WorldWideScience

Sample records for quinolones

  1. Quinolone pharmacokinetics.

    Science.gov (United States)

    Robson, R A

    1992-12-01

    Fluoroquinolones have broad antibacterial spectra and are active against most Gram-negative and many Gram-positive species. They exhibit excellent oral bioavailability, extensive tissue penetration, low protein binding, and a long elimination half-life. This review compares and contrasts the pharmakonetics of some quinolone antibiotics - especially pefloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, fleroxacin and lomefloxacin - in terms of their adsorption, distribution, metabolism, elimination, and interactions with other drugs and with food. In addition, the pharmacokinetics of these agents in the elderly and in patients with renal or hepatic impairment is discussed. The fluoroquinolones are established as a major class of antibiotics in the treatment of infections but pharmacokinetics factors should be considered when deciding on the most appropriate of these agents to use in individual patients.

  2. Dysglycemia associated with quinolones.

    Science.gov (United States)

    El Ghandour, Sarah; Azar, Sami T

    2015-06-01

    Antimicrobial therapy is well known to be associated with fluctuations of blood glucose levels. This review aims at exploring the association between glycemic fluctuations and antibiotics mainly focusing on quinolones. Quinolones are associated with hypoglycemia and hyperglycemia. Several mechanism are proposed to explain this causality.

  3. Photoprocesses in quinolone substituted

    Science.gov (United States)

    Vasilyeva, N. Y.; Vusovich, O. V.

    2002-03-01

    In the present work the analysis of the possible ways of energy degradation of electron excited states of 4-methyl-7- hydxyquinolone-2 (Q) and its protolytic species is presented (Figure 1); a ratio of radiative and nonradiative channels of deactivation of energy of electronic excitation is established; constants of photophysical processes (internal and intercrossing conversion), proceeding after act of absorption of light are designed. Study of exited state intramolecular proton transfer (ESIPT) in quinolones is interesting as a source of information on the relative importance of these processes in the photophysics and photochemistry of such molecular systems.

  4. Quinolone resistance: much more than predicted

    Directory of Open Access Journals (Sweden)

    Alvaro eHernandez

    2011-02-01

    Full Text Available Since quinolones are synthetic antibiotics, it was predicted that mutations in target genes would be the only mechanism through which resistance could be acquired, because there will not be quinolone resistance genes in nature. Contrary to this prediction, a variety of elements ranging from efflux pumps, target-protecting proteins and even quinolone-modifying enzymes have been shown to contribute to quinolone resistance. The finding of some of these elements in plasmids indicates that quinolone resistance can be transferable. As a result, there has been a developing interest on the reservoirs for quinolone resistance genes and on the potential risks associated with the use of these antibiotics in non-clinical environments. As a matter of fact, plasmid-encoded, quinolone-resistance qnr genes originated in the chromosome of aquatic bacteria, thus the use of quinolones in fish farming might constitute a risk for the emergence of resistance. Failure to predict the development of quinolone resistance reinforces the need of taking into consideration the wide plasticity of biological systems for future predictions. This plasticity allows pathogens to deal with toxic compounds, including those with a synthetic origin as quinolones.

  5. Mechanism of quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

    2014-03-18

    Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.

  6. In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria.

    Science.gov (United States)

    López, Y; Tato, M; Espinal, P; Garcia-Alonso, F; Gargallo-Viola, D; Cantón, R; Vila, J

    2013-12-01

    In vitro activity of ozenoxacin, a novel nonfluorinated topical (L. D. Saravolatz and J. Leggett, Clin. Infect. Dis. 37:1210-1215, 2003) quinolone, was compared with the activities of other quinolones against well-characterized quinolone-susceptible and quinolone-resistant Gram-positive bacteria. Ozenoxacin was 3-fold to 321-fold more active than other quinolones. Ozenoxacin could represent a first-in-class nonfluorinated quinolone for the topical treatment of a broad range of dermatological infections.

  7. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  8. [Quinolones. Nowadays perspectives and mechanisms of resistance].

    Science.gov (United States)

    Álvarez-Hernández, Diego Abelardo; Garza-Mayén, Gilda Sofía; Vázquez-López, Rosalno

    2015-10-01

    Quinolones are a family of synthetic broad-spectrum antimicrobial drugs whose target is the synthesis of DNA. They directly inhibit DNA replication by interacting with two enzymes; DNA gyrase and topoisomerase IV. They have been widely used for the treatment of several community and hospital acquired infections, in the food processing industry and in the agricultural field, making the increasing incidence of quinolone resistance a frequent problem associated with constant exposition to diverse microorganisms. Resistance may be achieved by three non-exclusive mechanisms; through chromosomic mutations in the Quinolone Resistance-Determining Regions of DNA gyrase and topoisomerase IV, by reducing the intracytoplasmic concentrations of quinolones actively or passively and by Plasmid-Mediated Quinolones-Resistance genes, [Qnr determinant genes of resistance to quinolones, variant gene of the aminoglycoside acetyltransferase (AAC(6')-Ib-c)] and encoding genes of efflux pumps (qepA and oqxAB)]. The future of quinolones is uncertain, however, meanwhile they continue to be used in an irrational way, increasing resistance to quinolones should remain as an area of primary priority for research.

  9. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  10. [Review and categorization of quinolone antibiotics].

    Science.gov (United States)

    Benes, Jirí

    2005-02-01

    No standard categorization of quinolone antibiotics into generations may be found in either Czech or world literature. The author recommends a categorization into four groups defined according to their spectrum of action and utilization: 1) preparations for the treatment of urinary tract infections; 2) systemically acting quinolones chiefly efficacious against Gram-negative bacteria; 3) so-called respiratory quinolones; and 4) quinolones with a very broad spectrum of action suitable for the treatment of very complicated infections. The author describes the chief characteristics of the most important quinolone antibiotics, including preparations either in their development stage or whose development has been prematurely interrupted because of adverse side-effects. The list includes all preparations that are or were temporarily registered in the Czech Republic.

  11. Evaluation of quinolone antibacterial consumption

    Directory of Open Access Journals (Sweden)

    E. P. Bernaz

    2016-08-01

    Full Text Available Quinolones are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected and as first-line therapy is recommended. To determine the place, compare and analyze the use of quinolone antibacterial in the most important departments of EMI during 2009 to 2014 and to assess their results for improvement of patients treatment quality was designed this study. In the evaluated period consumption of quinolone antibacterial in EMI recorded a decline from 91 to 46 DDD/1000 or by 49.45%, in IC departaments from 338.6 to 132.07 or by 61%, and vice versa in SSOT departments an increase from 41.28 to 57.59 DDD/1000 or by 31.51%. Medium annual consumption in all institution recorded 63.03 DDD/1000, respectvely 174.90 in IC and 45.10 in SSOT departments. In 2014 IC departments recorded 2439.8 lei per DDD/1000, that was 8.72 times more than cost of 279.9 lei in SSOT departments and 7.51 times than 324.96 lei per DDD/1000 in all EMI. The yearly medium in EMI is around the same with all other international hospitals of 66.13 DDD/1000 and by 27.23% higher than 49.54 DDD/1000 recorded in large acute Australian public hospitals. The obtained results will be an important data for optimization in planning annual hospital necessities and rational antimicrobial prescribing as well as suggest the idea for expansion development and support antimicrobial stewardship initiatives.

  12. Conjugation between quinolone-susceptible bacteria can generate mutations in the quinolone resistance-determining region, inducing quinolone resistance.

    Science.gov (United States)

    Pitondo-Silva, André; Martins, Vinicius Vicente; Silva, Carolina Fávero da; Stehling, Eliana Guedes

    2015-02-01

    Quinolones are an important group of antibacterial agents that can inhibit DNA gyrase and topoisomerase IV activity. DNA gyrase is responsible for maintaining bacteria in a negatively supercoiled state, being composed of subunits A and B. Topoisomerase IV is a homologue of DNA gyrase and consists of two subunits codified by the parC and parE genes. Mutations in gyrA and gyrB of DNA gyrase may confer resistance to quinolones, and the majority of resistant strains show mutations between positions 67 and 106 of gyrA, a region denoted the quinolone resistance-determining region (QRDR). The most frequent substitutions occur at positions 83 and 87, but little is known about the mechanisms promoting appearance of mutations in the QRDR. The present study proposes that some mutations in the QRDR could be generated as a result of the natural mechanism of conjugation between bacteria in their natural habitat. This event was observed following conjugation in vitro of two different isolates of quinolone-susceptible Pseudomonas aeruginosa, which transferred plasmids of different molecular weights to a recipient strain of Escherichia coli (HB101), also quinolone-susceptible, generating two different transconjugants that presented mutations in DNA gyrase and acquisition of resistance to all quinolones tested.

  13. Mechanisms of drug resistance: quinolone resistance.

    Science.gov (United States)

    Hooper, David C; Jacoby, George A

    2015-09-01

    Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.

  14. Synthesis of Quinolone Analogues:7-[(2S, 4R)-2-Aminomethyl-4- hydroxypyrrolidin-1-yl] Quinolones

    Institute of Scientific and Technical Information of China (English)

    Jiu Yu LIU; Hui Yuan GUO

    2004-01-01

    New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone-3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.

  15. The safety of quinolones in pregnancy.

    Science.gov (United States)

    Yefet, Enav; Salim, Raed; Chazan, Bibiana; Akel, Hiba; Romano, Shabtai; Nachum, Zohar

    2014-11-01

    Quinolones and fluoroquinolones are highly efficient antibiotics. However, concerns regarding possible harmful effects have limited their use during pregnancy. Nevertheless, accumulating clinical data suggest that they may be safe during pregnancy. This review aimed to explore the mechanisms of action of the quinolones and fluoroquinolones, which set the stage for concerns regarding possible teratogenic and mutagenic effects; to clarify the clinical dilemmas that brought forth the necessity in reevaluating the use of those medications during pregnancy; and to review the accumulated data regarding their safety during pregnancy in animal models and humans.

  16. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and

  17. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  18. Proficiency study for quinolones in egg

    NARCIS (Netherlands)

    Berendsen, B.J.A.; Stolker, A.A.M.

    2008-01-01

    Studie naar het voorkomen van quinolonen in eieren, beschrijving van de testmaterialen, evaluatie van de toegepaste methoden, resultaten en discussieThe aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of quinolones i

  19. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  20. The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Abdul Naeem

    2016-03-01

    Full Text Available Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites—the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1 mutation in the target site (gyrase and/or topoisomerase IV of quinolones; (2 plasmid-mediated resistance; and (3 chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV. In the case of

  1. The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.

    Science.gov (United States)

    Naeem, Abdul; Badshah, Syed Lal; Muska, Mairman; Ahmad, Nasir; Khan, Khalid

    2016-03-28

    Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites--the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1) mutation in the target site (gyrase and/or topoisomerase IV) of quinolones; (2) plasmid-mediated resistance; and (3) chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV). In the case of chromosome

  2. Quinolones in the treatment of Salmonella carriers.

    Science.gov (United States)

    Rodríguez-Noriega, E; Andrade-Villanueva, J; Amaya-Tapia, G

    1989-01-01

    Infections caused by Salmonella typhi are commonly followed by a chronic carrier state despite positive clinical and initial bacteriologic responses. The use of primary antibiotics like chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole has several major drawbacks, including in some instances the failure to prevent the carrier state. The appearance worldwide of strains with multiple resistance to the most commonly used regimens has prompted the search for new forms of therapy. Among the agents studied have been third-generation cephalosporins and quinolones, which are active in vitro against bacterial enteropathogens like S. typhi. Resolution of chronic carriage of S. typhi and other salmonellae is difficult, and regimens commonly fail (including those that combine antibiotic administration with removal of the gallbladder). In addition to being active in vitro against Salmonella species, the newer quinolones adequately penetrate the intestinal lumen, liver, bile, and gallbladder. Initial experience with norfloxacin and ciprofloxacin in oral treatment of the chronic S. typhi carrier state in adults has been promising.

  3. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance.

    Science.gov (United States)

    Aldred, Katie J; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2013-04-01

    Although quinolones are the most commonly prescribed antibacterials, their use is threatened by an increasing prevalence of resistance. The most common causes of quinolone resistance are mutations of a specific serine or acidic residue in the A subunit of gyrase or topoisomerase IV. These amino acids are proposed to serve as a critical enzyme-quinolone interaction site by anchoring a water-metal ion bridge that coordinates drug binding. To probe the role of the proposed water-metal ion bridge, we characterized wild-type, GrlA(E85K), GrlA(S81F/E85K), GrlA(E85A), GrlA(S81F/E85A) and GrlA(S81F) Bacillus anthracis topoisomerase IV, their sensitivity to quinolones and related drugs and their use of metal ions. Mutations increased the Mg(2+) concentration required to produce maximal quinolone-induced DNA cleavage and restricted the divalent metal ions that could support quinolone activity. Individual mutation of Ser81 or Glu85 partially disrupted bridge function, whereas simultaneous mutation of both residues abrogated protein-quinolone interactions. Results provide functional evidence for the existence of the water-metal ion bridge, confirm that the serine and glutamic acid residues anchor the bridge, demonstrate that the bridge is the primary conduit for interactions between clinically relevant quinolones and topoisomerase IV and provide a likely mechanism for the most common causes of quinolone resistance.

  4. New Role of Quinolones in Respiratory Tract Infections

    Directory of Open Access Journals (Sweden)

    Ronald F Grossman

    1998-01-01

    Full Text Available Because of limited activity of the standard quinolones such as ciprofloxacin and ofloxacin against some clinically important organisms including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus, new quinolones have been developed. In addition to their improved activity against S pneumoniae, some also demonstrate excellent anaerobic activity. None of the quinolones have a role to play in the treatment of paediatric infections. Quinolones (both older and newer agents have demonstrated equivalent efficacy to standard antimicrobials in the treatment of acute sinusitis. Several groups have suggested that quinolones are excellent agents in the treatment of high risk patients with acute exacerbations of chronic bronchitis. These patients include the elderly, and those with frequent exacerbations, significant comorbid conditions. long duration of chronic bronchitis and major impairment of lung function. There is no evidence to suggest that the newer quinolones will differ from the currently available agents for th is disease. The major advantage of the newer quinolones appears to be in the treatment of patients with community-acquired pneumonia where pneumococcal infection is a real concern. A new parenteral quinolone with pneumococcal activity may replace the standard macrolide/cephalosporin combination that is commonly prescribed. For patients with nosocomial pneumonia, the newer agents are alternative choices, especially among patients with early onset pneumonia (less than five days of hospitalization, but are unlikely to replace ciprofloxacin in the intensive care unit setting because of poor Pseudomonas aeruginosa coverage.

  5. Metal Complexes of Quinolone Antibiotics and Their Applications: An Update

    Directory of Open Access Journals (Sweden)

    Valentina Uivarosi

    2013-09-01

    Full Text Available Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle at the 7-position, and a carbonyl oxygen atom at the 4-position quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  6. Metal complexes of quinolone antibiotics and their applications: an update.

    Science.gov (United States)

    Uivarosi, Valentina

    2013-09-11

    Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  7. Regional variations in quinolone use in France and associated factors.

    Science.gov (United States)

    Gallini, A; Taboulet, F; Bourrel, R

    2012-11-01

    The purpose of this study was to investigate geographic variations in the use of quinolones in France and their associated factors. All reimbursement claims of antimicrobials were collected for 90 % of the French population for the year 2007. Dispensed quantities were then converted into defined daily doses (DDD) and adjusted for the age structure of the national population. Correlations between quinolone use and total antimicrobial use and some morbidity and socio-economic factors were studied using Spearman's rank correlation coefficients. On average, 2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007 in France, accounting for 10.2 % of the total antimicrobial consumption in adults. A 40 % variation was observed between the regions with the lowest (1.73 DID) and the highest use (2.44 DID). This variation was more important for anti-pneumococcal quinolones than for quinolones directed against urinary tract infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated with some regional socio-economic factors (unemployment, growth domestic product, health expenditures) and physician density, but was independent of the total antimicrobial use. After adjustment for age, large variations in quantitative and qualitative quinolone use were observed across French regions, especially for anti-pneumococcal fluoroquinolones. These results, though not controlled for potential epidemics variations, argue in favour of a possible improvement in quinolone prescribing to be achieved in some regions.

  8. Antibacterial action of quinolones: from target to network.

    Science.gov (United States)

    Cheng, Guyue; Hao, Haihong; Dai, Menghong; Liu, Zhenli; Yuan, Zonghui

    2013-08-01

    Quinolones are widely used broad-spectrum antibacterials with incomplete elucidated mechanism of action. Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated. Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug-enzyme-DNA cleavage complexes, resulting in bacteriostasis. Cell death arises from chromosome fragmentation in protein synthesis-dependent or -independent pathways according to distinguished quinolone structures. In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually. Toxin-antitoxin mazEF is triggered as an additional lethal action. Bacteria survive and develop resistance by SOS and other stress responses. Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance.

  9. Vibrational spectra study on quinolones antibiotics

    Science.gov (United States)

    Wang, Yu; Yu, Ke; Wang, Sihuan

    2006-09-01

    In order to be able to fully understand and easily identify the quilonoles, we collected IR and Raman spectra of six quinolones, and attempted to assign the attribution of the observed frequencies and their association with specific modes of vibration. According to the structure, the compounds were divided into the groups, and the similarities and differences were further studied by comparing. The result of the study shows that the frequency and intensity are comparable to the corresponding structure. The spectra not only have the commonness but also the individualities.

  10. Apigenin as an anti-quinolone-resistance antibiotic.

    Science.gov (United States)

    Morimoto, Yuh; Baba, Tadashi; Sasaki, Takashi; Hiramatsu, Keiichi

    2015-12-01

    We previously reported the first 'reverse antibiotic' (RA), nybomycin (NYB), which showed a unique antimicrobial activity against Staphylococcus aureus strains. NYB specifically suppressed the growth of quinolone-resistant S. aureus strains but was not effective against quinolone-susceptible strains. Although NYB was first reported in 1955, little was known about its unique antimicrobial activity because it was before the synthesis of the first quinolone ('old quinolone'), nalidixic acid, in 1962. Following our re-discovery of NYB, we looked for other RAs among natural substances that act on quinolone-resistant bacteria. Commercially available flavones were screened against S. aureus, including quinolone-resistant strains, and their minimum inhibitory concentrations (MICs) were compared using the microbroth dilution method. Some of the flavones screened showed stronger antimicrobial activity against quinolone-resistant strains than against quinolone-susceptible ones. Amongst them, apigenin (API) was the most potent in its RA activity. DNA cleavage assay showed that API inhibited DNA gyrase harbouring the quinolone resistance mutation gyrA(Ser84Leu) but did not inhibit 'wild-type' DNA gyrase that is sensitive to levofloxacin. An API-susceptible S. aureus strain Mu50 was also selected using agar plates containing 20mg/L API. Whole-genome sequencing of selected mutant strains was performed and frequent back-mutations (reverse mutations) were found among API-resistant strains derived from the API-susceptible S. aureus strains. Here we report that API represents another molecular class of natural antibiotic having RA activity against quinolone-resistant bacteria.

  11. A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

    Science.gov (United States)

    Shoji, Hisashi; Shirakura, Tetsuro; Fukuchi, Kunihiko; Takuma, Takahiro; Hanaki, Hideaki; Tanaka, Kazuo; Niki, Yoshihito

    2014-04-01

    The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC ≥2 μg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125-1 and 2-4 μg/ml had one and two mutations, respectively. The strains with a MFLX MIC of ≥8 μg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5-1 and ≥2 μg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with β-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.

  12. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    Science.gov (United States)

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  13. Microbial transformations of antimicrobial quinolones and related drugs.

    Science.gov (United States)

    Parshikov, Igor A; Sutherland, John B

    2012-12-01

    The quinolones are an important group of synthetic antimicrobial drugs used for treating bacterial diseases of humans and animals. Microorganisms transform antimicrobial quinolones (including fluoroquinolones) and the pharmacologically related naphthyridones, pyranoacridones, and cinnolones to a variety of metabolites. The biotransformation processes involve hydroxylation of methyl groups; hydroxylation of aliphatic and aromatic rings; oxidation of alcohols and amines; reduction of carboxyl groups; removal of methyl, carboxyl, fluoro, and cyano groups; addition of formyl, acetyl, nitrosyl, and cyclopentenone groups; and cleavage of aliphatic and aromatic rings. Most of these reactions greatly reduce or eliminate the antimicrobial activity of the quinolones.

  14. Insight into Prodrugs of Quinolones and Fluoroquinolones.

    Science.gov (United States)

    Sharma, Prabodh Chander; Piplani, Mona; Mittal, Monika; Pahwa, Rakesh

    2016-01-01

    Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

  15. Use of antibiotics and about quinolones in veterinary therapy (ro

    Directory of Open Access Journals (Sweden)

    Crina L. Mosneang

    2012-12-01

    Full Text Available In Romania are being done extensively efforts in the veterinarians education to emphasize the importance and the European regulations familiar behavior, relating to veterinary drugs prescribing, the issues of residues, of antibacterial resistance and of judicious use of the veterinary conditionigs. In this respect, the present synthesis presents an overview, a useful and necessary bibliographical remembrance to veterinary practitioner about antibiotics and quinolones in particular. Are summarized: bacterial antagonism, methods for studying the effectiveness of antibiotics, the mode of action of antibiotics, the phenomenon of resistance to antibiotics and toxic secondary phenomena caused by antibiotics, continued by information about quinolone-carbonic acid derivatives (quinolones them action mechanism, classification and presentation of the main representatives, indications and contraindications, etc. Referate is conceived in two parts about antibiotics and about quinolones.

  16. Oxidation of quinolones with peracids (an in situ EPR study).

    Science.gov (United States)

    Staško, Andrej; Milata, Viktor; Barbieriková, Zuzana; Brezová, Vlasta

    2014-01-01

    4-Oxoquinoline derivatives (quinolones) represent heterocyclic compounds with a variety of biological activities, along with interesting chemical reactivity. The quinolone derivatives possessing secondary amino hydrogen at the nitrogen of the enaminone system are oxidized with 3-chloroperbenzoic acid to nitroxide radicals in the primary step while maintaining their 4-pyridone ring. Otherwise, N-methyl substituted quinolones also form nitroxide radicals coupled with the opening of the 4-pyridone ring in a gradual oxidation of the methyl group via the nitrone-nitroxide spin-adduct cycle. This was confirmed in an analogous oxidation using N,N-dimethylaniline as a model compound. N-Ethyl quinolones in contrast to its N-methyl analog form only one nitroxide radical without a further degradation.

  17. Increasing quinolone resistance in Salmonella enterica serotype enteritidis

    DEFF Research Database (Denmark)

    Mølbak, K.; Gerner-Smidt, P.; Wegener, Henrik Caspar

    2002-01-01

    Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use...... of quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use....

  18. New cytotoxic quinolone alkaloids from fruits of Evodia rutaecarpa.

    Science.gov (United States)

    Huang, Xin; Li, Wei; Yang, Xiu-Wei

    2012-06-01

    Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1-methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these compounds were determined by spectroscopic analyses. The cytotoxic activities of all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and Hep G(2) cells were evaluated by MTT assay. The results showed that these alkaloids inhibited cell proliferation with IC(50) values between 14μM and 22μM.

  19. Quinolones: review of psychiatric and neurological adverse reactions.

    Science.gov (United States)

    Tomé, Ana M; Filipe, Augusto

    2011-06-01

    Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim of this article was to review the neurological and psychiatric adverse drug reaction (ADR) profile of quinolones, using a literature search strategy designed to identify case reports and case series. A literature search using PubMed/MEDLINE (from inception to 31 October 2010) was performed to identify case reports and case series related to quinolone-associated neurological and psychiatric ADRs. The search was conducted in two phases: the first phase was the literature search and in the second phase relevant articles were identified through review of the references of the selected articles. Relevant articles were defined as articles referring to adverse events/reactions associated with the use of any quinolone. Abstracts referring to animal studies, clinical trials and observational studies were excluded. Identified case reports were analysed by age group, sex, active substances, dosage, concomitant medication, ambulatory or hospital-based event and seriousness, after Medical Dictionary for Regulatory Activities (MedDRA®) coding. From a total of 828 articles, 83 were identified as referring to nervous system and/or psychiatric disorders induced by quinolones. 145 individual case reports were extracted from the 83 articles. 40.7% of the individual case reports belonged to psychiatric disorders only, whereas 46.9% related to neurological disorders only. Eight (5.5%) individual case reports presented both neurological and psychiatric ADRs. Ciprofloxacin, ofloxacin and pefloxacin were the quinolones with more neurological and psychiatric ADRs reported in the literature. Ciprofloxacin has been extensively used worldwide, which may explain the higher number

  20. [Sample preprocessing method for residual quinolones in honey using immunoaffinity resin].

    Science.gov (United States)

    Ihara, Yoshiharu; Kato, Mihoko; Kodaira, Tsukasa; Itoh, Shinji; Terakawa, Mika; Horie, Masakazu; Saito, Koichi; Nakazawa, Hiroyuki

    2009-06-01

    A sample preparation method was developed for determination of quinolones in honey using immunoaffinity resin. For this purpose, an immunoaffinity resin for quinolones was prepared by coupling a quinolone-specific monoclonal antibody to agarose resin. Honey samples diluted with phosphate buffer were reacted with immunoaffinity resin. After the resin was washed, quinolones were eluted with glycine-HCl. Quinolones in the eluate were determined by HPLC with fluorescence detection. No interfering peak was found on the chromatograms of honey samples. The recoveries of quinolones from samples were over 70% at fortification levels of 20 ng/g (for norfloxacin, ciprofloxacin and enrofloxacin) and 10 ng/g (for danofloxacin). The quantification limits of quinolones were 2 ng/g. This sample preprocessing method using immunoaffinity resin was found to be effective and suitable for determining residual quinolones in honey.

  1. Prevalence and characterisation of quinolone resistance mechanisms in Salmonella spp.

    Science.gov (United States)

    Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena

    2014-07-16

    The study was focused on characterisation of quinolone resistance mechanisms in Salmonella isolated from animals, food, and feed between 2008 and 2011. Testing of Minimal Inhibitory Concentrations revealed 6.4% of 2680 isolates conferring ciprofloxacin resistance. Simultaneously 37.7% and 40.8% were accounted for, respectively, nalidixic acid and ciprofloxacin Non Wild-Type populations. Amplification and sequencing of quinolone resistance determining region of topoisomerases genes in 44 isolates identified multiple amino-acid substitutions in gyrA at positions Ser83 (N=22; → Leu, → Phe, → Tyr), Asp87 (N=22; → Asn, → Gly, → Tyr) and parC (Thr57Ser, N=23; Ala141Ser, N=1). No relevant mutations were identified in gyrB and parE. Twelve patterns combining one or two substitutions were related to neither serovar nor ciprofloxacin MIC. In 92 isolates suspected for plasmid mediated quinolone resistance two qnr alleles were found: qnrS1 (or qnrS3; N=50) and qnrB19 (or qnrB10; N=24). Additionally, two isolates with chromosomally encoded mechanisms carried qnrS1 and qnrS2. All tested isolates were negative for qnrA, qnrC, qnrD, qepA, aac(6')-Ib-cr. Both chromosomal and plasmid mediated quinolone resistance determinants were found in several Salmonella serovars and Pulsed Field Gel Electrophoresis was used to assess phylogenetic similarity of selected isolates (N=82). Salmonella Newport was found to accumulate quinolone resistance determinants and the serovar was spreading clonally with either variable gyrA mutations, qnrS1/S3, or qnrB10/B19. Alternatively, various determinants are dispersed among related S. Enteritidis isolates. Antimicrobial selection pressure, multiple resistance determinants and scenarios for their acquisition and spread make extremely difficult to combat quinolone resistance.

  2. The regioselective iodination of quinolines, quinolones, pyridones, pyridines and uracil.

    Science.gov (United States)

    Dutta, Uttam; Deb, Arghya; Lupton, David W; Maiti, Debabrata

    2015-12-28

    A radical based direct C-H iodination protocol for quinolines, quinolones, pyridones, pyridines, and uracil has been developed. The iodination occurs in a C3 selective manner for quinolines and quinolones. Pyridones and pyridines undergo C3 and C5 iodination, while dimethyl uracil undergoes C5 iodination. Scope of the method was demonstrated through the rapid synthesis of both electron rich as well as electron poor heteroaromatic iodides. The protocol was found to be scalable and general, while a mechanism has been proposed.

  3. Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Du, Yuguo

    2014-09-01

    Acute toxicity of 21 quinolone antibiotics was monitored using photobacterium Vibrio fischeri assay. The minimum IC20 (inhibitory concentration for 20% luminescence elimination) was obtained at the least 18.86μmol/L for the tested quinolones. A quantitative structure-activity relationship model was established to investigate the possible mechanism for the acute toxicity. The critical physicochemical descriptors, describing σ and π atom electronegativity, implied that the electron transfer might occur between the quinolones and photobacterium V. fischeri. Although the quinolones exhibited limited acute toxicity to photobacterium, toxicity elevation was detected after their chlorination. Hence, chlorination disinfection treatment of quinolone-containing water should be of concerns.

  4. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; McPherson, Sylvia A; Wang, Pengfei; Kerns, Robert J; Graves, David E; Turnbough, Charles L; Osheroff, Neil

    2012-01-10

    Bacillus anthracis, the causative agent of anthrax, is considered a serious threat as a bioweapon. The drugs most commonly used to treat anthrax are quinolones, which act by increasing the levels of DNA cleavage mediated by topoisomerase IV and gyrase. Quinolone resistance most often is associated with specific serine mutations in these enzymes. Therefore, to determine the basis for quinolone action and resistance, we characterized wild-type B. anthracis topoisomerase IV, the GrlA(S81F) and GrlA(S81Y) quinolone-resistant mutants, and the effects of quinolones and a related quinazolinedione on these enzymes. Ser81 is believed to anchor a water-Mg(2+) bridge that coordinates quinolones to the enzyme through the C3/C4 keto acid. Consistent with this hypothesized bridge, ciprofloxacin required increased Mg(2+) concentrations to support DNA cleavage by GrlA(S81F) topoisomerase IV. The three enzymes displayed similar catalytic activities in the absence of drugs. However, the resistance mutations decreased the affinity of topoisomerase IV for ciprofloxacin and other quinolones, diminished quinolone-induced inhibition of DNA religation, and reduced the stability of the enzyme-quinolone-DNA ternary complex. Wild-type DNA cleavage levels were generated by mutant enzymes at high quinolone concentrations, suggesting that increased drug potency could overcome resistance. 8-Methyl-quinazoline-2,4-dione, which lacks the quinolone keto acid (and presumably does not require the water-Mg(2+) bridge to mediate protein interactions), was more potent than quinolones against wild-type topoisomerase IV and was equally efficacious. Moreover, it maintained high potency and efficacy against the mutant enzymes, effectively inhibited DNA religation, and formed stable ternary complexes. Our findings provide an underlying biochemical basis for the ability of quinazolinediones to overcome clinically relevant quinolone resistance mutations in bacterial type II topoisomerases.

  5. Synthesis and anticancer activity of novel curcumin-quinolone hybrids.

    Science.gov (United States)

    Raghavan, Saiharish; Manogaran, Prasath; Gadepalli Narasimha, Krishna Kumari; Kalpattu Kuppusami, Balasubramanian; Mariyappan, Palanivelu; Gopalakrishnan, Anjana; Venkatraman, Ganesh

    2015-09-01

    A number of new curcumin-quinolone hybrids were synthesised from differently substituted 3-formyl-2-quinolones and vanillin and their in vitro cytotoxicity was determined on a panel of representative cell lines (A549, MCF7, SKOV3 and H460) using MTT assay. The most potent compound 14, was analysed for its mode of action using various cell biology experiments. SKOV3 cells treated with compound 14 showed distorted cell morphology under phase contrast imaging and induction of apoptosis was confirmed by Annexin V/PE assay. Further experiments on generation of reactive oxygen species (ROS) and cell cycle analysis revealed that these hybrids induce apoptosis by ROS generation and arrest cell cycle progression in S and G2/M phase.

  6. Recent progress in the development of anti-malarial quinolones.

    Science.gov (United States)

    Beteck, Richard M; Smit, Frans J; Haynes, Richard K; N'Da, David D

    2014-08-30

    Available anti-malarial tools have over the ten-year period prior to 2012 dramatically reduced the number of fatalities due to malaria from one million to less than six-hundred and thirty thousand. Although fewer people now die from malaria, emerging resistance to the first-line anti-malarial drugs, namely artemisinins in combination with quinolines and arylmethanols, necessitates the urgent development of new anti-malarial drugs to curb the disease. The quinolones are a promising class of compounds, with some demonstrating potent in vitro activity against the malaria parasite. This review summarizes the progress made in the development of potential anti-malarial quinolones since 2008. The efficacy of these compounds against both asexual blood stages and other stages of the malaria parasite, the nature of putative targets, and a comparison of these properties with anti-malarial drugs currently in clinical use, are discussed.

  7. Antagonism of vitamin C and vitamin E on action of quinolones

    Directory of Open Access Journals (Sweden)

    Julius E. Surdjawidjaja

    2015-12-01

    Full Text Available The quinolone antibiotics are potent drugs for combating infections caused by various bacterial species with satisfactory results and relatively minimal adverse effects. Antioxidant dietary supplements, such as vitamin C (ascorbic acid and vitamin E (a-tocopherol, are occasionally prescribed along with quinolone antibiotics during the course of treatment of an infection. Therefore it is important to understand the effects of these antioxidants on the antibacterial action of quinolone antibiotics.

  8. Quinolone-based drugs against Toxoplasma gondii and Plasmodium spp.

    Science.gov (United States)

    Anquetin, Guillaume; Greiner, Jacques; Vierling, Pierre

    2005-09-01

    Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.

  9. Plasmid-Mediated Quinolone Resistance (PMQR) Genes and Class 1 Integrons in Quinolone-Resistant Marine Bacteria and Clinical Isolates of Escherichia coli from an Aquacultural Area.

    Science.gov (United States)

    Tomova, Alexandra; Ivanova, Larisa; Buschmann, Alejandro H; Godfrey, Henry P; Cabello, Felipe C

    2017-06-23

    Antimicrobial usage in aquaculture selects for antimicrobial-resistant microorganisms in the marine environment. The relevance of this selection to terrestrial animal and human health is unclear. Quinolone-resistance genes qnrA, qnrB, and qnrS were chromosomally located in four randomly chosen quinolone-resistant marine bacteria isolated from an aquacultural area with heavy quinolone usage. In quinolone-resistant uropathogenic clinical isolates of Escherichia coli from a coastal area bordering the same aquacultural region, qnrA was chromosomally located in two E. coli isolates, while qnrB and qnrS were located in small molecular weight plasmids in two other E. coli isolates. Three quinolone-resistant marine bacteria and three quinolone-resistant E. coli contained class 1 integrons but without physical association with PMQR genes. In both marine bacteria and uropathogenic E. coli, class 1 integrons had similar co-linear structures, identical gene cassettes, and similarities in their flanking regions. In a Marinobacter sp. marine isolate and in one E. coli clinical isolate, sequences immediately upstream of the qnrS gene were homologous to comparable sequences of numerous plasmid-located qnrS genes while downstream sequences were different. The observed commonality of quinolone resistance genes and integrons suggests that aquacultural use of antimicrobials might facilitate horizontal gene transfer between bacteria in diverse ecological locations.

  10. Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones.

    Science.gov (United States)

    Changkwanyeun, Ruchirada; Usui, Masaru; Kongsoi, Siriporn; Yokoyama, Kazumasa; Kim, Hyun; Suthienkul, Orasa; Changkaew, Kanjana; Nakajima, Chie; Tamura, Yutaka; Suzuki, Yasuhiko

    2015-08-01

    Quinolones have long been used as the first-line treatment for Campylobacter infections. However, an increased resistance to quinolones has raised public health concerns. The development of new quinolone-based antibiotics with high activity is critical for effective, as DNA gyrase, the target of quinolones, is an essential enzyme for bacterial growth in several mechanisms. The evaluation of antibiotic activity against Campylobacter jejuni largely relies on drug susceptibility tests, which require at least 2 days to produce results. Thus, an in vitro method for studying the activity of quinolones against the C. jejuni DNA gyrase is preferred. To identify potent quinolones, we investigated the interaction of C. jejuni DNA gyrase with a number of quinolones using recombinant subunits. The combination of purified subunits exhibited DNA supercoiling activity in an ATP dependent manner. Drug concentrations that inhibit DNA supercoiling by 50% (IC50s) of 10 different quinolones were estimated to range from 0.4 (sitafloxacin) to >100 μg/mL (nalidixic acid). Sitafloxacin showed the highest inhibitory activity, and the analysis of the quinolone structure-activity relationship demonstrated that a fluorine atom at R-6 might play the important role in the inhibitory activity against C. jejuni gyrase. Measured quinolone IC50s correlated well with minimum inhibitory concentrations (R = 0.9943). These suggest that the in vitro supercoiling inhibition assay on purified recombinant C. jejuni DNA gyrase is a useful and predictive technique to monitor the antibacterial potency of quinolones. And furthermore, these data suggested that sitafloxacin might be a good candidate for clinical trials on campylobacteriosis.

  11. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves.

    Science.gov (United States)

    Hordijk, Joost; Veldman, Kees; Dierikx, Cindy; van Essen-Zandbergen, Alieda; Wagenaar, Jaap A; Mevius, Dik

    2012-04-23

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional data on quinolone resistance mechanisms in non-pathogenic bacteria from healthy veal calves is limited. The purpose of this study was to determine the prevalence and characteristics of quinolone resistance mechanisms in Escherichia coli isolates from veal calves, after more than 20 years of quinolone usage in veal calves. MIC values were determined for all isolates collected as part of a national surveillance program on antimicrobial resistance in commensal bacteria in food-producing animals in The Netherlands. From the strains collected from veal calves in 2007 (n=175) all isolates with ciprofloxacin MIC ≥ 0.125 mg/L (n=25) were selected for this study, and screened for the presence of known quinolone resistance determinants. In this selection only chromosomal mutations in the topoisomerase type II and IV genes were detected. The number of mutations found per isolate correlated with an increasing ciprofloxacin MIC. No plasmid-mediated quinolone resistance genes were found. The contribution of efflux pumps varied from no contribution to a 16-fold increase in susceptibility. No correlation was found with the presence of resistance genes of other antimicrobial classes, even though all quinolone non-wild type isolates were resistant to 3 or more classes of antibiotics other than quinolones. Over twenty years of quinolone usage in veal calves in The Netherlands did not result in a widespread occurrence of plasmid-mediated quinolone resistance, limiting the transmission of quinolone resistance to clonal distribution.

  12. Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni.

    Science.gov (United States)

    Changkwanyeun, Ruchirada; Yamaguchi, Tomoyuki; Kongsoi, Siriporn; Changkaew, Kanjana; Yokoyama, Kazumasa; Kim, Hyun; Suthienkul, Orasa; Usui, Masaru; Tamura, Yutaka; Nakajima, Chie; Suzuki, Yasuhiko

    2016-10-01

    Amino acid substitutions providing quinolone resistance to Campyloabcter jejuni have been found in the quinolone resistance-determining region of protein DNA gyrase subunit A (GyrA), with the highest frequency at position 86 followed by position 90. In this study, wild-type and mutant recombinant DNA gyrase subunits were expressed in Escherichia coli and purified using Ni-NTA agarose column chromatography. Soluble 97 kDa GyrA and 87 kDa DNA gyrase subunit B were shown to reconstitute ATP-dependent DNA supercoiling activity. A quinolone-inhibited supercoiling assay demonstrated the roles of Thr86Ile, Thr86Ala, Thr86Lys, Asp90Asn, and Asp90Tyr amino acid substitutions in reducing sensitivity to quinolones. The marked effect of Thr86Ile on all examined quinolones suggested the advantage of this substitution in concordance with recurring isolation of quinolone-resistant C. jejuni. An analysis of the structure-activity relationship showed the importance of the substituent at position 8 in quinolones to overcome the effect of Thr86Ile. Sitafloxacin (SIT), which has a fluorinate cyclopropyl ring at R-1 and a chloride substituent at R-8, a characteristic not found in other quinolones, showed the highest inhibitory activity against all mutant C. jejuni gyrases including ciprofloxacin-resistant mutants. The results suggest SIT as a promising drug for the treatment of campylobacteriosis caused by CIP-resistant C. jejuni. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Contribution of topoisomerase IV mutation to quinolone resistance in Mycoplasma genitalium.

    Science.gov (United States)

    Yamaguchi, Yuko; Takei, Masaya; Kishii, Ryuta; Yasuda, Mitsuru; Deguchi, Takashi

    2013-04-01

    The mechanism of quinolone resistance in Mycoplasma genitalium remains poorly understood due to difficulties with in vitro culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2- to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of M. genitalium harboring substitutions in the parC or parE gene in vitro and to measure the inhibitory activities against the purified topoisomerases of M. genitalium.

  14. Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations in quinolone-resistant Escherichia coli isolated from humans and swine in Denmark

    DEFF Research Database (Denmark)

    Cavaco, Lina; Frimodt-Møller, Niels; Hasman, Henrik;

    2008-01-01

    Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were investigated in 124 Escherichia coli isolated from humans (n = 85) and swine (n = 39) in Denmark. The collection included 59 high-level CIP......-resistant isolates (MIC >= 4) from human (n = 51) and pig origin (n = 8) and 65 low-level CIP-resistant isolates (MIC >= 0.125) from human (n = 34) and pig origin (n = 31). Resistance by target modification was screened by PCR amplification and sequencing, of the quinolone resistance determining regions (QRDRs......A and qnrS genes conferring quinolone resistance by target protection were detected in two human low-level CIP-resistant isolates that did not display NAL resistance. As expected, target mutation in QRDRs was the most prevalent mechanism of quinolone resistance. This mechanism was complemented by efflux...

  15. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  16. Thermodynamic study by infrared spectroscopy of the association of 2-quinolone, some carboxylic acids, and the corresponding 2-quinolone--acid mixed dimers

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, J.C.

    1971-01-01

    Self-association of 2-quinolone in carbon tetrachloride was studied by infrared spectroscopy, using the absorption bands in the amide NH and carbonyl stretching regions. 2-Quinolone forms a cyclic dimer from which the enthalpy (..delta..H/sup 0/, kcal/mol), free energy (..delta..G/sup 0//sub 22/, kcal/mol), and entropy (..delta..S/sup 0/, eu) of association are -8.69, -6.11, and -8.76, respectively. Dimer formation is via a carbonyl-hydrogen bond, although evidence exists for the formation of a small amount of dimer via a ..pi..-hydrogen bond. 2-Quinolone was also found to form cyclic mixed dimers with carboxylic acids. Mixed dimers of 2-quinolone with benzoic, cyclohexanecarboxylic, and 4-cyclohexylbutanoic acids gave ..delta..H/sup 0/ values of -12.2, -10.3, and -10.4; ..delta..G/sup 0//sub 22/ values of -6.36, -5.94, and -5.78; and ..delta..S/sup 0/ values of -19.9, -14.8, and -15.6, respectively. Thermodynamic data on the acid dimers and spectral data on the different systems studied are also reported. The 2-quinolone-carboxylic acid interaction is of importance because of the simultaneous occurrence of quinolones and carboxylic acids in many biologically derived materials.

  17. Comparative in vitro activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, and other quinolones against clinical isolates.

    Science.gov (United States)

    Lauderdale, Tsai-Ling; Shiau, Yih-Ru; Lai, Jui-Fen; Chen, Hua-Chien; King, Chi-Hsin R

    2010-03-01

    The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, Neisseria gonorrhoeae, and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae.

  18. [Investigation of plasmid-mediated quinolone resistance in Escherichia coli strains].

    Science.gov (United States)

    Aktepe, Orhan Cem; Aşık, Gülşah; Cetinkol, Yeliz; Biçmen, Meral; Gülay, Zeynep

    2012-01-01

    Quinolones are widely used antimicrobial agents, particularly for the treatment of infections caused by gram-negative bacilli such as E.coli. As a consequence, quinolone resistance has been increasing among this species in recent years. Bacterial resistance to quinolones usually results from mutations in the chromosomal genes which encode topoisomerases and also the expression of efflux pumps and loss of porines contributed to development of quinolone resistance. However, recent studies have shown that the spread and increase of quinolone resistance may be due to the transfer of plasmid-mediated genes. To date, three groups of plasmid-mediated quinolone resistance genes, namely qnr, aac(6')-Ib-cr, and qepA, have been described. The aim of this study was to investigate the presence of plasmid-mediated quinolone resistance genes in E.coli clinical isolates. A total of 112 quinolone-resistant E.coli strains isolated from different clinical specimens (84 urine, 16 blood, 10 wound, 2 bronchoalveolar lavage) of which 78 (69.6%) were extended-spectrum beta-lactamase (ESBL) positive, in Afyon Kocatepe University Hospital, Microbiology Laboratory were included in the study. In the isolates, qnrA, qnrB, qnrS, qnrC, qepA, and aac(6')-1b-cr plasmid genes were analysed by polymerase chain reaction (PCR). After aac(6')- 1b determinant was amplified by PCR, all aac(6')-1b positive amplicons were analyzed by digestion with BseGI restriction enzyme to identify aac(6')-1b-cr variant. It was found that, none of the strains horboured qnrA, qnrB, qnrS, qnrC and qepA genes, however, plasmid-mediated quinolone resistance gene aac(6')-1b-cr was found positive in 59.8% (67/112) of the strains. It was notable that 86.6% (58/67) of those isolates were ESBL producers. The rates of quinolone resistance among E.coli isolates infections were high in our region and an increasing trend has been observed in recent years. Our data indicated that the presence of plasmid- mediated resistance genes

  19. Design and synthesis of modified quinolones as antitumoral acridones.

    Science.gov (United States)

    Tabarrini, O; Cecchetti, V; Fravolini, A; Nocentini, G; Barzi, A; Sabatini, S; Miao, H; Sissi, C

    1999-06-17

    The bacterial topoisomerase II (DNA gyrase) and the mammalian topoisomerase II represent the cellular targets for quinolone antibacterials and a wide variety of anticancer drugs, respectively. In view of the mechanistic similarities and sequence homologies exhibited by the two enzymes, tentative efforts to selectively shift from an antibacterial to an antitumoral activity was made by synthesizing a series of modified tricyclic quinolones, in which the essential 3-carboxylic function is surrogated by phenolic OH and the classic C-6 fluorine atom is replaced by a NH2 group. The resulting 7-amino-9-acridone derivatives were assayed for their antibacterial as well as cytotoxic activities. No antibacterial activity was found. On the other hand, many derivatives showed significant cytotoxic activity against both HL-60 and P388 leukemias and a wide panel of human and rodent solid tumor cells, derivatives 25 and 26 displaying the best overall antiproliferative activity. Against the LoVo cell line, derivative 25 exhibited higher cytotoxic effects than etoposide.

  20. Quantifying Pseudomonas aeruginosa quinolones and examining their interactions with lipids.

    Science.gov (United States)

    Palmer, Gregory C; Schertzer, Jeffrey W; Mashburn-Warren, Lauren; Whiteley, Marvin

    2011-01-01

    Pseudomonas aeruginosa produces a quorum sensing molecule termed the Pseudomonas Quinolone Signal (2-heptyl-3-hydroxy-4-quinolone; PQS) that regulates an array of genes involved in virulence. This chapter addresses four related techniques useful for detecting and quantifying PQS. First, extraction of PQS from complex mixtures (e.g. cell cultures) is described. Separation of PQS from extracts by Thin-Layer Chromatography (TLC) is used in combination with the natural fluorescence of the molecule for quantification. A second separation technique for the PQS precursor HHQ using High-Performance Liquid Chromatography (HPLC) is also described, and this assay exploits the molecule's characteristic absorbance for quantification. A third method for quantification of PQS from simple mixtures (e.g. enzyme assays) using fluorescence is outlined. Finally, a protocol for determining PQS interactions with membrane lipids through Fluorescence Resonance Energy Transfer (FRET) is presented. These techniques allow for quantification and characterization of PQS from diverse environments, a prerequisite to understanding the biological functions of QS molecules.

  1. Quinolone-resistant Escherichia coli in Poultry Farming.

    Science.gov (United States)

    Hricová, Kristýna; Röderová, Magdaléna; Pudová, Vendula; Hanulík, Vojtěch; Halová, Dana; Julínková, Pavla; Dolejská, Monika; Papoušek, Ivo; Bardoň, Jan

    2017-06-01

    Increasing bacterial resistance to quinolone antibiotics is apparent in both humans and animals. For humans, a potential source of resistant bacteria may be animals or their products entering the human food chain, for example poultry. Between July 2013 and September 2014, samples were collected and analyzed in the Moravian regions of the Czech Republic to isolate the bacterium Escherichia coli. As a result, 212 E. coli isolates were obtained comprising 126 environmental isolates from poultry houses and 86 isolates from cloacal swabs from market-weight turkeys. Subsequently, the E. coli isolates were tested for susceptibility to selected antibiotics. Resistance of the poultry isolates to quinolones ranged from 53% to 73%. Additionally, the presence of plasmid-mediated resistance genes was studied. The genes were confirmed in 58% of the tested strains. The data on resistance of isolates from poultry were compared with results of resistance tests in human isolates obtained in the same regions. The high levels of resistance determined by both phenotyping and genotyping methods and reported in the present study confirm the fact that the use of fluoroquinolones in poultry should be closely monitored. Copyright© by the National Institute of Public Health, Prague 2017.

  2. N-Substituted piperazinyl quinolones as potential cytotoxic agents: structure-activity relationships study.

    Science.gov (United States)

    Foroumadi, Alireza; Emami, Saeed; Rajabalian, Saeed; Badinloo, Marziyeh; Mohammadhosseini, Negar; Shafiee, Abbas

    2009-03-01

    As part of a continuing search for new potential anticancer candidates in the piperazinyl quinolone series, the cytotoxicity evaluation of new N-substituted piperazinyl quinolones was of our interest. The growth inhibitory activities of 12 new compounds, namely N-[2-(5-chlorothiophen-2-yl)-2-oxoethyl] and N-[2-(5-chlorothiophen-2-yl)-2-oxyiminoethyl] piperazinyl quinolones 1-12 were determined against six cancer cell lines using MTT colorimetric assay. Preliminary screening showed that most of the new N-[2-(5-chlorothiophen-2-yl)ethyl]piperazinyl quinolones 4-12 containing (un)substituted oxime moiety showed significant cytotoxic activity and the modification of functionality on ethyl spacer produced a relatively minor change of activity. Thus, in the piperazinyl quinolone series, cytotoxic activity can be positively modulated through the introduction of 2-(5-chlorothiophen-2-yl)ethyl residue on the piperazine ring. The results revealed that the introduction of 2-(5-chlorothiophen-2-yl)ethyl moiety on the piperazine ring of quinolone antibacterials (ciprofloxacin, norfloxacin and enoxacin) changes the biological profile of piperazinyl quinolones from antibacterials to cytotoxic agents.

  3. Responses of plasmid-mediated quinolone resistance genes and bacterial taxa to (fluoro)quinolones-containing manure in arable soil.

    Science.gov (United States)

    Xiong, Wenguang; Sun, Yongxue; Ding, Xueyao; Zhang, Yiming; Zhong, Xiaoxia; Liang, Wenfei; Zeng, Zhenling

    2015-01-01

    The aim of the present study was to investigate the fate of plasmid-mediated quinolone resistance (PMQR) genes and the disturbance of soil bacterial communities posed by (fluoro)quinolones (FQNs)-containing manure in arable soil. Representative FQNs (enrofloxacin (ENR), ciprofloxacin (CIP) and norfloxacin (NOR)), PMQR genes (qepA, oqxA, oqxB, aac(6')-Ib-cr and qnrS) and bacterial communities in untreated soil, +manure and +manure+FQNs groups were analyzed using culture independent methods. The significantly higher abundance of oqxA, oqxB and aac(6')-Ib-cr, and significantly higher abundance of qnrS in +manure group than those in untreated soil disappeared at day 30 and day 60, respectively. All PMQR genes (oqxA, oqxB, aac(6')-Ib-cr and qnrS) dissipated 1.5-1.7 times faster in +manure group than those in +manure+FQNs group. The disturbance of soil bacterial communities posed by FQNs-containing manure was also found. The results indicated that significant effects of PMQR genes (oqxA, oqxB, aac(6')-Ib and qnrS) on arable soils introduced by manure disappeared 2 month after manure application. FQNs introduced by manure slowed down the dissipation of PMQR genes. The presence of high FQNs provided a selective advantage for species affiliated to the phylum including Acidobacteria, Verrucomicrobia and Planctomycetes while suppressing Proteobacteria and Actinobacteria.

  4. Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A; Lin, Gengrong; Bozdogan, Bülent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C

    2006-06-01

    DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 microg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.

  5. A novel synthesis of carbon-labelled quinolone-3-carboxylic acid antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Carr, R.M.; Sutherland, D.R. (Glaxo Research and Development Ltd., Greenford (United Kingdom). Isotope Chemistry Group)

    1994-10-01

    3-Iodoquinolones were prepared from the corresponding quinolone-3-carboxylic acids by Hunsdiecker-type iododecarboxylation reactions with lead tetraacetate and iodine. Cyanation of the iodo compounds with mixtures of potassium [[sup 13]C]cyanide and copper (1) iodide, gave [3-[sup 13]C]cyanoquinolones which on acidic hydrolysis afforded quinolone-[3-[sup 13]C]carboxylic acids. In this way, nalidixic acid, an immediate precursor of norfloxacin, and quinolone WIN57273 were labelled with carbon-13 in the metabolically stable carboxylic acid fragment. (author).

  6. New luminophor-activators based on (fluoro)quinolone antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, A.V. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Karaseva, E.T. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Korpela, T. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Karasev, V.E. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation)], E-mail: karasev@ich.dvo.ru

    2008-11-15

    It was shown that (fluoro)quinolone antibiotics form strongly fluorescent solid-state complexes with Eu(III) and Tb(III) lanthanide ions, with a wavelength red-shift beneficial for applications to greenhouse-cover polymers. Complexes with optimal properties were prepared by the mechanical activation of fine-dispersed composite mixtures with the lanthanide salts. The spectral properties, photo-stability to UV-light, and compatibility with the polyethylene matrix were investigated. The formulation additives of the tablet forms of the antibiotic medicines did not quench the fluorescence from the lanthanide ions. Therefore, the outdated drug forms of the antibiotics can serve as cheap recyclable sources for the covering material of greenhouses. In addition, diphenylguanidine (DPG) was investigated as a coligand. DPG enhanced fluorescence of the fluoroquinolone complexes by decreasing the non-radiative energy loss through O-H vibration of H{sub 2}O.

  7. Quinolones for the Treatment of Neisseria Gonorrhoeae and Chlamydia Trachomatis

    Directory of Open Access Journals (Sweden)

    Sebastian Faro

    1993-01-01

    Full Text Available The most commonly sexually transmitted bacteria are Neisseria gonorrhoeae and Chlamydia trachomatis. The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment of N. gonorrhoeae and C. trachomatis cervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID. Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

  8. Overcoming target-mediated quinolone resistance in topoisomerase IV by introducing metal-ion-independent drug-enzyme interactions.

    Science.gov (United States)

    Aldred, Katie J; Schwanz, Heidi A; Li, Gangqin; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2013-12-20

    Quinolones, which target gyrase and topoisomerase IV, are the most widely prescribed antibacterials worldwide. Unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. Greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme-drug interactions coordinated by a critical water-metal ion bridge. Quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. These compounds are of clinical interest, however, because they retain activity against the most common quinolone resistance mutations. We utilized a chemical biology approach to determine how quinazolinediones overcome quinolone resistance in Bacillus anthracis topoisomerase IV. Quinazolinediones that retain activity against quinolone-resistant topoisomerase IV do so primarily by establishing novel interactions through the C7 substituent, rather than the drug skeleton. Because some quinolones are highly active against human topoisomerase IIα, we also determined how clinically relevant quinolones discriminate between the bacterial and human enzymes. Clinically relevant quinolones display poor activity against topoisomerase IIα because the human enzyme cannot support drug interactions mediated by the water-metal ion bridge. However, the inclusion of substituents that allow quinazolinediones to overcome topoisomerase IV-mediated quinolone resistance can cause cross-reactivity against topoisomerase IIα. Therefore, a major challenge in designing drugs that overcome quinolone resistance lies in the ability to identify substituents that mediate strong interactions with the bacterial, but not the human, enzymes. On the basis of our understanding of quinolone-enzyme interactions, we have identified three compounds that display high activity against quinolone-resistant B. anthracis topoisomerase IV but low activity against human topoisomerase IIα.

  9. The Impact of Antibiotic Stewardship Programs in Combating Quinolone Resistance: A Systematic Review and Recommendations for More Efficient Interventions.

    Science.gov (United States)

    Pitiriga, Vasiliki; Vrioni, Georgia; Saroglou, George; Tsakris, Athanasios

    2017-04-01

    Quinolones are among the most commonly prescribed antibiotics worldwide. A clear relationship has been demonstrated between excessive quinolone use and the steady increase in the incidence of quinolone-resistant bacterial pathogens, both in hospital and community sites. In addition, exposure to quinolones has been associated with colonization and infection with healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus and Clostridium difficile in hospitalized patients. Therefore, the management of quinolone prescribing in hospitals through antibiotic stewardship programs is considered crucial. Although suggestions have been made by previous studies on the positive impact of stewardship programs concerning the emergence and spread of multidrug-resistant bacteria at hospital level, the association of quinolone-targeted interventions with reduction of quinolone resistance is vague. The purpose of this article was to evaluate the impact of stewardship interventions on quinolone resistance rates and healthcare-associated infections, through a literature review using systematic methods to identify and select the appropriate studies. Recommendations for improvements in quinolone-targeted stewardship programs are also proposed. Efforts in battling quinolone resistance should combine various interventions such as restriction formulary policies, prospective audits with feedback to prescribers, infection prevention and control measures, prompt detection of low-level resistance, educational programs, and guidelines for optimal quinolone usage. However, the effectiveness of such strategies should be assessed by properly designed and conducted clinical trials. Finally, novel approaches in diagnostic stewardship for rapidly detecting bacterial resistance, including PCR-based techniques, mass spectrometry, microarrays, and whole-genome sequencing as well as the prompt investigation on the clonality of quinolone-resistant strains, will strengthen our

  10. Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Melissa Agnello

    Full Text Available Pseudomonas aeruginosa is a leading pathogen that has become increasingly resistant to the fluoroquinolone antibiotics due to widespread prescribing. Adverse outcomes have been shown for patients infected with fluoroquinolone-resistant strains. The type III secretion system (TTSS is a major virulence determinant during acute infections through the injection of effector toxins into host cells. Most strains exhibit a unique TTSS virulence genotype defined by the presence of either exoS or exoU gene encoding two of the effector toxins, ExoS and ExoU, respectively. Specific TTSS effector genotype has been shown previously to differentially impact virulence in pneumonia. In this study, we examined the relationship between TTSS effector genotype and fluoroquinolone resistance mechanisms in a collection of 270 respiratory isolates. We found that a higher proportion of exoU+ strains were fluoroquinolone-resistant compared to exoS+ strains (63% vs 49%, p = 0.03 despite its lower overall prevalence (38% exoU+ vs 56% exoS+. Results from sequencing the quinolone resistance determining regions (QRDRs of the 4 target genes (gyrA, gyrB, parC, parE indicated that strains containing the exoU gene were more likely to acquire ≥ 2 mutations than exoS+ strains at MICs ≤ 8 µg/ml (13% vs none and twice as likely to have mutations in both gyrA and parC than exoS+ strains (48% vs 24% p = 0.0439. Our findings indicate that P. aeruginosa strains differentially develop resistance-conferring mutations that correlate with TTSS effector genotype and the more virulent exoU+ subpopulation. Differences in mutational processes by virulence genotype that were observed suggest co-evolution of resistance and virulence traits favoring a more virulent genotype in the quinolone-rich clinical environment.

  11. [The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones].

    Science.gov (United States)

    Long, Quan-xin; He, Ying; Xie, Jian-ping

    2012-08-01

    The fluoroquinolones are the most widely used broad-spectrum antibiotics, accounting for 18% of global antibacterial market share. They can kill bacteria rapidly with variety of derivatives available. Different quinolones vary significantly in rate and spectrum of killing, oxygen requirement for metabolism and reliance upon protein synthesis. Further understanding the sophisticated mechanisms of action of this important antibiotic family based on the molecular genetic response of bacteria can facilitate the discovery of better quinolone derivatives. Factors such as SOS response, bacterial toxin-antitoxin system, programmed death, chromosome fragmentation and reactive oxygen have been implicated in the action to some extent. "Two steps characteristic" of quinolones killing is also emphasized, which might inspire future better quinolones modification.

  12. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

    Science.gov (United States)

    Kocsis, Bela; Domokos, J; Szabo, D

    2016-05-23

    Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

  13. Evaluating the impact of a novel restricted reimbursement policy for quinolone antibiotics: A time series analysis

    Directory of Open Access Journals (Sweden)

    Manns Braden

    2012-08-01

    Full Text Available Abstract Background Publicly-funded drug plans often use prior authorization policies to limit drug prescribing. To guide physician prescribing of a class of antibiotics with broad antimicrobial activity (quinolone antibiotics in accordance with new prescribing guidelines, Alberta’s provincial health ministry implemented a new mechanism for formulary restriction entitled the optional special authorization (OSA program. We conducted an observational study to determine the impact of this new formulary restriction policy on antimicrobial prescription rates as well as any clinical consequences. Methods Quinolone antibiotic use, and adherence with quinolone prescribing guidelines, was assessed before and after implementation of the OSA program in patients with common outpatient infections using an administrative data cohort and a chart review cohort, respectively. At the same time this policy was implemented to limit quinolone prescribing, two new quinolone antibiotics were added to the formulary. Using administrative data, we analysed a total of 397,534 unique index visits with regard to overall antibiotic utilization, and through chart review, we analysed 1681 charts of patients with infections of interest to determine the indications for quinolone usage. Results Using segmented regression models adjusting for age, sex and physician enrollment in the OSA program, there was no statistically significant change in the monthly rate of all quinolone use (−3.5 (95% CI −5.5, 1.4 prescriptions per 1000 index visits following implementation of the OSA program (p = 0.74. There was a significant level change in the rate of quinolone antibiotic use for urinary tract infection (−33.6 (95% CI: -23.8, -43.4 prescriptions and upper respiratory tract infection (−16.1 (95%CI: -11.6, -20.6 prescriptions per 1000 index visits. Among quinolone prescriptions identified on chart review, 42.5% and 58.5% were consistent with formulary guidelines before and

  14. Dynamics of Quinolone Resistance in Fecal Escherichia coli of Finishing Pigs after Ciprofloxacin Administration

    OpenAIRE

    Huang, Kang; Xu, Chang-Wen; Zeng, Bo; XIA, Qing-Qing; Zhang, An-Yun; LEI, Chang-Wei; Guan, Zhong-Bin; Cheng, Han; Wang, Hong-ning

    2014-01-01

    ABSTRACT Escherichia coli resistance to quinolones has now become a serious issue in large-scale pig farms of China. It is necessary to study the dynamics of quinolone resistance in fecal Escherichia coli of pigs after antimicrobial administration. Here, we present the hypothesis that the emergence of resistance in pigs requires drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days old, about 30 kg) not fed any antimicrobial after weaning were selected and divided in...

  15. Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.

    Directory of Open Access Journals (Sweden)

    Ross J Davidson

    Full Text Available BACKGROUND: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. METHODS: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB. Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR mutations. RESULTS: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01. Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. CONCLUSIONS: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.

  16. Occurrence of (fluoro)quinolones and (fluoro)quinolone resistance in soil receiving swine manure for 11 years.

    Science.gov (United States)

    Xu, Yonggang; Yu, Wantai; Ma, Qiang; Zhou, Hua

    2015-10-15

    Because of the widespread use of antibiotics in animal breeding, the agricultural application of animal manure can lead to the introduction of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes to the soil and surrounding environment, which may pose a threat to public health. In this study, we investigated the status of (fluoro)quinolone (FQ) residues and FQ resistance levels in soil with and without receiving long-term swine manure. Six FQs (pipemidic acid, lomefloxacin, enrofloxacin, norfloxacin, ciprofloxacin, and ofloxacin) were only detected in manured soil, with individual concentrations ranging from below the detection limit to 27.2 μg kg(-1) and increasing with the increase in swine manure application rates. Higher load rates of swine manure yielded a higher number of ciprofloxacin-resistant (CIPr) bacteria after spreading. A total of 24 CIPr bacterial isolates were obtained from the tested soil, which belonged to four phyla (Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes) or were related to nine different genera. Only 18 isolates from manured soil were positive for five plasmid-mediated quinolone resistance (PMQR) genes (aac(6')-Ib-cr, qnrD, qepA, oqxA, and oqxB). To our knowledge, this study is the first to examine the occurrence of PMQR genes in FQ-resistant bacteria from the soil environment. A similar result was observed for the total DNA from soil, with the exception of aac(6')-Ib being detected in the control sample. The absolute and relative abundances of total PMQR genes also increased with fertilization quantity. Significant correlations were observed between FQ resistance levels and FQ concentrations. These results indicated that the agricultural application of swine manure led to FQ residues and enhanced FQ resistance. This investigation provides baseline data on FQ resistance profiles in soils receiving long-term swine manure. Copyright © 2015. Published by Elsevier B.V.

  17. Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis.

    Science.gov (United States)

    Hong, W David; Gibbons, Peter D; Leung, Suet C; Amewu, Richard; Stocks, Paul A; Stachulski, Andrew; Horta, Pedro; Cristiano, Maria L S; Shone, Alison E; Moss, Darren; Ardrey, Alison; Sharma, Raman; Warman, Ashley J; Bedingfield, Paul T P; Fisher, Nicholas E; Aljayyoussi, Ghaith; Mead, Sally; Caws, Maxine; Berry, Neil G; Ward, Stephen A; Biagini, Giancarlo A; O'Neill, Paul M; Nixon, Gemma L

    2017-05-11

    A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified ∼100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further ∼90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  18. [Multiresidue determination of quinolones in animal and fishery products by HPLC].

    Science.gov (United States)

    Chonan, Takao; Fujimoto, Toru; Inoue, Maki; Tazawa, Teijiro; Ogawa, Hiroshi

    2008-06-01

    A simple and rapid multiresidue method was developed for the determination of twelve quinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, nalidixic acid, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid and sarafloxacin) in muscle, liver, chicken eggs, milk, prawn and rainbow trout. The quinolones were extracted from a sample with acetonitrile-water (95 : 5). A fifth part of the filtered extract was diluted with water to keep the acetonitrile ratio at ca. 60%, and passed through a C18 mini-column. The eluate was evaporated to dryness, and the residues were dissolved in methanol-water (30 : 70) for HPLC analysis. The quinolones were separated on a Inertsil ODS-3V column (4.6 mm i.d.x250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with fluorescence detection.No interfering peak was found on the chromatograms of animal and fishery products, except for milk. The recoveries of the quinolones were over 60% from the animal and fishery products fortified at 0.1 microg/g, and the quantification limits of the quinolones were 0.005 microg/g. This proposed method was found to be effective and suitable for the screening of the quinolones in animal and fishery products.

