Search Results (2,159)

Background/Objectives: Fluoroquinolones (FQNs) are widely prescribed broad-spectrum antibiotics but are associated with central and peripheral nervous system adverse reactions (ARs). Regulatory agencies have issued multiple safety warnings regarding their neuropsychiatric effects; however, large-scale, comparative evaluations across individual FQNs remain limited. This study aimed to comprehensively characterise and compare neuropsychiatric profiles associated with Ciprofloxacin, Levofloxacin, and Moxifloxacin using pharmacovigilance data. Methods: A retrospective pharmacovigilance study was conducted using reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between 2010 and 2025. Neuropsychiatric ARs were identified using MedDRA terms, including neurological and psychiatric manifestations. Reporting trends, demographic characteristics, and event frequencies were descriptively analysed. Signal detection was performed using the Information Component (IC), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR). Results: A total of 95,968 individual case safety reports involving neuropsychiatric ARs were included. Levofloxacin accounted for the highest number of reported events, followed by Ciprofloxacin and Moxifloxacin. Disproportionality analyses identified peripheral neuropathy as the strongest neurological signal for Levofloxacin and Moxifloxacin, while Ciprofloxacin showed stronger central nervous system associations. Psychiatric ARs were drug-specific, with anxiety predominating for Ciprofloxacin and Moxifloxacin, and insomnia for Levofloxacin. All major signals were statistically robust (IC025 > 0), confirming distinct compound-specific neuropsychiatric risk profiles. Conclusions: The large-scale 16-year analysis demonstrates distinct, drug-specific neuropsychiatric risk profiles. The available evidence supports a non-interchangeable safety profile among FQNs and emphasises the importance of drug-specific risk–benefit assessment in clinical practice. Full article

Background/objectives: Infections caused by multidrug-resistant (MDR) bacteria are becoming increasingly difficult to treat with recommended antimicrobials. Considering the critical and growing challenge of antimicrobial resistance (AMR), this study aims to evaluate the antimicrobial susceptibility patterns of Escherichia coli clinical isolates from dogs in Grenada. This research project consists of two distinct studies: a retrospective analysis of AMR in canine E. coli isolates collected between 2010 and 2020, and a cross-sectional study characterizing the genotypic AMR profiles of E. coli isolates obtained between April and June 2023. Methods: A retrospective analysis of antibacterial sensitivity test (ABST) reports from canine clinical samples submitted to the Small Animal Clinic at St. George’s University (SGU), St. George’s, Grenada, between 2010 and 2020 revealed a notable prevalence of AMR among canine E. coli isolates. To further investigate the underlying mechanisms of this resistance, the study analyzed canine E. coli isolates that exhibited phenotypic resistance in ABST assays. These isolates were subsequently screened for AMR-associated genes using polymerase chain reaction (PCR) and next-generation sequencing (NGS). Results: The retrospective study identified 153 canine clinical isolates positive for E. coli. The antimicrobial drugs, imipenem, cefotaxime and ciprofloxacin were found to be highly effective against these isolates. However, a gradual increase in AMR was observed for amoxicillin–clavulanic acid (34.88%), ampicillin–sulbactam (17.31%), cephalexin (43.08%), cefpodoxime (22.31%), cephalothin (68.42%), and doxycycline (37.04%). In the prospective study, PCR analysis of resistant canine E. coli isolates detected the tetA (577 bp) and blaTEM (686 bp) genes. These AMR determinants were further confirmed through analysis of NGS reads and assembled contigs. Additionally, NGS-based predictions identified genes associated with resistance to aminoglycosides and potentiated sulfonamides. Conclusions: This study demonstrates that E. coli from dogs in Grenada exhibits resistance to tetracycline and several β-lactam antimicrobials. These findings underscore the need for rational antimicrobial stewardship and continuous AMR surveillance in small animal practice within the region. Full article

