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The presence of emergent antibiotics, in livestock wastewater may affect constructed wetlands (CWs) performance in the removal of other pollutants. The main objective of this study was to evaluate the influence of two antibiotics commonly used in livestock industry, enrofloxacin and ceftiofur, on metal removal by CWs. Microcosms (0.4 m×0.3 m×0.3 m), simulating CWs, were constructed with Phragmites australis to treat livestock wastewater spiked or not with 100 µg/L of enrofloxacin or ceftiofur (individually or in mixture). Wastewater was treated during 20 one-week cycles. After one-week cycle wastewater was removed and replaced by new wastewater (with or without spiking). At weeks 1, 2, 4, 8, 14, 18 and 20, treated wastewater was analysed to determine the removal rates of metals (Zn, Cu, Fe and Mn) and of each antibiotic. At weeks 1, 8 and 20 portions of the plant root substrate were collected and metals determined. At the end of the experiment metal levels were also determined in plant tissues. Removal rate of Fe from wastewater was 99%. Removal rates of Cu and Zn were higher than 85% and 89%, respectively, whereas for Mn removal rates up to 75% were obtained. In general, no significant differences were observed through time in the removals of the different metals, indicating that the systems maintained their functionality during the experimental period. Antibiotics did not interfere with the system depuration capacity, in terms of metals removals from wastewater, and ceftiofur even promoted metal uptake by P. australis. Therefore, CWs seem to be a valuable alternative to remove pollutants, including antibiotics and metals, from livestock wastewaters, reducing the risk the release of these wastewaters might pose into the environment, although more research should be conducted with other antibiotics in CWs. © 2016 Elsevier This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT – Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020 and by the structured Programme of R&D&I INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources, reference NORTE-01-0145-FEDER-000035, namely within the Research Line ECOSERVICES (Assessing the environmental quality, vulnerability and risks for the sustainable management of the NW coast natural resources and ecosystem services in a changing world) within the R&D Institution CIIMAR (Interdisciplinary Centre of Marine and Environmental Research), supported by the Northern Regional Operational Programme (NORTE2020), through the European Regional Development Fund (ERDF).

The synthesis of a novel series of substituted 1,4-dihydropyridines was achieved in aqueous media by base-catalyzed three-component Hantzsch reaction of 2chloroquinoline-3-carbaldehydes, ammonium acetate, and alkyl acteoacetate in good to high yields. Important advantages of this method are easy access to a library of novel quinoline and quinolone derivatives, green reaction conditions with water as solvent, and ease of purification.

Stool samples from 38 travelers returning from India were screened for extended-spectrum cephalosporin- and carbapenem-resistant Enterobacteriaceae implementing standard selective plates. Twenty-six (76.3%) people were colonized with CTX-M or DHA producers, but none of the strains was colistin resistant and/or mcr-1 positive. Nevertheless, using overnight enrichment and CHROMagar Orientation plates supplemented with colistin, four people (10.5%) were found to be colonized with colistin-resistant Escherichia coli . One cephalosporin-susceptible sequence type 10 (ST10) strain carried a 4,211-bp IS Apl1-mcr-1 -IS Apl1 element in an IncHI2 plasmid backbone.

Background/aim: Community-onset urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli have increased in many parts of the world. This study aimed to determine the prevalence and risk factors for community-onset UTI caused by ESBL-producing E. coli. Materials and methods: This prospective cohort study was conducted between January 2012 and March 2014 in cases of community-onset UTI caused by E. coli. Patients with UTI due to ESBL-producing E. coli and patients with UTI due to non-ESBL-producing E. coli were compared to identify risk factors for ESBL-producing E. coli in the community. Results: A total of 305 patients (116 males [46.4%]; mean age: 57.76 ± 18.06 years) were included in the study. Among these patients, 154 (50.5%) were infected with ESBL-producing E. coli. In multivariate analysis, the healthcare-associated UTI (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.02–3.18; P = 0.041), upper urinary tract infection (OR: 3.05; 95% CI: 1.76–5.29; P < 0.0001), use of antibiotics in the preceding 6 months (OR: 2.28; 95% CI: 1.21–4.30; P = 0.011), and having two or more risk factors (OR: 4.03; 95% CI: 1.73–9.35; P = 0.001) were the significant factors associated with increased risk of community-onset UTIs due to ESBL-producing E. coli. Conclusion: The increasing prevalence of ESBL-producing E. coli makes it difficult to decide the empirical therapy in UTIs, especially in patients with two or more of the risk factors. A better understanding of the epidemiology and risk factors associated with community-onset UTIs due to ESBL-producing E. coli may have significant implications in decision-making for empirical antimicrobial treatment. © TÜBİTAK.

