The effect of combinations of a glyphosate-based herbicide with various clinically used antibiotics on phenotypic traits of Gram-negative species from the ESKAPEE group.

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Exploring antibiotic-induced persister formation and bacterial persistence genes in clinical isolates from Burkina Faso.

BACKGROUND: In addition to antibiotic resistance, persistence is another cause of treatment failure in bacterial infections, representing a significant public health concern. Due to a lack of adequate data on clinical isolates, this study was initiated to investigate persistence in clinical isolates in Burkina Faso. METHODS: Eighty (80) clinical isolates, including 32 Pseudomonas aeruginosa, 41 Staphylococcus aureus, and 7 Salmonella sp. obtained from clinical laboratories in Burkina Faso, were analyzed to assess their susceptibility to ciprofloxacin and gentamicin, as well as to determine the presence of persistence genes. The effects of ciprofloxacin and gentamicin on persister formation were evaluated by conducting colony counts at 1, 3, 5, 7, and 20 h after exposing the bacteria to high concentrations of these antibiotics. RESULTS: Results showed high sensitivity to both antibiotics (72.5% for ciprofloxacin and 82.5% for gentamicin). Persister formation occurred in Staphylococcus aureus with gentamicin and in Salmonella sp. with ciprofloxacin, while Pseudomonas aeruginosa did not form persisters. The mazF gene was found in 28.13% of P. aeruginosa and 2.44% of S. aureus isolates, and the hipA gene in 28.57% of Salmonella sp. None of the relE1 or relE2 genes were detected. CONCLUSIONS: The study revealed high sensitivity in clinical bacterial isolates to ciprofloxacin and gentamicin. Staphylococcus aureus and Salmonella sp. showed persister formation under antibiotic stress, with low frequencies of the studied persistence genes. These findings enhance understanding of clinical bacterial behavior and inform strategies against antibiotic-resistant infections.

Desorption hysteresis of antibiotics on biochar produced at high temperature: The role of amine groups and amidation reaction.

Knowledge of antibiotic desorption from high-temperature biochar is essential for assessing their environmental risks, and for the successful application of biochar to remove antibiotics. In previous studies, irreversible pore deformation, formation of charge-assisted hydrogen bonds or amide bonds were individually proposed to explain the desorption hysteresis of antibiotics on biochars, leading to a debate on hysteresis mechanism. In this study, desorption of sulfamethoxazole (SMX), ciprofloxacin (CFX) and tetracycline (TET) on a wood chip biochar produced at 700 °C (WBC700) and its oxidized product (O-WBC700) was investigated to explore the underlying hysteresis mechanism. Significant desorption hysteresis was observed for SMX, CFX and TET on WBC700 and O-WBC700. Hysteresis index (HI) of each antibiotic was higher on O-WBC700 with more oxygen-containing groups than WBC700, and was higher at lower equilibrium concentration. HI of antibiotics on WBC700 (or O-WBC700) increased in the order of SMX < CFX < TET. The calculated adsorption enthalpy of each antibiotic on WBC700 was positive, indicating an endothermic process. These phenomena together with FTIR, XPS spectra confirmed that the desorption hysteresis mechanism of antibiotics on high-temperature biochar is the formation of amide bonds by amidation reaction, but not the pore deformation or the hydrogen bond. Moreover, antibiotic can form amide bonds with WBC700 only if the amine group with pKa > 4.0, and the HI values were positively correlated with their pKa values. Amine group of antibiotics with higher pKa value show more nucleophilicity and could form stronger amide bonds with carboxyl group of biochar. The obtained results could help to solve the debate on desorption hysteresis mechanism of antibiotics on high-temperature biochars, and provide a new insight into the role of amine groups and amidation reaction on the hysteresis.

Investigation on the Synergy between Membrane Permeabilizing Amphiphilic α-Hydrazido Acids and Commonly Used Antibiotics against Drug-Resistant Bacteria.