  19. Genotoxicity of quinolone antibiotics in chlorination disinfection treatment: formation and QSAR simulation.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Du, Yuguo

    2016-10-01

    Lots of unexpected disinfection by-products were formed during the chlorination disinfection of contaminated water bodies, leading to a potential threat to human health and ecological safety. In this study, SOS/umu assay was used to trace the genotoxicity variation of 20 quinolone compounds during the chlorination disinfection. Furthermore, two- and three-dimensional quantitative structure-activity relationship models were developed based on the electronic and hydrophobic properties of the quinolones, which were used to quantify the impact of the different structural features of the compounds on their genotoxicity variation. The results revealed that quinolones bearing hydrophilic substituents with less H-bond donors and negative charge at the 1-position of the quinolone ring exhibited a positive correlation with genotoxicity elevation. More notably, the chlorination of quinolones in both ultrapure water and secondary effluent matrices provided comparable levels of genotoxicity, indicating that our research could potentially be used to evaluate the environmental risk of quinolone antibiotics in chlorination disinfection treatment.

  20. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Zhi, Ying; Gao, Li-Xin; Jin, Yi; Tang, Chun-Lan; Li, Jing-Ya; Li, Jia; Long, Ya-Qiu

    2014-07-15

    Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  1. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

    Directory of Open Access Journals (Sweden)

    Jérémie Piton

    Full Text Available Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

  2. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia.

    Science.gov (United States)

    García-León, Guillermo; Salgado, Fabiola; Oliveros, Juan Carlos; Sánchez, María Blanca; Martínez, José Luis

    2014-05-01

    To analyse whether the mutation-driven resistance-acquisition potential of a given bacterium might be a function of its intrinsic resistome, quinolones were used as selective agents and Stenotrophomonas maltophilia was chosen as a bacterial model. S. maltophilia has two elements - SmQnr and SmeDEF - that are important in intrinsic resistance to quinolones. Using a battery of mutants in which either or both of these elements had been removed, the apparent mutation frequency for quinolone resistance and the phenotype of the selected mutants were found to be related to the intrinsic resistome and also depended on the concentration of the selector. Most mutants had phenotypes compatible with the overexpression of multidrug efflux pump(s); SmeDEF overexpression was the most common cause of quinolone resistance. Whole genome sequencing showed that mutations of the SmeRv regulator, which result in the overexpression of the efflux pump SmeVWX, are the cause of quinolone resistance in mutants not overexpressing SmeDEF. These results indicate that the development of mutation-driven antibiotic resistance is highly dependent on the intrinsic resistome, which, at least for synthetic antibiotics such as quinolones, did not develop as a response to the presence of antibiotics in the natural ecosystems in which S. maltophilia evolved.

  3. Screening of quinolone antibiotic residues in chicken meat and beef sold in the markets of Ankara, Turkey.

    Science.gov (United States)

    Er, Buket; Onurdag, Fatma Kaynak; Demirhan, Burak; Ozgacar, Selda Özgen; Oktem, Aysel Bayhan; Abbasoglu, Ufuk

    2013-08-01

    This study aimed to find the effects of quinolone antibiotics in chicken and beef used in Ankara, Turkey. Total number of 127 chicken and 104 beef meat samples were collected randomly from local markets for analysis. Extraction and determination of quinolones were made by ELISA procedure. One hundred eighteen of 231 (51.1%) examined chicken meat and beef samples were found to contain quinolone antibiotic residue. Among the chicken meat and beef samples, 58 (45.7%) of chicken meat samples and 60 (57.7%) of beef meat samples were positive for quinolones, respectively. The mean levels (±SE) of quinolones were found to be 30.81 ± 0.45 µg/kg and 6.64 ± 1.11 µg/kg in chicken and beef samples, respectively. This study indicated that some chicken and beef meat sold in Ankara contains residues of quinolone antibiotics.

  4. Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 7. Synthesis and Pharmacological Evaluation of 4-Quinolone-3-carboxamides and 4-Hydroxy-2-quinolone-3-carboxamides as High Affinity Cannabinoid Receptor 2 (CB2R) Ligands with Improved Aqueous Solubility.

    Science.gov (United States)

    Mugnaini, Claudia; Brizzi, Antonella; Ligresti, Alessia; Allarà, Marco; Lamponi, Stefania; Vacondio, Federica; Silva, Claudia; Mor, Marco; Di Marzo, Vincenzo; Corelli, Federico

    2016-02-11

    4-Quinolone-3-carboxamide derivatives have long been recognized as potent and selective cannabinoid type-2 receptor (CB2R) ligands. With the aim to improve their physicochemical properties, basically aqueous solubility, two different approaches were followed, entailing the substitution of the alkyl chain with a basic replacement or scaffold modification to 4-hydroxy-2-quinolone structure. According to the first approach, compound 6d was obtained, showing slightly reduced receptor affinity (K(i) = 60 nM) compared to the lead compound 4 (0.8 nM) but greatly enhanced solubility (400-3400 times depending on the pH of the medium). On the other hand, shifting from 4-quinolone to 4-hydroxy-2-quinolone structure enabled the discovery of a novel class of CB2R ligands, such as 7b and 7c, characterized by K(i) 1300. At pH 7.4, compound 7c resulted by 100-fold more soluble than 4.

  5. Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Liu, Shao-Ying; Huang, Xi-Hui; Wang, Xiao-Fang; Jin, Quan; Zhu, Guo-Nian

    2014-05-01

    This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 μg/kg. The precision for determining the quinolones was quinolones in real cosmetic samples.

  6. Quinolone resistance in absence of selective pressure: the experience of a very remote community in the Amazon forest.

    Directory of Open Access Journals (Sweden)

    Lucia Pallecchi

    Full Text Available BACKGROUND: Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002. METHODS: The community exhibited a considerable level of geographical isolation, limited contact with the exterior and minimal antibiotic use (not including quinolones. In December 2009, fecal carriage of antibiotic resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in 48 animals reared in the community. All fluoroquinolone-resistant isolates were genotyped and characterized for the mechanisms of plasmid- and chromosomal-mediated quinolone resistance. PRINCIPAL FINDINGS: Despite the characteristics of the community remained substantially unchanged during the period 2002-2009, carriage of quinolone-resistant E. coli was found to be common in 2009 both in humans (45% nalidixic acid, 14% ciprofloxacin and animals (54% nalidixic acid, 23% ciprofloxacin. Ciprofloxacin-resistant isolates of human and animal origin showed multidrug resistance phenotypes, a high level of genetic heterogeneity, and a combination of GyrA (Ser83Leu and Asp87Asn and ParC (Ser80Ile substitutions commonly observed in fluoroquinolone-resistant clinical isolates of E. coli. CONCLUSIONS: Remoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli. Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation. Interventions aimed at reducing the spreading of resistant isolates (by improving sanitation

  7. Rh(III) and Ru(II)-catalyzed site-selective C-H alkynylation of quinolones.

    Science.gov (United States)

    Kang, Dahye; Hong, Sungwoo

    2015-04-17

    C2- and C5-alkynylated quinolone scaffolds are core structures of numerous biologically active molecules. Utilizing TIPS-EBX as an alkynylating agent, we have developed an efficient and site-selective C5 alkynylation of 4-quinolones that is directed by the weakly coordinating carbonyl group. In addition, Ru(II) catalyzed C2-selective alkynylation was successfully realized via N-pyrimidyl group-directed cross-couplings to access valuable C2-alkynylated 4-quinolones. This strategy provides direct access to the C2 or C5 alkynylated 4-quinolones. Furthermore, the reaction was applied to isoquinolones for C3-selective alkynylation.

  8. Actualidad de las quinolonas Present situation of quinolones

    Directory of Open Access Journals (Sweden)

    Manuel Cué Brugueras

    2005-04-01

    Full Text Available Las quinolonas son los antimicrobianos que han tenido un mayor desarrollo en los últimos años. Después de obtenerse el ácido nalidíxico, en 1962, se desarrollaron varios compuestos con características muy similares, que solo se establecieron como antisépticos urinarios, y que constituyeron la primera generación de quinolonas, hasta que en 1978, mediante la adición de un grupo piperacinil en posición 7 y un átomo de flúor en posición 6 comenzó a desarrollarse un conjunto de agentes antibacterianos llamados piperacinil fluoroquinolonas o simplemente fluoroquinolonas. El primero de ellos fue el norfloxacino, con el cual se logró una mayor actividad antimicrobiana del grupo y su uso sistémico. Durante años las fluroquinolonas fueron consideradas como un grupo homogéneo de antibióticos, con propiedades semejantes y, por tanto, como la segunda y última posibilidad de generación de quinolonas, pero las posibilidades de transformación de su estructura química ha producido un desarrollo vertiginoso de este grupo, que lo ha convertido en el más acelerado dentro de los antibióticos, con compuestos de mayor espectro antibacteriano, penetración tisular y seguridad, y con menor manifestación de resistencia antimicrobiana, demostrada hasta el presente, lo cual ha hecho que actualmente existan 4 generaciones de quinolonas, que se haya ampliado su uso y que continúe su desarrollo. Por tal motivo, se presenta una revisión que incluye espectro y mecanismo de acción, resistencia bacteriana, farmacodinamia y farmacocinética, interacciones medicamentosas, efectos adversos, indicaciones y dosificación de las más usadas.The quinolones are antimicrobial agents that have attained their highest development in the last years. After obtaining nalidixic acid, in 1962, several compounds were developed with similar characteristics that were only established as urinary antiseptics and that were the first generation of quinolones until 1978, when

  9. [The history of the development and changes of quinolone antibacterial agents].

    Science.gov (United States)

    Takahashi, Hisashi; Hayakawa, Isao; Akimoto, Takeshi

    2003-01-01

    The quinolones, especially the new quinolones (the 6-fluoroquinolones), are the synthetic antibacterial agents to rival the Beta-lactam and the macrolide antibacterials for impact in clinical usage in the antibacterial therapeutic field. They have a broad antibacterial spectrum of activity against Gram-positive, Gram-negative and mycobacterial pathogens as well as anaerobes. Further, they show good-to-moderate oral absorption and tissue penetration with favorable pharmacokinetics in humans resulting in high clinical efficacy in the treatment of many kinds of infections. They also exhibit excellent safety profiles as well as those of oral Beta-lactam antibiotics. The bacterial effects of quinolones inhibit the function of bacterial DNA gyrase and topoisomerase IV. The history of the development of the quinolones originated from nalidixic acid (NA), developed in 1962. In addition, the breakthrough in the drug design for the scaffold and the basic side chains have allowed improvements to be made to the first new quinolone, norfloxacin (NFLX), patented in 1978. Although currently more than 10,000 compounds have been already synthesized in the world, only two percent of them were developed and tested in clinical studies. Furthermore, out of all these compounds, only twenty have been successfully launched into the market. In this paper, the history of the development and changes of the quinolones are described from the first quinolone, NA, via, the first new quinolone (6-fluorinated quinolone) NFLX, to the latest extended-spectrum quinolone antibacterial agents against multi-drug resistant bacterial infections. NA has only modest activity against Gram-negative bacteria and low oral absorption, therefore a suitable candidate for treatment of systemic infections (UTIs) is required. Since the original discovery of NA, a series of quinolones, which are referred to as the old quinolones, have been developed leading to the first new quinolone, NFLX, with moderate improvements

  10. Mechanisms of quinolone resistance and implications for human and animal health

    Directory of Open Access Journals (Sweden)

    Velhner Maja

    2010-01-01

    Full Text Available Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance. The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .

  11. [Role of reactive oxygen species in the bactericidal action of quinolones--inhibitors of DNA gyrase].

    Science.gov (United States)

    Kotova, V Iu; Mironov, A S; Zavigel'skiĭ, G B

    2014-01-01

    Quinolone antibiotics inhibit DNA gyrase, but the induced degradation of chromosomal DNA is determined by a complex process of joint action quinolones and hydroxyl radical OH'. To quantify the level of stress responses and their time dependence in bacterial cells the induced specific lux-biosensors--the bacterium Escherichia coli, containing hybrid plasmids pColD'::lux; pSoxS'::lux; pKatG'::lux were used in this study. It is shown that quinolones (nalidixic acid, norfloxacin) induce SOS-response and oxidative stress with the formation of superoxide anion O2(-) in E. coli cells. The main parameters of SOS-response and oxidative stress, which depend on the quinolone concentration, are determined. Formation of superoxide anion O2(-) occurs almost simultaneously with the SOS-response. The mutant strain of E. coli sodA sodB, which do not contain active forms of superoxide dismutases SodA and SodB, is characterized by an increased resistance to quinolones as compared to the wild type cells. At high concentrations of quinolones (nalidixic acid-->20 μg/mL; norfloxacin-->500 ng/mL) their bactericidal effect is partially caused by conversion of the superoxide anion to hydrogen peroxide H2O2, conducted by superoxide dismutases SodA and SodB, which is followed by the Fenton reaction and the formation of toxic hydroxyl radical OH'. At low concentrations of quinolones (nalidixic acid--<20 μg/mL; norfloxacin--<500 ng/mL), the role of active oxygen species in the antimicrobial effect is practically nonexistent.

  12. Characterization of quinolone resistance in Salmonella enterica serovar Indiana from chickens in China.

    Science.gov (United States)

    Lu, Yan; Zhao, Hongyu; Liu, Yuqi; Zhou, Xuping; Wang, Jinyuan; Liu, Tiantian; Beier, Ross C; Hou, Xiaolin

    2015-03-01

    The aim of this study was to characterize the quinolone resistance of Salmonella enterica serovar Indiana isolated from chickens in China. A total of 293 Salmonella strains were isolated from chicken farms and slaughterhouses in Shandong province of China, and 130 (44.4%) were characterized as Salmonella enterica Indiana (chicken farms, n=52 strains; slaughter houses, n=78 strains). All isolate serotypes were tested with the Kauffmann-White classification system and examined for susceptibility to the quinolones: nalidixic acid, enrofloxacin, norfloxacin, and ciprofloxacin. The resistance of the Salmonella Indiana strains to nalidixic acid, enrofloxacin, norfloxacin, and ciprofloxacin were 100, 73.1, 71.2, and 82.7%, and 100, 59.0, 79.5, and 80.2%, respectively. Selected quinolone resistant strains were evaluated for mutations in genes (gyrA, gyrB, parC, and marA) by DNA sequencing. The gyrA mutation was found in all isolates, the parC mutation was only found in some isolates, and the gyrB and marA mutations were not observed. Quinolone resistance was evaluated in the representative isolates by screening for the quinolone resistance determinants, qnrA, qnrB, qnrS, qepA, and aac (6 ')-Ib-cr using PCR technology. The quinolone resistance determinants in Salmonella, qnrA, qnrB, qnrS, and qepA were negative by PCR, but aac(6 ')-Ib-cr had high detection rates of 90.4 and 96.2% in chicken farms and slaughterhouses, respectively. Salmonella Indiana containing the gyrA mutation was prevalent in farms and slaughterhouses and possessed a high frequency of the quinolone resistance determinant aac(6 ')-Ib-cr. These bacteria may have originated from the same source.

  13. Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates.

    Science.gov (United States)

    Patel, Rahul V; Keum, Young-Soo; Park, Se Won

    2015-01-01

    Tuberculosis is a leading killer of lives worldwide and the global curse of multi-drug resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the twin epidemics in resource-limited countries as each potentiate progression of the other. The increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB with currently available drugs. The situation urgently demands for the discovery of new drugs with novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles, Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin, gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical synthetic routes and results of clinical studies.

  14. Effect of various storage conditions on the stability of quinolones in raw milk.

    Science.gov (United States)

    Chen, Meixia; Wen, Fang; Wang, Hui; Zheng, Nan; Wang, Jiaqi

    2016-07-01

    Research on the storage stability of antibiotic residues in milk is important for method development or validation, milk quality control and risk assessment during screening, confirmation, qualitative or quantitative analysis. This study was conducted using UPLC-MS/MS to determine the stability of six quinolones - ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), difloxacin (DIF) and flumequine (FLU) - in raw milk stored under various conditions to investigate if quinolones degrade during storage of milk, and finally to determine optimal storage conditions for analysis and scientific risk assessment of quinolone residues in raw milk. The storage conditions included different temperatures and durations (4°C for 4, 8, 24 and 48 h; -20°C for 1, 7 and 30 days; -80°C for 1, 7 and 30 days), thawing temperatures (25, 40 and 60°C), freeze-thaw cycles (1-5), and the addition of different preservatives (sodium thiocyanate, sodium azide, potassium dichromate, bronopol and methanal). Most quinolones exhibited high stability at 4°C for up to 24 h, but began to degrade after 48 h. In addition, no degradation of quinolones was seen when milk samples were stored at -20°C for up to 7 days; however, 30 days of storage at -20°C resulted in a small amount of degradation (about 30%). Similar results were seen when samples were stored at -80°C. Moreover, no losses were observed when frozen milk samples were thawed at 25, 40 or 60°C. All the quinolones of interest, except sarafloxacin, were stable when milk samples were thawed at 40°C once and three times, but unstable after five freeze-thaw cycles. Preservatives affected the stability of quinolones, but the effects differed depending on the preservative and quinolone. The results of this study indicate optimum storage protocols for milk samples, so that residue levels reflect those at the time of initial sample analysis, and should improve surveillance programmes for quinolones in raw milk.

  15. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

    Science.gov (United States)

    Klopman, G; Li, J Y; Wang, S; Pearson, A J; Chang, K; Jacobs, M R; Bajaksouzian, S; Ellner, J J

    1994-08-01

    The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

  16. Fluorescence quenching as a tool to investigate quinolone antibiotic interactions with bacterial protein OmpF.

    Science.gov (United States)

    Neves, Patrícia; Sousa, Isabel; Winterhalter, Mathias; Gameiro, Paula

    2009-02-01

    The outer membrane porin OmpF is an important protein for the uptake of antibiotics through the outer membrane of gram-negative bacteria; however, the possible binding sites involved in this uptake are still not recognized. Determination, at the molecular level, of the possible sites of antibiotic interaction is very important, not only to understand their mechanism of action but also to unravel bacterial resistance. Due to the intrinsic OmpF fluorescence, attributed mainly to its tryptophans (Trp(214), Trp(61)), quenching experiments were used to assess the site(s) of interaction of some quinolone antibiotics. OmpF was reconstituted in different organized structures, and the fluorescence quenching results, in the presence of two quenching agents, acrylamide and iodide, certified that acrylamide quenches Trp(61) and iodide Trp(214). Similar data, obtained in presence of the quinolones, revealed distinct behaviors for these antibiotics, with nalidixic acid interacting near Trp(214) and moxifloxacin near Trp(61). These studies, based on straightforward and quick procedures, show the existence of conformational changes in the protein in order to adapt to the different organized structures and to interact with the quinolones. The extent of reorganization of the protein in the presence of the different quinolones allowed an estimate on the sites of protein/quinolone interaction.

  17. The evidence for clonal spreading of quinolone resistance with a particular clonal complex of Campylobacter jejuni.

    Science.gov (United States)

    Kovač, J; Cadež, N; Lušicky, M; Nielsen, E Møller; Ocepek, M; Raspor, P; Možina, S Smole

    2014-12-01

    Campylobacter is the most prevalent cause of bacterial gastroenteritis worldwide and it represents a significant public health risk of increasing severity due to its escalating resistance to clinically important quinolone and macrolide antibiotics. As a zoonotic pathogen Campylobacter is transmitted along the food chain and naturally cycles from environmental waters, feedstuff, animals and food to humans. We determined antibiotic resistance profiles, as well as multilocus sequence types and flaA-SVR types for 52 C. jejuni isolated in Slovenia from human, animal, raw and cured chicken meat and water samples. Twenty-eight different sequence types, arranged in ten clonal complexes, three new allele types and five new sequence types were identified, indicating the relatively high diversity in a small group of strains. The assignment of strains from different sources to the same clonal complexes indicates their transmission along the food supply chain. The most prevalent clonal complex was CC21, which was also the genetic group with 95% of quinolone-resistant strains. Based on the genetic relatedness of these quinolone-resistant strains identified by polymerase chain reaction with a mismatch amplification mutation assay and sequencing of the quinolone resistance-determining region of the gyrA gene, we conclude that the high resistance prevalence observed indicates the local clonal spread of quinolone resistance with CC21.

  18. Introduction of quinolone resistant Escherichia coli to Swedish broiler population by imported breeding animals.

    Science.gov (United States)

    Börjesson, Stefan; Guillard, Thomas; Landén, Annica; Bengtsson, Björn; Nilsson, Oskar

    2016-10-15

    During recent years a rapid increase of quinolone resistant Escherichia coli have been noted in the Swedish broiler population, despite the lack of a known selective pressure. The current study wanted to investigate if imported breeding birds could be a source for the quinolone resistant E. coli. The occurrence of quinolone resistant E. coli was investigated, using selective cultivation with nalidixic acid, in grand-parent birds on arrival to Sweden and their progeny. In addition, sampling in hatcheries and empty cleaned poultry houses was performed. Clonality of isolates was investigated using a 10-loci multiple-locus variable number tandem repeat analysis (MLVA). To identify the genetic basis for the resistance isolates were also analysed for occurrence of plasmid-mediated quinolone resistance (PMQR) determinants and characterization of chromosomal mutations. E. coli resistant to nalidixic acid occurred in grandparent birds imported to Sweden for breeding purposes. Four predominant MLVA types were identified in isolates from grandparent birds, parent birds and broilers. However, resistant E. coli with identical MLVA patterns were also present in hatcheries and poultry houses suggesting that the environment plays a role in the occurrence. Nalidixic acid resistance was due to a mutation in the gyrA gene and no PMQR could be identified. The occurrence of identical clones in all levels of the production pyramid points to that quinolone resistant E. coli can be introduced through imported breeding birds and spread by vertical transmission to all levels of the broiler production pyramid.

  19. Semiempirical MNDO and UV Absorption Studies on Tautomerism of 2-Quinolones

    Science.gov (United States)

    Mirek, Julian; Syguła, Andrzej

    1982-11-01

    Semiempirical MNDO calculations with geometry optimization were carried out for seven 4-X-2-quinolone tautomers (X = H, CH3, Cl, OCH3, N(CH3)2, COOH, COOCH3). The results show that 2-hydroxyquinolines are less stabilized compared to 2-quinoIones than 2-hydroxypyridines vs. 2-pyridones. The earlier estimated correction applied to these MNDO results suggests that 4-X-2-quinolones have lower chemical binding energies than the corresponding 4-X-2- hydroxyquinolines by ca. 2.1-3.3 kcal/mol. It is additionally shown that the substituent in position 4 does not influence significantly the relative stabilities of the tautomers. The results of the calculations are verified by UV absorption studies of diluted decane solutions of 2-quinolones at ca. 120°. CNDO/S-Cl-1 calculations based on the optimal MNDO geometries were carried out for 4-X-2- quinolone tautomers. The results generally agree well with the experimental data. A disagreement of the data for 4-COOR-2-quinolones is rationalized.

  20. Study of the luminescence behavior of seven quinolones on a paper substrate

    Energy Technology Data Exchange (ETDEWEB)

    Li Junfen [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: fenjunli@sina.com; Li Jianqing [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Shuang Shaomin [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Dong Chuan [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: dc@sxu.edu.cn

    2005-08-29

    Studies on the luminescence spectra behaviors of seven quinines on solid substrate (SS-RTP) were performed. Experimental conditions, such as heavy atom type, pH and drying time of the sample, etc. on solid substrate room temperature phosphorescence (SS-RTP) or solid substrate delayed fluorescence (SS-DF), were studied in detail. CdCl{sub 2} could induce strongest RTP or DF emission of these quinolones. In addition, a comparative study on the spectral behavior of seven quinolones was given, including low temperature phosphorescence (LTP), low temperature fluorescence (LTF) and spectra methioned above. New determination methods for the analysis of seven quinolones by solid substrate room temperature fluorescence (SS-RTF), SS-RTP or SS-DF with filter paper as solid substrate were presented. Analytical characteristics of these methods of seven quinolones were studied. The linear dynamic ranges (LDR), the limit of detection (LOD) and the relative standard deviation (R.S.D.) were valued. Recoveries of seven quinolones in human urine samples were from 98.1% to 104.3%.

  1. Protective effect of Qnr on agents other than quinolones that target DNA gyrase.

    Science.gov (United States)

    Jacoby, George A; Corcoran, Marian A; Hooper, David C

    2015-11-01

    Qnr is a plasmid-encoded and chromosomally determined protein that protects DNA gyrase and topoisomerase IV from inhibition by quinolones. Despite its prevalence worldwide and existence prior to the discovery of quinolones, its native function is not known. Other synthetic compounds and natural products also target bacterial topoisomerases. A number were studied as molecular probes to gain insight into how Qnr acts. Qnr blocked inhibition by synthetic compounds with somewhat quinolone-like structure that target the GyrA subunit, such as the 2-pyridone ABT-719, the quinazoline-2,4-dione PD 0305970, and the spiropyrimidinetrione pyrazinyl-alkynyl-tetrahydroquinoline (PAT), indicating that Qnr is not strictly quinolone specific, but Qnr did not protect against GyrA-targeting simocyclinone D8 despite evidence that both simocyclinone D8 and Qnr affect DNA binding to gyrase. Qnr did not affect the activity of tricyclic pyrimidoindole or pyrazolopyridones, synthetic inhibitors of the GyrB subunit, or nonsynthetic GyrB inhibitors, such as coumermycin A1, novobiocin, gyramide A, or microcin B17.Thus, in this set of compounds the protective activity of Qnr was confined to those that, like quinolones, trap gyrase on DNA in cleaved complexes.

  2. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

    Science.gov (United States)

    Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Aksenova, Inna V; Frolova, Liliya V; Kornienko, Alexander; Magedov, Igor V; Rubin, Michael

    2013-10-18

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

  3. [Investigation of plasmid-mediated quinolone resistance genes in quinolone-resistant Escherichia coli and Klebsiella spp. isolates from bloodstream infections].

    Science.gov (United States)

    Buruk, Celal Kurtuluş; Öztel Ocak, Hikmet; Bayramoğlu, Gülçin; Aydın, Faruk

    2016-04-01

    One of the treatment options of Escherichia coli and Klebsiella spp. infections which are the most common opportunistic pathogens of gram-negative sepsis is quinolones. Resistance to quinolones which act by disrupting DNA synthesis has been increasing. Horizontal transfer of plasmid-mediated quinolone resistance (PMQR) genes play an important role in the spread of resistance. The data about the prevalence of PMQR genes in our country is quite limited. The aim of this study was to investigate the presence of known PMQR genes namely qnrA, qnrB, qnrC, qnrS, qnrD, aac(6')-Ib-cr, qepA and oqxAB amongst quinolone-resistant E. coli and Klebsiella spp. strains isolated from blood cultures. One hundred twenty seven E.coli and 66 Klebsiella isolates detected as nalidixic acid- and/or ciprofloxacin-resistant by phenotypical methods, from 193 blood samples of 187 patients admitted to Karadeniz Technical University, Faculty of Medicine, Department of Medical Microbiology, Bacteriology Unit of Patient Service Laboratory between January 2012 to August 2013 were included in the study. The presence of PMQR genes were investigated by polymerase chain reaction (PCR) and for the detection of aac(6')-Ib-cr variants PCR-restriction fragment length polymorphism (PCR-RFLP) method was used. The positive bands were sequenced using the same primers, and aligned with formerly defined resistance gene sequences, and confirmed. In the study, 56.7% (72/127) of E.coli and 19.7% (13/66) of Klebsiella spp. isolates, with a total of 44% (85/193) of all the isolates were found to be phenotypically resistant to quinolones. Of the 13 resistant Klebsiella isolates, 11 were K.pneumoniae, and two were K.oxytoca. Extended-spectrum beta-lactamase (ESBL)-producing isolates showed higher resistance (50/80, 62.5%) to quinolones than the negative ones (35/113, 30.9%). The prevalence of quinolone resistance genes among resistant E. coli and Klebsiella spp. isolates was determined as qnrA, 1.4% and 15.4%; qnrB, 4

  4. Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment and antibiotic resistance in Indochina

    Directory of Open Access Journals (Sweden)

    Satoru eSuzuki

    2012-02-01

    Full Text Available Southeast Asia has become the center of rapid industrial development and economic growth. However, this growth has far outpaced investment in public infrastructure, leading to the unregulated release of many pollutants, including wastewater-related contaminants such as antibiotics. Antibiotics are of major concern because they can easily be released into the environment from numerous sources, and can subsequently induce development of antibiotic-resistant bacteria. Recent studies have shown that for some categories of drugs this source-to-environment antibiotic resistance relationship is more complex. This review summarizes current understanding regarding the presence of quinolones, sulfonamides, and tetracyclines in aquatic environments of Indochina and the prevalence of bacteria resistant to them. Several noteworthy findings are discussed: 1 quinolone contamination and the occurrence of quinolone resistance are not correlated; 2 occurrence of the sul sulfonamide resistance gene varies geographically; and 3 microbial diversity might be related to the rate of oxytetracycline resistance.

  5. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

    Directory of Open Access Journals (Sweden)

    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  6. Prediction of Quinolone Activity against Mycobacterium avium by Molecular Topology and Virtual Computational Screening

    Science.gov (United States)

    Gozalbes, Rafael; Brun-Pascaud, Monique; García-Domenech, Ramon; Gálvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

    2000-01-01

    We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti-M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (r2 = 0.88; r2cv [cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the M. avium- M. intracellulare complex, with MICs of 0.2, 0.4, and 0.9 μg/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity. PMID:10991858

  7. A "Double-Edged" Scaffold: Antitumor Power within the Antibacterial Quinolone.

    Science.gov (United States)

    Bisacchi, Gregory S; Hale, Michael R

    2016-01-01

    In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today's predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents.

  8. Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones.

    Science.gov (United States)

    Kongsoi, Siriporn; Yokoyama, Kazumasa; Suprasert, Apinun; Utrarachkij, Fuangfa; Nakajima, Chie; Suthienkul, Orasa; Suzuki, Yasuhiko

    2015-08-01

    Quinolones exhibit good antibacterial activity against Salmonella spp. isolates and are often the choice of treatment for life-threatening salmonellosis due to multi-drug resistant strains. To assess the properties of quinolones, we performed an in vitro assay to study the antibacterial activities of quinolones against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity. Drug concentrations that suppressed DNA supercoiling by 50% (IC50 s) or generated DNA cleavage by 25% (CC25 s) demonstrated that quinolones highly active against S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between the minimum inhibitory concentrations (MICs), IC50 s and CC25 s were assessed by estimating a linear regression between two components. MICs measured against S. Typhimurium NBRC 13245 correlated better with IC50 s (R = 0.9988) than CC25 s (R = 0.9685). These findings suggest that the DNA supercoiling inhibition assay may be a useful screening test to identify quinolones with promising activity against S. Typhimurium. The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents are desirable structural features in targeting S. Typhimurium gyrase.

  9. [Bactericidal activity of sitafloxacin and other new quinolones against antimicrobial resistant Streptococcus pneumoniae].

    Science.gov (United States)

    Kobayashi, Intetsu; Kanayama, Akiko; Hasegawa, Miyuki; Kaneko, Akihiro

    2013-02-01

    We conducted a study assess the bactericidal activity of sitafloxacin (STFX) against Streptococcus pneumoniae isolates recovered from respiratory infections including penicillin-resistant (PRSP) isolates, macrolide resistant isolates possessing mefA and ermB resistance genes and quinolone resistance isolates with mutations in gyrA or gyrA and parC. Each isolate tested was grown in hemosupplemented Mueller-Hinton broth and adjusted to approximately 10(5) CFU/ mL. Isolates were than exposed to a Cmax antimicrobial blood level that would be attained with routine antimicrobial administration and an antimicrobial level that would be expected 4 hours post-Cmax (Cmax 4hr). Bactericidal activity was measured for up to 8 hours. Excluding a subset of S. pneumoniae isolates with mutations in the quinolone resistance determining region (QRDR), all quinolones showed bactericidal activity at Cmax and Cmax 4 hr antimicrobial concentrations for up to 8 hours. Against S. pneumoniae isolates with either gyrA or gyrA and parC mutations, bactericidal activity of STFX was shown for up to 4 to 8 hours following Cmax based on a limit of detection of quinolones tested where adjusted to concentrations corresponding to their MICs, STFX showed the most rapid bactericidal activity against PRSP. This rapid bactericidal activity in PRSP is a key to the effectiveness of STFX. Our findings show that beyond inhibition of bacterial replication by blocking their DNA replication pathway and synthesis of proteins, STFX demonstrated characteristics contributing to greater bactericidal activity compared to GRNX. In conclusion, of the newer quinolones, STFX showed the strongest bactericidal activity against S. pneumoniae isolates with mutations in the QRDR which indicates that it may show the most effective clinical utility among the quinolones in respiratory infections.

  10. Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Skalsky, K; Yahav, D; Lador, A; Eliakim-Raz, N; Leibovici, L; Paul, M

    2013-04-01

    The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63-1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67-0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients' benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49-0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.

  11. Plasmid-mediated quinolone resistance; interactions between human, animal and environmental ecologies

    Directory of Open Access Journals (Sweden)

    Laurent ePOIREL

    2012-02-01

    Full Text Available Resistance to quinolones and fluoroquinolones is being increasingly reported among human but also veterinary isolates during the last two to three decades, very likely as a consequence of the large clinical usage of those antibiotics. Even if the principle mechanisms of resistance to quinolones are chromosome-encoded, due to modifications of molecular targets (DNA gyrase and topoisomerase IV, decreased outer-membrane permeability (porin defect and overexpression of naturally-occurring efflux, the emergence of plasmid-mediated quinolone resistance (PMQR has been reported since 1998. Although these PMQR determinants confer low-level resistance to quinolones and/or fluoroquinolones, they are a favorable background for selection of additional chromosome-encoded quinolone resistance mechanisms. Different transferable mechanisms have been identified, corresponding to the production of Qnr proteins, of the aminoglycoside acetyltransferase AAC(6’-Ib-cr, or of the QepA-type or OqxAB-type efflux pumps. Qnr proteins protect target enzymes (DNA gyrase and type IV topoisomerase from quinolone inhibition (mostly nalidixic acid. The AAC(6’-Ib-cr determinant acetylates several fluoroquinolones, such as norfloxacin and ciprofloxacin. Finally, the QepA and OqxAB efflux pumps extrude fluoroquinolones from the bacterial cell. A series of studies have identified the environment to be a reservoir of PMQR genes, with farm animals and aquatic habitats being significantly involved. In addition, the origin of the qnr genes has been identified, corresponding to the waterborne species Shewanella sp. Altogether, the recent observations suggest that the aquatic environment might constitute the original source of PMQR genes, that would secondly spread among animal or human isolates.

  12. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis.

    Science.gov (United States)

    Willemsen, Ina; Cooper, Ben; van Buitenen, Carin; Winters, Marjolein; Andriesse, Gunnar; Kluytmans, Jan

    2010-09-01

    The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions.

  13. Novel application of Wiener vis-à-vis Szeged indices: Antitubercular activities of quinolones

    Indian Academy of Sciences (India)

    Vijay K Agarwal; Shahnaz Bano; Keshav C Mathur; Padmakar V Khadikar

    2000-04-01

    The paper gives a brief account of the recently introduced Szeged index (Sz). Using this index antitubercular activities of N-2,4-difluorophenyl quinolones are subjected to quantitative structure-activity relationship analysis. The potential of Sz related to the Wiener index (W) is critically discussed. In addition, Huckel molecular orbital energies: HOMO, LUMO and total were also used for comparing and modelling antitubercular activities of the quinolones. The results, based on univariate as well as multivariate regressions, have shown that W, Sz and total give better results and that the correlations improve in multivariate regression analyses.

  14. The DNA gyrase-quinolone complex. ATP hydrolysis and the mechanism of DNA cleavage

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    Quinolone binding to the gyrase-DNA complex induces a conformational change that results in the blocking of supercoiling. Under these conditions gyrase is still capable of ATP hydrolysis which now proceeds through an alternative pathway involving two different conformations of the enzyme (Kampranis......, S. C., and Maxwell, A. (1998) J. Biol. Chem. 269, 22606-22614). The kinetics of ATP hydrolysis via this pathway have been studied and found to differ from those of the reaction of the drug-free enzyme. The quinolone-characteristic ATPase rate is DNA-dependent and can be induced in the presence...

  15. Prevalence of plasmid-mediated quinolone resistance determinants among oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina

    Directory of Open Access Journals (Sweden)

    Giovanna Rincon Cruz

    2013-11-01

    Full Text Available High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6'-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6'-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers.

  16. Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations in quinolone-resistant Escherichia coli isolated from humans and swine in Denmark.

    Science.gov (United States)

    Cavaco, Lina Maria; Frimodt-Møller, Niels; Hasman, Henrik; Guardabassi, Luca; Nielsen, Lene; Aarestrup, Frank Møller

    2008-06-01

    Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were investigated in 124 Escherichia coli isolated from humans (n=85) and swine (n=39) in Denmark. The collection included 59 high-level CIP-resistant isolates (MIC >or= 4) from human (n=51) and pig origin (n=8) and 65 low-level CIP-resistant isolates (MIC >or= 0.125) from human (n=34) and pig origin (n=31). Resistance by target modification was screened by PCR amplification and sequencing of the quinolone resistance determining regions (QRDRs) of gyrA, gyrB, parC, and parE. QRDR mutations occurred in all except two isolates (98%). All high-level CIP-resistant E. coli had one or two mutations in gyrA in combination with mutations in parC or parE. Mutations in parC and parE were only found in combination with gyrA mutations, and no mutations were observed in gyrB. Efflux pump mechanisms were detected in 10 human (11.8%) and 29 porcine (74.4%) isolates by an efflux pump inhibitor (EPI) agar dilution assay. The aac(6')-Ib-cr gene mediating resistance by enzymatic modification was found in 12 high-level CIP-resistant human isolates. The qnrA and qnrS genes conferring quinolone resistance by target protection were detected in two human low-level CIP-resistant isolates that did not display NAL resistance. As expected, target mutation in QRDRs was the most prevalent mechanism of quinolone resistance. This mechanism was complemented by efflux mechanisms in most porcine isolates. Transferable resistance by target protection or enzymatic modification was less common (10%) and restricted to human isolates.

  17. Nickel-quinolones interaction. Part 5-Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones.

    Science.gov (United States)

    Skyrianou, Kalliopi C; Perdih, Franc; Papadopoulos, Athanasios N; Turel, Iztok; Kessissoglou, Dimitris P; Psomas, George

    2011-10-01

    The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N'-donor heterocyclic ligand 2,2'-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2'-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2'-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)(2)(2,2'-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)(2)(H(2)O)(2)], [Ni(quinolonato)(2)(2,2'-bipyridine)] and [Ni(quinolonato)(2)(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase.

  18. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    Directory of Open Access Journals (Sweden)

    Alejandra eBernardini

    2015-10-01

    Full Text Available Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained S. maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457.. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  19. Quinolone resistant campylobacter infections in Denmark: risk factors and clinical consequences

    DEFF Research Database (Denmark)

    Engberg, J.; Neimann, J.; Nielsen, E. M.

    2004-01-01

    origin) was associated with a decreased risk. Typing data showed an association between strains from retail food products and broiler chickens and quinolone-sensitive domestically acquired C. jejuni infections. An association between treatment with a fluoroquinolone before stool-specimen collection...

  20. In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

    Science.gov (United States)

    Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

    2004-05-01

    We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

  1. Distinguishing importation from diversification of quinolone-resistant Neisseria gonorrhoeae by molecular evolutionary analysis

    Directory of Open Access Journals (Sweden)

    Dan Michael

    2007-06-01

    Full Text Available Abstract Background Distinguishing the recent introduction of quinolone resistant gonococci into a population from diversification of resistant strains already in the population is important for planning effective infection control strategies. We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping genes and gyrA, parC and porB of 24 quinolone resistant N. gonorrhoeae (QRNG and 24 quinolone sensitive isolates collected in Israel during 2000–2001. Results Phylogenetic and eBURST analyses and estimates of divergence time indicated QRNG were introduced on 3 separate occasions and underwent limited diversification by mutation, deletion and horizontal gene transfer. Reconstruction of N. gonorrhoeae demography showed a slowly declining effective strain population size from 1976 to 1993, rapid decline between 1994 and 1999, and an increase from 1999 to 2001. This is partially attributable to declining gonorrhea case rates from 1973 to 1994. Additional contributing factors are selective sweeps of antibiotic resistant gonococci and increased transmission from sex workers. The abrupt decline in the mid-1990s heralded an increased incidence of gonorrhea from 1997 to the present. The subsequent increase in effective strain population size since 1999 reflects the increased gonococcal census population and introduction of quinolone resistance strains. Conclusion Our study demonstrates the effective use of population genetic approaches to assess recent and historical population dynamics of N. gonorrhoeae.

  2. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: Comparison of pefloxacin, ciprofloxacin, and ofloxacin

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Elliott, T.B.; Ledney, G.D. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-05-01

    Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.

  3. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates...

  4. Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives

    Directory of Open Access Journals (Sweden)

    Nagatoshi Nishiwaki

    2010-07-01

    Full Text Available The 1-methyl-2-quinolone (MeQone framework is often found in alkaloids and recently attention was drawn to unnatural MeQone derivatives with the aim of finding new biologically active compounds, however, low reactivity of the MeQone framework prevents the syntheses of versatile derivatives. A nitro group is one of the useful activating groups for this framework that enables a concise chemical transformation. Among nitroquinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ exhibits unusual reactivity favoring region-selective cine-substitutions that afford 4-substituted 1-methyl-6,8-dinitro-2-quinolones upon treatment with nucleophilic reagents. Contrary to this, 1-methyl-3,6-dinitro-2-quinolone (3,6-DNQ does not undergo any reaction under the same conditions. The unusual reactivity of TNQ is caused by steric repulsion between the methyl group at the 1-position and the nitro group at the 8-position, which distorts the MeQone framework. As a result, the pyridone ring of TNQ loses aromaticity and acts rather as an activated nitroalkene. Indeed, the pyridone moiety of TNQ undergoes cycloaddition with electron-rich alkenes or dienes under mild conditions, whereby a new fused ring is constructed on the [c]-face of the MeQone. Consequently, TNQ can be used as a new scaffold leading to versatile unnatural MeQone derivatives.

  5. Improved microbial screning assay for the detection of quinolone residues in poultry and eggs

    NARCIS (Netherlands)

    Pikkemaat, M.G.; Mulder, P.P.J.; Elferink, J.W.A.; Cocq, A.; Nielen, M.W.F.; Egmond, van H.J.

    2007-01-01

    An improved microbiological screening assay is reported for the detection of quinolone residues in poultry muscle and eggs. The method was validated using fortified tissue samples and is the first microbial assay to effectively detect enrofloxacin, difloxacin, danofloxacin, as well as flumequine and

  6. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves

    NARCIS (Netherlands)

    Hordijk, J.; Veldman, K.T.; Dierikx, C.M.; Essen-Zandbergen, van A.; Wagenaar, J.A.; Mevius, D.J.

    2012-01-01

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional dat

  7. Plasmid-mediated quinolone resistance among non-typhi Salmonella enterica isolates, USA

    Science.gov (United States)

    We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella (NTS) spp. isolates from humans, food animals, and retail meat in the United States in 2007. Fifty-one (2.4%) of human isolates (n=2165), 5 (1.6%) of isolates from animal isolates (n=1915) an...

  8. Generation and characterization of quinolone-specific DNA aptamers suitable for water monitoring.

    Science.gov (United States)

    Reinemann, C; Freiin von Fritsch, U; Rudolph, S; Strehlitz, B

    2016-03-15

    Quinolones are antibiotics that are accredited in human and veterinary medicine but are regularly used in high quantities also in industrial livestock farming. Since these compounds are often only incompletely metabolized, significant amounts contaminate the aquatic environment and negatively impact on a variety of different ecosystems. Although there is increasing awareness of problems caused by pharmaceutical pollution, available methods for the detection and elimination of numerous pharmaceutical residues are currently inefficient or expensive. While this also applies to antibiotics that may lead to multi-drug resistance in pathogenic bacteria, aptamer-based technologies potentially offer alternative approaches for sensitive and efficient monitoring of pharmaceutical micropollutants. Using the Capture-SELEX procedure, we here describe the selection of an aptamer pool with enhanced binding qualities for fluoroquinolones, a widely used group of antibiotics in both human and veterinary medicine. The selected aptamers were shown to detect various quinolones with high specificity, while specific binding activities to structurally unrelated drugs were not detectable. The quinolone-specific aptamers bound to ofloxacin, one of the most frequently prescribed fluoroquinolone, with high affinity (KD=0.1-56.9 nM). The functionality of quinolone-specific aptamers in real water samples was demonstrated in local tap water and in effluents of sewage plants. Together, our data suggest that these aptamers may be applicable as molecular receptors in biosensors or as catcher molecules in filter systems for improved monitoring and treatment of polluted water.

  9. Synthesis of quinolones by nickel-catalyzed cycloaddition via elimination of nitrile.

    Science.gov (United States)

    Nakai, Kenichiro; Kurahashi, Takuya; Matsubara, Seijiro

    2013-02-15

    Substituted quinolones were efficiently synthesized via the nickel-catalyzed cycloaddition of o-cyanophenylbenzamide derivatives with alkynes. The reaction involves elimination of a nitrile group by cleavage of the two independent aryl-cyano and aryl-carbonyl C-C bonds of the amides.

  10. [Determination of 25 quinolones in cosmetics by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Lin, Li; Zhang, Yi; Tu, Xiaoke; Xie, Liqi; Yue, Zhenfeng; Kang, Haining; Wu, Weidong; Luo, Yao

    2015-03-01

    An analytical method was developed for the simultaneous determination of 25 quinolones, including danofloxacin mesylate, enrofloxacin, flumequine, oxloinic acid, ciprofloxacin, sarafloxacin, nalidixic acid, norfloxacin, and ofloxacin etc in cosmetics using direct extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Cosmetic sample was extracted by acidified acetonitrile, defatted by n-hexane and separated on Poroshell EC-C18 column with gradient elution program using acetonitrile and water (both containing 0. 1% formic acid) as the mobile phases and analyzed by LC-ESI-MS/MS under the positive mode using multiple reaction monitoring (MRM). The interference of matrix was reduced by the matrix-matched calibration standard curve. The method showed good linearities over the range of 1-200 mg/kg for the 25 quinolones with good linear correlation coefficients (r ≥ 0.999). The method detection limit of the 25 quinolones was 1.0 mg/kg, and the recoveries of all analytes in lotion, milky and cream cosmetics matrices ranged from 87.4% to 105% at the spiked levels of 1, 5 and 10 mg/kg with the relative standard deviations (RSD) of 4.54%-19.7% (n = 6). The results indicated that this method is simple, fast and credible, and suitable for the simultaneous determination of the quinolones in the above three types of cosmetics.

  11. Bartonella bacilliformis, endemic pathogen of the Andean region, is intrinsically resistant to quinolones.

    Science.gov (United States)

    del Valle, Luis J; Flores, Lidia; Vargas, Martha; García-de-la-Guarda, Ruth; Quispe, Ruth L; Ibañez, Zoila B; Alvarado, Débora; Ramírez, Pablo; Ruiz, Joaquim

    2010-06-01

    To analyze the sequence of the region involved in the development of quinolone resistance of the gyrA and parC genes in a series of Bartonella bacilliformis isolates recovered prior to the introduction of quinolones, as well as one clinical isolate recovered in the 1970s, establishing the susceptibility levels to nalidixic acid and ciprofloxacin. Five B. bacilliformis were studied: four isolated before 1957, prior to the introduction of quinolones in clinical practice. The remaining strain was isolated in 1977. A fragment of the gyrA and parC genes was amplified and sequenced. Susceptibility to nalidixic acid and ciprofloxacin was established by the E-test method. All the strains were resistant to nalidixic acid (minimum inhibitory concentration (MIC) >256 mg/l). Three isolates presented decreased susceptibility to ciprofloxacin and two were highly resistant (MIC >32 mg/l). All the strains presented an Ala at position 91 of GyrA and position 85 of ParC. B. bacilliformis presents a constitutive resistance to quinolones, which may be related to the presence of Ala at position 91 of GyrA and 85 of ParC. These results advise against the current clinical guidelines recommending the use of ciprofloxacin to treat bartonellosis in some countries of the Andean area. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves

    NARCIS (Netherlands)

    Hordijk, J.; Veldman, K.T.; Dierikx, C.M.; Essen-Zandbergen, van A.; Wagenaar, J.A.; Mevius, D.J.

    2012-01-01

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional dat

  13. [Preliminary study on occurrence and health risk assessment of quinolone antibiotics in vegetables from Guangzhou, China].

    Science.gov (United States)

    Li, Yan-Wen; Zhang, Yan; Mo, Ce-Hui; Tai, Yi-Ping; Wu, Xiao-Lian; Wang, Ji-Yang; Su, Qing-Yun

    2010-10-01

    Quinolone antibiotics (QNs) including norfloxacin (NOR), enrofolxacin (ENR), ciprofloxacin (CIP) and lomefloxacin (LOM) in vegetable samples collected from Guangzhou were determined by high performance liquid chromatography (HPLC) coupled with fluorescent detector (FLD). The detected frequency of QNs was 96% in vegetables. The total concentration of quinolones (sigma QNs) detected in vegetable ranged from 1.0 microg/kg to 1 683.1 microg/kg (F.W.). Leafy vegetable topped the content of quinolones among the three types of vegetables, followed by the melon-fruit vegetable and rhizome vegetable. The detected frequency of the four quinolone antibiotics ranked as NOR > CIP > LOM > ENR. Except ENR, concentrations of CIP, NOR, LOM and sigma QNs in pollution-free vegetable, green vegetable and organic vegetable were higher than those in routine cultivated vegetables. The maximum contribution to ADI value (caculated by the sum of CIP and ENR) is estimated up to 41.5% and 83% for adults and children respectively via consumption of vegetables.

  14. CE determination of quinolones in the presence of bovine serum albumin.

    Science.gov (United States)

    Qin, Weidong; Liu, Qingchun; Fan, Yongxia

    2009-01-01

    This article describes the influence of bovine serum albumin (BSA) as an additive on the capillary electrophoresis-potential gradient determination of five quinolones, enoxacin, norfloxacin, ofloxacin, fleroxacin, and pazufloxacin. With 10 mg/L of BSA present in the buffer of 30 mM Tris and 3 mM phosphoric acid at pH 9, the detection limits of the five quinolones were in the range of 0.24-0.68 mg/L, i. e. 5.8-16.5-fold lower than those obtained with the buffer devoid of BSA, and the analysis time was shortened. We suggest that the inner wall-adsorbed BSA suppresses the adsorption of quinolones and simultaneously enhances the electroosmotic flow rate. Our experiments indicated that adopting the potential gradient detection technique could eliminate the interference of the UV-active proteins on the detection of quinolones that would occur with conventional optical detection, and therefore offer high detection sensitivity. As a demonstration, the method was applied to the determination of QNs in fortified chicken muscle sample with satisfactory results.

  15. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Energy Technology Data Exchange (ETDEWEB)

    He, Jiang-Hong [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Xiao, Dong-Rong, E-mail: xiaodr98@yahoo.com.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Luo, Qun-Li, E-mail: qlluo@swu.edu.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Wang, En-Bo, E-mail: wangeb889@nenu.edu.cn [Key Laboratory of Polyoxometalate Science of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024 (China)

    2013-02-15

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]{center_dot}H{sub 2}O (1), [M(norfH)(bpdc)]{center_dot}H{sub 2}O (M=Cd (2) and Mn (3)), [Mn{sub 2}(cfH)(odpa)(H{sub 2}O){sub 3}]{center_dot}0.5H{sub 2}O (4), [Co{sub 2}(norfH)(bpta)({mu}{sub 2}-H{sub 2}O)(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O (5) and [Co{sub 3}(saraH){sub 2}(Hbpta){sub 2}(H{sub 2}O){sub 4}]{center_dot}9H{sub 2}O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4 Prime -biphenyldicarboxylate, odpa=4,4 Prime -oxydiphthalate, bpta=3,3 Prime ,4,4 Prime -biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed. - Graphical abstract: Six novel 2D metal-quinolone complexes have been prepared by self-assemblies of the quinolones and metal salts in the presence of long aromatic polycarboxylates. Highlights: Black-Right-Pointing-Pointer Compounds 1-3 consist of novel 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Black-Right-Pointing-Pointer Compounds 4 and 5 are two novel 2D layers based on tetranuclear Mn or Co clusters with kgd topology. Black-Right-Pointing-Pointer Compound 6 is the first example of metal-quinolone complexes with 2D bilayer structure. Black-Right-Pointing-Pointer Compounds 1-6 represent six unusual

  16. Microbial screening for quinolones residues in cow milk by bio-optical method.

    Science.gov (United States)

    Appicciafuoco, Brunella; Dragone, Roberto; Frazzoli, Chiara; Bolzoni, Giuseppe; Mantovani, Alberto; Ferrini, Anna Maria

    2015-03-15

    The use of antibiotics on lactating cows should be monitored for the possible risk of milk contamination with residues. Accordingly, Maximum Residue Levels (MRLs) are established by the European Commission to guarantee consumers safety. As pointed out by Dec 2002/657/EC, screening is the first step in the strategy for antibiotic residue control, thus playing a key role in the whole control procedure. However, current routine screening methods applied in milk chain still fail to detect residues of quinolones at concentrations of interest. This paper reports the findings of a new bio-optical method for the screening of quinolones residues in bovine milk, based on E. coli ATCC 11303 growth inhibition. The effect of blank and spiked cow milk samples (aliquots equivalents to 0.8%, v/v) is evaluated in Mueller Hinton Broth (MHb) and MHb enriched with MgSO4 2% (MHb-Mg) inoculated with the test strain at the concentration of 10(4)CFU/mL. The presence of quinolones inhibits the cellular growth in MHb, while this effect is neutralized in MHb-Mg allowing both detection and presumptive identification of quinolones. Growth of the test strain is monitored at 37 °C in a Bioscreen C automated system, and Optical Density (OD) at 600 nm is recorded every 10 min after shaking for 10s. Growth curves (OD vs. time) of E. coli ATCC 11303 are assessed in milk samples, with and without quinolones, and their differences in terms of ΔOD (ΔOD600nm=ODMHb-Mg-ODMHb) are calculated. The presence of quinolones is detected by the cellular growth inhibition (OD vs time, none increase in the value OD) and presumptively identified through the increase of the slope of ΔOD600nm curve (ΔOD vs. time), after about 3h of incubation. The detection limit for ciprofloxacin and enrofloxacin is at the level of MRL, for marbofloxacin is at 2-fold the MRL whereas for danofloxacin is at 4-fold the MRL. Although the sensitivity of the method could be further improved and the procedure automated, it is a

  17. Sub-inhibitory concentrations of vancomycin prevent quinolone-resistance in a penicillin-resistant isolate of Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Moreillon Philippe

    2001-07-01

    Full Text Available Abstract Background The continuous spread of penicillin-resistant pneumococci represents a permanent threat in the treatment of pneumococcal infections, especially when strains show additional resistance to quinolones. The main objective of this study was to determine a treatment modality impeding the emergence of quinolone resistance. Results Exposure of a penicillin-resistant pneumococcus to increasing concentrations of trovafloxacin or ciprofloxacin selected for mutants resistant to these drugs. In the presence of sub-inhibitory concentrations of vancomycin, development of trovafloxacin-resistance and high-level ciprofloxacin-resistance were prevented. Conclusions Considering the risk of quinolone-resistance in pneumococci, the observation might be of clinical importance.

  18. Decay mechanisms of protonated 4-quinolone antibiotics after electrospray ionization and ion activation.

    Science.gov (United States)

    Kovačević, Borislav; Schorr, Pascal; Qi, Yulin; Volmer, Dietrich A

    2014-11-01

    This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pK a and proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO(2) loss) and charge-mediated (H(2)O loss) fragmentation of the piperazinyl quinolones, depending on whether the proton resides on the more basic keto or the piperazinyl group, followed by a number of secondary dissociation reactions. The proposed mechanisms were supported by calculated energies of precursors, transition states, and products for competing pathways.

  19. Detection of quinolones in poultry meat obtained from retail centers in Santiago Province, the Dominican Republic.

    Science.gov (United States)

    Silfrany, R O; Caba, R E; Solís de Los Santos, F; Hanning, I

    2013-02-01

    In the Dominican Republic, poultry consumption per capita is greater than 34 kg of poultry meat per year. However, antibiotics, specifically the quinolone group, may be overused and can result in residues in the poultry meat. These residues are of concern because consumers may have allergies to antibiotics and antibiotic-resistant bacteria can develop from overuse of antibiotics in production. Little is known concerning this issue specifically for Santiago Province in the Dominican Republic. Thus, the main purpose of this research was to evaluate the incidence of residual quinolones in poultry meat and determine whether any residues detected were higher than the residue maximum limits (100 μg/kg) established by food industry authorities, including the U.S. Food and Drug Administration and European Food Safety Authority. A total of 135 samples of chicken breast were taken from different retail meat centers in the nine municipalities of Santiago Province (Santiago, Tamboril, Sabana Iglesia, Villa Bisonó, Puñal, Villa González, Licey, Jánico, and San José De Las Matas) and were analyzed using the Equinox test (Immunotec, Swanton, VT). Of the 135 samples analyzed, 50% from Sabana Iglesia, 20% from Licey, 20% from San Jose De Las Matas, and 6.25% from Santiago contained residues of quinolones higher than the residue maximum limits. No quinolone residues were detected in samples obtained from Janico, Punal, Tamboril, Villa Bisono, or Villa Gonzalez. The results of this investigation suggest that some poultry meat sold for human consumption in Santiago Province of the Dominican Republic contains quinolone residues and may represent a health risk to some consumers.

  20. 喹诺酮类药物的研究进展%Progress on the Research of Pharmaceuticals of Quinolones

    Institute of Scientific and Technical Information of China (English)

    曾焕君; 王怀生

    2014-01-01

    Quinolones are synthetic antibacterial agents. many quinolones have one or two chiral centers and some of enantiomers show dif erent feature in pharmacology, toxicology and pharmacodynamics. In this paper, chiral separation and determination of quinolones about recent years were reviewed for providing some reference in the research of quinolones.%喹诺酮类药物是人工合成的抗菌药,很多药物都具有1~2个手性中心,且有些对映体呈现不同的药理学的、毒理学的、药效学的特性。本文对近几年喹诺酮类的药物手性的拆分与定量进行了研究,为临床上研究喹诺酮类的药物提供了一系列参考依据。

  1. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  2. Prevalence of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae strains isolated in North-East Italy.

    Science.gov (United States)

    Kocsis, B; Mazzariol, A; Kocsis, E; Koncan, R; Fontana, R; Cornaglia, G

    2013-02-01

    We investigated the prevalence of plasmid-mediated quinolone resistance genes in 756 clinical isolates of Enterobacteriaceae originating from Microbiology Diagnostic Laboratories of North-East Italy. Five point zero two percent of isolates carried a qnr determinant while the aac(6')-Ib-cr determinant was detected in 9·25% of isolates. We also investigated the association between the plasmid-mediated quinolone resistance and the beta-lactamase genes, and characterized the plasmids carrying these determinants of resistance.

  3. Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance.

    Science.gov (United States)

    Kim, Hyun; Nakajima, Chie; Yokoyama, Kazumasa; Rahim, Zeaur; Kim, Youn Uck; Oguri, Hiroki; Suzuki, Yasuhiko

    2011-08-01

    Amino acid substitutions conferring resistance to quinolones in Mycobacterium tuberculosis have generally been found within the quinolone resistance-determining regions (QRDRs) in the A subunit of DNA gyrase (GyrA) rather than the B subunit of DNA gyrase (GyrB). To clarify the contribution of an amino acid substitution, E540V, in GyrB to quinolone resistance in M. tuberculosis, we expressed recombinant DNA gyrases in Escherichia coli and characterized them in vitro. Wild-type and GyrB-E540V DNA gyrases were reconstituted in vitro by mixing recombinant GyrA and GyrB. Correlation between the amino acid substitution and quinolone resistance was assessed by the ATP-dependent DNA supercoiling assay, quinolone-inhibited supercoiling assay, and DNA cleavage assay. The 50% inhibitory concentrations of eight quinolones against DNA gyrases bearing the E540V amino acid substitution in GyrB were 2.5- to 36-fold higher than those against the wild-type enzyme. Similarly, the 25% maximum DNA cleavage concentrations were 1.5- to 14-fold higher for the E540V gyrase than for the wild-type enzyme. We further demonstrated that the E540V amino acid substitution influenced the interaction between DNA gyrase and the substituent(s) at R-7, R-8, or both in quinolone structures. This is the first detailed study of the contribution of the E540V amino acid substitution in GyrB to quinolone resistance in M. tuberculosis.

  4. Prevalence of quinolone resistance determinants in non-typhoidal Salmonella isolates from human origin in Extremadura, Spain.

    Science.gov (United States)

    Campos, Maria Jorge; Palomo, Gonzalo; Hormeño, Lorena; Herrera-León, Silvia; Domínguez, Lucas; Vadillo, Santiago; Píriz, Segundo; Quesada, Alberto

    2014-05-01

    Resistance to the quinolones nalidixic acid (NAL) and ciprofloxacin (CIP) and the occurrence of quinolone resistance determinants have been investigated in 300 non-typhoidal Salmonella from human origin, isolated in the years between 2004 and 2008, in 6 hospitals within Extremadura (Spain). Salmonella Enteritidis was the major serotype found among quinolone-resistant isolates, most of which were clustered by clonal analysis to a single clone, which presented D87 or S83 substitutions in GyrA. Eleven isolates presented the non-classical quinolone resistance phenotype (resistance to CIP and susceptibility to NAL), lacking mutations in the quinolone resistance determinant region of topoisomerase genes. Among them, one Salmonella Typhimurium isolate carried a qnrS1 gene in a low-molecular-weight plasmid, pQnrS1-HLR25, identical to plasmids previously found in the UK, Taiwan, and USA. The occurrence of this genetic element could represent a risk for the horizontal transmission of quinolone resistance among Enterobacteriaceae in the Iberian Peninsula.

  5. Comparative Analysis of Quinolone Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli from Chinese Children and Adults

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2015-01-01

    Full Text Available The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P>0.05. The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P=0.5444. Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

  6. Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation using 2D and 3D models.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Zhao, Huimin; Du, Yuguo

    2014-01-01

    The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay. Some quinolones exhibited high genotoxicity, and the chemical substituent on quinolone ring significantly affected genotoxicity. To establish the relationship between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical parameters was developed. Calculation suggested that both steric and electrostatic properties were correlated well with genotoxicity. Furthermore, the specific effect on three key active sites (1-, 7- and 8-positions) of quinolone ring was investigated using a 3D-QSAR (comparative molecular field analysis, CoMFA) method. From our modeling, the genotoxicity increased when substituents had: (1) big volume and/or positive charge at 1-position; (2) negative charge at 7-position; and (3) small volume and/or negative charge at 8-position. The developed QSAR models were applicable to estimate genotoxicity of quinolones antibiotics and their transformation products. It is noted that some of the transformation products exhibited higher genotoxicity comparing to their precursor (e.g., ciprofloxacin). This study provided an alternative way to understand the molecule genotoxicity of quinolones derivatives, as well as to evaluate their potential environmental risks.

  7. Comparative analysis of quinolone resistance in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese children and adults.

    Science.gov (United States)

    Huang, Ying; Ogutu, James O; Gu, Jiarui; Ding, Fengshu; You, Yuhong; Huo, Yan; Zhao, Hong; Li, Wenjing; Zhang, Zhiwei; Zhang, Wenli; Chen, Xiaobei; Fu, Yingmei; Zhang, Fengmin

    2015-01-01

    The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P > 0.05). The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P = 0.5444). Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

  8. Plasmid-related quinolone resistance determinants in epidemic Vibrio parahaemolyticus, uropathogenic Escherichia coli, and marine bacteria from an aquaculture area in Chile.

    Science.gov (United States)

    Aedo, Sandra; Ivanova, Larisa; Tomova, Alexandra; Cabello, Felipe C

    2014-08-01

    Marine bacteria from aquaculture areas with industrial use of quinolones have the potential to pass quinolone resistance genes to animal and human pathogens. The VPA0095 gene, related to the quinolone resistance determinant qnrA, from clinical isolates of epidemic Vibrio parahaemolyticus conferred reduced susceptibility to quinolone after cloning into Escherichia coli K-12 either when acting alone or synergistically with DNA gyrase mutations. In addition, a plasmid-mediated quinolone resistance gene from marine bacteria, aac(6')-Ib-cr, was identical to aac(6')-Ib-cr from urinary tract isolates of E. coli, suggesting a recent flow of this gene between these bacteria isolated from different environments. aac(6')-Ib-cr from E. coli also conferred reduced susceptibility to quinolone and kanamycin when cloned into E. coli K-12.

  9. Survey of Tetracyclines, Sulfonamides, Sulfamethazine, and Quinolones in UHT Milk in China Market

    Institute of Scientific and Technical Information of China (English)

    HAN Rong-wei; ZHENG Nan; WANG Jia-qi; ZHEN Yun-peng; LI Song-li; YU Qun-li

    2013-01-01

    This study surveyed 180 samples of ultra high temperature (UHT) milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were<1.5, 26.2, 22.6, and 58.8μg kg-1, respectively. None of the samples exceeded the maximum residue levels (MRLs) for these four veterinary drugs, according to the regulations set by China, the European Union (EU) and the Codex Alimentarius Commission (CAC).

  10. An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype typhimurium DT104

    DEFF Research Database (Denmark)

    Molbak, K.; Baggesen, Dorte Lau; Aarestrup, Frank Møller

    1999-01-01

    , and tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones. Methods The Danish salmonella surveillance program determines the phage types of all typhimurium strains from the food chain, and in the case of suspected outbreaks, five-drug-resistant strains...... findings here. Results Until 1997, DT104 infections made up less than 1 percent of all human salmonella infections. The strain isolated from patients in the first community outbreak of DT104 in Denmark, in 1998, was resistant to nalidixic acid and had reduced susceptibility to fluoroquinolones...... with fluoroquinolones. Conclusions Our investigation of an outbreak of DT104 documented the spread of quinolone-resistant bacteria from food animals to humans; this spread was associated with infections that were difficult to treat. Because of the increase in quinolone resistance in salmonella, the use...

  11. Resistance to quinolones in Campylobacter jejuni and Campylobacter coli from Danish broilers at farm level

    DEFF Research Database (Denmark)

    Pedersen, Karl; Wedderkopp, A.

