Note: This page contains sample records for the topic quinolone antibacterial drug from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Interactions between new quinolone antibacterials and diagnostic drug containing manganese.  

PubMed

A diagnostic drug containing manganese chloride tetrahydrate as a major ingredient is available since 2006. It is used in magnetic resonance imaging as a negative contrast medium for magnetic resonance cholangiopancreatography of the gastrointestinal tract. However, there is no report regarding interaction between manganese and new quinolone antibacterials. We investigated the interactions between new quinolone antibacterials and a diagnostic drug containing manganese in vitro. We evaluated the rate of formation of chelate complex by reacting new quinolone antibacterials (levofloxacin, ofloxacin, ciprofloxacin) with a diagnostic drug containing manganese. The EC50 values of the formation of chelate complex for levofloxacin, ofloxacin, and ciprofloxacin were 5.14 ± 0.14, 5.29 ± 0.14, and 0.96 ± 0.04 mM, respectively. The rates of formation of chelate complex by levofloxacin, ofloxacin, and ciprofloxacin in a reaction with the diagnostic drug were 17.0, 18.9, and 55.5 % in clinical condition, respectively. Our results suggest that a complex of each antibacterial and manganese was formed, with ciprofloxacin causing the strongest interaction. In addition, our findings indicate that the degree of interaction may be an important problem in clinical settings with concomitant administration of a new quinolone antibacterial and diagnostic drug containing manganese. PMID:23444035

Hosono, Moeko; Yokoyama, Haruko; Takayanagi, Risa; Yamada, Yasuhiko

2013-12-01

2

Mutational resistance to 4-quinolone antibacterial agents  

Microsoft Academic Search

The activity of ten 4-quinolone drugs was tested against fiveEscherichia coli mutants. Mutational resistance was found to reduce the activity of all ten drugs, indicating that they display biochemical cross-resistance with each other. However, ciprofloxacin and, to a lesser extent, ofloxacin and norfloxacin were so highly active that the most resistance exhibited by any mutant fell well within the serum

J. T. Smith

1984-01-01

3

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

PubMed

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 in over all properties starting in 1962 through and continuing throughout the 1970's. Especially, the drug design for pipemidic acid (PPA) indicated one of the important breakthroughs that lead to NFLX. The introduction of a piperazinyl group, which ia a basic moiety at the C7-position of the quinolone nuclei, improved activity against Gram-negative organisms broadening the spectrum to include Pseudomonas aeruginosa. PPA also showed soem activity against Gram-positive bac teria. The basic piperazine ring, which can form the zwitterionic natrure with the carboxylic acid at the C3-position, has subsequently been shown to increase the ability of the drugs to penetrate the bacterial cells resulting in enhanced activity. Further, the zwitterionic forms resulted in significant tissue penetration in the pharmacokinetics. On the other hand, the first compound with a fluorine atom at the C6-position of the related quinolone scaffold was flumequine and the compound indicated that activity against Gram-positive bacteria could be improved in the old quinolones. The addition of a flourine atom at the C6-position is essential for the inhibition of target enzymes. The results show the poten antibacterial activity and the penetration of the quinolone molecule into the bacterial cells and human tissue. The real breakthrough came with the combination of these two features in NFLX, a 6-fluorinated quinolone having a piperazinyl group at the C7-position, NFLX features significant differences from the old quinolones in the activities and pharmacokinetics in humans, resulting in high clinical efficacy in the treatment of many kinds of infections including RTIs.Consequently, those great discoveries are rapidly superseded by even better compounds and NFLX proved to be just the beginning of a highly successful period of research into the modifications of the new quinolone antibacterials. Simce the chemical structure and important features of NFLX had become apparent in 1978, many compounds were patented in the next three years, several of which reached the market. Among the drugs, oflo

Takahashi, Hisashi; Hayakawa, Isao; Akimoto, Takeshi

2003-01-01

4

Nickel-quinolones interaction. Part 1 - Nickel(II) complexes with the antibacterial drug sparfloxacin: structure and biological properties.  

PubMed

The mononuclear nickel(II) complexes with the third-generation quinolone antibacterial agent sparfloxacin in the absence or presence of nitrogen donor heterocyclic ligands (1,10-phenanthroline or 2,2'-bipyridine) have been synthesized and characterized. The experimental data suggest that sparfloxacin acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (1,10-phenanthroline)bis(sparfloxacinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and 2 exhibits the highest binding constant to CT DNA. 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 for the intercalative binding site. The antimicrobial activity of the complexes has been tested on three different microorganisms and has revealed that the inhibition provided by the complexes is slightly decreased in comparison to free sparfloxacin. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values. PMID:19783053

Skyrianou, Kalliopi C; Efthimiadou, Eleni K; Psycharis, Vassilis; Terzis, Aris; Kessissoglou, Dimitris P; Psomas, George

2009-12-01

5

Interactions of the 4-quinolones with other antibacterials  

Microsoft Academic Search

Summary. The effect of sub-inhibitory concentrations of 16 antibacterials on the bactericidal activity of the 4-quinolones nalidixic acid, ciprofloxacin and ofloxacin against Escherichia coli KL16 in nutrient broth was investigated. Sub-inhibitory concentrations of rifampicin, clindamycin, chloramphenicol, erythromycin or tetracycline antagonised the bactericidal activity of the 4-quinolones. Conversely, all seven aminoglycosides tested enhanced the bactericidal activity of the 4-quinolones whereas the

C. S. Lewin; J. T. Smith

1989-01-01

6

Computer Automated Structure Evaluation of Quinolone Antibacterial Agents.  

National Technical Information Service (NTIS)

The Computer Automated Structure Evaluation (CASE) program was used to study a series of quinolone antibacterial agents for which experimental data pertaining to DNA gyrase inhibition as well as MICs against several strains of gram-positive and gram-negat...

G. Klopman O. T. Macina M. E. Levinson H. S. Rosenkranz

1987-01-01

7

Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro.  

PubMed Central

Inhibition of cytochrome P450IA2 activity is an important adverse effect of quinolone antibacterial agents. It results in a prolonged half-life for some drugs that are coadministered with quinolones, such as theophylline. The objective of the study described here was to define the parameters for quantifying the inhibitory potencies of quinolones against cytochrome P450IA2 in vivo and in vitro and to investigate the relationship between the results of both approaches. Cytochrome P450IA2 activity in vitro was measured by using the 3-demethylation rate of caffeine (500 microM) in human liver microsomes. The inhibitory potency of a quinolone in vitro was determined by calculating the decrease in the activity of cytochrome P450IA2 caused by addition of the quinolone (500 microM) into the incubation medium. The mean values (percent reduction of activity without quinolone) were as follows: enoxacin, 74.9%; ciprofloxacin, 70.4%; nalidixic acid, 66.6%; pipemidic acid, 59.3%; norfloxacin, 55.7%; lomefloxacin, 23.4%; pefloxacin, 22.0%; amifloxacin, 21.4%; difloxacin, 21.3%; ofloxacin, 11.8%; temafloxacin, 10.0%; fleroxacin, no effect. The inhibitory potency of a quinolone in vivo was defined by a dose- and bioavailability-normalized parameter calculated from changes of the elimination half-life of theophylline and/or caffeine reported in previously published studies. Taking the pharmacokinetics of the quinolones into account, it was possible to differentiate between substances with and without clinically relevant inhibitory effects by using results of in vitro investigations. The in vitro test described here may help to qualitatively predict the relevant drug interactions between quinolones and methylxanthines that occur during therapy.

Fuhr, U; Anders, E M; Mahr, G; Sorgel, F; Staib, A H

1992-01-01

8

Target Preference of 15 Quinolones against Staphylococcus aureus, Based on Antibacterial Activities and Target Inhibition  

Microsoft Academic Search

The antibacterial activities and target inhibition of 15 quinolones against grlA and gyrA mutant strains were studied. The strains were obtained from wild-type Staphylococcus aureus MS5935 by selection with norfloxacin and nadifloxacin, respectively. The antibacterial activities of most quinolones against both mutant strains were lower than those against the wild-type strain. The ratios of MICs for the gyrA mutant strain

MASAYA TAKEI; HIDEYUKI FUKUDA; RYUTA KISHII; MASAKI HOSAKA

2001-01-01

9

Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition.  

PubMed

The antibacterial activities and target inhibition of 15 quinolones against grlA and gyrA mutant strains were studied. The strains were obtained from wild-type Staphylococcus aureus MS5935 by selection with norfloxacin and nadifloxacin, respectively. The antibacterial activities of most quinolones against both mutant strains were lower than those against the wild-type strain. The ratios of MICs for the gyrA mutant strain to those for the grlA mutant strain (MIC ratio) varied from 0.125 to 4. The ratios of 50% inhibitory concentrations (IC(50)s) of quinolones against topoisomerase IV to those against DNA gyrase (IC(50) ratios) also varied, from 0.177 to 5.52. A significant correlation between the MIC ratios and the IC(50) ratios was observed (r = 0.919; P < 0.001). These results suggest that the antibacterial activities of quinolones against the wild-type strain are involved not only in topoisomerase IV inhibition but also in DNA gyrase inhibition and that the target preference in the wild-type strain can be anticipated by the MIC ratios. Based on the MIC ratios, the quinolones were classified into three categories. Type I quinolones (norfloxacin, enoxacin, fleroxacin, ciprofloxacin, lomefloxacin, trovafloxacin, grepafloxacin, ofloxacin, and levofloxacin) had MIC ratios of <1, type II quinolones (sparfloxacin and nadifloxacin) had MIC ratios of >1, and type III quinolones (gatifloxacin, pazufloxacin, moxifloxacin, and clinafloxacin) had MIC ratios of 1. Type I and type II quinolones seem to prefer topoisomerase IV and DNA gyrase, respectively. Type III quinolones seem to target both enzymes at nearly the same level in bacterial cells (a phenomenon known as the dual-targeting property), and their IC(50) ratios were approximately 2. PMID:11709337

Takei, M; Fukuda, H; Kishii, R; Hosaka, M

2001-12-01

10

Synthesis and in vitro antibacterial activity of quinolone/naphthyridone derivatives containing 3-alkoxyimino-4-(methyl)aminopiperidine scaffolds.  

PubMed

We report herein the synthesis of a series of 7-[3-alkoxyimino-4-(methyl)aminopiperidin-1-yl]quinolone/naphthyridone derivatives. In vitro antibacterial activity of these derivatives was evaluated against representative strains, and compared with ciprofloxacin (CPFX), levofloxacin (LVFX) and gemifloxacin (GMFX). The results reveal that all of the target compounds 19a-c and 20 have considerable Gram-positive activity, although they are generally less active than the reference drugs against the Gram-negative strains with some exceptions. Especially, novel compounds 19a2, 19a4 and 19a5 were found to show strong antibacterial activity (MICs: <0.008-0.5?g/mL) against all of the tested 15 Gram-positive strains including MRSA, LVFX- and GMFX-resistant MRSE, and CPFX-, LVFX- and GMFX-resistant MSSA. PMID:23402878

Lv, Kai; Wu, Jinwei; Wang, Jian; Liu, Mingliang; Wei, Zengquan; Cao, Jue; Sun, Yexin; Guo, Huiyuan

2013-03-15

11

[Antibacterial activity in vitro of 10 quinolones against 20 strains of Legionella pneumophila].  

