Search Results (1,630)

The current study has yielded promising results in the evaluation of a new ciprofloxacin-chalcone hybrid (CP derivative) for its anticancer activity as potential Topoisomerases (Topo) I and II inhibitors. The in vitro results showed that the CP derivative significantly suppressed the growth of HCT-116 and LOX IMVI cells, with IC₅₀ values of 5.0 μM and 1.3 μM, respectively, outperforming Staurosporine, which had IC₅₀ values of 8.4 μM and 1.6 μM, respectively. Flow cytometry analysis revealed that the new CP derivative triggered apoptosis and cell cycle arrest at the G2/M phase, associated with the up-regulation of pro-apoptotic genes (Bax and Caspase 9) and downregulation of the anti-apoptotic gene (Bcl-2). Further investigations showed that the CP derivative inhibited Topo I and II enzymes, as expected molecular targets; docking studies further supported its dual inhibitory action on Topo I and II. These findings suggest that the ciprofloxacin-chalcone hybrid could be a promising lead compound for developing new anticancer therapy. Full article

Community-acquired urinary tract infections account for 15% of all outpatient use of antibiotics, and women are primarily affected; the major causative microorganism is uropathogenic Escherichia coli (E. coli). Treatment is indicated for cystitis and pyelonephritis and includes B-lactams (amoxicillin-clavulanic acid or third-generation cephalosporins), fluoroquinolones (ciprofloxacin or levofloxacin), nitrofurantoin, fosfomycin, and trimethoprim–sulfamethoxazole. Resistance to antibiotic treatment is of concern; several mechanisms have been associated with the acquisition of genes that confer antimicrobial resistance to fluoroquinolones, which are often associated with other patterns of resistance, especially in extended-spectrum beta-lactamase (ESBL) producers. Several studies have addressed the prevalence of uropathogens producing ESBLs, but only a few have focused on fluoroquinolone resistance, and, to our knowledge, none have addressed the prevalence of phylotypes or genes responsible for antimicrobial resistance to fluoroquinolones. The focus of the present review was to analyze recently published papers that described the E. coli phylotype causing community-acquired UTIs in association with fluoroquinolone resistance. Full article

Emerging pharmaceutical pollutants like ciprofloxacin (CIP) and ibuprofen (IBU) are frequently detected in aquatic environments, posing risks to ecosystems and human health. Since pollutants rarely exist alone in the environment, understanding the thermal stability and degradation kinetics of these compounds, especially in mixtures, is crucial for developing effective removal strategies. This study therefore investigates the thermal stability and degradation kinetics of CIP and IBU, under different heating rates. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were employed to examine the thermal behavior of these compounds individually and in mixture (CIP + IBU) at heating rates of 10, 20, and 30 °C/min. The kinetics of thermal degradation were analyzed using both model-fitting (Coats–Redfern (CR)) and model-free (Kissinger–Akahira–Sunose (KAS), Flynn–Wall–Ozawa (FWO), and Friedman (FR)) methods. The results showed distinct degradation patterns, with CIP decomposing between 280 and 550 °C and IBU between 152 and 350 °C, while the mixture exhibited multistep decomposition in the 157–500 °C range. The CR model indicated first-order kinetics as a better fit for the degradation (except for IBU). Furthermore, CIP exhibits higher thermal stability and activation energy compared to IBU, with the KAS model yielding activation energies of 58.09 kJ/mol for CIP, 11.37 kJ/mol for IBU, and 41.09 kJ/mol for CIP + IBU mixture. The CIP + IBU mixture generally showed intermediate thermal properties, suggesting synergistic and antagonistic interactions between the compounds. Thermodynamic parameters (ΔH°, ΔG°, ΔS°) were calculated, revealing non-spontaneous, endothermic processes for all samples (except in the FWO method) with a decrease in molecular disorder and positive ΔG° values across all models and heating rates. The study found that higher heating rates led to less thermodynamically favorable conditions for degradation. These findings provide important information concerning the thermal behavior of these pharmaceutical pollutants, which can inform strategies for their removal from the environment and the development of more effective waste-treatment processes. Full article