    2003-01-01

    Aims : To investigate the prevalence of quinolone resistance among Campylobacter jejuni and Camp. coli isolates from Danish poultry at the farm level, as well as for the whole country. Methods and Results : Data and isolates were collected from a national surveillance of Campylobacter in poultry......-resistant variant. Conclusions : Overall, quinolone resistance among Campylobacter isolates from Danish broilers was 7.5% in 1998 and 1999; it was higher among Camp. coli than Camp. jejuni . Genetic diversity among resistant isolates was lower than among susceptible isolates, and certain clones existed in both...... a resistant and a susceptible variant. Some resistant clones appeared to persist on the farms and were repeatedly isolated from poultry flocks. Significance and Impact of the Study : The study is important for the understanding of persistence and dynamics of Campylobacter in broiler houses. It also highlights...

  12. Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives.

    Science.gov (United States)

    Manetti, Fabrizio; Petricci, Elena; Gabrielli, Annalisa; Mann, Andrè; Faure, Hélène; Gorojankina, Tatiana; Brasseur, Laurent; Hoch, Lucile; Ruat, Martial; Taddei, Maurizio

    2016-10-04

    Smoothened (Smo) is the signal transducer of the Hedgehog (Hh) pathway and its stimulation is considered a potential powerful tool in regenerative medicine to treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new quinolones (0.4-0.9 μM) is comparable to or better than that of SAG and purmorphamine, two reference Smo agonists. Structure-activity relationships allow identification of several molecular determinants important for the activity of these compounds.

  13. Determination of fluorinated quinolone antibacterials by ion chromatography with fluorescence detection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan-zhen; ZHANG Zheng-yi; ZHOU Yan-chun; LIU Li; ZHU Yan

    2007-01-01

    For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluorescence detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column with an eluent of 15 mmol/L H2SO4 and 35% methanol (v/v) at a flow-rate of 1.0 ml/min and detected with fluorescence with excitation and emission wave lengths of 347 nm and 420 nm respectively. The detection limits (S/N=3) ofnorfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively. The relative standard deviations of retention time, peak area and peak height were less than 1.1% and good linear relationship resulted.The developed method was applied to pharmaceutical formulations and biological fluids.

  14. Origins of the Quinolone Class of Antibacterials: An Expanded "Discovery Story".

    Science.gov (United States)

    Bisacchi, Gregory S

    2015-06-25

    Published descriptions of the specific lines of research leading to the discovery of therapeutically important medicines, especially major new class medicines, have long provided value to the biopharmaceutical community as models of success, often influencing the strategies and methods of subsequent drug research. Quinolone antibacterials represent one of medicine's most important classes of anti-infective agents; yet in contrast to many other classes of anti-infectives, astonishingly few details concerning the origin of the class or the rationale leading to the selection of the first clinical agent, nalidixic acid, were ever published by the discoverers. Moreover, earlier disclosures of an independent discovery of the quinolone class of antibacterials have been almost entirely overlooked by the scientific literature. This review brings together all the available information from primary literature sources relating to both discoveries and provides for the first time a much fuller, if still partially speculative, story of the earliest years of this important class of drugs.

  15. 4(1H)-Quinolones with liver stage activity against Plasmodium berghei.

    Science.gov (United States)

    Lacrue, Alexis N; Sáenz, Fabián E; Cross, R Matthew; Udenze, Kenneth O; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S; Manetsch, Roman; Kyle, Dennis E

    2013-01-01

    With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

  16. Occurrence of quinolone- and beta-lactam-resistant Escherichia coli in danish broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    ). In Denmark, antimicrobial resistance is annually monitored in both clinical and indicator E. coli isolated from poultry (DANMAP, 2006). However, very little is known on the prevalence of resistance at the flock level. The aim of this study was to determine the prevalence of flocks positive for E. coli...... resistant to quinolones or ß-lactams. Sock samples were collected from 10 broiler parent flocks and 10 broiler offspring flocks. Five pairs of socks were collected from each house. Samples were enriched in McConkey broth and streaked on McConkey agar added with nalidixic acid (32 µg/ml), ciprofloxacin (2 µg...... and nalidixic acid resistances were detected in all flocks. The numbers of E. coli resistant to these drugs were higher in plates from parent flocks than in those from offspring flocks. A broiler parent flock without any history of quinolone usage tested positive for ciprofloxacin-resistant E. coli, although...

  17. Dynamics of quinolone resistance in fecal Escherichia coli of finishing pigs after ciprofloxacin administration.

    Science.gov (United States)

    Huang, Kang; Xu, Chang-Wen; Zeng, Bo; Xia, Qing-Qing; Zhang, An-Yun; Lei, Chang-Wei; Guan, Zhong-Bin; Cheng, Han; Wang, Hong-Ning

    2014-09-01

    Escherichia coli resistance to quinolones has now become a serious issue in large-scale pig farms of China. It is necessary to study the dynamics of quinolone resistance in fecal Escherichia coli of pigs after antimicrobial administration. Here, we present the hypothesis that the emergence of resistance in pigs requires drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days old, about 30 kg) not fed any antimicrobial after weaning were selected and divided into 2 equal groups: the experimental (EP) group and control (CP) group. Pigs in the EP group were orally treated daily with 5 mg ciprofloxacin/kg of body weight for 30 days, and pigs in the CP group were fed a normal diet. Fresh feces were collected at 16 time points from day 0 to day 61. At each time point, ten E. coli clones were tested for susceptibility to quinolones and mutations of gyrA and parC. The results showed that the minimal inhibitory concentration (MIC) for ciprofloxacin increased 16-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin administration for 3 days and decreased 256-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin withdrawal for 26 days. GyrA (S83L, D87N/ D87Y) and parC (S80I) substitutions were observed in all quinolone-resistant E. coli (QREC) clones with an MIC ≥8 µg/ml. This study provides scientific theoretical guidance for the rational use of antimicrobials and the control of bacterial resistance.

  18. Design, synthesis and antitumor activity of 3-substituted quinolone derivatives (Ⅰ)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor cells are comparable to that of topotecan, one of topoisomerase I inhibitors.

  19. "Changes in cartilage of rats after treatment with Quinolone and in Magnesium-deficient diet "

    Directory of Open Access Journals (Sweden)

    Shakibaei M

    2002-07-01

    Full Text Available Ultrastructural changes in immature articular carilage were studied after treatment of 5-weeks-old rats with ofloxacin, a fluoroquinolone, and in magnesium deficiency.We concluded that quinolone-induced arthropathy is probably due to chelation of functionally available magnesium in joint cartilage as magnesium deficiency in joint cartilage could impair chondrocyte-matrix- interaction which is mediated by cation-dependent integrin-receptors of the β1-subfamily. With immuno-histochemical methods using monoclonal and polyclonal antibodies we showed that B1 integrins were expressed in rat joint cartilage. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2×600 mg ofloxacin/kg body wt for one day. Gross-structural lesions (e.g. cleft formation, unmasked collagen fibres in magnesium deficient rats were very similar but changes in intergrin expression were less pronounced. Alterations observed on the ultrastructural level showed striking similarities in magnesium-deficient rats and in rats treated with single doses of 600 mg ofloxacin per kg body wt.Typical observation were: bundle shaped, electron-dense aggregates on the surface and in the cytoplasm of chondrocytes, detachement of the cell membrance from the matrix and necrotic chondrocytes, reduced synthesis and/or reduced of extracellular matrix and swelling of cell organelles such as mitochondria.The results of this study confirm our previously reported finding that quinolone-induced arthropathy probably is caued by a reduction of functionally available magnesium (ionized Mg2+ in cartilage. Furthermore, they provide a basis for aimed studies with human cartilage samples from quinolone-treated patients which might be available postmortal or after hip replacement surgery

  20. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil

    Science.gov (United States)

    Pribul, Bruno Rocha; Festivo, Marcia Lima; de Souza, Miliane Moreira Soares; dos Prazeres Rodrigues, Dalia

    2016-01-01

    Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n = 62) and human (n = 67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6′)-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6′)-Ib. The conserved integron region was detected in 67 isolates as variable regions, from ±600 to >1000 pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored. PMID:26887245

  1. Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jesús Machuca

    2017-07-01

    Full Text Available Bactericidal activity of quinolones has been related to a combination of DNA fragmentation, reactive oxygen species (ROS production and programmed cell death (PCD systems. The underlying molecular systems responsible for reducing bactericidal effect during antimicrobial therapy in low-level quinolone resistance (LLQR phenotypes need to be clarified. To do this and also define possible new antimicrobial targets, the transcriptome profile of isogenic Escherichia coli harboring quinolone resistance mechanisms in the presence of a clinical relevant concentration of ciprofloxacin was evaluated. A marked differential response to ciprofloxacin of either up- or downregulation was observed in LLQR strains. Multiple genes implicated in ROS modulation (related to the TCA cycle, aerobic respiration and detoxification systems were upregulated (sdhC up to 63.5-fold in mutants with LLQR. SOS system components were downregulated (recA up to 30.7-fold. yihE, a protective kinase coding for PCD, was also upregulated (up to 5.2-fold. SdhC inhibition sensitized LLQR phenotypes (up to ΔLog = 2.3 after 24 h. At clinically relevant concentrations of ciprofloxacin, gene expression patterns in critical systems to bacterial survival and mutant development were significantly modified in LLQR phenotypes. Chemical inhibition of SdhC (succinate dehydrogenase validated modulation of ROS as an interesting target for bacterial sensitization.

  2. Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries.

    Science.gov (United States)

    Yanat, B; Rodríguez-Martínez, J-M; Touati, A

    2017-03-01

    Quinolones are a family of synthetic broad-spectrum antimicrobial drugs. These molecules have been widely prescribed to treat various infectious diseases and have been classified into several generations based on their spectrum of activity. Quinolones inhibit bacterial DNA synthesis by interfering with the action of DNA gyrase and topoisomerase IV. Mutations in the genes encoding these targets are the most common mechanisms of high-level fluoroquinolone resistance. Moreover, three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998 and include Qnr proteins, the aminoglycoside acetyltransferase AAC(6')-Ib-cr, and plasmid-mediated efflux pumps QepA and OqxAB. Plasmids with these mechanisms often encode additional antimicrobial resistance (extended spectrum beta-lactamases [ESBLs] and plasmidic AmpC [pAmpC] ß-lactamases) and can transfer multidrug resistance. The PMQR determinants are disseminated in Mediterranean countries with prevalence relatively high depending on the sources and the regions, highlighting the necessity of long-term surveillance for the future monitoring of trends in the occurrence of PMQR genes.

  3. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil.

    Science.gov (United States)

    Pribul, Bruno Rocha; Festivo, Marcia Lima; de Souza, Miliane Moreira Soares; Rodrigues, Dalia dos Prazeres

    2016-01-01

    Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n=62) and human (n=67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6')-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6')-Ib. The conserved integron region was detected in 67 isolates as variable regions, from ±600 to >1000pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored.

  4. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li; Luo, Qun-Li; Wang, En-Bo

    2013-02-01

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]rad H2O (1), [M(norfH)(bpdc)]rad H2O (M=Cd (2) and Mn (3)), [Mn2(cfH)(odpa)(H2O)3]rad 0.5H2O (4), [Co2(norfH)(bpta)(μ2-H2O)(H2O)2]rad H2O (5) and [Co3(saraH)2(Hbpta)2(H2O)4]rad 9H2O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4'-biphenyldicarboxylate, odpa=4,4'-oxydiphthalate, bpta=3,3',4,4'-biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {M(COO)}nn+ chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed.

  5. 喹诺酮类药物的研究进展%Research Progress of Quinolones

    Institute of Scientific and Technical Information of China (English)

    田秋月

    2014-01-01

    喹诺酮类药物是一类人工合成的抗菌药物,目前广泛应用于临床抗感染治疗中,具有较强的抗菌活性。本文主要从喹诺酮类药物的作用机制、临床应用、不良反应及耐药机制等方面进行分析和整理,综述其研究进展并对其未来的研究方向提出了建议,希望为今后喹诺酮药物的研究提供一定的参考依据。%Quinolones are a group of synthetic antibacteril drugs with strong antibacterial activity which have a broad range of clinic applications in recent years. In this article, research progress of quinolones was analyzed and summarized from the aspects of action mechanism, clinical application, adverse reactions and drug resistance mechanism, and the future research direction of quinolones was proposed.

  6. Liquid chromatographic determination of quinolones in water and human urine samples after microextraction by packed sorbent.

    Science.gov (United States)

    Rani, Susheela; Kumar, Ashwini; Malik, Ashok Kumar; Singh, Baldev

    2012-01-01

    A method for the simultaneous determination of quinolones in water and urine samples by microextraction in a sorbent-packed syringe (MEPS) with LC is described. MEPS is a new miniaturized SPE technique that can be used with chromatographic instruments without any modifications. In MEPS, approximately 1 mg of the solid packing material is inserted into a syringe (100-250 microL) as a plug. Sample preparation takes place on the packed bed. The new method is promising, easy to use, economical, and rapid. The determination of quinolones in groundwater and urine was performed using MEPS as a sample preparation method with LC-UV determination. Four quinolone antibiotics--enrofloxacin, enoxacin, danofloxacin, and nalidixic acid--in groundwater and urine samples were used as analytes. The extraction recovery was found to be between 64.9 and 98.9%. The results showed high correlation coefficients (R2 > 0.992) for all of the analytes within the calibration range. The LOQ was between 0.091 and 0.315 ng/mL.

  7. Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.

    Science.gov (United States)

    Van Bambeke, Françoise

    2014-11-01

    Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

  8. Characteristics of Quinolone Resistance in Salmonella spp. Isolates from the Food Chain in Brazil.

    Science.gov (United States)

    Pribul, Bruno R; Festivo, Marcia L; Rodrigues, Marcelle S; Costa, Renata G; Rodrigues, Elizabeth C Dos P; de Souza, Miliane M S; Rodrigues, Dalia Dos P

    2017-01-01

    Salmonella spp. is an important zoonotic pathogen related to foodborne diseases. Despite that quinolones/fluoroquinolones are considered a relevant therapeutic strategy against resistant isolates, the increase in antimicrobial resistance is an additional difficulty in controlling bacterial infections caused by Salmonella spp. Thus, the acquisition of resistance to quinolones in Salmonella spp. is worrisome to the scientific community along with the possibility of transmission of resistance through plasmids. This study investigated the prevalence of plasmid-mediated quinolone resistance (PMQR) in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. We evaluated 129 isolates, 39 originated from food of animal sources, and 14 from environmental samples and including 9 from animals and 67 from humans, which were referred to the National Reference Laboratory of Enteric Diseases (NRLEB/IOC/RJ) between 2009 and 2013. These samples showed a profile of resistance for the tested quinolones/fluoroquinolones. A total of 33 serotypes were identified; S. Typhimurium (63) was the most prevalent followed by S. Enteritidis (25). The disk diffusion test showed 48.8% resistance to enrofloxacin, 42.6% to ciprofloxacin, 39.53% to ofloxacin, and 30.2% to levofloxacin. According to the broth microdilution test, the resistance percentages were: 96.1% to nalidixic acid, 64.3% to enrofloxacin, 56.6% to ciprofloxacin, 34.1% to ofloxacin, and 30.2% to levofloxacin. Qnr genes were found in 15 isolates (8 qnrS, 6 qnrB, and 1 qnrD), and the aac(6')-Ib gene in 23. The integron gene was detected in 67 isolates with the variable region between ±600 and 1000 bp. The increased detection of PMQR in Salmonella spp. is a serious problem in Public Health and must constantly be monitored. Pulsed-field gel electrophoresis was performed to evaluated clonal profile among the most prevalent serovars resistant to different classes of quinolones. A total of 33 pulsotypes of S

  9. Detection of quinolones in commercial eggs obtained from farms in the Espaíllat Province in the Dominican Republic.

    Science.gov (United States)

    Moscoso, S; de los Santos, F Solís; Andino, A G; Diaz-Sanchez, Sandra; Hanning, I

    2015-01-01

    Previously, we reported the use of quinolones in broiler chickens resulted in residues in retail poultry meat obtained from nine districts in the Santiago Province of the Dominican Republic. Residues in poultry products are a concern due to consumer allergies and the potential to develop antibiotic-resistant bacteria. Given the use of quinolones in poultry production and our previous findings in poultry meat, the objective of this study was to evaluate the presence of quinolone residues in eggs. Samples were collected from 48 different farms located in three of the four municipalities (Moca, Cayetano Germosén, and Jamao) of the Espaíllat Province. Each farm was sampled three times between July and September for a total of 144 samples. Samples were evaluated qualitatively and quantitatively for quinolone residues using the Equinox test. Operation systems (cage or floor), seasonality, and location were considered along with egg-producer sizes that were defined as small scale, 60,000 eggs per day. From small-, medium-, and large-scale producers, 69, 50, and 40% of samples were positive for quinolone residues, respectively. A greater number of samples were positive (61%) in floor-laying hen producers compared with those using cages (40%). In the Jamao municipality, 67% of the samples were positive compared with Moca and Cayetano Germosén, where 56 and 25% of samples were positive, respectively. Sampling time had an effect on percent positives: samples collected in July, August, and September were 71, 19, and 63% positive, respectively. Overall, 51% of the samples obtained from eggs produced in the province of Espaíllat were positive for quinolone residues at levels higher than the maximum limits for edible tissue established by the regulatory agencies, including the European Union and U.S. Department of Agriculture. The results obtained from this research confirmed the presence of quinolone residue in eggs, which may present a health risk to some consumers.

  10. Looking for the new preparations for antibacterial therapy III. New antimicrobial agents from the quinolones group in clinical trials.

    Science.gov (United States)

    Karpiuk, Izabela; Tyski, Stefan

    2013-01-01

    There is an essential need for searching for the new compounds effective in the treatment of infections caused by multidrug-resistant bacteria. This paper is the third part of a series associated with the exploration of new antibacterial agents and it discusses the compounds belonging to the group of quinolones and substances possessing a hybrid structure composed of the quinolone molecule and other compounds. Eleven new substances at the stage of clinical trials are presented. Three of them belong to the group of non-fluorinated quinolone (nemonoxacin, ozenoxacin and KRP-AM 1977X), while six are the quinolones containing fluorine atom at 6 position of the carbon atom in the quinoline ring (zabofloxacin, finafloxacin, delafloxacin, JNJ-Q2, WCK771 and KPI-10). The remaining two compounds possess a hybrid construction composed of the quinolone structure and other molecules (cadazolid and CBR-2092). There is a chance in the near future, that the presented compounds can extend the range of existing antibacterial drugs and provide an alternative to currently available medicinal products.

  11. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates.

    Science.gov (United States)

    García-León, G; Ruiz de Alegría Puig, C; García de la Fuente, C; Martínez-Martínez, L; Martínez, J L; Sánchez, M B

    2015-05-01

    Stenotrophomonas maltophilia is the only known bacterium in which quinolone-resistant isolates do not present mutations in the genes encoding bacterial topoisomerases. The expression of the intrinsic quinolone resistance elements smeDEF, smeVWX and Smqnr was analysed in 31 clinical S. maltophilia isolates presenting a minimum inhibitory concentration (MIC) range to ciprofloxacin between 0.5 and > 32 μg/mL; 11 (35.5%) overexpressed smeDEF, 2 (6.5%) presenting the highest quinolone MICs overexpressed smeVWX and 1 (3.2%) overexpressed Smqnr. Both strains overexpressing smeVWX presented changes at the Gly266 position of SmeRv, the repressor of smeVWX. Changes at the same position were previously observed in in vitro selected S. maltophilia quinolone-resistant mutants, indicating this amino acid is highly relevant for the activity of SmeRv in repressing smeVWX expression. For the first time SmeVWX overexpression is associated with quinolone resistance of S. maltophilia clinical isolates.

  12. Using SAR and QSAR analysis to model the activity and structure of the quinolone-DNA complex.

    Science.gov (United States)

    Llorente, B; Leclerc, F; Cedergren, R

    1996-01-01

    A set of 78 quinolone derivatives were used in a structure-activity study to identify structural features correlating with antibacterial activity. Distinct combinations of functional properties were identified for Gram-negative and Gram-positive bacteria. 3-D Quantitative structure-activity relationship (QSAR) studies identified specific hydrophobic, topologic and electronic properties of the molecules for both in vitro and in vivo activities. From these results, a three-dimensional model of a DNA-quinolone complex was built using molecular modeling techniques. It was based on the intercalation of quinolone into the double helix of DNA. We conclude that the intercalation model is consistent with most available data on the structure of the quinolone complex. This predicted structure is stabilized by the binding of magnesium ion with the sp2 oxygens present in quinolone, a phosphate and a purine base of the DNA. Substituents R1 and R7 are predicted to make hydrophobic interactions in the major and minor groove of DNA, respectively. R7 could also form hydrogen bonds with amino groups of guanines and the aspartic acid residue at position 87 in DNA gyrase subunit A.

  13. Mild and efficient Winterfeldt oxidation of 1,2,3,4-tetrahydro-γ-carbolines for the synthesis of dihydropyrrolo[3,2-b]-quinolones and pyrrolo[3,2-b]quinolones.

    Science.gov (United States)

    Sheng, Rong; Zhu, Jiangwei; Hu, Yongzhou

    2012-01-30

    The Winterfeldt oxidation (NaOH, DMF, air, rt) of substituted 1,2,3,4-tetrahydro-γ-carbolines has been developed, which provides a convenient and efficient method for the synthesis of the corresponding dihydropyrrolo[3,2-b]quinolones in moderate to excellent yields (38-94%). The generality and substrate scope of this reaction are explored and a possible mechanism is proposed. The results imply that electron-withdrawing groups on N2 of tetrahydro-γ-carbolines and N5-H are necessary. The synthesis of 5 or 7-substituted pyrrolo[3,2-b]quinolones in near quantitative yields was also achieved through deprotection and aromatization of N1-Boc-dihydropyrrolo[3,2-b]quinolones.

  14. Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones.

    Science.gov (United States)

    Harris, A S; Elhassan, H A; Flook, E P

    2016-01-01

    This systematic review aimed to establish that quinolones are as effective as aminoglycosides when used to treat chronic suppurative otitis media. The review included good quality, randomised, controlled trials on human subjects, published in English, that compared topical aminoglycosides with topical quinolones for the treatment of chronic suppurative otitis media. Nine trials met the criteria. Two studies showed a higher clinical cure rate in the quinolone group (93 per cent vs 71 per cent, p = 0.04, and 76 per cent vs 52 per cent, p = 0.009). Four studies showed no statistically significant difference in clinical outcome. A significant difference in microbiological clearance in favour of quinolones was shown in two studies (88 per cent vs 30 per cent, p otitis media and when used as prophylaxis post-myringotomy. Topical quinolones should be considered a first-line treatment for these patients.

  15. USE OF QUINOLONES IN BULL SEMEN EXTENDERS TO REDUCE SPERM DEOXYRIBONUCLEIC ACID DAMAGE

    Directory of Open Access Journals (Sweden)

    Clara Gonzalez-Marin

    2012-01-01

    Full Text Available Cryopreserved sperm samples from Holstein bulls (n = 20 were examined for bacterial presence and Sperm DNA Fragmentation (SDF dynamics. SDF was assessed after thawing (T0 and at 4, 24 and 48 h of incubation (37°C and the rate of SDF (r-SDF, as an estimator of the DNA degradation over time, was calculated. Two groups of bulls were identified based on the presence or absence of bacteria: One group (n = 10 had a readily detectable bacterial presence, while the other group (n = 10 had an undetectable bacterial presence. Differences in the SDF at T0 were not observed between these two groups. However, statistically different results were found after 24 h of incubation at 37°C (Kaplan-Meier estimator; Log-Rank Matel-Cox, p-1 of ciprofloxacin at T0. Differences in the r-SDF (p>0.05 were not detected between the control and the quinolone treated sample for those samples without bacteria. However, differences (p<0.000 in SDF were observed for quinolone treated samples that previously presented bacteria. Incubation of sealed straws showed that bacterial contamination occurred prior to cryopreservation. These results call attention to three points: (1 sperm samples were in contact with bacteria before cryopreservation; (2 the r-SDF can be directly correlated with bacterial presence but this effect remains cryptic after thawing and (3 the r-SDF can be reduced by treating the semen samples with an adequate antibiotic such as quinolones, a finding not previously reported in the scientific literature, but important in terms of reproduction.

  16. Characterization of quinolone resistance mechanisms in Enterobacteriaceae recovered from diseased companion animals in Europe.

    Science.gov (United States)

    Guillard, T; de Jong, A; Limelette, A; Lebreil, A L; Madoux, J; de Champs, C

    2016-10-15

    ComPath is a European monitoring programme dedicated to the collection of bacterial pathogens from diseased dogs and cats to determine their antibiotic susceptibility. The objective was to characterize genetic determinants associated with quinolone resistance among 69 enrofloxacin non-wild type strains selected among 604 non-duplicate Enterobacteriaceae isolates collected in 10EU countries from 2008 to 2010: quinolone resistance determining region (QRDR) and plasmid-mediated quinolone resistance (PMQR). Among them, 17% (12/69) carried at least one PMQR (9/12 qnrB, qnrS or qnrD and 4/12 aac(6')-Ib-cr) and 83% (57/69) no PMQR. All the Klebsiella pneumoniae isolates chromosomally carried oqxAB . No qepA genes were detected. Eight strains did not carry any mutations in QRDR (4 PMQR-positive and 4 PMQR-negative strains). From the 12 PMQR-positive strains, 4 showed enrofloxacin MICs≤2μg/mL, and 8 MICs≥8μg/mL (resistant). These latter strains carried 1-5 mutations in QRDR, including a ParE I529L mutation. qnrD was found in 2 Proteus mirabilis and the plasmids were similar to pDIJ09-518a previously described. For the 57 non-PMQR strains, 29 strains showed MICs≤2μg/mL (4 with no QRDR mutations, 21 with 1 mutation in GyrA, 4 with 2 mutations in GyrA) and 28 showed enrofloxacin MICs≥8μg/mL carrying at least 2 mutations in QRDR, including a ParE I529L mutation for 2 Escherichia coli strains with a total of 5 QRDR mutations. No GyrB mutations were found. qnr was the major PMQR and qnrD was only detected in Proteus spp. Twelve strains carried at least 4 mutations.

  17. Genetic analysis of a pediatric clinical isolate of Moraxella catarrhalis with resistance to macrolides and quinolones.

    Science.gov (United States)

    Iwata, Satoshi; Sato, Yoshitake; Toyonaga, Yoshikiyo; Hanaki, Hideaki; Sunakawa, Keisuke

    2015-04-01

    During the surveillance conducted in 2012 by the Drug-resistant Pathogen Surveillance Group in Pediatric Infectious Disease, we isolated a strain of Moraxella catarrhalis that demonstrated resistance to both macrolides and quinolones from a male pediatric patient aged 1.5 years who had developed acute bronchitis. Then we evaluated the susceptibility of this strain to different types of antibacterial agents and conducted a genetic analysis. The results of the susceptibility evaluation showed that the MIC values of azithromycin, clarithromycin, and rokitamycin were >64 μg/mL, >64 μg/mL, and 4 μg/mL, respectively; clearly demonstrating resistance to macrolides. The MIC values of the quinolones levofloxacin, tosufloxacin, and garenoxacin were 4 μg/mL, 2 μg/mL, and 1 μg/mL, respectively; indicating decreased susceptibility. The genetic analysis of this strain revealed one mutation in 23s rRNA with a replacement of adenine by thymine at nucleotide position 2330 (A2330T) and another mutation in gyrB at nucleotide position 1481 by replacement of adenine with guanine (A1481G) that caused a substitution of the 494 th asparagine acid by glycine, as being associated with the observed resistance to macrolides and quinolones, respectively. Similar to drug-resistant bacteria Streptococcus pneumoniae and Haemophilus influenzae, the prevalence of which has recently increased, the treatment of drug-resistant M. catarrhalis infections is considered difficult due to the development of resistance to different types of antibacterial agents. It is vital to maintain an unwavering focus on the trend toward an increasing number of drug-resistant M. catarrhalis strains and ensure the proper use of each antibacterial agent.

  18. Molecular epidemiological survey on quinolone resistance genotype and phenotype of Escherichia coli in septicemic broilers in Hebei, China.

    Science.gov (United States)

    Xie, Rong; Huo, Shuying; Li, Yurong; Chen, Ligong; Zhang, Feiyan; Wu, Xianjun

    2014-02-01

    In this study, the quinolone-resistant determining region (QRDR) of gyrA of Escherichia coli and plasmid-mediated quinolone resistance (PMQR) genes, qnr(qnrA, qnrB, and qnrS), and aac(6 ')-Ib-cr were detected, sequenced, and analyzed. In addition, antimicrobial susceptibility tests (using the Kirby-Bauer disc diffusion method) were performed for all 111 E. coli isolates from septicemic broilers in Hebei, China. The results show that the resistance rates were as follows: ofloxacin 99.10%, ciprofloxacin 93.69%, levofloxacin 91.89%, norfloxacin 90.09%, and gatifloxacin 76.58%. Of the PMQR genes examined, aac(6 ')-Ib-cr (36.04%) was the most frequently identified gene in all isolates, followed by qnrS (8.11%), qnrB (0.90%), and qnrA (0%). Of the QRDR examined in the 40 phenotypic quinolone-resistant isolates, compared with the gyrA(+) gene of E. coli K-12, 4 amino acid exchanges were found, namely Ser-83→Asp, Asp-87→Asn, Asp-87→Tyr, and Asp-87→Ala, and all 40 isolates had 1 or 2 exchanges in QRDR. It was concluded that quinolone-resistance in E. coli remains a serious problem in Hebei, China. Therefore, there is considerable local surveillance of quinolone resistance. Plasmid-mediated quinolone resistance of the qnr type remains rare in Hebei, China, and mutation in QRDR may be the main problem.

  19. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates......, and one from 1999 were resistant to nalidixic acid. All the nalidixic acid-resistant isolates had reduced susceptibility to fluoroquinolones. Sequence analysis of the gyrA gene in 37 nalidixic-resistant isolates identified two different base substitutions at codon serine-83 and two at aspartate-87...

  20. Comparison of Antimicrobial Properties of Nano Quinolone with its Microscale Effects

    Science.gov (United States)

    Behbahani, G. Rezaie; Sadr, M. Hossaini; Nabipour, H.; Behbahani, H. Rezaei; Vahedpour, M.; Barzegar, L.

    2013-06-01

    Nano nalidixic acid was prepared by ultrasonic method in carbon tetrachloride. Nano nalidixic acid (quinolone antibiotic) was characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and scanning electron microscope (SEM). The antibacterial activities of nano nalidixic acid were tested against microorganisms and compared with the microscale drug. The results show that nano nalidixic acid has good inhibitory properties against two Gram-positive species, Staphylococcus aureus and Bacillus subtilis. Nano nalidixic acid also showed good antifungal activity against Candida albicans. Nano nalidixic acid can be injected into the human body as a decontaminating agent to prevent the growth of harmful microorganisms more effectively than the micro-sized drug.

  1. QSAR study and VolSurf characterization of anti-HIV quinolone library

    Science.gov (United States)

    Filipponi, Enrica; Cruciani, Gabriele; Tabarrini, Oriana; Cecchetti, Violetta; Fravolini, Arnaldo

    2001-03-01

    Antiviral quinolones are promising compounds in the search for new therapeutically effective agents for the treatment of AIDS. To rationalize the SAR for this new interesting class of anti-HIV derivatives, we performed a 3D-QSAR study on a library of 101 6-fluoro and 6-desfluoroquinolones, taken either from the literature or synthesized by us. The chemometric procedure involved a fully semiempirical minimization of the molecular structures by the AMSOL program, which takes into account the solvatation effect, and their 3D characterization by the VolSurf/GRID program. The QSAR analysis, based on PCA and PLS methods, shows the key structural features responsible for the antiviral activity.

  2. Lanthanum triflate triggered synthesis of tetrahydroquinazolinone derivatives of N-allyl quinolone and their biological assessment

    Directory of Open Access Journals (Sweden)

    Jardosh Hardik H.

    2012-01-01

    Full Text Available A series of 24 derivatives of tetrahydroquinazolinone has been synthesized by one-pot cyclocondensation reaction of N-allyl quinolones, cyclic β-diketones and (thiourea/N-phenylthiourea in presence of lanthanum triflate catalyst. This methodology allowed us to achieve the products in excellent yield by stirring at room temperature. All the synthesized compounds were investigated against a representative panel of pathogenic strains using broth microdilution MIC (minimum inhibitory concentration method for their in vitro antimicrobial activity. Amongst these sets of heterocyclic compounds 5h, 6b, 6h, 5f, 5l, 5n and 6g found to have admirable activity.

  3. Synthesis of Some 4-Quinolones and Related Structures for Evaluation as Potential Antimalarial Agents

    Science.gov (United States)

    1974-11-30

    evaluation new com- pounds related to either endochin (2-methyl-3-heptyl-7-.nethoxy-4(lH)- quino - lone) or the 3-carbomethoxy-4(lH)-quinolones that had shown...of aliphatic aldehydes with 2-methyl-4(lH)- quino - lones to give the 3(1-alkenyl) derivatives proved its generality, since it pro- ceeds when both...yields. Tnis facile reaction indicates, once more, the activated nature of the 3 position in the ’(lDOi- quino - lone ring system. 0 0 + CH20 ) CCHYN(CH3

  4. [Residues of tetracycline and quinolones in wild fish living around a salmon aquaculture center in Chile].

    Science.gov (United States)

    Fortt Z, Antonia; Cabello C, Felipe; Buschmann R, Alejandro

    2007-02-01

    The presence of residues of tetracycline, quinolones and antiparasitic drugs was investigated in wild fish captured around salmon aquaculture pens in Cochamó, Region X, Chile. Residues of both antibiotics were found in the meta [corrected] of two species of wild fish that are consumed by humans, robalo (Elginops maclovinus) and cabrilla (Sebastes capensis) [corrected] These findings suggest that the antibiotic usage in salmon aquaculture in Chile has nvironmental implications that may affect human and animal health. More studies are needed in Chile to determine the relevance of these findings for human and animal health and the environment to regulate this use of antibiotics.

  5. Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors

    DEFF Research Database (Denmark)

    Lager, Erik; Nilsson, Jakob; Nielsen, Elsebet Østergaard

    2008-01-01

    The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABA(A) receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones......). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an alpha...

  6. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... resistance in Campylobacter and track resistance trends in human clinical isolates in relation to use of these agents in food animals. Susceptibility data suggest that erythromycin and other macrolides should remain the drugs of choice in most regions, with systematic surveillance and central measures...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  7. Functions of a GyrBA fusion protein and its interaction with QnrB and quinolones.

    Science.gov (United States)

    Chen, Chunhui; Villet, Regis; Jacoby, George A; Hooper, David C

    2015-11-01

    In order to study the interactions between Escherichia coli DNA gyrase and the gyrase interacting protein QnrB in vivo, we constructed a gyrB-gyrA fusion and validated its ability to correct the temperature-sensitive growth of gyrA and gyrB mutants. Like wild-type gyrA, the gyrB-gyrA fusion complemented a quinolone-resistant gyrA mutant to increase susceptibility. It functioned as an active type II topoisomerase, catalyzed negative supercoiling of DNA, was inhibited by quinolone, and was protected by QnrB.

  8. Quantitative determination of quinolones residues in milk by HPLC-FLD

    Directory of Open Access Journals (Sweden)

    Marilena Gili

    2012-10-01

    Full Text Available Veterinary drugs have become an integral part of the livestock production and play an important role in maintenance of animal welfare. The use of veterinary medicines may be cause of the presence of drug residues in animal food products if appropriate withdrawal periods are not respected or if contaminated feeds are used. This work presents the development of an HPLC-FLD method for the quantitative de-tection of eight quinolones – norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, difloxacin, oxolinic acid, nalidixic acid, flumequine– in bovine milk. After deproteination and extraction with a metaphos-phoric acid 1% w/v / methanol / acetonitrile (60/20/20 v/v/v solution, the sample is partially evaporated and cleaned up on a reversed phase SPE cartridge.The extract is analyzed using an high performance liquid chromatograph with fluorescence detector. Mean recovery ranged between 65% - 88%. All the an-alytes can be identified and quantified in the concentration range 15 - 60 μg/Kg for danofloxacin and 25 - 150 μg/Kg for the other quinolones.

  9. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Science.gov (United States)

    Kumar, Manoj; Dahiya, Sushila; Sharma, Priyanka; Sharma, Sujata; Singh, Tej P; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  10. Adsorption of quinolone, tetracycline, and penicillin antibiotics from aqueous solution using activated carbons: Review.

    Science.gov (United States)

    Ahmed, Muthanna J

    2017-03-01

    Antibiotics, an important type of pharmaceutical pollutant, have attracted many researchers to the study of their removal from aqueous solutions. Activated carbon (AC) has been widely used as highly effective adsorbent for antibiotics because of its large specific surface area, high porosity, and favorable pore size distribution. In this article, the adsorption performance of AC towards three major types of antibiotics such as tetracyclines, quinolones, and penicillins were reviewed. According to collected data, maximum adsorption capacities of 1340.8, 638.6, and 570.4mg/g were reported for tetracyclines, quinolones, and penicillins, respectively. The values of 1/n for Freundlich isotherm were less than unity, suggesting that the adsorption was nonlinear and favorable. Adsorption kinetics followed closely the pseudo-second-order model and analysis using the Weber-Morris model revealed that the intra-particle diffusion was not the only rate controlling step. AC adsorption demonstrated superior performance for all selected drugs, thus being efficient technology for treatment of these pollutants.

  11. [Effect of pazufloxacin mesilate, a new quinolone antibacterial agent, for intravenous use on QT interval].

    Science.gov (United States)

    Fukuda, Hitoshi; Morita, Yukie; Shiotani, Norio; Mizuo, Midori; Komae, Norihisa

    2004-08-01

    The potential for QT interval prolongation of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, was investigated by in vitro and in vivo electrophysiology studies. Following results were obtained. In vitro electrophysiology study using guinea pig papillary muscles: PZFX mesilate (30-300 microM) had no effects on resting membrane potential (RMP), action potential amplitude (APA) and action potential duration (APD). Reference quinolones, sparfloxacin (3-30 microM) and moxifloxacin (10-100 microM), had no effects on RMP and APA, but significantly prolonged APD at more than 3 and 10 microM, respectively, while ciprofloxacin (10-100 microM) had no effect on each parameter. In vivo electrophysiology study using anesthetized dogs: PZFX mesilate had no effects on electrocardiograph parameter (PR interval, QRS interval, QT interval and QTc) after intravenous administration of 3-30 mg/kg. These results suggest that PZFX mesilate has low potential for QT interval prolongation.

  12. Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens

    Directory of Open Access Journals (Sweden)

    Orhiosefe Omigie

    2009-08-01

    Full Text Available Orhiosefe Omigie, Lawrence Okoror, Patience Umolu, Gladys IkuuhDepartment of Microbiology, Ambrose Alli University, Ekpoma, NigeriaAbstract: A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%, Escherichia coli (26.3%, and Proteus spp. (17.1%. Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase, Staphylococcus aureus (9.8%, and E. coli (9.7%. The highest potency was exhibited by ciprofloxacin (91.2%, levofloxacin (89.2%, and moxifloxacin (85.1%, while there were high rates of resistance to nalidixic acid (51.7% and pefloxacin (29.0%. Coliforms, particularly E. coli (>45%, remain the most prevalent causative agents of UTI while females within the age range of 20–50 years were most vulnerable to UTI.Keywords: UTI, microorganisms, antibiotics, resistance

  13. Bacterial plasmid-mediated quinolone resistance genes in aquatic environments in China

    Science.gov (United States)

    Yan, Lei; Liu, Dan; Wang, Xin-Hua; Wang, Yunkun; Zhang, Bo; Wang, Mingyu; Xu, Hai

    2017-01-01

    Emerging antimicrobial resistance is a major threat to human’s health in the 21st century. Understanding and combating this issue requires a full and unbiased assessment of the current status on the prevalence of antimicrobial resistance genes and their correlation with each other and bacterial groups. In aquatic environments that are known reservoirs for antimicrobial resistance genes, we were able to reach this goal on plasmid-mediated quinolone resistance (PMQR) genes that lead to resistance to quinolones and possibly also to the co-emergence of resistance to β-lactams. Novel findings were made that qepA and aac-(6′)-Ib genes that were previously regarded as similarly abundant with qnr genes are now dominant among PMQR genes in aquatic environments. Further statistical analysis suggested that the correlation between PMQR and β-lactam resistance genes in the environment is still weak, that the correlations between antimicrobial resistance genes could be weakened by sufficient wastewater treatment, and that the prevalence of PMQR has been implicated in environmental, pathogenic, predatory, anaerobic, and more importantly, human symbiotic bacteria. This work provides a comprehensive analysis of PMQR genes in aquatic environments in Jinan, China, and provides information with which combat with the antimicrobial resistance problem may be fought. PMID:28094345

  14. Analysis of quinolones by voltage-assisted liquid-phase microextraction combined with LC-MS.

    Science.gov (United States)

    Wang, Mi-Hung; Wang, Shu-Ping

    2012-03-01

    The method of liquid-phase microextraction assisted with voltage was developed and applied on determination of quinolones in water sample in this study. Both of the reproducibility and extraction time were improved with the aid of applying voltage. Four analytes in neutral state such as cinoxacin, oxolinic acid, nalidixic acid, and flumequine were extracted from a sample solution at pH 2.0, through a polypropylene hollow fiber which was immobilized with 2-octanone, and then into a 25 μL of the acceptor phase of 40 mM borate buffer at pH 10.0 by applying voltage of 100 V. Subsequently, the acceptor solution was directly subjected to analysis by LC-MS. The performance of the method for four quinolones was also evaluated. Linearity was obtained in the range of 1.0-25.0 ng/mL with R(2) > 0.996. Limits of detection were below 0.6 ng/mL, and recoveries of water sample were ranged from 90.8 to 109.6%.

  15. Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones.

    Science.gov (United States)

    Miliutina, Mariia; Ejaz, Syeda Abida; Khan, Shafi Ullah; Iaroshenko, Viktor O; Villinger, Alexander; Iqbal, Jamshed; Langer, Peter

    2017-01-27

    New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 μM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 μM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes.

  16. Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A

    Directory of Open Access Journals (Sweden)

    Sylvie eBaucheron

    2014-01-01

    Full Text Available Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e. in gyrA, gyrB, or parC correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications.

  17. Structure Based In Silico Analysis of Quinolone Resistance in Clinical Isolates of Salmonella Typhi from India

    Science.gov (United States)

    Sharma, Priyanka; Sharma, Sujata; Singh, Tej P.; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase. PMID:25962113

  18. Multiresidue determination of quinolone antibacterials in eggs of laying hens by liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Hassouan, M K; Ballesteros, O; Taoufiki, J; Vílchez, J L; Cabrera-Aguilera, M; Navalón, A

    2007-06-01

    An analytical method for the simultaneous determination of seven quinolones (ciprofloxacin, enrofloxacin, danofloxacin, difloxacin, flumequine, oxolinic acid and sarafloxacin) in egg samples of laying hens was developed. Their use is totally prohibited in animals from which eggs are produced for human consumption. Protein precipitation was achieved by addition of acetonitrile and ammonia, removal of acetonitrile with dichloromethane, the quinolones remaining in the basic aqueous extract. The aqueous extract was analysed by liquid chromatography with fluorescence detection (LC-FD). The mobile phase was composed of acetonitrile and 10 mM citrate buffer solution of pH 4.5, with an initial composition of acetonitrile-water (12:88, v/v) and using linear gradient elution. Norfloxacin was used as an internal standard. The limits of detection found were 4-12 ng g(-1). These values were lower than the maximum residue limits (MRLs) established by the European Union for these compounds in different tissues of eggs-producing animals.

  19. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    Full Text Available Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  20. Genotypic characterization of quinolone resistant-Escherichia coli isolates from retail food in Morocco.

    Science.gov (United States)

    Nayme, Kaotar; Barguigua, Abouddihaj; Bouchrif, Brahim; Karraouan, Bouchra; El Otmani, Fatima; Elmdaghri, Naima; Zerouali, Khalid; Timinouni, Mohammed

    2017-02-01

    This study was conducted to assess the retail food as a possible vehicle for antimicrobial resistant, particularly quinolones resistant and pathogenic Escherichia coli. We determined the prevalence and characteristics of nalidixic acid (Nal) resistant E. coli isolates from diverse retail food samples. In all, 70 (28%) of 250 E. coli isolates studied were Nal-resistant E. coli and 91% of these were multi-drug resistant. Plasmid mediated quinolone resistance genes were identified in 32 isolates, including aac(6')-Ib-cr (n = 16), qnrS1 (n = 11) and qnrB19 (n = 7). Mutations in gyr A and par C genes were detected among 80% of the isolates, and the isolates showed substitution Ser83-Leu and Asp87-Asn in gyrA and Ser80-Ile in parC. In addition, three different gene cassettes were identified (aadA1, aadA7, aac(3)-Id) in 18%. Virulence-associated genes stx1, eae, sfa, hlyA and stx2 were found in six (8%), three (4%), two (3%), three (4%) and three (4%) isolates, respectively. E. coli isolates of phylogenetic group A were dominant (64%, 45/70). Pulsed field gel electrophoresis revealed none epidemiological relationship between these isolates. The results of this work report the higher frequency of Nal-resistant E. coli isolates from Moroccan retail food samples including MDR and pathogenic isolates.

  1. Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

    Directory of Open Access Journals (Sweden)

    Mingliang Chen

    2015-06-01

    Full Text Available Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84% in 1965-1973 to serogroup A CC1 (58% in 1974-1985, then to serogroup C or B CC4821 (62% in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37 in 2005-2013 (p < 0.001. Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31 were assigned to either CC4821 (n = 20 or CC5 (n = 7. The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31 of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31 of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15 among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available

  2. Quinolone- and ß-lactam-resistance in Escherichia coli from Danish and Italian broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    Frederiksberg C, Denmark 2Dipartimento di Sanità Pubblica Veterinaria e Patologia Animale, Facoltà di Medicina Veterinaria, Università di Bologna, 40064 Ozzano Emilia (BO), Italy   The prevalence of quinolone- and ß-lactam-resistant E. coli was investigated among broiler flocks in Denmark and Italy. In Denmark...

  3. Studies on the antagonistic action between chloramphenicol and quinolones with presence of bovine serum albumin by fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Liu Baosheng, E-mail: lbs@hbu.edu.c [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China); Zhao Fengli; Xue Chunli; Wang Jing; Lu Yunkai [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China)

    2010-05-15

    Chloramphenicol (CHL) and quinolone drugs like ofloxacin (OFLX), lomefloxacin (LMX) and ciprofloxacin (CPFX) can all quench the fluorescence of bovine serum albumin (BSA) in the aqueous solution of pH=7.40. This quenching effect becomes more significant when CHL and quinolone drugs coexist. Based on this, further studies on the interactions between CHL and quinolone drugs using fluorescence spectrum are established. The results showed that the interaction between the drugs would increase the binding constant and binding stability of the drug and protein, thus reducing the amount of drugs transported to their targets. Therefore, free drug concentration at targets would decrease, reducing the efficacy of the drugs. It indicated that there exists antagonistic action between drugs. The results also showed that the quenching mechanism of BSA by the drugs is a static procedure. The number of binding sites is 1 in various systems. Due to the existence of the antagonistic action between drugs, the binding distance r is reduced. Studies utilizing synchronous spectra showed that the antagonistic action between the drugs would affect the conformation of BSA, making protein molecules extend and hydrophobic decrease. The order of antagonistic action between CHL and quinolone drugs is: CPFX>OFLX>LMX with presence of BSA.

  4. Analysis of the gyrA gene of clinical Yersinia ruckeri isolates with reduced susceptibility to quinolones.

    Science.gov (United States)

    Gibello, Alicia; Porrero, M Concepción; Blanco, M Mar; Vela, Ana I; Liébana, Pilar; Moreno, Miguel A; Fernández-Garayzábal, José F; Domínguez, Lucas

    2004-01-01

    Antimicrobial susceptibility of seven clinical strains of Yersinia ruckeri representative of those isolated between 1994 and 2002 from a fish farm with endemic enteric redmouth disease was studied. All isolates displayed indistinguishable pulsed-field gel electrophoresis restriction patterns, indicating that they represented a single strain. However, considering both inhibition zone diameters (IZD) and MICs, the isolates recovered in 2001-2002 formed a separate cluster with lower levels of susceptibility to all the quinolones tested, especially nalidixic acid (NA) and oxolinic acid (OA), compared with the isolates recovered between 1994 and 1998. Analysis of the PCR product of the quinolone resistance-determining region of the gyrA gene from clinical isolates of Y. ruckeri with reduced susceptibility to OA and NA revealed a single amino acid substitution, Ser-83 to Arg-83 (Escherichia coli numbering). Identical substitution was observed in induced OA-resistant mutant strains, which displayed IZD and MICs of quinolones similar to those of the clinical isolates of Y. ruckeri with reduced susceptibility to these antimicrobial agents. These data indicate in that for Y. ruckeri, the substitution of Ser by Arg at position 83 of the gyrA gene is associated with reduced susceptibility to quinolones.

  5. Synthesis and in vitro antibacterial activities of 7-(4-alkoxyimino-3-hydroxypiperidin-1-y1)quinolone derivatives

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of novel 7-(4-alkoxyimino-3-hydroxypiperidin-1-yl)quinolone derivatives were designed,synthesized and evaluated for in vitro antibacterial activities.Compounds 8f,8g,8i and 8j with the potencies similar to or better than those of levofloxacin and IMB against Staphylococcus aureus and Staphylococcus epidermidis,worth further investigation.

  6. Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows.

    Science.gov (United States)

    Duse, Anna; Waller, Karin Persson; Emanuelson, Ulf; Unnerstad, Helle Ericsson; Persson, Ylva; Bengtsson, Björn

    2015-09-01

    Quinolone resistance may emerge in gut bacteria (e.g., in Escherichia coli) of animals. Such bacteria could cause infections in the animal itself or be transmitted to humans via the food chain. Quinolone resistance is also observed in fecal E. coli of healthy dairy cattle, but the prevalence varies between farms, not solely as a result of varying degree of fluoroquinolone exposure. The objective of this study was to identify risk factors for the fecal shedding of quinolone-resistant E. coli (QREC) from dairy calves and postpartum cows. Rectal swabs from 15 preweaned calves and 5 postpartum cows per farm were collected on 23 Swedish dairy farms to determine the prevalence of QREC. Risk factors for the shedding of QREC were investigated using multivariable statistical models. Quinolone-resistant E. coli were found on all but one farm. Factors associated with QREC shedding by calves were being younger than 18 d, being fed milk from cows treated with antimicrobials, recent use of fluoroquinolones in the herd, carriage of QREC by postpartum cows, and using the calving area never or rarely as a sick pen compared with often. Factors associated with QREC shedding by cows were calving in group pens or freestalls compared with single pens or tiestalls, purchasing cattle, sharing animal transports with other farmers, and poor farm hygiene. Proper biosecurity and improved hygiene, as well as minimizing fluoroquinolone exposure and waste milk feeding, may be important factors to reduce the burden of QREC on dairy farms.

  7. Progress in research on quinolone antibacterials%喹诺酮类抗菌药物研究新进展

    Institute of Scientific and Technical Information of China (English)

    蒋晓磊; 崔玉彬; 曹胜华

    2011-01-01

    This article has reviewed progress in research on quinolone antibacterials in recent years,which consisted of newly launched products, agents in clinical trials and future development of this kind of drugs. It focused on some clinical promising candidates. Among these drugs, delafloxacin would be the most potential candidate.Moreover it introduced new fields of the future development, including modifying side chain, quinolone-like compounds, antibacterial quinolone hybrids and anti-TB quinolone-drug conjugates.%本文简述了喹诺酮类药物近几年的研究进展,分为上市药物、临床试验药物和未来发展趋势三部分,对目前处于临床研究阶段的药物做了重点讲述,其中delafloxacin是最有希望的喹诺酮类候选药物,同时介绍了喹诺酮类抗菌药物的未来发展方向,即侧链修饰、喹诺酮类似物、喹诺酮杂合物和TB药物与喹诺酮扼合物.

  8. Rational use of quinolones antibiotics%合理应用喹诺酮类抗菌药物

    Institute of Scientific and Technical Information of China (English)

    宋惠珠

    2011-01-01

    目的 了解喹诺酮类抗菌药物的作用机制,不良反应及使用时的注意事项. 方法 对喹诺酮类抗菌药物在临床使用中的注意事项及所涉及的不良反应进行汇总. 结果 随着临床使用喹诺酮类抗菌药物的增加,药物的不良反应也随着上升,其不良反应发生率<2.0%,肾损害的发生率为0.9%~4.3%. 结论 在广泛应用喹诺酮类抗菌药物的同时,要更多地关注其安全性.%OBJECTIVE To understand the mechanism of quinolones, adverse reactions and precautions when using.METHODS The precautions of quinolones in clinical use and the adverse reactions involved were aggregated.RESULTS With the increased clinical use of quinolones, the incidence of adverse drug reactions was increased more than <2.0%. CONCLUSION In the widely use of quinolones antibiotics, their safety should be more concerned about.

  9. Distribution and risk assessment of quinolone antibiotics in the soils from organic vegetable farms of a subtropical city, Southern China.

    Science.gov (United States)

    Wu, Xiao-Lian; Xiang, Lei; Yan, Qing-Yun; Jiang, Yuan-Neng; Li, Yan-Wen; Huang, Xian-Pei; Li, Hui; Cai, Quan-Ying; Mo, Ce-Hui

    2014-07-15

    Organic fertilizer or manure containing antibiotics has been widely used in organic farms, but the distribution and potential impacts of antibiotics to the local environment are not well understood. In this study, four quinolone antibiotics in soil samples (n=69) from five organic vegetable farms in a subtropical city, Southern China, were analyzed using high performance liquid chromatography-tandem mass spectrometry. Our results indicated that quinolone compounds were ubiquitous in soil samples (detection frequency>97% for all compounds), and their concentrations ranged from not detectable to 42.0 μg/kg. Among the targets, enrofloxacin (ENR) was the dominant compound, followed by ciprofloxacin (CIP) and norfloxacin (NOR). The average total concentrations of four compounds in the soils were affected by vegetable types and species cultivated, decreasing in the order of fruit>rhizome>leaf vegetables. Moreover, the average concentrations of quinolone compounds (except ENR) in open-field soils were higher than those in greenhouse soils. The concentrations of quinolone antibiotics in this study were lower than the ecotoxic effect trigger value (100 μg/kg) proposed by the Veterinary Medicine International Coordination commission. Risk assessment based on the calculated risk quotients indicated that NOR, CIP, and ENR posed mainly medium to low risks to bacteria.

  10. A Facile Solid Phase Synthesis of 2—Alkylthio—4(1H)—quinolones

    Institute of Scientific and Technical Information of China (English)

    TANG,Jing; WU,Ming-Guang; HUANG,Xian

    2003-01-01

    The resin-bound cyclic malonic acid ester 2 reacted with aryl isothiocyanate and alkyl halides to afford the key intermediate arylthioaminomethylene cyclic malonic ester resin 3.Subsequently,resin 3 proceeded thermal cyclizaiton giving the 2-alkylthio-4(1H)-quinolones in good yields and excellent purties.

  11. Quinolones control in milk and eggs samples by liquid chromatography using a surfactant-mediated mobile phase.

    Science.gov (United States)

    Rambla-Alegre, M; Collado-Sánchez, M A; Esteve-Romero, J; Carda-Broch, S

    2011-05-01

    Four quinolones (danofloxacin, difloxacin, flumequine and marbofloxacin) were determined in milk and egg samples by a simplified high-performance liquid chromatographic procedure using a micellar mobile phase. No extraction was needed to precipitate the proteins from the matrices since they were solubilised in micelles. The only pretreatment steps required were homogenisation, dilution and filtration before injecting the sample into the chromatographic system. An adequate resolution of the quinolones was achieved by a chemometrics approach where retention was modelled as a first step using the retention factors in only five mobile phases. Afterwards, an optimisation criterion was applied to consider the position and shape of the chromatographic peaks. Analytical separation involved a C18 reversed-phase column, a hybrid micellar mobile phase of 0.05 M sodium dodecyl sulphate, 10% (v/v) butanol and 0.5% (v/v) triethylamine buffered at pH 3 and fluorimetric detection. Quinolones were eluted in less than 15 min without the protein band or other endogenous compounds from the food matrices interfering. The calculated relevant validation parameters, e.g., decision limit (CC(α)), detection capability (CC(β)), repeatability, within-laboratory reproducibility, recoveries and robustness, were acceptable and complied with European Commission Decision 2002/657/EC. Finally, the proposed method was successfully employed in quantifying the four quinolones in spiked egg and milk samples.

  12. Fluorimetric study of the interaction between human serum albumin and quinolones-terbium complex and its application

    Science.gov (United States)

    Wang, Yusheng; Feng, Lin; Jiang, Chongqiu

    2005-10-01

    A highly sensitive spectrofluorimetric method is proposed for determination of human serum albumin (HSA) and some quinolone drugs. Using quinolones-terbium (Tb 3+) complex as a fluorescent probe, in the buffer solution of pH 7.8, HSA can remarkably enhance the fluorescence intensity of the quinolones-Tb 3+ complex at 545 nm and the enhanced fluorescence intensity of Tb 3+ ion is in proportion to the concentration of HSA and quinolone drugs. Optimum conditions for the determination of HSA were also investigated. The linear ranges and limits of detection are 8.0 × 10 -9 to 8.0 × 10 -8 mol L -1, 4.20 × 10 -9 mol L -1 (for HSA); 1.0 × 10 -6 to 4.0 × 10 -6 mol L -1, 1.87 × 10 -8 mol L -1 (for norfloxacin) and 1.0 × 10 -7 to 1.0 × 10 -6 mol L -1, 4.82 × 10 -8 mol L -1 (for enoxacine), respectively. This method is simple, practical and relatively free interference from coexisting substances, as well as much more sensitive than most of the existing assays.

  13. Development of an optical surface plasmon resonance biosensor assay for (fluoro) quinolones in egg, fish, and poultry meat

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Singh, G.; Benrejeb Godefroy, S.; Leivo, J.; Vehniainen, M.; Nielen, M.W.F.; Weigel, S.; Delahaut, P.

    2008-01-01

    The aim of this study was to develop an optical biosensor inhibition immunoassay, based on the surface plasmon resonance (SPR) principle, for use as a screening test for 13 (fluoro)quinolones, including flumequine, used as veterinary drugs in food-producing animals. For this, we immobilised various

  14. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in E

  15. Orally bioavailable 6-chloro-7-methoxy-4(1H)-quinolones efficacious against multiple stages of Plasmodium.

    Science.gov (United States)

    Cross, R Matthew; Flanigan, David L; Monastyrskyi, Andrii; LaCrue, Alexis N; Sáenz, Fabián E; Maignan, Jordany R; Mutka, Tina S; White, Karen L; Shackleford, David M; Bathurst, Ian; Fronczek, Frank R; Wojtas, Lukasz; Guida, Wayne C; Charman, Susan A; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

    2014-11-13

    The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.

  16. Quinolone resistance and ESBL/AmpC’s in commensal Escherichia coli in veal calves : prevalence and molecular characterization

    NARCIS (Netherlands)

    Hordijk, J.

    2013-01-01

    In this thesis the prevalence and molecular characteristics of resistance to (fluoro)quinolones and Extended Spectrum Cephalosporins (ESC) in veal calves were described using Escherichia coli as an indicator organism. Ciprofloxacin and nalidixic acid were used as indicator antimicrobials for quinolo

  17. Quinolone resistance and ESBL/AmpC’s in commensal Escherichia coli in veal calves : prevalence and molecular characterization

    NARCIS (Netherlands)

    Hordijk, J.

    2013-01-01

    In this thesis the prevalence and molecular characteristics of resistance to (fluoro)quinolones and Extended Spectrum Cephalosporins (ESC) in veal calves were described using Escherichia coli as an indicator organism. Ciprofloxacin and nalidixic acid were used as indicator antimicrobials for quinolo

  18. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in E

  19. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in

  20. Development of an optical surface plasmon resonance biosensor assay for (fluoro) quinolones in egg, fish, and poultry meat

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Singh, G.; Benrejeb Godefroy, S.; Leivo, J.; Vehniainen, M.; Nielen, M.W.F.; Weigel, S.; Delahaut, P.

    2008-01-01

    The aim of this study was to develop an optical biosensor inhibition immunoassay, based on the surface plasmon resonance (SPR) principle, for use as a screening test for 13 (fluoro)quinolones, including flumequine, used as veterinary drugs in food-producing animals. For this, we immobilised various

  1. Detection of mutations in mtrR gene in quinolone resistant strains of N.gonorrhoeae isolated from India

    Directory of Open Access Journals (Sweden)

    S V Kulkarni

    2015-01-01

    Full Text Available Background and Objectives: Emergence of multi-drug resistant Neisseria gonorrhoeae resulting from new genetic mutation is a serious threat in controlling gonorrhea. This study was undertaken to identify and characterise mutations in the mtrR genes in N.gonorrhoeae isolates resistant to six different antibiotics in the quinolone group. Materials and Methods: The Minimum inhibitory concentrations (MIC of five quinolones for 64 N.gonorrhoeae isolates isolated during Jan 2007-Jun 2009 were determined by E-test method. Mutations in MtrR loci were examined by deoxyribonucleic acid (DNA sequencing. Results: The proportion of N.gonorrhoeae strains resistant to anti-microbials was 98.4% for norfloxacin and ofloxacin, 96.8% for enoxacin and ciprofloxacin, 95.3% for lomefloxacin. Thirty-one (48.4% strains showed mutation (single/multiple in mtrR gene. Ten different mutations were observed and Gly-45 → Asp, Tyr-105 → His being the most common observed mutation. Conclusion: This is the first report from India on quinolone resistance mutations in MtrRCDE efflux system in N.gonorrhoeae. In conclusion, the high level of resistance to quinolone and single or multiple mutations in mtrR gene could limit the drug choices for gonorrhoea.

  2. Anti-Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Techniques

    Science.gov (United States)

    Gozalbes, Rafael; Brun-Pascaud, Monique; Garcia-Domenech, Ramon; Galvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

    2000-01-01

    The apicoplast, a plastid-like organelle of Toxoplasma gondii, is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones against T. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti-Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC50s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro activity. LDA and MLR analysis were applied to virtual structures to identify the influence of each atom or substituent of the quinolone ring on anti-Toxoplasma activity. LDA predicted that 20 of the 24 quinolones would be active against T. gondii. This was confirmed in vitro for most of the quinolones. Trovafloxacin, grepafloxacin, gatifloxacin, and moxifloxacin were the quinolones most potent against T. gondii, with IC50s of 0.4, 2.4, 4.1, and 5.1 mg/liter, respectively. Using MLR analysis, a good correlation was found between measured and predicted IC50s (r2 = 0.87, cross-validation r2 = 0.74). MLR analysis showed that the carboxylic group at position C-3 of the quinolone ring was not essential for anti-Toxoplasma activity. In contrast, activity was totally dependent on the presence of a fluorine at position C-6 and was enhanced by the presence of a methyl group at C-5 or an azabicyclohexane at C-7. A nucleophilic substituent at C-8 was essential for the activity of gatifloxacin and moxifloxacin. PMID:10991859

  3. Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization

    Directory of Open Access Journals (Sweden)

    Frank Thierry

    2011-08-01

    Full Text Available Abstract Background Cross-resistance to quinolones and beta-lactams is frequent in Enterobacteriaceae, due to the wide use of these antibiotics clinically and in the food industry. Prescription of one of these categories of antibiotic may consequently select for bacteria resistant to both categories. Genetic mechanisms of resistance may be secondary to a chromosomal mutation located in quinolone resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid acquisition. The insertion sequence ISCR1 is often associated with qnr and may favour its dissemination in Gram-negative bacteria. The aim of this study was to determine the genetic mechanism of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in the Central African Republic. Findings Among seventeen ESBL-producing Enterobacteriaceae isolated from urine, pus or stool between January 2003 and October 2005 in the Central African Republic, nine were resistant to ciprofloxacin (seven from community patients and two from hospitalized patients. The ESBL were previously characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid, norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these drugs were determined by disc diffusion and agar dilution methods, respectively. The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and amplicons, if any, were sent for sequencing. Quinolone resistance determining region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for mutation characterization. We found that all CTX-M-producing strains were resistant to the tested quinolones. All the isolates had the same nucleotide mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might favour dissemination of resistance to quinolone and perhaps other antibiotics among Enterobacteriaceae

  4. Monte Carlo simulation for evaluation of the efficacy of carbapenems and new quinolones against ESBL-producing Escherichia coli.

    Science.gov (United States)

    Nakamura, Tatsuya; Shimizu, Chihiro; Kasahara, Mayumi; Okuda, Kazuyuki; Nakata, Chiyo; Fujimoto, Hiroko; Okura, Hiroe; Komatsu, Masaru; Shimakawa, Kouichi; Sueyoshi, Noriyuki; Ura, Toshiro; Satoh, Kaori; Toyokawa, Masahiro; Wada, Yasunao; Orita, Tamaki; Kofuku, Tomomi; Yamasaki, Katsutoshi; Sakamoto, Masako; Nishio, Hisaaki; Kinoshita, Shohiro; Takahashi, Hakuo

    2009-02-01

    Extended-spectrum beta-lactamase (ESBL)-producing bacteria are known to be resistant to penicillins, cephalosporins, and monobactams because of their substrate specificity, and these bacteria are sensitive only to a narrow range of antimicrobial agents. The present study was undertaken to evaluate the efficacy of carbapenems and the new quinolones against ESBL-producing Escherichia coli, using a Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic (PK/PD) theory. The time above MIC (TAM, %) served as the PK/PD parameter for carbapenems, with the target level set at 40%. The AUC/MIC served as the PK/PD parameter for the new quinolones, with the target level set at more than 125. In the analysis of drug sensitivity, the MIC50 of all carbapenems other than imipenem was low (0.03 microg/ml), while the MIC50 of the new quinolones was higher (1-2 microg/ml). The probability of achieving the PK/PD target with carba penems after two doses at the usual dose level, as determined by the Monte Carlo simulation, was high for each of the carbapenems tested (99.0% for biapenem, 99.60% for meropenem, and 95.03% for doripenem), except for imipenem. Among the new quinolones, the highest probability of achieving the PK/PD target was obtained with pazufloxacin (42.90%). Thus, the results of the present study have revealed that carbapenems are effective at the regular dose and can be used as the first-choice antibiotics for ESBL-producing E. coli because the resistance ratios for carbapenems are low compared to those of the new quinolones.

