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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In this study, an ultrasound/CCl4 system was used to degrade the fluoroquinolone antibiotic, ciprofloxacin, in aqueous solution. The effect of CCl4 concentration and initial solution pH on ciprofloxacin degradation were investigated. The results showed that ciprofloxacin degraded effectively under an ultrasound/CCl4 system, with degradation efficiency increasing from 0.51% to 50.92%, when the CCl4 concentration ranged from 0.0 to 41.4 mmol/L in 40 min. Radical scavenging experiments certified that both •OH and chlorine-containing radicals contributed to ciprofloxacin degradation. Eight intermediates were detected using ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) method, including three chloro-intermediates. Based on these results, the possible degradation pathways of ciprofloxacin are proposed. Agar diffusion tests with E. coli and S. aureus showed that ciprofloxacin's antibacterial activity was completely removed in 40 min. This study indicates that an ultrasound/CCl4 system can degrade ciprofloxacin and remove its antibacterial activity, and thus is a promising process for treating fluoroquinolone antibiotics in wastewater.

WFQ-101 with a unique N-1 substituent, 5-amino-4-fluoro-2-(hydroxymethyl)phenyl group, was selected as a lead compound through combination screening based on antimicrobial activity and the efflux index against quinolone-resistant (QR) Pseudomonas aeruginosa (P. aeruginosa). Through structural optimization, we identified WFQ-228 as a novel fluoroquinolone antibiotic candidate. WFQ-228 had potent and superior activity in comparison to levofloxacin (LVX) and ciprofloxacin (CIP) against clinical isolates of P. aeruginosa, Escherichia coli and Acinetobacter baumannii, including QR strains. Furthermore, WFQ-228 demonstrated the potential to overcome major mechanisms of drug resistance; its antimicrobial activity was less affected by both pump-mediated efflux and mutations of the quinolone resistance-determining region in P. aeruginosa compared with LVX and CIP. These results suggest that WFQ-228 is a promising candidate for further evaluation in the treatment of infections caused by QR Gram-negative pathogens.

Antimicrobial resistance is a major global threat to human health due to the rise, spread and persistence of multi-drug-resistant bacteria or ‘superbugs’. There is an urgent need to develop novel chemotherapeutics to overcome this overarching challenge. The authors derivatized a clinically used fluoroquinolone antibiotic ciprofloxacin (Cip), and complexed it to a copper phenanthrene framework. This resulted in the development of two novel metallo-antibiotics of general formula [Cu(N,N)(CipHA)]NO3 where N,N represents a phenanthrene ligand and CipHA represents a hydroxamic acid of Cip derivative. Comprehensive studies, including a detailed proteomic study in which Staphylococcus aureus cells were exposed to the complexes, were undertaken to gain an insight into their mode of action. These new complexes possess potent antibacterial activity against S. aureus and methicillin-resistant S. aureus. In addition, they were found to be well tolerated in vivo in Galleria mellonella larvae, which has both functional and structural similarities to the innate immune system of mammals. These findings suggest that proteins involved in virulence, pathogenesis, and the synthesis of nucleotides and DNA repair mechanisms are most affected. In addition, both complexes affected similar cell pathways when compared with clinically used Cip, including cationic antimicrobial peptide resistance. The Cu-DPPZ-CipHA (DPPZ = dipyrido[3,2-a:2’,3’-c]phenazine) analogue also induces cell leakage, which leads to an altered proteome indicative of reduced virulence and increased stress.