Background Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC ß-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. Methods The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC ß-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. Results Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5 mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. Conclusion qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC ß-lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints. © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

In the past few years, accumulating evidence in the literature supports the existence of pathways of caspase-independent programmed cell death (CI-PCD). These pathways are likely to be acting as 'death backup systems' that ensure effective removal of defective cells from the organism. Similar to classical apoptosis i.e. caspase-dependent programmed cell death (CD-PCD), the mitochondrion is the main organelle orchestrating the series of events which are required for the induction of CI-PCD. In addition, the pro-apoptotic proteins Bax and Bid are also key participants in CI-PCD. However, contrary to CD-PCD, CI-PCD involves executioners other than the caspases which include the cathepsins, the calpains and serine proteases. The protein AIF may also play an important role in the induction of CI-PCD. In this review we report current knowledge on CI-PCD and provide evidence for its regulation by chemotherapeutic agents currently used in the clinic and under investigation in clinical trials. Lastly, we discuss how the study of natural and synthetic agents triggering CI-PCD may help in the pharmacological design of a new generation of more effective chemotherapeutic drugs. The use of such drugs activating both CD-PCD and CI-PCD pathways should achieve a more successful eradication of carcinogenic cells and the attainment of lower levels of tumor resistance. © 2009 Bentham Science Publishers Ltd. 9 717 728 Tradenames: azaspirane bzl 101 chm 1 cy 103 rb 110 rb 49 xyotax Cited By :47

Mast cells are primary effectors in allergic reactions, and may have important roles in disease by secreting histamine and various inflammatory and immunomodulatory substances. Although they are classically activated by immunoglobulin (Ig)E antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions. The pathogenic roles of these substances have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, Mrgprb2, the orthologue of the human G-protein-coupled receptor MRGPRX2. Secretagogue-induced histamine release, inflammation and airway contraction are abolished in Mrgprb2-null mutant mice. Furthermore, we show that most classes of US Food and Drug Administration (FDA)-approved peptidergic drugs associated with allergic-type injection-site reactions also activate Mrgprb2 and MRGPRX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that Mrgprb2 and MRGPRX2 are targets of many small-molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice; and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MRGPRX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.

1-Arylsulfonyl-5-methoxycarbonyl-2(1H)-pyridones bearing an electron-withdrawing group at ortho or meta position for sulfonyl group were chemoselectively prepared using NaH as a base in good yields. Diels-Alder reactions of 1-arylsulfonyl-2(1H)-pyridones with 2, 3-dimethyl-1, 3-butadiene afforded stereoselectively quinolone derivatives under atmospheric pressures. But it seems the substituent group on the benzene ring have a little influence on the yields.