The growth of (multi)drug resistance in bacteria is among the most urgent global health issues. Monocationic amphiphilic α-hydrazido acid derivatives are structurally simple mimics of antimicrobial peptides (AMPs) with fewer drawbacks. Their mechanism of membrane permeabilization at subtoxic concentrations was found to begin with an initial electrostatic attraction of isolated amphiphile molecules to the phospholipid heads, followed by a rapid insertion of the apolar portions. As the accumulation into the bilayer proceeded, the membrane increased its fluidity and permeability without being subjected to major structural damage. After having ascertained that α-hydrazido acid amphiphiles do not interact with bacterial DNA, they were subjected to synergy evaluation for combinations with conventional antibiotics. Synergy was observed for combinations with tetracycline against sensitive S. aureus and E. coli, as well as with ciprofloxacin and colistin against resistant strains. Additivity with a remarkable recovery in activity of conventional antibiotics (from 2-fold to ≥32-fold) together with largely subtoxic concentrations of α-hydrazido acid derivatives was found for combinations with ciprofloxacin toward susceptible S. aureus and methicillin toward MRSa. However, no potentiation of conventional antibiotics was observed for combinations with linezolid and gentamicin against the corresponding resistant S. aureus and E. coli strains.

Heterogeneous Photocatalytic Degradation of Selected Pharmaceuticals and Personal Care Products (PPCPs) Using Tungsten Doped TiO2: Effect of the Tungsten Precursors and Solvents.

Pharmaceuticals and personal care products (PPCPs) which include antibiotics such as tetracycline (TC) and ciprofloxacin (CIP), etc., have attracted increasing attention worldwide due to their potential threat to the aquatic environment and human health. In this work, a facile sol-gel method was developed to prepare tungsten-doped TiO2 with tunable W5+/W6+ ratio for the removal of PPCPs. The influence of solvents in the synthesis of the three different tungsten precursors doped TiO2 is also taken into account. WCl6, ammonium metatungstate (AMT), and Na2WO4●2H2O not only acted as the tungsten precursors but also controlled the tungsten ratio. The photocatalyst prepared by WCl6 as the tungsten precursor and ethanol as the solvent showed the highest photodegradation performance for ciprofloxacin (CIP) and tetracycline (TC), and the photodegradation performance for tetracycline (TC) was 2.3, 2.8, and 7.8 times that of AMT, Na2WO4●2H2O as the tungsten precursors and pristine TiO2, respectively. These results were attributed to the influence of the tungsten precursors and solvents on the W5+/W6+ ratio, sample crystallinity and surface properties. This study provides an effective method for the design of tungsten-doped TiO2 with tunable W5+/W6+ ratio, which has a profound impact on future studies in the field of photocatalytic degradation of PPCPs using an environmentally friendly approach.

Preparation of Multistage Pore TS-1 with Enhanced Photocatalytic Activity, Including Process Studies and Artificial Neural Network Modeling for Synergy Assessment.

Antibiotic residues have been found in several aquatic ecosystems as a result of the widespread use of antibiotics in recent years, which poses a major risk to both human health and the environment. At present, photocatalytic degradation is the most effective and environmentally friendly method. Titanium silicon molecular sieve (TS-1) has been widely used as an industrial catalyst, but its photocatalytic application in wastewater treatment is limited due to its small pores and few active sites. In this paper, we report a method for preparing multistage porous TS-1 with a high specific surface area by alkali treatment. In the photocatalytic removal of CIP (ciprofloxacin) antibiotic wastewater experiments, the alkali-treated catalyst showed better performance in terms of interfacial charge transfer efficiency, which was 2.3 times higher than that of TS-1 synthesized by the conventional method, and it was found to maintain better catalytic performance in the actual water source. In addition, this research studied the effects of solution pH, contaminant concentration, and catalyst dosage on CIP degradation, while liquid chromatography-mass spectrometry (LC-MS) was used to identify intermediates in the degradation process and infer possible degradation pathways and the toxicity of CIP, and its degradation product was also analyzed using ECOSAR 2.2 software, and most of the intermediates were found to be nontoxic and nonharmful. Finally, a 3:5:1 artificial neural network model was established based on the experiments, and the relative importance of the influence of experimental conditions on the degradation rate was determined. The above results confirmed the feasibility and applicability of photocatalytic treatment of wastewater containing antibiotics using visible light excitation alkali post-treatment TS-1, which provided technical support and a theoretical basis for the photocatalytic treatment of wastewater containing antibiotics.

