureus at 100µl concentration on lowest MIC at 0.5 µl. This study concludes that Ziziphus honey was more effective in curing surgical wounds compared with Acacia honey. However, further Studies needed to be done for Ziziphus honey to utilize it as an efficient treatment approach.

Synthesis, characterization, biomolecular interaction, cytotoxicity, and computational studies of quinoxaline-based platinum(II) complexes

The combination of ninhydrin and o-phenylenediamine, followed by their reaction with a phenylhydrazine derivative produces quinoxaline-based ligands (L1 – L6). These ligands react with K2PtCl4 to form Pt(II) complexes (I – VI). The ligands and Pt(II) chelate were characterized through various spectroscopic and analytical techniques, like 1H NMR, 13C NMR, C, H, N-elemental analysis, IR spectroscopy, and mass spectrometry. DFT calculations were used to optimizethe structures of metal complexes. To investigate the binding mode of complexes to CT-DNA/BSA, absorption titration, viscosity measurements, and molecular docking analysis were employed. The results indicated that the DNA binding mechanism involved intercalation. The antibacterial efficacy of the compounds was evaluated against five strains of bacteria. The lower minimum inhibitory concentration (MIC) of complexes suggests that they are more potent than quinoxaline-based ligands. The synthesized compounds were evaluated for cytotoxicity using brine shrimp. The LC50 values of ligands and complexes ranged from 7.64 to 11.45 μg/mL and 5.27 to 7.02 μg/mL, respectively. The capacity of the molecule to suppress cell proliferation using the MCF-7 cancer cell was tested, and the IC50 value was discovered to be comparable to that of astandard drug. Thus in this work, complexes demonstrated intercalation as the binding mode with CT-DNA/BSA and exhibited enhanced antibacterial efficacy compared to the ligands. The compounds also showed promising cytotoxicity against brine shrimp and MCF-7 cancer cells, with comparable IC50 values to a standard drug, indicating their potential as therapeutic agents.

Antimicrobial and Antioxidant Activity of Rhamnolipids Biosurfactant is Produced by Pseudomonas aeruginosa

Rhamnolipids are the glycolipid biosurfactant produced by different Pseudomonas species; they show antimicrobial activity and antioxidant. The findings of antimicrobial activity showed the rhamnolipid biosurfactant had an antimicrobial effect against the microorganisms at different concentrations, such as toward Bacillus cereus and Klebsiella pneumoniae, while a lower inhibitory effect toward Staphylococcus aureus and Pseudomonas aeruginosa. The rhamnolipid biosurfactant was shown to have a lower inhibitory effect against fungal strains Candida albicans and Aspergillus niger. The lower minimum inhibitory concentration (MIC) values of rhamnolipid biosurfactant toward the investigated microorganisms were 2 mg/ml for E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and 3 mg/ml for Staphylococcus aureus, Enterobacter cloacae, Bacillus cereus, Proteus mirabilis, Candida albicans and Aspergillus niger. Rhamnolipid biosurfactant was tested as an antioxidant agent; the results showed 22.7 %, 47.4 %, 79.8 %, 85 % and 91.4 % of antioxidant activity at concentrations 5, 10. 15, 20 and 25 mg/ml, respectively. Cytotoxicity of the rhamnolipid biosurfactant was also examined at different concentrations against human erythrocytes. Hemolysis of the erythrocytes was observed at concentrations 100, 75, 50, 40 and 35 mg/ml, whereas the results exhibited no hemolysis at concentrations 25 and 15 mg/ ml. The study concluded that rhamnolipid biosurfactant showed effective antioxidant activity, no hemolysis at lower concentrations and has a high antimicrobial effect. The rhamnolipid biosurfactant is a suitable and great alternative to be employed as an effective and safe therapeutic agent. Keywords: Antimicrobial; Antioxidant; Cytotoxicity; Rhamnolipid; Pseudomonas aeruginosa

Antibacterial activity of Clove Syzygium aromaticum L. and synergism with antibiotics against multidrug-resistant uropathogenic E. coli