A multilayer gradient composite membrane was fabricated on a PES ultrafiltration substrate through layer-by-layer assembly of chitosan (CS) and montmorillonite (MMT), followed by Ca²⁺ crosslinking. The designed architecture forms a multi-layer gradient composite membrane through successive self-assembly, aiming to balance adsorption, interfacial transport and structural stability. SEM observations showed a clear stratified configuration with relatively uniform thickness distribution, including a relatively dense MMT-rich surface layer and a porous PES support that preserved mass-transfer channels. FTIR confirmed the introduction of hydroxyl/amino-containing CS and aluminosilicate-related MMT species onto the membrane surface, indicating successful incorporation of both organic and inorganic components. TG–DTG results further suggested enhanced thermal stability arising from the cooperative effect of the inorganic lamellae and the polymer framework. In dynamic tests, the membrane displayed concentration-responsive adsorption behavior toward gatifloxacin, ciprofloxacin and ofloxacin, and different pollutants reached equilibrium or quasi-steady states at different rates. Comparative kinetic results at the same initial concentration showed that diclofenac, gatifloxacin and ciprofloxacin approached stable plateaus much faster, whereas ofloxacin increased slowly and did not reach an obvious plateau within the tested period. These results indicate that pollutant removal was jointly governed by interfacial interactions, gradient-layer diffusion resistance and overall transport behavior rather than by concentration alone. Overall, the layer-by-layer strategy provided a controllable route for constructing gradient functional layers on PES membranes, demonstrating potential for advanced treatment of antibiotic-containing wastewater and related pharmaceutical effluents. Full article

Background: Biofilm-associated urinary tract infections (UTIs) pose a significant therapeutic challenge due to the increased tolerance of biofilm-embedded bacteria to antimicrobial agents and the high risk of infection recurrence. The increasing prevalence of multidrug-resistant uropathogens necessitates the evaluation of alternative therapeutic strategies, including antibiotic combination therapy. This study aimed to assess the antibiofilm activity of selected antibiotics used individually and in combination against biofilms formed by clinically relevant uropathogens. Methods: Biofilms of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Enterococcus faecalis isolated from patients with UTIs were developed on polystyrene microtiter plates and exposed to ciprofloxacin, nitrofurantoin, amikacin, and imipenem applied as monotherapy and in combinations. Biofilm biomass reduction was quantified spectrophotometrically using crystal violet staining and expressed as a percentage relative to untreated controls. Results: Antibiotic monotherapy produced moderate reductions in biofilm biomass, with efficacy dependent on bacterial species and antibiotic concentration. In contrast, antibiotic combinations demonstrated enhanced antibiofilm activity. The ciprofloxacin–nitrofurantoin combination showed increased biofilm biomass reduction compared with monotherapy against P. aeruginosa and E. coli. The imipenem–amikacin combination reduced P. mirabilis biofilm biomass by over 80%. Conclusions: These findings suggest that rationally selected antibiotic combinations may represent a more effective strategy than monotherapy for controlling biofilm-associated UTIs. Full article

Objectives: To examine the long-term trends in antimicrobial resistance (AMR) among major Gram-negative pathogens including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa collected from inpatient and outpatient specimens in Mubarak Al-Kabeer Hospital in Kuwait from 2007 to 2022. Methods: The antimicrobial resistance data for 39,200 non-duplicate Gram-negative isolates were collected from the Hospital Laboratory Information System (LIS). Retrospectively antibiotic susceptibility data were interpreted according to Clinical and Laboratory Standards Institute (CLSI) breakpoints with intermediate results classified as resistant. Logistic regression was applied to assess temporal trends in resistance for the following antibiotic cefotaxime, ceftazidime, ciprofloxacin, meropenem and imipenem. False discovery rate (FDR) correction was performed for multiple comparisons. Results: Third-generation cephalosporin resistance increased significantly, from 27% to 60% in Klebsiella pneumoniae and from 19% to 45% in Escherichia coli. Resistance to ciprofloxacin also increased, from 22% to 49% in K. pneumoniae and from 28% to 41% in E. coli. Notably, meropenem resistance in K. pneumoniae increased from 1% to 35% during the study period. Acinetobacter baumannii showed high resistance to most antibiotics (>75%), while colistin retained good activity (<2% resistance). By contrast, Pseudomonas aeruginosa showed relatively stable resistance patterns with only modest changes in susceptibility to key antibiotics. Conclusions: From 2007 to 2022, increasing resistance among major Gram-negative pathogens was observed, with cefotaxime resistance rising from 27% in 2007 to 60% in 2022 in Klebsiella pneumoniae and from 19% to 45% in Escherichia coli. Resistance to ciprofloxacin also increased over time. These findings highlight the increasing burden of antimicrobial resistance over time and emphasize the need for continued surveillance. Full article

