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Ultrafine linen and powdered cotton celluloses were modified with fluoroquinolone antibiotic ciprofloxacin. The modification was carried out by means of interaction of cellulose tosylates with ciprofloxacin hydrochloride in DMF medium at 100°C for 25 h. The modified cellulose samples were characterized using IR and NMR 1H spectroscopy. The antimicrobial activity of the obtained samples was assessed and their bacteriostatic and bactericidal activity against gram-positive bacteria S. aureus 209 and B. cereus 8035 was revealed.

Fluoroquinolone antibiotic is used extensively and, is obtained to reasoninfluences neurologically on living microorganisms. In the present study, the photocatalyst/H2O2underUV light photo-degradat...

Ciprofloxacin hydrochloride and Norfloxacin are second-generation fluoroquinolone antibiotic against bacterial DNA gyrase, which reduces DNA strain throughout replication. As DNA gyrase is essential through DNA replication, subsequent DNA synthesis and cell division are inhibited. Direct photolysis of fluoroquinolones was studied by using UV irradiation in the presence or absence of other substances that generate free radicals. This study aimed to assess the effect of Ultraviolet B (UVB) irradiation in removing ciprofloxacin and norfloxacin by using a simulating model of wastewater contained urea at pH 4. A known concentration of ciprofloxacin and norfloxacin were prepared in an appropriate aqueous solution in presence or absence 0.2M urea and adjusted at pH 4. The dis­solved drugs were irradiated with UVB-lamp in a dark place for 60 minutes. The percent of removal and the rate of elimination (k) of each drug were calculated. The direct photolysis effect of UVB irradiation was observed with ciprofloxacin which amounted to 24.4% removal compared with12.4% removal of norfloxacin after 60 minutes of irradiation. The effect of UVB irradiation was enhanced by urea to reach 38.9% and 15% for ciprofloxacin and norfloxacin. The calculated k of ciprofloxacin has amounted to three folds of that of norfloxacin. Direct photolysis of ciprofloxacin and norfloxacin can be achieved simply by using a simulation model of 0.2 M urea and UVB irradiation at pH 4. UVB is highly effective in removing ciprofloxacin compared with norfloxacin by 2-3 folds.

Formation of reactive oxygen species (ROS) induced by bactericidal antibiotics has been associated with a common, non-specific, mechanism of cellular death. Herein we report real-time single cell fluorescence studies on E. coli stained with a fluorogenic probe for lipid peroxyl radicals showing generation of this form of ROS when exposed to the minimum inhibitory concentration (MIC) and 10xMIC of the fluoroquinolone antibiotic ciprofloxacin (3 and 30 μM, respectively). Single-cell intensity-time trajectories show an induction period followed by an accelerating phase for cells treated with antibiotic, where initial and maximum intensity achieved following 3.5 h incubation with antibiotic showed dose dependent average values. A large fraction of bacteria remains viable after the studies, indicating ROS formation is occurring a priori of cell death. Punctate structures are observed, consistent with membrane blebbing. Addition of a membrane embedding lipid peroxyl radical scavenger, an α-tocopherol analogue, to the media increased the MIC of ciprofloxacin. Lipid peroxyl radical formation precedes E. coli cell death and may be invoked in a cascade event including membrane disruption and consequent cell wall permeabilization. Altogether, our work illustrates that lipid peroxidation is caused by ciprofloxacin in E. coli, and suppressed by α-tocopherol analogues. Lipid peroxidation may be invoked in a cascade event including membrane disruption and consequent cell wall permeabilization. Our work provides a methodology to assess antibiotic induced membrane peroxidation at the single cell level, this methodology provides opportunities to explore the scope and nature of lipid peroxidation in antibiotic induced cell lethality. Fil: Martinez, Sol Romina. McGill University; Canadá. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina Fil: Durantini, Andres Matías. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Becerra, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Cosa, Gonzalo. McGill University; Canadá

Gut microbiota in fish plays an important role in the nutrient digestion, immune responses and disease resistance. To understand the effect of fluoroquinolone antibiotic bath administration on fish gut microbiota, the gut microbiota community in the coral trout Plectropomus leopardus (Lacepède, 1802) was studied after enrofloxacin bathing treatment at two concentrations (5 and 10 mg/L) and 0 mg/L as control. A total of 90 fish were used in this study, and three replicates were used for each treatment. After a 24‐hr bath, the gut bacterial composition was analyzed using high‐throughput Illumina sequencing. The results indicated that the richness, diversity and the dominant bacterial taxa of P. leopardus gut bacteria were not affected by enrofloxacin bathing (p > .05). Proteobacteria and Firmicutes were the dominant phyla, and Exiguobacterium, Citrobacter, Vibrio, Acinetobacter, Pseudomonas were the dominant genus. The findings in the present study provide an understanding on the relationship between fish gut bacteria community and antibiotic bath administration. The findings of this study are instructive on the antibiotic bath administration applied for the management of P. leopardus health in aquaculture., The gut microbiota community in the coral trout Plectropomus leopardus (Lacepède, 1802) was studied after enrofloxacin bathing treatment at two concentrations (5 and 10 mg/L) and 0 mg/L as control. After a 24‐hr bath, the gut bacterial composition was analyzed using high‐throughput Illumina sequencing. The results indicated that the richness, diversity and the dominant bacterial taxa of P. leopardus gut bacteria were not affected by enrofloxacin bathing (p > .05).

Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC(6’)-Ib-cr enzyme that inactivates the fluoroquinolone (FQ) antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the aac(6’)-Ib-cr gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both aac(6’)-Ib-cr and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages.

Most of the physiological activities of organisms are realized by protein-protein interactions (PPIs), which are one of the fundamental research fields in biomedicine. Investigation of micromechanical behaviour of proteins is important for understanding its biological functions. In this study, after the fabrication of self-assemble monolayers (SAMs), eight fluoroquinolone antibiotics were used as experimental subjects and their influence on the interactions between BSA and anti-BSA were investigated by atomic force microscopy (AFM). The Poisson distribution method was used to statistically calculate the adhesion forces obtained by AFM. The results showed that salified fluoroquinolone antibiotics could decrease the adhesion forces between BSA and anti-BSA, especially the non-specific interactions. In contrast, the non-salified fluoroquinolone antibiotics had no significant effect on PPIs between BSA and anti-BSA. The specific interaction notably changed at low (40 μg/mL) and high (200 μg/mL) concentrations of fluoroquinolone antibiotics. Together with AFM topographical analysis, this phenomenon was attributed to the pH reaching a value closer to the BSA isoelectric point and a higher ionic strength, which led to the reduction of antigen and antibody specific binding sites, respectively. These interpretations provide a foundation to better understand the mechanical behaviour of proteins.

A simple not solvent and time consuming Fe3O4@MIL-100(Fe), synthesized in the presence of a small amount of magnetite (Fe3O4) nanoparticles (27.3 wt%), is here presented and discussed. Layer-by-layer alone (20 shell), and combined layer-by-layer (5 shell)/reflux or /hydrothermal synthetic procedures were compared. The last approach (Fe3O4@MIL-100_H sample) is suitable (i) to obtain rounded-shaped nanoparticles (200–400 nm diameter) of magnetite core and MIL-100(Fe) shell; (ii) to reduce the solvent and time consumption (the layer-by-layer procedure is applied only 5 times); (iii) to give the highest MIL-100(Fe) amount in the composite (72.7 vs. 18.5 wt% in the layer-by-layer alone); (iv) to obtain a high surface area of 3546 m2 g−1. The MIL-100(Fe) sample was also synthesized and both materials were tested for the absorption of Ofloxacin antibiotic (OFL). Langmuir model well describes OFL adsorption on Fe3O4@MIL-100_H, indicating an even higher adsorption capacity (218 ± 7 mg g−1) with respect to MIL-100 (123 ± 5 mg g−1). Chemisorption regulates the kinetic process on both the composite materials. Fe3O4@MIL-100_H performance was then verified for OFL removal at µg per liter in tap and river waters, and compared with MIL-100. Its relevant and higher adsorption efficiency and the magnetic behavior make it an excellent candidate for environmental depollution.

Pyocins are phage tail-like protein complexes that can be used by Pseudomonas aeruginosa to enact intraspecies competition by killing competing strains. The pyocin gene cluster also encodes holin and lysin enzymes that lyse producer cells to release the pyocins. The best-known inducers of pyocin production under laboratory conditions are DNA-damaging agents, including fluoroquinolone antibiotics, that activate the SOS response. Here, we report the discovery of an alternate, RecA-independent pathway of strong pyocin induction that is active in cells deficient for the tyrosine recombinase XerC. When ΔxerC cells were examined at the single-cell level, only a fraction of the cell population strongly expressed pyocins before explosively lysing, suggesting a that a built-in heterogenous response system protects the cell population from widespread lysis. Disabling the holin and lysin enzymes or deleting the entire pyocin gene cluster blocked explosive lysis and delayed but did not prevent the death of pyocin-producing cells, suggesting that ΔxerC cells activate other lysis pathways. Mutating XerC to abolish its recombinase activity induced pyocin expression to a lesser extent than the full deletion, suggesting that XerC has multiple functions with respect to pyocin activation. Our studies uncover a new pathway for pyocin production and highlight its response across a genetically identical population. Moreover, our finding that ΔxerC populations are hypersensitive to fluoroquinolones raises the intriguing possibility that XerC inhibition may potentiate the activity of these antibiotics against P. aeruginosa infections. IMPORTANCE Pseudomonas aeruginosa is a versatile and ubiquitous bacterium that frequently infects humans as an opportunistic pathogen. P. aeruginosa competes with other strains within the species by producing killing complexes termed pyocins, which are only known to be induced by cells experiencing DNA damage and the subsequent SOS response. Here, we discovered that strains lacking a recombinase enzyme called XerC strongly produce pyocins independently of the SOS response. We also show that these strains are hypersensitive to commonly used fluoroquinolone antibiotic treatment and that fluoroquinolones further stimulate pyocin production. Thus, XerC is an attractive target for future therapies that simultaneously sensitize P. aeruginosa to antibiotics and stimulate the production of bactericidal pyocins.