Green synthesis of polyethylene glycol coated, ciprofloxacin loaded CuO nanoparticles and its antibacterial activity against Staphylococcus aureus.

Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment.

Differential effects of polystyrene microplastics on the adsorption of cadmium and ciprofloxacin by tea leaf litter-derived magnetic biochar: Influencing factors and mechanisms.

Water pollution involves the coexistence of microplastics (MPs) and traditional pollutants, and how can MPs influence the adsorption of other pollutants by biochar during the treatment process remains unclear. This study aimed to investigate the influence of polystyrene microplastics (PS MPs) on the adsorption of cadmium (Cd) and ciprofloxacin (CIP) by magnetic biochar (MTBC) in the single and binary systems. MTBC was prepared using tea leaf litter; the effects of time, pH, and salt ions on the adsorption behaviors were investigated; and X-ray photoelectronic spectroscopy (XPS) and density flooding theory analysis were conducted to elucidate the influence mechanisms. Results indicated that PS MPs reduced the pollutants adsorption by MTBC due to the heterogeneous aggregation between PS MPs and MTBC and the surface charge change of MTBC induced by PS MPs. The effects of PS MPs on heavy metals and antibiotics adsorption were distinctly different. PS MPs reduced Cd adsorption on MTBC, which were significantly influenced by the solution pH and salt ions contents, suggesting the participation of electrostatic interaction and ion exchange in the adsorption, whereas the effects of PS MPs on CIP adsorption were inconspicuous. In the hybrid system, PS MPs reduced pollutants adsorption by MTBC with 66.3% decrease for Cd and 12.8% decrease for CIP, and the more remarkable reduction for Cd was due to the predominated physical adsorption, and CIP adsorption was mainly a stable chemisorption. The influence of PS MPs could be resulted from the interaction between PS MPs and MTBC with changing the functional groups and electrostatic potential of MTBC. This study demonstrated that when using biochar to decontaminate wastewater, it is imperative to consider the antagonistic action of MPs, especially for heavy metal removal. PRACTITIONER POINTS: Magnetic biochar (MTBC) was prepared successfully using tea leaf litter. MTBC could be used for cadmium (Cd) and ciprofloxacin (CIP) removal. Polystyrene microplastics (Ps MPs) reduced Cd/CIP adsorption by MTBC. Ps MPs effects on Cd adsorption were more obvious than that of CIP. Ps MPs changed the functional groups and electrostatic potential of MTBC, thus influencing MTBC adsorption.

Comparative evaluation of antimicrobial efficacy of various intracanal medicament in young permanent teeth: An in vivo study.

INTRODUCTION: Bacteria and their byproducts are key contributors to the onset and perpetuation of pulpoperiapical pathosis. Intracanal medication is vital in achieving successful endodontic outcomes as it targets and eradicates remaining microorganisms following biomechanical preparation. AIM AND OBJECTIVE: The aim of the study was to compare and evaluate the antimicrobial efficacy of calcium hydroxide (CH) paste, triple antibiotic paste (TAP), and probiotics (PBs) as intracanal medicament in 12-17-year-old children undergoing root canal treatment for the management of infected pulpal tissues in young permanent teeth. MATERIALS AND METHODS: A total of 30 patients aged 12-17 years indicated for endodontic therapy in maxillary incisors and with no systemic complications were selected. They were randomly divided into three groups, i.e., Group I - CH group, Group II - TAP, and Group III - PB allocating 10 teeth in each group. After access opening, the first sample (S1) was collected by inserting a paper point into the root canal, the second sample (S2) was collected immediately after biomechanical preparation, and the third sample (S3) was collected after 7 days, i.e., postintracanal medication. Samples were sent for microbiological analysis to assess the microbial count, and statistical analysis was done for the obtained data. RESULTS: The three intracanal medicaments were successful in reducing the microbial counts of Enterococcus faecalis in the infected root canals. However, according to the results of the study, the PB group demonstrated greater effectiveness against E. faecalis compared to the CH group and displayed similar antimicrobial efficacy as the TAP group. CONCLUSION: PB exhibited antimicrobial efficacy comparable to TAP but greater than Ca (OH) 2 paste. Hence, PB can be utilized as an intracanal medicament in young permanent teeth.