PubMed

Minimal inhibitory concentrations (MICs) of 10 quinolones were determined by dilution method on BCYE, for 20 strains of Legionella pneumophila. Since the BCYE Agar medium reduces the antibacterial activity of some antimicrobials, a correction factor was calculated. It was found to be 1 to 16 according to the antibiotic tested. The following mode adjusted MIC show the good in vitro antibacterial activity of quinolones on L. pneumophila: ofloxacin, pefloxacin, ciprofloxacin, norfloxacin, A 56620 cMIC: 0.06 microgram/ml), A 56619, enoxacin (cMIC: 0.12 microgram/ml), rosoxacin (cMIC: 0.25 microgram/ml). Pipemidic acid (cMIC: 2 micrograms/ml) and nalidixic acid (cMIC: 1 microgram/ml) were the least active. PMID:3534757

Deforges, L; Fournet, M P; Soussy, C J; Duval, J

1986-06-01

12

Factor analysis of microbiological activity data and structural parameters of antibacterial quinolones.  

PubMed

Factor analysis (FA) was performed on quinolone derivatives with antibacterial activity to model relationships between molecular descriptors and microbiological activities determined on five bacterial cell lines (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae). Molecular modeling studies were performed with the use of HyperChem software and MM+ molecular mechanics with the semi-empirical AM1 method. Factor analysis led to the extraction of two main factors, with the share of factor 1 amounting to about 76% and factor 2 to about 24% for all the parameters used in the statistical analysis. Moreover, FA results indicated that energy of orbitals lowest unoccupied molecular orbital, energy of ionization, electron affinity, electronegativity, maximum electron density, refraction and polarizability appeared to be descriptors important for the antibacterial activity of quinolones. PMID:19603202

Koba, Marcin; Baczek, Tomasz; Macur, Katarzyna; Bober, Leszek; Frackowiak, Teresa; Buci?ski, Adam; Rystok-Grabska, Danuta; Stasiak, Jolanta; Koba, Katarzyna

2010-02-01

13

Interaction of Zn(II) with quinolone drugs: structure and biological evaluation.  

PubMed

Zinc complexes with the third-generation quinolone antibacterial drugs levofloxacin and sparfloxacin have been synthesized and characterized. The deprotonated quinolones act as bidentate ligands coordinated to zinc ion through the pyridone and a carboxylato oxygen atom. The crystal structures of [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10-phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have revealed that they can bind to CT DNA probably by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The DNA binding constants have been also calculated. A competitive study with ethidium bromide (EB) showed that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The interaction of the complexes with human and bovine serum albumin proteins has been studied by fluorescence spectroscopy showing that the complexes exhibit good binding propensity to these proteins having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the previously reported Zn(II) complexes with the first- and second-generation quinolones oxolinic acid and enrofloxacin. PMID:21853189

Tarushi, Alketa; Polatoglou, Eleni; Kljun, Jakob; Turel, Iztok; Psomas, George; Kessissoglou, Dimitris P

2011-10-01

14

Antimicrobial use in Hungarian long-term care facilities: High proportion of quinolone antibacterials.  

PubMed

The aim of this survey was to estimate the burden of antimicrobial use and to describe the determinants for antimicrobial use in Hungarian long-term care facilities (LTCFs) in order to increase the attention given to the proper prescription for this vulnerable population. A one-day point-prevalence study was undertaken between April and May 2013. Data on resident treated with an antibacterial, antimycotic or tuberculostatic for systemic use were collected prospectively on a single day in each participating LTCF with over 50 beds. Descriptive statistics were used to present the data. 91 LTCFs with 11,823 residents participated in this survey. 156 residents (1.3%) were given antimicrobials. 96.8% of antimicrobials were mostly prescribed for therapy included urinary tract infections (40.3%), respiratory tract infections (38.4%) and skin and soft tissue infections (13.2%). The most common therapeutic antimicrobials (97.5%) belonged to the ATC J01 class of 'antibacterials for systemic use'. The most important J01 subclasses were J01M quinolone antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other beta-lactam antibacterials (11.3%) and J01F macrolides, lincosamides and streptogramins (11.3%). Antimicrobials were mostly prescribed empirically whereas 3.8% was microbiologically documented treatments. 3.2% of all prescribed antimicrobials were prescribed for the prophylaxis of urinary tract infections (60%) and ear, nose, mouth infections (40%). Our results emphasize the need of a national recommendation for good practice in LTCFs in order to avoid inappropriate antimicrobial therapy leading to spread of multidrug resistant pathogens. In addition, continuing education of prescribers on antimicrobial treatment is essential. PMID:24679670

Szabó, Rita; Böröcz, Karolina

2014-01-01

15

Protonation equilibria of quinolone antibacterials in acetonitrile-water mobile phases used in LC.  

PubMed

Ionization constants of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 5.5, 10, 16.3, 25, 30, 40, 50 and 70% (w/w) acetonitrile were obtained and assignment of these pK values to the several potentially ionizable functional groups was made. The variation of the pK values obtained over the whole composition range studied can be explained by consideration of the preferential solvation of electrolytes in acetonitrile-water mixtures. In order to obtain pK values in any of the unlimited number of possible binary solvent acetonitrile-water mixtures, relationships between pK values and different bulk properties (such as dielectric constant) were examined. The linear solvation energy relationships method, LSER, was applied to study the correlation of pK values with the solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allow calculation of the pK values of the quinolone antimicrobials in any acetonitrile-water mixtures up to 70% (w/w) and thus permit the knowledge of the acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media. PMID:18966863

Barbosa, J; Bergés, R; Toro, I; Sanz-Nebot, V

1997-07-01

16

Recent advances in antibacterial drugs  

PubMed Central

The incidence of antimicrobial resistance is on continued rise with a threat to return to the “pre-antibiotic” era. This has led to emergence of such bacterial infections which are essentially untreatable by the current armamentarium of available treatment options. Various efforts have been made to develop the newer antimicrobials with novel modes of action which can act against these multi-drug resistant strains. This review aims to focus on these newly available and investigational antibacterials approved after year 2000, their mechanism of actions/resistance, and spectrum of activity and their phases of clinical trials. Newer unexploited targets and strategies for the next generation of antimicrobial drugs for combating the drug resistance and emerging pathogens in the 21st century have also been reviewed in the present article.

Rai, Jaswant; Randhawa, Gurpreet Kaur; Kaur, Mandeep

2013-01-01

17

Structure-based discovery of antibacterial drugs  

Microsoft Academic Search

The modern era of antibacterial chemotherapy began in the 1930s, and the next four decades saw the discovery of almost all the major classes of antibacterial agents that are currently in use. However, bacterial resistance to many of these drugs is becoming an increasing problem. As such, the discovery of drugs with novel modes of action will be vital to

Katie J. Simmons; Ian Chopra; Colin W. G. Fishwick

2010-01-01

18

Effects of 2 quinolone antibacterials, temafloxacin and enoxacin, on theophylline pharmacokinetics.  

PubMed

Certain quinolone and naphthyridone antibacterial agents reduce the clearance of theophylline, posing potential clinical risks for patients maintained on this bronchodilator. Whether temafloxacin also affects theophylline pharmacokinetics was assessed in a randomised double-blind 3-way crossover study in 12 healthy volunteers, using placebo and enoxacin as controls. Each volunteer participated in all 3 phases of the study, receiving theophylline plus daily divided doses of temafloxacin 800mg, enoxacin 800mg, or placebo, orally for 7 days. Aminophylline 200mg (containing 146mg theophylline) was given orally twice daily on the first 4 days. On the fifth morning, theophylline 200mg was administered intravenously, and serial blood and urine samples were collected for the following 72h. Coadministration of enoxacin significantly reduced the metabolic clearance of theophylline (approximately 65%). In contrast, during coadministration of temafloxacin, theophylline pharmacokinetics did not differ significantly from those during coadministration of placebo. No clinically significant adverse events occurred; total reported adverse events during enoxacin-theophylline administration (n = 33) were higher than those reported during temafloxacin-theophylline administration (n = 22) and theophylline alone (n = 23). Administration of temafloxacin to patients on long term theophylline therapy appears to be a safe and rational choice when treatment with a broad spectrum antibiotic is indicated. PMID:1319873

Sörgel, F; Mahr, G; Granneman, G R; Stephan, U; Nickel, P; Muth, P

1992-01-01

19

Physicochemical Studies and Anticancer Potency of Ruthenium ?6-p-Cymene Complexes Containing Antibacterial Quinolones  

PubMed Central

With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (2) and cinoxacin (3) were synthesized, and their physicochemical properties were compared to those of chlorido(?6-p-cymene)(ofloxacinato-?2O,O)ruthenium(II) (1). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. 2 and 3 are significantly more stable than 1 and undergo minor conversion to an unreactive [(cym)Ru(?-OH)3Ru(cym)]+ species (cym = ?6-p-cymene). In the presence of human serum albumin 1?3 form adducts with this transport protein within 20 min of incubation. With guanosine 5?-monophosphate (5?-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for 1 in CH1 ovarian cancer cells, whereas 2 and 3 turned out to be inactive.

2011-01-01

20

Antibacterial Spectrum of a Novel Des-Fluoro(6) Quinolone, BMS-284756  

Microsoft Academic Search

The in vitro spectrum of a novel des-fluoro(6) quinolone, BMS-284756, was compared with those of five fluoro- quinolones (trovafloxacin, moxifloxacin, levofloxacin, ofloxacin, and ciprofloxacin). BMS-284756 was among the most active and often was the most active quinolone against staphylococci (including methicillin-resistant strains), streptococci, pneumococci (including ciprofloxacin-nonsusceptible and penicillin-resistant strains), and Enterococcus faecalis. BMS-284756 inhibited '60 to '70% of the Enterococcus

JOAN C. FUNG-TOMC; BEATRICE MINASSIAN; BENJAMIN KOLEK; ELIZABETH HUCZKO; LAUREN ALEKSUNES; TERRY STICKLE; THOMAS WASHO; ELIZABETH GRADELSKI; LOURDES VALERA; DANIEL P. BONNER

2000-01-01

21

Participation of Reactive Oxygen Species in Phototoxicity Induced by Quinolone Antibacterial Agents  

Microsoft Academic Search

To elucidate the mechanism of phototoxicity induced as a side effect by some of the new quinolone antibiotics, we studied sparfloxacin (SPFX), lomefloxacin, enoxacin, ofloxacin, and ciprofloxacin. We first examined the photosensitized formation of reactive oxygen species such as singlet oxygen (1O2) and superoxide anion (O?2) mediated by the new quinolones. Although a large number of studies have been reported,

Naoki Umezawa; Kumi Arakane; Akemi Ryu; Shinro Mashiko; Masaaki Hirobe; Tetsuo Nagano

1997-01-01

22

Antibacterial Cleaning Products and Drug Resistance  

PubMed Central

We examined whether household use of antibacterial cleaning and hygiene products is an emerging risk factor for carriage of antimicrobial drug–resistant bacteria on hands of household members. Households (N = 224) were randomized to use of antibacterial or nonantibacterial cleaning and hygiene products for 1 year. Logistic regression was used to assess the influence of antibacterial product use in homes. Antibacterial product use did not lead to a significant increase in antimicrobial drug resistance after 1 year (odds ratio 1.33, 95% confidence interval 0.74–2.41), nor did it have an effect on bacterial susceptibility to triclosan. However, more extensive and longer term use of triclosan might provide a suitable environment for emergence of resistant species. Further research on this issue is needed.