Fluoroquinolone associated toxicity after along-term fluoroquinolone antibiotic therapy appears as a significant medical and social problem. The objective of this review was mainly to identify, collect and evaluate the available evidence regarding the toxicological aspects of fluoroquinolone with focus on the causes of fluoroquinolone chondrotoxicity in juvenile animals. The present review was conducted using the PubMed/Medline databases. English language publications, original studies and reviews were included. All works about the fluoroquinolones regarding human, in vitro, and animal studies published in the medical and dental literature between 1985 and 2021 were reviewed. The existing data studies demonstrate that fluoroquinolone administration can cause different side effects, and the fluoroquinolone chondrotoxicity in juvenile animals is one of them. The cause could be due to binding of fluoroquinolone with the divalent cations such as Mg2+ and this can induce a deficiency of the functionally available magnesium, increase level of tissue apoptotic markers like activated caspase‐3, reactive oxygen species (ROS) overproduction, mitochondrial damage, enhanced the expression of matrix metalloproteinases, with chondrocytes loss and decrease in the formation of the cartilage extracellular matrix. Depending on these toxicological findings in animal’s studies during the postnatal growth, fluoroquinolones are contraindicated during pregnancy, lactation, and in children.

A putative type II toxin-antitoxin (TA) module almost exclusively associated with conjugative IncC plasmids is homologous to the higBA family of TA systems found in chromosomes and plasmids of several species of bacteria. Despite the clinical significance and strong association with high-profile antimicrobial resistance (AMR) genes, the TA system of IncC plasmids remains largely uncharacterized. In this study, we present evidence that IncC plasmids encode a bona fide HigB-like toxin that strongly inhibits bacterial growth and results in cell elongation in Escherichia coli. IncC HigB toxin acts as a ribosome-dependent endoribonuclease that significantly reduces the transcript abundance of a subset of adenine-rich mRNA transcripts. A glycine residue at amino acid position 64 is highly conserved in HigB toxins from different bacterial species, and its replacement with valine (G64V) abolishes the toxicity and the mRNA cleavage activity of the IncC HigB toxin. The IncC plasmid higBA TA system functions as an effective addiction module that maintains plasmid stability in an antibiotic-free environment. This higBA addiction module is the only TA system that we identified in the IncC backbone and appears essential for the stable maintenance of IncC plasmids. We also observed that exposure to subinhibitory concentrations of ciprofloxacin, a DNA-damaging fluoroquinolone antibiotic, results in elevated higBA expression, which raises interesting questions about its regulatory mechanisms. A better understanding of this higBA-type TA module potentially allows for its subversion as part of an AMR eradication strategy. IMPORTANCE Toxin-antitoxin (TA) systems play vital roles in maintaining plasmids in bacteria. Plasmids with incompatibility group C are large plasmids that disseminate via conjugation and carry high-profile antibiotic resistance genes. We present experimental evidence that IncC plasmids carry a TA system that functions as an effective addiction module and maintains plasmid stability in an antibiotic-free environment. The toxin of IncC plasmids acts as an endoribonuclease that targets a subset of mRNA transcripts. Overexpressing the IncC toxin gene strongly inhibits bacterial growth and results in cell elongation in Escherichia coli hosts. We also identify a conserved amino acid residue in the toxin protein that is essential for its toxicity and show that the expression of this TA system is activated by a DNA-damaging antibiotic, ciprofloxacin. This mobile TA system may contribute to managing bacterial stress associated with DNA-damaging antibiotics.

The adverse effects of fluoroquinolones are yet to be fully elucidated. We present an interesting case of a 41-year-old male with binocular diplopia most likely induced by the use of a fluoroquinolone antibiotic.

Objectives: Enrofloxacin, a fluoroquinolone antibiotic, is an inhibitor of prokaryotic topoisomerase II with antibacterial and antiparasitic activities. The study aimed to evaluate the inhibitory effect of enrofloxacin on Babesia species and Theileria equi in vitro and in vivo. Methods: The inhibitory effects of enrofloxacin were evaluated in vitro cultures using in vitro inhibition assay of three Babesia species and Theileria equi; furthermore, the in vivo inhibitory effect of enrofloxacin was evaluated in the mice model of Babesia microti. Results: The IC50 values of enrofloxacin were 4.9, 4.5, 4, and 3.9 nM for B. bovis, B. bigemina, B. caballi, and B. equi, respectively. Enrofloxacin at a dose rate of 10 mg/kg resulted in a 92.9 % inhibition of Babesia microti growth in BALB/c mice. Combination therapy of enrofloxacin at a dose rate of 5 mg/kg with diminazene aceturate at a dose rate of 12.5 mg/kg resulted in 93.83 % inhibition of Babesia microti growth in BALB/c mice. Conclusions: Enrofloxacin might be used for drug therapy in babesiosis.

A hybrid graphene-TiO2 nanocomposites have been prepared by a facile hydrothermal method to improve the photocatalytic performance and applied for synergetic degradation of fluoroquinolone antibiotic in pulsed discharge plasma (PDP) system. The characterizations of the structure and morphology, chemical bonding state, optical property and electrochemical property show that the graphene-TiO2 nanocomposites can be hybridized successfully. Compared to the pure TiO2, the light absorption range can extend to visible light ( OH, h+ and O2− play the critical role for FLU degradation in PDP/graphene-TiO2 system. The graphene-TiO2 samples can further decompose the O3 and improve the generation of OH and H2O2. The degradation intermediates are determined by LC–MS and IC. The toxicity evolution of FLU reaction solutions is evaluated based on inhibition of photobacterium V. fischeri. Finally, the FLU degradation mechanism in the PDP/graphene-TiO2 system is proposed. This research would provide a novel insight into the application of graphene-based nanocomposites in PDP system as a promising remediation methodology for organic contaminants in water.

Purpose: Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there ...