Pasteurellosis is a major bacterial disease of domestic rabbits, commonly associated with respiratory disorders, abscesses, reproductive pathology, and systemic infections. This study investigated the occurrence, clinical manifestations, pathological lesions, and antimicrobial susceptibility of bacterial isolates obtained from rabbits raised in traditional extensive systems in western Romania, with identification of Pasteurella multocida performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A total of 308 rabbits from 23 holdings were clinically examined, necropsied when applicable, and subjected to bacteriological analysis. Clinical signs compatible with pasteurellosis were observed in 132 rabbits (42.9%), including respiratory diseases, abscess formation, otitis, and reproductive disorders. Samples collected from affected and deceased rabbits were cultured and analyzed using MALDI-TOF MS, confirming 87 isolates as P. multocida. Antimicrobial susceptibility testing using the VITEK 2 system revealed high resistance to tetracyclines (63.22%) and beta-lactams (55.17%), while higher susceptibility was observed for enrofloxacin (91.95%), gentamicin (89.66%), ciprofloxacin (86.21%), and florfenicol (80.46%). The presence of multidrug-resistant isolates highlights the need for laboratory-guided antimicrobial therapy and improved biosecurity measures in traditional rabbit holdings. Full article

This study used three complementary datasets to investigate the relationship between human Campylobacter infections in Estonia and potential sources. A targeted dataset of 15 C. jejuni genomes with overlapping sequence types from human cases and broiler chicken meat was analysed using genotyping and in silico antimicrobial resistance profiling, alongside 20 human isolates for source attribution. Additionally, 12,111 isolates were analysed to provide population-level context. The core genome multilocus sequence typing showed a high similarity (less than three allelic differences) between the human and broiler isolates of ST122, ST464, and ST7355, indicating poultry as a likely source, whereas ST9882 was more divergent (13–18 allelic differences). The resistance profiles were consistent within ST122, ST464, and ST7355, and all were resistant to ciprofloxacin, nalidixic acid, ampicillin, and tetracycline, while ST9882 additionally exhibited aminoglycoside (streptomycin) resistance. The source attribution linked 77.8% of the human cases to chicken and 22.2% to cattle. A novel genotype, ST11001, was identified in humans and attributed to cattle source, while C. coli isolates were linked to birds and sheep. Poultry dominated the larger dataset (87.3%). Gastroenteritis was the predominant clinical presentation (98.5%), whereas ST22 and ST122 were associated with Guillain–Barré syndrome. These findings support poultry as a major reservoir of human Campylobacter infections and highlight the need for coordinated cross-border surveillance. Full article

Ciprofloxacin (CIP) is a persistent fluoroquinolone antibiotic frequently detected in water bodies, and its efficient mineralization remains a challenge in wastewater treatment. In this work, iron oxide–chitosan macroporous nanocomposite hydrogels were developed as heterogeneous catalysts for the electro-Fenton degradation of CIP. The materials were synthesized via Pickering high internal phase emulsion templating, yielding monoliths with a three-dimensional interconnected porous structure, an average pore size of 18.9 ± 0.7 µm, a window size of 8.1 ± 0.7 µm, an openness degree of 39.6%, a specific surface area of 1.77 m² g⁻¹, an iron content of 64.2 mg g⁻¹, and a crosslinking degree of 92.1%. The monoliths exhibited controlled swelling in aqueous medium at pH 3, with a gravimetric water uptake of 142.1 ± 2.3% and a volumetric swelling of 39.3 ± 1.2% at equilibrium. Iron oxide particles remained exposed on the porous surface, providing accessible catalytic sites, while the interconnected porosity favored reactant diffusion. Compared with direct anodic oxidation, which achieved 32% total organic carbon removal after 20 min, the heterogeneous electro-Fenton process using the synthesized monoliths as catalysts showed superior performance, reaching nearly 95% removal within 2 min and complete mineralization within 15 min. This enhanced performance was associated with higher hydroxyl radical generation (~3.5 µM) than that observed for anodic oxidation alone (~1.5 µM). These findings highlight the potential of biodegradable iron oxide–chitosan macroporous hydrogels as sustainable catalysts for antibiotic removal from water. Full article