Escherichia coli (E. coli) is a predominant pathogen of urinary tract infections (UTIs) in the United States. We analyzed resistance patterns by geographic location in Washington State to assess the need for regional antibiograms. The study included urinary E. coli antibiotic susceptibility tests performed by Quest Diagnostics on Washington outpatient isolates from 2013 to 2019. We conducted logistic regressions with robust standard errors for five antibiotics (ceftriaxone, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole), with isolates classified as “susceptible” or “resistant” for each antibiotic tested. Analyses were adjusted for sex, year of isolate collection, and age group (0–18, 19–50, >50). The state’s nine Public Health Emergency Preparedness Regions (PHEPRs) were used as the geographic level for the analysis. The analysis included 40,217 isolates (93% from females, mean age 47 years). Compared to the Central PHEPR (containing Seattle), most other regions had significantly lower adjusted prevalence ratios (aPORs) of antimicrobial resistance (AMR), with aPORs as low as 0.20 (95% CI: 0.06–0.63) for ceftriaxone in the North Central region. Additionally, no regions had significantly higher aPOR of resistance for any antibiotic. Differences in resistance between the Central and other regions varied by antibiotic with the largest difference for ceftriaxone and smallest for ampicillin. The finding of regional variation of E. coli AMR calls for more specific community antibiograms to enable a precise approach to antibiotic prescribing and stewardship. Full article

This paper presents the findings of a large-scale study on antibiotic resistance in bacteria found in farm animal feces across Russia. The study included 6578 samples of farm animal manure from 13 regions in Russia, with the help of citizen scientists. Molecular and microbiological methods were used to analyze 1111 samples of E. coli. The microbiological analysis focused on culturing the microorganisms present in the fecal samples on selective media for E. coli and evaluating the sensitivity of the bacteria to different antibiotics, including ampicillin, tetracycline, chloramphenicol, cefotaxime, and ciprofloxacin. The molecular analysis involved isolating the genomic DNA of the bacteria and conducting PCR assays to detect the vanA, vanB, and mcr-1 antibiotic resistance genes. The results demonstrated significant differences in antibiotic sensitivity of the samples that are morphologically identical to E. coli from different regions. For example, 98.0% and 82.5% of E. coli and other fecal bacterial isolates from the Omsk and Vologda regions lacked antibiotic resistance genes, while 97.7% of samples from the Voronezh region possessed three resistance genes simultaneously. The phenotypic antibiotic sensitivity test also revealed regional differences. For instance, 98.1% of fecal bacterial samples from cattle in the Udmurt Republic were sensitive to all five antibiotics tested, whereas 92.8% of samples from the Voronezh region showed resistance to all five antibiotics. The high level of antibiotic resistance observed may be attributed to their use in farming practices. The distinctive feature of our research is that comprehensive geographical coverage was achieved by using a citizen science platform. Citizen scientists, specifically students from colleges and universities, were responsible for the collection and initial analysis of samples. The project attracted 3096 student participants, enabling the collection and analysis of a significant number of samples from various locations in Russia. Full article

To gain insights into the prevalence and antimicrobial resistance patterns of major bacterial pathogens affecting largemouth bass (Micropterus salmoides) in the Pearl River Delta (PRD) region, Guangdong, China, a study was conducted from August 2021 to July 2022. During this period, bacteria were isolated and identified from the internal organs of diseased largemouth bass within the PRD region. The antimicrobial resistance patterns of 11 antibiotics approved for use in aquaculture in China were analyzed in 80 strains of Edwardsiella piscicida using the microbroth dilution method. The results showed that 151 bacterial isolates were obtained from 532 samples, with E. piscicida (17.29%, 92/532), Aeromonas veronii (4.70%, 25/532), and Nocardia seriolae (2.26%, 12/532) being the main pathogens. Notably, E. piscicida accounted for the highest proportion of all isolated bacteria, reaching 60.92% (92/151), and mainly occurred from November to April, accounting for 68.48% (63/92) of the cases. The symptoms in largemouth bass infected with E. piscicida included ascites, enteritis, and hemorrhaging of tissues and organs. The drug sensitivity results showed that the resistance rates of all E. piscicida strains to ciprofloxacin, all sulfonamides, thiamphenicol, florfenicol, enrofloxacin, doxycycline, flumequine, and neomycin were 96.25%, 60–63%, 56.25%, 43.75%, 40%, 32.5%, 16.25%, and 1.25%, respectively. In addition, 76.25% (61/80) of these strains demonstrated resistance to more than two types of antibiotics. Cluster analysis revealed 23 antibiotic types (A–W) among the 80 isolates, which were clustered into two groups. Therefore, tailored antibiotic treatment based on regional antimicrobial resistance patterns is essential for effective disease management. The findings indicate that in the event of an Edwardsiella infection in largemouth bass, neomycin, doxycycline, and flumequine are viable treatment options. Alternatively, one may choose drugs that are effective as determined by clinical drug sensitivity testing. Full article