Marshall, Bonnie; Levy, Stuart B.; Della-Latta, Phyllis; Lin, Susan X.; Larson, Elaine

2005-01-01

23

Newer Antibacterial Drugs for a New Century  

PubMed Central

Antibacterial drug discovery and development has slowed considerably in recent years with novel classes discovered decades ago and regulatory approvals tougher to get. This article describes newer classes of antibacterial drugs introduced or approved after year 2000, their mechanisms of action/ resistance, improved analogs, spectrum of activity and clinical trials. It also discusses new compounds in development with novel mechanisms of action as well as novel unexploited bacterial targets and strategies which may pave the way for combating drug resistance and emerging pathogens in the 21st century.

Devasahayam, Gina; Scheld, W. Michael; Hoffman, Paul S.

2010-01-01

24

Comparative in vitro antibacterial activity of sparfloxacin (AT-4140; RP 64206), a new quinolone.  

PubMed Central

The in vitro activity of sparfloxacin (AT-4140; RP 64206), a new fluoroquinolone, was compared with those of 10 other agents against 1,222 clinical isolates. Sparfloxacin and ciprofloxacin were the most active quinolones against members of the family Enterobacteriaceae and nonfermenting gram-negative bacilli; sparfloxacin had superior activity against gram-positive cocci in comparison with the activities of ciprofloxacin and the other quinolones tested (norfloxacin, lomefloxacin, and pefloxacin). Among the inhibited strains, several were resistant to the tested beta-lactam antibiotics or to aminoglycosides. The activity of sparfloxacin was not influenced by the medium that was used; lowering of the pH to 5 had a marked effect on the MICs for two strains each of Enterobacter cloacae and Pseudomonas aeruginosa and one strain each of Escherichia coli and Staphylococcus aureus; the MBC of sparfloxacin was within 1 to 2 dilution steps of the MIC for the strains that were tested.

Visser, M R; Rozenberg-Arska, M; Beumer, H; Hoepelman, I M; Verhoef, J

1991-01-01

25

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice  

Microsoft Academic Search

We investigated whether or not the generation of reactive oxygens and toxic photoproducts participated in the cutaneous phototoxicity mechanisms induced by the quinolone derivatives, ofloxacin (OFLX), enoxacin, lomefloxacin, ciprofloxacin and DR-3355 (the s-isomer of OFLX) in a mouse model. Pretreatment of Balb\\/c mice with allopurinol, soybean trypsin inhibitor, catalase and beta-carotene gave significant protection against ear swelling reactions induced by

Nobuhiko Wagai; Katsuhiko Tawara

1991-01-01

26

Molecular mechanisms that confer antibacterial drug resistance.  

PubMed

Antibiotics--compounds that are literally 'against life'--are typically antibacterial drugs, interfering with some structure or process that is essential to bacterial growth or survival without harm to the eukaryotic host harbouring the infecting bacteria. We live in an era when antibiotic resistance has spread at an alarming rate and when dire predictions concerning the lack of effective antibacterial drugs occur with increasing frequency. In this context it is apposite to ask a few simple questions about these life-saving molecules. What are antibiotics? Where do they come from? How do they work? Why do they stop being effective? How do we find new antibiotics? And can we slow down the development of antibiotic-resistant superbugs? PMID:10963607

Walsh, C

2000-08-17

27

[Altered gut bacterial flora and organic acids in feces of patients undergoing autologous stem cell transplantation with quinolone-based antibacterial prophylaxis].  

PubMed

Gastrointestinal toxicity and various infections are serious problems associated with high-dose chemotherapy. Antibacterial chemoprophylaxis reduces the incidence of gram-negative bacterial infection; however, it may affect the normal intestinal flora and induce drug resistance in organisms. We evaluated the chronological changes in fecal bacteria and organic acids in 6 patients undergoing autologous stem cell transplantation with quinolone-based chemoprophylaxis. All patients developed grade 2-3 diarrhea. Four patients developed grade 3 febrile neutropenia. The total count of obligatory anaerobic bacteria was significantly decreased on Day 7, but total facultative anaerobic bacterial count did not change throughout transplantation. However, Enterobacteriaceae and Lactobacillus were decreased on Day 7 and Staphylococcus was increased after transplantation. Total organic acid concentration and short-chain fatty acids were decreased on Day 7. The bacterial flora and organic acids in the gut were significantly altered in patients who underwent autologous stem cell transplantation with quinolonebased chemoprophylaxis. These changes may contribute to gastrointestinal toxicity and infections. PMID:20567111

Hagiwara, Shotaro; Hagiwara, Shotaro; Asahara, Takashi; Nomoto, Koji; Morotomi, Masami; Ishizuka, Naoki; Miwa, Akiyoshi; O Yoshida, Takato

2010-06-01

28

Mechanisms of Quinolone resistance  

Microsoft Academic Search

Conclusion  Quinolone resistance is induced by mutations on quinolone target enzymes such as gyrase and topo IV, and by mutations that\\u000a prevent drug accumulation as a result of changes in outer membrane proteins and\\/or activation of drug-efflux pumps. Mutations\\u000a on the target enzymes usually cause resistance to quinolones specifically, but mutations affecting drug accumulation confer\\u000a resistance to multiple drugs. In most

Shinichi Nakamura

1997-01-01

29

In Vitro Antibacterial Activities of DQ113, a Potent Quinolone, against Clinical Isolates  

Microsoft Academic Search

The antibacterial activity of DQ-113, formerly D61-1113, was compared with those of antibacterial agents currently available. MICs at which 90% of the isolates tested are inhibited (MIC90s) of DQ-113 against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and methicillin-susceptible and -resis- tant coagulase-negative staphylococci were 0.03, 0.008, 0.03, and 0.06 g\\/ml, respectively. Moreover, DQ-113 showed the most potent activity

Mayumi Tanaka; Emi Yamazaki; Megumi Chiba; Kiyomi Yoshihara; Takaaki Akasaka; Makoto Takemura; Kenichi Sato

2002-01-01

30

75 FR 33317 - Antibacterial Resistance and Diagnostic Device and Drug Development Research for Bacterial...  

Federal Register 2010, 2011, 2012, 2013

...and antibacterial drug development. The workshop will address antibacterial drug resistance, mechanisms of resistance, epidemiology of resistance, and issues in the development of rapid diagnostic devices and antibacterial drugs for the diagnosis and...

2010-06-11

31

Antibacterial drug leads targeting isoprenoid biosynthesis  

PubMed Central

With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)90 ?0.25 µg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies.

Zhu, Wei; Zhang, Yonghui; Sinko, William; Hensler, Mary E.; Olson, Joshua; Molohon, Katie J.; Lindert, Steffen; Cao, Rong; Li, Kai; Wang, Ke; Wang, Yang; Liu, Yi-Liang; Sankovsky, Anna; de Oliveira, Cesar Augusto F.; Mitchell, Douglas A.; Nizet, Victor; McCammon, J. Andrew; Oldfield, Eric

2013-01-01

32

Targeted drug-carrying bacteriophages as antibacterial nanomedicines.  

PubMed

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of approximately 20,000 compared to the free drug. PMID:17404004

Yacoby, Iftach; Bar, Hagit; Benhar, Itai

2007-06-01

33

Residues of antibacterial drugs in honey from the Italian market.  

PubMed

Antibacterial drugs are used worldwide for the control of American and, less often, European foulbrood. Their administration is mostly uncontrolled and applied without approved protocols and instructions for use as well as precautionary recommendations. Consequently, this practice is responsible for the contamination of beehive products and contributes to the problem of food safety. According to this situation, 4672 analyses were carried out on 5303 honeys collected from 2001 to 2007. These samples were investigated for antibacterial residues of tetracyclines, sulphonamides, streptomycin, chloramphenicol and tylosin. Honeys were classified according to their origin: imported honey and honey from the Italian market. In the last group (only for samples collected from 2001 to 2004), another type of honey was distinguished: that of local honey. A total of 6.3% of all samples were positive for the antibacterial drugs analysed; in particular, 6.8% of imported honeys and 6.1% of honeys on the Italian market. Only 1.7% of local honey had antibacterial residues. These results are indicative of a rather frequent presence of antibacterial drug residues in both Italian and imported honeys. Furthermore, the data showed that among the active substances analysed, sulphonamides are the most used antibacterial substance followed by tetracyclines, streptomycin, tylosin, and chloramphenicol. Finally, a continuous monitoring programme is needed, accompanied by an education programme to beekeepers on proper hive management. PMID:24784967

Baggio, A; Gallina, A; Benetti, C; Mutinelli, F

2009-01-01

34

Availability and usage of new antibacterial drugs in Europe.  

PubMed

The present-day availability and usage of established and new antibacterial drugs approved for clinical and therapeutic purposes in food-producing animals and poultry in the United States and Europe were compared. Presently, 42 such drugs are approved in Europe, 13 of which were approved since Dec 31, 1974. In the United States, 17 such drugs are currently approved, only four were approved since Dec 31, 1974. Most drug products approved in Europe contain two or more antibacterial agents, whereas most of the products approved in the United States are single drug entities. Drugs approved in Europe but not in the United States include sulfonamide and trimethoprim combinations, nafcillin, oxacillin, metampicillin, cephoxazole, cephalonium, cephacetrile, cephalexin, gentamicin, rifamycin SV, nifuroquine, tiamulin, chloramphenicol, colistin, and polymyxin B. Pharmacologic and clinical features of several of these drugs are briefly described. PMID:7216885

Ziv, G

1980-05-15

35

Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin  

Microsoft Academic Search

The in-vitro activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin were compared. Gram-positive cocci were most susceptible to Bay 12-8039, clinafloxacin and trovafloxacin; Enterobacteriaceae and fas- tidious organisms were most susceptible to ciprofloxacin ; Pseudomonas spp. were most susceptible to clinafloxacin and ciprofloxacin; anaerobes, Helicobacter pylori and Campylo - bacter jejuni were most susceptible

A. Bauernfeind

1997-01-01

36

The introduction of antibacterial drug pipemidic acid into the POM field: Syntheses, characterization and antitumor activity  

NASA Astrophysics Data System (ADS)

Two new compounds based on polyoxometalates (POMs) and the quinolone antibacterial drug pipemidic acid (HPPA), {[Ni(PPA) 2]H 4[SiW 12O 40]}·HPPA·3H 2O ( 1), and {[Zn(PPA) 2] 2H 4[SiW 12O 40]}·3H 2O ( 2), have been synthesized under hydrothermal conditions and structurally characterized by routine technique. Single-crystal X-Ray diffraction analysis shows that compound 1 is constructed by Keggin clusters grafted by binuclear nickel clusters, isolated HPPA and water molecules, while compound 2 consists of Keggin clusters grafted by binuclear zinc clusters and water molecules. Due to the selection of different transition metal (TM) ions, compounds 1 and 2 exhibit different structures and antitumor activities. Compound 1 possesses 0D structure and shows no antitumor activities. However, compound 2 possesses 1D structure and exhibits higher antitumor activities than its parent compound. The results show that introduction of different TM-PPA moieties onto the polyoxoanion surface can affect not only the final structures but also their antitumor activities.