Four new triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl nucleoside analogues were synthesized by coupling with 8-bromoctyl- or 10- bromdecyltriphenylphosphonium bromide and evaluated for the in vitro antibacterial activity against S. aureus, B. cereus, E. faecalis, two MRSA strains isolated from patients and resistant to fluoroquinolone antibiotic ciprofloxacin and β-lactam antibiotic amoxicillin, E. coli, antifungal activity against T. mentagrophytes C. albicans and cytotoxicity against human cancer cell lines M−HeLa, MCF-7, A549, HuTu-80, PC3, PANC-1 and normal cell line Wi-38. In these compounds a TPP cation was attached via an octyl or a decyl linker to the N 3 atom of the heterocycle moiety (thymine, 6-methyluracil, quinazoline-2,4-dione) which was bonded with 2′,3′,5′-tri- O - acetyl-greek beta- d -ribofuranose residue by the (1,2,3-triazol-4-il)methyl bridge. All synthesized compounds showed high antibacterial activity against S. aureus within the range of MIC values 1.2–4.3 greek muM, and three of them appeared to be bactericidal with respect to tis bacterium at MBC values 4.1–4.3 greek muM. Two lead compounds showed both high antibacterial activity against the MRSA strains resistant to Ciprofloxacin and Amoxicillin within the range of MIC values 1.0–4.3 greek muM and high cytotoxicity against human cancer cell lines HuTu-80 and MCF-7 within the range of IC50 values 6.4–10.2 greek muM. This is one of the few examples when phosphonium salts exhibited both antibacterial activity and cytotoxicity against human cancer cell lines. According to the results obtained the bactericidal effect of the lead compounds, unlike classical surfactants, was not caused by a violation of the integrity of the cytoplasmic membrane of bacteria and their cytotoxic activity is most likely associated both with the induction of apoptosis along the mitochondrial pathway and the arrest of the cell cycle in the G0/G1 phase.

Refereed/Peer-reviewed Efficient methods for the removal of fluoroquinolone antibiotics from both surface and wastewaters are urgently required due to the significant global ecosystem disturbances elevated concentrations of such substances are causing. In this study, calcined magnetic iron nanoparticles (nFe) fabricated via a biosynthetic route were successfully used to remove two representative fluoroquinolone antibiotics, ofloxacin and pefloxacin from aqueous solution. The prepared nanoparticles were spherical with a particle diameter between 20 and 50 nm and were highly magnetic with a saturation magnetization of 58.5 emu g−1. Energy dispersion spectrum (EDS), Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectra (XPS) characterization all indicated the existence of substantial organic capping agent on the nanoparticles surface, which facilitated fluoroquinolone adsorption. The adsorption efficiency of ofloxacin and pefloxacin reached 100% within 300 min for a FQ concentration of 5 mg L−1. The adsorption of both ofloxacin and pefloxacin followed pseudo-second-order kinetics model and best fit the Freundlich adsorption isotherm model, with adsorption capacities of 12.8 and 16.2 mg g−1, respectively. Thermodynamic studies showed that for both fluoroquinolone adsorption was endothermic and spontaneous. A probable removal mechanism of ofloxacin and pefloxacin by nFe was proposed, involving pore-filling, hydrogen bonding, and electrostatic interaction. Regeneration and application studies, exposing nFe to real water samples, practically demonstrated that nFe was a high-quality adsorption material with significant potential for environmental remediation applications.

Recently, a lot of attentions were paid on sulfate (SO4-∙) and hydroxyl (∙OH) radicals-based advanced oxidation processes in degradation of fluoroquinolone antibiotic due to their favorable oxidation potential. This work reported an integrated peroxymonosulfate (PMS) activation process by coupling ZnFe2O4 (ZFO) with energy-saving LED for degradation and defluorination of levofloxacin (LEV). The LEV degradation efficiency reached 88.52 % within 180 min in the ZFO-500/LED/PMS system, which was higher than those of other activation systems. Both SO4-∙ and ∙OH were generated in the integrated ZFO-500/LED/PMS system by the photo-generated electrons and holes activation of PMS under the LED irradiation. The recombination of photo-generated electrons and holes was reduced. Plenty of ∙O2– and 1O2 were produced contributing to LEV degradation. The possible degradation pathways and mechanisms were proposed. This study presented a promising LED-assisted PMS activation process by ZnFe2O4 for antibiotic degradation.