Background: It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone (“new quinolone”) antibiotics that would inhibit LC-mediated Th2 cell development. Methods: Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay. Results: Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production, as well as Th1 cell development, as represented by down-regulation of interferon (IFN)- g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo , and controlling the severity of AD.

Antibacterial activity against a series of potentially pathogenic bacterial strains was evaluated in both liquid and solid matrices using ciprofloxacin (a well-known fluoroquinolone antibiotic) based polymeric systems with pendant cationic charge and zwitterionic units. The ciprofloxacin containing polymeric architecture was designed to incorporate bioactive killing properties of cationic moieties, whereas biopassive activity was regulated by the bacterial cell repelling capacity of the zwitterionic group. tert-Butyl carbamate (Boc)-leucine hydroxyethylmethacrylate (Boc-Leu-HEMA), Boc-ciprofloxacin hydroxyethylmethacrylate (Boc-Cipro-HEMA) and zwitterionic sulphabetaine methacrylate (SBMA) are copolymerized, followed by deprotection of Boc groups from the copolymer under acidic conditions. Boc deprotection resulted in water soluble polymers with cationic charge from the leucine moiety and retained the antibiotics in their active original form. The antibacterial activity of the polymeric system was evaluated against several bacterial species, namely, Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Vibrio alginolyticus (V. alginolyticus), and Vibrio chemaguriensis Iso1 (V. chemaguriensis), in both liquid and solid matrices. The copolymer displayed significant bactericidal efficacy against non-biofilm forming E. coli and B. subtilis in both liquid and solid matrices. However, the antibacterial effect on biofilm forming V. chemaguriensis was comparatively less prominent in the liquid matrix. Optical microscope images of Gram staining revealed an enhanced surface area of individual cells and chain formation in cells of V. chemaguriensis. The non-cytotoxic profile of the polymer towards mammalian red blood cells (RBCs) and enhanced bactericidal effect in the physiological to basic pH (7.0–9.5) range against potentially pathogenic V. chemaguriensis using a multitude of microscopic techniques hinted toward the need to develop new antibiotics to combat possible clinical infections in the near future.

Aim: The present study was carried out to determine the prevalence and molecular detection of fluoroquinolone-resistant Escherichia coli carrying qnrA and qnrS genes in healthy broiler chickens in Mymensingh, Bangladesh, and also to identify the genes responsible for such resistance. Materials and Methods: A total of 65 cloacal swabs were collected from apparently healthy chickens of 0-14 days (n=23) and 15-35 days (n=42) old. The samples were cultured onto Eosin Methylene Blue Agar, and the isolation and identification of the E. coli were performed based on morphology, cultural, staining, and biochemical properties followed by polymerase chain reaction (PCR) targeting E. coli 16S rRNA genes. The isolates were subjected to antimicrobial susceptibility test against five commonly used antibiotics under fluoroquinolone (quinolone) group, namely gatifloxacin, levofloxacin, moxifloxacin, ofloxacin, and pefloxacin by disk diffusion method. Detection of qnrA and qnrS genes was performed by PCR. Results: Among the 65 cloacal samples, 54 (83.08%) were found to be positive for E. coli. Antibiotic sensitivity test revealed that, of these 54 isolates, 18 (33.33%) were found to be resistant to at least one fluoroquinolone antibiotic. The highest resistance was observed against pefloxacin (61.11%). By PCR, of 18 E. coli resistant to fluoroquinolone, 13 (72.22%) were found to be positive for the presence of qnrS. None of the isolates were found positive for qnrA. Conclusion: Fluoroquinolone-resistant E. coli harboring qnrS genes is highly prevalent in apparently healthy broiler chickens and possesses a potential threat to human health.

There was a development of low-level tolerance to fluoroquinolone antibiotic ciprofloxacin in Listeria monocytogenes after sublethal adaptation to quaternary ammonium compound (QAC). Using eight L. monocytogenes strains, we determined the changes in short-range MIC, growth rate, and survival for heterologous stress response to ciprofloxacin, after sublethal exposure to daily cycles of fixed or gradually increasing concentration of QAC. Three main findings were observed. (1) MIC increase—QAC-adapted subpopulations exhibited a significant increase in short-range MIC of ciprofloxacin, by 1.5 to 2.9 fold, as compared to non-adapted control for 4/8 strains (p &lt, 0.05). (2) Growth rate increase—QAC-adapted subpopulations exhibited significant 2.1- to 6.8- fold increase in growth rate (OD600 at 10 h) in ciprofloxacin-containing broth, as compared to non-adapted control for 5/8 strains (p &lt, 0.05). (3) Survival increase—QAC-adapted subpopulations of L. monocytogenes yielded significantly higher survival in ciprofloxacin-containing agar by 2.2 to 4.3 log CFU/mL for 4/8 strains, as compared to non-adapted control (p ˂ 0.05). However, for other 4/8 strains of L. monocytogenes, there was no increase in survival of QAC-adapted subpopulations, as compared to non-adapted control in ciprofloxacin. These findings suggest the potential formation of low-level ciprofloxacin-tolerant subpopulations in some L. monocytogenes strains when exposed to residual QAC concentrations (where QAC might be used widely) and such cells if not inactivated might create food safety risk.