During the COVID-19 pandemic carbapenem-resistant Acinetobacter baumannii (CRAB) was found to be the major pathogen associated with ventilator-associated pneumonia in mechanically ventilated patients. This prompted us to analyze the post-pandemic mechanisms of carbapenem resistance, antibiotic resistance trends, and molecular epidemiology of CRAB in Croatia. In total, 94 CRAB isolates from two hospital centers, including outpatient settings, were investigated. Antimicrobial susceptibility testing was performed by broth microdilution. PCR was used to detect genes encoding carbapenemases of group A, B and D and extended-spectrum β-lactamases (ESBL). Randomly selected isolates were subjected to whole resistome analysis by Inter-array CarbaResist Kit and whole-genome sequencing (WGS). Phylogenetic tree and sequence types (STs) were retrieved from WGS. Plasmid incompatibility groups were determined by PCR-based replicon typing (PBRT). All isolates were extensively drug resistant (XDR), showing resistance to ceftazidime, cefepime, piperacillin–tazobactam, imipenem, meropenem, gentamicin, amikacin and ciprofloxacin, and 13% (n = 12) were also resistant to colistin. The Hodge and CIM test exhibited poor sensitivity with only 32 and 30% of isolates being identified as carbapenemase producers, respectively. PCR identified bla_OXA-23 as the dominant carbapenemase gene in both hospitals, found in 71% of the isolates (67/94). In an outpatient setting, bla_OXA-24/40 was dominant. bla_OXA-23 and bla_OXA-72 were the only allelic variants. The Inter-array CarbaResist Kit and whole-genome sequencing (WGS) identified a variety of aminoglycoside (armA, ant(3″)-IIa, aph(3″)-Ib, aph(6)-Id) and sulphonamide resistance (sul1 and sul2) genes. The representative bla_OXA-23-positive isolates belonged to ST2, while bla_OXA-72-positive isolates were allocated to ST492. These data show that there are different populations of XDR A. baumannii between hospital and outpatients. Full article

Background/Objectives: Drug-induced hypersensitivity and cardiotoxicity are important yet often underrecognized clinical concerns, and fluoroquinolones are widely used antibiotics with well-documented safety issues. Given the limited systematic evidence and underreporting in pharmacovigilance databases, this study explored a potential association between fluoroquinolones and Kounis syndrome (KS) and the possibility of a class-related effect. Methods: This retrospective descriptive study analyzed individual case safety reports from VigiBase, complemented by published case reports to capture additional cases not recorded in the database. All fluoroquinolones reported as suspected drugs in KS cases were included, and a systematic search of major literature databases was undertaken to identify further case-level evidence. Quantitative data were explored using VigiLyze, while qualitative clinical data were extracted for case characterization. Literature cases underwent Naranjo assessment, and the overall body of evidence was evaluated using a qualitative Bradford Hill framework. Results: A descriptive disproportionality signal for fluoroquinolones was identified in VigiBase (IC₀₂₅ = 1.3). Seventeen cases of fluoroquinolone-associated KS were identified across VigiBase and the published literature, all originating from unsolicited sources. Most cases involved ciprofloxacin and levofloxacin, whereas other fluoroquinolones were only rarely reported. Across cases, a consistent clinical pattern was observed, including a clear temporal relationship between drug exposure, allergic manifestations, and acute coronary events, compatible with hypersensitivity-mediated coronary involvement. Conclusions: KS cases associated with several fluoroquinolones were identified in pharmacovigilance data and the published literature, with the most consistent evidence observed for ciprofloxacin and levofloxacin. Although a class effect was not confirmed, a potential association cannot be excluded. These findings should be interpreted as hypothesis-generating, and further research is required to clarify underlying mechanisms, drug-specific risks, and clinical relevance. Full article