Silica–poly (vinylpyrrolidone) hybrid material was prepared using the sol–gel method. Tetramethyl ortosilane (TMOS) was used as a silica precursor. XRD analysis established that the as-prepared material is amorphous. The morphological structure of the final product was determined by the incorporated PVP. The UV–Vis analysis showed that the obtained hybrid exhibited absorption in the ultraviolet range. The antimicrobial activity of the SiO₂/15PVP hybrid material was tested on Staphylococcus epidermidis ATCC 14990, Salmonella typhimurium ATCC BAA-2162, Candida albicans, and Saccharomyces cerevisiae in combination with the following antibiotics: Vancomycin for Gram-positive bacteria, Ciprofloxacin for Gram-negative bacteria, and Nystatin for yeast. The results confirmed a concentration-dependent synergistic effect of the antibiotic in combination with the TM15/PVP hybrid particles, especially at their highest concentration of 100 mg/mL on Gram-positive bacteria and for the Gram-negative Salmonella. On Candida albicans ATCC 18804 and Saccharomyces cerevisiae CCY 21-6-3, the effect was synergistic again, and a fungicidal effect was observed at 6.25 and 1.50 mg/mL for the antibiotic concentration and concentrations of hybrid material at 100 mg/mL. The toxicity on Daphnia magna was also tested. The registered prooxidant activity of SiO₂/15PVP shows possible applications at very low concentrations. The obtained results demonstrate the possibility of clinical implementations of the newly synthesized hybrid material. Full article

Objectives: Uncomplicated cystitis is a leading form of bacterial UTI; the most common causative bacterium worldwide is Escherichia coli. This internet-based, prospective, multicenter, and national observational study aimed to report the antimicrobial resistance of E. coli in patients with uncomplicated cystitis through the use of the Korean Antimicrobial Resistance Monitoring System (KARMS) in 2023. Results: Data for a total of 654 patients were retrieved from the KARMS database. The mean (standard deviation) patient age was 55.9 (18.3) years. The numbers of postmenopausal women and patients with recurrent cystitis were 381 (59.4%) and 78 (11.9%), respectively. Regarding antimicrobial susceptibility, 96.8% were susceptible to fosfomycin, 98.9% to nitrofurantoin, 50.9% to ciprofloxacin, and 82.4% to cefotaxime. Extended-spectrum beta-lactamase positivity was 14.4% (89/616), and was significantly higher in tertiary hospitals (24.6%, p < 0.001) and recurrent cystitis (27.6%, p < 0.001). Fluoroquinolone resistance was significantly higher in tertiary hospitals (57.8%, p < 0.001), postmenopausal women (54.2%, p < 0.001), and recurrent cystitis (70.3%, p < 0.001). In addition, postmenopausal status (95% confidence interval [CI]: 1.44–3.17, odds ratio [OR] 2.13, p < 0.001), recurrent cystitis (95% CI: 1.40–4.66, OR 2.56, p = 0.002) and tertiary hospitals (95% CI: 1.00–2.93, OR 1.71, p = 0.049) were associated with significantly increased fluoroquinolone resistance. Methods: Any female patient diagnosed with clinical uncomplicated cystitis and microbiologically proven E. coli infection in 2023 was eligible for this study. Patient data were obtained from the web-based KARMS database. The antimicrobial susceptibility of E. coli was analyzed according to clinical factors, including hospital region, hospital type, menopause status, and recurrence status. Conclusions: The antimicrobial resistance of E. coli in patients with uncomplicated cystitis in the Republic of Korea has reached a serious level, especially in fluoroquinolone resistance. Therefore, major efforts should be made to reduce antimicrobial resistance. Full article

Background/Objectives: The spread of antibiotic resistance, particularly through Enterococcus spp., in wastewater treatment plants (WWTPs) poses significant public health risks. Given that research on antibiotic-resistant enterococci and their antibiotic-resistance genes in aquatic environments is limited, we evaluated the role of Enterococcus spp. in WWTPs by comparing the antibiotic resistance rates, gene prevalence, biofilm formation, and residual antibiotics in the influent and effluent using culture-based methods. Methods: In 2022, influent and effluent samples were collected from 11 WWTPs in South Korea. Overall, 804 Enterococcus strains were isolated, and their resistance to 16 antibiotics was assessed using the microdilution method. Results: High resistance to tetracycline, ciprofloxacin, kanamycin, and erythromycin was observed. However, no significant differences in the overall resistance rates and biofilm formation were observed between the influent and effluent. Rates of resistance to ampicillin, ciprofloxacin, and gentamicin, as well as the prevalence of the tetM and qnrS genes, increased in the effluent, whereas resistance rates to chloramphenicol, florfenicol, erythromycin, and tylosin tartrate, along with the prevalence of the optrA gene, decreased. E. faecium, E. hirae, and E. faecalis were the dominant species, with E. faecalis exhibiting the highest resistance. Conclusions: Our results suggest that WWTPs do not effectively reduce the rates of resistant Enterococcus spp., indicating the need for continuous monitoring and improvement of the treatment process to mitigate the environmental release of antibiotic-resistant bacteria. Full article