Objective WFQ-228 is a novel developed fluoroquinolone (FQ) displaying potent antimicrobial activity against various clinical isolates of pathogens, including FQ-resistant isolates. The aim was to comparatively analyze in vitro susceptibilities of WFQ-228, levofloxacin (LFX), and moxifloxacin (MFX) against Mycobacterium tuberculosis (MTB) isolates, especially with gyrA mutations. Methods We selected a panel of 75 MTB isolates, consisting of 25 FQ-susceptible and 50 FQ-resistant isolates determined by conventional drug susceptibility testing. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of FQs to MTB isolates were assessed. Results MFX exhibited the most potent activity against FQ-susceptible MTB, demonstrating a MIC50 of 0.031 mg/L, which was lower than that of LFX and WFQ-228. Against FQ-resistant MTB isolates, the MIC50 of WFQ-228 was higher than that of MFX but lower than that of LFX. For WFQ-228, there was a significant overlap existing in the MIC distributions between the probable susceptible (PS) and probable resistant (PR) groups. Six out of 50 PR isolates were classified as susceptible based on a proposed critical concentration (CC) of 0.5 mg/L, yielding a poor sensitivity of 88.0%. These discordant isolates had GyrA substitution in Ala90Val, Ser91Pro, and Asp94Tyr. Additionally, MFX exhibited bactericidal activity against MTB isolates without gyrA mutations, which was significantly higher than that of isolates with gyrA mutations. Conclusion WFQ-228 is more efficacious than LFX in isolates with specific mutations conferring low-level FQ resistance. The bactericidal effect is noted more frequently in FQ-susceptible isolates than FQ-resistant isolates for MFX.

Background: Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer death in men. Enoxacin, a third-generation fluoroquinolone antibiotic, was found with anti-proliferative effects against many cancer types. This study was to further investigate its effects against prostate cancer and explore the underlying molecular mechanisms. Methods: PC-3 cells were treated with Enoxacin at different concentrations. Tumor model was established by subcutaneously injecting PC-3 cells into nude mice. MTT assay was used to detect cell viability. ELISA assay, Annexin V/PI staining and TUNEL assay were used to detect apoptosis. RT-qPCR and western blot were used to detect the gene and protein expression, respectively. Results: Our data showed that Enoxacin inhibited PC-3 cell proliferation and induced the apoptosis through up-regulating the expression of pro-apoptotic proteins, while down-regulating expression levels of anti-apoptotic proteins. Moreover, Enoxacin increased the gene and protein expression of the autophagy and endoplasmic reticulum stress markers. Treating tumor-bearing mice with Enoxacin significantly inhibited tumor growth in xenograft tumor model. Conclusion: Our results suggested that Enoxacin could be developed as a potential anti-tumor agent against prostate carcinoma.

Herein, the hydrophobic carboxyl-functionalized ionic liquid (IL-COOH) was encapsulated into the prepared Fe3O4@Zr-MOFs, and the novel water-stable IL-COOH/Fe3O4@Zr-MOF nanocomposites were first sy...

Plasma technology is increasingly being used for the degradation of residual antibiotics in aquatic environments. However, the electrodes in conventional plasma generators are subject to erosion, which can pollute the reaction system and shorten its lifetime. To overcome these drawbacks, we developed an electrodeless high-flow atmospheric microwave plasma jet (MPJ) for fast and efficient degradation of residual norfloxacin (NOR), a typical fluoroquinolone antibiotic that is frequently detected in the aquatic environment owing to its widespread use in the treatment of various infectious diseases. Stable plasma was generated through a low-cost magnetron with the assistance of injection-locking technology. The degradation efficiency of NOR (20 mg/L) reached 98.27 ± 1.03% at 6 min and the mineralisation efficiency reached 68.67 ± 3.21% at 15 min. The fast degradation process of the NOR solution contributes to the large cross-section (approximately 153 mm2) of the plasma in direct contact with the solution. Hydroxyl radical (•OH) scavengers were used to identify the generated oxidising species, which indicated that their non-selective oxidation plays a major role in NOR degradation. Three main possible degradation pathways and mechanisms were proposed, namely the attack of •OH on the piperazine ring, quinolone ring, and benzene ring. The NOR solution was not toxic to Escherichia coli after 20 min of degradation. Thus, the high-flow atmospheric MPJ is an effective technology for the degradation of antibiotics in aqueous solutions.

Ciprofloxacin (Cip), a fluoroquinolone antibiotic, was determined by linear sweep adsorptive stripping voltammetric method using multilayer reduced graphene oxide electrode (m-rGO). The m-rGO electrode was fabricated directly, simply and promptly from graphite platform by potentiostatic technique without further modification. The produced electrode exhibited excellent performance for ciprofloxacin (Cip) determination with a much higher signal of Cip than that on the initial graphite electrode (13.4 times). This dominance of the m-rGO electrode resulted from the large electrochemically active surface area, electrochemical catalysis, suitable functional groups on the electrode surface. Experimental conditions such as the electrode fabrication time, the supporting solution, and accumulation time were optimised to obtain the Cip highest signal. A Cip analytical method established under the optimal conditions had a good linear relationship between the Cip signal with its concentration range from 0.5 to 20 µM (R2 = 0.9953). The method showed a low detection limit (LOD = 0.078 µM), satisfactory reproducibility (RSD = 1.50%), and high accuracy. Cip concentration in a spiked lake water sample determined by the proposed method with acceptable precision (RSD = 5.59%) and trueness (recovery = 94.2–106.3%) was comparable with LC-MS/MS method.