Mutations in the efflux regulator gene oqxR provide a simple genetic switch for antimicrobial resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae is a pathogen of major concern in the global rise of antimicrobial resistance and has been implicated as a reservoir for the transfer of resistance genes between species. The upregulation of efflux pumps is a particularly concerning mechanism of resistance acquisition as, in many instances, a single point mutation can simultaneously provide resistance to a range of antimicrobials and biocides. The current study investigated mutations in oqxR, which encodes a negative regulator of the RND-family efflux pump genes, oqxAB, natively found in the chromosome of K. pneumoniae. Resistant mutants in four K. pneumoniae strains (KP6870155, NTUH-K2044, SGH10, and ATCC43816) were selected from single exposures to 30 µg/mL chloramphenicol and 12 mutants were selected for whole genome sequencing to identify mutations associated with resistance. Resistant mutants generated by single exposures to chloramphenicol, tetracycline, or ciprofloxacin at ≥4 X MIC were replica plated onto all three antibiotics to observe simultaneous cross-resistance to all compounds, indicative of a multidrug resistance phenotype. A variety of novel mutations, including single point mutations, deletions, and insertions, were found to disrupt oqxR leading to significant and simultaneous increases in resistance to chloramphenicol, tetracycline, and ciprofloxacin. The oqxAB-oqxR locus has been mobilized and dispersed on plasmids in many Enterobacteriaceae species and the diversity of these loci was examined to evaluate the evolutionary pressures acting on these genes. Comparison of the promoter regions of oqxR in plasmid-borne copies of the oqxR-oqxAB operon indicated that some constructs may produce truncated versions of the oqxR transcript, which may impact on oqxAB regulation and expression. In some instances, co-carriage of chromosomal and plasmid encoded oqxAB-oqxR was found in K. pneumoniae, implying that there is selective pressure to maintain and expand the efflux pump. Given that OqxR is a repressor of oqxAB, any mutation affecting its expression or function can lead to multidrug resistance. This is in contrast to antibiotic target site mutations that must occur in limited sequence space to be effective and not impact the fitness of the cell. Therefore, oqxR may act as a simple genetic switch to facilitate resistance via OqxAB mediated efflux.

The fluoroquinolones may positively affect tendon healing after surgical repair.

OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.

Infection Inspection: using the power of citizen science for image-based prediction of antibiotic resistance in Escherichia coli treated with ciprofloxacin.

Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its threat. This study uses citizen science and image feature analysis to profile the cellular features associated with antibiotic resistance in Escherichia coli. Between February and April 2023, we conducted the Infection Inspection project, in which 5273 volunteers made 1,045,199 classifications of single-cell images from five E. coli strains, labelling them as antibiotic-sensitive or antibiotic-resistant based on their response to the antibiotic ciprofloxacin. User accuracy in image classification reached 66.8 ± 0.1%, lower than our deep learning model's performance at 75.3 ± 0.4%, but both users and the model were more accurate when classifying cells treated at a concentration greater than the strain's own minimum inhibitory concentration. We used the users' classifications to elucidate which visual features influence classification decisions, most importantly the degree of DNA compaction and heterogeneity. We paired our classification data with an image feature analysis which showed that most of the incorrect classifications happened when cellular features varied from the expected response. This understanding informs ongoing efforts to enhance the robustness of our diagnostic methodology. Infection Inspection is another demonstration of the potential for public participation in research, specifically increasing public awareness of antibiotic resistance.