  5. Antistaphylococcal activity of DX-619, a new des-F(6)-quinolone, compared to those of other agents.

    Science.gov (United States)

    Bogdanovich, Tatiana; Esel, Duygu; Kelly, Linda M; Bozdogan, Bülent; Credito, Kim; Lin, Gengrong; Smith, Kathy; Ednie, Lois M; Hoellman, Dianne B; Appelbaum, Peter C

    2005-08-01

    The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC(50)s/MIC(90)s (microg/ml) against 131 Staphylococcus aureus strains (32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 microg/ml and sitafloxacin at 1.0 microg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 microg/ml after 32 microg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including

  6. A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots.

    Science.gov (United States)

    García-León, Guillermo; Hernández, Alvaro; Hernando-Amado, Sara; Alavi, Peyman; Berg, Gabriele; Martínez, José Luis

    2014-08-01

    Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It thus seems unlikely that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last few decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT. Our work shows that plant-produced flavonoids can bind to SmeT, releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicates that they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually downregulated unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned that this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots. Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and that colonization of plant roots is likely one original function of this efflux pump.

  7. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Rachael E Hawtin

    Full Text Available BACKGROUND: Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research. METHODS/PRINCIPAL FINDINGS: Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more

  8. Resistance patterns to beta-lactams and quinolones in clinical isolates of bacteria from Cuban hospitals.

    Science.gov (United States)

    Gonzáles, I; Niebla, A; Vallin, C

    1995-01-01

    The resistance patterns to 26 beta-lactams and 8 quinolones of clinical isolates from Cuban hospitals were evaluated using the disk susceptibility test, according to the NCCLS guidelines (1992). The genera studied were Escherichia sp (320), Enterobacter sp (10), Klebsiella sp (90), Proteus sp (10), Pseudomonas sp (90), Serratia sp (20), and Staphylococcus sp (80). Higher resistance to beta-lactams was observed in the genera Pseudomonas, Escherichia and Klebsiella. For fluoroquinolones we found no significant resistance, with the exception of the genus Klebsiella. The most effective antibiotics were cephalosporins of the second and third generations, fluoroquinolones, and non-classical beta-lactams (cephamycins, moxalactam and monobactams). On the contrary, a pronounced resistance was found to penicillin, oxacillin, ticarcillin, ampicillin, methicillin, nalidixic acid and cinoxacin. These resistance patterns correspond to the high consumption of these antibiotics throughout the country.

  9. C-6 aryl substituted 4-quinolone-3-carboxylic acids as inhibitors of hepatitis C virus.

    Science.gov (United States)

    Chen, Yue-Lei; Zacharias, Jeana; Vince, Robert; Geraghty, Robert J; Wang, Zhengqiang

    2012-08-01

    Quinolone-3-carboxylic acid represents a highly privileged chemotype in medicinal chemistry and has been extensively explored as antibiotics and antivirals targeting human immunodeficiency virus (HIV) integrase (IN). Herein we describe the synthesis and anti-hepatitis C virus (HCV) profile of a series of C-6 aryl substituted 4-quinlone-3-carboxylic acid analogues. Significant inhibition was observed with a few analogues at low micromolar range against HCV replicon in cell culture and a reduction in replicon RNA was confirmed through an RT-qPCR assay. Interestingly, evaluation of analogues as inhibitors of NS5B in a biochemical assay yielded only modest inhibitory activities, suggesting that a different mechanism of action could operate in cell culture.

  10. Capillary electrophoresis with electrochemiluminescence detection for the analysis of quinolone drugs and pharmacokinetics study

    Institute of Scientific and Technical Information of China (English)

    Yan Ming Liu; Jun Tao Cao; Hui Wang

    2008-01-01

    A novel method for the determination of two quinolone drugs norfloxacin (NOR) and levofloxacin (LVX) was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship (r ≥ 0.9991) between peak area and concentration of analytes was established over two orders of magnitude. The limits of detection (LOD, S/N = 3) in standard solution are 4.8 × 10-7 mol/L for NOR and 6.4 × 10-7 mol/L for LVX, respectively. The limits of quantitation (LOQ, S/N = 10) in real human urine samples are 1.2 × 10-6 mol/L for NOR and 1.4 × 10-6 mol/L for LVX, respectively. The present method was successfully applied to the determination of NOR and LVX in human urine and the study of pharmacokinetics of NOR.

  11. Plasmid-mediated quinolone resistance among extended spectrum beta lactase producing Enterobacteriaceae from bloodstream infections.

    Science.gov (United States)

    Domokos, Judit; Kristóf, Katalin; Szabó, Dóra

    2016-09-01

    The purpose of this study was to determine prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR) genes [qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, qepA, and oqxAB] among extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. isolates from bloodcultures in Hungary. A total of 103 isolates were tested for quinolone susceptibility by microdilution method and PMQR genes were detected by polymerase chain reaction. About 40 ESBL-producing E. coli (39%) and 50 ESBL-producing Klebsiella spp. strains (48%) were resistant to ciprofloxacin; 40 ESBL-producing E. coli (39%) and 47 ESBL-producing Klebsiella spp. strains (45%) were resistant to levofloxacin; and 88 strains including 40 ESBL-producing E. coli (39%) and 48 (47%) ESBL-producing Klebsiella spp. were resistant to moxifloxacin. Among the 103 ESBL-producing isolates, 77 (75%) isolates (30 E. coli and 47 Klebsiella spp.) harbored PMQR genes. The most commonly detected gene was aac(6')-Ib-cr (65%). The occurrence of qnrS gene was 6%. Interestingly, qnrA, qnrB, qnrC, qnrD, and qepA were not found in any isolates. Among 77 PMQR-positive isolates, 27 (35.1%) and 1 (1.3%) carried two and three different PMQR genes, respectively. Only Klebsiella spp. harbored more than one PMQR genes. Observing prevalence of PMQR genes in the last 8 years, the increasing incidence of aac(6')-Ib-cr and oqxAB can be seen. Our results highlight high frequency of PMQR genes among ESBL-producing Klebsiella pneumoniae and E. coli isolates with an increasing dynamics in Hungary.

  12. QUINOLONE- AND ETA-LACTAM- RESISTANCE IN Escherichia coli FROM DANISH AND ITALIAN BROILER FLOCKS

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-03-01

    Full Text Available The prevalence of quinolone- and -lactam-resistant E. coli was investigated among healthy broiler flocks in Denmark and Italy. In Denmark, sock samples were collected from 10 parent flocks and 10 offspring flocks, according to the procedure currently used for the surveillance of Salmonella in the EU. Samples were enriched in McConkey broth and streaked on McConkey agar plates added with nalidixic acid (32 g/ml, ciprofloxacin (2 g/ml, ampicillin (32 g/ml, cefotaxime (2 g/ml or ceftiofur (8 g/ml. The -glucuronidase test was performed for verification of presumptive E. coli. The same methods were used to analyse sock samples collected from 6 Italian broiler flocks. PCR with primers for the CTX-M-type extended-spectrum -lactamases (ESBLs was performed on cephalosporin-resistant isolates. While resistance to ampicillin and nalidixic acid was widespread in both countries, resistance to ciprofloxacin and cephalosporins was more common among Italian flocks. In Denmark, ciprofloxacin resistance was only detected in 1 parent flock without any history of quinolone usage and none of the flocks was positive for cephalosporin-resistant E. coli. In Italy, resistance to ciprofloxacin was detected in all flocks and resistance to ceftiofur and cefotaxime were detected in 5 flocks. Primers specific for the CTX-M-type ESBLs generated PCR amplicons from isolates from 3 of these flocks. In industrialized countries, the poultry production system is highly standardized, and therefore comparable. However, the use of broad-spectrum antimicrobials is particularly limited in Danish poultry production. Accordingly, the results of this study could reflect the different policies in antimicrobial usage between the two countries.

  13. Coexistence of blaOXA-23 with armA in quinolone-resistant Acinetobacter baumannii from a Chinese university hospital.

    Science.gov (United States)

    Shen, Min; Luan, Guangxin; Wang, Yanhong; Chang, Yaowen; Zhang, Chi; Yang, Jingni; Deng, Shanshan; Ling, Baodong; Jia, Xu

    2016-03-01

    A total of 101 Acinetobacter baumannii isolates were collected to determine the mechanisms of quinolone resistance and investigate the occurrence of carbapenem and high-level aminoglycoside resistance genes among quinolone-resistant strains. Among 77 quinolone-resistant A. baumannii harbored mutations of gyrA and parC, 41 isolates, which belonged to European clone II, had resistance to aminoglycosides and carbapenems due to the expression of armA and acquisition of blaOXA-23. Most of sequence type belonged to clonal complex 92. These results suggested hospital dissemination of multidrug-resistant A. baumannii carrying blaOXA-23, armA, and mutations of quinolone resistance-determining regions in western China.

  14. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Ciprofloxacin-Nonsusceptible Escherichia coli and Klebsiella pneumoniae Isolated from Blood Cultures in Korea

    Directory of Open Access Journals (Sweden)

    Hee Young Yang

    2014-01-01

    Full Text Available OBJECTIVES:To analyze the prevalence of plasmid-mediated quinolone resistance (PMQR determinants in ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea.

  15. Characterization of HmqF, a protein involved in the biosynthesis of unsaturated quinolones produced by Burkholderia thailandensis.

    Science.gov (United States)

    Agarwal, Aparna; Kahyaoglu, Caroline; Hansen, Darren B

    2012-02-28

    The opportunistic pathogen Burkholderia thailandensis produces a number of structurally similar unsaturated quinolones involved in quorum sensing. However, little is known about the biosynthesis of these unsaturated quinolones. In this study, we have characterized the starting point of the biosynthesis of unsaturated quinolone molecules produced in B. thailandensis. We have shown by using in vitro enzymology, liquid chromatography, and mass spectrometry that protein HmqF is involved in the biosynthesis of unsaturated quinolones produced by B. thailandensis. HmqF consists of three domains: an adenylation domain (A domain), a dehydrogenase domain (DH domain), and an acyl carrier domain (ACP). The three domains (A, DH, and ACP) were cloned and expressed individually in Escherichia coli, and their reactivity was studied using high-performance liquid chromatography (HPLC) and mass spectrometry (MS) based assays. Our in vitro studies show that the A domain catalyzes ATP-dependent activation of medium chain (C6-C14) fatty acids without activation by coenzyme A (CoA). Results from competition assays are consistent with decanoic acid being the preferred substrate. Incubation of the ACP domain with 4'-phosphopantetheine transferase and CoA led to the formation of phosphopantetheinylated ACP (Ppant-ACP). In a Ppant ejection assay using tandem MS (MS/MS), a mass consistent with the mass of a cyclic variant of dephosphorylated Ppant was detected. We further demonstrated that Ppant-ACP could be loaded with medium chain fatty acids in the presence of ATP and the A domain. MS analysis was consistent with the formation of Ppant-ACP thiol esters of the fatty acids. MS/MS Ppant ejection experiments confirmed the loss of 2H in samples of fatty acid-loaded Ppant-ACP in the presence of the DH domain. HPLC analysis of benzyl amide ligation products allowed us to conclude that dehydrogenation produced trans-β,γ-unsaturation in the fatty acid chains. Our results are in good agreement

  16. Characterization of antimicrobial resistance in Salmonella enterica food and animal isolates from Colombia: identification of a qnrB19-mediated quinolone resistance marker in two novel serovars

    DEFF Research Database (Denmark)

    Karczmarczyk, M.; Martins, M.; McCusker, M.

    2010-01-01

    Ninety-three Salmonella isolates recovered from commercial foods and exotic animals in Colombia were studied. The serotypes, resistance profiles and where applicable the quinolone resistance genes were determined. Salmonella Anatum (n=14), Uganda (19), Braenderup (10) and Newport (10) were the most...... hitherto unrecognized in various Salmonella serovars in Colombia. We also report unusual high-level quinolone resistance in the absence of any DNA gyrase mutations in serovars S. Carrau, Muenchen and Uganda....

  17. 金属离子对喹诺酮活性影响的研究进展%Research Progress of Metal Ions Influence The Activity of Quinolone

    Institute of Scientific and Technical Information of China (English)

    范卓文; 朱丽华; 杨爽爽; 闫丽莉; 孙建华

    2014-01-01

    喹诺酮类药物以抗菌活性强、抗菌谱广、疗效确切等优点被广泛应用于临床,一些研究结果表明金属离子对喹诺酮类药物的活性有一定的影响。本文概述了喹诺酮类药物的发展及作用机制,总结了金属离子对喹诺酮类的作用及喹诺酮类药物金属配合物的活性,最后展望了喹诺酮类药物今后的发展。%Quinolone are widely used clinically because of its antibacterial activity, widely spectrum antimicrobial, curative ef-fect, etc.Some studies show that the metal ions affect the activity of quinolone.This paper outlines the development and action mecha-nism of quinolone. Summarizes the role of metal ions on metal quinolone and the biological activity of quinolone complexes. Finally, prospects of the development of quinolone.

  18. Alarmingly High Segregation Frequencies of Quinolone Resistance Alleles within Human and Animal Microbiomes Are Not Explained by Direct Clinical Antibiotic Exposure.

    Science.gov (United States)

    Field, Wesley; Hershberg, Ruth

    2015-05-26

    Antibiotic resistance poses a major threat to human health. It is therefore important to characterize the frequency of resistance within natural bacterial environments. Many studies have focused on characterizing the frequencies with which horizontally acquired resistance genes segregate within natural bacterial populations. Yet, very little is currently understood regarding the frequency of segregation of resistance alleles occurring within the housekeeping targets of antibiotics. We surveyed a large number of metagenomic datasets extracted from a large variety of host-associated and non host-associated environments for such alleles conferring resistance to three groups of broad spectrum antibiotics: streptomycin, rifamycins, and quinolones. We find notable segregation frequencies of resistance alleles occurring within the target genes of each of the three antibiotics, with quinolone resistance alleles being the most frequent and rifamycin resistance alleles being the least frequent. Resistance allele frequencies varied greatly between different phyla and as a function of environment. The frequency of quinolone resistance alleles was especially high within host-associated environments, where it averaged an alarming ∼ 40%. Within host-associated environments, resistance to quinolones was most often conferred by a specific resistance allele. High frequencies of quinolone resistance alleles were also found within hosts that were not directly treated with antibiotics. Therefore, the high segregation frequency of quinolone resistance alleles occurring within the housekeeping targets of antibiotics in host-associated environments does not seem to be the sole result of clinical antibiotic usage.

  19. Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity.

    Science.gov (United States)

    Cross, R Matthew; Monastyrskyi, Andrii; Mutka, Tina S; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

    2010-10-14

    Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of multidrug resistant W2 and TM90-C2B isolates of Plasmodium falciparum. Follow-up structure-activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure-property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.

  20. In vivo sequential selection of Escherichia coli with topoisomerase- and efflux-mediated misleading quinolone resistance phenotypes.

    Science.gov (United States)

    Smati, Mounira; Emond, Jean-Philippe; Arlet, Guillaume; Tankovic, Jacques

    2012-02-01

    Two mutants of Escherichia coli (V1 and V2) with acquired mechanisms of resistance to fluoroquinolones were isolated sequentially from blood cultures of a patient with cholangiocarcinoma treated repeatedly with ofloxacin; a third mutant (V3) was isolated under ciprofloxacin therapy. All mutants were related clonally. V1 was susceptible to quinolones but with diminished susceptibility to ofloxacin. V2 was hypersusceptible to nalidixic acid but had high-level resistance to ofloxacin. V3 was resistant to all quinolones. Ofloxacin selected for original gyrA and parC mutations, leading to the unusual and misleading resistance phenotypes of V1 and V2, whereas efflux played a major role in the increased resistance of V3.

  1. Switching electrical conductivity in an AOT-isooctane-water microemulsion through photodimerization of solubilized N-methyl-2-quinolone.

    Science.gov (United States)

    Bufe, Markus; Wolff, Thomas

    2006-09-28

    The electrical conductivity of microemulsions composed of Aerosol OT (AOT), isooctane and water as a function of temperature was studied in the absence and presence of N-methyl-2-quinolone (NMQ), and consequences of an in situ photodimerization of NMQ were investigated. A conductivity increase upon raising the temperature of a water-in-oil microemulsion indicates percolation. Percolation temperatures (Tp) can be influenced specifically by the addition of certain substances. Small amounts of solubilized N-methyl-2-quinolone induce lower Tp (by up to 9 K), and photodimerization of NMQ shifts Tp back to higher values. Consequently, the microemulsion can be switched from conducting to non-conducting without varying temperature or composition by exposing samples to UV light at lambda > 310 nm. The effect can be reverted in part by irradiation at lambda = 250 nm. Coumarin derivatives--structurally related to NMQ--show much slighter effects.

  2. Synthesis and Antimicrobial Activity of some Tetrahydro Quinolone Diones and Pyrano[2,3-d]pyrimidine Derivatives

    Science.gov (United States)

    Shahi, Masoume; Foroughifar, Naser; Mobinikhaledi, Akbar

    2015-01-01

    There has been special interest in the chemistry of quinolone and pyrimidine derivatives due to their diverse biological activities such as anticonvulsant, anti-malarial agents, antibacterial, antiviral, cytostatic, antithelemintic, antigenotoxic, anti-cancer agents. These compounds are also used as targeting delayed-type hypersensivity and anti-convulsant agents. As a part of our research works in the synthesis of pyrimidine derivatives containing biological activities, a series of novel pyrano[2,3-d]pyrimidine derivatives 2 and tetrahydro quinolone dione derivatives 3 were synthesized via reaction of tetrahydrobenzo[b]pyrano derivatives 1 with different reagents in suitable yields. The characterization of these synthesized compounds was established by IR, 1H NMR and 13C NMR spectroscopic data. Furthermore, all compounds were subsequently evaluated for their in-vitro antibacterial activity against three bacteria: Staphylococcus aureus (ATTC-25923), Escherichia Coli (ATTC-25922) and Bacillus anthracic (ATTC-25924). PMID:26330864

  3. Quinolone-resistance in Salmonella is associated with decreased mRNA expression of virulence genes invA and avrA, growth and intracellular invasion and survival.

    Science.gov (United States)

    Wang, Yu-Ping; Li, Lin; Shen, Jian-Zhong; Yang, Fu-Jiang; Wu, Yong-Ning

    2009-02-01

    A variety of environmental factors, such as oxygen, pH, osmolarity and antimicrobial agents, modulate the expression of Salmonella pathogenicity islands (SPI) genes. This study investigated SPI-1 gene expression and the pathogenicity of quinolone-resistant Salmonella. mRNA expression levels of the invA and avrA genes, located in SPI-1, in quinolone-susceptible and quinolone-resistant Salmonella strains were determined using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Twenty-five quinolone-resistant Salmonella mutants were derived from quinolone-susceptible strains by multiple-passage selection through increasing concentrations of ciprofloxacin in vitro, while an additional 15 strains were quinolone-resistant Salmonella clinical isolates. Sequence analysis showed no gene deletion or point mutations of nine SPI-1 genes (including invA and avrA) occurred in either the selected or clinical quinolone-resistant strains, while a single gyrA point mutation (S83F) was observed in all 40 quinolone-resistant strains. The mRNA expression levels of invA and avrA were significantly decreased (P<0.005) in quinolone-resistant strains (clinically acquired or experimentally selected in vitro), compared to the quinolone-susceptible strains. The resistant strains also had a slower growth rate combined with decreased epithelial cell invasion and intracellular replication in epithelial cells and macrophages. The results suggest that quinolone-resistance may be associated with lower virulence and pathogenicity than in quinolone-susceptible strains.

  4. Pharmacokinetics of Sparfloxacin in the Serum and Vitreous Humor of Rabbits: Physicochemical Properties That Regulate Penetration of Quinolone Antimicrobials

    Science.gov (United States)

    Liu, Weiguo; Liu, Qing Feng; Perkins, Ruth; Drusano, George; Louie, Arnold; Madu, Assumpta; Mian, Umar; Mayers, Martin; Miller, Michael H.

    1998-01-01

    We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% ± 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (r2 > 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed Staphylococcus epidermidis decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin

  5. Novel derivatives of benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, and antitumor evaluation.

    Science.gov (United States)

    Dogan Koruznjak, Jasna; Grdisa, Mira; Slade, Neda; Zamola, Branimir; Pavelić, Kresimir; Karminski-Zamola, Grace

    2003-10-01

    Novel derivatives of benzo[b]thieno[2,3-c]quinolones 3a-j were synthesized in a multistep synthesis starting from substituted benzo[b]thiophene-2-carbonyl chlorides, to their corresponding benzo[b]thiophene-2-carboxamides, which were photochemically dehydrohalogenated to their corresponding substituted benzo[b]thieno[2,3-c]quinolones. Compound 4 was prepared from 3i by alkylation with 3-dimethylaminopropyl chloride in the presence of NaH. Compounds 7a,b were prepared from 3g in the multistep synthesis from compounds 5 and 6. Compounds 3b, 3c-f, 3h, 7a, and 7b were found to exert cytostatic activity against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), human fibroblast cell lines (WI-38). The compounds that bear a 3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma cells (HBL, ME 67.3, and ME 67.1), a potential mechanism of action was examined. Analysis of DNA and Annexin-V-FLUOS staining indicated that compound 4 causes cell death by apoptosis.

  6. Luminescent determination of quinolones in milk samples by liquid chromatography/post-column derivatization with terbium oxide nanoparticles.

    Science.gov (United States)

    Yánez-Jácome, G S; Aguilar-Caballos, M P; Gómez-Hens, A

    2015-07-31

    The usefulness of terbium oxide nanoparticles (Tb4O7NPs) as post-column derivatizing reagent for the liquid chromatographic determination of residues of quinolone antibiotics in milk samples has been studied. Seven quinolones of veterinary use have been chosen as model analytes to develop this method. The derivatization step is based on the formation of luminescent chelates of quinolones with Tb4O7NPs, which are monitored at λex=340nm and λem=545nm. Another relevant feature of the method is that the use of a 10-cm column and a ternary mixture of methanol, acetonitrile and acetic acid as mobile phase in gradient elution mode allow the chromatographic separation of the quinolones in about 13min, whereas previously described chromatographic methods require about 20min. The dynamic ranges of the calibration graphs and limits of detection are, respectively: 65-900ngmL(-1) and 35ngmL(-1) for marbofloxacin, 7.2-900ngmL(-1) and 2.5ngmL(-1) for ciprofloxacin, 6-900ngmL(-1) and 2ngmL(-1) for danofloxacin, 50-900ngmL(-1) and 20ngmL(-1) for enrofloxacin, 35-900ngmL(-1) and 12ngmL(-1) for sarafloxacin, 5-900ngmL(-1) and 2ngmL(-1) for oxolinic acid, and 7-900ngmL(-1) and 2.5ngmL(-1) for flumequine. The precision, established at two concentration levels of each analyte and expressed as the percentage of the relative standard deviation is in the range of 1.9-8.1% using standards, and of 3.4-10.7% in the presence of milk samples. The method has been satisfactorily applied to the analysis of skimmed, semi-skimmed and whole milk samples, with recoveries ranging from 89.0 to 106.5%.

  7. In Vitro Resistance Development to Nemonoxacin in Streptococcus pneumoniae: A Unique Profile for a Novel Nonfluorinated Quinolone

    Science.gov (United States)

    Roychoudhury, Siddhartha; Makin, Kelly; Twinem, Tracy; Leunk, Robert

    2016-01-01

    Selection of resistant strains in Streptococcus pneumoniae was studied in vitro with nemonoxacin, a novel nonfluorinated quinolone (NFQ), in comparison with quinolone benchmarks, ciprofloxacin, garenoxacin, and gatifloxacin. In stepwise resistance selection studies, a 256-fold loss of potency was observed after three to four steps of exposure to ciprofloxacin or garenoxacin. In contrast, the loss of potency was limited to eightfold after three steps of exposure to nemonoxacin and repeated attempts to isolate highly resistant organisms after four steps of exposure yielded isolates that could not be subcultured in liquid medium. The quinolone resistance-determining regions of the target genes, parC, parE, gyrA, and gyrB, were analyzed through DNA sequencing. Known mutations, especially in the hotspots of parC and gyrA, were selected with exposure to garenoxacin, ciprofloxacin, and gatifloxacin. In contrast, mutations selected with nemonoxacin were limited to GyrA, GyrB, and ParE, sparing ParC, which is known as a key driver of resistance in clinical isolates of S. pneumoniae. This observation is consistent with previous data using other NFQs, which showed no loss of potency due to ParC mutations in clinical isolates. This apparently unique feature of nemonoxacin is potentially attributable to the structural uniqueness of the NFQs, distinguishing them from the fluoroquinolones that are commonly prescribed for infections by S. pneumoniae. PMID:27267788

  8. High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Soo Tein Ngoi

    2014-01-01

    Full Text Available The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n=52; S83F, S83Y, S83I, D87G, D87Y, and D87N and parE (n=1; M438I. Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16>256 μg/mL. Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes.

  9. Removal of quinolone antibiotics from wastewaters by sorption and biological degradation in laboratory-scale membrane bioreactors.

    Science.gov (United States)

    Dorival-García, N; Zafra-Gómez, A; Navalón, A; González, J; Vílchez, J L

    2013-01-01

    Laboratory-scale batch experiments were developed to investigate the main removal routes for 6 commonly found quinolones (ciprofloxacin, moxifloxacin, norfloxacin, ofloxacin, pipemidic acid, and piromidic acid), in wastewaters from a wastewater treatment plant, at μg L(-1) levels in an aerobic sludge system from a membrane bioreactor (MBR) pilot plant. It was demonstrated that sorption and biotransformation were the main removal routes for the target antibiotics over other possible pathways, as volatilization or hydrolysis, under the experimental conditions. Mass balances indicated that sorption on sludge played a dominant role in the elimination of antibiotics from waters. The sorption coefficient K(d) depended strongly on temperature and on the quinolone type and were higher at lower temperatures and for piperazinylic quinolones. K(d) values were between 516 and 3746 L kg(-1) in the temperature range of 9-38°C. Higher mixed liquor suspended solids (MLSS) increased quinolone removal efficiency mainly by sorption. Quinolone biodegradation constituted a secondary pathway, and could be described by first-order kinetics with degradation-rate constants ranging from 8.0 × 10(-4)h(-1) to 1.4 × 10(-2)h(-1) within the same temperature range and MLSS from 7000 to 15,000 mg L(-1). Biodegradation depended on the MLSS and temperature, but also on the initial chemical oxygen demand (COD). Higher biodegradation rates were observed at higher MLSS and temperature, as well as at low initial COD. Ciprofloxacin and moxifloxacin registered the highest biodegradation percentages (52.8% and 47.2%, respectively, at 38°C and 15,000 mg L(-1) MLSS), which is evidence that, despite the known persistence of this group of antibiotics and removal from waters mainly by sorption, it was possible to improve their removal by biodegradation, with an appropriate selection of conditions and control of process variables, as a preliminary step towards the elimination of these antibiotics from the

  10. Quinolone co-resistance in ESBL- or AmpC-producing Escherichia coli from an Indian urban aquatic environment and their public health implications.

    Science.gov (United States)

    Bajaj, Priyanka; Kanaujia, Pawan Kumar; Singh, Nambram Somendro; Sharma, Shalu; Kumar, Shakti; Virdi, Jugsharan Singh

    2016-01-01

    Quinolone and β-lactam antibiotics constitute major mainstay of treatment against infections caused by pathogenic Escherichia coli. Presence of E. coli strains expressing co-resistance to both these antibiotic classes in urban aquatic environments which are consistently being used for various anthropogenic activities represents a serious public health concern. From a heterogeneous collection of 61 E. coli strains isolated from the river Yamuna traversing through the National Capital Territory of Delhi (India), those harboring blaCTX-M-15 (n = 10) or blaCMY-42 (n = 2) were investigated for co-resistance to quinolones and the molecular mechanisms thereof. Resistance was primarily attributed to amino acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA (S83L ± D87N) and ParC (S80I ± E84K). One of the E. coli strains, viz., IPE, also carried substitutions in GyrB and ParE at positions Ser492→Asn and Ser458→Ala, respectively. The phenotypically susceptible strains nevertheless carried plasmid-mediated quinolone resistance (PMQR) gene, viz., qnrS, which showed co-transfer to the recipient quinolone-sensitive E. coli J53 along with the genes encoding β-lactamases and led to increase in minimal inhibitory concentrations of quinolone antibiotics. To the best of our knowledge, this represents first report of molecular characterization of quinolone co-resistance in E. coli harboring genes for ESBLs or AmpC β-lactamases from a natural aquatic environment of India. The study warrants true appreciation of the potential of urban aquatic environments in the emergence and spread of multi-drug resistance and underscores the need to characterize resistance genetic elements vis-à-vis their public health implications, irrespective of apparent phenotypic resistance.

  11. Application of Sigmoidal Transformation Functions in Optimization of Micellar Liquid Chromatographic Separation of Six Quinolone Antibiotics.

    Science.gov (United States)

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2016-03-01

    A chemometrics approach has been used to optimize the separation of six quinolone compounds by micellar liquid chromatography (MLC). A Derringer's desirability function, a multicriteria decision-making (MCDM) method, was tested for evaluation of two different measures of chromatographic performance (resolution and analysis time). The effect of three experimental parameters on a chromatographic response function (CRF) expressed as a product of two sigmoidal desirability functions was investigated. The sigmoidal functions were used to transform the optimization criteria, resolution and analysis time into the desirability values. The factors studied were the concentration of sodium dodecyl sulfate, butanol content and pH of the mobile phase. The experiments were done according to the face-centered cube central composite design, and the calculated CRF values were fitted to a polynomial model to correlate the CRF values with the variables and their interactions. The developed regression model showed good descriptive and predictive ability (R(2) = 0.815, F = 6.919, SE = 0.038, [Formula: see text]) and used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture. The efficiency of prediction of polynomial model was confirmed by performing the experiment under the optimal conditions.

  12. Study of fluorescence characteristics of the charge-transfer reaction of quinolone agents with bromanil

    Science.gov (United States)

    Li, Wen-Ying; Chen, Xiao-Fang; Xuan, Chun-Sheng

    2009-01-01

    A spectrofluorimetric method was discussed for the determination of three antibacterial quinolone derivatives, ofloxacin (OFL), norfloxacin (NOR) and ciprofloxacin (CIP) through charge-transfer complexation (CTC) with 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil, TBBQ). The method was based on the reaction of these drugs as n-electron donors with the π-acceptor TBBQ. TBBQ was found to react with these drugs to produce a kind of yellow complexes and the fluorescence intensities of the complexes were enhanced by 29-36 times more than those of the corresponding monomers. UV-vis, 1H NMR and XPS techniques were used to study the complexes formed. The various experimental parameters affecting the fluorescence intensity were studied and optimized. Under optimal reaction conditions, the rectilinear calibration graphs were obtained in the concentration range of 0.021-2.42 μg mL -1, 0.017-2.63 μg mL -1 and 0.019-2.14 μg mL -1 for OFL, NOR and CIP, respectively. The methods developed were applied successfully to the determination of the subject drugs in their pharmaceutical dosage forms with good precision and accuracy compared to official and reported methods as revealed by t- and F-tests.

  13. Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains

    Directory of Open Access Journals (Sweden)

    Kumari N

    2008-01-01

    Full Text Available Genes encoding the quinolones resistance determining regions (QRDRs in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (≥2 μg/mL. These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.

  14. Antimicrobial susceptibility testing of newer quinolones against gram positive and gram negative clinical isolates.

    Science.gov (United States)

    Iffat, Wajiha; Shoaib, Muhammad Harris; Muhammad, Iyad Naeem; Rehana; Tasleem, Samiah; Gauhar, Shahnaz

    2010-07-01

    Antibiotic resistance development is an ongoing process associated with irrational antibiotic use. WHO recommends regular surveillance programs for monitoring of antibiotic resistance. The present study is a step in this direction. A total of 124 clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different hospitals in Karachi. In vitro antimicrobial susceptibility studies were carried out by agar dilution method using newer quinolones that included Gatifloxacin and Levofloxacin. It was observed that 50% (n=30) isolates of Staphylococcus aureus were resistant to gatifloxacin. Gatifloxacin was more active against Pseudomonas aeruginosa (n=23) and showing complete susceptibility with MIC 1mg/L except for three very resistant strains that shown resistance at even higher concentrations. Escherichia coli (n=45) has shown 15.5% and Klebsiella pneumoniae (n=26) 34.61% resistance to gatifloxacin. Levofloxacin was more active against Staphylococcus aureus and Escherichia coli showing complete susceptibility at 0.5 mg /L concentration. Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be resistant to Levofloxacin showing 36.36% and 23.08% resistance respectively. The study strongly recommends the adherence to the antibiotic policy and regular susceptibility testing to overcome the problem associated with antimicrobial resistance.

  15. Activated carbon adsorption of quinolone antibiotics in water: Performance, mechanism, and modeling.

    Science.gov (United States)

    Fu, Hao; Li, Xuebing; Wang, Jun; Lin, Pengfei; Chen, Chao; Zhang, Xiaojian; Suffet, I H Mel

    2017-06-01

    The extensive use of antibiotics has led to their presence in the aquatic environment, and introduces potential impacts on human and ecological health. The capability of powdered activated carbon (PAC) to remove six frequently used quinolone (QN) antibiotics during water treatment was evaluated to improve drinking water safety. The kinetics of QN adsorption by PAC was best described by a pseudo second-order equation, and the adsorption capacity was well described by the Freundlich isotherm equation. Isotherms measured at different pH showed that hydrophobic interaction, electrostatic interaction, and π-π dispersion force were the main mechanisms for adsorption of QNs by PAC. A pH-dependent isotherm model based on the Freundlich equation was developed to predict the adsorption capacity of QNs by PAC at different pH values. This model had excellent prediction capabilities under different laboratory scenarios. Small relative standard derivations (RSDs), i.e., 0.59%-0.92% for ciprofloxacin and 0.09%-3.89% for enrofloxacin, were observed for equilibrium concentrations above the 0.3mg/L level. The RSDs increased to 11.9% for ciprofloxacin and 32.1% for enrofloxacin at μg/L equilibrium levels, which is still acceptable. This model could be applied to predict the adsorption of other chemicals having different ionized forms. Copyright © 2016. Published by Elsevier B.V.

  16. Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-08-01

    Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(ΙΙΙ), Zr(ΙV) and U(VΙ) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

  17. Determination of quinolones in plasma samples by capillary electrophoresis using solid-phase extraction.

    Science.gov (United States)

    Hernández, M; Borrull, F; Calull, M

    2000-06-09

    The potential of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) have been investigated for the separation and quantitative determination of 10 quinolone antibiotics. The influence of different conditions, such as the buffer and pH of the electrolyte, the surfactant and the ion-pairing agents added to the electrolyte and the organic modifier were studied. A buffer consisting of 40 mM sodium tetraborate at pH 8.1 containing 10% (v/v) methanol was found to be a highly efficient electrophoretic system for separating lomefloxacin, enoxacin, norfloxacin, pipemidic acid, ofloxacin, piromidic acid, flumequine, oxolinic acid, cinoxacin and nalidixic acid. A solid-phase extraction method to remove the sample matrix (pig plasma samples) was developed on a C(18) cartridge using a mixture of methanol-water (70:30, v/v). The method is specific and reproducible and mean recoveries were in the range 94.0+/-4.2% and 123.3+/-4.1% for pig plasma samples over the range used. A linear relationship between concentration and peak area for each compound in pig plasma samples was obtained in the concentration range 5-20 mg l(-1) and detection limits were between 1.1 and 2.4 mg l(-1).

  18. Phage-Antibiotic Synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Science.gov (United States)

    Comeau, André M; Tétart, Françoise; Trojet, Sabrina N; Prère, Marie-Françoise; Krisch, H M

    2007-08-29

    Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  19. Degradation of quinolone antibiotic, norfloxacin, in aqueous solution using gamma-ray irradiation.

    Science.gov (United States)

    Sayed, Murtaza; Khan, Javed Ali; Shah, Luqman Ali; Shah, Noor S; Khan, Hasan M; Rehman, Faiza; Khan, Abdur Rahman; Khan, Asad M

    2016-07-01

    This study reports the efficiency of gamma-ray irradiation to degrade quinolone antibiotic, norfloxacin, in aqueous solution. Laboratory batch experiments were conducted to determine the "pseudo-first" order degradation kinetics of norfloxacin in the concentration ranges of 3.4-16.1 mg L(-1) by gamma-ray irradiation. The dose constant was found to be dependent on the initial concentration of norfloxacin and gamma-ray irradiation dose rate (D r). The saturation of norfloxacin sample solutions with N2, air or N2O, and the presence of tert-butanol and 2-propanol showed that (•)OH played more crucial role in the degradation of norfloxacin. The second order rate constants of (•)OH, eaq (-), and (•)H with norfloxacin were calculated to be 8.81 × 10(9), 9.54 × 10(8), and 1.10 × 10(9) M(-1) s(-1), respectively. The effects of various additives including CO3 (2-), HCO3 (-), NO3 (-), NO2 (-), and thiourea and the pH of the medium on the degradation of norfloxacin were also investigated. Norfloxacin degradation was lower in surface water and wastewater than in ultrapure water. Several degradation byproducts of norfloxacin were identified from which the possible degradation pathway was proposed.

  20. Phage-Antibiotic Synergy (PAS: beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Directory of Open Access Journals (Sweden)

    André M Comeau

    Full Text Available Although the multiplication of bacteriophages (phages has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS. A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  1. Association of mutation patterns in GyrA and ParC genes with quinolone resistance levels in lactic acid bacteria.

    Science.gov (United States)

    Li, Shaoying; Li, Zhen; Wei, Wan; Ma, Chunyan; Song, Xiaomin; Li, Shufen; He, Wenying; Tian, Jianjun; Huo, Xiaoyan

    2015-02-01

    The quinolone resistance of 19 lactic acid bacterial strains belonging to the genera Enterococcus and Lactobacillus isolated from the natural fermented koumiss and yoghurt were investigated. The objective of this study was to determine the quinolone resistance levels and to explore the association of the resistance with the mutation patterns in gyrA and parC genes, as is currently recommended by the Food and Agriculture Organization/World Health Organization Joint Expert Committee in Guidelines for Evaluation of Probiotics in Food for probiotic lactic acid bacteria drug resistance in 2001. The Oxford Cup method and double-tube dilution method were used to determine the quinolone resistance levels of the isolated strains. Generally, all of the 19 strains showed resistance towards norfloxacin and ciprofloxacin when the Oxford cup method was used, whereas the incidence was lower (to norfloxacin 89.5% and to ciprofloxacin 68.4%) when minimum inhibitory concentration breakpoints (CLSI M100-S23) were tested. Furthermore, gene sequencing was conducted on gyrA and parC of topoisomerase II of these isolated strains. The genetic basis for quinolone resistance may be closely related to mutations in gyrA genes as there were 10 mutation sites in amino-acid sequences encoded by gyrA genes in 10 quinolone resistance strains and 14 mutation sites in Enterococcus durans HZ28, whereas no typical mutations were detected in parC genes.

  2. Characterization of Plasmid-Mediated Quinolone Resistance Determinants in High-Level Quinolone-Resistant Enterobacteriaceae Isolates from the Community: First Report of qnrD Gene in Algeria.

    Science.gov (United States)

    Yanat, Betitera; Machuca, Jesús; Díaz-De-Alba, Paula; Mezhoud, Halima; Touati, Abdelaziz; Pascual, Álvaro; Rodríguez-Martínez, José-Manuel

    2017-01-01

    The objective was to assess the prevalence of plasmid-mediated quinolone resistance (PMQR)-producing isolates in a collection of quinolone-resistant Enterobacteriaceae of community origin isolated in Bejaia, Algeria. A total of 141 nalidixic acid-resistant Enterobacteriaceae community isolates were collected in Bejaia (Northern Algeria) and screened for PMQR genes using polymerase chain reaction (PCR). For PMQR-positive strains, antimicrobial susceptibility testing was performed by broth microdilution and disk diffusion. Mutations in the quinolone resistance-determining regions of the target genes, gyrA and parC, were detected with a PCR-based method and sequencing. Southern blotting, conjugation and transformation assays and molecular typing by pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing were also performed. The prevalence of PMQR-producing Enterobacteriaceae isolates was 13.5% (19/141); 11 of these isolates produced Aac(6')-Ib-cr and 8 were qnr-positive (4 qnrB1-like, 2 qnrS1-like, and 2 qnrD1-like), including the association with aac(6')-Ib-cr gene in three cases. PMQR gene transfer by conjugation was successful in 6 of 19 isolates tested. PFGE revealed that most of the PMQR-positive Escherichia coli isolates were unrelated, except for two groups comprising two and four isolates, respectively, including the virulent multidrug-resistant clone E. coli ST131 that were clonally related. Our findings indicate that PMQR determinants are prevalent in Enterobacteriaceae isolates from the community studied. We describe the first report of the qnrD gene in Algeria.

  3. Intramolecular hydrogen bond between 4-oxo and 3-carboxylic groups in quinolones and their analogs. Crystal structures of 7-methyl- and 6-fluoro-1,4-dihydro-4-oxocinnoline-3-carboxylic acids

    Science.gov (United States)

    Główka, Marek L.; Martynowski, Dariusz; Olczak, Andrzej; Bojarska, Joanna; Szczesio, Małgorzata; Kozłowska, Krystyna

    2003-09-01

    Crystal structures of two cinnoline analogs of quinolones and statistics on quinolones molecular forms observed in the crystal state have been determined. It has been shown that common quinolones may be divided into two main types, depending on presence of proton acceptor, usually aliphatic amine group, capable of protonation under mild conditions. Quinolones lacking amine group or having one(s) bound to an aromatic system exist at physiological pH mainly in a free acid form, in which acidic hydrogen atom is locked into an intramolecular hydrogen bond. The phenomenon enhances permeability of quinolones through lipophilic cell membranes but decreases the concentration of carboxylate form capable of specific binding with bacterial DNA. Molecular (neutral) form was observed exclusively in the crystalline state for these quinolones. The dominant forms seem different for quinolones having amine substituents with unconjugated lone pair electrons at N atom. Even in the crystalline state, they may exist also in a zwitterionic form, which was found to dominate in secondary amines crystallised at neutral pH. Our limited data suggest that position and order of amine group may play important role in controlling quinolones absorption, transport and concentration and thus their biological profile.

  4. Intravenous nursing progress quinolones The research progress of nursing on quinolones with intravenous injection%喹诺酮类药物静脉应用护理进展

    Institute of Scientific and Technical Information of China (English)

    杨希芳; 王静; 胡玉美

    2011-01-01

    对喹诺酮类药物的用药现状、不良反应及护理、配伍禁忌等进行了综述,旨在提高护理员对该药的认识,以提高疗效,保证用药安全。%Status of quinolones, adverse reactions and nursing, incompatibility etc.were reviewed, In order to improve cognition of care workers for the drugs, to improve efficacy and ensure safety of drugs.

  5. Using second-order calibration method based on trilinear decomposition algorithms coupled with high performance liquid chromatography with diode array detector for determination of quinolones in honey samples.

    Science.gov (United States)

    Yu, Yong-Jie; Wu, Hai-Long; Shao, Sheng-Zhi; Kang, Chao; Zhao, Juan; Wang, Yu; Zhu, Shao-Hua; Yu, Ru-Qin

    2011-09-15

    A novel strategy that combines the second-order calibration method based on the trilinear decomposition algorithms with high performance liquid chromatography with diode array detector (HPLC-DAD) was developed to mathematically separate the overlapped peaks and to quantify quinolones in honey samples. The HPLC-DAD data were obtained within a short time in isocratic mode. The developed method could be applied to determine 12 quinolones at the same time even in the presence of uncalibrated interfering components in complex background. To access the performance of the proposed strategy for the determination of quinolones in honey samples, the figures of merit were employed. The limits of quantitation for all analytes were within the range 1.2-56.7 μg kg(-1). The work presented in this paper illustrated the suitability and interesting potential of combining second-order calibration method with second-order analytical instrument for multi-residue analysis in honey samples.

  6. Structural optimization of quinolon-4(1H)-imines as dual-stage antimalarials: toward increased potency and metabolic stability.

    Science.gov (United States)

    Ressurreição, Ana S; Gonçalves, Daniel; Sitoe, Ana R; Albuquerque, Inês S; Gut, Jiri; Góis, Ana; Gonçalves, Lídia M; Bronze, Maria R; Hanscheid, Thomas; Biagini, Giancarlo A; Rosenthal, Philip J; Prudêncio, Miguel; O'Neill, Paul; Mota, Maria M; Lopes, Francisca; Moreira, Rui

    2013-10-10

    Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including the obligatory developmental phase in the liver, which precedes the erythrocytic stage. We have previously reported that N-Mannich-based quinolon-4(1H)-imines are potent antiplasmodial agents but present several stability liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual-stage antiplasmodial agents endowed with chemical and metabolic stability. We report compounds active against both the erythrocytic and exoerythrocytic forms of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and 710 nM against the erythrocytic and exoerythrocytic forms), which constitute excellent starting points for further lead optimization as dual-stage antimalarials.

  7. Changes of the Quinolones Resistance to Gram-positive Cocci Isolated during the Past 8 Years in the First Bethune Hospital

    Science.gov (United States)

    Xu, Jiancheng; Chen, Qihui; Yao, Hanxin; Zhou, Qi

    This study was to investigate the quinolones resistance to gram-positive cocci isolated in the First Bethune Hospital during the past 8 years. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). The rates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCNS) were 50.8%∼83.3% and 79.4%∼81.5%during the past 8 years, respectively. In recent 8 years, the quinolones resistance to gram-positive cocci had increased. Monitoring of the quinolones resistance to gram-positive cocci should be strengthened. The change of the antimicrobial resistance should be investigated in order to guide rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  8. Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.

    Science.gov (United States)

    Arakawa, Hiroshi; Kamioka, Hiroki; Kanagawa, Masahiko; Hatano, Yasuko; Idota, Yoko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction.

  9. Determinants of quinolone resistance in Escherichia coli causing community-acquired urinary tract infection in Bejaia, Algeria.

    Science.gov (United States)

    Betitra, Yanat; Teresa, Vinuesa; Miguel, Viñas; Abdelaziz, Touati

    2014-06-01

    To investigate the mechanisms of quinolone resistance and the association with other resistance markers among Esherichia coli (E. coli) strains isolated from outpatient with urinary tract infection in north of Algeria. A total of 30 nalidixic acid-resistant E. coli isolates from outpatient with urinary tract infections from January 2010 to April 2011 in north of Algeria (Bejaia) were studied. Antimicrobial susceptibility was determined by disc diffusion assay, minimal inhibitory concentrations (MIC) of quinolone were determined by microdilution. Mutations in the Quinolone Resistance-Determining Region (QRDR) of gyrA and parC genes and screening for qnr (A, B and S) and bla genes were done by PCR and DNA sequencing. Most of the E. coli isolates (56.66%) were shown to carry mutations in gyrA and parC (gyrA: Ser83Leu + Asp87Asn and parC:Ser80Ile). While, 16.66% had only an alteration in gyrA: Ser83Leu. One isolate produced qnrB-like and two qnrS-like. Four isolates were CTX-M-15 producers associated with TEM-1 producing in one case. Co-expression of blaCTX-M-15 and qnrB was determined in one E. coli isolate. Our findings suggested the community emergence of gyrA and parC alterations and Qnr determinants that contributed to the development and spread of fluoroquinolone resistance in Algerian E. coli isolates. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  10. Different types of copper complexes with the quinolone antimicrobial drugs ofloxacin and norfloxacin: structure, DNA- and albumin-binding.

    Science.gov (United States)

    Živec, Petra; Perdih, Franc; Turel, Iztok; Giester, Gerald; Psomas, George

    2012-12-01

    Three novel copper(II) complexes with the second-generation quinolone antibacterial agents norfloxacin (nfH) and ofloxacin (ofloH) have been synthesized resulting in the complexes [Cu(nfH)(phen)Cl]Cl·5H(2)O (1·5H(2)O), [Cu(nfH)(2)]Cl(2)·6H(2)O (2·6H(2)O) and [Cu(II)(ofloH)(2)][(Cu(I)Cl(2))(2)] (3), respectively. The crystal structures of the complexes have been determined by X-ray crystallography revealing that the quinolones act as bidentate ligands coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. UV study of the interaction of the quinolones and the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA with [Cu(II)(ofloxacin)(2)][(Cu(I)Cl(2))(2)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through electrostatic binding. DNA solution viscosity measurements have shown that the interaction of the compounds with CT DNA by classical intercalation may be ruled out. Competitive studies with ethidium bromide (EB) indicate that the complexes can partially displace the DNA-bound EB suggesting low to moderate competition with EB. Norfloxacin, ofloxacin and their copper complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Susceptibility to β-lactams and quinolones of Enterobacteriaceae isolated from urinary tract infections in outpatients

    Science.gov (United States)

    Marchisio, Martín; Porto, Ayelén; Joris, Romina; Rico, Marina; Baroni, María R.; Di Conza, José

    2015-01-01

    Abstract The antibiotic susceptibility profile was evaluated in 71 Enterobacteriaceae isolates obtained from outpatient urine cultures in July 2010 from two health institutions in Santa Fe, Argentina. The highest rates of antibiotic resistance were observed for ampicillin (AMP) (69%), trimethoprim/sulfamethoxazole (TMS) (33%), and ciprofloxacin (CIP) (25%). Meanwhile, 21% of the isolates were resistant to three or more tested antibiotics families. Thirty integron-containing bacteria (42.3%) were detected, and a strong association with TMS resistance was found. Third generation cephalosporin resistance was detected in only one Escherichia coli isolate, and it was characterized as a bla CMY-2 carrier. No plasmid-mediated quinolone resistance (PMQR) was found. Resistance to fluoroquinolone in the isolates was due to alterations in QRDR regions. Two mutations in GyrA (S83L, D87N) and one in ParC (S80I) were observed in all CIP-resistant E. coli. It was determined to be the main phylogenetic groups in E. coli isolates. Minimum Inhibitory Concentration (MIC) values against nalidixic acid (NAL), levofloxacin (LEV), and CIP were determined for 63 uropathogenic E. coli isolates as MIC50 of 4 μg/mL, 0.03125 μg/mL, and 0.03125 μg/mL, respectively, while the MIC90 values of the antibiotics were determined as 1024 μg/mL, 64 μg/mL, and 16 μg/mL, respectively. An association between the phylogenetic groups, A and B1 with fluoroquinolone resistance was observed. These results point to the importance of awareness of the potential risk associated with empirical treatment with both the families of antibiotics. PMID:26691475

  12. Susceptibility to β-lactams and quinolones of Enterobacteriaceae isolated from urinary tract infections in outpatients

    Directory of Open Access Journals (Sweden)

    Martín Marchisio

    2015-01-01

    Full Text Available AbstractThe antibiotic susceptibility profile was evaluated in 71 Enterobacteriaceae isolates obtained from outpatient urine cultures in July 2010 from two health institutions in Santa Fe, Argentina. The highest rates of antibiotic resistance were observed for ampicillin (AMP (69%, trimethoprim/sulfamethoxazole (TMS (33%, and ciprofloxacin (CIP (25%. Meanwhile, 21% of the isolates were resistant to three or more tested antibiotics families. Thirty integron-containing bacteria (42.3% were detected, and a strong association with TMS resistance was found. Third generation cephalosporin resistance was detected in only one Escherichia coli isolate, and it was characterized as a blaCMY-2 carrier. No plasmid-mediated quinolone resistance (PMQR was found. Resistance to fluoroquinolone in the isolates was due to alterations in QRDR regions. Two mutations in GyrA (S83L, D87N and one in ParC (S80I were observed in all CIP-resistant E. coli. It was determined to be the main phylogenetic groups in E. coli isolates. Minimum Inhibitory Concentration (MIC values against nalidixic acid (NAL, levofloxacin (LEV, and CIP were determined for 63 uropathogenic E. coli isolates as MIC50 of 4 μg/mL, 0.03125 μg/mL, and 0.03125 μg/mL, respectively, while the MIC90 values of the antibiotics were determined as 1024 μg/mL, 64 μg/mL, and 16 μg/mL, respectively. An association between the phylogenetic groups, A and B1 with fluoroquinolone resistance was observed. These results point to the importance of awareness of the potential risk associated with empirical treatment with both the families of antibiotics.

  13. Different Dynamic Patterns of β-Lactams, Quinolones, Glycopeptides and Macrolides on Mouse Gut Microbial Diversity.

    Science.gov (United States)

    Yin, Jia; M, Prabhakar; Wang, Shan; Liao, Shuo-Xi; Peng, Xin; He, Yan; Chen, Yi-Ran; Shen, Hua-Fang; Su, Jin; Chen, Ye; Jiang, Yun-Xia; Zhang, Guo-Xia; Zhou, Hong-Wei

    2015-01-01

    The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.

  14. In vitro susceptibility pattern of acinetobacter species to commonly used cephalosporins, quinolones, and aminoglycosides

    Directory of Open Access Journals (Sweden)

    Prashanth K

    2004-01-01

    Full Text Available PURPOSE: Acinetobacter spp. is an emerging important nosocomial pathogen. Clinical isolates of this genus are often resistant to many antibiotics. The in vitro susceptibility of Acinetobacter isolates obtained from patients were tested for currently used antibiotics. In addition, the study aimed at biotyping of Acinetobacter baumannii. METHODS: A total of 66 isolates were phenotypically characterised through a large panel of 25 carbon assimilation tests and susceptibility through disc diffusion method with 10 antimicrobial agents were tested. MICs were determined only for second line broad-spectrum drugs such as cefotaxime, ceftazidime, amikacin, ciprofloxacin, and ofloxacin using NCCLS guidelines. RESULTS: Multiple drug resistance (MDR was only witnessed in A. baumannii and not in other Acinetobacter species. Aminoglycosides such as amikacin, netilmicin were most active against the MDR isolates tested (60% susceptibility. Ceftazidime was more active than cefotaxime. MDR A. baumannii strains were susceptible only to amikacin, netilmicin and ceftadizime. Ciprofloxacin had poor activity irrespective of isolates belonging to different DNA groups tested (58% resistance overall, 79% among A. baumannii. Strains of Biotypes 6 and 19 of A. baumannii showed broader resistance than those of biotype 10 and others. CONCLUSIONS: Strains of A. baumannii from patients in our hospital, were generally more resistant to quinolones, -lactam antibiotics, first and second generation cephalosporins and partially resistant to third generation cephalosporins and aminoglycosides. The strains belonging to other DNA groups of Acinetobacter were comparatively less resistant than A.baumannii, except ciprofloxacin. This study suggests that, a combination therapy, using a third generation cephalosporin and amikacin, would be best choice for treating Acinetobacter infections.

  15. Occurrence and fate of quinolone and fluoroquinolone antibiotics in a municipal sewage treatment plant.

    Science.gov (United States)

    Jia, Ai; Wan, Yi; Xiao, Yang; Hu, Jianying

    2012-02-01

    This study developed a method for analysis of nineteen quinolone and fluoroquinolone antibiotics (FQs) in sludge samples, and investigated the occurrence and fate of the FQs in a municipal sewage treatment plant (STP) with anaerobic, anoxic, and aerobic treatment processes. Eleven compounds, including pipemidic acid, fleroxacin, ofloxacin, norfloxacin, ciprofloxacin, enrofloxacin, lomefloxacin, sparfloxacin, gatifloxacin, moxifloxacin, and sarafloxacin (only in sludge), were detected in the STP. The predominance of ofloxacin and norfloxacin, followed by lomefloxacin, ciprofloxacin, gatifloxacin, and moxifloxacin, were found in wastewater, suspended solids, and sludge. The total concentrations of FQs were 2573 ± 241 ng/L, 1013 ± 218 ng/L, and 18.4 ± 0.9 mg/kg in raw sewage, secondary effluent, and sludge, respectively. Extremely low mass change percentages were observed for FQs in anaerobic, anoxic, and aerobic treatment units, suggesting biodegradation to be of minor importance in the removal of FQs in STPs. 50-87% of the initial FQs loadings (except for pipemidic acid (36%)) were ultimately found in the dewatered sludge. Mean removal efficiencies of FQs in the STP were 56-75%, except for new generation drugs such as moxifloxacin (40 ± 5%) and gatifloxacin (43 ± 13%). A significant positive correlation was found between removal efficiencies and K(d) of FQs. The major factor in the removal of FQs in the STP was sorption to sludge, which was not governed by hydrophobic interactions. The long-term cycling and persistence of FQs in the STP has made activated sludge as a huge reservoir of FQ antibiotics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Plasmid-mediated quinolone resistance in typhoidal Salmonellae: A preliminary report from South India

    Directory of Open Access Journals (Sweden)

    V K Geetha

    2014-01-01

    Full Text Available Background: Fluoroquinolones are the drugs extensively employed for the treatment of Salmonella infections. Over the couple of decades that have elapsed since the introduction of fluoroquinolones, resistance to these agents by Enterobacteriaceae family members has become common and widespread. Although fluoroquinolone resistance is mediated by genomic DNA (deoxyribonucleic acid as well as plasmid DNA, the plasmid-mediated quinolone resistance (PMQR facilitates higher level resistance by interacting with genomic mechanism and is capable of horizontal spread. Materials and Methods: During a period of 1-year, 63 typhoidal Salmonellae were isolated from 14,050 blood cultures and one parietal wall abscess. 36 (56.25% were Salmonella Typhi and 27 (42% were Salmonella Paratyphi A. They were all screened for resistance by the disc diffusion method and their minimum inhibitory concentrations were determined using agar dilution, broth dilution and E-strip method. Ciprofloxacin resistant isolates were screened for PMQR determinants by polymerase chain reaction assay. Results: All the 63 isolates were resistant to nalidixic acid. Among the 36 S. Typhi isolates 20 were resistant to ciprofloxacin, of which 14 carried the plasmid gene qnrB and one carried the aac(6′-Ib-cr gene. qnrA and qnrS genes were not detected. Ciprofloxacin resistance was not seen in any of the S. Paratyphi A isolates. Conclusion: The antibiotic sensitivity pattern of typhoidal Salmonellae shows an increasing trend of PMQR. The allele B of qnr gene was found to be the predominant cause of PMQR in this study.

  17. 喹诺酮类药物临床应用及不良反应%Clinical application of quinolone antibiotics and analysis of adverse reactions

    Institute of Scientific and Technical Information of China (English)

    戴丽

    2012-01-01

    OBJECTIVE To analyze the structure feature of quinolone antibacterials, antibacterial spectrum and clinical application and adverse reactions. METHODS The clinical prescriptions on quinolone antibacterial statistics in 2010 were analyzed, including the drug using times, frequency and sorting, as well as the using purpose of quinolone drugs and the effects. RESULTS The quinolone drug using frequency = appearing times of a drug on prescriptions/total number of prescriptions. The top three antibiotics most frequently used were nofloxacin, ciprofloxacin and ofloxacin, which were widely used and accounted for 85. 3% of quinolone prescription drugs on prescriptions. CONCLUSION Quinolone drugs are important antibiotics which should be used reasonably and standardly to avoid adverse drug reactions.%目的 对喹诺酮类抗菌药物的结构特点、抗菌谱及临床应用范围、不良反应进行分析.方法 对医院2010年喹诺酮类抗菌药物临床处方进行统计,分析其药品临床使用处方数、频率和排序及喹诺酮类药物的用途及作用.结果 喹诺酮类药物使用频率=药品处方数/药品总处方数,其中使用频率最高的前3位为诺氟沙星、依诺沙星和氧氟沙星,占喹诺酮类抗菌药物处方总量的85.3%,在抗菌药物中运用广泛.结论 喹诺酮类在抗菌药物中占有重要地位,应规范、合理应用,防止造成药物不良反应.

  18. Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 8-chloro-4-hydroxyl-2-quinolone

    Science.gov (United States)

    Yahyazadeh, Asieh; Yousefi, Hessamoddin

    2014-01-01

    In this study, 8-chloro-4-hydroxyl-2-quinolone was synthesized from cyclocondensation of corresponding dianilide and subsequently used as a potent coupling component with some diazotized heterocyclic amines. These compounds were characterized by UV-vis, FT-IR, 1H NMR spectroscopic techniques and elemental analysis. Absorption spectra of these dyes were measured in six polar solvents and discussed with respect to the nature of solvents and substituted groups. The effects of acid, base, temperature and concentration on the visible absorption spectra of the dyes were reported. In addition, the antimicrobial activity of the dyes was explored in detail.

  19. Isolation, molecular identification and quinolone-susceptibility testing of Arcobacter spp. isolated from fresh vegetables in Spain.

    Science.gov (United States)

    González, Ana; Bayas Morejón, Isidro Favián; Ferrús, María Antonia

    2017-08-01

    Some species of the Arcobacter genus are considered emerging foodborne and waterborne enteropathogens. However, the presence of Arcobacter spp. in vegetables very little is known, because most studies have focused on foods of animal origin. On the other hand, quinolones are considered as first-line drugs for the treatment of infection by campylobacteria in human patients, but few data are currently available about the resistance levels to these antibiotics among Arcobacter species. Therefore, the aim of this study was to investigate the presence and diversity of arcobacters isolated from fresh vegetables such as lettuces, spinaches, chards and cabbages. Resistance to quinolones of the isolates was also investigated. One hundred fresh vegetables samples purchased from seven local retail markets in Valencia (Spain) during eight months were analysed. The study included 41 lettuces, 21 spinaches, 34 chards and 4 cabbages. Samples were analysed by culture and by molecular methods before and after enrichment. By culture, 17 out of 100 analysed samples were Arcobacter positive and twenty-five isolates were obtained from them. Direct detection by PCR was low, with only 4% Arcobacter spp. positive samples. This percentage increased considerably, up 20%, after 48 h enrichment. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), 17 out of the 25 isolates were identified as A. butzleri and 8 as A. cryaerophilus. Only two A. butzleri isolates showed resistance to levofloxacin and ciprofloxacin. The sequencing of a fragment of the QRDR region of the gyrA gene from the quinolones-resistant isolates revealed the presence of a mutation in position 254 of this gene (C-T transition). This study is the first report about the presence of pathogenic species of Arcobacter spp. in chards and cabbages and confirms that fresh vegetables can act as transmission vehicle to humans. Moreover, the presence of A. butzleri quinolone resistant in vegetables could

  20. Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae.

    Science.gov (United States)

    Bernard, J; Armand-Lefèvre, L; Luce, E; El Mniai, A; Chau, F; Casalino, E; Andremont, A; Ruppé, E

    2016-07-01

    Emergence of resistant Enterobacteriaceae in the intestinal microbiota during antibiotic treatment is well documented but its early dynamic is not. Here, we compared the densities of total Enterobacteriaceae and relative abundance (RA) of quinolone-resistant Enterobacteriaceae (QRE) in the first stool passed by patients who had a short exposure to levofloxacin (levofloxacin, n=12) or not (control, n=8). Mean densities (SD) (log CFU/g stool) of total Enterobacteriaceae were lower in the levofloxacin group than in the control group-3.4 (1.6) versus 6.7 (1.7), respectively, p Enterobacteriaceae and the QRE-RA.

  1. Simultaneous Quantification of Limonin, Two Indolequinazoline Alkaloids, and Four Quinolone Alkaloids in Evodia rutaecarpa (Juss.) Benth by HPLC-DAD Method

    OpenAIRE

    Pei-ting Zhang; Bi-yan Pan; Qiong-feng Liao; Mei-cun Yao; Xin-jun Xu; Jin-zhi Wan; Dan Liu; Zhi-yong Xie

    2013-01-01

    A simple and efficient HPLC-DAD (225 nm) method was developed and validated for the simultaneous determination of limonin and six key alkaloids (evodiamine, rutaecarpine, 1-methyl-2-undecyl-4(1H)-quinolone, evocarpine, 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone, and dihydroevocarpine) in Evodia rutaecarpa (Juss.) Benth, which has been widely used as one of the Traditional Chinese Medicines. The chromatographic separation was carried out on a Hypersil BDS C18 column, and gradient...

  2. Determination of quinolone residues in shrimp using liquid chromatography with fluorescence detection and residue confirmation by mass spectrometry.

    Science.gov (United States)

    Karbiwnyk, Christine M; Carr, Lori E; Turnipseed, Sherri B; Andersen, Wendy C; Miller, Keith E

    2007-07-23

    The quinolones, oxolinic acid (OXO), flumequine (FLU), and nalidixic acid (NAL), are antibacterial drugs effective against gram-negative bacteria. Quinolones are used in both human and veterinary medicine, but are currently not approved by the U.S. Food and Drug Administration for use in food fish. A liquid chromatography-fluorescence (LC-FL) method was developed to determine OXO, FLU, and NAL residues in shrimp. An additional liquid chromatography-mass spectrometry (LC-MS(n)) method was created to confirm these residues using the same sample extract. Samples were prepared with a simple ethyl acetate extraction followed by solvent exchange into 0.2% formic acid and cleaned-up with hexane. Reverse phase chromatography was used to separate the three compounds in both procedures. For the LC-FL determinative method, fluorescence emission was monitored at 369 nm with excitation at 327 nm. With electrospray ionization, the three most abundant ions from the MS3 product ion spectrum were used to identify OXO, FLU, and NAL in the confirmation procedure. Shrimp samples fortified at levels ranging from 7.5 to 100 ng g(-1) were used to validate both methods.

  3. Identification of the main quinolone resistance determinant in Campylobacter jejuni and Campylobacter coli by MAMA-DEG PCR.

    Science.gov (United States)

    Hormeño, Lorena; Palomo, Gonzalo; Ugarte-Ruiz, María; Porrero, M Concepción; Borge, Carmen; Vadillo, Santiago; Píriz, Segundo; Domínguez, Lucas; Campos, Maria J; Quesada, Alberto

    2016-03-01

    Among zoonotic diseases, campylobacteriosis stands out as the major bacterial infection producing human gastroenteritis. Antimicrobial therapy, only recommended in critical cases, is challenged by resistance mechanisms that should be unambiguously detected for achievement of effective treatments. Quinolone (ciprofloxacin) resistance of Campylobacter jejuni and Campylobacter coli, the 2 main Campylobacter detected in humans, is conferred by the mutation gyrA C-257-T, which can be genotyped by several methods that require a previous identification of the pathogen species to circumvent the sequence polymorphism of the gene. A multiplex PCR, based on degenerated oligonucleotides, has been designed for unambiguous identification of the quinolone resistance determinant in Campylobacter spp. isolates. The method was verified with 249 Campylobacter strains isolated from humans (141 isolates) and from the 3 most important animal sources for this zoonosis: poultry (34 isolates), swine (38 isolates), and cattle (36 isolates). High resistance to ciprofloxacin, MIC above 4μg/mL, linked to the mutated genotype predicted by MAMA-DEG PCR (mismatch amplification mutation assay PCR with degenerated primers) was found frequently among isolates from the different hosts.

  4. Synthesis of chromone, quinolone, and benzoxazinone sulfonamide nucleosides as conformationally constrained inhibitors of adenylating enzymes required for siderophore biosynthesis.