This study explored the antimicrobial potential of Piper betle L. (PBL) and Piper nigrum L. (PNL) extracts against MRSA. Plant parts including stem, leaf, and fruit were extracted using aquadest, methanol, and hexane, resulting in 18 distinct extracts. FT-IR combined with cluster analysis (CA) categorized the extracts, and anti-MRSA activity was assessed through the paper disk diffusion method. The most potent extracts were further analyzed using GC-MS to identify bioactive compounds. Additionally, molecular docking studies were conducted for MRSA protein targets (4DKI, 6H5O, and 4CJN). The hexane extract of PNL and the aqueous extract of PBL fruit showed the strongest inhibitory effects. GC-MS identified piperine (14.22%) and diisooctyl phthalate (14.67%) as major compounds, with piperolein B, piperanine, β-caryophyllene oxide, and α-caryophylladienol as minor compounds in the hexane extract of PNL, while hydroxychavicol (81.89%) and chavibetol (12.01%) were predominant in the aquadest extract of PBL. Molecular docking revealed that piperolein B and piperine had strong binding affinities to MRSA proteins 4DKI, 6H5O, and 4CJN, comparable to ciprofloxacin. In conclusion, this study confirms the potential of PBL and PNL as sources of novel anti-MRSA agents, supporting further research to develop new therapies. Full article

This study explores the functional attributes of Lactiplantibacillus plantarum (L. plantarum) strains isolated from fermented tomato juice, focusing on their physiological, biochemical, and probiotic characteristics. The identified 66 gram-positive strains included 36 L. plantarum ones, which exhibited robust growth in acidic environments (pH 2.0–5.0) and utilization of various carbohydrates. Notably, seven strains outperformed a commercial strain in extreme acidic conditions. Antioxidant activity varied, with strain A24 showing the highest hydroxyl radical scavenging ability, while strains with high surface hydrophobicity had lower DPPH scavenging activity, indicating no direct correlation between these properties. Strains also showed strain-specific differences in carbohydrate utilization and antibiotic resistance, with some resistant to gentamicin and ciprofloxacin. Survival rates under simulated gastrointestinal conditions were strain-specific, with some strains demonstrating high survival rates, indicating their potential as probiotics. Furthermore, 13 strains used as fermentation starters in tomato juice significantly enhanced antioxidant activity and reduced pH and total soluble solids, indicating efficient sugar utilization and lactic acid production. These findings suggest that L. plantarum strains are well-suited for functional food fermentation and probiotic applications, with strain-specific traits offering versatility for use in acidic food products and probiotic formulations. Full article

Caseous lymphadenitis (CLA), caused by the bacteria Corynebacterium pseudotuberculosis, is a highly contagious disease of small ruminants, especially of goats and sheep. Here, we report an outbreak of the disease in goats for the first time from the Andaman and Nicobar Islands along with isolation and molecular characterization of the pathogen. A total of 22 goats were affected, with an attack rate of 12.02%, and six isolates were identified from the clinical samples. Molecular characterization of the pathogen was carried out based on the sequence information of 16S rRNA and RNA polymerase β subunit (rpoB) gene fragments. rpoB-based phylogenetic analysis indicated that the isolates belonged to Corynebacterium pseudotuberculosis biovar ovis. The antimicrobial resistance study revealed that the isolates were 100% resistant against erythromycin and rifampicin. Fifty percent resistance was found against amoxicillin/clavulanic acid, ciprofloxacin, penicillin, and vancomycin. All the isolates were sensitive to tetracycline, chloramphenicol, cotrimoxazole, sulphafurazole, ampicillin/cloxacillin, and oxytetracycline. In conclusion, the present study reports the occurrence of CLA in goats for the first time from an isolated archipelago of India and unveils the molecular signature and antibiotic resistance patten of the pathogen. The findings of this study will be helpful to control or eradicate the disease from the Andaman and Nicobar Islands. Full article