Ciprofloxacin Accelerates Angiotensin-II-Induced Vascular Smooth Muscle Cells Senescence Through Modulating AMPK/ROS pathway in Aortic Aneurysm and Dissection.

Aortic aneurysm and dissection (AAD) is a cardiovascular disease that poses a severe threat to life and has high morbidity and mortality rates. Clinical and animal-based studies have irrefutably shown that fluoroquinolones, a commonly prescribed antibiotic for treating infections, significantly increase the risk of AAD. Despite this, the precise mechanism by which fluoroquinolones cause AAD remains unclear. Therefore, this study aims to investigate the molecular mechanism and role of Ciprofloxacin definitively-a type of fluoroquinolone antibiotic-in the progression of AAD. Aortic transcriptome data were collected from GEO datasets to detect the genes and pathways expressed differently between healthy donors and AAD patients. Human primary Vascular Smooth Muscle Cells (VSMCs) were isolated from the aorta. After 72 h of exposure to 110ug/ml Ciprofloxacin or 100 nmol/L AngII, either or combined, the senescent cells were identified through SA-ß-gal staining. MitoTracker staining was used to examine the morphology of mitochondria in each group. Cellular Reactive Oxygen Species (ROS) levels were measured using MitoSox and DCFH-DA staining. Western blot assay was performed to detect the protein expression level. We conducted an analysis of transcriptome data from both healthy donors and patients with AAD and found that there were significant changes in cellular senescence-related signaling pathways in the latter group. We then isolated and identified human primary VSMCs from healthy donors (control-VSMCs) and patients' (AAD-VSMCs) aortic tissue, respectively. We found that VSMCs from patients exhibited senescent phenotype as compared to control-VSMCs. The higher levels of p21 and p16 and elevated SA-ß-gal activity demonstrated this. We also found that pretreatment with Ciprofloxacin promoted angiotensin-II-induced cellular senescence in control-VSMCs. This was evidenced by increased SA-ß-gal activity, decreased cell proliferation, and elevation of p21 and p16 protein levels. Additionally, we found that Angiotensin-II (AngII) induced VSMC senescence by promoting ROS generation. We used DCFH-DA and mitoSOX staining to identify that Ciprofloxacin and AngII pretreatment further elevated ROS levels than the vehicle or alone group. Furthermore, JC-1 staining showed that mitochondrial membrane potential significantly declined in the Ciprofloxacin and AngII combination group compared to others. Compared to the other three groups, pretreatment of Ciprofloxacin plus AngII could further induce mitochondrial fission, demonstrated by mitoTracker staining and western blotting assay. Mechanistically, we found that Ciprofloxacin impaired the balance of mitochondrial fission and fusion dynamics in VSMCs by suppressing the phosphorylation of AMPK signaling. This caused mitochondrial dysfunction and ROS generation, thereby elevating AngII-induced cellular senescence. However, treatment with the AMPK activator partially alleviated those effects. Our data indicate that Ciprofloxacin may accelerate AngII-induced VSMC senescence through modulating AMPK/ROS signaling and, subsequently, hasten the progression of AAD.

Construction of carbon quantum dots/riboflavin fluorescent probe and its application in the detection of ciprofloxacin.

The research outlined a novel approach for creating a sensitive and efficient ratio fluorescent probe for ciprofloxacin (CIP) detection. The method used the biomass materials passionfruit shell and diethylenetriamine as carbon and nitrogen sources, respectively, to prepare blue fluorescent carbon quantum dots (b-CQDs) with an average size of 3.29 nm and a quantum yield of 19.6% by a hydrothermal method. The newly designed b-CQDs/riboflavin ratio fluorescent probe demonstrates a distinct advantage for CIP monitoring, exhibiting a marked increase in fluorescence intensity at 445 nm upon interaction with CIP, while maintaining a stable intensity at 510 nm. In the water system, the I445 nm/I510 nm ratio of the fluorescent probe showed a significant linear relationship with CIP at the concentrations of 0-250 µmol·L-1, and the probe boasts a low detection limit of 0.86 µmol·L-1. The outstanding selectivity, broad detection range, low detection limits, and high quantum yield of the b-CQDs highlight their significant potential in the development of advanced sensing probes for efficient detection of ciprofloxacin, offering promising insights for future sensor technology advancements.