Two different zinc-based metal-organic frameworks (MOFs) were investigated to remove one of the most used fluoroquinolone antibiotic, Ofloxacin (OFL), from polluted water. The most common zeolitic imidazolate framework-8 (ZIF-8) and the green Zn(II) and benzene-1,3,5-tri-carboxylate (Zn3(BTC)2) were prepared through a facile synthetic route and characterized by means of Fourier-Transform Infrared (FT-IR) Spectroscopy, X-ray Powder Diffraction (XRPD), and Scanning Electron Microscopy (SEM) analyses. The two MOFs were compared in terms of both adsorption and kinetic aspects under real conditions (tap water, natural pH). Results showed that OFL was adsorbed in remarkable amounts, 95 ± 10 and 25.3 ± 0.8 mg g−1 on ZIF-8 and Zn3(BTC)2, respectively, following different mechanisms. Specifically, a Langmuir model well described the ZIF-8 profile, while for Zn3(BTC)2, cooperative adsorption occurred. Moreover the kinetic results were quite different, pseudo-second-order and sigmoidal, respectively. The suitability of ZIF-8 and Zn3(BTC)2 as adsorbent phases for water depollution was tested on tap water samples spiked with OFL 10 µg L−1. The obtained removal efficiencies, of 88% for ZIF-8 and 72% for Zn3(BTC)2, make these materials promising candidates for removing fluoroquinolone antibiotics (FQs) from polluted waters, notwithstanding their limited reusability in tap water, as demonstrated by in-depth characterization of the two MOFs after usage.

Increased use of antibiotics globally has led to the threat of antibiotic resistance; this drove the urge of researchers toward discovering more potent and broad-spectrum antibiotics. Levonadifloxacin (LND) is the very first antibiotic developed by an Indian company Wockhardt. It is S (-) isomer of another broad-spectrum antibiotic Nadifloxacin which is used topically for skin, soft tissue bacterial infection. LND belongs to the benzo quinolizine category which is a subclass of fluoroquinolone, indicated for ABSSIS, CABP, and other infections including diabetic foot infection; formulated as l-arginine salt of levonadifloxacin (WCK177) for IV and l-alanine ester mesylate salt as alalevonadifloxacin (WCK2349) for oral administration. It generally shows dominant antibacterial activity against Gram-negative, and positive bacterial infections, particularly toward methicillin-resistant Staphylococcus aureus (MRSA) by dual inhibition of DNA gyrase and topoisomerase IV. Producing quality product that complies to regulatory requirements is a big concern for pharma industries. To this context, validated analytical methods for routine quality control are essential for quantification of LND as an API alone and together with pharmaceutical formulations. This review suggests therapeutic, pharmacological, and analytical aspects regarding the novel drug LND and particularly focuses on discussing various reported analytical methods present for analytical or bioanalytical estimation of the drug and suggest to develop a simple and validated method which also complies to green chemistry.

In this article, a simple, fast and inexpensive methodology has been developed for the determination of fluoroquinolone class antibiotic norfloxacin (NFX) in anionic surfactant media (sodium dodecyl sulphate, SDS) using an anodically pretreated boron-doped diamond (APT-BDD) electrode. Cyclic voltammetric studies showed that the NFX gave an irreversible and adsorption controlled anodic oxidation signal at a potential of about +1.32 V on the APT-BDD electrode. The effects of parameters such as the electrode pre-treatment procedure, SDS concentration, and instrumental variables on the electrochemical sensitivity of NFX were evaluated. Under optimized conditions, the linearity was achieved in the range of 0.05 to 4.0 mu g mL(-1) (1.57x10(-7)-1.25x10(-5) mol L-1), with a detection limit of 0.013 mu g mL(-1) (4.07x10(-8) mol L-1) by using square-wave adsorptive stripping voltammetry (SW-AdSV). The feasibility of the developed approach for the quantification of NFX in urine samples was tested.

BackgroundStaphylococcus epidermidisis the most common pathogen in postoperative endophthalmitis and causes various infectious eye diseases. However, there is very little information on fluoroquinolone antibiotic resistance toS. epidermidisidentified in conjunctival microbe and analysis of related genes. Here, the authors investigated the rate of resistance to fluoroquinolones ofStaphylococcus epidermidisisolated from normal conjunctival microbes and mutations in the quinolone-resistance determining region (QRDR).Methods377 eye samples from 187 patients who underwent intravitreal injection and cataract surgery were included. Specimens were taken from the bilateral lower conjunctival sacs using a cotton swab and cultured. The cultures were identified using MALDI-TOP MS andgyrA, gyrB, parC, andparEgene mutations of QRDR were confirmed by DNA extraction from resistant strains ofS. epidermidiswith a micro-dilution method using ciprofloxacin, levofloxacin, and moxifloxacin.ResultsThe culture positive rate was 61.8% (231) for 374 eye samples. Of the 303 total strains cultured,S. epidermidiswas the most common with 33.7% (102). Ten types of gene mutations were observed in the resistantS. epidermidisof 21 strains. One-point mutation was observed mainly ingyrAandparC, and a small number of mutations were observed inparEin the form of a double point mutations. When there were multiple point mutations in bothgyrAandparC, the highest minimum inhibitory concentration was observed.ConclusionsThe quinolone resistance rate ofS. epidermidisincreased in comparison with previous studies, and resistantS. epidermidisshowed mostly QRDR mutations, which were mainly found ingyrAandparC, and showed strong resistance when mutated in both genes.