    Science.gov (United States)

    Engelhart, Curtis A; Aldrich, Courtney C

    2013-08-02

    MbtA catalyzes the first committed step of mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) and is responsible for the incorporation of salicylic acid into the mycobactin siderophores. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS) is an extremely potent nucleoside inhibitor of MbtA that possesses excellent activity against whole-cell Mtb but suffers from poor bioavailability. In an effort to improve the bioavailability, we have designed four conformationally constrained analogues of Sal-AMS that remove two rotatable bonds and the ionized sulfamate group on the basis of computational and structural studies. Herein we describe the synthesis, biochemical, and microbiological evaluation of chromone-, quinolone-, and benzoxazinone-3-sulfonamide derivatives of Sal-AMS. We developed new chemistry to assemble these three heterocycles from common β-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a β-ketosulfonamide employing dimethylformamide dimethyl acetal to afford an enaminone that can react intramolecularly with a phenol or intermolecularly with a primary amine via addition-elimination reaction(s). The benzoxazinone-3-sulfonamide was prepared by nitrosation of a β-ketosulfonamide followed by intramolecular nucleophilic aromatic substitution. Mitsunobu coupling of these bicyclic sulfonamides with a protected adenosine derivative followed by global deprotection provides a concise synthesis of the respective inhibitors.

  5. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

    Directory of Open Access Journals (Sweden)

    Ivan Laponogov

    Full Text Available The 2.7 A crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo IV subunit A (ParC from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a 'closed' dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA, but distinct from the 'open' gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts.

  6. A series of novel 1D coordination polymers constructed from metal?quinolone complex fragments linked by aromatic dicarboxylate ligands

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Yan, Shi-Wei; Sun, Dian-Zhen; Chen, Hai-Yan; Wang, Xin; Yang, Juan; Ye, Zhong-Li; Yuan, Ruo; Wang, En-Bo

    2012-08-01

    Self-assembly of quinolones with metal salts in the presence of aromatic dicarboxylate ligands affords a series of novel 1D metal-quinolone complexes, namely [Mn(Hppa)(oba)]·3H2O (1), [Co(Hppa)(oba)]·3.25H2O (2), [Zn(Hppa)(sdba)]·1.5H2O (3), [Mn(Hcf)(bpda)(H2O)]·2H2O (4), [Mn(Hppa)2(bpdc)] (5) and [Mn(Hlome)2(bpdc)]·4H2O (6) (Hppa = Pipemidic acid, Hcf = ciprofloxacin, Hlome = lomefloxacin). The structures of compounds 1-3 consist of novel polymeric chains spanning two different directions, which display an intriguing 1D → 3D inclined polycatenation of supramolecular ladders. Compound 4 exhibits a chain compound formed from the interconnection of [Mn2(Hcf)2(μ-CO2)2] dimers with bpda ligands. Compounds 5 and 6 are similar chain compounds constructed from [Mn(Hppa)2] (or [Mn(Hlome)2]) fragments linked by bpdc ligands. The magnetic properties of 4 have been studied, which indicate the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compound 3 are discussed.

  7. Synthesis and biological evaluation of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives as potential topoisomerase I inhibitors.

    Science.gov (United States)

    Ge, Raoling; Zhao, Qian; Xie, Zhouling; Lu, Lu; Guo, Qinglong; Li, Zhiyu; Zhao, Li

    2016-10-21

    The design and synthesis of a new series of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives, built on the structure of 1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone, are described. These compounds provide new scaffold for the discovery of Topoisomerase I (Top I) inhibitors and target based assay showed that they can obviously inhibited Top I at 100 μM. The in vitro anti-proliferative activity of these new compounds was evaluated against A549, Hela, BGC-823, and HepG2 cell lines. Compounds 18a-g showed potent inhibitory activity against the growth of those cancer cell lines. The most positive compounds 18f and 18g demonstrated as potent as camptothecin in Top I inhibition assay and MTT assay. Compounds 18f and 18g led to an obvious increase in the percentage of S phase of the cells in 24 h. The in vivo data showed that 18f and 18g inhibited tumor growth with the inhibitory rate of 29.25% and 42.75% at 20 mg/kg, respectively. The data suggested the therapeutic potential for further development.

  8. Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolone.

    Science.gov (United States)

    Li, Qing; Xing, Junhao; Cheng, Haibo; Wang, Hui; Wang, Jing; Wang, Shuai; Zhou, Jinpei; Zhang, Huibin

    2015-01-01

    A novel series of 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolones 6a-o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram-positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram-positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2-hydroxy-3-(nitroimidazolyl)-propyl group formed two additional hydrogen bonds.

  9. Environment-sensitive quinolone demonstrating long-lived fluorescence and unusually slow excited-state intramolecular proton transfer kinetics

    Science.gov (United States)

    Zamotaiev, O. M.; Shvadchak, V.; Sych, T. P.; Melnychuk, N. A.; Yushchenko, D.; Mely, Y.; Pivovarenko, V. G.

    2016-09-01

    A new small fluorescent dye based on 3-hydroxybenzo[g]quinolone, a benzo-analogue of Pseudomonas quinolone signal species, has been synthesized. The dye demonstrates interesting optical properties, with absorption in the visible region, two band emission due to an excited-state intramolecular proton transfer (ESIPT) reaction and high fluorescence quantum yield in both protic and aprotic media. Time-resolved fluorescence spectroscopy shows that the ESIPT reaction time is unusually long (up to 8 ns), indicating that both forward and backward ESIPT reactions are very slow in comparison to other 3-hydroxyquinolones. In spite of these slow rate constants, the ESIPT reaction was found to show a reversible character as a result of the very long lifetimes of both N* and T* forms (up to 16 ns). The ESIPT reaction rate is mainly controlled by the hydrogen bond donor ability in protic solvents and the polarity in aprotic solvents. Using large unilamellar vesicles and giant unilamellar vesicles of different lipid compositions, the probe was shown to preferentially label liquid disordered phases.

  10. Enzyme-mediated quenching of the Pseudomonas quinolone signal (PQS promotes biofilm formation of Pseudomonas aeruginosa by increasing iron availability

    Directory of Open Access Journals (Sweden)

    Beatrix Tettmann

    2016-12-01

    Full Text Available The 2-alkyl-3-hydroxy-4(1H-quinolone 2,4-dioxygenase HodC was previously described to cleave the Pseudomonas quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS system of Pseudomonas aeruginosa, an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of P. aeruginosa attenuated production of virulence factors, and reduced virulence in planta. However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of P. aeruginosa to be responsible for HodC degradation. In static biofilms of the P. aeruginosa PA14 lasB::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as pvdS, pvdL, pvdA and pvdQ. This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating P. aeruginosa biofilms.

  11. A rapid and sensitive resonance Rayleigh scattering spectra method for the determination of quinolones in human urine and pharmaceutical preparation.

    Science.gov (United States)

    Qiao, Man; Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Zhu, Jinghui; Hu, Xiaoli

    2015-03-01

    A new method based on resonance Rayleigh scattering (RRS) was proposed for the determination of quinolones (QNS) at the nanogram level. In pH 3.3-4.4 Britton-Robinson buffer medium, quinolones such as ciprofloxacin, pipemidic acid (PIP), lomefloxacin (LOM), norfloxacin (NOR) and sarafloxacin (SAR) were protonated and reacted with methyl orange (MO) to form an ion-pair complex, which then further formed a six-membered ring chelate with Pd(II). As a result, new RRS spectra appeared and the RRS intensities were enhanced greatly. RRS spectral characteristics of the MO-QNS-Pd(II) systems, the optimum conditions for the reaction, and the influencing factors were investigated. Under optimum conditions, the scattering intensity (∆I) increments were directly proportional to the concentration of QNS with in certain ranges. The method had high sensitivity, and the detection limits (3σ) ranged from 6.8 to 12.6 ng/mL. The proposed method had been successfully applied for the determination of QNS in pharmaceutical formulations and human urine samples. In addition, the mechanism of the reaction system was discussed based on IR, absorption and fluorescence spectral studies. The reasons for the enhancement of scattering spectra were discussed in terms of fluorescence-scattering resonance energy transfer, hydrophobicity and molecular size.

  12. Study of the quenching effect of quinolones over CdTe-quantum dots using sequential injection analysis and multicommutation.

    Science.gov (United States)

    Molina-García, L; Llorent-Martínez, E J; Fernández-de Córdova, M L; Santos, J L M; Rodrigues, S S M; Ruiz-Medina, A

    2013-06-01

    The field of light-emitting nanoparticles has experienced an enormous development over the past two decades. The fluorescence of these nanometer-size crystalline particles, called quantum dots (QDs), can be both quenched and enhanced by different compounds. Since a high percentage of articles related to QDs are focused on theoretical studies, the development of analytical methods with real applications is an important step in order to progressively demonstrate the versatility of these particles. Moreover, taking into account that most of the QDs-based analytical methods are non-automated, the development of automated flow methodologies is still a field that presents an important analytical potential. With this purpose, two automatic methodologies, multicommutated flow injection analysis and sequential injection analysis, have been here applied to the analysis of quinolones in pharmaceutical formulations, making use of the quenching effect caused by the analytes over mercaptopropionic acid-capped CdTe QDs fluorescence. Both methodologies were compared in terms of versatility, sample throughput, sensitivity, etc., and applied to the determination of five quinolones in pharmaceutical preparations available in the Spanish Pharmacopoeia. The detection limits ranged between 26 and 50μmolL(-1), and Relative Standard Deviations lower than 3% were observed in all cases.

  13. QapR (PA5506) represses an operon that negatively affects the Pseudomonas quinolone signal in Pseudomonas aeruginosa.

    Science.gov (United States)

    Tipton, Kyle A; Coleman, James P; Pesci, Everett C

    2013-08-01

    Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that can cause disease in varied sites within the human body and is a significant source of morbidity and mortality in those afflicted with cystic fibrosis. P. aeruginosa is able to coordinate group behaviors, such as virulence factor production, through the process of cell-to-cell signaling. There are three intercellular signaling systems employed by P. aeruginosa, and one of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). PQS is required for virulence in multiple infection models and has been found in the lungs of cystic fibrosis patients colonized by P. aeruginosa. In this study, we have identified an RpiR family transcriptional regulator, QapR, which is an autoregulatory repressor. We found that mutation of qapR caused overexpression of the qapR operon. We characterized the qapR operon to show that it contains genes qapR, PA5507, PA5508, and PA5509 and that QapR directly controls the transcription of these genes in a negative manner. We also show that derepression of this operon greatly reduces PQS concentration in P. aeruginosa. Our results suggest that qapR affects PQS concentration by repressing an enzymatic pathway that acts on PQS or a PQS precursor to lower the PQS concentration. We believe that this operon comprises a novel mechanism to regulate PQS concentration in P. aeruginosa.

  14. Molecular characterization of quinolone resistance mechanisms and extended-spectrum β-lactamase production in Escherichia coli isolated from dogs.

    Science.gov (United States)

    Meireles, D; Leite-Martins, L; Bessa, L J; Cunha, S; Fernandes, R; de Matos, A; Manaia, C M; Martins da Costa, P

    2015-08-01

    The increasing prevalence of antimicrobial resistances is now a worldwide problem. Investigating the mechanisms by which pets harboring resistant strains may receive and/or transfer resistance determinants is essential to better understanding how owners and pets can interact safely. Here, we characterized the genetic determinants conferring resistance to β-lactams and quinolones in 38 multidrug-resistant Escherichia coli isolated from fecal samples of dogs, through PCR and sequencing. The most frequent genotype included the β-lactamase groups TEM (n=5), and both TEM+CTX-M-1 (n=5). Within the CTX-M group, we identified the genes CTX-M-32, CTX-M-1, CTX-M-15, CTX-M-55/79, CTX-M-14 and CTX-M-2/44. Thirty isolates resistant to ciprofloxacin presented two mutations in the gyrA gene and one or two mutations in the parC gene. A mutation in gyrA (reported here for the first time), due to a transversion and transition (TCG→GTG) originating a substitution of a serine by a valine in position 83 was also detected. The plasmid-encoded quinolone resistance gene, qnrs1, was detected in three isolates. Dogs can be a reservoir of genetic determinants conferring antimicrobial resistance and thus may play an important role in the spread of antimicrobial resistance to humans and other co-habitant animals.

  15. Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada

    Directory of Open Access Journals (Sweden)

    Melano Roberto

    2010-01-01

    Full Text Available Abstract Background The objective of this study was to examine Streptococcus pneumoniae isolates collected from a longitudinal surveillance program in order to determine their susceptibility to currently used fluoroquinolones and of the frequency and type of mutations in the quinolone-resistant determining regions (QRDRs of their parC and gyrA genes. Methods The Canadian Bacterial Surveillance Network has been collecting clinical isolates of S. pneumoniae from across Canada since 1988. Broth microdilution susceptibility testing was carried out according to the Clinical and Laboratory Standards Institute guidelines. The QRDRs of the parC and gyrA genes were sequenced for all isolates with ciprofloxacin MIC ≥ 4 mg/L, and a large representative sample of isolates (N = 4,243 with MIC ≤ 2 mg/L. Results A total of 4,798 out of 30,111 isolates collected from 1988, and 1993 to 2007 were studied. Of those isolates that were successfully sequenced, 184 out of 1,032 with mutations in parC only, 11 out of 30 with mutations in gyrA only, and 292 out of 298 with mutations in parC and gyrA were considered resistant to ciprofloxacin (MIC ≥ 4 mg/L. The most common substitutions in the parC were at positions 137 (n = 722, 79 (n = 209, and 83 (n = 56, of which substitutions at positions 79 and 83 were associated with 4-fold increase in MIC to ciprofloxacin, whereas substitutions at position 137 had minimal effect on the ciprofloxacin MIC. A total of 400 out of 622 isolates with Lys-137 parC mutation belonged to serotypes 1, 12, 31, 7A, 9V, 9N and 9L, whereas only 49 out of 3064 isolates with no mutations belonged to these serotypes. Twenty-one out of 30 isolates with substitutions at position 81 of the gyrA gene had an increased MIC to ciprofloxacin. Finally, we found that isolates with mutations in both parC and gyrA were significantly associated with increased MIC to fluoroquinolones. Conclusions Not all mutations, most frequently Lys-137, found in the

  16. In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan.

    Science.gov (United States)

    Kawai, Yasuhiro; Nakura, Yukiko; Wakimoto, Tetsu; Nomiyama, Makoto; Tokuda, Tsugumichi; Takayanagi, Toshimitsu; Shiraishi, Jun; Wasada, Kenshi; Kitajima, Hiroyuki; Fujita, Tomio; Nakayama, Masahiro; Mitsuda, Nobuaki; Nakanishi, Isao; Takeuchi, Makoto; Yanagihara, Itaru

    2015-04-01

    Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L-GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan.

  17. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Studies of the Mode of Action in Staphylococcus aureus▿

    Science.gov (United States)

    Robertson, Gregory T.; Bonventre, Eric J.; Doyle, Timothy B.; Du, Qun; Duncan, Leonard; Morris, Timothy W.; Roche, Eric D.; Yan, Dalai; Lynch, A. Simon

    2008-01-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections. PMID:18443108

  18. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.

    Science.gov (United States)

    Robertson, Gregory T; Bonventre, Eric J; Doyle, Timothy B; Du, Qun; Duncan, Leonard; Morris, Timothy W; Roche, Eric D; Yan, Dalai; Lynch, A Simon

    2008-07-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.

  19. Analysis of 155 reports of ADR Induced by Quinolones%155例喹诺酮类药品不良反应分析

    Institute of Scientific and Technical Information of China (English)

    钟晗; 刘晓琰; 崔敏; 苏颖杰

    2013-01-01

    目的 研究喹诺酮类药物在临床治疗中发生的不良反应(ADR)情况,寻找应对该类药物ADR的临床策略.方法 采用回顾性研究方法,对我院2004~2011年上报的喹诺酮类药物ADR进行系统分析.结果 155例ADR报表中涉及9种喹诺酮类药物,左氧氟沙星ADR例次最多(105例次).主要不良反应表现为过敏反应(40.4%)和消化系统症状(27.1%).结论 对喹诺酮类药物的临床应用需加强监测,促进合理用药.%Objective To determine adverse drug reaction (ADR) occurrence associated with quinolones in clinical practices. Methods 155 reports of quinolones-induced ADR from 2010 to 2011 were analyzed. Results Nine drugs of quinolones were involved in 155 ADR reports, among which levofloxacin resulted in ADR most frequently(105 cases). The ADRs manifestations mainly covered allergies(40.4%) and digestive system disease symptoms(27.1%). Conclusion It is necessary to monitor clinical application of quinolones, therefore promote rational use of drug.

  20. 喹诺酮类药物的严重不良反应及合理应用%Serious ADRs of Quinolones and TheirRational Use

    Institute of Scientific and Technical Information of China (English)

    付铁梅; 田丽娟

    2011-01-01

    目的 促进喹诺酮类药物的合理使用,减少药品不良反应和耐药性的发生.方法 通过查阅文献等,对喹诺酮类药物的严重不良反应及产生原因进行分析,并提出合理使用的对策建议.结果 与结论随着喹诺酮类药物临床使用量不断增加,其严重药品不良反应的发生也越来越多.临床用药,一定要增强合理用药意识,确保患者用药安全有效.%Objective To promote the rational use of quinolones to reduce serious adverse drug reactions (ADRs) and occurrence of resistance to qmnolones. Methods The literature review was conducted to analyze the serious ADRs of quinolones and their causes, and the countermeasures of their rational use were proposed. Results and Conclusion As the clinical use of quinolones increasing, serious ADRs occur more and more, Both doctors and patients should enhance Erie awareness of rational use of quinolones to reduce the serious ADRs and ensure lhe safe and effective drug use m patients.

  1. 沙眼衣原体对喹诺酮类耐药机制的进展%Update on the mechanism of Chlamydia trachomatis resistance to quinolones

    Institute of Scientific and Technical Information of China (English)

    杨晓静; 刘全忠

    2009-01-01

    Quinolones are commonly used to treat Chlamydiatra chomatis inection in clinic at present.However,the resistance of Chlamydia trachomatis to quinolones has been increasingly reported.It has becn shown that the resistance is related to point mutations in the quinolone-resistance-determinning region of DNA gyrase gene and topoisomerase IV subunit genes.These mutations are located most commonly at Ser-83,less frequently at Asp-87.There are also some other mechanisms underlying the resistance.Further studies are needed for the elucidation of exact mechanism of Chlamydia trachomatis resistance to quinolones.%喹诺酮类药物目前在临床上常用于治疗沙眼衣原体感染,但近年来有关沙眼衣原体对其耐药的报道不断出现.研究发现,喹诺酮类耐药的产生与DNA回旋酶和拓扑异构酶Ⅳ亚单位基因的喹诺酮耐药决定区域的点突变有关.最常见的突变位于Ser-83,少数情况下位于Asp-87,还有一些其他可能的耐药机制.沙眼衣原体对喹诺酮类耐药的确切机制尚待进一步研究.

  2. Research progress on the metal complexes of quinolone drug ligands%喹诺酮类药物金属配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    Objective The article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes, in order to provide a foundation for further research. Methods The ralated literatures were summarized. Results The development of the research of the quinolone drug metal complexes is fast,but exists many questions. Conclusion Some suggestions of the in-depth research of the quinolone drug metal complexes are presented.%目的 对喹诺酮类药物的发展过程及其金属配合物的配位结构和活性等方面进行综述,为进一步研究喹诺酮类药物金属配合物提供科学依据.方法 对相关文献进行归纳、总结和综述.结果 喹诺酮类药物金属配合物的研究取得较快发展,但还存在着许多有待解决的问题.结论 展望了喹诺酮类药物金属配合物研究的发展趋势.

  3. [Simultaneous determination of 11 quinolones in hotpot ingredients by dispersive solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Cao, Peng; Mou, Yan; Gao, Fei; Geng, Jinpei; Zhang, Xiqing; Sui, Tao; Liang, Junni; Sha, Meilan; Guan, Lili

    2013-09-01

    A method for the simultaneous determination of the residues of 11 quinolones in hotpot ingredients by quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and ultra performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was established. The sample was extracted with acetonitrile (containing 5% formic acid) and followed by stratifying with a salting-out agent. Clean-up of the extracts was processed by C18 and PSA, a modified QuEChERS procedure. The analytes were then separated on a Poroshell 120 EC-C18 column, and finally detected by tandem mass spectrometry in positive ESI mode. The linearity of all the 11 quinolones in the range from 1.0 to 100.0 microg/kg had correlation coefficients greater than 0.998. The limits of detection (LOD) of the method were from 1.8 to 3.1 microg/kg and the limits of quantification (LOQ) were from 6.0 to 10.3 microg/kg. The average recoveries of the 11 quinolones were in the range from 70.1% to 100.3%, with relative standard deviations from 2.42% to 10.88%. The established method is sensitive and of good recoveries. It can be applied as a rapid and reliable method for the determination of the 11 quinolones in hotpot ingredients.

  4. 4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni.

    Science.gov (United States)

    Sáenz, Fabián E; Lacrue, Alexis N; Cross, R Matthew; Maignan, Jordany R; Udenze, Kenneth O; Manetsch, Roman; Kyle, Dennis E

    2013-12-01

    Malaria kills approximately 1 million people a year, mainly in sub-Saharan Africa. Essential steps in the life cycle of the parasite are the development of gametocytes, as well as the formation of oocysts and sporozoites, in the Anopheles mosquito vector. Preventing transmission of malaria through the mosquito is necessary for the control of the disease; nevertheless, the vast majority of drugs in use act primarily against the blood stages. The study described herein focuses on the assessment of the transmission-blocking activities of potent antierythrocytic stage agents derived from the 4(1H)-quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H)-quinolones (P4Qs), one 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), and one 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) were assessed for their transmission-blocking activity against the mosquito stages of the human malaria parasite (Plasmodium falciparum) and the rodent parasite (P. berghei). Results showed that all of the experimental compounds reduced or prevented the exflagellation of male gametocytes and, more importantly, prevented parasite transmission to the mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of sporozoites that reached the Anopheles salivary glands. These findings suggest that 4(1H)-quinolones, which have activity against the blood stages, can also prevent the transmission of Plasmodium to the mosquito and, hence, are potentially important drug candidates to eradicate malaria.

  5. Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis.

    Science.gov (United States)

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Uzelac, Lidija; Jarak, Ivana; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kralj, Marijeta; Tomić, Sanja; Karminski-Zamola, Grace

    2012-06-14

    A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties.

  6. Clinical application of a ligation-independent pathway of multiplex ligation-dependent probe amplification for the determination of quinolone susceptibility of Streptococcus pneumoniae.

    Science.gov (United States)

    Uno, Naoki; Araki, Nobuko; Kaku, Norihito; Kosai, Kosuke; Hasegawa, Hiroo; Yanagihara, Katsunori

    2016-09-01

    We previously uncovered a ligation-independent pathway of multiplex ligation-dependent probe amplification (MLPA) through which products of MLPA could be amplified without both hybridization and ligation reactions. Here, we utilized this pathway to detect an antibiotic resistance mutation of quinolones in Streptococcus pneumoniae.

  7. 我院门诊喹诺酮类药物临床应用调查%Investigation on Clinical Use of Quinolones in Outpatient Clinic

    Institute of Scientific and Technical Information of China (English)

    田雪莉; 周霞

    2011-01-01

    Objective To understand the use status of quinolone- related drugs in the outpatient clinic for standardizing rational drug use in clinic. Methods The prescriptions involving quinolone- related drugs in the outpatient clinic were extracted and statistically analyzed in aspects of disease category, age, drug variety and rationality of drug use. Results Quinolone medication accounted for 21.50% of all antibiotic uses in the outpatient clinic. 43.06% of quinolones were used for respiratory diseases. Among them, levofloxacin had the highest use frequency(48.79% ). Unreasonable prescriptions included the use of quinolones for the patients yomger than 18 years old and without clear diagnosis of infectious diseases. Conclusion Quinolones are commonly used in anti- infection treatment in the outpatient clinic. The use indicators are rationally grasped as a whole. But using quinolones in children still exists, which should be needed to pay attention. The dosage in different ages has no apparent difference. The medieation dose in elderly patients should be adjusted.%目的 了解医院门诊喹诺酮类药物的使用情况,规范临床合理用药.方法 抽取喹诺酮类药物的处方,从痛种、患者年龄、用药品种、用药合理性等方面进行统计分析.结果 喹诺酮类药物的使用占全部抗茵药物的21.50%,43.06%用于呼吸系统疾病,其中左氧氟沙星使用频率最高(占喹诺酮类的48.79%).不合理用药包括18岁以下儿童用药、无感染性疾病诊断用药等.结论 喹诺酮类药物在医院门诊抗感染治疗中比较常见,应用指征掌握基本合理,但仍存在儿童用药,应予以重视.不同年龄用量差异不明显,对老年患者用药应进行剂量调整.

  8. Characterization of CTX-M enzymes, quinolone resistance determinants, and antimicrobial residues from hospital sewage, wastewater treatment plant, and river water.

    Science.gov (United States)

    Conte, Danieli; Palmeiro, Jussara Kasuko; da Silva Nogueira, Keite; de Lima, Thiago Marenda Rosa; Cardoso, Marco André; Pontarolo, Roberto; Degaut Pontes, Flávia Lada; Dalla-Costa, Libera Maria

    2017-02-01

    Multidrug-resistant (MDR) bacteria are widespread in hospitals and have been increasingly isolated from aquatic environments. The aim of the present study was to characterize extended-spectrum β-lactamase (ESBL) and quinolone-resistant Enterobacteriaceae from a hospital effluent, sanitary effluent, inflow sewage, aeration tank, and outflow sewage within a wastewater treatment plant (WWTP), as well as river water upstream and downstream (URW and DRW, respectively), of the point where the WWTP treated effluent was discharged. β-lactamase (bla) genes, plasmid-mediated quinolone resistance (PMQR), and quinolone resistance-determining regions (QRDRs) were assessed by amplification and sequencing in 55 ESBL-positive and/or quinolone-resistant isolates. Ciprofloxacin residue was evaluated by high performance liquid chromatography. ESBL-producing isolates were identified in both raw (n=29) and treated (n=26) water; they included Escherichia coli (32), Klebsiella pneumoniae (22) and Klebsiella oxytoca (1). Resistance to both cephalosporins and quinolone was observed in 34.4% of E. coli and 27.3% of K. pneumoniae. Resistance to carbapenems was found in 5.4% of K. pneumoniae and in K. oxytoca. Results indicate the presence of blaCTX-M (51/55, 92.7%) and blaSHV (8/55, 14.5%) ESBLs, and blaGES (2/55, 3.6%) carbapenemase-encoding resistance determinants. Genes conferring quinolone resistance were detected at all sites, except in the inflow sewage and aeration tanks. Quinolone resistance was primarily attributed to amino acid substitutions in the QRDR of GyrA (47%) or to the presence of PMQR (aac-(6')-Ib-cr, oqxAB, qnrS, and/or qnrB; 52.9%) determinants. Ciprofloxacin residue was absent only from URW. Our results have shown strains carrying ESBL genes, PMQR determinants, and mutations in the gyrA QRDR genes mainly in hospital effluent, URW, and DRW samples. Antimicrobial use, and the inefficient removal of MDR bacteria and antibiotic residue during sewage treatment, may

  9. Research progress on the metal complexes of quinolone drug ligands%金属与喹诺酮类药物构筑的配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    This article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes. Some suggestions of the quinolone drug metal complexes in-depth in the future were presented.%本文综述了喹诺酮类药物的发展过程,以及各种金属离子与该类药物构筑形成配合物晶体结构方面的研究进展,展望了此类研究的发展趋势.

  10. Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Tereza Cristina Rocha Moreira de Oliveira

    2010-07-01

    Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

  11. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

    KAUST Repository

    Bräuer, Alois

    2015-11-10

    © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

  12. Quinolone- and ß-lactam-resistance in Escherichia coli from Danish and Italian broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    , sock samples were collected from 10 parent flocks and 10 offspring flocks, according to the procedure currently used for the surveillance of Salmonella in the EU. Samples were enriched in McConkey broth and streaked on McConkey agar plates added with nalidixic acid (32 µg/ml), ciprofloxacin (2 µg...... on cephalosporin-resistant isolates. While resistance to ampicillin and nalidixic acid was widespread in both countries, resistance to ciprofloxacin and cephalosporins was more common among Italian flocks. In Denmark, ciprofloxacin resistance was only detected in one parent flock without any history of quinolone...... usage and none of the flocks was positive for cephalosporin-resistant E. coli. In Italy, resistance to ciprofloxacin was detected in all flocks and resistances to ceftiofur and cefotaxime were detected in five flocks. Primers specific for the CTX-M-type ESBLs generated PCR amplicons from isolates from...

  13. Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents.

    Science.gov (United States)

    Zhang, Ling; Addla, Dinesh; Ponmani, Jeyakkumar; Wang, Ao; Xie, Dan; Wang, Ya-Nan; Zhang, Shao-Lin; Geng, Rong-Xia; Cai, Gui-Xin; Li, Shuo; Zhou, Cheng-He

    2016-03-23

    A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.

  14. Optimal control of ultrafast laser driven many-electron dynamics in a polyatomic molecule: N-methyl-6-quinolone

    Science.gov (United States)

    Klamroth, Tillmann

    2006-04-01

    We report time-dependent configuration interaction singles calculations for the ultrafast laser driven many-electron dynamics in a polyatomic molecule, N-methyl-6-quinolone. We employ optimal control theory to achieve a nearly state-selective excitation from the S0 to the S1 state, on a time scale of a few (≈6) femtoseconds. The optimal control scheme is shown to correct for effects opposing a state-selective transition, such as multiphoton transitions and other, nonlinear phenomena, which are induced by the ultrashort and intense laser fields. In contrast, simple two-level π pulses are not effective in state-selective excitations when very short pulses are used. Also, the dependence of multiphoton and nonlinear effects on the number of states included in the dynamical simulations is investigated.

  15. Simultaneous determination of multiple (fluoro)quinolone antibiotics in food samples by a one-step fluorescence polarization immunoassay.

    Science.gov (United States)

    Mi, Tiejun; Wang, Zhanhui; Eremin, Sergei A; Shen, Jianzhong; Zhang, Suxia

    2013-10-02

    This paper describes a rapid one-step fluorescence polarization immunoassay (FPIA) for the simultaneous determination of multiple (fluoro)quinolone antibiotics (FQs) in food samples. Several fluorescent tracers were synthesized and evaluated in the FPIA method based on a broad-specificity of monoclonal antibodies toward FQs. The heterogeneous tracer, SAR-5-FAM, was considered as the optimal choice to prepare the immunocomplex single reagent, which allows a rapid and sensitive displacement reaction by addition of analytes. Optimized single-reagent FPIA exhibited broad cross-reactivities in the range of 7.8-172.2% with 16 FQs tested and was capable of determining most FQs at the level of maximum residue limits. Recoveries for spiked milk and chicken muscle samples were from 77.8 to 116%, with relative standard deviation lower than 17.4%. Therefore, this method could be applicable in routine screening analysis of multiple FQ residues in food samples.

  16. Adsorption of quinolone antibiotics in spherical mesoporous silica: Effects of the retained template and its alkyl chain length.

    Science.gov (United States)

    Liang, Zhijie; Zhaob, Zhiwei; Sun, Tianyi; Shi, Wenxin; Cui, Fuyi

    2016-03-15

    In this study, mesoporous silica (meso-silica) MCM-41 and those with the templates retained were synthesized and characterized. Adsorption capacities of the synthesized materials towards typical quinolone antibiotic pollutants, enrofloxacin and norfloxacin as representative, were investigated, and effects of the alkyl chain length of the templates on the adsorption capacity were evaluated. The results of this study indicated that the retained templates enhanced the adsorption capacities (Qmax) of the meso-silica MCM-41 toward hydrophobic enrofloxacin, but had an inhibitory effect on that towards hydrophilic norfloxacin, which were attributed to the hydrophobic inter-environment created by the long alkyl chains of the retained templates. Importantly, the adsorption capacity increased with the increase of the alkyl chain length of the retained templates. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Multidrug Resistance in Quinolone-Resistant Gram-Negative Bacteria Isolated from Hospital Effluent and the Municipal Wastewater Treatment Plant.

    Science.gov (United States)

    Vaz-Moreira, Ivone; Varela, Ana Rita; Pereira, Thamiris V; Fochat, Romário C; Manaia, Célia M

    2016-03-01

    This study is aimed to assess if hospital effluents represent an important supplier of multidrug-resistant (MDR) Gram-negative bacteria that, being discharged in the municipal collector, may be disseminated in the environment and bypassed in water quality control systems. From a set of 101 non-Escherichia coli Gram-negative bacteria with reduced susceptibility to quinolones, was selected a group of isolates comprised by those with the highest indices of MDR (defined as nonsusceptibility to at least one agent in six or more antimicrobial categories, MDR ≥6) or resistance to meropenem or ceftazidime (n = 25). The isolates were identified and characterized for antibiotic resistance phenotype, plasmid-mediated quinolone resistance (PMQR) genes, and other genetic elements and conjugative capacity. The isolates with highest MDR indices were mainly from hospital effluent and comprised ubiquitous bacterial groups of the class Gammaproteobacteria, of the genera Aeromonas, Acinetobacter, Citrobacter, Enterobacter, Klebsiella, and Pseudomonas, and of the class Flavobacteriia, of the genera Chryseobacterium and Myroides. In this group of 25 strains, 19 identified as Gammaproteobacteria harbored at least one PMQR gene (aac(6')-Ib-cr, qnrB, qnrS, or oqxAB) or a class 1 integron gene cassette encoding aminoglycoside, sulfonamide, or carbapenem resistance. Most of the E. coli J53 transconjugants with acquired antibiotic resistance resulted from conjugation with Enterobacteriaceae. These transconjugants demonstrated acquired resistance to a maximum of five classes of antibiotics, one or more PMQR genes and/or a class 1 integron gene cassette. This study shows that ubiquitous bacteria, other than those monitored in water quality controls, are important vectors of antibiotic resistance and can be disseminated from hospital effluent to aquatic environments. This information is relevant to support management options aiming at the control of this public health problem.

  18. Occurrence of plasmid-mediated quinolone resistance and virulence genes in avian Escherichia coli isolates from Algeria.

    Science.gov (United States)

    Laarem, Meradi; Barguigua, Abouddihaj; Nayme, Kaotar; Akila, Abdi; Zerouali, Khalid; El Mdaghri, Naima; Timinouni, Mohammed

    2017-02-28

    The emergence and spread of quinolone-resistant Escherichia coli in poultry products puts consumers at risk of exposure to the strains of E. coli that resist antibiotic treatment. The objective of this study was to define the prevalence and virulence potential of poultry-associated nalidixic acid (NAL)-resistant E. coli in the Annaba city, Algeria. In total, 33 samples of retail chicken meat were purchased from various butcher shops and examined for bacterial contamination with NAL-resistant E. coli. These isolates were subjected to antimicrobial susceptibility testing and were also investigated for the presence of plasmid-mediated quinolone resistance (PMQR) genes and virulence genes using conventional polymerase chain reaction (PCR) and DNA sequencing. Phylogenetic grouping of the NAL-resistant E. coli isolates was determined by the conventional multiplex PCR method. Twenty-nine (87.8%) products yielded NAL-resistant E. coli. Antibiograms revealed that 96.55% of NAL-resistant E. coli isolates were multidrug resistant (MDR). Resistance was most frequently observed against sulfamethoxazole-trimethoprim (96.6%), tetracycline (96.6%), ciprofloxacin (72%), and amoxicillin (65.5%). Group A was the most prevalent phylogenetic group, followed by groups D, B1, and B2. The PMQR determinants were detected in three isolates with qnrB72 and qnrS1 type identified. Four (13.8%) isolates carried one of the Shiga toxin E. coli-associated genes stx1, stx2, and ehxA alleles. The high prevalence of NAL-resistant E. coli isolated from retail chicken meat with detection of MDR E. coli harboring Shiga toxin genes in this study gives a warning signal for possible occurrence of foodborne infections with failure in antibiotic treatment.

  19. Quinolone resistant Aeromonas spp. as carriers and potential tracers of acquired antibiotic resistance in hospital and municipal wastewater.

    Science.gov (United States)

    Varela, Ana Rita; Nunes, Olga C; Manaia, Célia M

    2016-01-15

    Members of the genus Aeromonas are recognized carriers of antibiotic resistance in aquatic environments. However, their importance on the spread of resistance from hospital effluents to the environment is poorly understood. Quinolone resistant Aeromonas spp. (n = 112) isolated from hospital effluent (HE) and from raw (RWW) and treated wastewater (TWW) of the receiving urban wastewater treatment plant (UWTP) were characterized. Species identification and genetic intraspecies diversity were assessed based on the 16S rRNA, cpn60 and gyrB genes sequence analysis. The antibiotic resistance phenotypes and genotypes (qnrA, qnrB, qnrC, qnrD, qnrS, qnrVC; qepA; oqxAB; aac(6′)-Ib-cr; blaOXA; incU) were analyzed in function of the origin and taxonomic group. Most isolates belonged to the species Aeromonas caviae and Aeromonas hydrophila (50% and 41%, respectively). The quinolone and the beta-lactamase resistance genes aac(6′)-Ib-cr and blaOXA, including gene blaOXA-101, identified for the first time in Aeromonas spp., were detected in 58% and 56% of the isolates, respectively, with identical prevalence in HE and UWTP wastewater. In contrast, the gene qnrS2 was observed mainly in isolates from the UWTP (51%) and rarely in HE isolates (3%), suggesting that its origin is not the clinical setting. Bacterial groups and genes that allow the identification of major routes of antibiotic resistance dissemination are valuable tools to control this problem. In this study, it was concluded that members of the genus Aeromonas harboring the genes aac(6′)-Ib-cr and blaOXA are relevant tracers of antibiotic resistance dissemination in wastewater habitats, while those yielding the gene qnrS2 allow the traceability from non-clinical sources.

  20. Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus.

    Science.gov (United States)

    Takenouchi, T; Tabata, F; Iwata, Y; Hanzawa, H; Sugawara, M; Ohya, S

    1996-08-01

    The elevated expression of the norA gene is responsible for efflux-mediated resistance to quinolones in Staphylococcus aureus (E.Y.W. Ng, M. Trucksis, and D.C. Hooper, Antimicrob. Agents Chemother. 38:1345-1355, 1994). For S. aureus transformed with a plasmid containing the cloned norA gene, SA113(pTUS20) (H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, J. Bacteriol. 172:6942-6949, 1990), and an overexpressed mutant, SA-1199B (G.W. Kaatz, S.M. Seo, and C.A. Ruble, J. Infect. Dis. 163:1080-1086, 1991), the MICs of norfloxacin increased 16 and 64 times compared with its MICs for the recipient and wild-type strains, SA113 and SA-1199, respectively. MICs of CS-940, however, increased only two and eight times, even though these two fluoroquinolones are similarly hydrophilic (apparent logPs of approximately -1). No good correlation was found, among 15 developed and developing quinolones, between the increment ratio in MICs and hydrophobicity (r = 0.61). Analysis of the quantitative structure-activity relationship among 40 fluoroquinolones revealed that the MIC increment ratio was significantly correlated with the bulkiness of the C-7 substituent and bulkiness and hydrophobicity of the C-8 substituent of fluoroquinolones (r = 0.87) and not with its molecular hydrophobicity (r = 0.47). Cellular accumulation of norfloxacin in SA-1199B was significantly lower than that in SA-1199, and it was increased by addition of carbonyl cyanide m-chlorophenyl hydrazone. On the other hand, accumulations of CS-940 in these strains were nearly identical, and they were not affected by addition of the protonophore.

  1. Shyntesis and cytotoxicity evaluation in vitro of new compounds with hybrid structures of 8-flavoneacetic acid and quinolones; Sintesis y evaluacion citotoxica in vitro de nuevos compuestos con estructuras hibridas del acido 8-flavonacetico quinolonas

    Energy Technology Data Exchange (ETDEWEB)

    Biaa, M.F.; Castellano, J.M.; Emling, F.; Schlick, E. [Knoll, S.a., Madrid (Spain)

    1994-12-31

    Using the structural similarity between 8-flavoneacetic acid the antitumor quinolones, we have prepared some hybrid compounds on both systems and studied their cytotoxicity. None of the sinthesized compounds have shown sufficient interest for further development. 33 refs.

  2. Utilization of Quinolones in Our Hospital from 2009 to 2011%2009~2011年喹诺酮类药物应用分析

    Institute of Scientific and Technical Information of China (English)

    徐春燕

    2013-01-01

      目的探讨我院喹诺酮类药物的应用现状及趋势。方法采用限定日剂量方法,对我院2009~2011年喹诺酮类药物的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析。结果3年来,在口服喹诺酮类药物中,销售金额处于前三位的是加替沙星胶囊、左氧氟沙星胶囊、氟罗沙星胶囊;在注射喹诺酮类药物中,销售金额和DDDs排序列前四位的有盐酸左氧氟沙星注射液、加替沙星针、氟罗沙星针、依诺沙星注射液。结论我院喹诺酮类药物应用基本合理,但仍应进一步加强其使用监督管理。%Objective To evaluate the utilization and tendency of quinolones in our hospital. Methods Using DDD meth-od, the utilization of quinolones in our hospital from 2009 to 2011 were analyzed statistical y in terms of drug variety, consump-tion sum, DDDs and DDC, etc. Results The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Gatifloxacin capsules, Levofloxacin capsules and Fleroxacin capsules.The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection, Gatifloxacin injection, Fleroxacin injection, Enoxacin injection. Conclusion The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.

  3. Utilization of Quinolones in Our Hospital from 2007 to 2009%我院2007-2009年喹诺酮类药应用分析

    Institute of Scientific and Technical Information of China (English)

    张桂芬; 支伟锋; 归莱; 谢丹

    2011-01-01

    OBJECTIVE: To evaluate the utilization and tendency of quinolones in our hospital. METHODS: Using DDD method, the utilization of quinolones in our hospital from 2007 to 2009 were analyzed statistically in terms of drug variety, consumption sum, DDDs and DDC, etc. RESULTS: The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Lomefloxacin tablets,Gatifloxacin capsules and Levofloxacin tablets (domestic). The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection(domestic), Ciprofloxacin sodium chloride injection, Fleroxacin glucose injection. CONCLUSION: The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.%目的:评价我院喹诺酮类药的应用现状及趋势.方法:采用限定日剂量方法,对我院2007-2009年喹诺酮类药的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析.结果:喹诺酮类药销售金额在抗菌药物中所占比例逐年下降.3年来,在口服喹诺酮类药中,销售金额、DDDs排序列前3位的依次是洛美沙星片、加替沙星胶囊、左氧氟沙星片(国产);在注射喹诺酮类药中,销售金额、DDDs排序列前4位的均有左氧氟沙星注射液(国产)、环丙沙星氯化钠注射液、氟罗沙星葡萄糖注射液.结论:我院喹诺酮类药应用基本合理,但仍应进一步加强其使用监管.

  4. Substitutions of Ser83Leu in GyrA and Ser80Leu in ParC Associated with Quinolone Resistance in Acinetobacter pittii.

    Science.gov (United States)

    Gu, Dan-xia; Hu, Yun-jian; Zhou, Hong-wei; Zhang, Rong; Chen, Gong-xiang

    2015-06-01

    To investigate the prevalence and the mechanism of quinolone-resistant Acinetobacter pittii, 634 Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolates were collected throughout Zhejiang Province. Identification of isolates was conducted by matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS), blaOXA-51-like gene, and partial RNA polymerase β-subunit (rpoB) amplification. Twenty-seven isolates of A. pittii were identified. Among the 634 isolates, A. baumannii, A. pittii, Acinetobacter nosocomialis, and A. calcoaceticus counted for 87.22%, 4.26%, 8.20%, and 0.32%, respectively. Antimicrobial susceptibility of nalidixic acid, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, levofloxacin, sparfloxacin, moxifloxacin, and gatifloxacin for 27 A. pittii were determined by the agar dilution method. Detection of quinolone-resistant determining regions of gyrA, gyrB, parC, and parE was performed for the A. pittii isolates. In addition, plasmid-mediated quinolone resistance (PMQR) determinants (qnrA, qnrB, qnrS, qnrC, qnrD, aac(6')-Ib-cr, qepA, oqxA, and oqxB) were investigated. All the 27 isolates demonstrated a higher minimum inhibitory concentration (MIC) to old quinolones than the new fluoroquinolones. No mutation in gyrA, gyrB, parC, or parE was detected in 20 ciprofloxacin-susceptible isolates. Seven ciprofloxacin-resistant A. pittii were identified with a Ser83Leu mutation in GyrA. Among them, six isolates with simultaneous Ser83Leu amino acid substitution in GyrA and Ser80Leu in ParC displayed higher MIC values against ciprofloxacin. Additionally, three were identified with a Met370Ile substitution in ParE, and two were detected with a Tyr317His mutation in ParE, which were reported for the first time. No PMQR determinants were identified in the 27 A. pittii isolates. In conclusion, mutations in chromosome play a major role in quinolone resistance in A. pittii, while resistance mechanisms mediated by plasmid have

  5. [Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain].

    Science.gov (United States)

    Machuca, Jesús; Agüero, Jesús; Miró, Elisenda; Conejo, María Del Carmen; Oteo, Jesús; Bou, Germán; González-López, Juan José; Oliver, Antonio; Navarro, Ferran; Pascual, Álvaro; Martínez-Martínez, Luis

    2016-06-23

    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 β-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. 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 β-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. 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 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC β-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. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Prevalence and characterisation of plasmid-mediated quinolone resistance and mutations in the gyrase and topoisomerase IV genes among Shigella isolates from Henan, China, between 2001 and 2008.

    Science.gov (United States)

    Yang, Haiyan; Duan, Guangcai; Zhu, Jingyuan; Zhang, Weidong; Xi, Yuanlin; Fan, Qingtang

    2013-08-01

    A total of 293 Shigella isolates were isolated from patients with diarrhoea in four villages of Henan, China. This study investigated the prevalence of the plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, qnrS, qepA and aac(6')-Ib-cr and compared the polymorphic quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE. Of the isolates, 292 were found to be resistant to nalidixic acid and pipemidic acid, whereas 77 were resistant to ciprofloxacin (resistance rate of 26.3%). Resistance of the Shigella isolates to ciprofloxacin significantly increased from 2001 to 2008 (PShigella isolates are common in China. This study found that there was a significant increase in mutation rates of the QRDR and the resistant rates to ciprofloxacin. Other mechanisms may be present in the isolates that also contribute to their resistance to ciprofloxacin.

  7. Identification of metabolites and thermal transformation products of quinolones in raw cow's milk by liquid chromatography coupled to high-resolution mass spectrometry.

    Science.gov (United States)

    Junza, Alexandra; Barbosa, Sergio; Codony, M Rosa; Jubert, Anna; Barbosa, José; Barrón, Dolores

    2014-02-26

    The presence of residues of antibiotics, metabolites, and thermal transformation products (TPs), produced during thermal treatment to eliminate pathogenic microorganisms in milk, could represent a risk for people. Cow's milk samples spiked with enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF), and sarafloxacin (SAR) and milk samples from cows medicated with ENR were submitted to several thermal treatments. The milk samples were analyzed by liquid chromatography-mass spectrometry (LC-MS) to find and identify TPs and metabolites. In this work, 27 TPs of 4 quinolones and 24 metabolites of ENR were found. Some of these compounds had been reported previously, but others were characterized for the first time, including lactose-conjugated CIP, the formamidation reaction for CIP and SAR, and hydroxylation or ketone formation to produce three different isomers for all quinolones studied.

  8. Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.

    Science.gov (United States)

    Cui, Sheng-Feng; Peng, Li-Ping; Zhang, Hui-Zhen; Rasheed, Syed; Vijaya Kumar, Kannekanti; Zhou, Cheng-He

    2014-10-30

    A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.

  9. Lactococcus garvieae carries a chromosomally encoded pentapeptide repeat protein that confers reduced susceptibility to quinolones in Escherichia coli producing a cytotoxic effect.

    Science.gov (United States)

    Gibello, Alicia; Díaz de Alba, Paula; Blanco, M Mar; Machuca, Jesus; Cutuli, M Teresa; Rodríguez-Martínez, José Manuel

    2014-09-01

    This study characterises a chromosomal gene of Lactococcus garvieae encoding a pentapeptide repeat protein designated as LgaQnr. This gene has been implicated in reduced susceptibility to quinolones in this bacterium, which is of relevance to both veterinary and human medicine. All of the L. garvieae isolates analysed were positive for the lgaqnr gene. The expression of lgaqnr in Escherichia coli reduced the susceptibility to quinolones, producing an adverse effect. The reduced susceptibility to ciprofloxacin was 16-fold in E. coli ATCC 25922 and 32-fold in E. coli DH10B, compared to the control strains. The minimum inhibitory concentration of nalidixic acid was also increased 4 or 5-fold. The effect of the expression of lgaqnr in E. coli was investigated by electron microscopy and was observed to affect the structure of the cell and the inner membrane of the recombinant cells.

  10. Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan.

    Science.gov (United States)

    Takeuchi, Noriko; Ohkusu, Misako; Hoshino, Tadashi; Naito, Sachiko; Takaya, Akiko; Yamamoto, Tomoko; Ishiwada, Naruhiko

    2017-04-01

    Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g. penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae. The evolution of bacterial resistance since TFLX approval is not known. To clarify the influence of quinolones administered to children since their approval, we examined the resistance mechanism of TFLX-resistant S. pneumoniae isolated from paediatric patients as well as patient clinical characteristics. TFLX-resistant strains (MIC ≥ 2 mg/L) were detected among clinical isolates of S. pneumoniae derived from children (≤15 years old) between 2010 and 2014. These strains were characterised based on quinolone resistance-determining regions (QRDRs), i.e. gyrA, gyrB, parC, and parE. In addition, the antimicrobial susceptibility, serotype, and multilocus sequence type of strains were determined, pulsed-field gel electrophoresis was performed, and patient clinical characteristics based on medical records were assessed for cases with underling TFLX-resistant strains. Among 1168 S. pneumoniae isolates, two TFLX-resistant strains were detected from respiratory specimens obtained from paediatric patients with frequent exposure to TFLX. Both strains had mutations in the QRDRs of gyrA and parC. One case exhibited gradual changes in the QRDR during the clinical course. This is the first study of quinolone-resistant S. pneumoniae isolated from children, including clinical data, in Japan. These data may help prevent increases in infections of quinolone-resistant S. pneumoniae in children; specifically, the results emphasise the importance of administering fluoroquinolones only in appropriate cases. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Monitoring quinolone antibacterial residues in bovine tissues: extraction with hot water and liquid chromatography coupled to a single- or triple-quadrupole mass spectrometer.

    Science.gov (United States)

    Bogialli, Sara; D'Ascenzo, Giuseppe; Di Corcia, Antonio; Innocenti, Giorgiana; Laganà, Aldo; Pacchiarotta, Tiziana

    2007-01-01

    A rapid and sensitive procedure for determining residues of seven quinolone antibacterials in bovine muscle, kidney and liver is presented. The method is based on the matrix solid-phase dispersion (MSPD) technique with hot water as extractant followed by liquid chromatography/single quadrupole mass spectrometry (LC/MS) or triple-quadrupole mass spectrometry (LC/MS/MS). After dispersing tissue samples on hydrazine sulfate treated sand, target compounds were eluted from the MSPD column by passing through it 4 mL of water heated at 100 degrees C. After pH adjustment and filtration, 200 and 5 microL of the aqueous extracts were respectively injected into the LC/MS and LC/MS/MS instruments. With the former instrument, MS data were acquired in the three-ion selected ion monitoring mode, while MS/MS data acquisition was performed in the multi-reaction monitoring mode by selecting two precursor ion to product ion transitions for each target compound. Hot water appeared to be an efficient extracting medium, since absolute recoveries of the analytes were 84-102%. Using norfloxacin (a quinolone not used in veterinary medicine) as surrogate internal standard, the accuracy of the method at three concentration levels equal to 0.5, 1 and 1.5 times the maximum residue limits (MRLs) set by the european union was 88-109% with relative standard deviations (RSDs) not higher than 7%. The use of LC/MS/MS allowed detection and quantification of the analytes in any tissue considered to be performed at concentrations by far lower than half of their MRLs. Vice versa, the single-quadrupole MS arrangement, while succeeding in monitoring quinolones in muscle tissue at the 0.5 MRL level, showed to be not sufficiently selective for unambiguous identification of some quinolones in kidney and liver.

  12. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Human Isolates in Iran

    Directory of Open Access Journals (Sweden)

    Ehsaneh Shams

    2015-01-01

    Full Text Available The purpose of this study was to determine the prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR genes (qnrA, qnrB, qnrS, aac(6′-Ib-cr, and qepA among ESBL-producing Klebsiella pneumoniae isolates in Kashan, Iran. A total of 185 K. pneumoniae isolates were tested for quinolone resistance and ESBL-producing using the disk diffusion method and double disk synergy (DDST confirmatory test. ESBL-producing strains were further evaluated for the blaCTX-M genes. The PCR method was used to show presence of plasmid-mediated quinolone resistance genes and the purified PCR products were sequenced. Eighty-seven ESBL-producing strains were identified by DDST confirmatory test and majority (70, 80.5% of which carried blaCTX-M genes including CTX-M-1 (60%, CTX-M-2 (42.9%, and CTX-M-9 (34.3%. Seventy-seven ESBL-producing K. pneumoniae isolates harbored PMQR genes, which mostly consisted of aac(6′-Ib-cr (70.1% and qnrB (46.0%, followed by qnrS (5.7%. Among the 77 PMQR-positive isolates, 27 (35.1% and 1 (1.3% carried 2 and 3 different PMQR genes, respectively. However, qnrA and qepA were not found in any isolate. Our results highlight high ESBL occurrence with CTX-M type and high frequency of plasmid-mediated quinolone resistance genes among ESBL-producing K. pneumoniae isolates in Kashan.

  13. 喹诺酮类药物的不良反应报告分析%Analysis of Quinolones Adverse Reaction Reports

    Institute of Scientific and Technical Information of China (English)

    王惠霞; 陆建平

    2012-01-01

      Objective:Explore the occurrence of adverse reactions of quinolones and clinical control measures.Method:A total of 27 cases of quinolone ADR reports collected in our hospital in 2009 were analyzed statistically in respect of patients age and sex,route of administration,drug varieties,organs or systems involved and the clinical manifestation.Result:Lesions of skin and its appendages were the most common damages of quinolone ADR.Conclusion:Importance should be attached to the reporting and monitoring of quinolone ADR reports in the clinic and reduce the incidence of adverse reactions.%  目的:探讨喹诺酮类药物不良反应(ADR)的发生情况与临床控制措施。方法:对笔者所在医院2011年1-12月上报的27例喹诺酮类药物 ADR 报告,按患者年龄、性别、药品类别、ADR 累及器官或系统及临床表现等进行统计、分析。结果:喹诺酮类抗菌药物药物的不良反应临床表现以皮肤及附件损害最多见。结论:临床应重视喹诺酮类药物的不良反应,加强 ADR 监测工作,促进临床合理用药,减少不良反应的发生。

  14. Synthesis and antibacterial evaluation of a new series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones.

    Science.gov (United States)

    Wube, Abraham; Guzman, Juan-David; Hüfner, Antje; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Gibbons, Simon; Bhakta, Sanjib; Bucar, Franz

    2012-07-09

    To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 µM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 µM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3-364.7 µM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 µM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 µM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity.

  15. Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).

    Science.gov (United States)

    Pidathala, Chandrakala; Amewu, Richard; Pacorel, Bénédicte; Nixon, Gemma L; Gibbons, Peter; Hong, W David; Leung, Suet C; Berry, Neil G; Sharma, Raman; Stocks, Paul A; Srivastava, Abhishek; Shone, Alison E; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Hill, Alasdair; Fisher, Nicholas E; Warman, Ashley J; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

    2012-03-08

    A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the rational selection of 17 000 compounds for high-throughput screening. Twelve distinct chemotypes were identified and briefly examined leading to the selection of the quinolone core as the key target for structure-activity relationship (SAR) development. Extensive structural exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for further biological evaluation. The lead compound within this series 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl)quinolin-4(1H)-one (CK-2-68) has antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is selective for PfNDH2 over other respiratory enzymes (inhibitory IC(50) against PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability in the presence of human liver microsomes. This lead compound and its phosphate pro-drug have potent in vivo antimalarial activity after oral administration, consistent with the target product profile of a drug for the treatment of uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc(1), and studies to determine the potential advantage of this dual-targeting effect are in progress.

  16. Simultaneous Quantification of Limonin, Two Indolequinazoline Alkaloids, and Four Quinolone Alkaloids in Evodia rutaecarpa (Juss. Benth by HPLC-DAD Method

    Directory of Open Access Journals (Sweden)

    Pei-ting Zhang

    2013-01-01

    Full Text Available A simple and efficient HPLC-DAD (225 nm method was developed and validated for the simultaneous determination of limonin and six key alkaloids (evodiamine, rutaecarpine, 1-methyl-2-undecyl-4(1H-quinolone, evocarpine, 1-methy-2-[(6Z,9Z]-6,9-pentadecadienyl-4-(1H-quinolone, and dihydroevocarpine in Evodia rutaecarpa (Juss. Benth, which has been widely used as one of the Traditional Chinese Medicines. The chromatographic separation was carried out on a Hypersil BDS C18 column, and gradient elution was employed with a mobile phase containing acetonitrile and water. Contents of the analytes in 18 batches of samples were analyzed by ultrasonic extraction with ethanol and water mixture (80 : 20, v/v followed by HPLC analysis. Separation of the seven analytes was achieved within 60 min with good linearity (. The RSD of both the intraday and interday precision was below 1.85%. The accuracy at different concentrations was within the range of 97.91 to 100.49%. Hierarchical clustering analysis was performed to differentiate and classify the samples based on the contents of the seven constituents. This study indicated that the quality control of E. rutaecarpa could be simplified to the measurement of four constituents, and that limonin, 1-methyl-2-undecyl-4(1H-quinolone, and dihydroevocarpine should also be served as the chemical markers together with evodiamine for the quality control of Evodia rutaecarpa (Juss. Benth.

  17. On-line anion exchange solid-phase extraction coupled to liquid chromatography with fluorescence detection to determine quinolones in water and human urine.

    Science.gov (United States)

    Lara, Francisco J; Del Olmo-Iruela, Monsalud; García-Campaña, Ana M

    2013-10-04

    An analytical method based on on-line solid-phase extraction coupled to liquid chromatography with fluorescence detection has been developed to determine quinolones in tap water and human urine. A home-made setup was used to percolate 10 mL of sample through a solid-phase extraction column. Analytes were retained onto the sorbent by an anion exchange mechanism which ensures an optimum compatibility with the subsequent chromatographic separation. A C-18 column containing core-shell particles (2.6 μm) was used to achieve peak efficiencies up to 200,000 plates/m, at a flow rate of 1.2 mL/min and without the need for special pumps. The method allowed the determination of 11 quinolones directly in tap water samples in less than 20 min and with limits of detection ranging between 7 and 110 ng/L. The sensitivity achieved made possible the direct determination of 9 quinolones in human urine without any sample treatment, just dilution with water. Relative recoveries between 94 and 109% were obtained meaning that the matrix effect in human urine is negligible after dilution. Satisfactory results were also obtained in terms of precision since relative standard deviations were always below 13%.

  18. Functional analysis of spoT, relA and dksA genes on quinolone tolerance in Pseudomonas aeruginosa under nongrowing condition.

    Science.gov (United States)

    Viducic, Darija; Ono, Tsuneko; Murakami, Keiji; Susilowati, Heni; Kayama, Shizuo; Hirota, Katsuhiko; Miyake, Yoichiro

    2006-01-01

    To assess the contribution of ppGpp in antibiotic tolerance to quinolone in Pseudomonas aeruginosa, knockout mutants of the genes involved or linked with the stringent response, such as relA, spoT and dksA, were constructed and investigated for their antibiotic susceptibility to quinolones. The survival of the dksA and spoT mutants in the presence of 8 microg/ml of ofloxacin and 1 microg/ml of ciprofloxacin were shown to be approximately 20-180 and 10-40 times respectively, higher than the same for the wild type strain. The intracellular levels of ppGpp determined with high performance liquid chromatography (HPLC) demonstrated that spoT and dksA mutants possess higher basal levels of ppGpp. The data suggest that elevated basal levels of ppGpp may be responsible for rendering these mutants tolerant to quinolones and expand the importance of ppGpp as an antimicrobial target in P. aeruginosa.

  19. Characteristics of Quinolone Resistance in Escherichia coli Isolates from Humans, Animals, and the Environment in the Czech Republic

    Science.gov (United States)

    Röderova, Magdalena; Halova, Dana; Papousek, Ivo; Dolejska, Monika; Masarikova, Martina; Hanulik, Vojtech; Pudova, Vendula; Broz, Petr; Htoutou-Sedlakova, Miroslava; Sauer, Pavel; Bardon, Jan; Cizek, Alois; Kolar, Milan; Literak, Ivan

    2017-01-01

    Escherichia coli is a common commensal bacterial species of humans and animals that may become a troublesome pathogen causing serious diseases. The aim of this study was to characterize the quinolone resistance phenotypes and genotypes in E. coli isolates of different origin from one area of the Czech Republic. E. coli isolates were obtained from hospitalized patients and outpatients, chicken farms, retailed turkeys, rooks wintering in the area, and wastewaters. Susceptibility of the isolates grown on the MacConkey agar with ciprofloxacin (0.05 mg/L) to 23 antimicrobial agents was determined. The presence of plasmid-mediated quinolone resistance (PMQR) and ESBL genes was tested by PCR and sequencing. Specific mutations in gyrA, gyrB, parC, and parE were also examined. Multilocus sequence typing and pulsed-field gel electrophoresis were performed to assess the clonal relationship. In total, 1050 E. coli isolates were obtained, including 303 isolates from humans, 156 from chickens, 105 from turkeys, 114 from the rooks, and 372 from wastewater samples. PMQR genes were detected in 262 (25%) isolates. The highest occurrence was observed in isolates from retailed turkey (49% of the isolates were positive) and inpatients (32%). The qnrS1 gene was the most common PMQR determinant identified in 146 (56%) followed by aac(6′)-Ib-cr in 77 (29%), qnrB19 in 41 (16%), and qnrB1 in 9 (3%) isolates. All isolates with high level of ciprofloxacin resistance (>32 mg/L) carried double or triple mutations in gyrA combined with single or double mutations in parC. The most frequently identified substitutions were Ser(83)Leu; Asp(87)Asn in GyrA, together with Ser(80)Ile, or Glu(84)Val in ParC. Majority of these isolates showed resistance to beta-lactams and multiresistance phenotype was found in 95% isolates. Forty-eight different sequence types among 144 isolates analyzed were found, including five major clones ST131 (26), ST355 (19), ST48 (13), ST95 (10), and ST10 (5). No isolates

  20. [Susceptibility of clinically-isolated bacteria strains to respiratory quinolones and evaluation of antimicrobial agent efficacy by Monte Carlo simulation].

    Science.gov (United States)

    Kosaka, Tadashi; Yamada, Yukiji; Kimura, Takeshi; Kodama, Mai; Fujitomo, Yumiko; Masaki, Nakanishi; Toshiaki, Komori; Keisuke, Shikata; Fujita, Naohisa

    2016-02-01

    Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients' renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n = number of strains) [Streptococcus pneumoniae (n = 15), Streptococcus pyogenes (n = 14), Streptococcus agalactiae (n = 19), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24), Escherichia coli (n = 35), Haemophilus influenzae (n = 17), Klebsiella pneumoniae (n = 14), Pseudomonas aeruginosa (n = 31), and Moraxella catarrhalis (n = 11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, > 16, and 8 µg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being > 16, 16, 1, and 16 µg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration-time curve divided by the MIC₉₀ (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also

  1. Pseudomonas quinolone signalling system: a component of quorum sensing cascade is a crucial player in the acute urinary tract infection caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Bala, Anju; Chhibber, Sanjay; Harjai, Kusum

    2014-11-01

    Pseudomonas aeruginosa is an opportunistic pathogen which employs quorum sensing system to regulate several genes required for its survival and pathogenicity within the host. Besides acylhomoserine lactone (AHL) mediated las and rhl systems, this organism possesses Pseudomonas quinolone signalling (PQS) system based on alkyl quinolone signal molecules. The quinolone system represents another layer of sophistication in the complex quorum sensing cascade. Therefore, in the present study, we evaluated the contribution of the PQS system in the establishment of acute urinary tract infection (UTI) in the mouse model. For this, wild-type parent strain of P. aeruginosa MPAO1 and its isogenic single transposon mutant strains pqsH and pqsA were employed to induce UTI in mice. PQS molecules in the tissue homogenates of mice were detected by high performance thin layer chromatography (HP-TLC) method. Virulence of strains was assessed in terms of bacteriological count, histopathological lesions in the renal and bladder tissue and generation of pathological index markers like reactive nitrogen intermediates and malondialdehyde. HP-TLC analysis showed presence of PQS molecules in the renal and bladder tissue of mice infected with MPAO1 while no PQS was detected in case of pqsH and pqsA mutant strains. Results indicated that MPAO1 possessing fully functional PQS biosynthetic genes was highly virulent and caused acute pyelonephritis with severe inflammation and tissue destruction. On the contrary, significant reduction in the log count, mild tissue damage and declined levels of pathological markers were observed in mice infected with mutant strains as compared to MPAO1. Further among mutants, all these parameters were maximally impaired in the pqsA mutant in which synthesis of alkyl quinolones was completely abolished due to the transposon mutation in respective gene. Virulence of the pqsH mutant strain was lesser than that of the MPAO1 but higher than pqsA mutant. In addition, the

  2. Influence of solvent composition on the solid phase at equilibrium with saturated solutions of quinolones in different solvent mixtures.

    Science.gov (United States)

    Romero, Susana; Bustamante, Pilar; Escalera, Begoña; Mura, Paola; Cirri, Marzia

    2004-06-29

    The dissolution profiles and solubilities of three quinolonic drugs (oxolinic, pipemidic, and nalidixic acids) in different solvent mixtures were studied. The behavior of the solid phase, during solubility experiments was in-depth investigated with the aim of detecting possible crystalline modifications, such as polymorphic transitions or solvate formations, that might modify drug stability and/or solubility properties. In order to test the influence of both the nature and polarity of the co-solvents, aqueous and non-aqueous binary mixtures have been prepared by using Lewis base (dioxane and ethyl acetate) and amphiprotic co-solvents (ethanol and water). Differential scanning calorimetry (DSC), hot stage microscopy, IR spectroscopy and X-ray powder diffraction were used in combination with solubility and dissolution studies to characterize and investigate the solid state properties of the original powders and the corresponding ones at equilibrium with the different pure solvents and solvent mixtures examined. The solid phases of nalidixic and oxolinic acids did not show any change after equilibration with the various pure solvents or binary solvent mixtures, regardless the chemical nature of the examined solvents. On the contrary, in the case of pipemidic acid, the different analytical techniques used to characterize the drug solid state enabled identification of a solvated form at equilibrium with pure dioxane and a trihydrated form in aqueous mixtures of water with both ethanol (amphiprotic) or dioxane (Lewis base) in a concentration range from 10 to 100% water. Copyright 2004 Elsevier B.V.