Septicaemia due to Vibrio vulnificus: A tropical infection not to be taken lightly.

Vibrio vulnificus is a halophilic gram-negative bacillus that can cause fulminant septicaemia in immunocompromised patients. A 67-year-old man who was immunosuppressed as a result of cytotoxic chemotherapy presented with a brief history of fever, lethargy, myalgia, and reduced oral intake. He had recently travelled to the beach to consume seafood. His blood pressure was 81/47 mm Hg, necessitating fluid resuscitation followed by inotropic support and admission to the intensive care unit. His blood culture was positive for curved gram-negative bacilli. The isolate was oxidase-positive and produced an acid butt with an alkaline slant in triple sugar iron agar. Matrix-assisted laser desorption ionization-time of flight mass spectrometry conclusively identified the isolate as V. vulnificus. Intravenous ceftazidime plus ciprofloxacin were administered, and by the fifth day of admission, he was successfully transferred out to the general ward. In total, the patient completed a 14-day course of antibiotic therapy.

Nanocellulose-alginate composite beads for improving Ciprofloxacin bioavailability.

Nanocellulose is a potential material utilized in numerous biomedical applications. However, its hydrophilic characteristic and uncontrolled encapsulated drug release hinders nanocellulose uses in oral drug administration. Thus, this work developed novel nanocellulose/alginate composite (CNC/Alg) beads for oral delivery and bioavailability enhancement of a model drug, Ciprofloxacin (CIP). CNC was green synthesized employing electrolysis process from sugarcane bagasse. CNC/Alg beads were formulated by dropwise adding CNC-Alg mixture in CaCl2 solution at room temperature. CIP was incorporated into CNC/Alg beads by adsorption technique. X-ray diffractometry and Fourier-transform infrared spectra images showed that the beads were effectively produced with high crystallinity of 75.5 %, and the typical bond of cellulose and alginate. Within 4 h of adsorption, CIP loading efficiency reached 45.27 %, with 87.2 % molecules in the zwitterionic state. The adsorption followed Elovich and pseudo-second-order models, indicating a multi-mechanism including both physical and chemical adsorptions. Importantly, in gastrointestinal tract, the beads could protect CIP from acidic stomach environment while releasing it sustainably in simulated intestinal condition (75.05 %). The beads also showed strong antibacterial activity against both Gram(-) and Gram(+) bacteria, as evidenced by low IC50 and minimum inhibitory concentration values. Finally, CNC/Alg beads could improve CIP bioavailability for effective oral drug delivery route.

Detection of ciprofloxacin and pH by carbon dots and rapid, visual sensing analysis.

Food safety is a serious issue worldwide and practical detection method is vital for the supervision of food safety. It is necessary to establish efficient and economical methods to detect antibiotics, especially antibiotics in complex systems. This study employs citric acid and m-phenylenediamine to synthesize N, P-codoped carbon dots (N, P-CDs) by a microwave-assisted method. Anhydrous ethanol and phosphoric acid are essential to the properties of N, P-CDs. A "turn-on" fluorescent probe based on N, P-CDs was established for detecting ciprofloxacin (CIP) with detection limit down to 24.2 nm. Semiquantitative test stripe and a PS color detection system for CIP were developed to achieve visual and smart detection. The test stripe is applied to the visual detection of CIP residues in milk and a popular Chinese cuisine, Malatang, for the first time. N, P-CDs can also be used to detect pH in the range of pH 7.5-12.

Measuring single-cell susceptibility to antibiotics within monoclonal bacterial populations.