Ciprofloxacin is an extensively used fluoroquinolone antibiotic, which exists in aquatic environment, causing detrimental effects to the aquatic ecosystem and thus, indirectly to humans. Thus, an efficient and rapid removal method for ciprofloxacin is urgently needed. Intimately coupled photocatalysis and biodegradation has proven to be highly efficient, low-cost, and eco-friendly. In this study, cube polyurethane sponges modified with visible light-responsive g-C3N4 and mixed culture microbes were used to increase the ciprofloxacin removal efficiency. Subsequently, 94% of ciprofloxacin was removed by photocatalytic-biodegradation and 12 degradation products and possible degradation pathways were analyzed. Photocatalytic-biodegradation had a 1.57 times higher total organic carbon (TOC) removal rate than photocatalytic degradation. The microbial community structure after 72 h of photocatalytic biodegradation was examined. High microbial richness, evenness, and functional dominant species belong to Proteobacteria, which were closely associated with the utilization of antibiotics, may be majorly responsible for the highly efficient removal degradation process. Additionally, microbes retarded the interaction of photogenerated electrons and holes, which may contribute to the increasing mineralization. The findings demonstrated the potential ability of photocatalytic biodegradation in degrading bio-recalcitrant compounds and provide new insights into photocatalytic coupled with biodegradation for removal of ciprofloxacin.

Antibiotic resistance has risen in prominence to become one of the most significant threats to human health in the modern era. In order to combat this phenomenon and prevent the onset of a post-antibiotic age, a combination of different strategies is required. Along with changes to healthcare policy and implementation and discovery of new antibiotics, an improved understanding of bacterial resistance and infection is imperative. This thesis aims to contribute knowledge to this cause through the development of novel antibiotic probes that can be used to visualise bacteria and antibiotic localisation, with evaluation of their utility through microbiological testing.Two approaches were undertaken for probe design: fluorescently tagged antibiotics for analysis by spectrophotometry and microscopy; and radioactively tagged antibiotics for analysis by radiometry and radio-imaging. Bioactive cores were drawn a variety of antibiotic classes, with azide intermediates being prepared in order to allow for convergent synthesis by Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC) to alkyne tags incorporating the imaging moiety. Retention of antimicrobial activity was verified, and the fluorescent probes were used to quantify relevant properties such as bacterial localisation and efflux of the antibiotic. Isotope labelling studies were carried out with the radio-probes, followed by in vivo imaging with an mouse infection model.In Chapter 2, fluorescent derivatives of the fluoroquinolone antibiotic ciprofloxacin were prepared via an azide intermediate. The azide and fluorescent derivatives were tested for antimicrobial activity against Gram-positive and Gram-negative bacteria, and it was shown that the activity of the parent compound was generally retained. Next, confocal microscopy was used to evaluate intracellular penetration of the ciprofloxacin probes. Using an efflux upregulated Escherichia coli (E. coli) strain, it was shown that uptake of the probes was significantly increased in the presence of the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP). This study was published in MedChemComm, and demonstrates the utility of fluorescent probes in the study of resistance phenomena such as efflux. In Chapter 3, the macrolide class of antibiotics was explored, with a roxithromycin-based azide being synthesised as the core intermediate. Several different colours of fluorophore-alkynes were conjugated, and minimum inhibition concentrations (MICs) against a panel of susceptible and resistant bacteria were determined. Overall, the activity of the parent antibiotic was retained, and the probes were then used to study bacterial uptake and distribution with three different methodologies: a plate-based spectrophotometric assay, super-resolution confocal microscopy, and single-cell microfluidics. Extensive species- and strain-specific variation was seen in uptake and localisation of the probes, including heterogeneity between bacteria of the same strain. Future work should expand the set of bacteria tested to broaden our understanding of macrolide behaviour in susceptible and resistance bacteria. This work will be submitted for publication at Angewandte Chemie International Edition.In Chapter 4, focus switched to the b-lactam class of antibiotics. Synthesis of a proline side chain incorporating an azide handle was successful, as was attachment of a protected b-lactam-core. Deprotection of the azido-meropenem proved difficult, with catalytic conditions leading to reduction of the azide, hydrolysis of the b-lactam, or both. Model systems were used to attempt to optimise deprotection conditions, which, however, was unsuccessful. Future work in this field should involve either a different protection system, a different antibiotic scaffold, or the use of a tag attachment system other than azide-alkyne click chemistry.In Chapter 5, work moved from fluorescent tags to those suitable for use with radioactive metal isotopes. The vancomycin antibiotic scaffold was conjugated to metal-chelators with an alkyne handle to produce radio-probes. 64Cu was initially used as the radioisotope. Though further labelling optimisation is required, preliminary positron emission tomography (PET) imaging using a thigh infection mouse model was successfully performed. Localisation in the infected thigh provides proof of concept for diagnostic imaging of infection using radio-labelled antibiotics.Overall, this thesis demonstrates the potential challenges and successes involved with the preparation and use of fluorescent or radioactive antibiotics to study bacterial resistance and infection. Achieving efficient, convergent probe synthesis can represent a significant obstacle, and even when overcome, retention of antimicrobial activity is not guaranteed. Once an active probe has been prepared, however, a wide variety of analytical methods can be employed, such as microscopy, single-cell microfluidics, and PET imaging. Future research in this field should expand on the range of antibiotics used and delve deeper into emerging resistance mechanisms.