Relevance. Urinary tract infections pose a growing threat to humanity due to the rise of antibiotic resistance in uropathogens. Exploring natural sources for alternative treatments has become a prominent approach. The aim of the research was to investigate the antibacterial effects of clove (Syzygium aromaticum L.) against uropathogenic Escherichia coli (E. coli). Materials and Methods. The research was performed on three clinical multidrug-resistant uropathogenic E. coli isolates and E. coli ATCC 25922. Clove hydroalcoholic extract was obtained by cold maceration technique. To evaluate the antibacterial activity of the extract, agar well diffusion method was performed. Minimum inhibitory and minimum bactericidal concentrations of the extract were determined by microbroth dilution method. Light microscopy was used to investigate morphological changes in uropathogenic E. coli after exposure to clove extract. Checkerboard assay was used to assess synergism between clove extract and antibiotics. All obtained data were statistically processed. Results and Discussion. In well diffusion method, bacterial responses to clove extract were concentration-dependent with inhibition zone diameter of 7-10/10-15 mm for uropathogenic strains and E. coli ATCC 25922, respectively. Minimum inhibitory and minimum bactericidal concentrations of clove extract against uropathogenic strains were 25 mg/mL. The extract showed a lower minimum inhibitory concentration against E. coli ATCC 25922 (6.25 mg/ mL) with minimum bactericidal concentration being 25 mg/mL. Minimum inhibitory and minimum bactericidal concentrations ratio showed that clove extract tends to be bactericidal agent. Synergy test revealed that the combination of clove extract and nitrofurantoin or ciprofloxacin resulted in no interaction. However, minimum inhibitory concentrations of all tested agents in combinations exhibited varying degrees of decrease. Incubation of uropathogenic strains with the extract transformed them to unstable spherical L-form in percentage of 96-99 %. Conclusion. This study highlights clove as a potential natural antibacterial agent against multidrug-resistant uropathogenic E. coli, warranting further investigations into its antibacterial properties.

Comparative Meropenem Pharmacodynamics and Emergence of Resistance against Carbapenem-Susceptible Non-Carbapenemase-Producing and Carbapenemase-Producing Enterobacterales: A Pharmacodynamic Study in a Hollow-Fiber Infection Model.

Resistance to carbapenems has become a problem due to Klebsiella pneumoniae (K. pneumoniae), harboring carbapenemases. Among them, there are isolates that are recognized as carbapenem-susceptible; however, these carbapenemase-producing strains with low meropenem minimal inhibitory concentrations (MICs) may pose a threat to public health. We aimed to investigate the impact of the ability to produce carbapenemases by a bacterial isolate on the effectiveness of meropenem in the hollow-fiber infection model. K. pneumoniae and Escherichia coli (E. coli) strains with equal meropenem MICs but differing in their ability to produce carbapenemases were used in pharmacodynamic simulations with meropenem. In addition to standard MIC determination, we assessed the MICs against tested strains at high inoculum density to test if the inoculum effect occurs. According to pharmacodynamic data, the carbapenemase-producing strains were characterized with a relatively decreased meropenem effectiveness compared to non-producers. Meanwhile, the effect of meropenem perfectly correlated with the meropenem exposure expressed as the DOSE/MIC ratio when high-inoculum (HI) MICs but not standard-inoculum (SI) MICs were used for regression analysis. It could be concluded that meropenem-susceptible carbapenemase-producing strains may not respond to meropenem therapy; the antibiotic inoculum effect (IE) may have a prognostic value to reveal the meropenem-susceptible Enterobacterales that harbor carbapenemase genes.

Recent Trends in S. aureus and E. coli-Based Endometritis, and the Therapeutic Evaluation of Sodium Alginate-Based Antibiotics and Nanoparticles.