The bactericidal mechanisms of fluoroquinolones extend beyond their canonical inhibition of DNA topoisomerases, yet the associated metabolic perturbations remain incompletely understood. In this study, we systematically investigated the metabolic responses of Escherichia coli to three representative FQs—ofloxacin, enrofloxacin, and ciprofloxacin—using untargeted UPLC–Q Exactive Orbitrap–MS-based metabolomics. Bacterial cells were exposed to bactericidal concentrations (2 × MIC) for a single-time point (1 h), followed by comprehensive metabolomic profiling with six biological replicates per group. Our findings demonstrate that FQ-induced metabolic reprogramming serves as a primary driver of oxidative stress and nucleic acid damage, rather than a mere secondary effect. All three FQs induced substantial metabolic reprogramming characterized by disruptions in nucleotide biosynthesis, central carbon metabolism, and redox-related pathways, with notable drug-specific differences. Ciprofloxacin exhibited the most pronounced suppression of energy metabolism and antioxidant systems, whereas ofloxacin and enrofloxacin showed partial compensatory metabolic responses. Consistently, intracellular ROS levels were significantly elevated in all treatment groups, and this effect was attenuated by antioxidant supplementation. Furthermore, increased accumulation of 8-hydroxydeoxyguanosine and 8-hydroxyguanosine confirmed the occurrence of oxidative DNA and RNA damage. Collectively, these findings indicate that FQs induce distinct metabolic perturbations that are closely associated with oxidative stress and nucleic acid damage, providing a metabolic perspective on their bactericidal activity and suggesting potential targets for metabolic adjuvant strategies. Full article

Background: Fluoroquinolone prophylaxis during autologous stem cell transplantation (aSCT) reduces the risk of fever but raises the risk of bloodstream infection (BSI) with fluoroquinolone-resistant Enterobacterales (FRE). We performed a prospective cohort study to detect the presence and potential gain or loss of colonic FRE colonization using serial sampling before and after aSCT in a uniform population of patients with a diagnosis of multiple myeloma. Methods: Eligible subjects underwent aSCT after conditioning with dose-intense melphalan, 200 mg/m². Peri-anal swabs were obtained before aSCT, upon hospital discharge, and 12–16 weeks after transplantation. Samples were cultured in tryptic soy broth supplemented with either ciprofloxacin or ceftriaxone with subsequent plating onto selective chromogenic agar designed to facilitate recovery and differentiation of Enterobacterales. Results: FRE colonization on pre-transplant sampling was detected for 23 of 117 subjects (19.7%) and 29 of 98 (29.6%) subjects at hospital discharge after a course of fluoroquinolone (116/117 subjects) prophylaxis (p < 0.001) and 28 of 92 (30.4%) subjects at 12–16 weeks. Including all three sampling time points, 48 of 117 subjects (41.0%) tested positive for FRE colonization. In total, 58 of the 90 FRE isolates (64.4%) from 48 subjects expressed extended-spectrum beta-lactamase (ESBL). Three FRE-colonized subjects developed FRE BSI. Bloodstream isolates for two subjects were identical to the organisms identified on pre-transplant sampling. Conclusions: We hypothesize that fluoroquinolone prophylaxis of subjects with undetected low levels of FRE colonization allows the expansion of the FRE population, placing subjects at risk of BSI with fluoroquinolone-resistant (and ESBL-expressing) Enterobacterales. Pre-transplant testing for FRE colonization permits patient-specific design of prophylactic and empiric antibiotic regimens. Full article