Background: Foot infection is the most common cause of non-traumatic amputation in people with diabetes. Most diabetic foot infections (DFIs) require systemic antibiotic therapy and the initial choice is usually empirical. Although there are many antibiotics available, uncertainty exists about which is the best for treating DFIs. Objectives: To determine the effects and safety of systemic antibiotics in the treatment of DFIs compared with other systemic antibiotics, topical foot care or placebo. Search methods: In April 2015 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library); Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE, and EBSCO CINAHL. We also searched in the Database of Abstracts of Reviews of Effects (DARE; The Cochrane Library), the Health Technology Assessment database (HTA; The Cochrane Library), the National Health Service Economic Evaluation Database (NHS-EED; The Cochrane Library), unpublished literature in OpenSIGLE and ProQuest Dissertations and on-going trials registers. Selection criteria: Randomised controlled trials (RCTs) evaluating the effects of systemic antibiotics (oral or parenteral) in people with a DFI. Primary outcomes were clinical resolution of the infection, time to its resolution, complications and adverse effects. Data collection and analysis: Two review authors independently selected studies, assessed the risk of bias, and extracted data. Risk ratios (RR) were estimated for dichotomous data and, when sufficient numbers of comparable trials were available, trials were pooled in a meta-analysis. Main results: We included 20 trials with 3791 participants. Studies were heterogenous in study design, population, antibiotic regimens, and outcomes. We grouped the sixteen different antibiotic agents studied into six categories: 1) anti-pseudomonal penicillins (three trials); 2) broad-spectrum penicillins (one trial); 3) cephalosporins (two trials); 4) carbapenems (four trials); 5) fluoroquinolones (six trials); 6) other antibiotics (four trials). Only 9 of the 20 trials protected against detection bias with blinded outcome assessment. Only one-third of the trials provided enough information to enable a judgement about whether the randomisation sequence was adequately concealed. Eighteen out of 20 trials received funding from pharmaceutical industry-sponsors. The included studies reported the following findings for clinical resolution of infection: there is evidence from one large trial at low risk of bias that patients receiving ertapenem with or without vancomycin are more likely to have resolution of their foot infection than those receiving tigecycline (RR 0.92, 95% confidence interval (CI) 0.85 to 0.99; 955 participants). It is unclear if there is a difference in rates of clinical resolution of infection between: 1) two alternative anti-pseudomonal penicillins (one trial); 2) an anti-pseudomonal penicillin and a broad-spectrum penicillin (one trial) or a carbapenem (one trial); 3) a broad-spectrum penicillin and a second-generation cephalosporin (one trial); 4) cephalosporins and other beta-lactam antibiotics (two trials); 5) carbapenems and anti-pseudomonal penicillins or broad-spectrum penicillins (four trials); 6) fluoroquinolones and anti-pseudomonal penicillins (four trials) or broad-spectrum penicillins (two trials); 7) daptomycin and vancomycin (one trial); 8) linezolid and a combination of aminopenicillins and beta-lactamase inhibitors (one trial); and 9) clindamycin and cephalexin (one trial). Carbapenems combined with anti-pseudomonal agents produced fewer adverse effects than anti-pseudomonal penicillins (RR 0.27, 95% CI 0.09 to 0.84; 1 trial). An additional trial did not find significant differences in the rate of adverse events between a carbapenem alone and an anti-pseudomonal penicillin, but the rate of diarrhoea was lower for participants treated with a carbapenem (RR 0.58, 95% CI 0.36 to 0.93; 1 trial). Daptomycin produced fewer adverse effects than vancomycin or other semi-synthetic penicillins (RR 0.61, 95%CI 0.39 to 0.94; 1 trial). Linezolid produced more adverse effects than ampicillin-sulbactam (RR 2.66; 95% CI 1.49 to 4.73; 1 trial), as did tigecycline compared to ertapenem with or without vancomycin (RR 1.47, 95% CI 1.34 to 1.60; 1 trial). There was no evidence of a difference in safety for the other comparisons. Authors' conclusions: The evidence for the relative effects of different systemic antibiotics for the treatment of foot infections in diabetes is very heterogeneous and generally at unclear or high risk of bias. Consequently it is not clear if any one systemic antibiotic treatment is better than others in resolving infection or in terms of safety. One non-inferiority trial suggested that ertapenem with or without vancomycin is more effective in achieving clinical resolution of infection than tigecycline. Otherwise the relative effects of different antibiotics are unclear. The quality of the evidence is low due to limitations in the design of the included trials and important differences between them in terms of the diversity of antibiotics assessed, duration of treatments, and time points at which outcomes were assessed. Any further studies in this area should have a blinded assessment of outcomes, use standardised criteria to classify severity of infection, define clear outcome measures, and establish the duration of treatment. © 2015 The Cochrane Collaboration.

Objectives: To describe the prevalence and risk factors for infection due to AmpC ?-lactamase-producing Escherichia coli (AmpC-EC). Methods: For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1:2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. Results:We identified 243 (1.1%) AmpC-EC strains out of 21563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P,0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P,0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P1/40.008] was independently associated with AmpC-EC in the multivariate analysis. Conclusions: Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

In this study, we investigated the effects of antibacterial drugs (moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium) on human serum paraoxonase-1 (hPON1) enzyme activity from human serum in vitro conditions. For this purpose, hPON1 enzyme was purified from human serum using simple chromatographic methods. The antibacterial drugs exhibited inhibitory effects on hPON1 at low concentrations. Ki constants were calculated to be 2.641 ± 0.040 mM, 5.525 ± 0.817 mM, 35.092 ± 1.093 mM, 252.762 ± 5.749 mM and 499.244 ± 10.149 mM, respectively. The inhibition mechanism of moxifloxacin hydrochloride was competitive, whereas levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium were noncompetitive inhibitors. © 2014 Informa UK Ltd. All rights reserved.