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used to treat bacterial infections; however, its limited aqueous solubility inhibits its broader clinical uses. This study investigated the complexation effect of mono-6-deoxy-6-aminoethylamino-β-cyclodextrin on the aqueous solubility and bioavailability of ciprofloxacin. During complexation, the oval-shaped cavity induced by mono-aminoethylamine substitution on the primary rim of β-cyclodextrin, was considered to be a key factor according to NMR spectroscopy and molecular modeling studies. The ciprofloxacin with mono-6-deoxy-6-aminoethylamino-β-cyclodextrin complex was characterized using FE-SEM, DSC, FT-IR, T1 relaxation, 2D NOESY, and DOSY NMR spectroscopy and molecular modeling studies. The solubility property of ciprofloxacin complexed with mono-6-deoxy-6-aminoethylamino-β-cyclodextrin was enhanced by seven-fold compared to that of pure ciprofloxacin. Furthermore antibacterial activity of that complex against methicillin-resistant Staphylococcus aureus was enhanced and it clearly showed the growth inhibition. The mono-6-deoxy-6-aminoethylamino-β-cyclodextrin has the potential to be utilized for other oblong guest molecules besides ciprofloxacin based on the novel induced elliptical cavity.

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(e-caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 ± 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG–Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections.

The fluoroquinolones are one of the most widely used classes of antibiotics. Enrofloxacin belongs to the class of fluoroquinolone antibiotics that have been intensively used for the treatment of bacterial infections in veterinary medicine. When antibiotic residues enter the soil, the main processes determining their persistence are sorption to organic particles and degradation. The article presents the results of studies on the sorption of enrofloxacin by different crops, provided that it’s various concentrations in the soil (1000mg·kg−1, 100mg·kg−1, 10mg·kg−1). Experimental studies have shown that the activity of absorbed antibiotics depends on its concentration in the soil and species of an agricultural plant. It was found that the most active antibiotic absorbs Lactuca sativa var. Crispa and Calendula officinalis. The lowest content of enrofloxacin among the five plants was in Mentha piperita. Adding to the soil of enrofloxacin at a concentration of 1000 mg·kg−1 leads to the formation of a high level of soil toxicity. In model ecosystems with Thymus serpillum and Mentha piperita, soil toxicity was more than 70%. The toxicity of enrofloxacin in the soil within In vivo experiments was on average 10% lower than in laboratory tests. The highest phytotoxic effect was observed in the soil of model ecosystems, where the concentration of enrofloxacin was 1000 mg·kg−1. It should be noted that in the soil where Lactuca sativa was grown, the phytotoxic effect was 56.17 % (In vitro) and 49.22% (In vivo). This is due to the active absorption of antibiotic by plants, which minimized the toxicity of the soil. The different terrestrial toxicological effects of enrofloxacin were studied using a series of bioassays and including sorption of fluoroquinolone antibiotic by five crop plants. Enrofloxacin is highly resistant, its biodegradation process is longer than other antibiotics, it is actively absorbed by the plants, and therefore it is necessary to control it content in phytoproduction.

Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity-based protein profiling (AfBPP) in Gram-positive and Gram-negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellular P. aeruginosa in macrophages exposed to sub-inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.

Antibiotic residues have been detected in aquatic environments worldwide. Biofilms are one of the most successful life forms, and as a result are ubiquitous in natural waters. However, the response mechanism of freshwater biofilms to the stress of various antibiotic residues is still unclear. Here, the stress of veterinary antibiotic florfenicol (FF) and fluoroquinolone antibiotic ofloxacin (OFL) on freshwater biofilms were investigated by determining the changes in the key physicochemical and biological properties of the biofilms. The results showed that the chlorophyll a content in biofilms firstly decreased to 46&ndash, 71% and then recovered to original content under the stress of FF and OFL with high, mid, and low concentrations. Meanwhile, the activities of antioxidant enzymes, including superoxide dismutase and catalase, increased between 1.3&ndash, 6.7 times their initial values. FF was more toxic to the biofilms than OFL. The distribution coefficients of FF and OFL binding in extracellular polymeric substances (EPS)-free biofilms were 3.2 and 6.5 times higher than those in intact biofilms, respectively. It indicated that EPS could inhibit the FF and OFL accumulation in biofilm cells. The present study shows that the EPS matrix, as the house of freshwater biofilms, is the primary barrier that resists the stress from antibiotic residues.

Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(i)-catalysed azide-alkyne cycloaddition (CuAAC) to link a ciprofloxacin azide derivative with alkyne-substituted green and blue fluorophores. The azide (2) and fluorophore (3 and 4) derivatives retained antimicrobial activity against Gram-positive and Gram-negative bacteria. The use of confocal fluorescent microscopy showed intracellular penetration, which was substantially enhanced in the presence of carbonyl cyanide 3-chlorophenylhydrazone as an efflux pump inhibitor in Escherichia coli.

Immunocompromised cancer patients are often at high risk of developing infections. Standard infection control measures are required to prevent the onset of infection but, under some circumstances, antimicrobial prophylaxis is necessary. We have developed a family of innovative metallo-antibiotics of general formula [Cu(N,N)(CipA)Cl] where N,N represents a phenanthrene ligand and CipA stands for a derivative of the clinically used fluoroquinolone antibiotic ciprofloxacin. The X-ray crystal structure of one member from this family, [Cu(phen)(CipA)Cl] (where phen is 1,10-phenanthroline), is also reported. These complexes combine into one drug entity a Cu-N,N-framework with DNA binding and DNA oxidant properties and an antibiotic derivative with known anti-proliferative and anti-microbial activities. The complexes were all found to exhibit excellent DNA recognition with binding affinity of lead agents in the order of ∼107 M(bp)−1. Biophysical studies involving calf thymus DNA indicate the complexes intercalate or semi-intercalate DNA via the minor groove. All complexes exhibited excellent nuclease activity with DNA strand scission being mediated predominantly via superoxide and hydroxyl radicals. The complexes were found to have promising anti-proliferative effects against a human breast adenocarcinoma cell line (MCF-7) and a human prostate carcinoma cell line (DU145) with low micromolar and, in some cases, nanomolar cytotoxicities observed. Selective targeting of Gram positive bacteria was also identified by this complex class with one lead compound having an order of magnitude greater potency against Methicillin-resistant S. aureus (MRSA) as compared to the CipA ligand. Importantly, from a clinical stand point, these complexes were also found to be well tolerated in an in vivo Galleria mellonella larvae model, which has both functional and structural similarities to that of the innate immune system of mammals.

Norfloxacin, a fluoroquinolone antibiotic, is widely used to treat microbial infections. However, untreated norfloxacin-containing wastewater poses serious threats to the ecosystem and human health. The treatment of waste expanded polystyrene (EPS) by landfilling or incineration could cause environmental problems. In this research, the feasibility of converting EPS into a valuable adsorbent for norfloxacin was evaluated. Results showed that EPS treated with H2SO4 (EPSH2SO4) effectively adsorbed norfloxacin. The optimal sulfonation conditions were 95% H2SO4 and 100 °C. Addition of 0.001 M of persulfate during sulfonation obviously shortened the sulfonation time to 7.5 min, and the adsorption ability of modified EPS increased with increasing persulfate dose. Under the experimental conditions of 25 mg L−1 norfloxacin, pH0 6.2, and 0.4 g L−1 EPSH2SO4+persulfate (dry weight), 97.2% of norfloxacin could be removed after 30 min of adsorption. The adsorption ability of EPSH2SO4+persulfate decreased with increasing solution pH0, and the optimal pH0 was 6.2. The Langmuir isotherm best described the adsorption behavior of EPSH2SO4+persulfate (qmax = 140.9 mg L−1, b = 1.97 L mg−1, R2 = 0.9992). 1 M HCl effectively regenerated the exhausted EPSH2SO4+persulfate at the optimal solid/solution ratio of 8 g L−1. EPSH2SO4+persulfate maintained excellent adsorption capacity (>80.9%) after eight adsorption-regeneration cycles.

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.