Sha, Jing-Quan; Li, Xin; Zhou, Ying-Hua; Yan, Peng-Fei; Li, Guang-Ming; Wang, Cheng

2011-11-01

37

Use of quinolones in pediatrics  

Microsoft Academic Search

Compared to nalidixic acid, the new quinolones possess an enlarged antimicrobial spectrum, greatly enhanced bactericidal activity, and substantial pharmacokinetic advantages. Because their activity against streptococci is limited the quinolones presently available will never be included in routine regimens for children. Moreover, adequate pharmacokinetic studies are still lacking in pediatrics, and potential drug toxicity warrants further long-term monitoring. Nevertheless, various studies

U. B. Schaad

1991-01-01

38

Undecaprenyl diphosphate synthase inhibitors: antibacterial drug leads.  

PubMed

There is a significant need for new antibiotics due to the rise in drug resistance. Drugs such as methicillin and vancomycin target bacterial cell wall biosynthesis, but methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) have now arisen and are of major concern. Inhibitors acting on new targets in cell wall biosynthesis are thus of particular interest since they might also restore sensitivity to existing drugs, and the cis-prenyl transferase undecaprenyl diphosphate synthase (UPPS), essential for lipid I, lipid II, and thus, peptidoglycan biosynthesis, is one such target. We used 12 UPPS crystal structures to validate virtual screening models and then assayed 100 virtual hits (from 450,000 compounds) against UPPS from S. aureus and Escherichia coli. The most promising inhibitors (IC50 ?2 ?M, Ki ?300 nM) had activity against MRSA, Listeria monocytogenes, Bacillus anthracis, and a vancomycin-resistant Enterococcus sp. with MIC or IC50 values in the 0.25-4 ?g/mL range. Moreover, one compound (1), a rhodanine with close structural similarity to the commercial diabetes drug epalrestat, exhibited good activity as well as a fractional inhibitory concentration index (FICI) of 0.1 with methicillin against the community-acquired MRSA USA300 strain, indicating strong synergism. PMID:24827744

Sinko, William; Wang, Yang; Zhu, Wei; Zhang, Yonghui; Feixas, Ferran; Cox, Courtney L; Mitchell, Douglas A; Oldfield, Eric; McCammon, J Andrew

2014-07-10

39

Potent In Vitro Antibacterial Activity of DS-8587, a Novel Broad-Spectrum Quinolone, against Acinetobacter baumannii  

PubMed Central

We investigated the in vitro activity of DS-8587, a novel fluoroquinolone, against Acinetobacter baumannii. The MICs of DS-8587 against clinical isolates and its inhibitory activity against target enzymes were superior to those of ciprofloxacin and levofloxacin. Furthermore, the antibacterial activity of DS-8587 was less affected by adeA/adeB/adeC or abeM efflux pumps than was that of ciprofloxacin and the frequency of single-step mutations with DS-8587 was lower than that with ciprofloxacin. DS-8587 might be an effective agent against A. baumannii infection.

Onodera, Yoshikuni; Chiba, Megumi; Hoshino, Kazuki; Gotoh, Naomasa

2013-01-01

40

Preparation, structure and microbial evaluation of metal complexes of the second generation quinolone antibacterial drug lomefloxacin  

NASA Astrophysics Data System (ADS)

Lomefloxacinate of Y(III), Zr(IV) and U(VI) were isolated as solids with the general formula; [Y(LFX) 2Cl 2]Cl·12H 2O, [ZrO(LFX) 2Cl]Cl·15H 2O and [UO 2(LFX) 3](NO 3) 2·4H 2O. The new synthesized complexes were characterized with physicochemical and diverse spectroscopic techniques (IR, UV-Vis. and 1H NMR spectroscopies) as well as thermal analyses. In these complexes lomefloxacin act as bidentate ligand bound to the metal ions through the pyridone oxygen and one carboxylate oxygen. The kinetic parameters of thermogravimetric (TGA) and its differential (DTG), such as entropy of activation, activation energy, enthalpy of activation and Gibbs free energy evaluated by using Coats- Redfern and Horowitz- Metzger equations for free lomefloxacin and three complexes were carried out. The bond stretching force constant and length of the U dbnd O bond for the [UO 2(LFX) 3](NO 3) 2·4H 2O complex were calculated. The antimicrobial activity of lomefloxacin and its metal complexes was tested against different bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) as Gram-positive and Gram-negative bacterial species and also against two species of antifungal, penicillium ( P. rotatum) and trichoderma ( T. sp.). The three complexes are of a good action against three bacterial species but the Y(III) complex exhibit excellent activity against Pseudomonas aeruginosa ( P. aeruginosa), when compared to the free lomefloxacin.

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

2010-09-01

41

Quality assessment of drug sales data: the case of antibacterials in Iceland  

Microsoft Academic Search

Background: Two sets of drug sales data, published by the Icelandic Ministry of Health, did not match for antibacterials in 1989. The search for causes turned out to be a project in itself. Objective: To analyze quality problems in the sales data on antibacterials and describe a method for systematic quality assessment of drug sales data. Methods: Documentary analysis based

Ingunn Björnsdóttir; Ebba Holme Hansen; Almar Grímsson

1999-01-01

42

New screens and targets in antibacterial drug discovery.  

PubMed

As the supply of effective antibiotics dwindles and the emergence of multi-drug-resistant bacteria becomes more commonplace, there is an urgent need to identify novel antibacterial targets and leads with new mechanisms of action. Among the strategies to bolster our current scarcity of effective antibiotics are biochemical and phenotype-based screens, and the rational design of inhibitors. In this review we highlight some recent contributions that these methodologies have yielded, placing particular emphasis on screens capable of identifying novel leads involved in such processes as virulence; underexploited targets that reside in bacterial cell surfaces; the use of bacteriophage as antibiotic adjuvants; and novel targets of essential pathways. We discuss these findings in the context of the field of antibiotic drug discovery and how such discoveries position us to begin to fill the antibiotic gap that has been widening for the last half century. PMID:19651534

Falconer, Shannon B; Brown, Eric D

2009-10-01

43

The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial drug target  

Microsoft Academic Search

Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical\\u000a isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug\\u000a exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part,

K. Mazumdar; S. G. Dastidar; J. H. Park; N. K. Dutta

2009-01-01

44

Metal complexes of the third-generation quinolone antimicrobial drug sparfloxacin: Structure and biological evaluation.  

PubMed

Five metal complexes of the third-generation quinolone antimicrobial agent sparfloxacin with Fe(3+), VO(2+), Mn(2+), Ni(2+) and UO(2)(2+) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, sparfloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylate oxygen. The complexes are six-coordinate with distorted octahedral geometry. For VO(sparfloxacinato)(2)(H(2)O) the axial position, trans to the vanadyl oxygen, is occupied by a ketone oxygen atom. Molecular mechanics calculations have been performed in order to propose a model for the structure of each complex. The antimicrobial activity of the complexes has been tested against three microorganisms showing that they exhibit lower activity than free sparfloxacin. UV spectroscopic titration with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and the binding constants to CT DNA have been calculated. The cyclic voltammograms of the complexes in the presence of CT DNA have shown that they bind to CT DNA probably by the intercalative binding mode. Fluorescence competitive studies with ethidium bromide (EB) have revealed the ability of the complexes to displace the DNA-bound EB. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values. PMID:20106531

Efthimiadou, Eleni K; Karaliota, Alexandra; Psomas, George

2010-04-01

45

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

NASA Astrophysics Data System (ADS)

Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(???), Zr(?V) and U(V?) 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.

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

2010-08-01

46

Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection  

Microsoft Academic Search

Quinolones are broad-spectrum antibacterial agents, commonly used in both clinical and veterinary medicine. Their extensive use has resulted in bacteria rapidly developing resistance to these agents. Two mechanisms of quinolone resistance have been established to date: alter- ations in the targets of quinolones, and decreased accumulation due to impermeability of the membrane and\\/or an overexpression of efflux pump systems. Recently,

Joaquim Ruiz

2003-01-01

47

The promise of riboswitches as potential antibacterial drug targets.  

PubMed

Riboswitches represent promising novel RNA structures for developing compounds that artificially regulate gene expression and, thus, bacterial growth. The past years have seen increasing efforts to identify metabolite-analogues which act on riboswitches and which reveal antibacterial activity. Here, we summarize the current inventory of riboswitch-targeting compounds, their characteristics and antibacterial potential. PMID:24140145

Lünse, Christina E; Schüller, Anna; Mayer, Günter

2014-01-01

48

Acid-base behavior of quinolones in aqueous acetonitrile mixtures.  

PubMed

Quinolones are a family of antibacterial agents that are used extensively in both human and veterinary clinics. Their antibacterial activity is pH-dependent, and therefore an examination of protonation equilibria in quinolone solutions is essential. pK-Values of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 10, 30, 40, 50 and 70%(w/w) acetonitrile were determined according to the rules and procedures endorsed by IUPAC. In order to obtain quinolone pK-values in any acetonitrile-water mixture up to 70%(w/w) acetonitrile, relationships between pK-values and different bulk properties (such as dielectric constant) and some microscopic parameters (such as solvatochromic parameters alpha, beta and pi*) were established. These relationships and the application of the preferential solvation theory of electrolytes in acetonitrile-water mixtures permit the interpretation of acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media. PMID:9276916

Sanz-Nebot, V; Valls, I; Barbero, D; Barbosa, J

1997-09-01

49

Simple assay for monitoring seven quinolone antibacterials in eggs: extraction with hot water and liquid chromatography coupled to tandem mass spectrometry. Laboratory validation in line with the European Union Commission Decision 657/2002/EC.  