Coagulase negative Staphylococci often grow in cultures and form one of the most abundant flora among skin microbiome. It is important and challenging to identify and treat clinically significant infections caused by these organisms. Prosthetic devices, catheters and conditions causing immunocompromised states are the risk factors for such infections. We describe a case of clinically significant and symptomatic urinary tract infection (UTI) in a 65-year-old man with liver cirrhosis caused by Staphylococcus warneri which forms

As a broad-spectrum fluoroquinolone antibiotic drug, ciprofloxacin (CIP) is frequently used in the treatment of a wide variety of infections. However, the residues of this antibiotic pose a big threat to the aquatic environment and human health. In this research, Lactobacillus reuteri WQ-Y1 with CIP degradation ability was screened and identified. L. reuteri WQ-Y1 with a degradation rate of 65.1% for 4 µg mL−1 CIP was screened from 17 lactic acid bacteria (LAB), and cytochrome P450 enzyme was confirmed to promote the degradation of CIP by L. reuteri WQ-Y1. Meanwhile, the CIP degradation rate were also higher in 48 h’ culture time when co-cultured with 1 mg/mL of glucose in the culture media. Furthermore, result also proved that fluoroquinolone antibiotics with the similar piperazine ring structures could be degraded by L. reuteri WQ-Y1. L. reuteri WQ-Y1 could degrade fluoroquinolone antibiotics with the similar piperazine ring structure. However, future work still needs to be done on the confirmation of the key enzymes in the cytochrome P450 enzymes family in the biodegradation. The isolated ciprofloxacin-degrading strain L. reuteri WQ-Y1 had a CIP degradation rate of 65.1% at 24 hours, and one biodegradation metabolite was identified and proved to be an important metabolite of CIP from cytochrome P450 enzymes family hydrolysis with UPLC-MS/MS spectrograms approach.

Fluoroquinolones are synthetic antibiotics that are commonly used in animal husbandry, and the consumption of animal products with fluoroquinolone residues has imposed a serious threat to human health. Here, we report a plasmonic enzyme-linked immunosorbent assay (pELISA) method based on oxidative etching of silver nanoprisms (AgNPRs) for the quantitative and qualitative detection of danofloxacin (DAN), a fluoroquinolone antibiotic. AgNPRs that undergo colorimetric changes upon oxidative etching by H2O2 serve as the signal transducer in our design. An indirect competitive pELISA was constructed by introducing biotinylated monoclonal antibody (mAb), streptavidin and biotinylated glucose oxidase, which catalyzes the generation of H2O2 for etching AgNPRs. The quantitative detection limit of the proposed method was 0.24 ng mL-1 for DAN. The qualitative detection limit for DAN reached 0.32 ng mL-1, which was 32-fold lower than that of the assay using 3,3',5,5'-tetramethylbenzidine (TMB) as the signal transducer. The average recoveries of DAN in milk ranged from 103% to 121%, with a coefficient of variation of 0.6-3.41%. The recovery results were further confirmed using liquid chromatography-tandem mass spectrometry. In summary, the proposed AgNPR-etching pELISA exhibits high sensitivity, good accuracy and excellent reliability for the quantitative and qualitative detection of DAN in milk. This work was supported by the Program of State Key Laboratory of Food Science and Technology, Nanchang University (SKLF-ZZA-201912), the free explore issue of State Key Laboratory of Food Science and Technology of Nanchang University (SKLF-ZZB-201913), Jiangxi Science Foundation for Young Scientists (20181BAB214018) and the Singapore-MIT Alliance of Research and Technology Center (ING000383-ENG).

Untreated wastewater containing fluoroquinolone antibiotics poses serious hazards to aquatic species and human health; therefore, treatment of waste expanded polystyrene (EPS) is a crucial environmental matter. In this study, waste EPS was modified with a H2SO4/biodegradable chelating agent, [S,S]-ethylenediamine-N,N′-disuccinic acid (EDDS), and used for highly efficient adsorption of the fluoroquinolone antibiotic ciprofloxacin. When ciprofloxacin of 25 mg/L was used, the H2SO4-modified EPS (EPSH2SO4) adsorbed 60.5% of the ciprofloxacin. During sulfonation, adding a low dose of EDDS markedly improved the adsorption ability of EPSH2SO4+EDDS. The optimal modification conditions were 95% H2SO4, 0.002 M EDDS, 80 °C, and 40 min. The increased adsorbent doses enhanced the adsorption. Approximately 0.2 g/L of EPSH2SO4+EDDS could effectively adsorb 97.8% of the ciprofloxacin (554.3 mg/g) within 30 min. Solution pH0 greatly influenced the adsorption, and the most suitable pH0 was 6. The Langmuir isotherm accurately described the adsorption behaviors of both EPSH2SO4 and EPSH2SO4+EDDS (R2 = 0.997–0.998). The adsorption ability of EPSH2SO4+EDDS (qmax = 1250 mg/g) was 32 times higher than that of EPSH2SO4 (qmax = 38.6 mg/g). A total of 1 M HCl effectively regenerated the exhausted adsorbent. The optimal solid/liquid ratio and time were 0.08 g/20 mL and 60 min, respectively. The regenerated EPSH2SO4+EDDS maintained a high adsorption ability (87.2%) after 10 regeneration cycles. The results thus indicate that the EPSH2SO4+EDDS adsorption–regeneration process is a potential approach to remove ciprofloxacin from water.