Levofloxacin is a third generation fluoroquinolone antibiotic with a broad-spectrum including both Gram positive bacteria and Gram negative bacteria, as well atypical bacteria. In order to extend the spectrum of activity and to add new biological effects, several metal complexes of levofloxacin have been obtained and reported recently. The aim of our study was to obtain new silver complexes with levofloxacin with potential broad spectrum antibacterial and antifungal activity. Therefore three new silver complexes of levofloxacin with the proposed chemical structures (levofloxacin) 2 Ag(NO 3 ), (levofloxacin) 2 Ag(NO 3 )(CH 3 OH) and (levofloxacin)Ag(C 6 H 6 O 7 )·3H 2 O were synthesized. In order to characterize the obtained complexes elemental analysis, conductivity measurement, spectroscopic, and thermal methods were used. Optimized molecular structures were determined using DFT (density functional theory) analysis. The antibacterial activity against Gram negative and Gram positive bacteria and antifungal activity against Candida spp of the complexes was tested by determination of minimum inhibitory concentration through microtitre broth dilution method.

Ciprofloxacin is a broad spectrum fluoroquinolone antibiotic that acts by the inhibition of bacterial topoisomerase type II (DNA gyrase) and have a potent activity against Gram positive and negative bacteria. However, due to its rigid and solid-state structure it suffers from limited water solubility. Improving its pharmacokinetic properties especially its water solubility is the concern of this work through the synthesis of various derivatives of ciprofloxacin with ethylene glycols through prodrug strategy without reducing its antibacterial activity. Shake-flask method was used to measure the aqueous solubility in phosphate buffer. The ciprofloxacin analogues were adequately stable at acidic and physiological pH. Synthesized derivatives were subjected to esterase-mediated hydrolysis reaction for the release of the drug from its prodrug form and showed a total hydrolysis after 25 min. Also antibacterial activity was studied against Staphylococcus aureus and Escherichia coli. Compared to ciprofloxacin, the solubility was increased for the three derivatives, and the antimicrobial activity was enhanced up to 40%.

Rupture of the triceps brachii tendon is exceedingly rare, and surgical repair is generally indicated. Fluoroquinolone antibiotics have been implicated in tendon pathology, including tendon ruptures. Triceps rupture has not been previously reported in the setting of fluoroquinolone antibiotic therapy. We present 2 cases of triceps tendon rupture after treatment with fluoroquinolones. In both cases, triceps repair was performed with good outcomes. These cases highlight a risk of fluoroquinolone-induced tendinopathy to athletes. The sports medicine team should be aware of this risk and consider it when choosing antibiotics to treat athletes.

Background The development of new effective microbicide surfactants and the search for the structure–biological activity relationship is an important and promising problem. Surfactants containing imidazolium fragment attract attention of researchers in the field of chemotherapy, because these compounds often exhibit high antimicrobial activity. The aim of this work is to identify the newly synthesized surfactants from the viewpoint of their potential usefulness in pharmacology and medicine. For this purpose, a detailed study of antimicrobial, hemolytic and cytotoxic activity of dicationic alkylimidazolium surfactants of the m-s-m (Im) series with a variable length of a hydrocarbon tail (m = 10, 12) and a spacer fragment (s = 2, 3, 4) was carried out. Methods Aggregation of surfactants in solutions was estimated by tensiometry and conductivity. Antimicrobial activity was determined by the serial dilution technique. Cytotoxic effects of the test compounds on human cancer and normal cells were estimated by means of the multifunctional Cytell Cell Imaging system. Cell Apoptosis Analysis was made by flow cytometry. Results The test compounds show high antimicrobial activity against a wide range of test microorganisms and do not possess high hemolytic activity. Importantly, some of them display a bactericidal activity comparable to ciprofloxacin fluoroquinolone antibiotic against Gram-positive bacteria, including methicillin-resistant strains of S. aureus (MRSA). The cytotoxicity of the compounds against normal and tumor human cell lines has been tested as well, with cytotoxic effect and selectivity strongly controlled by structural factor and kind of cell line. Superior results were revealed for compound 10–4-10 (Im) in the case of HuTu 80 cell line (duodenal adenocarcinoma), for which IC50 value at the level of doxorubicin and a markedly higher selectivity index (SI 7.5) were demonstrated. Flow cytometry assay shows apoptosis-inducing effect of this compound on HuTu 80 cells, through significant changes in the potential of mitochondrial membrane. Major conclusions Antibacterial properties are shown to be controlled by alkyl chain length, with the highest activity demonstrated by surfactants with decyl tail, with the length of the spacer fragment showing practically no effect. The results indicate that the mechanism of cytotoxic effect of the compounds can be associated with the induction of apoptosis via the mitochondrial pathway. General significance Selectivity against pathogenic microorganisms and low toxicity against eukaryotic cells allow considering dicationic imidazolium surfactants as new effective antimicrobial agents. At the same time, high selectivity against some cancer cell lines indicates the prospect of their using as components of new anticancer drugs.