  3. Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with 5-chloro-2-thienyl group

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and the purpose of the study: Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Methods: Reaction of ciprofloxacin (1, norfloxacin (2 and enoxacin (3 with α-bromoketone 10 or α-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO3 at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7(a-c, respectively. Results and major conclusion: The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives (compounds 4a, 5a, 6a and 7a were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-(5-chlorothiophen-2-yl-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 μg/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug (ciprofloxacin against all Gram-positive bacteria with the exception of E. feacalis.

  4. Electrogenerated chemiluminescence: An oxidative-reductive mechanism between quinolone antibiotics and tris(2,2'-bipyridyl)ruthenium(II)

    Energy Technology Data Exchange (ETDEWEB)

    Burkhead, Matthew S.; Wang, Heeyoung; Fallet, Marcel [Department of Chemistry, Creighton University, Omaha, NE 68178 (United States); Gross, Erin M. [Department of Chemistry, Creighton University, Omaha, NE 68178 (United States)], E-mail: eringross@creighton.edu

    2008-04-21

    The cyclic voltammetry and electrogenerated chemiluminescent (ECL) reactions of a series of quinolone and fluoroquinolone antibiotics were investigated in a flow injection analysis (FIA) system. 7-Piperazinyl fluoroquinolone antibiotics were found to participate as a coreactant in an oxidative-reductive ECL mechanism with tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy){sub 3}{sup 2+}) as the luminescent reagent. The reaction mechanism was investigated in order to understand and optimize the processes leading to light emission. The optimal conditions included a solution pH {approx}7 at a flow rate of 3.0 mL min{sup -1} with no added organic modifier and application of 1.2 V vs. a Pt quasi-reference electrode (QRE). Fluoroquinolones containing a tertiary distal nitrogen on the piperazine ring, such as enrofloxacin and ofloxacin, reacted to produce more intense ECL than those with a secondary nitrogen, such as ciprofloxacin and norfloxacin. The method linear range, precision, detection limits, and sensitivity for the detection of enrofloxacin and ciprofloxacin were compared to that of tripropylamine. The method was applied to the determination of the ciprofloxacin content in a pharmaceutical preparation. The assay is discussed in terms of its analytical figures of merit, ease of use, speed, accuracy and application to pharmaceutical samples.

  5. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-02

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  6. 1,2-substituted 4-(1H)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro.

    Science.gov (United States)

    Wube, Abraham; Hüfner, Antje; Seebacher, Werner; Kaiser, Marcel; Brun, Reto; Bauer, Rudolf; Bucar, Franz

    2014-09-10

    A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC50 value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC50 value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities.

  7. Determination of quinolones and fluoroquinolones, tetracyclines and sulfonamides in bovine, swine and poultry liver using LC-MS/MS.

    Science.gov (United States)

    Martins, Magda Targa; Barreto, Fabiano; Hoff, Rodrigo Barcelos; Jank, Louise; Arsand, Juliana Bazzan; Feijó, Tiago Correa; Schapoval, Elfrides Eva Scherman

    2015-01-01

    Antibacterials are widely used in veterinary medicine. Residues of these drugs can remain in food of animal origin, including bovine liver. This paper describes a fast and simple analytical method for the determination of quinolones and fluoroquinolones, tetracyclines and sulfonamides in bovine liver samples. Deuterated enrofloxacin, sulfapyridine and demeclocycline were used as internal standards. The homogenised liver samples were extracted with acidified acetonitrile. Steps of non-solid-phase extraction (SPE) clean-up and concentration were used in the presented method. The final extracts were analysed by sensitive and selective detection of all components in a single run using LC-MS/MS. Acceptable recoveries between 66% and 110% were obtained. Good linearity (r(2)) above 0.96, considering three different days, for all drugs was achieved in concentrations ranging from 0.0 to 2.0 × the maximum residue limit (MRL). Intraday precision with coefficient of variation (CV%) (n = 6) lower than 14.7% and inter-day precision lower than 18.8% in agreement with European Commission Decision 2002/657/EC were obtained in concentrations ranging from 0.5 to 1.5 MRL. Accuracy was between 86% and 110%. Limits of detection and quantitation, as well as decision limit (CCα) and detection capability (CCβ), were also evaluated.

  8. Determination of 11 quinolones in bovine milk using immunoaffinity stir bar sorptive microextraction and liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Yao, Kai; Zhang, Wei; Yang, Linyan; Gong, Jianfang; Li, Liuan; Jin, Tianming; Li, Cun

    2015-10-15

    A sensitive, selective and reproducible immunoaffinity stir bar sorptive microextraction (SBSME) coupled with liquid chromatography-fluorescence method for determination of 11 quinolones (QNs) in bovine milk was developed and validated. It is first report of a broad-specificity monoclonal antibody to QNs that has been immobilized to glass bar for preparation of a re-usable immunoaffinity stir bar. Analytes were extracted by placing stir bar in milk and shaking on a rotary shaker for 30min at 30rpm, followed by liquid chromatography and fluorescence detection. The newly developed method has limits of detection for each QN from 0.05 to 0.1ng/g with intra-day and inter-day precision ranging from 3.2 to 11.9% and from 5.2 to 12.5%, respectively. This allowed us to quantitatively analyze drugs in bovine milk with the advantage of significantly simplified sample preparation. The proposed method was successfully applied to the bovine milk samples analyses with QNs, demonstrating its rare application in animal food safety analysis.

  9. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone.

    Science.gov (United States)

    Lawres, Lauren A; Garg, Aprajita; Kumar, Vidya; Bruzual, Igor; Forquer, Isaac P; Renard, Isaline; Virji, Azan Z; Boulard, Pierre; Rodriguez, Eduardo X; Allen, Alexander J; Pou, Sovitj; Wegmann, Keith W; Winter, Rolf W; Nilsen, Aaron; Mao, Jialing; Preston, Douglas A; Belperron, Alexia A; Bockenstedt, Linda K; Hinrichs, David J; Riscoe, Michael K; Doggett, J Stone; Ben Mamoun, Choukri

    2016-06-27

    Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis. © 2016 Lawres et al.

  10. Membrane Distribution of the Pseudomonas Quinolone Signal Modulates Outer Membrane Vesicle Production in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Catalina Florez

    2017-08-01

    Full Text Available The Pseudomonas quinolone signal (PQS is an important quorum-sensing molecule in Pseudomonas aeruginosa that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand how they are formed. Our group proposed the bilayer-couple model for OMV biogenesis, where PQS intercalates into the outer membrane, causing expansion of the outer leaflet and consequently inducing curvature. In accordance with the model, we hypothesized that PQS must be transported from the cytoplasm to the outer membrane before it can initiate OMV formation. We initially examined two laboratory strains of P. aeruginosa and found significant strain-dependent differences. PQS export correlated strongly with OMV production, even though equivalent amounts of total PQS were produced by both strains. Interestingly, we discovered that poor OMV producers sequestered the majority of PQS in the inner membrane, which appeared to be the result of early saturation of the export pathway. Further analysis showed that strain-specific PQS export and OMV biogenesis patterns were stable once established but could be significantly altered by changing the growth medium. Finally, we demonstrated that the associations described for laboratory strains also held for three clinical strains. These results suggest that factors controlling the export of PQS dictate OMV biogenesis. This work provides new insight into PQS-controlled virulence in P. aeruginosa and provides important tools to further study signal export and OMV biogenesis.

  11. Detection of plasmid-mediated IMP-1 metallo-β-lactamase and quinolone resistance determinants in an ertapenem-resistant Enterobacter cloacae isolate

    Institute of Scientific and Technical Information of China (English)

    Li-rong CHEN; Hong-wei ZHOU; Jia-chang CAI; Rong ZHANG; Gong-xiang CHEN

    2009-01-01

    Objective: To investigate the mechanism of carbapenem resistance and the occurrence of plasmid-mediated quinolone resistance determinants qnr and aac(6')-Ib-cr in a clinical isolate of Enterobacter cloacae. Methods: An ertapenem-resistant E. cloacae ZY106, which was isolated from liquor puris of a female gastric cancer patient in a Chinese hospital, was investigated. Antibiotic susceptibilities were determined by agar dilution method. Conjugation experiments, isoelectric focusing, polymerase chain reaction (PCR), and DNA sequence analyses of plasmid-mediated carbapenemases and quinolone resistance determinants were preformed to confirm the genotype. Outer membrane proteins (OMPs) were examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Urea-SDS-PAGE). Results: Minimum inhibitory concentrations (MCs) of imipenem, mer-openem, and ertapenem for ZY106 were 2,4, and 16 ug/ml, respectively. Conjugation studies with Escherichia coli resulted in the transfer of significantly reduced carbapenem susceptibility. ZY106 produced IMP-1 metallo-p-lactamase and CTX-M-3 extended-spectrum P-lactamase, and E. coli transconjugant produced IMP-1. Plasmid-mediated quinolone resistance determinant qnrSI was detected in ZY106. Transfer of the qnrSI-encoding-plasmid into E. coli by conjugation resulted in intermediate resistance to ciprofloxacin in E. coli transconjugant. Urea-SDS-PAGE analysis of OMPs showed that ZY106 lacked an OMP of approximately 38 KDa. Conclusion: It is the first IMP-1-producing Enterobacteriaceae in China and the first report of a clinical isolate that harbors both blaIMP and qnrS genes as well. The blaIMP-1, blaCTX-M-3, and qnrSl are encoded at three different plasmids. IMP-1 combined with the loss of an OMP possibly resulted in ertapenem resistance and reduced imipenem and mero-penem susceptibility in E. cloacae.

  12. Detection and quantification of quinolone signalling molecule: a third quorum sensing molecule of Pseudomonas aeruginosa by high performance-thin layer chromatography.

    Science.gov (United States)

    Bala, Anju; Gupta, Ravi Kumar; Chhibber, Sanjay; Harjai, Kusum

    2013-07-01

    Sophisticated network of quorum sensing involves the production of chemical signals which regulate the combined expression of virulence genes and biofilm formation in Pseudomonas aeruginosa. Two well-characterized acyl homoserine lactone based las and rhl systems together with alkyl quinolone based Pseudomonas quinolone signalling (PQS) are fundamental components of this network. Third signalling molecule, 2-heptyl-3-hydroxy-4-quinolone (PQS) is of paramount importance because of its interconnecting role in quorum sensing hierarchy in P. aeruginosa. Accurate detection of PQS molecule is very important to understand the involvement of this system in infection process of P. aeruginosa. In this study, high performance-thin layer chromatography (HP-TLC) method was developed for detection as well as quantification of PQS signal molecules in P. aeruginosa, which combines conventional method like TLC with sophisticated instrumentation. This method was validated using parameters like linearity, accuracy, precision, reproducibility and sensitivity. Intra- and inter-day accuracy and precision values were determined which were found to be within acceptable level and hence showed reproducibility. Measurement of PQS in the range of 0.01nmol indicated excellent sensitivity of this approach for quantifying PQS molecule. Automated sampling, rapid and simultaneous analysis of large number of samples and minimal errors make this method more suitable for analysis of PQS signalling molecules. Production of PQS was found to be strain dependent since variation in amount of PQS was observed among different P. aeruginosa isolates. Further, PQS production was also dependent on growth phase of P. aeruginosa with maximum production in late stationary phase.

  13. Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

    Science.gov (United States)

    Hooper, D C; Wolfson, J S; Souza, K S; Ng, E Y; McHugh, G L; Swartz, M N

    1989-03-01

    Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations. The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5. Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions. Both mutations also decreased norfloxacin accumulation in intact cells. This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane. These findings, in conjunction with those of Cohen et al. (S. P. Cohen, D. C. Hooper, J. S. Wolfson, K. S. Souza, L. M. McMurry, and S. B. Levy, Antimicrob. Agents Chemother. 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.

  14. Prevalence of plasmid-mediated quinolone resistance and aminoglycoside resistance determinants among carbapeneme non-susceptible Enterobacter cloacae.

    Directory of Open Access Journals (Sweden)

    Shifeng Huang

    Full Text Available BACKGROUND: Simultaneous resistance to aminoglycosides and fluoroquinolones in carbapeneme non-susceptible (CNS isolates will inevitably create problems. The present study was performed to characterize the prevalence of the plasmid-mediated quinolone resistance determinants (QRDs and aminoglycoside resistance determinants (ARDs among the CNS Enterobacter cloacae (E. cloacae isolates in a Chinese teaching hospital, and to acquire their molecular epidemiological characteristics. METHODS: The β-lactamases genes (including class A carbapenemase genes bla(KPC and bla(SME, metallo-β-lactamase genes (MBLs bla(IMP, bla(VIM and bla(NDM, and extended spectrum β-lactamases (ESBLs,bla(CTX-M, bla(TEM and bla(SHV, QRDs (including qnrA, qnrB, qnrS and aac(6'-Ib-cr and ARDs (including aac(6'-Ib, armA and rmtB of these 35 isolates were determined by PCR and sequenced bidirectionally. The clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE. RESULTS: Of the 35 isolates, 9 (25.7% harbored a carbapenemase gene; 23 (65.7% carried ESBLs; 24 (68.6% were QRD positive; and 27 (77.1% were ARD positive. Among the 5 bla(IMP-8 positive strains, 4 (80% contained both ESBL and QRD genes, and all the 5 (100% harbored ARD genes. Of the 23 ESBLs positive isolates, 6 (26.1% were carbapenemase positive, 14 (60.9% were QRD positive, and 18 (78.3% were ARD positive. PFGE revealed genetic diversity among the 35 isolates, indicating that the high prevalence of CNS E. cloacae isolates was not caused by clonal dissemination. CONCLUSION: QRD and ARD genes were highly prevalent among the CNS E. cloacae isolates. Multiple resistant genes were co-expressed in the same isolates. The CNS E. cloacae isolate co-expressing bla(NDM-1, bla(IMP-26, qnrA1 and qnrS1 was first reported.

  15. The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection.

    Science.gov (United States)

    Kasetty, Gopinath; Bhongir, Ravi K V; Papareddy, Praveen; Herwald, Heiko; Egesten, Arne

    2017-09-01

    Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused by Pseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimental P. aeruginosa lung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation of P. aeruginosa; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study. Copyright © 2017 American Society for Microbiology.

  16. Activity of gemifloxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

    Science.gov (United States)

    Azoulay-Dupuis, E; Bédos, J P; Mohler, J; Moine, P; Cherbuliez, C; Peytavin, G; Fantin, B; Köhler, T

    2005-03-01

    Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro activity against Streptococcus pneumoniae. We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia. Immunocompetent Swiss mice were infected with 10(5) CFU of a virulent, encapsulated S. pneumoniae strain, P-4241, or its isogenic parC, gyrA, parC gyrA, and efflux mutant derivatives (serotype 3); and leukopenic mice were infected with 10(7) CFU of two poorly virulent clinical strains (serotype 11A) carrying either a parE mutation or a parC, gyrA, and parE triple mutation. The drugs were administered six times every 12 h, starting at either 3 or 18 h postinfection. In vitro, gemifloxacin was the most potent agent against strains with and without acquired resistance to fluoroquinolones. While control mice died within 6 days, gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective (survival rates, 90 to 100%) against the wild-type strain and against mutants harboring a single mutation, corresponding to area under the time-versus-serum concentration curve at 24 h (AUC(24))/MIC ratios of 56.5 to 113, and provided a 40% survival rate against a mutant with a double mutation (parC and gyrA). A total AUC(24)/MIC ratio of 28.5 was associated with poor efficacy and the emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin against mutants with single mutations but did not provide any protection against the mutant with double mutations, despite treatment with a high dose of 200 mg/kg. Gemifloxacin preferentially selected for parC mutants both in vitro and in vivo.

  17. Plasmid-Mediated Quinolone Resistance in Escherichia coli Isolates from Wild Birds and Chickens in South Korea.

    Science.gov (United States)

    Oh, Jae-Young; Kwon, Yong-Kuk; Tamang, Migma Dorji; Jang, Hyung-Kwan; Jeong, Ok-Mi; Lee, Hee-Soo; Kang, Min-Su

    2016-01-01

    A total of 2,423 nonduplicate isolates of Escherichia coli recovered from wild birds (n=793) and chickens (n=1,630) in South Korea were investigated for plasmid-mediated quinolone resistance (PMQR) genes. Altogether, 56 isolates with PMQR genes were identified, including 25 (3.2%) from wild birds and 31 (1.9%) from chickens, which were further characterized using molecular methods. Among them, qnrS, aac(6')-Ib-cr, qnrB, and qepA genes were detected in 47 (1.9%), 6 (0.24%), 2 (0.08%), and 1 (0.04%) isolates, respectively. The most prevalent gene, qnrS, was identified in 21 (0.9%) and 26 (1.1%) isolates from wild birds and chickens, respectively. The qnrB gene was identified in two chicken isolates, which included qnrB19 and a novel qnrB44 gene. Plasmid isolation and Southern hybridization revealed that qnrS1 was located on a large (>200 kbp) plasmid. The spread of the PMQR genes was attributed to a combination of horizontal dissemination and clonal expansion. The horizontal dissemination of PMQR genes was mostly mediated by IncK plasmids. Molecular typing demonstrated that the majority of the PMQR-positive isolates were genetically diverse. Only one chicken isolate belonged to ST131, which harbored an additional CMY-2 gene. Our findings suggest that the wild birds could serve as reservoirs of PMQR genes and spread them over long distances through migration. To our knowledge, this is the first report of PMQR genes in Korean wild birds. This study also reports qnrS2, qnrB19, qnrB44, and qepA genes for the first time in animal E. coli isolates from South Korea.

  18. Preincubation of pneumococci with beta-lactams alone or combined with levofloxacin prevents quinolone-induced resistance without increasing intracellular levels of levofloxacin.

    Science.gov (United States)

    Cottagnoud, Philippe; Johnson, Maggie; Cottagnoud, Marianne; Piddock, Laura

    2005-08-01

    Preincubation of pneumococci with sub-MIC concentrations of ceftriaxone (1/16x MIC), cefotaxime (1/8x MIC), and meropenem (1/4x MIC) alone or combined with levofloxacin (1/8x MIC) over 6 h prevents the emergence of levofloxacin-resistant mutants after 96 h of incubation but does not affect the intracellular accumulation of levofloxacin in two penicillin-resistant pneumococcal strains, suggesting a link between the mechanism of action of beta-lactams and the emergence of quinolone-induced resistance in pneumococci.

  19. Simultaneous determination of trace levels of 10 quinolones in swine, chicken, and shrimp muscle tissues using HPLC with programmable fluorescence detection.

    Science.gov (United States)

    Zhao, Sijun; Jiang, Haiyang; Li, Xuelian; Mi, Tiejun; Li, Cun; Shen, Jianzhong

    2007-05-16

    A HPLC method using a modified sample preparation procedure was optimized and validated for the quantification of 10 quinolones (QNs), including marbofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid, and flumequine, in swine, chicken, and shrimp tissues. In this method, only a small mass (residue limits (10 ng g-1) established in many countries. The method was also applied to the measurement of QN residues in commercial muscle samples. The results showed it was rapid, simple, sensitive, and suitable for use in food surveillance programs.

  20. [Surveillance of Antimicrobial Resistant Esherichia coli by Rectal Swab Method--Annual Change of Prevalence of Quinolone-resistant and ESBL Producing Strains from 2009 to 2013].

    Science.gov (United States)

    Nasu, Yoshitsugu; Sako, Shinichi; Yano, Tomofumi; Kosaka, Noriko

    2015-09-01

    Although most of commonly used antimicrobial agents had been susceptible to Esherichia coli, recently there are a lot of reports concerning about community-acquired infection caused by resistant E. coli. The aim of this study is to define the prevalence of resistant E. coli in normal flora colonization by the rectal swab method. From June 2009 to December 2013, 251 male patients (50-85 year-old, median 68) planned to transrectal prostate biopsy participated in this study. Stools stuck on the glove at the digital examination were provided for culture specimen. Identification of E. coli and determination of MIC was performed by MicroScan WalkAway40plus (Siemens). Isolated E. coli were deemed quinolone-resistant strains when their MIC of levofloxacine was 4 μg/mL or above according to the breakpoint MIC by the CLSI criteria. ESBL producing ability was determined by the double disk method used by CVA contained ESBL definition disc (Eikenkagaku). Of the 251 study patients, 224 patients had positive cultures of E. coli. Twenty-four patients had quinolone-resistant strains and 9 patients had ESBL producing strains. The prevalence of quinolone-resistant strains in 2009, 2010, 2011, 2012 and 2013 were 5.9% (2 out of 34 strains), 13.5% (5 out of 37 strains), 12.5% (4 out of 32 strains), 9.0% (6 out of 67) and 13.0% (7 out of 54 strains), respectively. The prevalence of ESBL producing strains in 2009, 2010, 2011, 2012 and 2013 were 0% (0 out of 34 strains), 5.4% (2 out of 37 strains), 3.1% (1 out of 32 strains), 3.0% (2 out of 67 strains) and 7.4% (4 out of 54 strains), respectively. In 2013, the prevalence of antimicrobial resistant E. coli, both quinolone-resistant and ESBL producing strains, were increasing. We have to pay a close attention to the increase of resistant E. coli.

  1. Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

    OpenAIRE

    Hooper, D C; Wolfson, J S; Souza, K S; Ng, E Y; McHugh, G L; Swartz, M N

    1989-01-01

    Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, ...

  2. Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives.

    Science.gov (United States)

    Psomas, George; Kessissoglou, Dimitris P

    2013-05-14

    The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

  3. Evaluation of quinolones for use in detection of determinants of acquired quinolone resistance, including the new transmissible resistance mechanisms qnrA, qnrB, qnrS, and aac(6')Ib-cr, in Escherichia coli and Salmonella enterica and determinations of wild-type distributions.

    Science.gov (United States)

    Cavaco, L M; Aarestrup, F M

    2009-09-01

    Fluoroquinolone resistance in members of the Enterobacteriaceae family is mostly due to mutations in the quinolone resistance-determining regions of the topoisomerase genes. However, transferable genes encoding quinolone resistance have recently been described. The current methods for susceptibility testing are not adapted to the detection of new resistance determinants, which confer low levels of resistance. The aim of this study was to compare the ability of the screening of the different quinolones by disk diffusion assays and MIC determinations to detect fluoroquinolone resistance. Sixty-nine Escherichia coli strains and 62 Salmonella strains, including strains fully susceptible to quinolones, nalidixic acid-resistant strains, strains with resistance to fluoroquinolones (resistant to nalidixic acid), and strains showing low-level resistance to fluoroquinolones conferred by transferable quinolone resistance genes, including qnrA, qnrB, qnrS, and aac(6')Ib-cr, were selected. Disk diffusion assays and MIC determinations by the agar dilution method were performed, according to CLSI standards, with nalidixic acid, flumequine, oxolinic acid, ciprofloxacin, enrofloxacin, marbofloxacin, norfloxacin, ofloxacin, and levofloxacin. The MIC of levofloxacin was determined by an Etest. The results showed a trimodal distribution of the MICs for both E. coli and Salmonella. The MIC distributions for the isolates varied with the compounds tested. Screening for nalidixic acid resistance by MIC testing or disk diffusion assay was not efficient for the detection of some of the isolates carrying qnr and aac(6')Ib-cr. Transferable resistance genes would best be detected by testing for the MIC of ciprofloxacin or norfloxacin, as testing for the MICs of the other compounds would fail to detect isolates carrying aac(6')Ib-cr because the enzyme produced is able to reduce the activities of these two compounds only due to their chemical structures. In conclusion, screening with nalidixic

  4. Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

    Directory of Open Access Journals (Sweden)

    Vinayak Mahadev Adimule

    2014-12-01

    Full Text Available In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa, Caco-2 and MCF7. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole 4a-e. The 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e. Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

  5. Antibiotic therapy for inducible AmpC β-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?

    Science.gov (United States)

    Harris, P N A; Ferguson, J K

    2012-10-01

    Some bacteria that possess chromosomally determined AmpC β-lactamases may express these enzymes at a high level following exposure to β-lactams, either by induction or selection for derepressed mutants. This may lead to clinical failure even if an isolate initially tests susceptible in vitro, a phenomenon best characterised by third-generation cephalosporin therapy for Enterobacter bacteraemia or meningitis. Several other Enterobacteriaceae, such as Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (often termed the 'ESCPM' group), may also express high levels of AmpC. However, the risk of clinical failure with β-lactams that test susceptible in vitro is less clear in these species than for Enterobacter. Laboratories frequently do not report β-lactam or β-lactamase inhibitor combination drug susceptibilities for ESCPM organisms, encouraging alternative therapy with quinolones, aminoglycosides or carbapenems. However, quinolones and carbapenems present problems with selective pressure for multiresistant organisms, and aminoglycosides with potential toxicity. The risk of emergent AmpC-mediated resistance for non-Enterobacter spp. appears rare in clinical studies. Piperacillin/tazobactam may remain effective and may be less selective for AmpC derepressed mutants than cephalosporins. The potential roles for agents such as cefepime or trimethoprim/sulfamethoxazole are also discussed. Clinical studies that better define optimal treatment for this group of bacteria are required.

  6. Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe

    Science.gov (United States)

    Wu, Zhiyuan; Shao, Pin; Zhang, Shaojuan; Ling, Xiaoxi; Bai, Mingfeng

    2014-07-01

    Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CBR in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CBR-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CBR. To synthesize the CBR-targeted probe (NIR760-Q), a conjugable CBR ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CBR positive cancers and elucidating the role of CBR in the regulation of disease progression.

  7. Stability of frozen stock solutions of beta-lactam antibiotics, cephalosporins, tetracyclines and quinolones used in antibiotic residue screening and antibiotic susceptibility testing.

    Science.gov (United States)

    Okerman, Lieve; Van Hende, Johan; De Zutter, Lieven

    2007-03-14

    The stability of frozen stock solutions of antibiotics belonging to three different families was evaluated using an agar diffusion test, with Bacillus subtilis as a test strain. Diameters of inhibition zones were measured at monthly intervals during 6 months, and the decline in active substance was calculated. Penicillin and amoxicillin lost nearly half of their potency, the cephalosporins ceftiofur and cefapirin one quarter, but ampicillin was more stable. The quinolones flumequine, enrofloxacin and marbofloxacin were relatively stable; the loss of activity was less than 10% after 6 months of preservation at -20 degrees C. This was also the case for doxycycline and chlortetracycline, while oxytetracycline and tetracycline lost about 25% of their potency. When used in microbiology, i.e. for residue testing or for determination of minimum inhibitory concentrations, a diminution of activity less than 25% will not be noticed. For these applications, the four tetracyclines and three quinolones tested can be kept for 6 months at -20 degrees C, while the beta-lactam antibiotics should be discarded after 3 months. Standard stock solutions of beta-lactam antibiotics and cephalosporins should preferably be used the same day when they are intended for quantitative residue analysis.

  8. Trace analysis of trimethoprim and sulfonamide, macrolide, quinolone, and tetracycline antibiotics in chlorinated drinking water using liquid chromatography electrospray tandem mass spectrometry

    Science.gov (United States)

    Ye, Z.; Weinberg, H.S.; Meyer, M.T.

    2007-01-01

    A multirun analytical method has been developed and validated for trace determination of 24 antibiotics including 7 sulfonamides, 3 macrolides, 7 quinolones, 6 tetracyclines, and trimethoprim in chlorine-disinfected drinking water using a single solid-phase extraction method coupled to liquid chromatography with positive electrospray tandem mass spectrometry detection. The analytes were extracted by a hydrophilic-lipophilic balanced resin and eluted with acidified methanol (0.1% formic acid), resulting in analyte recoveries generally above 90%. The limits of quantitation were mostly below 10 ng/L in drinking water. Since the concentrated sample matrix typically caused ion suppression during electrospray ionization, the method of standard addition was used for quantitation. Chlorine residuals in drinking water can react with some antibiotics, but ascorbic acid was found to be an effective chlorine quenching agent without affecting the analysis and stability of the antibiotics in water. A preliminary occurrence study using this method revealed the presence of some antibiotics in drinking waters, including sulfamethoxazole (3.0-3.4 ng/L), macrolides (1.4-4.9 ng/L), and quinolones (1.2-4.0 ng/L). ?? 2007 American Chemical Society.

  9. Identification, design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2).

    Science.gov (United States)

    Leung, Suet C; Gibbons, Peter; Amewu, Richard; Nixon, Gemma L; Pidathala, Chandrakala; Hong, W David; Pacorel, Bénédicte; Berry, Neil G; Sharma, Raman; Stocks, Paul A; Srivastava, Abhishek; Shone, Alison E; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Hill, Alasdair; Fisher, Nicholas E; Warman, Ashley J; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

    2012-03-08

    Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC(50) = 15 nM PfNDH2; IC(50) = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED(50)/ED(90) of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  10. Determination of quinolones of veterinary use in bee products by ultra-high performance liquid chromatography-tandem mass spectrometry using a QuEChERS extraction procedure.

    Science.gov (United States)

    Lombardo-Agüí, Manuel; García-Campaña, Ana M; Gámiz-Gracia, Laura; Cruces-Blanco, Carmen

    2012-05-15

    A reliable and rapid ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of the eight quinolones of veterinary use regulated by European Union (marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, flumequine and oxolinic acid). Chromatographic conditions were optimized in order to increase sample throughput and sensitivity. The antibiotics were detected by electrospray ionization in positive ion mode with multiple reaction monitoring (MRM) and MS/MS conditions were optimized in order to increase selectivity, selecting the corresponding product ions for quantification and identification. The separation was achieved in 3 min, using a Zorbax Eclipse Plus C18 column (50 mm × 2.1mm, 1.8 μm), with a mobile phase of 0.02% aqueous formic acid solution and acetonitrile. A dispersive solid phase extraction methodology, often referred to as the "QuEChERS" (quick, easy, cheap, effective, rugged, and safe) method, was optimized for extraction of the quinolones from honey and also it was evaluated for other bee products such as royal jelly and propolis. The method was validated for each matrix in terms of linearity, trueness, precision, limits of detection (LODs) and quantification (LOQ). LODs ranged between 0.2 and 4.1 μg kg(-1) with precision lower than 12% and satisfactory recoveries in most cases. The method was also applied for studying the occurrence of these antibiotics in several market samples.

  11. Structural requirements of 3-carboxyl-4(1H)-quinolones as potential antimalarials from 2D and 3D QSAR analysis.

    Science.gov (United States)

    Li, Jiazhong; Li, Shuyan; Bai, Chongliang; Liu, Huanxiang; Gramatica, Paola

    2013-07-01

    Malaria is a fatal tropical and subtropical disease caused by the protozoal species Plasmodium. Many commonly available antimalarial drugs and therapies are becoming ineffective because of the emergence of multidrug resistant Plasmodium falciparum, which drives the need for the development of new antimalarial drugs. Recently, a series of 3-carboxyl-4(1H)-quinolone analogs, derived from the famous compound endochin, were reported as promising candidates for orally efficacious antimalarials. In this study, to analyze the structure-activity relationships (SAR) of these quinolones and investigate the structural requirements for antimalarial activity, the 2D multiple linear regressions (MLR) method and 3D comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods are employed to evolve different QSAR models. All these models give satisfactory results with highly accurate fitting and strong external predictive abilities for chemicals not used in model development. Furthermore, the contour maps from 3D models can provide an intuitive understanding of the key structure features responsible for the antimalarial activities. In conclusion, we summarize the detailed position-specific structural requirements of these derivatives accordingly. All these results are helpful for the rational design of new compounds with higher antimalarial bioactivities. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Multiresidue confirmatory method for determination of quinolones in milk by HPLC: method development and validation according to the criteria of Commission Decision 2002/657/EC

    Directory of Open Access Journals (Sweden)

    Federica Ostorero

    2013-04-01

    Full Text Available Veterinary drugs have become an integral part of the livestock production and play an important role in maintaining animal welfare. The use of veterinary medicines may be cause of the presence of drug residues in animal food products if appropriate withdrawal periods are not respected or if contaminated feeds are used. This work presents the development of an high performance liquid chromatography with postcolumn fluorescence derivatization (HPLC-FLD method for the quantitative detection of eight quinolones – norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, difloxacin, oxolinic acid, nalidixic acid, and flumequine – in bovine milk. After deproteination and extraction with a metaphosphoric acid 1% w/v/methanol/acetonitrile (60/20/20 v/v/v solution, the sample is partially evaporated and cleaned up on a reversed phase solid phase extraction (SPE cartridge. The extract is analyzed using an HPLC-FLD. Mean recovery ranged between 65-88%. The method is validated as a confirmatory method according to Decision 2002/657/EC. All the verified parameters (linearity, selectivity/specificity, trueness, precision, CC, ruggedness and stability were satisfactory and the method is able to quantify all the analytes in milk in the concentration range 15-60 μg/Kg for danofloxacin and 25-150 μg/Kg for the other quinolones.

  13. Evaluation and Intervention Study on Rational Use of Quinolones%喹诺酮类药合理应用评估与干预研究

    Institute of Scientific and Technical Information of China (English)

    张楠; 夏文斌; 杨悦

    2012-01-01

    OBJECTIVE: To investigate the effect of systematic prescription evaluation and intervention model on improving rational use of quinolones. METHODS: The systematic prescription evaluation and intervention model were put into practice which included establishing the expert evaluation group to develop the evaluation standards of rational use of quinolones, formulating the prescription checking standards before pharmacist dispensing drugs and making comprehensive intervention measures. All outpatient quinolone prescriptions in Jan. 2010(before intervention) and Jan. 2011 (after intervention) were sampled for rationality evaluation and contrast study before and after intervention. RESULTS: The utilization ratio of quinolone in outpatient department of our hospital decreased after intervention, the drug use of non-indications was reduced from 9.46% to 3.93%(/'<0.01) and drug use of contraindication was decreased from 0.34% to Q(P<0.0l), the occurrence of incorrect dosage and usage was reduced from 6.31% to 2.04%(p<0.01), and the occurrence of inappropriate drug combination was reduced from 12.17% to 6.68%(p<0.01). CONCLUSION: Systematic prescription evaluation and intervention model can significantly improve rational use of quinolone in our hospital.%目的:探讨系统化处方评估与干预工作模式对促进喹诺酮类药临床合理应用的效果.方法:运用系统化处方评估与干预工作模式,组建专家小组指导建立评估标准,制定药师发药前处方审核规范,综合制定医师合理用药干预策略,并抽取我院门诊2010年1月(干预前)和2011年1月(干预后)全部喹诺酮类药处方,分别为2 029张及1 961张,进行合理性评估及干预前、后对照研究.结果:干预后我院门诊喹诺酮类药应用率降低,非适应证用药由干预前的9.46%降至干预后的3.93%(P<0.01),禁忌证用药由干预前的0.34%降至0(P<0.01),用法用量不适宜由干预前的6.31%降至2.04%(P<0.01),联合

  14. Membrane Distribution of the Pseudomonas Quinolone Signal Modulates Outer Membrane Vesicle Production in Pseudomonas aeruginosa.

    Science.gov (United States)

    Florez, Catalina; Raab, Julie E; Cooke, Adam C; Schertzer, Jeffrey W

    2017-08-08

    The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule in Pseudomonas aeruginosa that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand how they are formed. Our group proposed the bilayer-couple model for OMV biogenesis, where PQS intercalates into the outer membrane, causing expansion of the outer leaflet and consequently inducing curvature. In accordance with the model, we hypothesized that PQS must be transported from the cytoplasm to the outer membrane before it can initiate OMV formation. We initially examined two laboratory strains of P. aeruginosa and found significant strain-dependent differences. PQS export correlated strongly with OMV production, even though equivalent amounts of total PQS were produced by both strains. Interestingly, we discovered that poor OMV producers sequestered the majority of PQS in the inner membrane, which appeared to be the result of early saturation of the export pathway. Further analysis showed that strain-specific PQS export and OMV biogenesis patterns were stable once established but could be significantly altered by changing the growth medium. Finally, we demonstrated that the associations described for laboratory strains also held for three clinical strains. These results suggest that factors controlling the export of PQS dictate OMV biogenesis. This work provides new insight into PQS-controlled virulence in P. aeruginosa and provides important tools to further study signal export and OMV biogenesis.IMPORTANCE Bacterial secretion has been recognized as an essential facet of microbial pathogenesis and human disease. Numerous virulence factors have been found to be transported within outer membrane vesicles (OMVs), and delivery using these biological nanoparticles often results in increased potency. OMV biogenesis is an important but poorly

  15. 分析药学干预对喹诺酮类药物使用情况的影响%Pharmacy Intervention impact analysis on the use of quinolones

    Institute of Scientific and Technical Information of China (English)

    郭芳

    2015-01-01

    Objective To observe the pharmacy intervention quinolones application value. Methods June 2013-June 2014 in our hospital pharmacy intervention quinolones were observed intervention effects. Results After the implementation of pharmaceutical intervention, our hospital quinolones amount spent significantly reduced the rate of irrational drug use and drug significantly reduced. Conclusion Pharmacy intervention has a higher value in quinolones applications, it is worth all levels of hospital applications.%目的:观察药学干预在喹诺酮类药物中的应用价值。方法2013年6月~2014年6月对我院喹诺酮类药物进行药学干预,观察干预效果。结果实施药学干预后,我院喹诺酮类药物花费金额明显降低,不合理用药率与耐药率明显减低。结论药学干预在喹诺酮类药物应用中具有较高的价值,值得各级医院应用。

  16. International collaborative study on the occurrence of plasmid mediated quinolone resisitance in Salmonella enterica en Escherichia coli isolated from animals, humans, food and the environment in 13 European countries.

    NARCIS (Netherlands)

    Veldman, K.T.; Cavaco, L.M.; Mevius, D.J.; Battisti, A.; Botteldoorn, N.; Bruneau, M.; Cerny, T.; Franco, A.; Frutos Escobar, De C.; Guerra, B.; Gutierrez, M.; Hopkins, K.; Myllyniemi, A.L.; Perrin-Guyomard, A.; Schroeter, A.; Sunde, M.; Wasyl, D.; Aarestrup, F.M.

    2011-01-01

    Objectives This study was initiated to collect retrospective information on the occurrence of plasmid-mediated quinolone resistance (PMQR) in Salmonella enterica and Escherichia coli isolates in Europe and to identify the responsible genes. Methods Databases of national reference laboratories contai

  17. A facile route to 5-methyl-5H-indeno[1,2-c]quinolones via palladium-catalyzed cyclization of 2-alkynylbromobenzenes with N,N-dimethyl-2-alkynylanilines.

    Science.gov (United States)

    Pan, Xiaolin; Luo, Yong; Kuang, Yunyan; Li, Guangming

    2014-08-21

    A tandem reaction catalyzed by palladium is developed to provide a facile and simple route for the synthesis of 5-methyl-5H-indeno[1,2-c]quinolones, which can introduce diversity and complexity into the products from readily available starting materials. This transformation proceeds well with good functional group tolerance.

  18. Anilides and quinolones with nitrogen-bearing substituents from benzothiophene and thienothiophene series: synthesis, photochemical synthesis, cytostatic evaluation, 3D-derived QSAR analysis and DNA-binding properties.

    Science.gov (United States)

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Depauw, Sabine; Martin-Kleiner, Irena; David-Cordonnier, Marie-Hélène; Tomić, Sanja; Kralj, Marijeta; Karminski-Zamola, Grace

    2014-01-01

    A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of photochemical dehydrohalogenation from corresponding anilides. Anilides and quinolones were tested for the antiproliferative activity. Fused quinolones bearing protonated aminium group, quaternary ammonium group, N-methylated and protonated aminium group, amino and protonated amino group (8a, 9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active one, having the IC50 concentration at submicromolar range in accordance with previous QSAR predictions. On the other hand, flexible anilides were among the less active. Chemometric analysis of investigated compounds was performed. 3D-derived QSAR analysis identified solubility, metabolitic stability and the possibility of the compound to be ionized at pH 4-8 as molecular properties that are positively correlated with anticancer activity of investigated compounds, while molecular flexibility, polarizability and sum of hydrophobic surface areas were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b, 8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases I/II inhibition as part of their mechanism of action. Among the anilides, only compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14, were clearly distinguished from the other compounds according to their molecular descriptors by the PCA and PLS analysis.

  19. 喹诺酮耐药大肠埃希菌尿道感染现状及危险因素分析%Quinolone resistant Escherichia coli isolated from urinary tract infection:clinical status and risk factors

    Institute of Scientific and Technical Information of China (English)

    张安兵

    2012-01-01

    Objective To investigate the quinolone resistant Escherkhia coli infection status and risk factors, and provide a basis for selecting appropriate antibiotics in the clinical practice. Methods This study is a retrospective review from 2010 to 2011. 348 strains Escherichia coli isolated from urine specimens were analysis, using the quinolone susceptible isolates as the control group. The risk factors for the quinolone resistance strains were analyzed. Results Of the 348 E.coli strains isolated from urinary tract infection patient, 58.3% (203)were quinolone resistant. Logistic regression analysis showed three generation cephalosporins and quinolones drug use, urinary drainage and bacterium producing extra-broad spectrum beta-lactamase were the independent risk factors for ciprofloxacin resistance of E.coli strains isolated from urinary tract infection patients. Conclusion The epidemic of quinolone resistant Escherichia coli isolated from urine specimens were extremely serious. The drug resistance of the quinolone resistant isolates was strong. The patients infected with quinolone resistant strains had high medical cost and longer average length of stay in hospital. The quinolone resistant E.coli infection with multiple independent risk factors, the strengthening of these independent risk factor controls can effectively prevent the spread of quinolone resistant strains infection.%目的 分析喹诺酮耐药大肠埃希菌尿道感染现状及危险因素,为临床合理选用抗生素提供依据.方法 回顾性分析348例大肠埃希菌尿道感染临床现状,以喹诺酮敏感大肠埃希菌为对照菌株,对喹诺酮耐药大肠埃希菌感染危险因素进行分析.结果 348株大肠埃希菌尿道感染中检出喹诺酮耐药菌203株,占58.3%.Logistic回归分析显示三代头孢菌素及喹诺酮类药物使用、尿路引流和细菌产超广谱β-内酰胺酶是喹诺酮耐药大肠埃希菌感染的独立危险因素.结论 尿道感染大肠埃

  20. Characterization of ESBLs and associated quinolone resistance in Escherichia coli and Klebsiella pneumoniae isolates from an urban wastewater treatment plant in Algeria.

    Science.gov (United States)

    Alouache, Souhila; Estepa, Vanesa; Messai, Yamina; Ruiz, Elena; Torres, Carmen; Bakour, Rabah

    2014-02-01

    The aim of the study was the characterization of extended spectrum beta-lactamases (ESBLs) and quinolone resistance in cefotaxime-resistant coliform isolates from a wastewater treatment plant (WWTP). ESBLs were detected in 19 out of 24 isolates (79%) from raw water and in 21 out of 24 isolates (87.5%) from treated water, identified as Klebsiella pneumoniae and Escherichia coli. Molecular characterization of ESBLs and quinolone resistance showed allele profiles CTX-M-15 (3), CTX-M-3 (5), CTX-M-15+qnrB1 (1), CTX-M-3+qnrB1 (1), CTX-M-15+aac-(6')-Ib-cr (4), and CTX-M-15+qnrB1+aac-(6')-Ib-cr (7). A double mutation S83L and D87N (GyrA) and a single mutation S80I (ParC) were detected in ciprofloxacin-resistant E. coli isolates. In K. pneumoniae, mutations S83I (GyrA)+S80I (ParC) or single S80I mutation were detected in ciprofloxacin-resistant isolates, and no mutation was observed in ciprofloxacin-susceptible isolates. bla(CTX-M), qnrB1, and aac-(6')-Ib-cr were found, respectively, in these genetic environments: ISEcp1-bla(CTX-M)-orf477, orf1005-orf1-qnrB1, and Tn1721-IS26-aac-(6')-Ib-cr-bla(OXA-1)-catB4. bla(CTX-M-15) was located on IncF plasmid in E. coli and bla(CTX-M-3) on IncL/M plasmid in both species (E. coli and K. pneumoniae). E. coli isolates were affiliated to the phylogroups/MLST: D/ST405 (CC405), A/ST10 (CC10), A/ST617 (CC10), and B1/ST1431. K. pneumoniae isolates belonged to phylogroup KpI and to sequence types ST15, ST17, ST36, ST48, ST54, and ST147. The study showed a multi-drug resistance at the inflow and outflow of the WWTP, with ESBL production, plasmid-mediated quinolones resistance, and mutations in topoisomerases. The findings highlight the similarity of antibiotic resistance mechanisms in the clinical setting and the environment, and the role of the latter as a source of dissemination of resistance genes.

  1. Determination of Quinolones and Nonsteroidal anti-Inflammatory Agents in Animal Tissues and Bovine Milk by Microwave-assisted Extraction High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xi-Liu; DING Lan; JIN Hai-Yan; LIU Miao; CHENG Jian-Hua; WU Xiu-Feng; ZHAI Yu-Juan; SUN Yan-Tao; ZHANG Han-Qi; YU Yong; WANG Xiu-Pin

    2008-01-01

    A rapid,specific microwave-assisted extraction high performance liquid chromatography is described for assaying three quinolones(fleroxacin,lomefloxacin and sparfloxacin)and two nonsteroidal anti-inflammatory agents(ketoprofen and ibuprofen)in samples of sheep liver,bovine muscle and milk.The optimal microwave-assisted extraction conditions such as extraction temperature(40 ℃),extraction time(6 min),solvent volume(10 mL)and solvent(acetonitrile)were determined by an orthogonal experiment.Recoveries were 60.0%-107% in the concentration range 0.25-0.75 μg·g with good precision(< 11%)from three varieties of spiked animal samples.

  2. The mechanism of Quinolone resistance and its research progress%喹诺酮类抗菌药的耐药机制及其研究进展

    Institute of Scientific and Technical Information of China (English)

    林惊世; 顾晟琰; 蒋震媚

    2012-01-01

    喹诺酮类(quinolones)药物是人工合成的含4-喹诺酮基本结构,对细菌DNA螺旋酶(DNA gyrase)具有选择性抑制作用,是一种DNA旋转酶抑制剂,干扰DNA超螺旋结构的解旋,从而阻碍DNA的复制,而呈现杀菌作用,故在分类上属慢效杀菌剂.笔者通过检索、查阅相应文献,综合归纳了喹诺酮类抗菌药物的耐药机制及其研究进展.

  3. Mechanistic study of electrochemical oxidation of o-dihydroxybenzenes in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Moghaddam, Abdolmajid Bayandori [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of)]. E-mail: bayandori@gmail.com; Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of); Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of); Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Davarani, Saied Saeed Hosseiny [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of)

    2005-11-01

    Electrochemical oxidation of o-dihydroxybenzenes (1a and 1b) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-quinones derived from o-dihydroxybenzenes (1a and 1b) participate in 1,4-(michael) addition reactions with 3 to form the corresponding new o-dihydroxybenzene derivatives (6a and 6b). We propose a mechanism for the electrode process. The efficient electrochemical synthesis of 6a and 6b has been successfully performed at carbon rod electrodes in an undivided cell in good yield and purity. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  4. 喹诺酮类药物色谱手性分析的进展%Advances in Chiral Chromatographic Analysis of Quinolones Drugs

    Institute of Scientific and Technical Information of China (English)

    洪建文; 胡昌勤; 盛龙生

    2003-01-01

    @@ 喹诺酮类(quinolones)药物是近年新开发的一类全合成抗菌药.此类以细菌的脱氧核糖核酸(DNA)为靶点,通过抑制细菌DNA消旋酶(grase)和 DNA拓扑异构酶Ⅳ(topoisomerase Ⅳ),干扰细菌DNA的复制,造成细胞不可逆的损害,使细菌死亡[1].近20年来因其抗菌谱广、抗菌活性强、制剂剂型较多、使用方便等优点,发展迅速并已被普遍应用.

  5. Mechanistic study of electrochemical oxidation of catechols in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)]. E-mail: a-zavareh@sbu.ac.ir; Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Moghaddam, Abdolmajid Bayandori [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)

    2005-09-20

    Electrochemical oxidation of catechols (1a-1c) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a-1c) participate in Michael addition reactions with 3 to form the corresponding benzofuran (or isochromeno[4,3-c]quinoline) derivatives (6a-6c). The electrochemical synthesis of (6a-6c) has been successfully performed in an undivided cell in good yield and purity. The oxidation mechanism was deduced from voltammetric data and by coulometry at controlled-potential. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  6. Extended-Spectrum-Beta-Lactamases, AmpC Beta-Lactamases and Plasmid Mediated Quinolone Resistance in Klebsiella spp. from Companion Animals in Italy

    DEFF Research Database (Denmark)

    Donati, Valentina; Feltrin, Fabiola; Hendriksen, Rene S.

    2014-01-01

    We report the genetic characterization of 15 Klebsiella pneumoniae (KP) and 4 isolates of K. oxytoca (KO) from clinical cases in dogs and cats and showing extended-spectrum cephalosporin (ESC) resistance. Extended spectrum beta-lactamase (ESBL) and AmpC genes, plasmid-mediated quinolone resistance...... patterns observed, including two clusters of two (ST340) and four (ST101) indistinguishable isolates, respectively. All isolates harbored at least one ESBL or AmpC gene, all carried on transferable plasmids (IncR, IncFII, IncI1, IncN), and 16/19 were positive for PMQR genes (qnr family or aac(6')-Ib...... of multidrug-resistant Klebsiella with ESBL, AmpC and PMQR determinants, poses further and serious challenges in companion animal therapy and raise concerns for possible bidirectional transmission between pets and humans, especially at household level....

  7. Determination of (fluoro)quinolone antibiotic residues in pig kidney using liquid chromatography-tandem mass spectrometry. Part II: intercomparison exercise.

    Science.gov (United States)

    Toussaint, B; Chedin, M; Vincent, U; Bordin, G; Rodriguez, A R

    2005-09-23

    A recently in-house validated method for the liquid chromatography-tandem mass spectrometry (LC-MS/MS) determination of eleven (fluoro)quinolone antibiotics (FQs) in pig kidney has been fully validated through an intercomparison exercise. This ring trial involved eight European laboratories and was based on the Commission Decision 2002/657/CE for validation of method and on the IUPAC protocol for method-performances studies. The laboratories data were submitted to a one-way analysis of variance. Satisfactory results were obtained for each FQ with regards to within- and between-laboratory reproducibility and accuracy. The method was validated for the simultaneous qualitative and quantitative determination of the eleven FQs in pig kidney around their maximum residue limit (MRL) as defined in the European Council Regulation 2377/90/EEC.

  8. Presence of quinolone resistance to qnrB1 genes and blaOXA-48 carbapenemase in clinical isolates of Klebsiella pneumoniae in Spain.

    Science.gov (United States)

    Rodríguez Martínez, J M; Díaz-de Alba, P; Lopez-Cerero; Ruiz-Carrascoso, G; Gomez-Gil, R; Pascual, A

    2014-01-01

    A study is presented on the presence of quinolone resistance qnrB1 genes in clinical isolates belonging to the largest series of infections caused by OXA-48-producing Klebsiella pneumoniae in a single-centre outbreak in Spain. Evidence is also provided, according to in vitro results, that there is a possibility of co-transfer of plasmid harbouring blaOXA-48 with an other plasmid harbouring qnrB1 in presence of low antibiotic concentrations of fluoroquinolones, showing the risk of multi-resistance screening. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Occurrence of Extended-Spectrum β-Lactamases, Plasmid-Mediated Quinolone Resistance, and Disinfectant Resistance Genes in Escherichia coli Isolated from Ready-To-Eat Meat Products

    DEFF Research Database (Denmark)

    Li, Lili; Ye, Lei; Kromann, Sofie

    2017-01-01

    There are growing concerns about the coselection of resistance against antibiotics and disinfectants in bacterial pathogens. The aim of this study was to characterize the antimicrobial susceptibility profiles, the prevalence of extended-spectrum β-lactamases (ESBLs), plasmid-mediated quinolone...... resistance genes (PMQRs), and quaternary ammonium compound resistance genes (QACs) in Escherichia coli isolated from ready-to-eat (RTE) meat products obtained in Guangzhou, China, and to determine whether these genes were colocalized in the isolates. A total of 64 E. coli isolates were obtained from 720 RTE...... meat samples. Multidrug resistance was observed in 70.3% of the isolates. A 100% of the isolates were resistant to benzalkonium chloride. Four types of β-lactamase genes were identified in the 16 ESBL-producing E. coli isolates: blaSHV (9.4%), blaTEM (7.8%), blaCTX-M-15 (1.6%), and blaCTX-M-9 (1...

  10. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Microbiology Profiling Studies with Staphylococci and Streptococci ▿

    Science.gov (United States)

    Robertson, Gregory T.; Bonventre, Eric J.; Doyle, Timothy B.; Du, Qun; Duncan, Leonard; Morris, Timothy W.; Roche, Eric D.; Yan, Dalai; Lynch, A. Simon

    2008-01-01

    We present data from antimicrobial assays performed in vitro that pertain to the potential clinical utility of a novel rifamycin-quinolone hybrid antibiotic, CBR-2092, for the treatment of infections mediated by gram-positive cocci. The MIC90s for CBR-2092 against 300 clinical isolates of staphylococci and streptococci ranged from 0.008 to 0.5 μg/ml. Against Staphylococcus aureus, CBR-2092 exhibited prolonged postantibiotic effects (PAEs) and sub-MIC effects (SMEs), with values of 3.2, 6.5, and >8.5 h determined for the PAE (3× MIC), SME (0.12× MIC), and PAE-SME (3× MIC/0.12× MIC) periods, respectively. Studies of genetically defined mutants of S. aureus indicate that CBR-2092 is not a substrate for the NorA or MepA efflux pumps. In minimal bactericidal concentration and time-kill studies, CBR-2092 exhibited bactericidal activity against staphylococci that was retained against rifampin- or intermediate quinolone-resistant strains, with apparent paradoxical cidal characteristics against rifampin-resistant strains. In spontaneous resistance studies, CBR-2092 exhibited activity consistent with balanced contributions from its composite pharmacophores, with a mutant prevention concentration of 0.12 μg/ml and a resistance frequency of <10−12 determined at 1 μg/ml in agar for S. aureus. Similarly, CBR-2092 suppressed the emergence of preexisting rifamycin resistance in time-kill studies undertaken at a high cell density. In studies of the intracellular killing of S. aureus, CBR-2092 exhibited prolonged bactericidal activity that was superior to the activities of moxifloxacin, rifampin, and a cocktail of moxifloxacin and rifampin. Overall, CBR-2092 exhibited promising activity in a range of antimicrobial assays performed in vitro that pertain to properties relevant to the effective treatment of serious infections mediated by gram-positive cocci. PMID:18443106

  11. Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.

    Science.gov (United States)

    Hou, Xiao-Lin; Chen, Guo; Zhu, Li; Yang, Ting; Zhao, Jian; Wang, Lei; Wu, Yin-Liang

    2014-07-01

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 38 veterinary drugs (18 sulfonamides, 11 quinolones and 9 benzimidazoles) and 8 metabolites of benzimidazoles in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were extracted with acidified acetonitrile, cleaned up with Oasis(®) MCX cartridges, and analyzed by LC-MS/MS on an Acquity UPLC(®) BEH C18 column with gradient elution. The method allows such multi-analyte measurements within a 13min runtime while the specificity is ensured through the MRM acquisition mode. The method was validated according to the European Commission Decision 2002/657/EC determining specificity, decision limit (CCα), detection capability (CCβ), recovery, precision, linearity and stability. For compounds which have MRLs in bovine milk, the CCα values fall into a range from 11 to 115μg/kg, and the CCβ values fall within a range of 12-125μg/kg. For compounds which have not MRLs in bovine milk, the CCα values fall into a range from 0.01 to 0.08μg/kg, and the CCβ values fall within a range of 0.02-0.11μg/kg. The mean recoveries of the 46 analytes were between 87 and 119%. The calculated RSD values of repeatability and within-laboratory reproducibility experiments were below 11% and 15% for the 46 compounds, respectively. The method was demonstrated to be suitable for the simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.

  12. Antibodies to the quinolones and fluoroquinolones for the development of generic and specific immunoassays for detection of these residues in animal products.

    Science.gov (United States)

    Bucknall, S; Silverlight, J; Coldham, N; Thorne, L; Jackman, R

    2003-03-01

    Several quinolone and fluoroquinolone haptens have been used to raise polyclonal antibodies exhibiting both specific and generic properties for these classes of antimicrobial compounds. The antisera have been assessed in rapid enzyme immunoassays (ELISAs) designed to exploit the specificities obtained. A direct generic ELISA for both the quinolones and fluoroquinolones has been developed that uses the cross-reactivity of an antibody raised against norfloxacin (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid) linked to ovalbumin via a secondary amine group on the piperazinyl moiety to detect nine different drugs in these classes. Specific ELISAs to ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid), enrofloxacin (1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid), flumequin (9-fluoro-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxylic acid) and nalidixic acid (1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid) have also been developed with a high degree of specificity to the individual compounds. The assays measure drug residues in bovine milk and ovine kidney with an interassay relative standard deviation (s(r)) of 10.5% or less and intra-assay s(r) of 11.2% or less. Sensitivity is less than 4 microg x kg(-1) for both the generic and specific assays for all but one of the compounds tested. (Pipemidic acid (8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido(2,3-d)pyrimidine-6-carboxylic acid) is detectable at 6 microg x kg(-1) in kidney.)

  13. Prevalence and Resistance Status of Escherichia Coli in Quinolones and Its Prevention and Cure Strategies%大肠埃希氏菌对喹诺酮类药物的耐药现状及防治

    Institute of Scientific and Technical Information of China (English)

    吴勇德; 唐志君

    2014-01-01

    喹诺酮类药物(Quinolones,Qs)是一类合成广谱抗菌药,自20世纪60年代萘啶酸被运用于临床医学以后,同时喹诺酮类药物的耐药问题便接踵而至,这使得喹诺酮类药物成为开发最活跃,更新换代最迅速的药物。由于其具有抗菌谱广,抗菌活性强,与常用抗菌药物无交叉耐药,已成为临床治疗感染性疾病的主要药物之一。然而,随着喹诺酮类药物在人医和兽医临床的广泛、长期、大量盲目滥用,使得其耐药性近年呈蔓延增长趋势,耐药程度越来越重,耐药菌株越来越多。其中,大场杆菌对喹诺酮类药物的耐药性问题是当前国内外研究的热点。本文综述了大肠杆菌对氟喹诺酮类药物耐药现状及特点,并分析了其耐药机制,简要综述了减缓耐药性的一些防治策略。%The Quinolones is a kind of synthetic wide table antimicrobial, Dixiben was applied to clinic medicine since the sixties of the 20th century the question of resistance of Quinolones appeared at the same time that made Quinolones become and develop the most active, update the fastest medicine. Because it has antibacterial wide tables, the antibacterial activity is strong and have not been cross resistance with daily antibacterial medicines, have become one of the clinical main medicines to treat the infective disease. However, as the Quinolones abuse in people and veterinarian's medicine and clinical y extensively and long-termly and in a large amount led to bacterias resistance to quinolones show a tendency to spread and increase in recent years, resistance degree to be more and more heavy , resistance of strains are more and more many. Quinolone resistance in Escherichia coli is a focus studied both at home and abroad at present . The review focuses on prevalence and resistance status of E.coli in Quinolones, the mechanism of Quinolones resistance in E.coli and provides some prevention and cure strategies

  14. 尿道感染大肠埃希菌对喹诺酮耐药性及相关因素分析%Drug Resistance and Risk Factors Analysis of Escherichia Coli Isolated from Urinary Tract Infection to Quinolone

    Institute of Scientific and Technical Information of China (English)

    张昭勇; 张吉才; 杜毅

    2013-01-01

    Objective To investigate the drug resistance and risk factors of Escherichia coli isolated from urinary tract infection (UTI) to quinolone. Methods Drug resistance of 705 strains of Escherichia coli isolated from 749 urine specimens of UTI from 2010 to 2011 in our hospital were detected and divided into the resistance group and the sensitive group according to sensitiveness to quinolone, and the risk factors of the quinolone resistance strains were analyzed. Results In 705 strains isolates E. coli, there were 474 strains (67. 2% ) of quinolone resistance in the resistance group, 231 strains (32. 8% ) of quinolone sensitiveness in the sensitive group and there was no carbapenem resistant strain. The differences in resistance rates of amoxicillin/clavulanic acid, cefotaxime, ceftazidime, aztreonam, piperacillin, amikacin, bactrim, gentamicin and cefepime of the two groups were statistically significant (P<0. 05) . Logistic regression analysis showed that the proportion of female patients, drug use of tert-cephalosporins and quinolones, urinary drainage and bacterium producing extended spectrum β lactamases (ESBLS) were independent risk factors of quinolone resistance E. coli. The differences in hospital stay and cost of the two groups were statistically significant (P<0. 05). Conclusion The detection rate of quinolone resistance escherichia coli isolated from UIT is high. The emergence of resistant strains is related to antibiotic application, invasive handling and bacterial variation. To strengthen the independent risk factors regulation can effectively prevent and control spread of infection.%目的 探讨尿道感染(urinary tract infection,UIT)大肠埃希菌对喹诺酮耐药性及其相关因素.方法 对我院2010-2011年749例UIT尿液标本中分离的705株大肠埃希菌的耐药性进行检测,以对喹诺酮敏感与否分为耐药株组和敏感株组,分析耐药株感染的相关因素.结果 705株大肠埃希菌中对喹诺酮耐药474株(67.2

  15. Mechanism of Quinolone Resistance and Its Research Progress%喹诺酮类药物的作用机制耐药机制及研究进展

    Institute of Scientific and Technical Information of China (English)

    刘杨; 欧宁

    2014-01-01

    Quinolones are broad spectrum antibiotics for clinical infections, by binding on topoisomerases to prevent DNA replication. But the problems of drug resistance increase seriously in recent years. This arti-cle reviews the mechanism of quinolone resistance and its research progress.%喹诺酮类药物主要作用于DNA拓扑异构酶,阻碍DNA复制,发挥广谱抗菌作用。但该类药物的耐药问题日益严重,耐药菌株频现。本文综述喹诺酮类药物的耐药机制及其研究进展。

  16. Research on the new resistance mechanism of quinolones mediated by aac(6')-Ib-cr%aac(6')-Ib-cr介导的喹喏酮类新耐药机制研究进展

    Institute of Scientific and Technical Information of China (English)

    孙攀; 殷瑜; 陈代杰

    2009-01-01

    AAC(6')- Ib are important aminoglycoside acetyltransferases.The variable gene aac(6')-Ib-cr acts on both quinolones and aminoglycosides, which belong to different classes of antibiotics based on their chemical structures, leading to the bacteria resistance. This paper briefly reviews the new resisitant mechanism of quinolones mediated by aac(6')-Ib-cr.%AAC(6')-Ib是重要的氨基糖苷乙酰基团转移酶,其变异基因aac(6')-Ib-cr可同时作用于氨基糖苷类和氟喹诺酮类两类结构不同的抗生素,是引起细菌耐药性的一种重要作用机制.该文主要对aac(6')-Ib-cr介导的喹诺酮类新耐药机制相关研究进行综述.

  17. 我院129例喹诺酮类抗菌药物致不良反应报告分析%Analysis of 129 Cases of Adverse Drug Reactions Induced by Quinolones

    Institute of Scientific and Technical Information of China (English)

    金伟华; 王晓蕙; 陈华; 谭永红

    2011-01-01

    目的:探讨喹诺酮类药物致不良反应(ADR)的特点,为其临床合理应用提供参考.方法:收集2004年1月-2011年1月我院应用喹诺酮类抗菌药物致ADR的临床资料,进行总结、分析.结果:我院共报告129例喹诺酮类致ADR,涉及8个药品种类,左氧氟沙星最多,发生86例,占66.67%;从受损系统或器官看,皮肤及附件最多,发生49例,占37.98%.结论:临床应重视合理使用喹诺酮类抗菌药物,杜绝或减少ADR的重复发生.%OBJECTIVE: To explore the characteristics of adverse drug reactions (ADR) induced by quinolones and to provide reference for rational drug use in the clinic. METHODS: Clinical information of ADR induced by quinolones collected from our hospital during Jan. 2004-Jan. 2011 were analyzed and summarized. RESULTS: 129 ADR cases induced by quinolones in our hospital involved 8 drug categories. Main type of ADR-inducing drugs was levofloxacin (86 cases, accounting for 66.67% ). In respective of injured system and site, lesion of skin and its appendants occupied great proportion and appeared in 49 cases, accounting for 37.98%. CONCLUSION: To use quinolones rationally and great importance should be attached to the adverse consequences of its ADR.

  18. 喹诺酮类药物的耐药、联合用药及不良反应分析%Analysis of drug resistance,drug combination and adverse reactions of quinolones

    Institute of Scientific and Technical Information of China (English)

    孙志勇

    2013-01-01

    目的研究喹诺酮类药物的耐药、联合用药和不良反应。方法对本院应用喹诺酮类药物治疗后出现不良反应的60例患者的临床资料进行回顾性分析。结果常见的不良反应主要为全身性损伤(14例,23.4%)、皮肤方面的损伤(12例,20.0%)和神经系统损伤(18例,30.0%)。喹诺酮类药物目前的耐药情况比较严重。结论喹诺酮类药物应合理使用,并掌握其临床适应证以及剂量,尽可能避免联合用药的不合理性和不良反应的发生。%Objective To investigate the resistance,drug combination and adverse reactions of quinolones. Methods Clinical data of 60 patients who had adverse reactions after using quinolones in our hospital were collected and analyzed retrospectively. Results The main common adverse reactions were systemic injury(14 patients,23.4%),skin injury (12 patients,20.0%) and nervous system injury(18 patients,30.0%). The current drug resistance situation of quinolones was severe. Conclusion Quinolones should be used rationally and their clinical indications and doses should be mastered in order to avoid the irrationality of drug combination and the occurrence of adverse reactions.

  19. 喹诺酮类药物致血糖异常107例分析%The analysis of unconventional blood sugar induced by quinolones in 107 clinical cases

    Institute of Scientific and Technical Information of China (English)

    张国忠; 虞晓红

    2010-01-01

    目的 了解喹诺酮类药物引起血糖异常的特点和规律,以促进临床合理用药.方法 检索1995年至2008年中国医院数字图书馆CHKD期刊数据网收载的医药卫生期刊,对其报道的喹诺酮类药物引起的血糖异常个案进行统计和分析.结果 引起血糖异常涉及9种喹诺酮类药物,共107例,致低血糖70例(其中因低血糖昏迷致死3例),致血糖升高37例.结论 加强喹诺酮类药物的合理使用,对于老年患者、肾功能不全的糖尿病患者使用该类药物时应监测患者血糖变化情况,以确保用药安全.%Objective To survey the unconventional blood sugar level induced by quinolones and promote the rational drug use in clinical. Methods Collecting and analysis the unconventional blood sugar level induced by quinolones reported during the period of 1995 ~ 2008 using CHKD net. Results 107 cases of unconventional blood sugar level were reported by using 9 kinds of quinolones and among them 70 cases with hypoglycemia and 3 cases died of hypoglycemic coma. Another 37 cases were found with hyperglycemia. Conclusion Should reinforce the supervi-sion of rational use of quinolones and monitor the blood sugar level when the elderly and the diabetic of renal insuffi-ciency in clinical use.