Contamination of marine ecosystems by pharmaceutically active compounds (PhACs) deserves more research since their environmental fate differs from that observed in freshwater systems. However, knowledge remains scarce, especially in semi-arid coastal regions of the Global South. This study investigates the occurrence and distribution of caffeine, carbamazepine, ciprofloxacin, and sulfamethoxazole in sediments from the La Paz lagoon, a coastal system in a semi-arid region of Mexico with inverse estuarine conditions. Samples of superficial sediments (0–5 cm depth) were collected from 18 sampling points distributed through the lagoon, encompassing sites heavily polluted by discharges of municipal sewage and 3 potentially pristine sites far from the urban and peri-urban zones. Also, a 25 cm length sediment core was taken and divided into 1 cm sub-samples to determine the deposition of target PhACs in the sediment bed through time. The extraction of the target PhACs was performed through the accelerated solvent extraction (ASE) technique and quantification was achieved using a validated HPLC-MS/MS analytical method. The concentration of caffeine, carbamazepine, ciprofloxacin, and sulfamethoxazole in superficial sediment oscillated in the range of 1 to 45 ng g⁻¹ (dry weight). The highest mass fraction of target PhACs was detected in sites impacted by wastewater discharges. The caffeine-to-carbamazepine ratio was determined for the first time in marine sediments impacted by wastewater discharges, resulting in values from 4.2 to 9.12. Analysis of the 25 cm length sediment core revealed a high dispersion of caffeine, which was attributed to high water solubility, while antibiotics were predominantly detected in the upper 20 cm of the core. Risk quotients were calculated, observing low risk for caffeine, carbamazepine, and ciprofloxacin, while sulfamethoxazole presented high risk in all the sampling points. PhACs are retained in superficial sediments from a lagoon impacted by wastewater discharges, and the level of impact depends on the properties of the compounds and the TOC content in sediments. Risk assessments should be performed in the future considering the combination of pharmaceuticals and byproducts in marine sediments. This research emphasizes the importance of sewage management in preserving marine ecosystems in semi-arid regions in the Global South. Full article

Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics and the emergence of antibiotic-resistant strains. In a previous study, a chitosan-based matrix crosslinked with tannic acid and loaded with gentamicin was reported. In this study, five different antibiotics (moxifloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole or linezolid) were loaded into these chitosan-based films, and their impact on the release behavior carefully assessed. Methods: The samples were characterized according to their thickness, swelling, and mass loss in phosphate-buffered saline (PBS), as well as by morphology using scanning electron microscopy (SEM) and optical phase contrast microscopy. Antibiotic release over time was quantified in PBS by high-performance liquid chromatography (HPLC). Antibacterial activity was investigated by disk diffusion test and antibiotic release over time. Finally, the cytotoxicity of the samples was assessed with human dermal fibroblasts. Results: The obtained results differed significantly, especially regarding the antibiotic release time and antibacterial activity, which varied from one day to six months, enabling classification of the films from burst/transient to prolonged release. The films also showed antibacterial features against bacteria mostly present in medical devices and displayed to be non-cytotoxic. Conclusions: In conclusion, it was demonstrated that the antibiotics structure significantly alters the release kinetics, and that by carefully selecting the antibiotic, the consequent release can be tuned. This approach yielded films that could be used for potentially-scalable release in antimicrobial coatings specific to medical devices, aiming to reduce biomaterial associated infections (BAIs). Full article

The emergence of multidrug-resistant pathogens necessitates the development of novel antimicrobial agents. BP100, a short α-helical antimicrobial peptide (AMP) derived from cecropin A and melittin, has shown promise as a potential therapeutic. To enhance its efficacy, we designed and synthesized 16 tryptophan-substituted BP100 analogs based on helical wheel projections. Among these, BP5, BP6, BP8, BP11, and BP13 exhibited 1.5- to 5.5-fold higher antibacterial activity and improved cell selectivity compared to BP100. These analogs demonstrated superior efficacy in suppressing pro-inflammatory cytokine release in LPS-stimulated RAW 264.7 cells and eradicating preformed biofilms of multidrug-resistant Pseudomonas aeruginosa (MDRPA). Additionally, these analogs showed greater resistance to physiological salts and serum compared to BP100. Mechanistic studies revealed that BP100 and its analogs exert their antibacterial effects through membrane disruption, depolarization, and permeabilization. Notably, these analogs showed synergistic antimicrobial activity with ciprofloxacin against MDRPA. Our findings suggest that these tryptophan-substituted BP100 analogs represent promising candidates for combating multidrug-resistant bacterial infections, offering a multifaceted approach through their antibacterial, anti-inflammatory, and antibiofilm activities. Full article