PubMed

A simple and rapid method able to determine residues of seven quinolone antibacterials in whole eggs is presented here. This method is based on the matrix solid-phase dispersion technique with hot water as extractant followed by liquid chromatography-tandem mass spectrometry. After depositing 1.5 g of an egg sample containing the analytes and the analyte surrogate (norfloxacin) on sand (crystobalite), this material was packed into an extraction cell. Quinolones were extracted by flowing 6 mL of water acidified with 50 mmol/L formic acid through the cell heated at 100 degrees C. After pH adjustment and filtration of the extract, 100 microL of it was injected into the LC column. MS data acquisition was performed in the multiple reaction monitoring mode, selecting two precursor ion to product ion transitions for each target compound. Hot water appeared an efficient extracting medium, since absolute recoveries of the analyte in egg at the level of 20 ng/g were 89-103%. Estimated limits of quantification (S/N=10) were 0.2-0.6 ng/g. Based on the EU Commission Decision 2002/657/EC, the method was validated in terms of ruggedness, specificity, linearity, within-laboratory reproducibility, decision limit (CCalpha and detection capability (CCbeta). Depending on the particular analyte, CCalphas ranged between 0.41 and 2.6 ng/g, while CCbetas were 0.64-3.7 ng/g. The method was linear in the 3-30 ng/g range, with typical R(2) values higher than 0.97. The within-laboratory reproducibility (n=21) at 6 ng/g level was in the 9.0-12% range. After validation, a depletion study of enrofloxacin and one of its metabolites, i.e. ciprofloxacin, in eggs was conducted. PMID:19095237

Bogialli, Sara; D'Ascenzo, Giuseppe; Di Corcia, Antonio; Laganà, Aldo; Tramontana, Giovanna

2009-01-30

50

Changes in antibacterial activity of triclosan and sulfa drugs due to photochemical transformations.  

PubMed

Sulfa drugs and triclosan represent two classes of antibacterials that have been found in natural waters and for which photodegradation is anticipated to be a significant loss process. Parent antibacterial compounds and the products of photolysis reactions were compared for three sulfa drugs and triclosan to determine the extent to which photolysis affects their antibacterial potency on Escherichia coli DH5alpha. Sulfathiazole (median effective concentration [EC50] = 20.0 microM), sulfamethoxazole (EC50 = 12.3 microM), and sulfachloropyridazine (EC50 = 6.9 microM) inhibited bacterial growth but did not affect respiratory activity. Photolysis products of these sulfa drugs did not retain any measurable ability to inhibit growth. Triclosan inhibited both the growth (EC50 = 0.24 microM) and respiratory activity of E. coli DH5alpha. Triclosan photolysis products also exhibited no measurable effect on growth or respiratory activity. These experiments indicate that the products of triclosan and sulfa drug photolysis are unlikely to possess antibacterial activity in natural waters. The rapid screening method used for these two classes of compounds will be useful for helping to identify photolabile antibacterial compounds, for which photoproducts could require further investigation. PMID:16764465

Wammer, Kristine H; Lapara, Timothy M; McNeill, Kristopher; Arnold, William A; Swackhamer, Deborah L

2006-06-01

51

The 2012 Garrod lecture: discovery of antibacterial drugs in the 21st century.  

PubMed

The discovery and development of antibacterial drugs in the twentieth century were major scientific and medical achievements that have had profound benefits for human society. However, in the twenty-first century the widespread global occurrence of bacteria resistant to the antibiotics and synthetic drugs discovered in the previous century threatens to reverse our ability to treat infectious diseases. Although some new drugs are in development they do not adequately cover growing medical needs. Furthermore, these drugs are mostly derivatives of older classes already in use and therefore prone to existing bacterial resistance mechanisms. Thus, new drug classes are urgently needed. Despite investment in antibacterial drug discovery, no new drug class has been discovered in the past 20 years. In this review, based upon my career as a research scientist in the field of antibacterial drug discovery, I consider some of the technical reasons for the recent failure and look to the future developments that may help to reverse the poor current success rate. Diversification of screening libraries to include new natural products will be important as well as ensuring that the promising drug hits arising from structure-based drug design can achieve effective concentrations at their target sites within the bacterial cell. PMID:23134656

Chopra, Ian

2013-03-01

52

Mechanisms of quinolone resistance  

Microsoft Academic Search

Summary Two mechanisms of resistance to fluoroquinolones are known: (i) alteration of the molecular target of quinolone action — DNA gyrase, and (ii) reduction of the quinolone accumulation. Mutations altering the N-terminus of the gyrase A subunit, especially those around residues Ser83 and Asp87, significantly reduce the susceptibilities towards all quinolones, while alterations of the gyrase B subunit are rarely

B. Wiedemann; P. Heisig

1994-01-01

53

Quinolones: from antibiotics to autoinducers  

PubMed Central

Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc1 complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression.

Heeb, Stephan; Fletcher, Matthew P; Chhabra, Siri Ram; Diggle, Stephen P; Williams, Paul; Camara, Miguel

2011-01-01

54

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.  

PubMed

Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III ? subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase ? subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp. PMID:24631121

Yin, Zhou; Wang, Yao; Whittell, Louise R; Jergic, Slobodan; Liu, Michael; Harry, Elizabeth; Dixon, Nicholas E; Kelso, Michael J; Beck, Jennifer L; Oakley, Aaron J

2014-04-24

55

Impact of antibacterial drugs on human serum paraoxonase-1 (hPON1) activity: an in vitro study  

PubMed Central

Objective To investigate the in vitro effects of the antibacterial drugs, meropenem trihydrate, piperacillin sodium, and cefoperazone sodium, on the activity of human serum paraoxonase (hPON1). Methods hPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography. Results The three antibacterial drugs decreased in vitro hPON1 activity. Inhibition mechanisms meropenem trihydrate was noncompetitive while piperacillin sodium and cefoperazone sodium were competitive. Conclusions Our results showed that antibacterial drugs significantly inhibit hPON1 activity, both in vitro, with rank order meropenem trihydrate piperacillin sodium cefoperazone sodium in vitro.

Soyut, Hakan; Kaya, Elif Duygu; Beydemir, Sukru

2014-01-01

56

Quinolone susceptibility of norA-disrupted Staphylococcus aureus.  

PubMed Central

The MIC of norfloxacin for the norA-disrupted mutant termed RDN1, obtained from quinolone-susceptible Staphylococcus aureus RN4220, was eightfold lower than that for RN4220. The increase in susceptibility was related to an increase of drug accumulation by RDN1. These results indicate that NorA plays an important role in the susceptibility of quinolone-susceptible S. aureus to selected quinolones.

Yamada, H; Kurose-Hamada, S; Fukuda, Y; Mitsuyama, J; Takahata, M; Minami, S; Watanabe, Y; Narita, H

1997-01-01

57

Comparative Evaluation of Recently Developed Quinolone Compounds – with a Note on the Frequency of Resistant Mutants  

Microsoft Academic Search

The antibacterial activity of the new quinolone compounds enoxacin, norfloxacin, ofloxacin and ciprofloxacin was evaluated in 300 Enterobacteriaceae, 50 Pseu-domonasaeruginosa, 30 Acinetobacter spp., 15 Haemophilus influenzae, 50 Streptococcus faecalis, and 70 Staphylococcus aureus isolates and compared to that of nalidixic acid, gentamicin and various ?-lactam compounds. Moreover, the rate of spontaneous mutants resistant to quinolone compounds was evaluated. In concentrations

W. Cullmann; M. Stieglitz; B. Baars; W. Opferkuch

1985-01-01

58

Susceptibility of Chlambydia to Antibacterial Drugs: Tests in Cell Cultures.  

National Technical Information Service (NTIS)

Concentrations of 20 micrograms of sulfadiazine or 30 micrograms of D-cycloserine/ml were found to be suitable for testing the differential susceptibility of Chlamydia trachomatis and C. psittaci to these drugs in cell cultures. (Author)

F. B. Gordon A. L. Quan

1972-01-01

59

Short Communication Kinetic assessment of the potassium ferrate(VI) oxidation of antibacterial drug sulfamethoxazole  

Microsoft Academic Search

Sulfamethoxazole (SMX), a worldwide-applied antibacterial drug, was recently found in surface waters and in sec- ondary wastewater effluents, which may result in ecotoxical effects in the environment. Herein, removal of SMX by environmentally-friendly oxidant, potassium ferrate(VI) (K2FeO4), is sought by studying the kinetics of the reaction between Fe(VI) and SMX as a function of pH (6.93-9.50) and temperature (15-45 ?

Virender K. Sharma; Santosh K. Mishra; Ajay K. Ray

60

Kinetic assessment of the potassium ferrate(VI) oxidation of antibacterial drug sulfamethoxazole  

Microsoft Academic Search

Sulfamethoxazole (SMX), a worldwide-applied antibacterial drug, was recently found in surface waters and in secondary wastewater effluents, which may result in ecotoxical effects in the environment. Herein, removal of SMX by environmentally-friendly oxidant, potassium ferrate(VI) (K2FeO4), is sought by studying the kinetics of the reaction between Fe(VI) and SMX as a function of pH (6.93–9.50) and temperature (15–45°C). The rate

Virender K. Sharma; Santosh K. Mishra; Ajay K. Ray

2006-01-01

61

Antibacterial activity of two limonoids from Swietenia mahagoni against multiple-drug-resistant (MDR) bacterial strains  

Microsoft Academic Search

Solvent partitioning followed by column chromatography of the MeOH extract of the seeds of Swietenia mahagoni afforded two limonoids, swietenolide (1) and 2-hydroxy-3-O-tigloylswietenolide (2). The compounds were identified by spectroscopic means. The antibacterial activity of these compounds was assessed against\\u000a eight multiple-drug-resistant bacterial strains (clinical isolates) by the conventional disc diffusion method. While both\\u000a compounds were active against all test

A. K. M. Shahidur Rahman; A. K. Azad Chowdhury; Husne-Ara Ali; Sheikh Z. Raihan; Mohammad S. Ali; Lutfun Nahar; Satyajit D. Sarker

2009-01-01

62

In vitro activities of new quinolones against Helicobacter pylori.  

PubMed Central

Compounds belonging to a new class of quinolones in which the fundamental C-6 fluorine atom was replaced were evaluated for in vitro antibacterial activity against 32 Helicobacter pylori strains. Since these substitutions resulted in higher inhibitory activities, these new desfluoroquinolones may be useful in eradicating H. pylori infections.

Carbone, M; Fera, M T; Cecchetti, V; Tabarrini, O; Losi, E; Cusumano, V; Teti, G

1997-01-01

63

Nanomechanics of drug-target interactions and antibacterial resistance detection.  

PubMed

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions. Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures. We developed a new model(1) which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (Kd) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections. PMID:24192763

Ndieyira, Joseph W; Watari, Moyu; McKendry, Rachel A

2013-01-01

64

Antibacterial activity of natural spices on multiple drug resistant Escherichia coli isolated from drinking water, Bangladesh  

PubMed Central

Background Spices traditionally have been used as coloring agents, flavoring agents, preservatives, food additives and medicine in Bangladesh. The present work aimed to find out the antimicrobial activity of natural spices on multi-drug resistant Escherichia coli isolates. Methods Anti-bacterial potentials of six crude plant extracts (Allium sativum, Zingiber officinale, Allium cepa, Coriandrum sativum, Piper nigrum and Citrus aurantifolia) were tested against five Escherichia coli isolated from potable water sources at kushtia, Bangladesh. Results All the bacterial isolates were susceptible to undiluted lime-juice. None of them were found to be susceptible against the aqueous extracts of garlic, onion, coriander, pepper and ginger alone. However, all the isolates were susceptible when subjected to 1:1:1 aqueous extract of lime, garlic and ginger. The highest inhibition zone was observed with lime (11 mm). Conclusion Natural spices might have anti-bacterial activity against enteric pathogens and could be used for prevention of diarrheal diseases. Further evaluation is necessary.