  20. COMPARISON OF ANTIMICROBIAL SENSITIVITY TO OLDER AND NEWER QUINOLONES VERSUS PIPERACILLIN-TAZOBACTAM, CEFEPIME AND MEROPENEM IN FEBRILE PATIENTS WITH CANCER IN TWO REFERRAL PEDIATRIC CENTERS IN TEHRAN, IRAN

    Directory of Open Access Journals (Sweden)

    Ali Nateghian

    2014-06-01

    Full Text Available Infection in pediatric cancer patients has become a concerning problem due to increasing antimicrobial resistance. The goal of this study was to determine the antimicrobial resistance patterns of blood isolates from pediatric oncology patients in Iran to determine if quinolones are appropriate for empiric therapy. Methods Children with cancer who were admitted with or developed fever during admission to Aliasghar Children’s Hospital or Mahak Hospitals July 2009 through June 2011 were eligible for enrollment. Two blood cultures were obtained.  Antimicrobial sensitivity test was performed for ciprofloxacin, moxifloxacin, gatifloxacin, meropenem, cefepime, and piperacillin-tazobactam on isolates from children who were bacteremic. Results Blood cultures were positive for 39 episodes in 169 enrolled children but 9 episodes were excluded as blood cultures were thought to be contaminated,  yielding a bacteremia rate of 29/160 (18%. The mean age of children and the stage of malignancy did not differ between those with and without bacteremia. Meropenem was the most likely antibiotic to cover isolates (97% with cefepime having the lowest coverage rate (21%. Quinolone coverage ranged from 63%  to 76%. Conclusion Quinolones are not suitable for use as empiric therapy in febrile pediatric oncology patients in Iran.

  1. 质粒介导细菌对喹诺酮类抗菌药物的耐药机制%Plasmid Mediated Mechanism of Bacterial Resistance to Quinolones

    Institute of Scientific and Technical Information of China (English)

    马晓波; 宋秀宇

    2009-01-01

    喹诺酮类抗菌药物是临床最为常用的抗菌药物之一,但其耐药的问题也日益严重。细菌对喹诺酮类抗菌药物的耐药机制有:(1)染色体介导的耐药,包括药物作用靶位的改变(特别是喹诺酮耐药决定区(QRDR)的基因突变]、外膜通透性的下降、主动外排作用。(2)质粒介导的耐药。质粒介导的喹诺酮类耐药(plasmid mediated quinolone resistance,PMQR)由qnr(quinolone resistance,后来更名为qnrA)、aac-(6’)-Ⅰb-cr及qepA(quinolone efflux proteinA)等参与。PMQR机制的发现使人们对细菌耐喹诺酮类药物的机制有了新的认识。

  2. Progress in research of plasmid-mediated quinolone resistance gene of enterobacteria%肠杆菌科细菌质粒介导的喹诺酮耐药基因研究进展

    Institute of Scientific and Technical Information of China (English)

    符浩; 夏兴; 陈代杰

    2011-01-01

    继首个质粒介导的喹诺酮耐药基因qnrAl之后,qnrB,qnrS,qnrC和qnrD等其他一些类似基因也相继被发现.另 外,两种质粒介导的喹诺酮耐药机制,即外排泵QepA和OqxAB以及氨基糖苷甲基转移酶Aac(6’)-Ib-cr陆续被报道.本文综述肠杆菌科细菌质粒介导的喹诺酮耐药基因研究进展.%Since the first plasmid-mediated quinolone antibiotics resistance gene (PMQR, currently named qnrAl) was reported, some other genes such as qnrB, qnrS, qnrC and qnrD have also been characterized. In addition, two other plasmid-mediated resistance mechanisms: the modification of quinolones with a piperazinyl substituent by the acetyltransferase, Aac (6') -Ib-cr, and active efflux by QepA and OqxAB have also been reported. This review describes the progress in research of plasmid-mediated quinolone resistance gene of enterobacteria.

  3. Research of quinolones plasmid-mediated resistance mechanisms and countermeasure%喹诺酮类药物的质粒介导耐药机制及其对抗防御措施研究

    Institute of Scientific and Technical Information of China (English)

    李建华; 宋丰贵

    2008-01-01

    随着喹诺酮类抗菌药物在临床上的广泛应用,细菌对喹诺酮类药物的耐药性上升迅速.研究发现,细菌对喹诺酮类药物耐药的机制主要为靶位改变及主动外排,两者均为染色体介导.近年发现与两者完全不同的质粒介导耐药机制,且越来越多的临床菌株得以证实.本文主要对喹诺酮类药物的质粒介导的耐药机制及如何采取相应对抗防御措施进行综述.%Along with widespread application of quinolones antibiotics in clinic,quinolones resistanceof bacteria has rapidly risen. It is discovered that mechanisms of quinolones resistance of bacteria are mainlyinvolves change of target site and initiative excretion, which are both mediated by chromosome. In recentyears,plasmid-mediated drug resistance mechanism has been discovered,which is completely different fromthem. More and more clinical bacteria strains have been confirmed. The paper summarizes plasmid-mediatedquinolones resistance mechanisms and measures taken.

  4. Drug Resistance Mechanism of Pseudomonas Aeruginosa to Quinolones Antibacterial%铜绿假单胞菌对喹诺酮类抗菌药物的耐药机制

    Institute of Scientific and Technical Information of China (English)

    刘文广

    2012-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen in nosocomial infection, the resistance of which to quinolones is becoming more and more serious. The main mechanisms of pseudomonas aeruginosa to quinolone resistance are: change of antibacterial drag target site structure to avoid the effect of antibacterial drags; efflux pump system makinge the drag excreted out of bacteria. There are many problems to be further explored for the mechanisms of Pseudomonas aeruginosa resistance to quinolones. Here is to make a review on the research progress.%铜绿假单胞菌是一种重要的医院内感染条件致病菌,对喹诺酮类药物耐药日趋严重.目前发现铜绿假单胞菌对喹诺酮类药物耐药的主要机制为:改变抗菌药物作用的靶位点结构,从而逃避抗菌药物的作用;主动泵出系统使药物排出细菌体外.有关铜绿假单胞菌对喹诺酮类药物的耐药机制,仍存在许多问题有待进一步探索.现就铜绿假单胞菌对喹诺酮类药物的耐药机制研究进展进行综述.

  5. Cepas de Campylobacter jejuni resistentes a quinolonas aisladas de humanos, gallinas y pollos Quinolone resistant Campylobacter jejuni strains isolated from humans and from poultry

    Directory of Open Access Journals (Sweden)

    Rodolfo Notario

    2011-08-01

    Full Text Available Se compararon 8 aislamientos de Campylobacter jejuni provenientes de humanos con enfermedad diarreica aguda, con 23 aislamientos de cloaca de gallinas y pollos obtenidos de zonas próximas a la ciudad de Rosario, todos resistentes a la ciprofloxacina. Las muestras se sembraron en agar selectivo y se incubaron en microaerofilia a 42 °C. Las colonias se identificaron con el método tradicional. Los aislamientos se conservaron a -70 °C en caldo cerebro corazón con 17% v/v de glicerina. La clonalidad se determinó por RAPD-PCR, utilizando el primer 1254 (Stern NJ. Se interpretaron los aislamientos como clones distintos cuando diferían en una banda de amplificación. Se obtuvieron 5 clones diferentes. Los patrones I, II y V fueron aislados en criaderos industriales de pollos y en humanos (el II también en un establecimiento de gallinas ponedoras de huevos. En un gallinero familiar se obtuvo el patrón I. El patrón III sólo se obtuvo de humanos. El patrón IV se halló en uno de los criaderos pero no en humanos. Se pudo determinar que 93.5% de las cepas se aislaron tanto de animales como de humanos, por lo que se considera posible que la colonización de criaderos con cepas resistentes a los antimicrobianos pudiera ser el origen de la infección de humanos.Eight quinolone resistant Campylobacter jejuni strains isolated from humans with diarrheal disease were compared with 23 isolates from chicken and from laying hens. Samples were cultured on selective agar in microaerophilia, identified by conventional tests, and conserved in 17% glycerol at -70 °C. Clones were determined by RAPD-PCR employing the 1254 primer (Stern NJ. Five patterns were obtained. Patterns I, II, and V were found in both poultry and human isolates. Pattern I was obtained from poultry in a domestic henhouse. Pattern III was only obtained from humans whereas pattern IV was only obtained from poultry. A 95.3% of clones were found in both, humans and poultry. According to these

  6. Experimental pleurodesis induced by antibiotics (macrolides or quinolones Pleurodese experimental induzida por antibióticos (macrolídeos e quinolonas

    Directory of Open Access Journals (Sweden)

    Lisete R. Teixeira

    2006-01-01

    Full Text Available PURPOSE: Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin or quinolones (levofloxacin and gatifloxacin in inducing experimental pleurodesis in rabbits. METHOD: Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. RESULTS: The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. CONCLUSION: The macrolides (azithromycin or clarithromycin and the quinolones (levofloxacin or gatifloxacin when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.OBJETIVO: A pleurodese química representa uma ferramenta terapêutica utilizada no tratamento dos processos pleurais recidivantes, principalmente nos derrames neoplásicos. A escolha do melhor esclerosante pleural é ainda motivo de controvérsia, não havendo consenso com relação ao agente considerado ideal. O objetivo deste estudo é avaliar a efetividade dos macrolídeos (azitromicina e claritromicina e das quinolonas (levofloxacina e gatifloxacina na indução de pleurodese experimental em coelhos. MÉTODOS: Quarenta animais randomizados em grupos de 10, receberam, em volume total de 2 mL, estas drogas através de injeção intrapleural. RESULTADOS: Após 28 dias, os animais foram sacrificados sendo avaliada a cavidade pleural. A

  7. Effects of quinolones on the expressions of Salmonella pathogenicity genes hilA and invA mRNA%喹诺酮对沙门菌毒力基因hilA和invA的mRNA表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玉平; 沈建忠

    2012-01-01

    目的:研究喹诺酮对沙门菌毒力岛基因hilA和invA的mRNA表达水平的影响.方法:用多阶段诱导方式体外筛选耐喹诺酮沙门菌株,用荧光定量PCR方法测定喹诺酮敏感株和耐药株的hilA和invA基因的mRNA表达水平.结果:与喹诺酮敏感株相比,喹诺酮耐药株的hilA和invA的mRNA的表达水平显著降低(P<0.01).结论:喹诺酮可导致沙门菌毒力相关基因表达水平降低,这意味着喹诺酮耐药株毒力和致病性的降低.%Objective To investigate the effects of quinolones on the expressions of SPI-1 genes hilA and invA mRNA. Methods Quinolone-resistant Salmonella mutants were obtained from quinolone-susceptible strains by multiple-passage induction with increasing concentrations of ciprofloxacin in vitro. The expressions of hilA and invA genes mRNA were determined by real-time fluorescent quantitative RT-PCR in quinolone-susceptible and-resistant Salmonella strains. Results The expressions of hilA and invA gene mRNA were significantly decreased in quinolone-resistant strains (clinically acquired or drug-induced in vitro) than those in quinolone-susceptible strains (P < 0.01). Conclusion Suppressed expression of virulence-associated genes of quinolone-resistant salmonella strains suggests reduced virulence and pathogenicity of these bacteria.

  8. Analysis of Quinolones used in 20 hospitals of Guangzhou area from 2006 to 2008%2006-2008年广州地区20家医院喹诺酮类药物的利用分析

    Institute of Scientific and Technical Information of China (English)

    黄广泰; 谭少华

    2009-01-01

    Objective To investigate and analyze the utilization status of Quinolones in 20 hospitals of Guangzhou in order to provide a basis for the management of clinical application of Quinolones in hospitals.Methods The Quinolones used in 20 hospitals of Guangzhou during the time 2006 to 2008 were statistically analyzed on the kinds,cost and DDDs,etc.Results During the 3-year period,the cost and DDDs of Quinolones reduced year by year.The mean annual rate of increase of the consumption sum and DDDs were-13.33% and -11.65% respectively.The DDDs of Quinolones were 17.8542 millions days and the sum of consumption of Quinolones were 274.2714 millions.Levofloxacin,which ranked the first in the DDDs and consumption,accounted for 42.02% of the total DDDs and 32.72% of the total consumption.Conclusions Although the consumption of Quinoiones has reducing slowly in these years,it is suggested that further standardization in the osage and management of Quinolones should be made to delay the bacteria resistance.%目的 了解广州地区20家医院喹诺酮类药物的利用情况,希望为该类药物临床合理使用提供科学依据.方法 对2006-2008年广州地区20家医院喹诺酮类药物的用药品种、用药金额、用药频度(DDDs)等进行统计分析.结果 3年中,喹诺酮类药物的用药频度、用药金额均逐年减少,总用药金额和用药频度的年平均增长率AARG分别为-13.33%和-11.65%.总用药频度DDDs为1 785.42万日,总用药金额为27 427.14万元.左氧氟沙星位于用药频度、用药金额的第一位,分别占喹诺酮类药物总DDDs的42.02%和总用药金额的32.72%.结论 广州地区20家医院喹诺酮类药物的应用虽逐年减少,但为延缓细菌耐药性的产生,建议进一步规范化管理喹诺酮类药物的使用.

  9. Interactions of the "piano-stool" [ruthenium(II)(η(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study.

    Science.gov (United States)

    Zábojníková, Tereza; Cajzl, Radim; Kljun, Jakob; Chval, Zdeněk; Turel, Iztok; Burda, Jaroslav V

    2016-07-15

    Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ∼6 kcal/mol) in basic environment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Multi-targeting exploration of new 2-aminothiazolyl quinolones: Synthesis, antimicrobial evaluation, interaction with DNA, combination with topoisomerase IV and penetrability into cells.

    Science.gov (United States)

    Cheng, Yu; Avula, Srinivasa Rao; Gao, Wei-Wei; Addla, Dinesh; Tangadanchu, Vijai Kumar Reddy; Zhang, Ling; Lin, Jian-Mei; Zhou, Cheng-He

    2016-11-29

    A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV-DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities.

  11. Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Grima, M.; Beguin, M.F.; Millanvoye-Van Brussel, E.M.; Decker, N.; Schwartz, J.

    1988-09-01

    To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on /sup 22/Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance /sup 22/Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the /sup 22/Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs.

  12. Molecularly imprinted polymer as in-line concentrator in capillary electrophoresis coupled with mass spectrometry for the determination of quinolones in bovine milk samples.

    Science.gov (United States)

    Moreno-González, David; Lara, Francisco J; Gámiz-Gracia, Laura; García-Campaña, Ana M

    2014-09-19

    In this work molecularly imprinted polymers have been evaluated as sorbent for the construction of an in-line solid phase extraction analyte concentrator in capillary electrophoresis coupled with mass spectrometry for the determination of the eight regulated veterinary quinolones in bovine milk samples. Different parameters affecting the analyte concentrator performance, such as sample pH, volume and composition of the elution plug and injection time, were studied. Sample volumes of 22μL (2bar for 15min) were loaded on the MISPE microcartridge and the retained analytes were eluted by injecting a plug of MeOH/H2O/NH3 (60/37/3 by volume) for 125s at 50mbar (60nL). The proposed method is simple for the monitoring of these antibiotic residues in milk samples, allowing the direct injection of the samples with minimum sample pretreatment, achieving limits of detection between 3.8 and 4.7μgkg(-1) and unequivocal identification of the compounds working in tandem mass spectrometry. Recoveries ranging from 70.0 to 102.3% were obtained and satisfactory intra-day and inter-day RSDs were achieved (≤12% and 15% respectively). Reproducibility among different constructed analyte concentrators showed RSD≤11%.

  13. Multiresidue analysis of sulfonamides, quinolones, and tetracyclines in animal tissues by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Zhiwen; Li, Xiaowei; Ding, Shuangyang; Jiang, Haiyang; Shen, Jianzhong; Xia, Xi

    2016-08-01

    A multiresidue method for the efficient identification and quantification of 38 compounds from 3 different classes of antibiotics (tetracyclines, sulfonamides, and quinolones) in animal tissues has been developed. The method optimization involved the selection of extraction solutions, comparison of different solid-phase extraction cartridges and different mobile phases. As a result, the samples were extracted with Mcllvaine and phosphate buffers, followed by clean-up step based on solid-phase extraction with Oasis HLB cartridge. All compounds were determined by ultra-high performance liquid chromatography-tandem mass spectrometry, in one single injection with a chromatographic run time of only 9min. The method efficiency was evaluated in 5 tissues including muscle, liver, and kidney, and the mean recoveries ranged from 54% to 102%, with inter-day relative standard deviation lower than 14%. The limits of quantification were between 0.5 and 10μg/kg, which were satisfactory to support future surveillance monitoring. The developed method was applied to the analysis of swine liver and chicken samples from local markets, and sulfamethazine was the most commonly detected compound in the animal samples, with the highest residue level of 998μg/kg.

  14. The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line.

    Science.gov (United States)

    Chen, Hung-Yi; Lu, Hsu-Feng; Yang, Jai-Sing; Kuo, Sheng-Chu; Lo, Chyi; Yang, Mei-Due; Chiu, Tsan-Hung; Chueh, Fu-Shin; Ho, Heng-Chien; Ko, Yang-Ching; Chung, Jing-Gung

    2010-10-01

    20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 μM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 μM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 μM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.

  15. Emerging quinolones resistant transfer genes among gram-negative bacteria, isolated from faeces of HIV/AIDS patients attending some Clinics and Hospitals in the City of Benin, Edo State, Nigeria

    Directory of Open Access Journals (Sweden)

    Enabulele IO

    2006-12-01

    Full Text Available A survey of 1431 gram-negative bacilli from June 2001 to September 2005 were obtained from the faeces of 920 HIV/AIDS patients attending some Clinics and Hospitals in Benin City, Nigeria, were screened for quinolones resistance gene. The HIV/AIDS patients CD4 cells range was ≤14/mm3 ≥800/mm3 of blood. Out of the 1431 isolates, 343 (23.9% were resistance to quinolones with a MIC ≥4μg/ml for norfloxacin, ciprofloxacin and pefloxacin while a MIC of ≥32 µg/ml for nalidixic acid. The screened isolates include Pseudomonas aeruginosa 64(18.7%, E coli 92(26.8%, Klebsiella pneumoniae 53(15.4%, Salmonella typhi 39(11.4%, Shigella dysenteriae 36(10.5%, Proteus mirabilis 34(9.9% and Serratia marcescens 25(7.3%. The average resistance of the isolates to the various quinolones ranged from 42.7% to 66.7%. Klebsiella were the most resistant isolates with a mean resistance of 66.7% while Proteus were the less resistant isolates with a mean resistance of 42.7%. Most isolates were resistant to Nalidixic acid followed by norfloxacin while the less resistant were to the pefloxacin. The frequency of qnr genes transfer to EJRifr as recipient ranged from 2 x 10-2 to 6 x 10-6 with an average of 2 plasmids per cell. The molecular weight of the plasmids ranged from <2.9kbp to <5.5 kbp. This indicated that plasmids allowed the movement of genetic materials including qnr resistant genes between bacteria species and genera in Benin City, Nigeria.

  16. Analysis of montmorillonite powder in vitro adsorption with 6 kinds of quinolones%蒙脱石散对6种喹诺酮类药物体外吸附的作用分析

    Institute of Scientific and Technical Information of China (English)

    向国云

    2015-01-01

    目的:研究蒙脱石散对几种常见喹诺酮类药物体外的吸附作用。方法将临床常用的几种喹诺酮类药物融入水及人工胃液中加入蒙脱石散,用紫外分光光度法进行测定比较。结果氧氟沙星、诺氟沙星、吡哌酸在水溶液中难溶,而在人工胃液中蒙脱石的吸附率均在98%以上;盐酸洛美沙星、盐酸环丙沙星、甲磺酸培氟沙星无论是在水溶液中还是在人工胃液中,蒙脱石散的吸附率均超过99%。结论蒙脱石散对于常用的几种喹诺酮类药物均具有明显的吸附作用,在实际操作中应严格控制两者的使用间隔时间。%Objective To study the adsorption of montmorillonite powder on several common quinolones objects in vitro.Methods Several commonly used clinical quinolones integration into the water and artificial gastric juice ,added mont-morillonite powder,measured by ultraviolet spectrophotometry .Results Ofloxacin,norfloxacin,pipemidate insoluble in aque-ous solutions ,and adsorption rate of montmorillonite in artificial gastric juice was more than 98%;lomefloxacin hydrochloride , ciprofloxacin hydrochloride ,mesylate pefloxacin whether in water or in artificial gastric juice , montmorillonite adsorption rate were over 99%.Conclusion Montmorillonite powder has obvious adsorption for several common quinolones , should strictly control the use of both interval time in the actual operation .

  17. Analysis of 748 cases of quinolone adverse drug reaction in Suzhou city of 2013%2013年宿州市748例喹喏酮类药物不良反应分析

    Institute of Scientific and Technical Information of China (English)

    郭秀秀

    2014-01-01

    目的:研究影响喹诺酮类药物不良反应的因素,以期减少药物不良反应。方法:收集宿州市2013年喹诺酮类合成抗菌药物不良反应报表进行汇总分析。结果:748例喹诺酮类药物不良反应报表以左氧氟沙星引起的不良反应最多(68.14%)。不良反应涉及器官或系统最主要表现在胃肠系统(42.80%)、皮肤(30.64%)、中枢及外周神经系统(5.73%)。结论:应加强喹诺酮类药物的临床监测,提高合理用药的安全性。%Objective Study on the influence factors of adverse drug reactions of quinolones, in order to reduce the occurrence of adverse drug reaction.Methods Collected and analyzed the reports of Quinolones synthetic antibacterial drug adverse reactions in Suzhou city of 2013.Results Levofloxacin induced adverse reaction is most(68.14%)in 748 cases of ADR reports .The adverse drug reactions involving organs or systems mainly reflected in the gastrointestinal system (42.80%), skin (30.64%), the central and peripheral nervous system (5.73%).Conclusion We should strengthen the clinical monitoring of quinolones, to improve security of rational use of drug.

  18. Seawater is a reservoir of multi-resistant Escherichia coli, including strains hosting plasmid-mediated quinolones resistance and extended-spectrum beta-lactamases genes.

    Science.gov (United States)

    Alves, Marta S; Pereira, Anabela; Araújo, Susana M; Castro, Bruno B; Correia, António C M; Henriques, Isabel

    2014-01-01

    The aim of this study was to examine antibiotic resistance (AR) dissemination in coastal water, considering the contribution of different sources of fecal contamination. Samples were collected in Berlenga, an uninhabited island classified as Natural Reserve and visited by tourists for aquatic recreational activities. To achieve our aim, AR in Escherichia coli isolates from coastal water was compared to AR in isolates from two sources of fecal contamination: human-derived sewage and seagull feces. Isolation of E. coli was done on Chromocult agar. Based on genetic typing 414 strains were established. Distribution of E. coli phylogenetic groups was similar among isolates of all sources. Resistances to streptomycin, tetracycline, cephalothin, and amoxicillin were the most frequent. Higher rates of AR were found among seawater and feces isolates, except for last-line antibiotics used in human medicine. Multi-resistance rates in isolates from sewage and seagull feces (29 and 32%) were lower than in isolates from seawater (39%). Seawater AR profiles were similar to those from seagull feces and differed significantly from sewage AR profiles. Nucleotide sequences matching resistance genes bla TEM, sul1, sul2, tet(A), and tet(B), were present in isolates of all sources. Genes conferring resistance to 3rd generation cephalosporins were detected in seawater (bla CTX-M-1 and bla SHV-12) and seagull feces (bla CMY-2). Plasmid-mediated determinants of resistance to quinolones were found: qnrS1 in all sources and qnrB19 in seawater and seagull feces. Our results show that seawater is a relevant reservoir of AR and that seagulls are an efficient vehicle to spread human-associated bacteria and resistance genes. The E. coli resistome recaptured from Berlenga coastal water was mainly modulated by seagulls-derived fecal pollution. The repertoire of resistance genes covers antibiotics critically important for humans, a potential risk for human health.

  19. Extended spectrum β-lactamase and plasmid mediated quinolone resistance in Escherichia coli fecal isolates from healthy companion animals in Algeria.

    Science.gov (United States)

    Yousfi, Massilia; Mairi, Assia; Touati, Abdelaziz; Hassissene, Lila; Brasme, Lucien; Guillard, Thomas; De Champs, Christophe

    2016-07-01

    The aim of this study was to evaluate the rate of fecal carriage of Escherichia coli strains producing Extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) isolated from healthy pets (dogs and cats) in Algeria. Fecal samples from 171 healthy pets (102 dogs and 69 cats) in one veterinary practice and private owners were included. After isolates identification, antibiotic susceptibility was determined by disk diffusion procedure. ESBL were detected by combination disk tests. PCR and sequencing were used to characterize genes encoding ESBLs and PMQR. Transfer of ESBL and PMQR genes was assessed by conjugation experiments. Phylogenetic groups of E. coli were determined by PCR. Of the 171 animals, 20 carried an ESBL producing E. coli giving a prevalence of ESBL fecal carriage of 11.7%. All isolates were susceptible to carbapenems, cefoxitin, piperacillin-tazobactam, amikacin and fosfomycine. For the rest of the tested β-lactams, susceptibility rates ranged from 35% to 70% for cefepime and amoxicillin-clavulanic acid respectively. Concerning the non-beta-lactams antibiotics, the rates of susceptibility ranged between 5% to trimethoprim and 95% for chloramphenicol. The beta-lactamase genes identified in E. coli isolates were blaCTX-M-15, blaCTX-M-1, blaSHV-12 and blaTEM-1. The PMQR determinants aac(6')-Ib-cr, qnrS1 and qnrB5 genes were identified in 15 isolates. Transconjugants were obtained for two isolates. Phylogenetic analysis showed that E. coli isolates belong to commensal phylogroups of A and B1. We reported here for the first time in Algeria ESBL and PMQR-producing E. coli in healthy cats and dogs.

  20. Seawater is a reservoir of multi-resistant Escherichia coli, including strains hosting plasmid-mediated quinolones resistance and extended-spectrum beta-lactamases genes

    Directory of Open Access Journals (Sweden)

    Marta S. Alves

    2014-08-01

    Full Text Available The aim of this study was to examine antibiotic resistance (AR dissemination in coastal water, considering the contribution of different sources of faecal contamination. Samples were collected in Berlenga, an uninhabited island classified as Natural Reserve and visited by tourists for aquatic recreational activities. To achieve our aim, AR in Escherichia coli isolates from coastal water was compared to AR in isolates from two sources of faecal contamination: human-derived sewage and seagull faeces. Isolation of E. coli was done on Chromocult agar. Based on genetic typing 414 strains were established. Distribution of E. coli phylogenetic groups was similar among isolates of all sources. Resistances to streptomycin, tetracycline, cephalothin and amoxicillin were the most frequent. Higher rates of AR were found among seawater and faeces isolates, except for last-line antibiotics used in human medicine. Multi-resistance rates in isolates from sewage and seagull faeces (29% and 32% were lower than in isolates from seawater (39%. Seawater AR profiles were similar to those from seagull faeces and differed significantly from sewage AR profiles. Nucleotide sequences matching resistance genes blaTEM, sul1, sul2, tet(A and tet(B, were present in isolates of all sources. Genes conferring resistance to 3rd generation cephalosporins were detected in seawater (blaCTX-M-1 and blaSHV-12 and seagull faeces (blaCMY-2. Plasmid-mediated determinants of resistance to quinolones were found: qnrS1 in all sources and qnrB19 in seawater and seagull faeces. Our results show that seawater is a relevant reservoir of AR and that seagulls are an efficient vehicle to spread human-associated bacteria and resistance genes. The E. coli resistome recaptured from Berlenga coastal water was mainly modulated by seagulls-derived faecal pollution. The repertoire of resistance genes covers antibiotics critically important for humans, a potential risk for human health.

  1. High-resolution mass spectrometry applied to the identification of transformation products of quinolones from stability studies and new metabolites of enrofloxacin in chicken muscle tissues.

    Science.gov (United States)

    Morales-Gutiérrez, F J; Hermo, M P; Barbosa, J; Barrón, D

    2014-04-01

    The aim of this work was the identification of new metabolites and transformation products (TPs) in chicken muscle from enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF) and sarafloxacin (SAR), which are antibiotics that belong to the fluoroquinolones family. The stability of ENR, CIP, DIF and SAR standard solutions versus pH degradation process (from pH 1.5 to 8.0, simulating the pH since the drug is administered until its excretion) and freeze-thawing (F/T) cycles was tested. In addition, chicken muscle samples from medicated animals with ENR were analyzed in order to identify new metabolites and TPs. The identification of the different metabolites and TPs was accomplished by comparison of mass spectral data from samples and blanks, using liquid chromatography coupled to quadrupole time-of-flight (LC-QqToF) and multiple mass defect filter (MMDF) technique as a pre-filter to remove most of the background noise and endogenous components. Confirmation and structure elucidation was performed by liquid chromatography coupled to linear ion trap quadrupole Orbitrap (LC-LTQ-Orbitrap), due to its mass accuracy and MS/MS capacity for elemental composition determination. As a result, 21 TPs from ENR, 6 TPs from CIP, 14 TPs from DIF and 12 TPs from SAR were identified due to the pH shock and F/T cycles. On the other hand, 14 metabolites were identified from the medicated chicken muscle samples. Formation of CIP and SAR, from ENR and DIF, respectively, and the formation of desethylene-quinolone were the most remarkable identified compounds.

  2. β-CD/ATP composite materials for use in dispersive solid-phase extraction to measure (fluoro)quinolone antibiotics in honey samples.

    Science.gov (United States)

    Cui, Xiangqian; Zhang, Panjie; Yang, Xiaoling; Yang, Miyi; Zhou, Wenfeng; Zhang, Sanbin; Gao, Haixiang; Lu, Runhua

    2015-06-09

    A novel sorbent (β-CD/ATP composite) for dispersive solid-phase extraction (d-SPE) prepared by bonding β-cyclodextrin to modified attapulgite via silane coupling was used to determine the concentrations of four (fluoro)quinolones (Qs) in honey samples. The subsequent quantification of the Qs (ciprofloxacin, norfloxacin, ofloxacin, and gatifloxacin) was accomplished using high-performance liquid chromatography (HPLC) with ultraviolet detection after the d-SPE procedure. Parameters that may influence the extraction efficiency, such as type and volume of the eluent, type and amount of the sorbent, times of the vortex and sonication process, and pH of the sample, were investigated using batch and column procedures. The optimal experimental conditions (5 mL sample at pH 3, 4 mg of β-CD/ATP composite as the sorbent, 200 μL of 40% ammonia in methanol as the eluent, with vortex time 60s and sonication time 6 min, and no addition of salt) were obtained from this statistical evaluation. The limits of detection (LODs) were determined to the range from 0.30 to 3.95 μg L(-1). Good recoveries (83.6-88.6%) were obtained under the optimum conditions, and the relative standard deviations (RSDs), which are used to indicate reproducibility, were less than 7.4%. The method was validated with three real honey samples, and the results demonstrated that β-CD/ATP composite possessed a high adsorption capacity for Qs. Although the LODs were slightly higher than expected, this study confirmed the possibility of using cyclodextrin grafted palygorskite in analytical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations.

    Science.gov (United States)

    Takiff, H E; Salazar, L; Guerrero, C; Philipp, W; Huang, W M; Kreiswirth, B; Cole, S T; Jacobs, W R; Telenti, A

    1994-04-01

    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in increased interest in the fluoroquinolones (FQs) as antituberculosis agents. To investigate the frequency and mechanisms of FQ resistance in M. tuberculosis, we cloned and sequenced the wild-type gyrA and gyrB genes, which encode the A and B subunits of the DNA gyrase, respectively; DNA gyrase is the main target of the FQs. On the basis of the sequence information, we performed DNA amplification for sequencing and single-strand conformation polymorphism analysis to examine the presumed quinolone resistance regions of gyrA and gyrB from reference strains (n = 4) and clinical isolates (n = 55). Mutations in codons of gyrA analogous to those described in other FQ-resistant bacteria were identified in all isolates (n = 14) for which the ciprofloxacin MIC was > 2 micrograms/ml. In addition, we selected ciprofloxacin-resistant mutants of Mycobacterium bovis BCG and M. tuberculosis Erdman and H37ra. Spontaneously resistant mutants developed at a frequency of 1 in 10(7) to 10(8) at ciprofloxacin concentrations of 2 micrograms/ml, but no primary resistant colonies were selected at higher ciprofloxacin concentrations. Replating of those first-step mutants selected for mutants with high levels of resistance which harbored gyrA mutations similar to those found among clinical FQ-resistant isolates. The gyrA and gyrB sequence information will facilitate analysis of the mechanisms of resistance to drugs which target the gyrase and the implementation of rapid strategies for the estimation of FQ susceptibility in clinical M. tuberculosis isolates.

  4. Status of quinolones residues in animal food in Suzhou City%苏州市动物性食品中喹诺酮类抗生素的残留状况

    Institute of Scientific and Technical Information of China (English)

    张秋萍; 王春民; 李建

    2012-01-01

    目的 了解苏州市市售动物性产品中喹诺酮类抗生素的残留现状.方法 2011年6月-2012年3月随机选择苏州市农贸市场上常见动物性食品及苏州市特色水产品,共采集175份样品,采用超高效液相色谱/质谱进行喹诺酮类抗生素检测.结果 175份样品中,阳性检出50份,总检出率达28.6%,不同种类(鱼虾类、猪肉和猪肝类、鸡鸭类、蟹类)动物性食品中喹诺酮类抗生素检出率相比,差异无统计学意义(x2 =1.42,P>0.05).50份阳性样品中,恩诺沙星检出比例最高,占47.4%;氧氟沙星其次,占21.1%.结论 苏州市市售动物性产品存在部分抗生素残留,需要加强水产品、禽肉产品养殖、销售的管理.%[Objective]To understand the current situation of quinolones residues in animal food in Suzhou City. [ Methods] From June 2011 to March 2012, 175 samples of animal food and aquatic products were randomly collected from farmers markets in Suzhou City, and the quinolones were detected by ultra performance liquid chromatography/mass spectrometry. [Results]50 of 175 samples were positive, and the total detection rate was 28.6%. There was no significant difference in detection rate of quinolones between different animal foods, including fish and shrimp, pork and pig liver, chickens and ducks, crabs, (X2= 1.42,P>0.05). Among 50 positive samples, the detection rate of enrofloxacin was the highest, which accounted for 47. 4% , followed by ofloxacin (21. 1 % ). [ Conclusion ] The quinolones residues are found in animal food in Suzhou City, so it is necessary to strengthen the management in breeding and sales of aquatic products and poultry products.

  5. ADR Caused by Quinolones: Analysis of 199 Cases in Our Hospital%我院199例喹诺酮类药不良反应报告分析

    Institute of Scientific and Technical Information of China (English)

    高杰; 谢诚; 缪丽燕

    2009-01-01

    OBJECTIVE: To investigate the characteristics of adverse drug reactions (ADR) caused by quinolones in our hospital and to promote their rational use in clinic. METHODS: By a retrospective review, a total of 199 quinolones - induced ADR cases collected from May 2004 to December 2007 in our hospital were analyzed statistically in respect of patients' gender and age, drug species involved, past ADR history, route of administration, clinic manifestations, etc. RESULTS: A total of 9 kinds of quinolones involved in the 199 ADR cases, of which, 118 cases were induced by levofloxacin, 16.1% had past ADR history, 93.5% of the ADR cases were induced via intravenous drip, and most common presentations of the ADR were lesions of skin and its appendants as well as digestive system. There were 7 serious ADR cases. CONCLUSION: The indications of quinolones should be controlled strictly, which should be preferably administered orally and monitoring of its administration should be emphasized in clinical practice to decrease and avoid the occurrence of ADR.%目的:了解我院喹诺酮类药不良反应发生的特点,促进临床合理用药.方法:采用回顾性调查方法,对我院2004年5月~2007年12月收集到的喹诺酮类药所致的199例不良反应报告表,分别从患者性别、年龄、涉及药品、既往不良反应史、给药途径、临床表现等方面进行统计、分析.结果:199例不良反应涉及9种喹诺酮类药,其中左氧氟沙星引起的不良反应118例;既往有不良反应史者占16.1%;93.5%的患者通过静脉滴注给药;临床表现主要以皮肤及其附件和消化系统损害最为常见,严重不良反应7例.结论:应严格掌握药物使用适应证,尽可能采用口服给药方式,重视用药监护,以减少和避免不良反应的发生.

  6. The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones%喹诺酮类药物作用的生理和遗传的分子机制

    Institute of Scientific and Technical Information of China (English)

    龙泉鑫; 何颖; 谢建平

    2012-01-01

    氟喹诺酮类药物是目前使用最广泛的广谱抗生素,占据了全球抗生素类药物市场约18%的份额.其杀菌快速,而且具备大量的衍生物库,为药物更新换代提供了良好的基础.但这些衍生物在杀菌的速度、代谢过程中对氧需求、对蛋白合成的依赖性等方面的差异很大.从药物作用后细菌分子遗传层面的应答特征揭示各类衍生物的深层次作用机制,可以为寻找更有效的新喹诺酮类药物提供坚实基础.SOS应答、毒素-抗毒素系统,细菌程序性死亡、染色体片段化以及活性氧簇等新机制可能不同程度参与了喹诺酮类药物的杀菌过程.本文重点介绍喹诺酮作用的“二步特征”.该特征的引入有助于理解不同喹诺酮类药物的杀菌特征,也有助于开发新的喹诺酮类药物.%The fluoroquinolones are the most widely used broad-spectrum antibiotics, accounting for 18% of global antibacterial market share. They can kill bacteria rapidly with variety of derivatives available. Different quinolones vary significantly in rate and spectrum of killing, oxygen requirement for metabolism and reliance upon protein synthesis. Further understanding the sophisticated mechanisms of action of this important antibiotic family based on the molecular genetic response of bacteria can facilitate the discovery of better quinolone derivatives. Factors such as SOS response, bacterial toxin-antitoxin system, programmed death, chromosome fragmentation and reactive oxygen have been implicated in the action to some extent. "Two steps characteristic" of quinolones killing is also emphasized, which might inspire future better quinolones modification.

  7. An efficient catalyst-free synthesis of novel chromeno[4,3-b]quinolones through Michael initiated ring closure (MIRC) reaction with in situ generated 3-(arylmethylene)chroman-2,4-diones

    Indian Academy of Sciences (India)

    SUDESH KUMARI; JITENDER M KHURANA

    2017-08-01

    A catalyst-free multicomponent reaction capable of affording a wide range of eighteen novel chromeno[4,3-b]quinolone derivatives (6a–6r) via one-pot two-step domino protocol, in ethylene glycol is reported. Catalyst-free conditions along with green solvent system make the process eco-friendly as well aseconomical. High yields of the products were obtained in short reaction times by forming three new bonds and one stereocenter in a single operation. The salient features of the present protocol are short reaction times, eco-friendly solvents, high yields and easy work-up procedure.

  8. Development and validation of a UHPLC-MS/MS procedure for quantification of the Pseudomonas Quinolone Signal in bacterial culture after acetylation for characterization of new quorum sensing inhibitors.

    Science.gov (United States)

    Maurer, Christine K; Steinbach, Anke; Hartmann, Rolf W

    2013-12-01

    The appearance of antibiotic resistance requires novel therapeutic strategies. One approach is to selectively attenuate bacterial pathogenicity by interfering with bacterial cell-to-cell communication known as quorum sensing. The PQS quorum sensing system of Pseudomonas aeruginosa employs as signal molecule the Pseudomonas Quinolone Signal (PQS; 2-heptyl-3-hydroxy-4-(1H)-quinolone), a key contributor to virulence and biofilm formation. Thus, interference with PQS production is considered as promising approach for the development of novel anti-infectives. Therefore, in this study, we developed and validated an ultra-high performance liquid chromatographic-tandem mass spectrometric approach for reliable quantification of PQS in P. aeruginosa cultures for activity determination of new quorum sensing inhibitors. The poor chromatographic properties of PQS reported by others could be overcome by fast microwave-assisted acetylation. The validation procedure including matrix effects, recovery, process efficiency, selectivity, carry-over, accuracy and precision, stability of the processed sample, and limit of quantification demonstrated that the method fulfilled all requirements of common validation guidelines. Its applicability was successfully proven in routine testing. In addition, two-point calibration was shown to be applicable for fast and reliable PQS quantification saving time and resources. In summary, the described method provides a powerful tool for the discovery of new quorum sensing inhibitors as potential anti-infectives and illustrated the usefulness of chemical derivatization, acetylation, in liquid chromatography-mass spectrometry analysis.

  9. Novel cyano- and N-isopropylamidino-substituted derivatives of benzo[b]thiophene-2-carboxanilides and benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, crystal structure determination, and antitumor evaluation. 2.

    Science.gov (United States)

    Jarak, Ivana; Kralj, Marijeta; Suman, Lidija; Pavlović, Gordana; Dogan, Jasna; Piantanida, Ivo; Zinić, Mladen; Pavelić, Kresimir; Karminski-Zamola, Grace

    2005-04-01

    Derivatives of 3-chlorobenzo[b]thiophene-2-carboxanilides and their "cyclic" analogues benzo[b]thieno[2,3-c]quinolones were synthesized. Spectroscopic study of the interactions of some representatives of "cyclic" derivatives and their "acyclic" precursors with ds-DNA/RNA supported strong intercalative binding of the former and weak nonintercalative binding of the latter group of compounds. All tested compounds showed a certain antiproliferative effect on a series of human tumor cells and on a normal cell line. Among the compounds, those with one amidino-substituent have shown the best effect. The most active benzo[b]thieno[2,3-c]quinolones induced apparent S and G2/M arrests of the cell cycle, which resulted in apoptosis. These results strongly suggest that the compounds may act as topoisimerase "poisons", which is in good agreement with their intercalative mode of binding to ds-DNA/RNA, in contrast to the studied "acyclic"group of derivatives. 6a and 6d showed the best selectivity by inhibiting the growth of tumor cells but not of normal fibroblasts.

  10. High Prevalence of β-lactamase and Plasmid-Mediated Quinolone Resistance Genes in Extended-Spectrum Cephalosporin-Resistant Escherichia coli from Dogs in Shaanxi, China

    Science.gov (United States)

    Liu, Xiaoqiang; Liu, Haixia; Li, Yinqian; Hao, Caiju

    2016-01-01

    Objective: The aim of this study was to investigate the occurrence and molecular characterization of extended-spectrum β-lactamases (ESBL), plasmid-mediated AmpC β-lactamase (pAmpC) and carbapenemases as well as plasmid-mediated quinolone-resistant (PMQR) among extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli from dogs in Shaanxi province in China. Methods: A total of 40 ESC-R Escherichia coli selected from 165 Extraintestinal pathogenic E. coli (ExPEC) isolated from dogs were screened and characterized for the genes encoding for the ESBLs, pAmpC, carbapenemases and PMQR genes by PCR and sequencing. Phylogenetic groups, virulence gene profiles and multilocus sequence typing (MLST) were used to investigate the genetic background of the ESC-R E. coli isolates. Results: Among 40 ESC-R E. coli, the predominant β-lactamase gene was blaCTX−Ms (n = 35), and followed by blaTEM−1 (n = 31), blaSHV−12 (n = 14), blaOXA−48 (n = 8), blaTEM−30 (n = 4), blaCMY−2 (n = 3) and blaDHA−1 (n = 2). The most common specific blaCTX−M gene subtype was blaCTX−M−15 (n = 31), and followed by blaCTX−M−123 (n = 14), blaCTX−M−1 (n = 10), blaCTX−M−14 (n = 10) and blaCTX−M−9 (n = 7). PMQR genes were detected in 32 (80%) isolates, and the predominant PMQR gene was aac(6′)-Ib-cr (n = 26), followed by qnrS (n = 12), qnrD (n = 9), qnrB (n = 8), qepA (n = 4), and all PMQR genes were detected in co-existence with β-lactamase genes. traT (n = 34) and fimH (n = 32) were the most prevalent virulence genes, and virulence genes fimH, iutA, fyuA, malX, iha, and sat were more prevalent in phylogenetic group B2. The 40 ESC-R isolates analyzed were assigned to 22 sequence types (STs), and the clonal lineages ST131 (n = 10) and ST10 (n = 9) were the predominant STs. Conclusion: High prevalence of β-lantamases and PMQR genes were detected among ESC-R E. coli from companion animals. This is also the first description of the co-existence of six

  11. 喹诺酮类药物合理应用评估与干预研究%Research of the Reasonable Assessment and Intervention of Quinolones

    Institute of Scientific and Technical Information of China (English)

    申金娥

    2012-01-01

      Objective To explore the impact of pharmacy intervention on quinolone treatment. Methods 52 cases of urinary tract infections and gastrointestinal infections were divided into control group and observation group, select the pipemidic acid tablets, norfloxacin tablets, fluoride hydrochloride acid tablets to treat patients with different diseases. Which the control group patients in accordance with the conventional treatment of the package insert for the study group patients, according to the actual physical condition of the patients and the specific condition in the choice of therapy were appropriate and reasonable regulation and pharmaceutical intervention. Results Control group in patients with total efficiency(87%) with the observation group were overall response rate(100%) the difference was statistically significant(P <0.05). Conclusion Rational use of drugs for the treatment of patients played a positive role.%  目的探讨药学干预对喹诺酮类药物治疗效果的影响.方法将52例尿路感染及胃肠道感染患者分为对照组和观察组,选取吡哌酸片剂、氟哌酸片剂、氟嗪酸片剂分别对不同病症的患者进行治疗.其中对照组患者按照药品说明书常规用药,观察组患者,根据患者的实际身体状况及具体病情,在选择治疗药物时进行了相应的合理调节和药学干预.结果对照组患者总有效率(87%)与观察组患者总有效率(100%)的差异有统计学意义(P <0.05).结论合理用药对患者的治疗起到了积极作用.

  12. Characterization of plasmid-mediated quinolone resistance (PMQR genes in extended-spectrum β-lactamase-producing Enterobacteriaceae pediatric clinical isolates in Mexico.

    Directory of Open Access Journals (Sweden)

    Jesus Silva-Sánchez

    Full Text Available This work describes the characterization of plasmid-mediated quinolone-resistance (PMQR genes from a multicenter study of ESBL-producing Enterobacteriaceae pediatric clinical isolates in Mexico. The PMQR gene-positive isolates were characterized with respect to ESBLs, and mutations in the GyrA and ParC proteins were determined. The phylogenetic relationship was established by PFGE and the transfer of PMQR genes was determined by mating assays. The prevalence of the PMQR genes was 32.1%, and the rate of qnr-positive isolates was 15.1%; 93.3% of the latter were qnrB and 6.4% were qnrA1. The distribution of isolates in terms of bacterial species was as follows: 23.5% (4/17 corresponded to E. cloacae, 13.7% (7/51 to K. pneumoniae, and 13.6% (6/44 to E. coli. In addition, the prevalence of aac(6'-Ib-cr and qepA was 15.1% and 1.7%, respectively. The molecular characteristics of qnr- and qepA-positive isolates pointed to extended-spectrum β-lactamase (ESBL CTX-M-15 as the most prevalent one (70.5%, and to SHV-12 in the case of aac(6'-Ib-cr-positive isolates. GyrA mutations at codons Ser-83 and Asp-87, and ParC mutations at codons Ser-80 were observed in 41.1% and 35.2% of the qnr-positive isolates, respectively. The analysis of the transconjugants revealed a co-transmission of bla(CTX-M-15 with the qnrB alleles. In general, the prevalence of PMQR genes (qnr and aac(6'-Ib-cr presented in this work was much lower in the pediatric isolates, in comparison to the adult isolates in Mexico. Also, ESBL CTX-M-15 was the main ESBL identified in the pediatric isolates, whereas in the adult ones, ESBLs corresponded to the CTX-M and the SHV families. In comparison with other studies, among the PMQR-genes identified in this study, the qnrB-alleles and the aac(6'-Ib-cr gene were the most prevalent, whereas the qnrS1, qnrA1 and qnrB-like alleles were the most prevalent in China and Uruguay.

  13. Identification of plasmid-mediated quinolone resistance qnr genes in multidrug-resistant Gram-negative bacteria from hospital wastewaters and receiving waters in the Jinan area, China.

    Science.gov (United States)

    Xia, Ruirui; Ren, Ye; Xu, Hai

    2013-12-01

    We investigated the prevalence of plasmid-mediated quinolone resistance (PMQR) qnr genes by the polymerase chain reaction (PCR) in antibiotic-resistant bacteria isolates collected from aquatic environments in Jinan during 2 years (2008.3-2009.11). Genes were identified to variant level by PCR restriction fragment length polymorphism analysis or sequencing. qnrA1, qnrB2, qnrB4, qnrB6, qnrB9, qnrS1, and the new qnrB variant qnrB26 were detected in 31 strains from six genera (Klebsiella spp., Escherichia coli, Enterobacter spp., Proteus spp., Shigella spp., and Citrobacter spp.), four of which contained double qnr genes. Other PMQR genes, aac(6')-Ib-cr and qepA, were found in 12 (38.7%) and 5 (16.1%) of 31 isolates, respectively; while qepA was found in Shigella spp. for the first time. Eight types of β-lactamase genes and eight other types of resistance genes were also present in the 31 qnr-positive isolates. The detection rate for five β-lactamase genes (blaTEM, blaCTX, ampR, blaDHA, and blaSHV) was >45%. Class 1 integrons and complex class 1 integrons were prevalent in these strains, which contained 15 different gene cassette arrays and 5 different insertion sequence common region 1 (ISCR1)-mediated downstream structures. qnrA1, qnrB2, and qnrB6 were present in three ISCR1-mediated downstream structures: qnrA1-ampR, sapA-like-qnrB2, and sdr-qnrB6. We also analyzed the horizontal transferability of PMQR genes and other resistance determinants. The qnr genes and some integrons and resistance genes from 18 (58.1%) of the 31 qnr-positive strains could be transferred to E. coli J53 Azi(R) or E. coli DH5α recipient strains using conjugation or transformation methods. The results showed that a high number of qnr genes were associated with other resistance genes in aquatic environments in Jinan. This suggests that we should avoid over-using antibiotics and monitor aquatic environments to control the spread of antibiotic resistance genes.

  14. High Prevalence of β-lactamase and Plasmid-mediated Quinolone Resistance Genes in Extended-spectrum Cephalosporin-resistant Escherichia coli from Dogs in Shaanxi, China

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Liu

    2016-11-01

    Full Text Available Objective: The aim of this study was to investigate the occurrence and molecular characterization of extended-spectrum β-lactamases (ESBL, plasmid-mediated AmpC β-lactamase (pAmpC and carbapenemases as well as plasmid-mediated quinolone-resistant (PMQR among extended-spectrum cephalosporin-resistant (ESC-R Escherichia coli from dogs in Shaanxi province in China.Methods: A total of 40 ESC-R Escherichia coli selected from 165 Extraintestinal pathogenic E. coli (ExPEC isolated from dogs were screened and characterized for the genes encoding for the ESBLs, pAmpC, carbapenemases and PMQR genes by PCR and sequencing. Phylogenetic groups, virulence gene profiles and multilocus sequence typing (MLST were used to investigate the genetic background of the ESC-R E. coli isolates. Results: Among 40 ESC-R E. coli, the predominant β-lactamase gene was blaCTX-Ms (n=35, and followed by blaTEM-1 (n=31, blaSHV-12 (n=14, blaOXA-48 (n=8, blaTEM-30 (n=4, blaCMY-2 (n=3 and blaDHA-1 (n=2. The most common specific blaCTX-M gene subtype was blaCTX-M-15 (n=31, and followed by blaCTX-M-123 (n=14, blaCTX-M-1 (n=10, blaCTX-M-14 (n=10 and blaCTX-M-9 (n=7. PMQR genes were detected in 32 (80% isolates, and the predominant PMQR gene was aac(6'-Ib-cr (n=26, followed by qnrS (n=12, qnrD (n=9, qnrB (n=8, qepA (n=4, and all PMQR genes were detected in co-existence with β-lactamase genes. traT (n=34 and fimH (n=32 were the most prevalent virulence genes, and virulence genes fimH, iutA, fyuA, malX, iha and sat were more prevalent in phylogenetic group B2. The 40 ESC-R isolates analyzed were assigned to 22 sequence types (STs, and the clonal lineages ST131 (n=10 and ST10 (n=9 were the predominant STs. Conclusion: High prevalence of β-lantamases and PMQR genes were detected among ESC-R E. coli from companion animals. This is also the first description of the co-existence of six β-lantamase genes and five PMQR genes in one E. coli isolate. Moreover, ten ST131 clones harboring CTX

  15. Extended-spectrum-beta-lactamases, AmpC beta-lactamases and plasmid mediated quinolone resistance in klebsiella spp. from companion animals in Italy.

    Directory of Open Access Journals (Sweden)

    Valentina Donati

    Full Text Available We report the genetic characterization of 15 Klebsiella pneumoniae (KP and 4 isolates of K. oxytoca (KO from clinical cases in dogs and cats and showing extended-spectrum cephalosporin (ESC resistance. Extended spectrum beta-lactamase (ESBL and AmpC genes, plasmid-mediated quinolone resistance (PMQR and co-resistances were investigated. Among KP isolates, ST101 clone was predominant (8/15, 53%, followed by ST15 (4/15, 27%. ST11 and ST340, belonging to Clonal Complex (CC11, were detected in 2012 (3/15, 20%. MLST on KP isolates corresponded well with PFGE results, with 11 different PFGE patterns observed, including two clusters of two (ST340 and four (ST101 indistinguishable isolates, respectively. All isolates harbored at least one ESBL or AmpC gene, all carried on transferable plasmids (IncR, IncFII, IncI1, IncN, and 16/19 were positive for PMQR genes (qnr family or aac(6'-Ib-cr. The most frequent ESBL was CTX-M-15 (11/19, 58%, detected in all KP ST101, in one KP ST15 and in both KP ST340. blaCTX-M-15 was carried on IncR plasmids in all but one KP isolate. All KP ST15 isolates harbored different ESC resistance genes and different plasmids, and presented the non-transferable blaSHV-28 gene, in association with blaCTX-M-15, blaCTX-M-1 (on IncR, or on IncN, blaSHV-2a (on IncR or blaCMY-2 genes (on IncI1. KO isolates were positive for blaCTX-M-9 gene (on IncHI2, or for the blaSHV-12 and blaDHA-1 genes (on IncL/M. They were all positive for qnr genes, and one also for the aac(6'-Ib-cr gene. All Klebsiella isolates showed multiresistance towards aminoglycosides, sulfonamides, tetracyclines, trimethoprim and amphenicols, mediated by strA/B, aadA2, aadB, ant (2"-Ia, aac(6'-Ib, sul, tet, dfr and cat genes in various combinations. The emergence in pets of multidrug-resistant Klebsiella with ESBL, AmpC and PMQR determinants, poses further and serious challenges in companion animal therapy and raise concerns for possible bi-directional transmission between

  16. 武汉地区7家医院连续5年喹诺酮类药用药频度与细菌耐药性分析%Analysis of the Use Density and Bacterial Resistance of Quinolones in 5 Consecutive Years in Wuhan

    Institute of Scientific and Technical Information of China (English)

    汪震; 刘东; 沈倩倩; 杜光; 孙自镛

    2012-01-01

    Objective: To investigate the relationship between the use density and bacterial resistance of quinolo-nes. Method: The consumption of quinolones in the past 5 years was investigated and the relationship between their consumption and bacterial resistance was statistically analyzed by linear correlation. Result;The resistance rates of most bacteria monitored exceeded the warning line by 30% . With the change of the use density of quinolones, the resistance rates of Acinetobacter baumannii bacteria changed in the past 5 years. There was a highly correlation between the use density of quinolones and the resistance rates of Acinetobacter baumannii bacteria. Conclusion: The bacterial resistance of quinolones was at a high level. The consumption of quinolones could create their affection on the bacterial resistance in some degree. The application of quinolones should be strictly managed to delay the bacterial resistance.%目的:研究喹诺酮类抗菌药的用量与细菌耐药率之间的关系,促进临床合理用药.方法:回顾性调查武汉地区7家医院2005~2009年喹诺酮类抗菌药的用量,并与监测菌的耐药率做相关分析.结果:大多数监测菌种对喹诺酮类药的耐药率均超过30%;鲍曼不动杆菌对喹诺酮类药的耐药率随喹诺酮类药用量的变化而变化,与喹诺酮类药总用药频度高度相关.结论:喹诺酮类药对多数常见菌种的耐药率较高,其用药频度对细菌耐药性变异也有一定影响.应严格把握喹诺酮类药的临床适应证,加强对喹诺酮类药的管理,以减少或延缓细菌耐药性的发生.

  17. Studies on Elimination Rule of Residues of Three Kinds of Quinolones in Eggs%三种喹诺酮类药物在鸡蛋中残留消除规律的研究

    Institute of Scientific and Technical Information of China (English)

    章敏; 宁军; 余军军; 韦田; 邰镝

    2014-01-01

    建立了一种检测三种喹诺酮类药物在鸡蛋中残留的高效液相色谱-荧光检测法。利用建立的方法对三种喹诺酮类药物在产蛋期蛋鸡用药后鸡蛋中的浓度进行了测定,并根据测定值研究了鸡蛋中药物的残留消除规律。400 kg水中分别添加不同含量的诺氟沙星、氧氟沙星、恩诺沙星,连续给药3 d,使用高效液相色谱法对鸡蛋中三种喹诺酮类药物残留进行分析。结果表明,停药8 d时,鸡蛋中检出的诺氟沙星和氧氟沙星的浓度均低于10μg/kg;停药12 d时,鸡蛋中检出的恩诺沙星的浓度低于10μg/kg。建议诺氟沙星和氧氟沙星在临床上蛋鸡产蛋前10 d左右停用,恩诺沙星在临床上蛋鸡产蛋前14 d左右停用。%A method for determination of quinolones residues in eggs by HPLC with fluorescence detector detection was established, and this method for determination the concentration in the laying hens, the elimination of quinolones residues in eggs was studied. Different content of norfloxacin,ofloxacin,enrofloxacin were added in the water for 3 days, the residues of quinolones were determined by HPLC. The results showed that the residues of norfloxacinand and ofloxacin in eggs were less than 10μg/kg at 8th withdrawal day;the residues of enrofloxacin in eggs was less than 10 μg/kg at 12th withdrawal day. So, the withdrawal period of norfloxacin, ofloxacin, enrofloxacin were found to be 10 d,10 d,14 d in clinical before the age at first egg, respectively.

  18. Analysis of antimicrobial resistance of Acinetobacter baumannii to quinolones%鲍氏不动杆菌对喹诺酮类抗菌药物的耐药性分析

    Institute of Scientific and Technical Information of China (English)

    王宝英; 张凤民; 王洪; 孟凡飞; 徐晖; 付英梅; 王金冬; 方文娟; 尤玉红; 钟秀丽

    2012-01-01

    目的 分析临床分离的鲍氏不动杆菌对喹诺酮类抗菌药物的耐药特点及耐药机制.方法 采用K-B纸片法测定33株鲍氏不动杆菌对喹诺酮类等21种抗菌药物的耐药性;用PCR技术扩增33株鲍氏不动杆菌的gyrA基因的耐药决定区,PCR产物经纯化后测序与GenBank中的标准序列比较,分析其突变情况.结果 33株鲍氏不动杆菌中,8株对环丙沙星耐药,占24.2%,4株对左氧氟沙星耐药占12.1%;对环丙沙星耐药的8个菌株均有gyrA基因突变,导致氨基酸变异为Ser-83→Leu,其中包括对左氧氟沙星耐药的4个菌株;所有对环丙沙星敏感的菌株未出现gyrA基因突变.结论 gyrA基因突变决定鲍氏不动杆菌对喹诺酮类抗菌药物的耐药.%OBJECTIVE To analyze the drug resistance characteristics and mechanisms to quinolones in 33 clinical isolates of Acinetobacter baumannii in Harbin. METHODS A total of 33 strains of A. Baumannii were collected and their susceptibility to 21 antimicrobial agents was determined by K-B disk diffusion method. Quinolone resistance determining regions in gyrA gene were amplified by PCR and the PCR products were purified and sequenced, which were then compared with the standard sequences in the GenBank to analyze mutations. RESULTS The resistance rates of A. Baumannii to ciprofloxacin and levofloxacin were 24. 2% (8/33) and 12. 1% (4/33) , respectively. DNA sequencing showed that all the ciprofloxacin-resistant isolates had gyrA mutation (Ser-83→Leu in 8 strains), which included the four isolates resistant to levofloxacin. No gyrA gene mutation was found in ciprofloxacin-susceptible strains. CONCLUSION Drug resistance of clinical isolates of A. Baumannii to quinolones is determined by the mutation in gyrA.

  19. Multiclass method for the determination of quinolones and β-lactams, in raw cow milk using dispersive liquid-liquid microextraction and ultra high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Junza, Alexandra; Dorival-García, Noemí; Zafra-Gómez, Alberto; Barrón, Dolores; Ballesteros, Oscar; Barbosa, José; Navalón, Alberto

    2014-08-22

    An analytical method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) followed by ultra high performance liquid chromatography-tandem mass spectrometry analysis (UHPLC-MS/MS) for the determination of 17 quinolones and 14 β-lactams (penicillins and cephalosporins) in raw cow milk, was validated according to the European Commission guidelines as cited in the Decision 2002/657/EC. The extraction efficiency of the DLLME depends on several parameters such as the nature and volumes of extractant and dispersive solvents, pH, concentration of salt, shaking time and time of centrifugation. These variables were accurately optimized using multivariate optimization strategies. A Plackett-Burman design to select the most influential parameters and a Doehlert design to obtain the optimum conditions have been applied. Two different pH values were used for the extraction of compounds (pH 3 for acidic quinolones and β-lactams and pH 8 for amphoteric quinolones). The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. The limits of quantification found ranged from 0.3 ng g(-1) for amoxicillin to 6.6 ng g(-1) for ciprofloxacin, and the precision was lower than 15% in all cases as is required by the European Regulation. The decision limits (CCα) ranged between 4.1 and 104.8 ng g(-1), while detection capabilities (CCβ) from 4.2 to 109.7 ng g(-1). These values were very close to the corresponding maximum residue limits (MLRs) for the studied antibiotics. Recoveries between 72 and 110% were also obtained. Finally, in order to evaluate the applicability of the method, 28 raw cow milk samples were analysed and it was observed that 28% of the samples were positive. However, only 11% were considered non-compliant with the current EU legislation (Commission Regulation 37/2010), due to some milk samples corresponded to treated cows with these antibiotics.

  20. The Pseudomonas Quinolone Signal (PQS)

    DEFF Research Database (Denmark)

    Sams, Thomas; Baker, Ysobel; Hodgkinson, James

    2015-01-01

    Pseudomonas aeruginosa is an opportunistichuman pathogen that routinely appears near the top ofpublic health threat lists worldwide. P. aeruginosa causes in-fections by secreting a wealth of exceptionally active exo-products, leading to tissue damage. The synthesis of manyof these virulence factors...

  1. The determination of plamid-mediated qnr gene in quinolone-resistant Shigella%氟喹诺酮耐药志贺菌中质粒介导qnr基因的检测

    Institute of Scientific and Technical Information of China (English)

    汪雅萍; 应春妹; 张灏旻; 叶杨芹; 于嘉屏

    2011-01-01

    目的 检测志贺菌对氟喹诺酮抗菌药物的耐药情况,探讨氟喹诺酮耐药与志贺菌携带质粒介导qnr基因的关系.方法 用纸片扩散法对100株志贺菌(福氏志贺菌50株,宋内志贺菌50株)进行耐药性检测,聚合酶链反应(PCR)检测志贺菌质粒介导qnr基因并进行DNA测序,分析qnr基因的存在与药敏结果的关系.结果 100株志贺菌中有9株检出qnr基因,检出率为9% (9/100),福氏志贺菌为4% (2/50),宋内志贺菌为14%(7/50);qnr基因阳性菌株对氧氟沙星的耐药率(11.1%)高于阴性菌株(5.5%),但差异无统计学意义.qnr基因阳性菌株对5种氟喹诺酮药物的抑菌圈中位数比较均缩小.结论宋内志贺菌质粒介导氟喹诺酮耐药qnr基因的携带率明显高于福氏志贺菌;志贺菌若携带质粒介导qnr基因则会导致对氟喹诺酮药物的敏感性下降.%Objective To investigate the quinolone-resistance of Shigella isolates and its relationship with the plamid-mediated qnr gene. Methods A total of 100 Shigella isolates were collected. SO isolates were ShigeUa flexneri, and 50 isolates were Shigella sonnei. The drug resistance was determined by disc diffusion method. The qnr gene was detected by polymerase chain reaction ( PCR). The qnr gene segments were amplified and sequenced to analyze the correlation between quinolone-resistance and the presence of qnr gene. Results The qnr gene was identified in 9 (9% )of the 100 ShigeUa isolates,2 (4% ) of the 50 Shigella flexneri and 7 ( 14% ) of the 50 Shigella sonnei. The resistance rate of ofloxacin in qnr positive isolates(11. 1% ) was higher than that in qnr negative isolates(5.5% ) , but there was no statistical significance. The median diameters of 5 quinolone inhibition zones of the isolates with qnr gene were smaller than those without qnr gene. Conclusions The plamid-mediated qnr gene in Shigella sonnei isolates is more than that in Shigella flexneri isolates. The plamid-mediated qnr

  2. Spectroscopic and structural studies of quinoline derivatives—II. Forrier transform i.r. spectroscopy. 1. Rotational isomerism in 3-ethoxycarbonyl-4(1H)-quinolone and some of its substituted derivatives,

    Science.gov (United States)

    Mirek, Julian; Urbanek, Zbigniew H.

    Rotational isomerism associated with internal rotation about the ring carbon(3)-ester carbonyl carbon single bond in a series of 3-ethoxycarbonyl-4(1H)-quinolones have been investigated spectroscopically in the solid state using Fourier transform i.r. and laser Raman spectroscopy. Particular attention is given to the 1700, 1300 and 1100 cm -1 spectral regions related primarily to the vibrations of the CO 2C 2H 5 group. Within these regions rotational isomerism appeared in the compounds examined. The conformational changes are discussed and evidence is reported for occurrence of the unsubstituted compound 1 itself in the solid state at ambient temperature as an equilibrium mixture of both the s-trans ( 1a) and s-cis ( 1b) rotamers (this is in contrast to previous findings), and of its Bz-substituted derivatives.

  3. International collaborative study on the occurrence of plasmid-mediated quinolone resistance in Salmonella enterica and Escherichia coli isolated from animals, humans, food and the environment in 13 European countries

    DEFF Research Database (Denmark)

    Veldman, Kees; Cavaco, Lina; Mevius, Dik

    2011-01-01

    containing MIC values for Salmonella and E. coli isolated between 1994 and 2009 in animals, humans, food and the environment from 13 European countries were screened for isolates exhibiting a defined quinolone resistance phenotype, i.e. reduced susceptibility to fluoroquinolones and nalidixic acid. PCR....... In Salmonella, qnrS1 (n = 125) and variants of qnrB (n = 138) were frequently identified, whereas qnrA1 (n = 3) and aac(6')-1b-cr (n = 3) were rarely found. qnrD was detected in 22 Salmonella isolates obtained from humans and animals. In E. coli, qnrS1 was identified in 19 isolates and qnrB19 was found in one...