Postpartum infection of the uterus by pathogenic bacteria is exacerbated due to a lack of sufficient epidemiological studies and evidence-based therapeutics. Therefore, this study was planned to find the prevalence, risk factors, and drug-resistance profile of S. aureus and E. coli isolated from bovine endometritis and to evaluate the antibacterial potential of sodium alginate-based antibiotics and nanoparticles. The study revealed 34.21% S. aureus and 31.57% E. coli, whereas most of the assumed risk factors presented significant association in this study. S. aureus showed the highest resistance against fusidic acid (60%) and cefoxitin (50%), while the highest resistance in E. coli was found against fusidic acid (60%), gentamicin (60%), chloramphenicol (50%), and cefoxitin (50%). Tylosin coupled with MgO nanoparticles stabilized in sodium alginate gel (Tylo + MgO + gel) presented significantly lower minimum inhibitory concentration (MIC) against E. coli, showing 13.88 ± 4.51 µg/mL after 24 h incubation. On the other hand, gel-based preparations showed MIC as 31.25 ± 0 µg/mL (Tylo + gel + MgO) and 26.04 ± 9.02 µg/mL (Tylo + Gel) against S. aureus. Generally, the MICs of non-gel-based preparations were significantly higher against bacteria except ampicillin against S. aureus in this study. The toxicity analysis of MgO nanoparticles presented 20-80% mortality of snails against a wider range of 0.01 mg/mL-10 mg/mL. The histopathological parameters concluded MgO nanoparticles safe to use on off targets. The current study thus concludes the rise in antimicrobial resistance while the gel-based products appearing as effective antimicrobials with sufficient safety margins for off-targets. The study thus invites further investigation for the development of suitable and affordable modified therapeutics for better health and production of animals.

Efficient, Green One-Pot Synthesis of Antimicrobial Agents: Functionalized DPTS Catalyst for the Preparation of 2-Amino-4-Aryl-5-Oxo-4HChromene- 3-Carbonitriles, with Theoretical Calculations

Background: In the search for a new and effective synthetic approach to bio-logically chromene-derived compounds, a series of 2-amino-7, 7-dimethyl-5-oxo-4H-tetrahydrochromene-3-carbonitrile derivatives (4a-i) were synthesized. This synthesis involved the use of 4-(dimethylamino)pyridiniump-toluenesulfonate (DPTS) as a catalyst in an aqueous medium. Additionally, the relative stability between isomers was investigated using DFT/B3LYP calculations. Methods: The target compounds were synthesized through a multicomponent reaction of 5,5-dimethyl-1,3-cyclohexanedione (dimedone) 1, various arylaldehydes (2a-i), and malononitrile 3 in water and were recrystallized in ethanol. The reaction was promoted using DPTS, which is a low-toxic, inexpensive, commercially available, and easy-to-handle catalyst. Results: The catalytic activity of DPTS was investigated in a condensation reaction conducted in an aqueous medium at room temperature. All synthesized compounds displayed considerable antimicrobial activities against human pathogenic bacteria and fungi. Conclusion: The developed synthetic protocol demonstrates energy efficiency, shorter reaction time, environmental friendliness, high product yields with purity, and scalability to gram-scale synthesis. DPTS proved to be a valuable contribution to the field of organocatalysis. The synthesized compounds were screened for in vitro antimicrobial activities, demonstrating varying potency against the microbial strains. Compound 4h exhibited the most potent activity with a zone of inhibition (ZOI) measuring 15 mm against E.coli. This was followed by compounds 4b, 4d, 4f, and 4g, which displayed a ZOI of 12 mm. Furthermore, the antifungal results revealed promising anticandidal activity for compounds 4b, 4e, and 4h, with a lower minimum inhibitory concentration (MIC) of 0.031 mg/ml. In addition, molecular electrostatic potential (MEP) mapping, reactivity indices such as electronegativity, electrophilic index, softness, and hardness, as well as frontier molecular orbitals (HOMO-LUMO), were used to provide further evidence regarding the stability and reactivity of the synthesized products.