2011-01-01

65

Quinolones: Action and Resistance Updated  

PubMed Central

The quinolones trap DNA gyrase and DNA topoisomerase IV on DNA as complexes in which the DNA is broken but constrained by protein. Early studies suggested that drug binding occurs largely along helix-4 of the GyrA (gyrase) and ParC (topoisomerase IV) proteins. However, recent X-ray crystallography shows drug intercalating between the -1 and +1 nucleotides of cut DNA, with only one end of the drug extending to helix-4. These two models may reflect distinct structural steps in complex formation. A consequence of drug-enzyme-DNA complex formation is reversible inhibition of DNA replication; cell death arises from subsequent events in which bacterial chromosomes are fragmented through two poorly understood pathways. In one pathway, chromosome fragmentation stimulates excessive accumulation of highly toxic reactive oxygen species that are responsible for cell death. Quinolone resistance arises stepwise through selective amplification of mutants when drug concentrations are above the MIC and below the MPC, as observed with static agar plate assays, dynamic in vitro systems, and experimental infection of rabbits. The gap between MIC and MPC can be narrowed by compound design that should restrict the emergence of resistance. Resistance is likely to become increasingly important, since three types of plasmid-borne resistance have been reported.

Drlica, Karl; Hiasa, Hiroshi; Kerns, Robert; Malik, Muhammad; Mustaev, Arkady; Zhao, Xilin

2009-01-01

66

Analysis toward innovative herbal antibacterial and antifungal drugs.  

PubMed

The antimicrobial activities of four medicinal plants Argemona mexicana, Achyranthes aspera, Catharanthus roseus, and Syzygium cumini were evaluated against Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae, Proteus vulgaris, Bacillus subtilis, Salmonella typhi and three Aspergillus species. Extracts from Achyranthes aspera and Catharanthus roseus showed the highest antimicrobial potential (MIC 0.375-0.750 mg/ml) while extract from Argemona mexicana and Syzygium cumini, showed less activity. In disc diffusion assay, only eight out of twenty extracts showed antimicrobial activity at a concentration of 25.0 ?g/ disc. The GCMS investigation reveals the existence of 2-bornanone; 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl) ester; hexadecanoic acid, methyl ester and hexatriacontane in water extract fraction of C. roseus. The present research article provides a review of some medicinal plants incorporating antimicrobial drugs, together with recent advances in emerging therapeutics in clinical development and related patents for exploitation of herbal medicine. PMID:23072646

Dhankhar, Sandeep; Dhankhar, Seema; Kumar, Manish; Ruhil, Sonam; Balhara, Meenakshi; Chhillar, Anil K

2012-12-01

67

The usage of veterinary antibacterial drugs for mastitis in cattle in Norway and Sweden during 1990–1997  

Microsoft Academic Search

The prescribing patterns and annual incidence of use of antibacterial drugs for the treatment of mastitis in cattle in Norway and Sweden during the period 1990–1997 were estimated from drug wholesaler statistics. Although the drugs included in this study are also used in other species and\\/or other indications, mastitis in cattle is by far the most-common indication for their use.

Kari Grave; Christina Greko; Lolita Nilsson; Kristina Odensvik; Tormod Mørk; Marit Rønning

1999-01-01

68

Non-ribosomal factors in ribosome subunit assembly are emerging targets for new antibacterial drugs.  

PubMed

It is becoming increasingly clear that bacterial ribosome assembly is catalyzed by a variety of non-ribosomal factors. Newly characterized factors in bacterial ribosome biogenesis are broadly conserved and often indispensable proteins that can be classified either as chaperones facilitating assembly, or enzymes with ribosomal RNA- and ribosomal protein-modifying functions. Accumulating evidence indicates that the proteins Era, Obg, YjeQ, YlqF and RimM are chaperones which may be crucial to bacterial ribosome assembly, and therefore represent novel targets for modern antibacterial drug discovery. Ongoing work aimed at understanding ribosome biogenesis is expected to continue to yield additional factors crucial to this process, and provide new targets with drug discovery potential. PMID:16890019

Comartin, David J; Brown, Eric D

2006-10-01

69

Microwave-assisted Heterocyclic Dicarboxylic Acids as Potential Antifungal and Antibacterial Drugs  

PubMed Central

A series of new dicarboxylic acid derivatives of 1,3,4-thiadiazines, 1,4-benzopiperizines, 1,4-thiazines, 1,3-thiazoles, 1,3-oxazoles and 1,3-imidazoles have been synthesized in 80-87% yield by the environmentally benign microwave induced technique involving the cyclocondensation of 2,3-dibromosuccinic acid with 2-aminothiophenol, o-phenylene diamine, 1,2,4-triazole, amidinothiocarbamide, amidinocarbamide and guanidine hydrochloride. The structures of all newly synthesized compounds have been established on the basis of analytical and spectral data. Evaluation of antibacterial and antifungal activity showed that almost all compounds exhibited better results than reference drugs thus they could be promising candidates for novel drugs.

Dabholkar, V. V.; Parab, S. D.

2011-01-01

70

Plasmid-Mediated Quinolone Resistance  

Microsoft Academic Search

In the 1990s quinolone resistance increased in parallel with increased quinolone utilization (1) and also with the emergence\\u000a of plasmid-mediated quinolone resistance. The fi rst type of plasmid-mediated resistance was discovered in a clinical strain\\u000a of Klebsiella pneumoniae isolated at the University of Alabama in 1994 that transferred low-level quinolone resistance along with resistance to several\\u000a other antibiotics to Escherichia

George A. Jacoby

71

Binding Interaction of a Prospective Chemotherapeutic Antibacterial Drug with ?-Lactoglobulin: Results and Challenges.  

PubMed

This Article reports a detailed characterization of the binding interaction of a potential chemotherapeutic antibacterial drug, norfloxacin (NOF), with the mammalian milk protein ?-lactoglobulin (?LG). The thermodynamic parameters, ?H, ?S, and ?G, for the binding phenomenon as-evaluated on the basis of van't Hoff relationship reveal the predominance of electrostatic/ionic interactions underlying the binding process. However, the drug-induced quenching of the intrinsic tryptophanyl fluorescence of the protein exhibits intriguing characteristics on Stern-Volmer analysis (displays an upward curvature instead of conforming to a linear regression). Thus, an extensive time-resolved fluorescence spectroscopic characterization of the quenching process has been undertaken in conjugation with temperature-dependent fluorescence quenching studies to unveil the actual quenching mechanism. The invariance of the fluorescence decay behavior of ?LG as a function of the quencher (here NOF) concentration coupled with the commensurate dependence of the drug-protein binding constant (K) on temperature, the drug-induced fluorescence quenching of ?LG is argued to proceed through static mechanism. This postulate is aided further support from absorption, fluorescence, and circular dichroism (CD) spectral studies. The present study also throws light on the important issue of drug-induced modification in the native protein conformation on the lexicon of CD, excitation-emission matrix spectroscopic techniques. Concurrently, the drug-protein interaction kinetics and the energy of activation of the process are also explored from stopped-flow fluorescence technique. The probable binding locus of NOF in ?LG is investigated from AutoDock-based blind docking simulation. PMID:24807302

Paul, Bijan K; Ghosh, Narayani; Mukherjee, Saptarshi

2014-05-27

72

Multi-target spectral moments for QSAR and Complex Networks study of antibacterial drugs.  

PubMed

There are many of pathogen bacteria species which very different susceptibility profile to different antibacterial drugs. There are many drugs described with very different affinity to a large number of receptors. In this work, we selected Drug-Bacteria Pairs (DBPs) of affinity/non-affinity drugs with similar/dissimilar bacteria and represented it as a large network, which may be used to identify drugs that can act on bacteria. Computational chemistry prediction of the biological activity based on one-target Quantitative Structure-Activity Relationship (ot-QSAR) studies substantially increases the potentialities of this kind of networks avoiding time and resource consuming experiments. Unfortunately almost all ot-QSAR models predict the biological activity of drugs against only one bacterial species. Consequently, multi-tasking learning to predict drug's activity against different species with a single model (mt-QSAR) is a goal of major importance. These mt-QSARs offer a good opportunity to construct drug-drug similarity Complex Networks. Unfortunately, almost QSAR models are unspecific or predict activity against only one receptor. To solve this problem, we developed here a multi-bacteria QSAR classification model. The model correctly classifies 202 out of 241 active compounds (83.8%) and 169 out of 200 non-active cases (84.5%). Overall training predictability was 84.13% (371 out of 441 cases). The validation of the model was carried out by means of external predicting series, classifying the model 197 out of 221 (89.4%) cases. In order to show how the model functions in practice a virtual screening was carried out recognizing the model as active 86.7%, 520 out of 600 cases not used in training or predicting series. Outputs of this QSAR model were used as inputs to construct a network. The observed network has 1242 nodes (DBPs), 772,736 edges or DBPs with similar activity (sDBPs). The network predicted has 1031 nodes, 641,377 sDBPs. After edge-to-edge comparison, we have demonstrated that the predicted network is significantly similar to the observed one and both have distribution closer to exponential than to normal. PMID:19631422

Prado-Prado, Francisco J; Uriarte, Eugenio; Borges, Fernanda; González-Díaz, Humberto

2009-11-01

73

Immunomodulating activity of DW116, a new quinolone antibiotic  

Microsoft Academic Search

DW-116, {1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride},\\u000a is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(?) bacteria. DW-116 was evaluated for\\u000a the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the goodin vivo antibacterial efficacy. The results ofin vitro studies revealed there was no statistically significant increase in B and

Eun Yi Moon; Chung Ha Choi; Suhkneung Pyo; Yong Ho Chung; Sung June Yoon; Dug Keun Lee

1998-01-01

74

Quinolone-based HDAC inhibitors.  

PubMed

Abstract HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM. PMID:25019596

Balasubramanian, Gopalan; Kilambi, Narasimhan; Rathinasamy, Suresh; Rajendran, Praveen; Narayanan, Shridhar; Rajagopal, Sridharan

2014-08-01

75

Transferable mechanisms of quinolone resistance.  

PubMed

Quinolones were introduced into clinical practice in the late 1960s. Although quinolone resistance was described early, no transferable mechanism of quinolone resistance (TMQR) was confirmed until 1998. To date, five different TMQRs have been described in the literature, including target protection (Qnr), quinolone modification (AAC(6')-Ib-cr), plasmid-encoded efflux systems (e.g. QepA or OqxAB, amongst others), effect on bacterial growth rates and natural transformation. Although TMQRs usually only result in a slight increase in the minimum inhibitory concentrations of quinolones, they possess an additive effect and may facilitate the acquisition of full quinolone resistance. The emergence of new related genes may continue in the next years. PMID:22831841

Ruiz, Joaquim; Pons, Maria J; Gomes, Cláudia

2012-09-01

76

Novel hydrogel particles and their IPN films as drug delivery systems with antibacterial properties.  