This study aimed to identify and characterize class 1 and 2 integrons and plasmid-mediated quinolones resistance (PMQR) genes in a collection of 113 multidrug resistance (MDR) Escherichia coli isolated from farm and wild lagomorphs between 2006 and 2008 in Northern Italy. Strains were examined for antimicrobial susceptibility by agar disk diffusion method and E-test for colistin (COL); integrons and gene cassettes content by real-time polymerase chain reaction (PCR) and DNA sequencing; PMQR genes by PCR and DNA sequencing; clonal relatedness by multilocus sequence typing; and plasmids by PCR-based replicon typing. Class 1 integrons were detected in 69 isolates (47 farm rabbits, 14 wild rabbits, and 8 wild hares). No class 2 integrons were found. Five different gene cassettes arrays were identified (aadA1, dfrA1-aadA1, orf in682-dhfrA5, orf in682-dfrA5-orfD ins21, and dfrA17-aadA5). Fifteen percent (17/113) of isolates carried oqxAB, no other PMQR determinants. All but one oqxAB-positive E. coli strains were recovered from farm rabbits. Seven out of 17 strains were associated with the predominant ST238 and carried from three to six different plasmid types, such as IncF, IncHI1, IncI1, IncN, IncP, IncX1, IncY, and ColE. COL resistance was identified in 6/113 strains (5.3%). This study provides new insights on the resistance phenotypes and the prevalence and dissemination of oqxAB in E. coli from farm and wild lagomorphs, suggesting that these animals may be reservoir of these genetic determinants in Italy and thus a potential source of PMQR E. coli for humans. PMQR mediated by oqxAB has not been detected in farm and wild lagomorphs before.

WOS: 000340538700017, PubMed ID: 24789652, The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17-21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.

BACKGROUND Bedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits mycobacterial ATP synthase, has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis, when added to a preferred background regimen for 8 weeks. METHODS In this phase 2b trial, we randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in combination with a preferred background regimen. The primary efficacy end point was the time to sputum-culture conversion in liquid broth. Patients were followed for 120 weeks from baseline. RESULTS Bedaquiline reduced the median time to culture conversion, as compared with placebo, from 125 days to 83 days (hazard ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80; P

The objective of this work was to investigate the bactericidal activity of enrofloxacin against gyrA mutant and qnr-containing Escherichia coli isolates from animals. The minimum inhibitory concentrations (MICs) of gyrA mutant and qnr-containing E coli isolates ranged from 1 mu g/ml to 32 mu g/ml for enrofloxacin. Time-kill experiments were performed using selected E coli isolates. For the time-kill experiments, the colony counts were determined by plating each diluted sample onto plate count agar and an integrated pharmacokinetic/pharmacodynamics area measure (log ratio area) was applied to the colony-forming units (cfu) data. In general, enrofloxacin exhibited bactericidal activity against all the gyrA mutant E coli isolates at all concentrations greater than four times the MIC. However, the bactericidal activity of enrofloxacin for all the qnr-containing E coli isolates was less dependent on concentration. The results of the present study indicated that the genetic mechanism of resistance might account for the different bactericidal activities of enrofloxacin observed for the gyrA mutant and the qnr-containing E coli isolates. Therefore, in addition to MIC assays, genetic mechanism-based pharmacodynamic models should be used to provide accurate predictions of the effects of drugs on resistant bacteria. European Cooperation in Science and Technology (COST) (BM0701)

The blaESBL and blaAmpC genes in Enterobacteriaceae are spread by plasmid-mediated integrons, insertion sequences, and transposons, some of which are homologous in bacteria from food animals, foods, and humans. These genes have been frequently identified in Escherichia coli and Salmonella from food animals, the most common being blaCTX-M-1, blaCTX-M-14, and blaCMY-2. Identification of risk factors for their occurrence in food animals is complex. In addition to generic antimicrobial use, cephalosporin usage is an important risk factor for selection and spread of these genes. Extensive international trade of animals is a further risk factor. There are no data on the effectiveness of individual control options in reducing public health risks. A highly effective option would be to stop or restrict cephalosporin usage in food animals. Decreasing total antimicrobial use is also of high priority. Implementation of measures to limit strain dissemination (increasing farm biosecurity, controls in animal trade, and other general postharvest controls) are also important.