Background: Suspicion of urinary tract infection (UTI) is the most common justification for prescribing antibiotics in nursing homes. More than half of antibiotic prescriptions for treatment of UTI in nursing homes are either unnecessary or inappropriate. Achieving a better understanding of the factors that underlie UTI treatment decisions is necessary to improve the quality of antibiotic prescribing in nursing homes. An ongoing hybrid type 2 effectiveness-implementation cluster randomized trial of a recently developed nursing home UTI recognition and management tool kit provided us with an opportunity to explore the influence of organizational, clinical, and staff attributes on UTI antibiotic prescribing practices in nursing homes. Methods: Data on antibiotic starts for suspected UTIs were collected in 29 nursing homes over a 9-month period. Antibiotic practices evaluated included total antibiotic starts per 1,000 resident days, % antibiotic starts with treatment duration >7 days, % antibiotic starts in which the initial antibiotic choice was a fluoroquinolone, and % antibiotic starts meeting UTI tool-kit criteria of appropriateness. Prior research and bivariate analyses were used to select clinical and organizational attributes as well as individual nursing staff-level retention rates for inclusion in a stepwise linear regression model for each antibiotic practice outcome. Results: In total, 602 UTI antibiotic events were evaluated. Four associations were identified for antibiotic starts including nursing home urine culture rate, ICP status, nonprofit and part-time LPN retention. Nursing homes with higher full-time LPN retention had a lower rate of antibiotic treatment duration >7 days. Full-time CNAs and part-time LPNs retention and for-profit status was associated with the proportion of fluoroquinolone antibiotic starts. No attributes influenced the proportion of antibiotic starts meeting appropriateness criteria (Fig. 1). Urine culture rates are driving overall nursing home antibiotic prescribing. Conclusions: Urine culture practices was strongly associated with UTI treatment rates in nursing homes. A variety of organizational characteristics were also associated with UTI treatment rates as well as other UTI antibiotic prescribing practices. Some of these associations appear paradoxical but may reflect increasing resident acuity and increased capacity to standardize practices through organizational centralization.Funding: Support for the project provided by the Wisconsin Partnership Program.Disclosures: None

To overcome the widespread misuse of antibiotics and reduce the growing problem of multidrug resistance, rapid, sensitive and specific novel methods to determine bacterial antibiotic susceptibility are needed. This study presents a combined dielectrophoresis (DEP) - Raman Spectroscopy (RS) method to obtain direct, real-time measurements of the susceptibility of a suspension of planktonic bacteria without labelling or other time-consuming and intrusive sample preparation processes. Using an in-house constructed DEP-Raman device, we demonstrated the susceptibility of Escherichia coli MG1655 towards the second-generation fluoroquinolone antibiotic ciprofloxacin (CP) after only 1 h of treatment, by monitoring spectral changes in the chemical fingerprint of bacteria related to the mode of action of the drug. Spectral variance was modelled by multivariate techniques and a classification model was calculated to determine bacterial viability in the exponential growth phase at the minimum bactericidal concentration (MBC) over a 3 h time span. Further tests at a sub-minimum inhibitory concentration (MIC) and with a CP-resistant E. coli were carried out to validate the model. The method was then successfully applied for class prediction in a biocide cross-induced tolerance assay that involved pre-treating E. coli with triclosan (TCS), an antimicrobial used in many consumer products. High specificity and adequate sensitivity of the proposed method was thereby demonstrated. Simultaneously, standard microbiological assays based on cell viability, turbidity and fluorescence microscopy, were carried out as reference methods to confirm the observed Raman response.