PubMed

Poly(acrylonitrile) (p(AN))-based materials such poly(acrylonitrile-co-(3-acrylamidopropyl)-trimethylammonium chloride (p(AN-co-APTMACl)), poly(acrylonitrile-co-4-viniyl pyridine) (p(AN-co-4-VP)) and poly(acrylonitrile-co-N-isopropylacrylamide) (p(AN-co-NIPAM)) core-shell nanoparticles were prepared. The core materials, AN, in p(AN-co-4-VP) nanoparticles, were amidoximated and the shell materials, 4-VP, were quaternized to generate p(AN-co-4-VP)(+) and p(AN-co-4-VP)(++), single and double positively charged core-shell nanoparticles, respectively. Furthermore, interpenetrating microgels-hydrogel (IPN) polymeric networks were prepared by mixing double quaternized p(AN-co-4-VP)(++) core-shell particles with acrylamide (AAm) and 2-hydroxyethylmethacrylate (HEMA) before polymerization. A model drug, fluorescein sodium salt (FSS) was used in absorption/release studies from these IPNs. Moreover, the prepared and chemically modified particles were tested against Staphylococcus aureus ATCC6538, Pseduomonas aeruginosa ATCC9027, Bacillus subtilis ATCC6633, and Escherichia coli ATCC8739, and found that some of these particles had antibacterial properties against tested bacteria. PMID:21978555

Silan, Coskun; Akcali, Alper; Otkun, Mu?erref Tatman; Ozbey, Nilgun; Butun, Sultan; Ozay, Ozgur; Sahiner, Nurettin

2012-01-01

77

Quinolone-induced upregulation of osteopontin gene promoter activity in human lung epithelial cell line A549.  

PubMed

Quinolones, in addition to their antibacterial activities, act as immunomodulators. Osteopontin (OPN), a member of the extracellular matrix proteins, was found to play a role in the immune and inflammatory response. We found that quinolones significantly enhanced OPN secretion, namely, garenoxacin (220%), moxifloxacin (62%), gatifloxacin (82%), sparfloxacin, (79%), and sitafloxacin (60%). Enhancement of OPN secretion was shown to be due to the effect of quinolones on the OPN gene promoter activity. We also examined the role of quinolones on apoptosis and found that sparfloxacin decreased the late apoptosis of A549 cells, but garenoxacin did not show the antiapoptotic effect. The antiapoptotic effects of quinolones do not appear to be associated with OPN elevation. PMID:22430970

Shiratori, Beata; Zhang, Jing; Usami, Osamu; Chagan-Yasutan, Haorile; Suzuki, Yasuhiko; Nakajima, Chie; Uede, Toshimitsu; Hattori, Toshio

2012-06-01

78

Quinolone-Induced Upregulation of Osteopontin Gene Promoter Activity in Human Lung Epithelial Cell Line A549  

PubMed Central

Quinolones, in addition to their antibacterial activities, act as immunomodulators. Osteopontin (OPN), a member of the extracellular matrix proteins, was found to play a role in the immune and inflammatory response. We found that quinolones significantly enhanced OPN secretion, namely, garenoxacin (220%), moxifloxacin (62%), gatifloxacin (82%), sparfloxacin, (79%), and sitafloxacin (60%). Enhancement of OPN secretion was shown to be due to the effect of quinolones on the OPN gene promoter activity. We also examined the role of quinolones on apoptosis and found that sparfloxacin decreased the late apoptosis of A549 cells, but garenoxacin did not show the antiapoptotic effect. The antiapoptotic effects of quinolones do not appear to be associated with OPN elevation.

Shiratori, Beata; Zhang, Jing; Usami, Osamu; Chagan-Yasutan, Haorile; Suzuki, Yasuhiko; Nakajima, Chie; Uede, Toshimitsu

2012-01-01

79

[Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].  

PubMed

As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, < or =0.06microg/mL for penicillin susceptible S. pneumoniae (PSSP) without any change, 0.5-1 microg/mL for penicillin intermediate resistant S. pneumoniae (PISP) with a twofold change and 1 microg/mL for PRSP with no change. The MIC90s of CVA/AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial activity intended for pediatric patients with otitis media or other infections, there was no significant change in antibacterial activity of CVA/AMPC (1: 14). PMID:24167843

Ishida, Atsuko; Hasegawa, Naomi; Okano, Hideyuki; Hara, Terufumi; Yoshida, Pascal

2013-06-01

80

Possible direct role of reactive oxygens in the cause of cutaneous phototoxicity induced by five quinolones in mice  

Microsoft Academic Search

The mechanisms of phototoxicity induced in mice by five quinolone antibacterial agents were investigated using mouse 3T3 fibroblast cells and Balb\\/c mice. In the in vitro study, the cultured cells were exposed to ultraviolet-A (UVA) in the presence of the five quinolones lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin). Cytotoxicity after irradiation was assayed by the neutral

Nobuhiko Wagai; Katsuhiko Tawara

1992-01-01

81

Photoprocesses in quinolone substituted  

NASA Astrophysics Data System (ADS)

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.

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

2002-03-01

82

Laser receptive polyelectrolyte thin films doped with biosynthesized silver nanoparticles for antibacterial coatings and drug delivery applications.  

PubMed

We report a simple method to fabricate multifunctional polyelectrolyte thin films to load and deliver the therapeutic drugs. The multilayer thin films were assembled by the electrostatic adsorption of poly (allylamine hydrochloride) (PAH) and dextran sulfate (DS). The silver nanoparticles (Ag NPs) biosynthesized from novel Hybanthus enneaspermus leaf extract as the reducing agent were successfully incorporated into the film. The biosynthesized Ag NPs showed excellent antimicrobial activity against the range of enteropathogens, which could be significantly enhanced when used with commercial antibiotics. The assembled silver nano composite multilayer films showed rupture and deformation when they are exposed to laser. The Ag NPs act as an energy absorption center, locally heat up the film and rupture it under laser treatment. The antibacterial drug, moxifloxacin hydrochloride (MH) was successfully loaded into the multilayer films. The total amount of MH release observed was about 63% which increased to 85% when subjected to laser light exposure. Thus, the polyelectrolyte thin film reported in our study has significant potential in the field of remote activated drug delivery, antibacterial coatings and wound dressings. PMID:24096301

Sripriya, Jaganathan; Anandhakumar, Sundaramurthy; Achiraman, Shanmugam; Antony, Jacob Joe; Siva, Durairaj; Raichur, Ashok M

2013-11-30

83

Mutations of the Bacteriophage T4 Type II DNA Topoisomerase That Alter Sensitivity to Antitumor Agent 4'-(9-Acridinylamino)methanesulfon- m-anisidide and an Antibacterial Quinolone1  

Microsoft Academic Search

Various antitumor and antibacterial agents target type II DNA topoi- somerases, stabilizing a cleaved DNA reaction intermediate and thereby converting topoisomerase into a cellular poison. Two 4'-<9-acridinylami- no)methanesulfon-m-anisidide (m-AMSA 1-resistant hacteriophage T4 to- poisomerases have previously been characterized biochemically, and we have now determined the sequence of the causative mutations. In one case, a mutation (K457K) in a conserved domain

Catherine H. Freudenreich; Christine Chang; Kenneth N. Kreuzer

84

Studies of the photooxidant properties of antibacterial fluoroquinolones and their naphthalene derivatives.  

PubMed

We synthesized and determined the production of reactive oxygen species (ROS) as 1O2, *-O2, *OH, H2O2 during the photolysis with UV-A light of three antibacterial quinolones and their naphthyl ester derivatives. Singlet oxygen and ROS dose-dependant generation from norfloxacin (1), enoxacin (2), ciprofloxacin (3) and their respective naphthyl ester derivatives 4-6 were detecting in cell-free systems by the histidine assay and by luminol-enhanced chemiluminescence (LCL). Both the electronic absorption and emission spectra were quantified and their photostability determined. The antibacterial activity in darkness and under irradiation of compounds 4, 5 and 6 was tested on E. coli and compared with their parent drugs. PMID:19320285

Vargas, F; Zoltan, T; Ramirez, A H; Cordero, T; Chavez, V; Izzo, C; López, V; Cárdenas, Y M; Fernández, A; Hincapie, L; Fuentes, A

2009-02-01

85

Kinetic assessment of the potassium ferrate(VI) oxidation of antibacterial drug sulfamethoxazole.  

PubMed

Sulfamethoxazole (SMX), a worldwide-applied antibacterial drug, was recently found in surface waters and in secondary wastewater effluents, which may result in ecotoxical effects in the environment. Herein, removal of SMX by environmentally-friendly oxidant, potassium ferrate(VI) (K(2)FeO(4)), is sought by studying the kinetics of the reaction between Fe(VI) and SMX as a function of pH (6.93-9.50) and temperature (15-45 degrees C). The rate law for the oxidation of SMX by Fe(VI) is first-order with respect to each reactant. The observed second-order rate constant decreased non-linearly from 1.33+/-0.08 x 10(3) M(-1)s(-1) to 1.33+/-0.10 x 10(0) M(-1)s(-1) with an increase of pH from 7.00 to 9.50. This is related to protonation of Fe(VI) (HFeO(4)(-) <==> H(+) + FeO(4)(2-); pK(a,HFeO(4)) = 7.23) and sulfamethoxazole (SH <==> H(+) + S(-); pK(a,SH)=5.7). The estimated rate constants were k(11)(HFeO(4)(-) + SH) = 3.0 x 10(4) M(-1)s(-1), k(12)(HFeO(4)(-) + S(-)) = 1.7 x 10(2) M(-1)s(-1), and k(13) (FeO(4)(2-) + SH) = 1.2 x 10(0) M(-1)s(-1). The energy of activation at pH 7.0 was found to be 1.86+/-0.04 kJ mol(-1). If excess potassium ferrate(VI) concentration (10 microM) is used than the SMX in water, the half-life of the reaction using a rate constant obtained in our study would be approximately 2 min at pH 7. The reaction rates are pH dependent; thus, so are the half-lives of the reactions. The results suggest that K(2)FeO(4) has the potential to serve as an oxidative treatment chemical for removing SMX in water. PMID:15950258

Sharma, Virender K; Mishra, Santosh K; Ray, Ajay K

2006-01-01

86

Synthesis and Characterization of Potential Dimers of Gatifloxacin - an Antibacterial Drug  

PubMed Central

Gatifloxacin is an antibacterial agent belonging to the fourth-generation fluoroquinolone family. Four piperazine-linked fluoroquinolone dimers of Gatifloxacin were observed during the laboratory process for Gatifloxacin and they were identified. The present work describes the origin, synthesis, characterization, and control of these dimers along with the synthesis of Despropylene Gatifloxacin (metabolite).