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23; P = 0.002) was the only independent predictor of subsequent isolation of a TR strain.

The aim of this study were to detect the gyrA, parC and marR mutations and qnr genes (qnrA, qnrB and qnrS) in 120 strains of Escherichia coli isolated from animals. European Committee on Antimicrobial Susceptibility Testing and Clinical Laboratory Standards Institute disc diffusion and minimum inhibitory concentration (MIC) tests, respectively, were used to determine fluoroquinolone (FQ) resistance, and molecular methods were used to detect the mutations and the genes. E coli isolates with an MIC of >= 8 mg/l had mutation at Ser-80 in parC in addition to mutations at Ser-83, Asp-87 or both in gyrA. The nucleotide change was detected in marR (Ser-3 -> Asn, Ala-53 -> Glu, Gly-103 -> Ser, Tyr-137 -> His). Only four E coli isolates (3.3 per cent) contained qnrA and qnrS, and qnrB was not detected. Two E coli isolates from healthy calves also contained qnrA and qnrS. The MICs of enrofloxacin and danofloxacin for qnr-containing E coli isolates ranged from 32 mg/l to 256 mg/l. The results of this study indicated that the FQ-resistant E coli isolates presented an alteration in gyrA (Ser-83 -> Leu, Asp-87 -> Asn) and parC (Ser-80 -> Ile) with high MICs (8-256 mg/l), and there was a low prevalence of qnr genes among E coli isolated from animals. European Cooperation in Science and Technology (COST) - BM0701

The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.

Background Fluoroquinolone resistance is a serious threat in the battle against the treatment of multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Fluoroquinolone resistant isolates from India had shown to have evolved several mutants in the quinolone resistance determining region (QRDR) of DNA gyrase A subunit (GyrA), the target of fluoroquinolone. In view of high prevalence of mutations in the 'hot spot' region, a study on combinatorial drug design was carried out to identify better analogues for the treatment of MDR-TB. The gyrA subunit 'hot spot' region of codons 90, 94 and 95 were modeled into their corresponding protein folds and used as receptors for the docking studies. Further, invitro tests were carried using the parent compounds, namely gatifloxacin and moxifloxacin and correlated with the obtained docking scores. Results Molecular docking and in vitro studies correlated well in demonstrating the enhanced activity of moxifloxacin, when compared to gatifloxacin, on ofloxacin sensitive and resistant strains comprising of clinical isolates of MDR-TB. The evolved lead structures targeting against mutant QRDR receptors were guanosine and cholesteryl esters of gatifloxacin and moxifloxacin. They showed consistently high binding affinity values of -10.3 and -10.1 kcal/mol respectively with the target receptors. Of these, the guanosine ester showed highest binding affinity score and its log P value lied within the Lipinski's range indicating that it could have better absorptivity when it is orally administered thereby having an enhanced activity against MTB. Conclusions The docking results showed that the addition of the cholesteryl and guanosine esters to the 'DNA gyrase binding' region of gatifloxacin and moxifloxacin enhanced the binding affinity of these parent molecules with the mutant DNA gyrase receptors. Viewing the positive correlation for the docking and in vitro results with the parent compounds, these lead structures could be further evaluated for their in vitro and in vivo activity against MDR-TB.

A 23-year-old female patient presented with a 3-day history of dysarthria and gait impairment. Her medical history was significant for peptic ulcus for which she was receiving ornidazole (1 g/day), amoxicillin (2 g/day) and lansoprazol (60 mg/day) treatment for 5 weeks. After consumption of a total dose of 35 g ornidazole, her neurological signs and symptoms appeared. There was no family history of neurological or autoimmune disorders. On examination at admission to hospital, she was alert, oriented to person, place and time, but emotionally labile. She had moderate scanning dysarthria, horizontal gaze-evoked nystagmus and bilateral severe limb dysmetria and dysdiadochokinesia. Her gait was ataxic. The rest of the general and neurological examination was unremarkable. Routine biochemistry and urine analysis findings were unremarkable. The values for peripheral blood leucocytes, erythrocyte sedimentation rate and analysis of cerebrospinal fluid obtained by lumbar puncture were normal. A brain MRI demonstrated markedly increased signal intensity symmetrically involving the dentate nuclei, dorsal pontine tegmentum lying in the …