  4. Application of dispersive liquid-liquid microextraction and dispersive micro-solid-phase extraction for the determination of quinolones in swine muscle by high-performance liquid chromatography with diode-array detection

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Wen-Hsien [Department of Food Science, National Pingtung University of Science and Technology, No. 1 Hseuh-Fu Road, Nei-Pu, 91201 Pingtung, Taiwan (China); The Health Bureau of Kaohsiung County Government, No. 834-1, Chengcing Road, Niaosong, Kaohsiung County 833, Taiwan (China); Chuang, Hung-Yi [The School of Public Health, Kaohsiung Medical University, and Department of Community Medicine, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan First Road, Kaohsiung 80708, Taiwan (China); Chen, Ho-Hsien [Department of Food Science, National Pingtung University of Science and Technology, No. 1 Hseuh-Fu Road, Nei-Pu, 91201 Pingtung, Taiwan (China); Huang, Joh-Jong [The Health Bureau of Kaohsiung County Government, No. 834-1, Chengcing Road, Niaosong, Kaohsiung County 833, Taiwan (China); Chen, Hwi-Chang; Cheng, Shou-Hsun [Southern Region Laboratory, Bureau of Food and Drug Analysis, Department of Health, Executive Yuan, No. 180, Zihyou 2nd Road, Zuoying District, Kaohsiung City 813-58, Taiwan (China); Huang, Tzou-Chi, E-mail: tchuang@mail.npust.edu.tw [Department of Food Science, National Pingtung University of Science and Technology, No. 1 Hseuh-Fu Road, Nei-Pu, 91201 Pingtung, Taiwan (China)

    2009-12-10

    Dispersive liquid-liquid microextraction (DLLME) and dispersive micro-solid-phase extraction (DMSPE) are two simple and low-cost sample preparation methods for liquid samples. In this work, these two methods were applied to solid tissue sample for the determination of seven quinolones by high-performance liquid chromatography with diode-array detection (HPLC-DAD). After the homogenization of the swine muscle with acetonitrile and salt-promoted partitioning, small amounts of the extract were used for the DLLME and DMSPE methods. In the DLLME approach, the target analytes in the extraction solvent were rapidly extracted into a small volume of dichloromethane for drying and the residue was reconstituted for HPLC-DAD analysis. In the DMSPE approach, the target analytes in the extraction solvent were trapped by dispersive silica-based PSA (primary and secondary amine) sorbents and desorbed into a small amount of desorption solution for HPLC-DAD analysis. Under the optimal conditions, relative recoveries were determined for swine muscle spiked 50-200 {mu}g kg{sup -1} and quantification was achieved by matrix-matched calibration. The calibration curves of seven quinolones showed linearity with a correlation coefficient value above 0.998 for both approaches. Relative recoveries ranged from 93.0 to 104.7% and from 95.5 to 111.0% for DLLME and DMSPE, respectively. Limits of detection (LODs) ranged from 5.6 to 23.8 {mu}g kg{sup -1} and from 7.5 to 26.3 {mu}g kg{sup -1} for DLLME and DMSPE, respectively.

  5. Application of dispersive liquid-liquid microextraction and dispersive micro-solid-phase extraction for the determination of quinolones in swine muscle by high-performance liquid chromatography with diode-array detection.

    Science.gov (United States)

    Tsai, Wen-Hsien; Chuang, Hung-Yi; Chen, Ho-Hsien; Huang, Joh-Jong; Chen, Hwi-Chang; Cheng, Shou-Hsun; Huang, Tzou-Chi

    2009-12-10

    Dispersive liquid-liquid microextraction (DLLME) and dispersive micro-solid-phase extraction (DMSPE) are two simple and low-cost sample preparation methods for liquid samples. In this work, these two methods were applied to solid tissue sample for the determination of seven quinolones by high-performance liquid chromatography with diode-array detection (HPLC-DAD). After the homogenization of the swine muscle with acetonitrile and salt-promoted partitioning, small amounts of the extract were used for the DLLME and DMSPE methods. In the DLLME approach, the target analytes in the extraction solvent were rapidly extracted into a small volume of dichloromethane for drying and the residue was reconstituted for HPLC-DAD analysis. In the DMSPE approach, the target analytes in the extraction solvent were trapped by dispersive silica-based PSA (primary and secondary amine) sorbents and desorbed into a small amount of desorption solution for HPLC-DAD analysis. Under the optimal conditions, relative recoveries were determined for swine muscle spiked 50-200 microg kg(-1) and quantification was achieved by matrix-matched calibration. The calibration curves of seven quinolones showed linearity with a correlation coefficient value above 0.998 for both approaches. Relative recoveries ranged from 93.0 to 104.7% and from 95.5 to 111.0% for DLLME and DMSPE, respectively. Limits of detection (LODs) ranged from 5.6 to 23.8 microg kg(-1) and from 7.5 to 26.3 microg kg(-1) for DLLME and DMSPE, respectively.

  6. High Prevalence of Plasmid-Mediated Quinolone Resistance and IncQ Plasmids Carrying qnrS2 Gene in Bacteria from Rivers near Hospitals and Aquaculture in China.

    Directory of Open Access Journals (Sweden)

    Yanping Wen

    Full Text Available Effluents from hospital and aquaculture are considered important sources of quinolone resistance. However, little information is available on the impact of this effluent on nearby rivers. In this study, 188 ciprofloxacin-resistant bacterial isolates obtained from rivers near hospitals and aquaculture were screened for plasmid-mediated quinolone resistance (PMQR genes. Species identification, antibiotic susceptibility testing, and PMQR gene transferability assessment were conducted for PMQR-positive bacteria. Representative qnrS2-encoding plasmids were subsequently sequenced using a primer-walking approach. In total, 44 isolates (23.4% were positive for qnr genes (16 qnrB2, 3 qnrS1, and 25 qnrS2 and 32 isolates (17.0% were positive for aac(6'-Ib-cr. Other PMQR genes were not detected. The qnrB2 and aac(6'-Ib-cr genes had a higher prevalence in aquaculture samples than in hospital samples, and were significantly associated with Enterobacteriaceae (p < 0.05. In contrast, the prevalence of qnrS2 was not site-related, but was significantly associated with Aeromonas spp. (p < 0.05. All PMQR isolates were resistant to three or more classes of antibiotics. Eleven qnrS2-harboring plasmids from Aeromonas spp., including a novel conjugative plasmid pHP18, were selected for sequencing. These plasmids were small in size (6,388-16,197 bp and belonged to the IncQ or IncU plasmid family, with qnrS2 being part of a mobile insertion cassette. Taken together, our findings suggest that aquaculture is a possible source for aac(6'-Ib-cr and qnrB2 dissemination, and demonstrate the ubiquity of qnrS2 in aquatic environments. Finally, Aeromonas spp. served as vectors for qnrS2 with the help of IncQ-type plasmids.

  7. First characterisation of plasmid-mediated quinolone resistance-qnrS1 co-expressed bla CTX-M-15 and bla DHA-1 genes in clinical strain of Morganella morganii recovered from a Tunisian Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    S Mahrouki

    2012-01-01

    Full Text Available Purpose: Aim of this study was to show the emergence of the qnr genes among fluoroquinolone-resistant, AMPC and ESBL (extended-spectrum-beta-lactamase co-producing Morganella morganii isolate. Materials and Methods: A multi resistant Morganella morganii SM12012 isolate was recovered from pus from a patient hospitalized in the intensive care unit at the Military hospital, Tunisia. Antibiotic susceptibility was tested with the agar disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. ESBLs were detected using a standard double-disk synergy test. The characterization of beta-lactamases and associated resistance genes were performed by isoelectric focusing, polymerase chain reaction and nucleotide sequencing. Results: The antimicrobial susceptibility testing showed the high resistance to penicillins, cephalosporins (MICs: 64-512 μg/ml and fluoroquinolones (MICs: 32-512 μg/ml. But M. morganii SM12012 isolate remained susceptible to carbapenems (MICs: 4-<0.25 μg/ml. The double-disk synergy test confirmed the phenotype of extended-spectrum β-lactamases (ESBLs. Three identical β-lactamases with pI values of 6.5, 7.8 and superior to 8.6 were detected after isoelectric focusing analysis. These β-lactamases genes can be successfully transferred by the conjugative plasmid. Molecular analysis demonstrated the co-production of bla DHA-1, bla CTX-M-15 and qnrS1 genes on the same plasmid. The detection of an associated chromosomal quinolone resistance revealed the presence of a parC mutation at codon 80 (Ser80-lle80. Conclusion: This is the first report in Tunisia of nosocomial infection due to the production of CTX-M-15 and DHA-1 β-lactamases in M. morganii isolate with the association of quinolone plasmid resistance. The incidence of these strains invites continuous monitoring of such multidrug-resistant strains and the further study of their epidemiologic evolution.

  8. Determination of Quinolone Antibiotics in Water Using Solid Phase Extraction-High Performance Liquid Chromatography-Fluorescence Method%固相萃取-高效液相色谱-荧光法测定水中喹诺酮类抗生素

    Institute of Scientific and Technical Information of China (English)

    王桥军; 亦如瀚; 莫测辉

    2011-01-01

    [目的]建立固相萃取-高效液相色谱-荧光检测法测定水中喹诺酮类抗生素含量.[方法]利用4种喹诺酮类抗生素(诺氟沙星、环丙沙星、洛美沙星和恩诺沙星)的标准品建立标准曲线、喹诺酮类抗生素在水中的检出限及回收率;对采集自不同地区、河段以及自来水的水样使用固相萃取法处理,进行高效液相色谱分析,采用荧光法测定样品中4种喹诺酮类抗生素的含量.[结果]这4种喹诺酮类抗生素在水中的检出限为0.083~0.248μg/L;回收率为63.7%-134.1%.各种水样均不同程度栓出这4种喹诺酮类抗生素,总合量为0.045-3.969μg/L.其中,深圳河水样的喹诺酮类抗生素总含量高于污水,而在自来水中均能检出这4种喹诺酮类抗生素.[结论]采用固相萃取-高效液相色谱-荧光同时测定环境水样中喹诺酮类抗生素是有效可行的,并且价格低廉,能够满足日常监测分析要求.%[ Objective ] To develop a solid phase extraction-high performance liquid chromatography -fluorescence method for determination of quinolone antibiotics in water. [ Method ] The standard curves of four quinolones (norfloxacin, ciprofloxacin, lomefloxacin and enrofloxacin)were prepared. The detection limit in water and recovery were determined. The water samples collected from different areas, river and tap water were treated using solid-phase extraction method and analyzed by high performance liquid chromatography. Then the concentration of quinolones antibiotics was determined by fluorescence method. [ Result] The detection limit of quinolone antibiotics in water was 0.083 -0. 248 μg/L, and their recovery was 63.7% - 134.1%. The four quinolone antibiotics at different levels were detected in various water samples,and the total concentration of quinolones antibiotics was 0.045 -3. 969 μg/L. The total concentration of quinolones antibiotics was higher in the water samples collected from rivers in Shenzhen area

  9. 专项整治前后某院喹诺酮类抗菌药应用情况对比分析%Comparative Analysis of the Usage of Quinolones before and after Special Rectification in a Hospital

    Institute of Scientific and Technical Information of China (English)

    杨杰; 王萍; 仲鹏磊; 周如君

    2015-01-01

    目的:分析评价南京某三甲医院抗菌药专项整治前后喹诺酮类抗菌药使用情况和发展趋势,为抗菌药临床应用专项整治活动及管理提供依据。方法:调取该院2010年(整治前)和2011~2013年(整治后)所用喹诺酮类抗菌药的使用记录,采用回顾性方法,对该类药物的销售金额、用药频度( DDDs)、限定日费用( DDC)、细菌耐药情况及药品不良反应进行统计分析。结果:整治后(2011~2013年)喹诺酮类抗菌药销售金额及占抗菌药总销售金额比例较整治前(2010年)有明显下降;整治前注射用门冬氨酸洛美沙星的销售金额和DDDs最高,整治后的2012~2013年,莫西沙星注射剂和盐酸左氧氟沙星注射液的销售金额最高,分别位于第1、2位;盐酸左氧氟沙星片和盐酸左氧氟沙星注射液的DDDs最高,分别位于第1、2位;莫西沙星注射剂DDC最高。主要耐药菌葡萄球菌、肠杆菌科细菌、非发酵菌对左氧氟沙星、诺氟沙星、环丙沙星的耐药率有所下降;整治后该院抗菌药所致不良反应例数及喹诺酮类抗菌药所致不良反应占抗菌药不良反应的比例低于整治前。结论:该院通过抗菌药专项整治,喹诺酮类抗菌药的各项应用指标明显改善,喹诺酮类抗菌药的合理应用也取得成效,专项整治的效果比较明显。但该院还应加强对第4代喹诺酮类抗菌药的临床应用加以督导。%Objective:To analyze and evaluate the usage and tendency of quinolones before and after the special rectification of antibacterial in one grade III level A hospital in üanjing to provide evidence for the special rectification of antibacterial and manage-ment. Methods:The usage records of quinolones in 2010( before the special rectification)and in 2011-2013( after the special rectifi-cation)were collected,and the sales revenue,DDDs,defined daily cost( DDC),drug resistance and

  10. 2009年-2011年重庆地区20家医院喹诺酮类抗菌药物用药分析%Analysis of Quinolones Used in 20 Hospitals of Chongqing During the Period of 2009-2011

    Institute of Scientific and Technical Information of China (English)

    郭茂华; 谭宏洁; 何丽蓉

    2013-01-01

    目的:评价重庆地区医院喹诺酮类抗菌药物的应用情况和发展趋势,为临床用药提供参考。方法:统计分析重庆地区20家医院2009年-2011年喹诺酮类抗菌药物的销售金额、用药频度、日均费用等数据。结果:重庆地区2009年-2011年抗喹诺酮类抗菌药物销售金额基本持平,销售金额排序前3位的是左氧氟沙星、加替沙星、莫西沙星,用药频度排序前3位的是左氧氟沙星、司帕沙星、加替沙星。结论:在重庆地区应用的喹诺酮类抗菌药物中,左氧氟沙星的应用占主导地位,莫西沙星的应用呈逐年上升趋势。%Objective: To evaluate the clinical application of quinolones in the hospitals of Chongqing City for the clinical references on rational administration. Methods: Statistical analysis on the application of quinolones in hospitals of ChongqingCity from 2009 to 2011 was conducted in terms of consumption sum, administration frequency, daily costs, etc. Results:Consumption sum of quinolones in the period of 2009-2011 was stable. During this period, the top three most consumed quinolones were levofloxacin, gatifloxacin, moxifloxacin. The top three most frequently used quinolones were levofloxacin, sparfloxacin and gatifloxacin. Conclusion: Levofloxacin was the dominant quinolone in clinic. Moxifloxacin would have a broad prospect in clinic therapy.

  11. Correlation of Mutation Patterns in gyrA and parC Genes in Ureaplasma Urealyticum Isolates with Quinolones Resistance%gyrA和parC基因突变与解脲支原体喹诺酮类药物耐药相关性研究

    Institute of Scientific and Technical Information of China (English)

    王春燕; 杜江; 吴森林; 孙爱华

    2012-01-01

    Objective To analyze mutations in the quinolone -resistance - determining - region ( QRDR) within genes of gyrA and parC patterns in gyrA and parC genes and quinolones resistance in ureaplasma urealyticum(Uu) isolates. Methods Mycoplasma detection kits were used to culture and identificate mycoplasma as well as drug sensitivity. PCR and DNA sequencing were conducted to analyze QRDR associated genes of gyrA and parC in 42 isolates. Results Only 1 isolate susceptible to all quinolones. Fourty - one isolates showed varying degree resistance to at least one kind of quinolones. Sequencing analysis of gyrA and parC revealed that the susceptible i-solate and 1 resistance isolate had no mutation, Fourty resistance isolates had mutation of D112E and/or S83L in GyrA and ParC. Conclusion Three quinolones should not be routine therapy for ureaplasma urealyticum infections. Mutations in gyrA and parC genes play an important role in the development of quinolones resistance in ureaplasma urealyticum.%目的 探讨解脲支原体gyrA和parC基因喹诺酮耐药决定区(QRDR)突变与喹诺酮类药物耐药的相关性.方法 用支原体培养、鉴定和药敏一体化试剂盒分离获得42株解脲支原体并检测对3种喹诺酮类药物的耐药性,同时PCR法扩增临床分离株的gyrA和parC基因喹诺酮耐药决定区并进行测序分析.结果 对3种喹诺酮均敏感1株,41株至少对1种药物呈现不同程度耐药.gyrA和parC基因喹诺酮耐药决定区测序发现上述敏感株和1株耐药株不发生突变,其余40株耐药株gyrA和parC基因发生D112E和(或)S83L突变.结论 3种喹诺酮类药物耐药均较严重,已不适合作为临床推荐用药,解脲支原体gyrA和parC基因喹诺酮耐药决定区突变与耐药密切相关.

  12. Utilization of Quinolones in 81 Hospitals in Shanghai During the Period 2006~2008%上海地区81家医院2006~2008年喹诺酮类抗菌药物利用分析

    Institute of Scientific and Technical Information of China (English)

    陈敏玲

    2009-01-01

    目的:评价上海地区医院喹诺酮类抗菌药物的应用情况.方法:采用回顾性方法,对上海地区2006~2008年81家医院喹诺酮类抗茼药物的销售金额、用药频度(DDDs)和限定日费用(DDC)等进行统计、分析.结果:上海地区81家医院喹诺酮类抗菌药物销售金额、DDDs和DDC的年均增长率分别为12.66%、0.48%和12.12%.特别是DDC较高的喹诺酮类注射用药增长速度较快,其销售金额和DDDs年均增长率达14.33%和3.10%,而口服喹诺酮类抗菌药物相应的增长率仅为8.59%和-0.05%.结论:应严格控制喹诺酮类抗菌药物的应用,以确保临床用药安全、有效和经济.%To evaluate the utilization of quinolones in 81 hospitals in Shanghai. METHODS: By a retrospective study, the quinolones used in 81 hospitals in Shanghai were analyzed statistically in respect of the consumption sum, DDDs and DDC,etc. RESULTS: During the period 2006~2008, the average annual growth rates of quinolones in consumption sum, DDDs and DDC were 12.66%, 0.48% and 12.12%, respectively; and the injections of quinolones that of higher DDC witnessed the more rapid mean growth rates, up to 14.33% in consumption sum and 3.10% in DDDs, while the mean growth rates for oral quinolones were 8.59% in consumption sum and -0.05% in DDDs. CONCLUSION: Measures should be taken to tighten control on the use of quinolones to ensure their safe, effective and economical clinical medication.

  13. Quinolone resistance and gyr gene mutations in multi-drug resistant of Mycobacterium tuberculosis%耐多药结核分枝杆菌对喹诺酮类药物的耐药性与gyr基因突变的初步研究

    Institute of Scientific and Technical Information of China (English)

    赵丽丽; 夏强; 赵秀芹; 刘志广; 万康林

    2011-01-01

    目的 分析耐多药结核分枝杆菌(Multiple drug-resistant tuberculosis,MDR-TB)临床分离株的gyr基因突变特点,探讨MDR-TB对喹诺酮类药物耐药产生与gyr基因突变的关系.方法 采用比例法对耐多药结核临床分离菌株进行氧氟沙星的药物敏感性检测,应用DNA直接测序法检测MDR-TB的gyr基因突变情况.结果 125株MDR-TB临床分离株中,50株对喹诺酮类耐药,耐药率为40%.50株耐药菌株中,40株gyr基因发生突变:其中39株gyrA基因突变,突变率为78%,突变位点包括90,91和94位氨基酸;5株gyrB基因突变,其中4株合并gyrA基因突变,gyrB基因突变位点为500,506,534和539位氨基酸.结论 MDR-TB中的喹诺酮类药物耐药态势比较严峻,其对喹诺酮类药物耐药机制主要与gyrA基因突变有关.%In order ot analyze the characteristics of gyr gene mutations in clinical isolates from the patients with multidrug resistant tuberculosis (MDR-TB) and the relation between MDR-TB with quinolone resistance and gyr gene mutations,the susceptibility of the MDR-TB clinical isolates to quinolones was tested by the proportion method.Gyr gene mutations of MDR-TB strains were detected by direct DNA sequencing.The results showed that there were 50 strains with quinolone resistance in 125 MDR-TB clinical isolates.The quinolone resistance rate was 40%.There were 40 with gyr mutations in 50 MDRTB with quinolone resistance.Of 40 quinolone resistant MDR-TB with gyr mutations, 39 mutated at condon 90, 91 and 94 of gyrA gene with a mutation rate of 78%.For 5 gyrB mutatans, 4 were associated with gyrA gene mutations.The mutation sites of gyrB were at condon 500, 506, 534 and 539 of gyrB gene.This study shows that the situation of MDR-TB with quinolone resistance is very serious.The mechanism of quinolone resistance in MDR-TB is mainly in connection with the mutation of gyrA gene.

  14. 伤寒杆菌耐喹诺酮类机制分子生物学基础研究%A study on the molecular basis of quinolone resistance mechanism in salmonella typhi

    Institute of Scientific and Technical Information of China (English)

    肖永红; 王其南

    2000-01-01

    Objective To study the relationship between the gene mutations of DNA gyrase subunit A(gyrA)and quinolone resistance in Salmonella typhi. Methods The genes of gyrA DNA of Salmonella typhi S275(a clinically isolated quinolone susceptible strain)and its spontaneous quinolone-re-sistant mutant RGl were examined in this study with polymerase chain reaction(PCR),restrictive frag-ments length polymorphism(RFLP),single strand conformational polymorphism(SSCP)and nucleotide sequencing. Results Nudeotide sequencing of gyrA in Salmonella typhi S275 revealed that the bases of 128~426 kept highly conservative as compared with those of Escherichia coli KL-16,with only 7.49%difference in the gyrA nucleotides 128~426 between the two strains.Most of the mutations were silent mutations,which contributed to 3 amino acid substitutions in gyrase(including Thr-45→His,Arg-49→Leu and Val-56→Gly),and all these substitutions were located outside the quinolone resistance determining re-gion(amino acids 67-106 of subunit A of gyrase).In comparison with Salmonella typhi S275,a single mutation was found at base 247 of gyrA of Salmonella typhi RG1,with change transferred from T to G and led to a substitution of Ser-83→Ala.The mutation might be responsible for the increase of MICs of nalidixic acid,ofloxacin and ciprofloxacin against Salmonella typhi from 2,0.06 and<0.03 to 512,2,and 1 mg/L respectively.Ser-83→A1a was also a newly discovered substitution in gyrA of Salmonella spp.The results of PCR-RFLP and SSCP were in concordance with results of nucleotide sequencing. Conclu.sions The mutation of gyrase at the 83rd amino acid maybe play a principal role in the resistance of Salmonella typhi to quinolone.%目的 研究伤寒杆菌DNA旋转酶A亚单位基因(gyrA)变异与其耐喹诺酮类的关系.方法 应用聚合酶链反应(PCR)检测、限制性片段长度多态性(RFLP)、单链构象多态性分析(SSCP)及序列测定,对伤寒杆菌$275(临床分离敏感菌株)及

  15. 尿路分离大肠埃希菌耐药性及喹诺酮类药物耐药株危险因素病例对照研究%The drug resistance of Escherichia coli isolated from urinary tract infection and risk factors of quinolone resistance strains

    Institute of Scientific and Technical Information of China (English)

    张昭勇; 张吉才; 杜毅

    2013-01-01

    Objective To analyze the drug resistance of Escherichia coli isolated from urinary tract infection and risk factors of quinolone resistance strains.Methods A total of 705 cases (strains) with Escherichia coli drug resistance isolated from urine specimens were divided into quinolone sensitive group [474 cases(strains)] and quinolone resistance group [231 cases(strains)].The risk factors of the quinolone resistance strains were analyzed.Results The sensitivity rate of amoxicillin/clavulanic acid,cefalotin,ceftazidime,aztreonam,piperacillin,amikacin,compound sulfamethoxazole,ciprofloxacin,gentamicin,levofloxacin,cefepime in quinolone resistance group was higher than that in quinolone sensitive group [50.2%(238/474) vs.78.8%(182/231),11.6%(55/474) vs.48.5%(112/231),17.9%(85/474) vs.63.2%(146/231),15.0%(71/474) vs.57.6%(133/231),3.2%(15/474) vs.27.7%(64/231),80.8%(383/474)vs.93.1%(215/231),16.0%(76/474) vs.49.8%(115/231),0 vs.100.0%(231/231),32.5% (154/474)vs.70.6% (163/231),3.8% (18/474) vs.98.7% (228/231),18.6% (88/474) vs.63.2% (146/231),P <0.05].Logistic regression analysis showed history of using the third generation cephalosporins and quinolones,urinary drainage and bacterium producing extra-broad spectrum beta-lactamase was independent risk factor for quinolone resistance Escherichia coli (P < 0.05).Conclusions The epidemic of quinolone resistance Escherichia coli isolated from urine specimens is extremely serious.The quinolone resistance is strong,and infection patients have a high medical cost and average length of stay.The quinolone resistance Escherichia coli infection has multiple independent risk factors.To strengthen the control of the independent risk factors can effectively prevent quinolone resistance strains infection spread.%目的 分析尿路感染大肠埃希菌耐药性及喹诺酮类药物耐药株感染危险因素.方法 监测705例(株)尿路感染大肠埃希菌的耐

  16. 喹诺酮类药对常见病原菌耐药变迁与耐药机制初探%Change of resistance and drug resistance mechanism of quinolone against common bacteria in clinical practice

    Institute of Scientific and Technical Information of China (English)

    黄小玲; 林渡娣; 杨春燕; 黄福新; 袁慧文

    2011-01-01

    Objective: To understand change of resistance and drug resistance mechanism of quinolone against common bacteria in clinical practice.Methods: To identify by Freneh Vitek-32 AMS analyzer, susceptibility test was performed with disc diffusion testing.The results were evaluated according to the standards of US Clinical and Laboratory Standards Institute (CLSI) to initially discuss bacterial resistance mechanisms by literature review.Results: Test results of resistance for 4 060 strains of common G+ and G- bacteria to quinolone indicated that drug resistance had increased in various degrees, the order of their resistance was: ciprofloxacin>levofloxacin>gatifloxacin>moxifloxacin, ciprofloxacin resistance against MRSA and MRCNS became more than 95.0% and 70.0% respectively.They were regarded as highly resistant to clinical medicine and should not be the first choice in clinical treatment any more.As for bacterial resistance mechanism it was mainly because of the decrease for intracellular drug accumulation concentration of bacteria and mutations at the target enzyme or target site, as well as resistance or multiple drug resistance caused by pLasmid mediation.Conclusion:Drug resistance against quinolone is increased annually.from the perspective of resistance mechanism, except drug sensitivity test should be performed in clinical practice, medicated drugs and dosage should also be optimized according to PK/PD parameters.%目的:了解喹诺酮类药对临床常见病原菌的耐药性变迁及耐药机制.方法:采用法国Vitek-32 AMS分析仪进行鉴定,纸片扩散法进行药敏试验;根据美国临床实验室标准化研究所(CLSI)标准判断结果,并查阅文献初探细菌耐药机制.结果:依据喹诺酮类药对常见G+和G-菌4060株耐药性的监测结果,耐药性均有不同程度增加,其耐药性排序为环丙沙星>左氧氟沙星>加替沙星>莫西沙星,环丙沙星对MRSA和MRCNS的耐药率分别超过95.0%和70.0%,已高度耐

  17. Study on Detection Method Quinolones Residues in Sheep Milk by HPLC%高效液相色谱法测定羊奶中五种氟喹诺酮类药物残留量的研究

    Institute of Scientific and Technical Information of China (English)

    李丹; 张玉洁; 孙志文; 王鹤佳; 李倩; 仲锋

    2016-01-01

    A method for determination of quinolones residues in sheep milk with HPLC by FLD detection was established.Ciprofloxacin、danofloxacin 、enrofloxacin、sarafloxacin and difloxacin were extracted from sheep milk with acetonitrile and degreased in hexane,dissolved with pH7.0 phosphate solution after evaporation,then the solution was purified with C18 column.The mobile phase were 0.05 mol /L triethylammonium phosphate solution and acetonitrile,the flow rate was 0.8 mL/min .Fluorescence detection was carried out at excitation and emission wavelengths of 280 nm and 450 nm .A good linearity of the calibration curve was obtained with the range of 10 ~200 ng/mL for ciprofloxacin、enrofloxacin、sarafloxacin and difloxacin,and 2 ~40 ng/mL for danofloxacin(R2 >0.999).The limit of quantification of ciprofloxacin、enrofloxacin、sarafloxacin and difloxacin was 30 μg/kg,and danofloxacin was 6 μg/kg.The average recoveries of quinolones residues from spiked sheep milk at the three concentrations of 30、100、200 μg/kg(ciprofloxacin、enrofloxacin、sarafloxacin and difloxacin)and 6、20、40 μg/kg (danofloxacin)ranged from 70 -100 %(n =5)respectively.In day -between days batch variation coefficients were both less than 20 %.This method can be applied for the determination of quinolones residues in sheep milk.%建立了一种可同时检测羊奶中五种氟喹诺酮类药物(环丙沙星、达氟沙星、恩诺沙星、沙拉沙星、二氟沙星)残留的高效液相色谱—荧光检测法。羊奶样品经乙腈提取,正己烷去脂肪,C18柱净化。以0.05 mol /L 磷酸三乙胺溶液和乙腈溶液为流动相,流速为0.8 mL/min,激发波长280 nm,发射波长450 nm。结果表明环丙沙星、恩诺沙星、沙拉沙星、二氟沙星在10~200 ng/mL,达氟沙星在2~40 ng/mL 呈良好的线性关系,R2均大于0.999。环丙沙星、恩诺沙星、沙拉沙星、二氟沙星的最低定量限为30μg/kg,达氟

  18. 耐碳青霉烯类与喹诺酮类肺炎克雷伯菌的耐药机制研究%Investigation of resistant mechanism of carbapenem and quinolone-resistant Klebsiella pneumoniae

    Institute of Scientific and Technical Information of China (English)

    郑红波; 黄东标; 王祥德

    2014-01-01

    OBJECTIVE To investigate the resistant mechanism of 20 strains of carbapenem-and quinolone-resistant K lebsiella pneumoniae .METHODS Totally 20 strains of K . pneumoniae were isolated from sputum specimens from inpatients in a third-grade hospital from Jan .to Jun .2012 .The modified Hodge test was performed to detect activities of carbapenemase ,then 40 kinds of class A-D beta-lactamase genes and quinolone-resistant genes were analyzed by PCR .RESULTS The modified Hodge test showed all 20 strains had carbapenemase activities ,TEM-1 and K PC-2 were all positive ,and TCC→ATC mutation emerged in 83rd codon of gyrA (amino acid sequence S→I) ,and GAC → GGC mutation emerged in 87th codon of gyrA (amino acid sequence D → G) .CONCLUSION Carrying K PC-2 and mutations of QRDR in gyrA was the resistant mechanism of carbapenem- and quinolone-resistant K . pneumoniae ,and the coincidence of phenotypes and genotypes suggested that hospital infection existed .%目的:研究20株耐碳青霉烯类与喹诺酮类肺炎克雷伯菌的耐药机制。方法20株肺炎克雷伯菌分离自2012年1-6月医院住院患者的痰液样本,采用改良的 Hodge试验检测碳青霉烯酶活性,再用PCR法检测A~D类40种β-内酰胺酶基因和喹诺酮类耐药基因。结果20株肺炎克雷伯菌经改良的Hodge试验检测均有碳青霉烯酶活性,均检出 TEM-1和 K PC-2型β-内酰胺酶基因,出现 gyrA基因第83位密码子 TCC→ATC突变(氨基酸序列S→I),第87位密码子GAC→GGC突变(氨基酸序列D→G )。结论肺炎克雷伯菌携带 K PC-2型β-内酰胺酶基因和存在 gyrA基因QRDR区突变,其是碳青霉烯类与喹诺酮类药物的耐药机制,肺炎克雷伯菌药敏表型与耐药基因型相同疑似医院感染。

  19. Antibiotic-Mediated Inhibition of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV Infection: A Novel Quinolone Function Which Potentiates the Antiviral Cytokine Response in MARC-145 Cells and Pig Macrophages

    Directory of Open Access Journals (Sweden)

    William A. Cafruny

    2008-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolonecontaining compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs. Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.

  20. Multiresidue LC-MS/MS analysis of cephalosporins and quinolones in milk following ultrasound-assisted matrix solid-phase dispersive extraction combined with the quick, easy, cheap, effective, rugged, and safe methodology.

    Science.gov (United States)

    Karageorgou, Eftichia; Myridakis, Antonis; Stephanou, Euripides G; Samanidou, Victoria

    2013-06-01

    A sensitive and selective confirmatory method for milk-residue analysis of ten quinolones and eight cephalosporins by LC-MS/MS has been developed herein. For the chromatographic separation of target analytes, a Perfectsil ODS-2 (250 × 4 mm, 5 μm) analytical column was used and gradient elution was applied, using a mobile phase of 0.1% w/w TFA in water and 0.1% w/w TFA in ACN. Ultrasound-assisted matrix solid-phase dispersion procedure was applied for the extraction and clean-up procedure of antimicrobials agents from milk matrix using a mixture of Bond Elut Plexa sorbent and QuEChERS. The method was validated meeting the European Legislation determining selectivity, linearity response, trueness, precision (repeatability and between-day reproducibility), decision limit, detection capability, and ruggedness following the Youden approach. Recoveries of all antibiotics ranged from 81.7 to 117.9%, while RSD values were lower than 13.7%. Limits of quantification for all examined compounds ranged from 2.4 to 15.0 μg/kg, substantially lower than the maximum residue limits established by the European Union (30-100 μg/kg).

  1. ESBL, plasmidic AmpC, and associated quinolone resistance determinants in coliforms isolated from hospital effluent: first report of qnrB2, qnrB9, qnrB19, and blaCMY-4 in Algeria.

    Science.gov (United States)

    Anssour, Lynda; Messai, Yamina; Derkaoui, Meriem; Alouache, Souhila; Estepa, Vanesa; Somalo, Sergio; Torres, Carmen; Bakour, Rabah

    2014-04-01

    The characterization of extended-spectrum beta-lactamases , plasmidic AmpC (pAmpC), and associated plasmid-mediated quinolone resistance (PMQR) determinants in cefotaxime-resistant coliforms isolated from hospital effluent in Algiers showed blaCTX-M genes in 89%, blaTEM-1 in 79·8%, and pAmpC genes (blaCIT) in 2·7% isolates. Association of ISEcp1B with blaCTX-M was found in all CTX-M+ isolates, and 97·2% harboured class 1 integrons. Sequencing showed blaCTX-M-15, blaCTX-M-3, and blaCMY-4 genes. blaCTX-M-3 and blaCTX-M-15 were located in Inc L/M conjugative plasmids. The PMQR determinants identified were qnrB1, qnrB2, qnrB9, qnrB19, qnrS2, and aac(6')-Ib-cr. qnrB2, qnrB9, qnrB19, and blaCMY-4 are described for the first time in Algeria and qnrB19 for the first time in non-clinical environments. This study highlights the major potential role of hospital effluents as providers of resistance genes to natural environments.

  2. Identification of plasmid-mediated quinolone resistance genes qnrA1, qnrB1 and aac(6′-1b-cr in a multiple drug-resistant isolate of Klebsiella pneumoniae from Chennai

    Directory of Open Access Journals (Sweden)

    H Magesh

    2011-01-01

    Full Text Available Purpose: Resistance to fluoroquinolones, a commonly prescribed antimicrobial for Gram-negative and Gram-positive microorganisms, is of importance in therapy. The purpose of this study was to screen for the presence of Plasmid-Mediated Quinolone Resistance (PMQR determinants in clinical isolates of Klebsiella pneumoniae. Materials and Methods: Extended-Spectrum Beta-Lactamase (ESBL isolates of K. pneumoniae collected during October 2009 were screened by the antimicrobial susceptibility test. The plasmids from these isolates were analysed by specific Polymerase chain Reaction (PCR for qnrA, qnrB and aac(6′-1b. The amplified products were sequenced to confirm the allele. Results: Our analysis showed that 61% out of the 23 ESBL K. pneumoniae isolates were resistant to ciprofloxacin and 56% to levofloxacin. The PMQR was demonstrated by transforming the plasmids from two isolates P12 and P13 into E. coli JM109. The PMQR gene qnrA was found in 16 isolates and qnrB in 11 isolates. The plasmid pKNMGR13 which conferred an minimum inhibitory concentration (MIC of more than 240 ΅g/ml in sensitive E. coli was found to harbour the qnrA1 and qnrB1 allele. Furthermore, the gene aac(6′-1b-cr encoding a variant aminoglycoside 6′-N Acetyl transferase which confers resistance to fluoroquinolones was found in the same plasmid. Conclusions: Our report shows the prevalence of PMQR mediated by qnrA and qnrB in multidrug-resistant K. pneumoniae isolates from Chennai. A multidrug-resistant plasmid conferring high resistance to ciprofloxacin was found to harbour another PMQR gene, aac(6′-1b-cr mutant gene. This is the first report screening for PMQR in K. pneumoniae isolates from India.

  3. Chemical stabilization of the polar fractions of petroleum for study by field ionization mass spectrometry. Study of the sulfoxides, quinolones and fluorenols in the most polar portion of the maltene fraction of Athabasca bitumen

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, D.S.; Elbrink, C.

    1983-03-31

    A survey of the chemical types present in the polar fraction of Athabasca maltene revealed the presence of three prominent homologous series of sulfoxides, C/sub n/H sub 2n-2SO, C/sub n/H/sub 2n-4/SO and C/sub n/H/sub 2n-6/SO. The volatile members of these series have been studied to determine the chemical structure and stereochemistry of the leading members of the terpenoid sulfoxides to provide new series of biological markers for geothermal studies and compounds of more appropriate thermal stability to monitor new approaches to refining and upgrading. Of the three oxygen-containing homologous series found to be present, C/sub n/H/sub 2n-18/O, C/sub n/H/sub 2n-24/O and C/sub n/H/sub 2n-16/O, the volatile members belonging to the C/sub n/H/sub 2n-16/O were studied in detail and shown to consist of a series of fluorenols in which the substitutent in the 9 position extends out to C/sub 8/. Mass spectral evidence was also found for methyl substitution on the ring system. Of the various nitrogen- and oxygen-containing species, the elemental composition of the homologous series C/sub n/H/sub 2n-11/NO was confirmed by high resolution mass spectrometry and tentatively assigned to a series of quinolones. The concentration of these nitrogen compounds and the sulfoxides have been found to be extremely variable within the same oil sand quarry, reflecting subtle changes in the biological source material. No relation between the concentration of the acids and sulfoxides has been found which might be related to the oxygen potential of the water during the deposition of the bitumen. 9 refs., 76 figs., 3tabs.

  4. 铜绿假单胞菌对喹诺酮类药物耐药的分子机制研究%Study on the molecular resistant mechanisms to quinolones in clinical isolates of Pseudomonas aeruginosa

    Institute of Scientific and Technical Information of China (English)

    陈树林; 陈利达; 陈茶; 黄彬; 屈平华; 吴强贵

    2012-01-01

    Objective: To study the molecular resistant mechanism of Pseudomonas aeruginosa to quinolones antibiotics and provide basis for clinical anti — infection therapy. Methods: The chromosome mediated — quinolones resistant genes gyrA, gyrB, parC, parE and plasmid — mediated resistant genes qnrA, qnrB, qnrC, qnrD, qnrS, qepA, oqxA, oqxB and aac(6') -Ib-cr were determinated by PCR. DNA sequencing was used for identification of gyrA and parC. Results: In 98 isolates of Pseudomonas aeruginosa resistant to ciprofloxacin, parE, qnrC and qnrS were not detected. The positive rates of gyrA, gyrB, parC, qnrA, qnrB, qnrD, qepA, aac(6') -1b -cr, oqxA and oqxB were 96.9% , 87.8% , 75.5% , 31.6% , 86.7% , 15. 3% , 11.2% , 53.1 % , 8.2% and 26.5% , respectively. By sequence analysis, 84 strains (85.7% ) had gyrA or parC mutation. 90 strains (91. 8% ) contained plasmid-mediated resistant genes, among them the positive rate of qnrB and aac (6') -Ib-cr were higher than other genes. Conclusion: Chromosome - mediated gene mutation as well as plasmid — mediated qnr, qepA, oqxAB and aac(6') — Ib — cr may be the main mechanisms of Pseudomonas aeruginos resistance to quinolones. qnrB and qnrD were found in Pseudomonas aeruginosa the first time.%目的:研究铜绿假单胞菌对喹诺酮类药物耐药的分子机制,为临床抗感染治疗提供依据.方法:用PCR法检测染色体介导的喹诺酮类耐药基因gyrA、gyrB、parC、parE和质粒介导的喹诺酮类耐药基因qnrA、qnrB、qnrC、qnrD、qnrS、qepA、aac(6’)-Ib-cr、oqxA和oqxB,并对gyrA和parC阳性结果进行测序分析.结果:98株耐环丙沙星的铜绿假单胞菌中未检出parE、qnrC和qnrS基因.gyrA、gyrB和parC的阳性率分别为96.9%、87.8%和75.5%.测序证实84株菌(85.7%)发生gyrA或parC基因突变.90株菌(91.8%)携带质粒介导的耐药基因,qnrA、qnrB、qnrD、qepA、aac(6’)-Ib-cr、oqxA和oqxB的阳性率分别为31.6%、86.7%、15.3%、11.2%、53.1

  5. 南京地区35家医院2009-2011年常用喹诺酮类药利用分析%Analysis of the Utilization of Commonly Used Quinolones in 35 Hospitals from Nanjing Area during the Period of 2009-2011

    Institute of Scientific and Technical Information of China (English)

    王陆军; 刘慧; 彭婕; 方芸

    2013-01-01

    目的:评价南京地区医院喹诺酮类药的应用情况.方法:对南京地区35家医院2009-2011年常用喹诺酮类药的销售金额、用药频度(DDDs)和日均费用(DDC)等进行回顾性统计、分析.结果:该地区医院喹诺酮类药的销售金额和DDDs整体呈逐年下降趋势,各年度的销售金额分别为83 172 965.10、76 225 513.46、62 876 382.09元,年均增长率为-13.05%;各年度的DDDs分别为2 910 542.73、2 478 391.70、2 512 051.15,年均增长率为-7.10%.左氧氟沙星的DDDs一直排在第1住,其DDDs分别为1 102 525.40、992 019.80、1 290 872.60,占喹诺酮类药总DDDs的42.85%;莫西沙星注射剂的销售金额和DDDs逐年上升,各年度的销售金额分别为11 781 874.56、13 120 229.39、15 527 001.24元,各年度的DDDs分别为41 092.00、45 903.00、56 016.00,各年度DDC分别为286.72、285.83、277.19元.除帕珠沙星注射剂外,其他品种的销售金额和DDDs皆呈下降趋势.2010年淘汰了3种药(吡哌酸、培氟沙星、妥舒沙星)并引进了1种新药(安妥沙星).结论:该地区医院喹诺酮类药的应用逐年减少,但为延缓细菌耐药性的产生,仍应继续严格控制喹诺酮类药的应用,以确保临床用药安全、有效和经济.%OBJECTIVE: To evaluate the utilization of quinolones in the hospitals from Nanjing areas. METHEDS: By a retrospective study, the consumption sum, DDDs and DDC of quinolones in 35 hospitals from Nanjing area during 2009 - 2011 were analyzed statistically in respect of consumption sum, DDDs and DDC, etc. RESULTS: During 3-year period, the consumption sum and DDDs of quinolones in 35 hospitals reduced year by year. The consumption sum were 83 172 965.10 yuan, 76 225 513.46 yuan,62 876 382.09 yuan, respectively, with annual growth rate of -13.05%. DDDs were 2 910 542.73,2 478 391.70 and 2 512 051.15, respectively, with annual growth rate of -7.10%. DDDs of levofloxacin had ranked first during 3-year period. The DDDs were 1

  6. 采用HPLC法和HPLC-MS/MS法检测水产品中喹诺酮类药物方法比较%Determination of quinolones in aquatic products by HPLC and HPLC-MS/MS:a comparison of the two methods

    Institute of Scientific and Technical Information of China (English)

    王丽娟; 张骊; 叶玫; 吴成业

    2015-01-01

    分别采用高效液相色谱/串联质谱法( HPLC-MS/MS )和高效液相色谱法( HPLC )对水产品中的诺氟沙星、环丙沙星和恩诺沙星喹诺酮类药物进行检测,旨在根据检测要求选择最佳的检测方法。通过分析检测限、线性范围、加标回收、精密度和方法比较2种检测方法,同时对22例市售水产品进行检测并比较分析。 HPLC-MS/MS法检测灵敏度高于HPLC法,且可快速、准确进行水产品中喹诺酮类药物检测。两种方法对恩诺沙星检测结果的相关系数为0.969,但HPLC检测数据低估于HPLC-MS/MS的2%。由于HPLC-MS/MS检测成本高,因此HPLC法可作为水产品中喹诺酮类药物残留检测的初步筛检方法,而HPLC -MS/MS法能准确定量水产品中喹诺酮类药物含量。%Quinolones which have demonstrated broad -spectrum activity against many pathogenic Gram -negative and Gram -positive bacteria are effective antibacterial drugs widely used against various important diseases of livestock and farmed fish. The European Union has established maximum residue limits ( MRL) for quinolone residues in animal tissues because of growing problem of microbial resistance. Thus, the estab-lishment of effective detection methods is required in order to control these drugs. Many papers have been published about the analysis of quinolone residues in animal products. High performance liquid chromatogra-phy/tandem mass spectrometry method ( HPLC - MS/MS ) and high performance liquid chromatography ( HPLC) method which are generally used were applied respectively to detect norfloxacin, ciprofloxacin and enrofloxacin in aquatic products because of their specificity, sensitivity, rapidity and robustness. The pur-pose of this paper was to select the suitable analytical method according to the requirement. The two methods had their own characteristics and were compared with regard to the detection limit, linear range, recovery, precision and influence factors of

  7. Occurrence of Quinolone and Sulfonamide Antibiotics in Swine and Cattle Manures from Large-scale Feeding Operations of Guangdong Province%广东省畜牧粪便中喹诺酮类和磺胺类抗生素的含量与分布特征研究

    Institute of Scientific and Technical Information of China (English)

    邰义萍; 罗晓栋; 莫测辉; 李彦文; 吴小莲; 刘兴跃

    2011-01-01

    利用超声提取-高效液相色谱技术分析广东省20个规模化猪牛养殖场粪便中4种喹诺酮类(QNs)和4种磺胺类(SAs)抗生素的含量与分布特征.结果表明,猪粪中喹诺酮类和磺胺类化合物均全部被检出,前者总含量(∑QNs,鲜重,下同)在24.5~1516.2μg/kg之间,平均为581.0μg/kg,以恩诺沙星和环丙沙星为主;后者总含量(∑SAs)在1 925.9~13 399.5μg/kg之间,平均为4403.9μg/kg,以磺胺甲基嘧啶和磺胺甲唑为主,牛粪中喹诺酮类化合物也全部被检出,磺胺类化合物检出率在90%以上,∑QNs在73.2~1 328.0μg/kg之间,平均为572.9 μg/kg,以诺氟沙星和环丙沙星为主;∑SAs在1 039.4~15 930.3μg/kg之间,平均为3 787.7μg/kg,以磺胺甲唑和磺胺甲基嘧啶为主.不同地区畜牧粪便中喹诺酮类和磺胺类化合物的含量与组成特征有明显差异,广州市猪粪和牛粪中两类抗生素的含量均较高,而佛山市、深圳市牛粪中磺胺-5-甲氧嘧啶和磺胺二甲嘧啶均低于检测限.%The occurrence and distribution of four quinolones and four sulfonamides in swine and cattle feces sampled from twenty largescale feeding operations in different areas of Guangdong province were detected using solid phase extraction (SPE) and high performance liquid chromatography (HPLC). Quinolone and sulfonamide compounds were observed in all pig dung samples. Their total concentrations ranged from 24.5 μg/kg to 1 516. 2 μg/kg( F. W. ) with an average of 581.0 μg/kg and ranged from I 925.9-13 399.5 μg/kg with an average of 4 403.9 μg/kg respectively. The dominant compounds in pig feces were ciprofioxacin and enrofloxacin for quinolones and sulfamerazine and sulfamethoxazole for sulfonamides. Quinolone compounds which dominated with norfloxacin and ciprofloxacin were also observed in all cattle dung samples, its total concentrations ranged from 73.2 μg/kg to 1 328.0 μg/kg which averaged 572.9 μg/kg. While the positive rates of sulfonamide

  8. Characterization of extended-spectrum beta-lactamase, carbapenemase, and plasmid quinolone determinants in Klebsiella pneumoniae isolates carrying distinct types of 16S rRNA methylase genes, and their association with mobile genetic elements.

    Science.gov (United States)

    Wei, Dan-Dan; Wan, La-Gen; Yu, Yang; Xu, Qun-Fei; Deng, Qiong; Cao, Xian-Wei; Liu, Yang

    2015-04-01

    Eighty-four multidrug-resistant Klebsiella pneumoniae (MDR-KP) isolates from a Chinese hospital from January to October 2012 were evaluated to characterize the coexistence of 16S rRNA methylase, extended-spectrum β-lactamase, carbapenemase, and plasmid-mediated quinolone resistance determinants and their association with mobile genetic elements. Among the 84 MDR-KP isolates studied, 19 isolates exhibited high-level resistance to amikacin mediated by the production of the 16S rRNA methylase. They carried 19 armA genes (22.9%) and three rmtB genes (3.6%). CTX-M genes were found in all of the isolates. Among these armA- or rmtB/CTX-M-producing K. pneumoniae isolates, 31.6% carried the carbapenemase genes (blaKPC-2 [26.3%], blaIMP-4 [10.5%], and blaNDM-1 [5.3%]), which made them resistant to imipenem (minimum inhibitory concentration [MIC] ≥16 mg/L). All positive strains possessed qnr-like genes (16 qnrA1, 10 qnrS1, and 7 qnrB4 genes) and 18 harbored an aac(6')-Ib-cr gene. Mobile elements ISEcp1, IS26, ISCR1, ISAba125, and sul-1 integrons were detected in 19/19 (100%), 16/19 (84.2%), 18/19 (94.7%), 9/19 (47.4%), and 18/19 (94.7%) isolates, respectively. The mobilizing elements occurred in different combinations in the study isolates. Majority of armA and qnr genes were in MDR-KP strains carrying integrons containing the ISCR1. Close to 80% of blaTEM-1 and blaSHV-12 were linked to IS26 while ≥90% of blaCTX-Ms and blaCMYs were linked to ISEcp1. ISAba125 was located upstream of blaNDM-1 and some blaCMY-2 genes. In addition, seven transconjugants were available for further analysis, and armA, qnrS1, acc(6')-Ib-cr, blaCTX-M-15, blaTEM-1, and blaNDM-1 were cotransferred. This study points to the dissemination of 16S rRNA methylase genes and the prevalence of selected elements implicated in evolution of resistance determinants in collection of clinical K. pneumoniae in China.

  9. Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takeshi [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Haradahira, Terushi [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)], E-mail: terushi@niu.ac.jp; Fujimoto, Noriko [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Okauchi, Takashi; Maeda, Jun; Suzuki, Kazutoshi; Suhara, Tetsuya [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Yamamoto, Fumihiko; Sasaki, Shigeki; Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Yamaguchi, Hiroshi [Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Maeda, Minoru [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-02-15

    High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[{sup 11}C]methoxyphenyl)-2(1H)-quinolone ([{sup 11}C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-D-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[{sup 11}C]4HQ (5Et-[{sup 11}C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[{sup 11}C]4HQ (5I-[{sup 11}C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[{sup 11}C]4HQ and 5I-[{sup 11}C]4HQ was quite similar to that previously observed between [{sup 11}C]L-703,717 and [{sup 11}C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these {sup 11}C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[{sup 11}C]4HQ at 1 min after intravenous injections were comparable to that of [{sup 11}C]4HQ, but they were 1.3-2.1 times higher than that of [{sup 11}C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [{sup 11}C]4HQ and 5Et-[{sup 11}C]4HQ in contrast to [{sup 11}C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[{sup 11}C]4HQ (16-36% inhibition) but not that of 5I-[{sup 11}C]4HQ. In this study, it was found that a small structural change in [{sup 11}C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [{sup 11}C]4-hydroxyquinolones on the NMDA ion channel

  10. Characterization of carbapenemases, extended spectrum β-lactamases, quinolone resistance and aminoglycoside resistance determinants in carbapenem-non-susceptible Escherichia coli from a teaching hospital in Chongqing, Southwest China.

    Science.gov (United States)

    Zhang, Chuanming; Xu, Xiuyu; Pu, Shuli; Huang, Shifeng; Sun, Jide; Yang, Shuangshuang; Zhang, Liping

    2014-10-01

    Carbapenem-resistant Escherichiacoli isolates harboring carbapenemases or combining an extended-spectrum β-lactamase (ESBL) enzyme with loss of porins present an increasingly urgent clinical danger. Combined resistance to aminoglycosides and fluoroquinolones in carbapeneme non-susceptible (CNS) isolates will inevitably create problems. In the current study, we characterized the carbapenemases and ESBLs, and the prevalence of quinolone resistance determinants and aminoglycoside resistance determinants in carbapenem-non-susceptible (CNS) E.coli isolates from a teaching hospital in Chongqing, Southwest China in 2012. Thirty non-duplicated CNS E.coli isolates were screened via antimicrobial susceptibility testing, and the drug resistance profiles of the 30 strains were analyzed. Carbapenemase genes blaKPC-2, ESBL genes including blaCTX-M-3, blaCTX-M-14, blaCTX-M-55 and blaTEM, ARD genes including aac(6')-Ib, armA and rmtB, and QRD genes including qnrA, qnrB, qnrC, qnrD, qnrS and aac(6')-Ib-cr were identified and clonal relatedness was investigated by pulsed-field gel electrophoresis. Of the 30 isolates, 2 (6.7%) harbored carbapenemase gene blaKPC-2; 29 (96.7%) carried ESBLs; 20 (66.7%) were QRD positive; and 11 (36.7%) were ARD positive. Between the two blaKPC-2 positive strains, one contained ESBL, QRD and ARD genes, while the other expressed ESBL genes but was negative for both QRD and ARD genes. Of the 29 ESBLs positive isolates, 2 (6.9%) were carbapenemase positive, 19 (65.5%) were QRD positive, and 11 (37.9%) were ARD positive. PFGE revealed genetic diversity among the 30 isolates, indicating that the high prevalence of CNS E. coli isolates was not caused by clonal dissemination. Production of ESBLs was associated with the carbapenem resistance and QRD genes were highly prevalent among the CNS E. coli isolates. Multiple resistant genes were co-expressed in the same isolates. This is the first report of a multidrug resistant carbapenem-non-susceptible E.coli co

  11. Role of the cystathionine β-synthase/H2S system in liver cancer cells and the inhibitory effect of quinolone-indolone conjugate QIC2 on the system.

    Science.gov (United States)

    Jia, Huina; Ye, Juan; You, Jing; Shi, Xiaoyan; Kang, Wenyi; Wang, Tianxiao

    2017-05-01

    Hydrogen sulfide (H2S), the third gasotransmitter, plays important roles in cancer biological processes. As endogenous H2S exerts pro-cancer functions, inhibition of its production in cancer cells may provide a new cancer treatment strategy and be achieved via regulation of the function of cystathionine β-synthase (CBS), one of the main metabolic enzymes synthesizing H2S. This enzyme plays important roles in the development and progression of colon and ovarian cancer, primarily regulating mitochondrial bioenergetics and accelerating cell cycle progression. In the present study, we firstly investigated the role of the CBS/H2S system in human hepatoma cells, and then the inhibitory effect of a quinolone-indolone conjugate QIC2 on this system. When CBS was overexpressed in human hepatoma HepG2 and SMMC-7721 cells, inhibition of endogenous CBS/H2S significantly reduced their viability and growth rate, as well as the proliferation of SMMC-7721 cells. Meanwhile, CBS knockdown caused multiple effects, including apoptosis of SMMC-7721 cells, an increase in the Bcl-2-associated X protein (Bax)/B cell lymphoma/leukemia (Bcl-2) ratio, activation of caspase-3 and polyADP-ribose polymerase (PARP), when compared with the scramble siRNA (Sc siRNA)-transfected groups. Heme oxygenase-1 (HO-1; a microsomal enzyme) expression was significantly decreased while the reactive oxygen species (ROS) level was increased in the CBS siRNA-transfected SMMC-7721 cells. QIC2 significantly reduced SMMC-7721 cell viability in a dose-dependent manner and showed a lower toxicity in human normal liver HL-7702 cells relative to the positive controls sunitinib and doxorubicin (DOX). The compound also inhibited cell proliferation and induced cell apoptosis in SMMC-7721 cells. Further analysis indicated that QIC2 downregulated the CBS/H2S system, decreased both HO-1 protein and glutathione (GSH) levels while increased the ROS level and activated the caspase-3 cascade. Collectively, our results

  12. Development of a Colloidal Gold Immunochromatographic Technique for Simultaneous Detection of Quinolones and Gentamicin in Milk%同时检测牛奶中喹诺酮类和庆大霉素残留的胶体金免疫层析方法研究

    Institute of Scientific and Technical Information of China (English)

    李向梅; 王战辉; 肖希龙; 王照鹏; 温凯; 吴小平; 夏曦; 武晋孝; 江海洋

    2014-01-01

    符,表明该方法准确可靠,适用于现场大批量样本的快速检测和筛选。实际操作过程中,可以采用胶体金免疫层析对样品进行现场快速初筛;筛选的疑似阳性样品,可以采用HPLC-MS/MS方法对样品中QNS和GEN的含量进一步确认。%[Objective]Quinolones and gentamicin are highly effective and broad-spectrum antibacterial drugs. They have significant antibiotic effects on gram-negative and gram-positive bacteria, and are widely used in agriculture in China. Because these two types of drug residues in foods of animal origin may cause harm to human health, therefore, in order to protect the consumers’ health, it is necessary to develop a detection method for simultaneous monitoring these two types of drugs residue level in food. A colloidal gold immunochromatographic method was developed for the simultaneous detection of 13 quinolones and gentamicin residues in milk.[Method]In this study, based on the quinolones and gentamicin monoclonal antibodies, the colloidal gold particles were prepared by sodium citrate reduction method, and mixed labeled with same ratio of these two types of monoclonal antibodies. The effect of pH and antibody amount for gold-antibody conjugation on the strip test sensitivity was investigated. Meanwhile, the coating condition of these two types of antigens was selected. A colloidal gold rapid test strip was developed to simultaneously detect 13 quinolones and gentamicin residue in milk on these bases, and the test strip using the principle of direct competition.[Result]The results showed that the method can simultaneously detect 13 quinolones and gentamicin. These 13 quinolones include enrofloxacin, ciprofloxacin, norfloxacin, flumequine, pefloxacin, ofloxacin, enoxacin, oxolinic acid, marbofloxacin, fleroxacin, orbifloxacin, danofloxacin and lomefloxacin. The test strip has no cross-reaction to other quinolones such as sarafloxacin, difloxacin, sparfloxacin and pazufloxacin, etc

  13. 枸橼酸杆菌中质粒介导喹诺酮耐药基因的检测%Study of plasmid-mediated quinolone resistance determinants in Citrobacter freundii

    Institute of Scientific and Technical Information of China (English)

    邵宜波; 李旭; 胡立芬; 谢琴秀

    2013-01-01

    目的 了解枸橼酸杆菌中质粒介导喹诺酮耐药(PMQR)基因的分布,以期发现新型PMQR基因.测定临床分离的PMQR基因阳性枸橼酸杆菌对临床常用抗菌药物的敏感性.方法 收集安徽医科大学第一附属医院检验科2009年临床分离的枸橼酸杆菌,PCR扩增qnr、aac(6′)-Ib-cr和qepA基因,产物纯化测序,测序结果在GenBank上比对并行转移接合实验.对收集的PMQR基因阳性枸橼酸杆菌及其接合子,采用琼脂对倍稀释法进行临床常用抗菌药物的药物敏感试验.结果 收集的枸橼酸杆菌共31株,8株菌株扩增出qnr,qnr基因阳性率为25.8%;其中6株扩增出qnrB.4株qnr阳性菌株的qnr基因转移接合成功.在qnr阳性的枸橼酸杆菌中,测序发现1种PMQR基因新亚型,命名为qnrB24.所有qnr阳性临床菌株对喹诺酮类药物的耐药率为87.5%,对头孢噻肟、阿米卡星、头孢他啶、头孢吡肟和庆大霉素的耐药率分别为75.0%、7.5%、62.5%、37.5%和87.5%,所有qnr阳性菌株对亚胺培南耐药表型为敏感.喹诺酮类药物对qnr阳性的接合子最低抑菌浓度升高10~23倍,敏感性下降.结论 安徽地区枸橼酸杆菌中qnr基因型的检出率较高,以qnrB基因型为主,qnr阳性枸橼酸杆菌对常用抗菌药物耐药性较高.%Objectives This study was conducted to detect and analyze the presence of plasmidmediated quinolone resistance (PMQR) determinants [qnr,aac-(6′)-Ib-cr and qepA] among clinical isolates of Citrobacter freundii strains isolated from patients in Anhui,China,and to understand the susceptibility of PMQR positive strains to commonly used antimicrobial agents.Methods During the year 2009,31 Citrobacter strains were collected from the First Affiliated Hospital of Anhui Medical University.Polymerase chain reaction (PCR) was used to detect PMQR genes.Amplicons were purified,sequenced and compared with data from the GenBank.Conjugation experiments were conducted to

  14. 耐喹诺酮类药物沙门菌毒力岛基因和耐药基因突变研究%Mutations of Salmonella pathogenicity island gene and QRDRs genes in quinolone-resistant Salmonella strains

    Institute of Scientific and Technical Information of China (English)

    王玉平; 康维钧

    2013-01-01

    Objective:To study the gene variations of Salmonella pathogenicity island-1 (SPI-1) genes and quinolone resistance-determining regions (QRDRs) genes in different serovars and ciprofloxacin-resistant Salomonella strains.Methods:The minimal inhibitory concentrations (MICs)for ciprofloxacin were determined u-sing the standard broth microdilution method-on 40 Salmonella strains in 6 serovars.Three SPI-1 genes and QRDRs genes were sequenced and compared in different Salmonella strains to analyze the gene mutations and the relationship with Salmonella virulence.Results:Three SPI-1 genes were detected in all the 40 Salmonella strains,but the base variations belonging to silent mutations were obse.rved in different serovars.No gene deletion or mutation was observed in SPI-1 genes,but gyrA point mutations (S83F and/or D87N/G) and parC point mutation (S87R)were observed in all the 40 ciprofloxacin-resistant strains.Conclusion:The SPI-1 gene variations showed the evolution of virulence in Salmonella.Ciprofloxacin may not induce gene sequence variation or deletion of SPI-1genes.However,the gyrA gene mutations may indicate the virulence reduction of Salmonella strains.%目的:研究耐喹诺酮类药物沙门菌毒力岛基因和喹诺酮耐药基因在不同血清型及耐环丙沙星菌株中基因变异情况.方法:对分属于6个不同血清型的40株沙门菌测定环丙沙星MIC;对沙门菌毒力岛Ⅰ的3个主要基因和喹诺酮耐药基因进行测序比对,分析其基因变异情况及与毒力的关系.结果:40株沙门菌其毒力岛Ⅰ的3个基因全部为阳性,不同血清型其基因序列存在不同程度的变异;环丙沙星耐药株喹诺酮耐药基因gyrA均发生了S83F和/或D87N/G点突变,parC基因发生了S87R的点突变.结论:毒力岛Ⅰ基因在不同血清型的变异,说明其毒力仍在进化中;环丙沙星并未引起沙门菌毒力岛基因突变或缺失,但喹诺酮耐药基因均发生了点突变,这可能与其毒力降低相关.

  15. Investigation and Heath Risk Assessment of Quinolone Antibiotics in Vegetables:Taking Supermarket Vegetables of Guangzhou City for an Exemple%蔬菜中喹诺酮类抗生素污染探查与风险评价:以广州市超市蔬菜为例

    Institute of Scientific and Technical Information of China (English)

    吴小莲; 莫测辉; 李彦文; 王纪阳; 苏青云; 黄显东; 屈相龙

    2011-01-01

    Quinolones ( QNs ) including norfloxacin ( NOR ) , enrofolxacin ( ENR ), ciprofloxacin (CIP) and lomefloxacin ( LOM ) in vegetables sampled from supermarkets of Guangzhou were determined using solid phase extraction and liquid chromatography-tandem mass spectrometry. The detected frequencies of four quinolone compounds in vegetables were all above 90%. The maximum concentration of individual compounds was about 150 μg/kg. Total concentrations of quinolones ( ∑ QNs ) ranged from 10.16 to 193.25 μg/kg( D. W. ), with the average of 74.38 μg/kg and the orders for different kinds of vegetables as followed: melon-fruit vegetable ( 91.29 μg/kg ) > rhizome vegetable ( 82. 09 μg/kg ) > leafy vegetable ( 52.30 μg/kg ), and green vegetable ( 104.49 μg/kg) > pollution-free vegetable( 79.06 μg/kg) > organic vegetable ( 62.38 μg/kg) > routinely cultivated vegetable( 61.23 μg/kg).The average intake and the maximum intake of CIP + ENR for human body via vegetable consumption were 1.8 μg and 3.7 μg respectively,which were lower than those with the maximum intake limit (10 μg) via meat consumption. So it can be concluded that quinolone antibiotics in vegetables were frequently detected. Though their concentrations and health risks to human body were relatively lower, potential health risk should not be neglected for long term intake and synergism of various antibiotics.%基于超声提取-固相萃取(MW-SPE)预处理方法和高效液相色谱-串联质谱(HPLC-MS/MS)分析技术,对广州市超市蔬菜中4种喹诺酮类抗生素(QNs)的污染状况进行探查与健康风险评价.结果表明,4种喹诺酮类化合物的检出率均大于90%,蔬菜(干重,下同)中单个化合物最高含量约150μg/kg,总含量(∑QNs)在10.16~193.25μg/kg之间,平均为74.38μg/kg,其中瓜果类(91.29μg/kg)>根茎类(82.09μg/kg)>叶菜类(52.30μg/kg),绿色蔬菜(104.49μg/kg)>无公害蔬菜(79.06μg/kg)>有机蔬菜(62.38μg/kg)>普通蔬菜(61.23μg/kg