Staphylococcus aureus is a common opportunistic pathogen in rabbits and may cause localized or systemic infections that affect animal health and farm productivity. The present study aimed to investigate the clinical evolution, pathological lesions, and antimicrobial susceptibility profile of S. aureus infections in rabbits raised under traditional extensive systems in Western Romania. A total of 251 rabbits from 11 holdings located in Arad, Timiș, and Caraș-Severin counties were evaluated through epidemiological investigation, clinical examination, necropsy, and bacteriological analysis. Samples were cultured on Brain Heart Infusion medium and 5% sheep blood agar, and isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using an automated system (VITEK 2, bioMérieux) and interpreted according to EUCAST guidelines. Among the examined animals, 68 rabbits (27.1%) showed clinical lesions compatible with S. aureus infection. The most common manifestations included subcutaneous abscesses, otitis externa, rhinitis, mammary abscesses, pyometra, and dental abscesses. Necropsy revealed suppurative and septicemic lesions affecting multiple organs. Antimicrobial susceptibility testing indicated high resistance to penicillin (100%), tetracycline (76.5%), doxycycline (67.6%), and amoxicillin (63.2%). In contrast, florfenicol (69.1% susceptible), ciprofloxacin (61.8%), gentamicin (54.4%), and enrofloxacin (52.9%) showed better antimicrobial activity. The results confirm the clinical and microbiological relevance of S. aureus infections in rabbits raised under traditional conditions and highlight the need for improved biosecurity measures and rational antimicrobial use. Full article

Antibiotic resistance (ABR) is a significant threat to human and animal health, as well as to the environment. Antibiotic residues, antibiotic-resistant bacteria and antibiotic resistance genes are emerging contaminants of water resources. The present study aimed to assess the prevalence of ABR among waterborne enterococci in an anthropogenic-affected section of the Yantra River (Bulgaria). The susceptibility of 426 strains to 13 antibiotics (ABs) was tested by the disk diffusion method, and the genes encoding resistance by PCR analyses. A total of 39% of isolates were found to be antibiotic-resistant, with 9% mainly being multidrug-resistant to three AB classes. The most common resistance was to erythromycin (19%), tetracycline (18%) and ampicillin (14%), encoded by the ermB, tetM and blaTEM genes. A total of 3% of isolates were ciprofloxacin-resistant and only 1% was resistant to vancomycin or high-level gentamicin. All isolates were susceptible to teicoplanin and linezolid. Spatial variations in ABR levels were found, with the lowest abundance of antibiotic-resistant enterococci occurring in upstream river waters, away from urban areas, and the highest in urban areas. The spread of waterborne antibiotic-resistant enterococci highlights the need for water pollution management, monitoring and control to limit anthropogenic pressures through wastewater discharges and diffuse fecal pollution, and to ensure the ecological well-being of receiving waters. Full article

Background/Objectives: Antimicrobial conjugates have attracted considerable interest in addressing the threat of antimicrobial resistance by minimising the likelihood of resistance onset. Antimicrobial peptide mimic–antibiotic conjugates offer a unique strategy to revitalise current clinical agents through increased membrane permeabilisation, prolonging the longevity of traditional antibiotics while broadening the spectrum of activity of the AMP mimic. Methods: This study explored non-cleavable, enzyme-cleavable, and pH-cleavable linked conjugates between an anthranilamide-based peptide mimic and current clinically available antibiotics to assess the viability of conjugation in enhancing antimicrobial activity as measured through MIC assays. Cleavage studies were conducted to assess the stimulus susceptibility of relevant compounds. Results: Four amide-linked non-cleavable conjugates were synthesised. Of these, a primary amide-linked conjugate between ciprofloxacin and the peptidomimetic had the most significant activity with an MIC of 15.6 µM towards Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, and an MIC of 7.8 µM towards Gram-negative Escherichia coli. A hydrazone-based pH-sensitive linker system was synthesised and had an MIC of 15.6 µM towards Gram-negative E. coli. Finally, an enzyme-cleavable cephalosporin conjugate system was investigated, which offered a unique method for the specific treatment of resistant bacterial strains. Cleavage studies of this conjugate suggested rapid degradation of the β-lactam ring and release of the subunit. Conclusions: This work presents conjugate systems between peptide mimics and antibiotics as a new, promising strategy to broaden the antimicrobial spectrum of novel antimicrobial agents. Full article