The antibacterial activity of ciprofloxacin-encapsulated silica nanoshells synthesized from gold@silica core-shell nanoparticles has been investigated. The minimum inhibitory concentration of the material was found using the agar dilution method, and it showed better antibacterial activity compared to free ciprofloxacin in the case of Escherichia coli DH5?, whereas the same activity was found for Lactococcus lactis MG 1363. Hydrophobicity measurements carried out in an octanol-water mixture suggested that ciprofloxacin @SiO 2 is distributed almost equally in the aqueous and nonaqueous phases. The kinetics of the uptake of ciprofloxacin @SiO2 was compared with that of free ciprofloxacin. Fluorescence imaging studies carried out using fluorescein isothiocyanate@SiO2 showed that the nanoshells enter the bacterial cell. The uptake of silica shells has been probed by transmission electron microscopy also. � 2006 American Chemical Society.

A facile amination of quinolone carboxylic acids to fluoroquinolone antibacterials under microwave irradiation is described. ? 2001 Elsevier Science Ltd. All rights reserved.

2-Heptyl-3-hydroxy-4-quinolone, known as the Pseudomonas Quinolone Signal, is a key regulator of bacterial cooperative behaviour known as quorum sensing. A simple electrochemical strategy was employed for its sensitive detection using a bare boron-doped diamond electrode by cyclic voltammetry and amperometry. PQS (and potentially other quinolones) was then detected in cultures of P. aeruginosa pqsL - mutant strains. © 2011 The Royal Society of Chemistry.

Fluoroquinolones constitute a group of emerging pollutants and their occurrence in different environmental compartments is becoming object of increasing public concern due to their ecotoxicological effects and the potential to develop resistant bacteria. This study aimed to investigate the biodegradation of moxifloxacin (MOX), for which studies in the literature are very scarce. An activated sludge (AS) consortium and three bacterial strains able to degrade fluoroaromatic compounds - strains F11, FP1 and S2 - were tested. Biodegradation studies were conducted using acetate as a bulk carbon source. Strain F11 showed the highest biodegradation capacity, being able to completely consume and dehalogenate 7.5 μM of the target antibiotic when daily co-supplemented with acetate present as a readily degradable organic substrate in wastewaters. MOX could be used by strain F11 as a sole nitrogen source but the presence of an external nitrogen source in the culture medium was essential for complete biodegradation. Strain F11 was capable of completely consuming MOX in a range between 2 and 11 μM, although stoichiometric fluoride release was not obtained for the highest tested concentration. The antibacterial activity of residual MOX and of the metabolic products potentially resultant from the biodegradation process was investigated by agar diffusion tests, demonstrating that MOX biodegradation is associated with the elimination of the antibacterial properties of the target antibiotic and of the produced metabolites, which is an important result, as the activity of antibiotics and/or their metabolites in the environment, even at low levels, may lead to the development of resistant bacterial strains. Overall, the results obtained in this study suggest that strain F11 is a promising microorganism for the treatment of waters contaminated with MOX, where it could be used for bioaugmentation/bioremediation purposes. To the best of our knowledge, this is the first study reporting complete removal and dehalogenation of MOX by a single microorganism. © 2015 Elsevier. M.F. Carvalho acknowledges the support of Fundação para a Ciência e a Tecnologia (FCT), Portugal, through the research grant SFRH/BPD/44670/2008 and Investigator FCT program (IF/00791/2013) supported by FCT, Fundo Social Europeu (FSE), Programa Operacional Potencial Humano (POPH) and Quadro de Referência Estratégico Nacional (QREN). A.S. Maia wishes to acknowledge a research grant from FCT (SFRH/BD/86939/2012), FSE, POPH and QREN. This work was supported by FCT through the projects PTDC/EBB-EBI/111699/2009, PEst-OE/EQB/LA0016/2013 and CEQUIMED-PEst-OE/SAU/UI4040/2014. The authors also thank to COST Action ES1202: Conceiving Wastewater Treatment in 2020 – Energetic, environmental and economic challenges and UID/Multi/04423/2013 through national funds provided by FCT – Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020.