The emergence of new resistant bacterial strains is a worldwide challenge. A resistant bacterial population can emerge from a single cell that acquires resistance or persistence. Hence, new ways of tackling the mechanism of antibiotic response, such as single cell studies are required. It is necessary to see what happens at the single cell level, in order to understand what happens at the population level. To date, linking the heterogeneity of single-cell susceptibility to the population-scale response to antibiotics remains challenging due to the trade-offs between the resolution and the field of view. Here we present a platform that measures the ability of individual E. coli cells to form small colonies at different ciprofloxacin concentrations, by using anchored microfluidic drops and an image and data analysis pipelines. The microfluidic results are benchmarked against classical microbiology measurements of antibiotic susceptibility, showing an agreement between the pooled microfluidic chip and replated bulk measurements. Further, the experimental likelihood of a single cell to form a colony is used to provide a probabilistic antibiotic susceptibility curve. In addition to the probabilistic viewpoint, the microfluidic format enables the characterization of morphological features over time for a large number of individual cells. This pipeline can be used to compare the response of different bacterial strains to antibiotics with different action mechanisms.

Formulations of poly(vinyl alcohol) functionalized silk fibroin nanoparticles for the oral delivery of zwitterionic ciprofloxacin.

Fibroin nanoparticles (FNP) have been employed in numerous biomedical applications. However, limited research has focused on the oral delivery of FNP and in-depth molecular interactions between the encapsulated drug and FNP. Therefore, this work developed the FNP, functionalized with poly(vinyl alcohol) (PVA), to orally deliver the zwitterionic ciprofloxacin, focused on the molecular interactions. The particles were formulated using both desolvation (the drug precipitated during the particles formulation) and adsorption (the drug adsorbed on the particles surfaces) methods. The optimal formula possessed a size of ~630 nm with narrow size distribution (measured by DLS method), spherical shape (determined by SEM), and moderate drug loading (confirmed by FT-IR, XRD, and DSC techniques) of ~50% for the desolvation method and ~43% for the adsorption method. More than 80% of the drug molecules resided on the particle surfaces, mainly via electrostatic forces with fibroin. The drug was physically adsorbed onto FNP, which followed Langmuir model and pseudo second-order kinetics. In the in-vitro simulated gastric condition at pH 1.2, the ciprofloxacin bound strongly with FNP via electrostatic forces, thus hindering the drug release (< 40%). Contrastingly, in the simulated intestinal condition at pH 6.8, the particles could control the drug release rates dependent on the PVA amount, with up to ~100% drug release. Lastly, the particles possessed adequate antibacterial activities on Bacillus subtilis, Escherichia coli, and Salmonella enterica, with MIC of 128, 8, and 32 µg/mL, respectively. In summary, the FNP and PVA functionalized FNP could be a potential oral delivery system for zwitterionic drugs.

Antimicrobial Susceptibility and Genetic Epidemiology of Extended-Spectrum ß-Lactamase-Positive Enterobacterales Clinical Isolates in Central Poland.

The extended-spectrum ß-lactamases (ESßLs) are bacterial enzymes capable of hydrolyzing penicillins, cephalosporins, and aztreonam. The prevalence of ESßL is increasing among clinically significant microorganisms worldwide, drastically reducing the therapeutic management of infectious diseases. The study aimed to determine the drug susceptibility of ESßL-positive clinical isolates acquired from patients hospitalized in Lodz, central Poland, and analyze the prevalence of specific genes, determining acquired resistance in these bacteria. The samples of ESßL-positive clinical isolates were gathered in 2022 from medical microbiological laboratories in the city of Lodz, central Poland. The strains were subjected to biochemical identification and antimicrobial susceptibility testing following EUCAST guidelines. The presence of studied genes (blaCTX-M, blaSHV, blaTEM, blaPER, blaVEB) was confirmed by PCR. Over 50% of studied isolates were resistant to gentamicin, cefepime, ceftazidime and ciprofloxacin. The most common ESßL gene was blaCTX-M. In most isolates, the resistance genes occurred simultaneously. The blaPER was not detected in any of the tested strains. ESßL-producing strains are largely susceptible to the currently available antibiotics. The observation of the coexistence of different genes in most clinical isolates is alarming.