In vitro pharmacodynamics of nemonoxacin and other antimicrobial agents against Mycoplasma pneumoniae

ABSTRACT Mycoplasma pneumoniae is the causative agent of respiratory infections in children and adults. Macrolide still plays a significant role in treating infections by M. pneumoniae . However, macrolide-resistant M. pneumoniae (MRMP) was encountered, causing more severe or prolonged disease worldwide from the early 2000s. Nemonoxacin is a newly developed C-8-methoxy non-fluorinated quinolone having broad-spectrum activity against gram-positive, gram-negative, and atypical pathogens in vitro , as well as general safety and well tolerance in vivo . This study aimed to assess the killing kinetics of nemonoxacin and other antimicrobial agents against MRMP and macrolide susceptible M. pneumoniae (MSMP) by static time-kill curves. In addition, the pharmacodynamic analyses of these drugs were determined by the sigmoid E max model. The static time-kill curves indicated that nemonoxacin had good mycoplasmacidal activity against both MSMP and MRMP strains. The pharmacodynamic analysis demonstrated that the mycoplasmacidal effect of nemonoxacin was greater than those of moxifloxacin and levofloxacin based on the K max , displaying a dualism of concentration dependency in low minimum inhibitory concentrations (MICs) and time dependency in high MICs. Therefore, nemonoxacin demonstrated efficacy against M. pneumoniae in vitro and is a potential candidate for clinical studies for assessing its therapeutic effects against M. pneumoniae infections. The killing pattern or PK/PD characteristics of nemonoxacin against M. pneumoniae from in vitro data, animal studies, or clinical studies merit further evaluation for treating infections caused by the organism. IMPORTANCE This study first reported the in vitro effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant M. pneumoniae (MRMP) and macrolide susceptible M. pneumoniae (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with M. pneumoniae .

In vitro manogepix susceptibility testing of South African Emergomyces africanus, Emergomyces pasteurianus, and Blastomyces emzantsi clinical isolates.

We performed in vitro antifungal susceptibility testing of manogepix against the yeast phase of 78 Emergomyces africanus, 2 Emergomyces pasteurianus, and 5 Blastomyces emzantsi isolates using a reference broth microdilution method following Clinical and Laboratory Standards Institute recommendations. All three pathogens had low minimum inhibitory concentrations ranging from <0.0005 to 0.008 mg/L. Manogepix should be investigated in animal models and potentially in future human clinical trials for endemic mycoses.

Investigation of the antimicrobial susceptibility patterns of marine cyanobacteria in Bohai Bay: Cyanobacteria may be important hosts of antibiotic resistance genes in marine environment

Marine cyanobacteria, as widely distributed and photosynthetically autotrophic bacteria in the ocean, may contribute to the global dissemination of antibiotic resistance genes (ARGs) and develop a different antimicrobial susceptibility pattern from heterotrophic bacteria and cyanobacteria from freshwater environments. However, studies on antimicrobial susceptibility and the carriage of ARGs in marine cyanobacteria are still very limited. In this study, the antibiotic resistance characteristics of cyanobacteria in nearshore waters were examined through field monitoring and laboratory investigations, which included PCR detection and ARG transformation. The results showed a positive correlation between marine cyanobacteria and some ARGs in the nearshore waters of Bohai Bay. Moreover, most screened cyanobacteria showed high minimum inhibitory concentration (MIC) values for polymyxins, tetracyclines, kanamycin, and sulfonamides, moderate MIC values for streptomycin, chloramphenicol, rifampicin, and norfloxacin, and low MIC values for roxithromycin and cephalosporins. The blaTEM, blaKPC, sul1, sul2, strA, tetA, tetB, tetC, tetM, mdfA, and intI1 genes were detected in the screened marine cyanobacteria. The highest detection rates were observed for blaTEM (93.3 %), sul1 (56.6 %), sul2 (90 %), and strA (73.3 %). The detection rate of tetA (33.3 %) was the highest among the tetracycline resistance genes, and mdfA, a multidrug-resistant pump gene with resistance to tetracycline, also showed a high detection level (23.3 %). Overall, most of the screened marine cyanobacteria were found to tolerate multiple antibiotics in seawater, and the condition of the ARGs carriage was serious. Furthermore, the screened marine Synechocystis sp. C12-2 demonstrated the ability to accept ARGs on the RP4 plasmid through natural transformation and showed reduced sensitivity to ampicillin, suggesting the possibility that some marine cyanobacteria could acquire ARGs from the environment through horizontal gene transfer. Thus, marine cyanobacteria may play an important role in the propagation of marine ARGs.