Garaga, Srinivas; Raghava Reddy, Ambati V.; Prabahar, Koilpillai Joseph; Korupolu, Raghu Babu; Sanasi, Paul Douglas

2013-01-01

87

Unique Biological Properties and Molecular Mechanism of 5,6-Bridged Quinolones  

PubMed Central

We have characterized an early series of 5,6-bridged dioxinoquinolones which behaved strikingly different from typical quinolones. The 5,6-bridged dioxinoquinolones inhibited Escherichia coli DNA gyrase supercoiling activity but, unlike typical quinolones, failed to stimulate gyrase-dependent cleavable complex formation. Analogous unsubstituted compounds stimulated cleavable complex formation but were considerably less potent than the corresponding 5,6-bridged compounds. Consistent with a previous report (M. Antoine et al., Chim. Ther. 7:434-443, 1972) and contrary to established quinolone SAR trends, a compound with an N-1 methyl substitution (PGE-8367769) was more potent than its analog with an N-1 ethyl substitution (PGE-6596491). PGE-8367769 was shown to antagonize ciprofloxacin-mediated cleavable complex formation in a dose-dependent manner, suggesting an interaction with the gyrase-DNA complex that overlaps that of ciprofloxacin. Resistance to PGE-8367769 in E. coli was found to arise through missense mutations in gyrA, implicating DNA gyrase as the primary antibacterial target. Notably, only 1 of 15 distinct mutations selected on PGE-8367769 (D87G) has previously been implicated in quinolone resistance in E. coli. The remaining 14 mutations (E16V, G31V, R38L, G40A, Y50D, V70A, A84V, I89L, M135T, G173S, T180I, F217C, P218T, and F513C) have not been previously reported, and most were located outside of the traditional quinolone resistance-determining region. These novel GyrA mutations decreased sensitivity to 5,6-bridged dioxinoquinolones by four- to eightfold, whereas they did not confer resistance to other quinolones such as ciprofloxacin, clinafloxacin, or nalidixic acid. These results demonstrate that the 5,6-bridged quinolones act via a mechanism that is related to but qualitatively different from that of typical quinolones.

Macinga, David R.; Renick , Paul J.; Makin, Kelly M.; Ellis, David H.; Kreiner, Allison A.; Li, Min; Rupnik, Kirk J.; Kincaid, Erica M.; Wallace, Cynthia D.; Ledoussal, Benoit; Morris, Timothy W.

2003-01-01

88

Quinolone-Based Third-Line Therapy for Helicobacter pylori Eradication  

PubMed Central

Currently, a standard third-line therapy for Helicobacter pylori (H. pylori) eradication remains to be established. Quinolones show good oral absorption, no major side effects, and marked activity against H. pylori. Several authors have studied quinolone-based third-line therapy and reported encouraging results, with the reported H. pylori cure rates ranging from 60% to 84%. Resistance to quinolones is easily acquired, and the resistance rate is relatively high in countries with a high consumption rate of these drugs. We recently reported a significant difference in the eradication rate obtained between patients infected with gatifloxacin-susceptible and gatifloxacin-resistant H. pylori, suggesting that the selection of quinolones for third-line therapy should be based on the results of drug susceptibility testing. As other alternatives of third-line rescue therapies, rifabutin-based triple therapy, high-dose proton pump inhibitor/amoxicillin therapy and furazolidone-based therapy have been suggested.

Nishizawa, Toshihiro; Suzuki, Hidekazu; Hibi, Toshifumi

2009-01-01

89

Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones.  

PubMed Central

A series of 11 fluoroquinolone antibacterial agents, including 8 newly synthesized molecules and 3 reference compounds (pefloxacin, ciprofloxacin, and sparfloxacin), were tested for their MICs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The intracellular accumulation of fluoroquinolones by these microorganisms was measured by centrifugation through silicone oil and a fluorescence assay. The minimal effective dose (MED) was determined for all agents in a supercoiling assay with E. coli DNA gyrase. The hydrophobicities of the quinolones were determined and expressed as the logarithm of the coefficient of distribution (log D) between 1-octanol and phosphate buffer (pH 7.2). No correlation was found between MICs and cell accumulation for the quinolones studied. A correlation was found between log D and accumulation by S. aureus (r = 0.71, n = 11), and an inverse correlation was found between log D and accumulation by E. coli (r = 0.73, n = 11) and P. aeruginosa (r = 0.64, n = 10). The correlation coefficients between MICs and MED for E. coli, which were 0.60, 0.64, and 0.74 (n = 11) for E. coli, P. aeruginosa, and S. aureus, respectively, rose to 0.85, 0.74, and 0.74 (n = 11) for the same microorganisms, respectively, when the accumulation of the drug by the cell was taken into account. It was concluded that the inhibitory activity against DNA gyrase remains the most important parameter for quinolone potency, but that intracellular accumulation must be taken into account, since, for a given organism, both parameters are under the control of the physicochemical properties of the quinolones.

Bazile, S; Moreau, N; Bouzard, D; Essiz, M

1992-01-01

90

Cultivation of Neisseria gonorrhoeae in liquid media and determination of its in vitro susceptibilities to quinolones.  

PubMed

The cultivation of Neisseria gonorrhoeae by use of fastidious broth (FB) was evaluated. FB was found to be able to support the growth of all N. gonorrhoeae strains tested in this study without a rapid decrease in the viable count after exponential growth. After 24 h of incubation at 35 degrees C with 5% CO(2), viable counts of all strains reached over 10(8) CFU/ml in FB. Similar growth of the wild-type strain and its target-altered quinolone-resistant derivatives was observed. The susceptibilities of laboratory-adapted strains and clinical isolates to quinolones were tested by the microdilution method using FB. The MICs determined by microdilution were not significantly different from those determined by the agar dilution method recommended by the CLSI (formerly National Committee for Clinical Laboratory Standards). Moreover, the concentration-dependent time-kill of quinolones such as gatifloxacin and ciprofloxacin was observed in FB. At 2 to 4 times the MIC, gatifloxacin and ciprofloxacin were predominantly bactericidal against N. gonorrhoeae WHO A. At the MIC, the activities of both quinolones ranged from bactericidal to bacteriostatic. At 0.25 to 0.5 times the MIC, gonococcal growth was comparable to that of the growth control. These results suggest that the cultivation of N. gonorrhoeae by use of FB may be useful for evaluation of the antibacterial effects of quinolones. PMID:16145072

Takei, Masaya; Yamaguchi, Yuko; Fukuda, Hideyuki; Yasuda, Mitsuru; Deguchi, Takashi

2005-09-01

91

Quinolone Resistance: Much More than Predicted  

PubMed Central

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.

Hernandez, Alvaro; Sanchez, Maria B.; Martinez, Jose L.

2011-01-01

92

Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase  

PubMed Central

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.

Piton, Jeremie; Petrella, Stephanie; Delarue, Marc; Andre-Leroux, Gwenaelle; Jarlier, Vincent; Aubry, Alexandra; Mayer, Claudine

2010-01-01

93

Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.  

PubMed

Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors. PMID:11181910

Anderson, M E; Mazur, A; Yang, T; Roden, D M

2001-03-01

94

Quinolone Resistance in Staphylococci: Activities of New Nonfluorinated Quinolones against Molecular Targets in Whole Cells and Clinical Isolates  

Microsoft Academic Search

The activity of three new, 8-methoxy-nonfluorinated quinolones (NFQs) against multiple-drug-resistant staph- ylococci was investigated. First, using Staphylococcus aureus strains containing point mutations in the serine 84-80 hot spots of the target genes (gyrA and grlA), cell growth inhibition potencies of the NFQs as a result of DNA gyrase and topoisomerase IV inhibition were estimated and compared with those of known

SIDDHARTHA ROYCHOUDHURY; CARL E. CATRENICH; ERIC J. MCINTOSH; HELANA D. MCKEEVER; KELLY M. MAKIN; PAULA M. KOENIGS; BENOIT LEDOUSSAL

2001-01-01

95

In Vitro Activity of Ozenoxacin against Quinolone-Susceptible and Quinolone-Resistant Gram-Positive Bacteria  

PubMed Central

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.

Lopez, Y.; Tato, M.; Espinal, P.; Garcia-Alonso, F.; Gargallo-Viola, D.; Canton, R.

2013-01-01

96

Structure, antimicrobial activity, DNA- and albumin-binding of manganese(II) complexes with the quinolone antimicrobial agents oxolinic acid and enrofloxacin.  

PubMed

The reaction of MnCl2 with the quinolone antibacterial drug oxolinic acid (Hoxo) results to the formation of [KMn(oxo)3(MeOH)3]. Interaction of MnCl2 with the quinolone Hoxo or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligand 1,10-phenanthroline (phen) results in the formation of metal complexes with the general formula [Mn(quinolonato)2(phen)]. The crystal structures of [KMn(oxo)3(MeOH)3] and [Mn(erx)2(phen)], exhibiting a 1D polymeric and a mononuclear structure, respectively, have been determined by X-ray crystallography. In these complexes, the deprotonated bidentate quinolonato ligands are coordinated to manganese(II) ion through the pyridone oxygen and a carboxylato oxygen. All complexes can act as potential antibacterial agents with [Mn(erx)2(phen)] exhibiting the most pronounced antimicrobial activity against five different microorganisms. Interaction of the complexes with calf-thymus DNA (CT DNA), studied by UV spectroscopy, has shown that they bind to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating their binding to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements and cyclic voltammetry. DNA electrophoretic mobility experiments suggest that [Mn(erx)2(phen)] binds strongly to supercoiled pDNA and to linearized pDNA possibly by an intercalative manner provoking double-stranded cleavage reflecting in a nuclease-like activity. The complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. The binding constants of the complexes towards CT DNA and albumins have been compared to their corresponding zinc(II) and nickel(II) complexes. PMID:23353085

Zampakou, Marianthi; Akrivou, Melpomeni; Andreadou, Eleni G; Raptopoulou, Catherine P; Psycharis, Vassilis; Pantazaki, Anastasia A; Psomas, George

2013-04-01

97

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

PubMed

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. PMID:24906513

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

2014-07-15

98

Design and formulation technique of a novel drug delivery system for azithromycin and its anti-bacterial activity against Staphylococcus aureus.  

PubMed

Azithromycin, an important member of the azalide subclass is effective against both Gram-positive and Gram-negative organisms. Certain physicochemical properties of the drug like poor water solubility and relatively low bioavailability of 37% due to incomplete absorption after ingestion, aroused the need for the development of a novel drug delivery system to enhance the solubilization potential and antibacterial activity against Staphylococcus aureus at a very low concentration. Cinnamon oil (Cinnamonum zeylanicum)-based microemulsion system formulated using non-ionic surfactant, Tween 20, and water was characterized. The drug-incorporated system F4 (oil to surfactant ratio of 1:4 (v/v)) showed enhanced solubilization of the drug, droplet diameter of 5-8 nm, and a good thermodynamic stability. The effect of surfactant concentration exhibited a negative correlation with droplet size diameter and turbidity and a positive correlation with stability and viscosity. The system was investigated for its antibacterial activity that demonstrated a significantly higher activity at a minimum concentration (4 ?g/ml) of the novel drug-loaded system in comparison with the conventional formulation (128 ?g/ml). Examination through scanning electron microscopy analysis further confirmed a considerable morphologic variation due to alteration in the membrane permeability of the microemulsion-treated system. The small droplet size of the microemulsion system and the antibacterial property of cinnamon oil, together, accounts clearly for the enhanced efficacy of the new formulated system F4 and not just azithromycin alone. Staining with acridine orange/ethidium bromide dyes as examined through fluorescence microscopy also substantiated with the results of membrane permeability of bacteria. Thus, our study discloses a potential oral drug delivery system of azithromycin with improved biocompatibility. PMID:23800858

Nirmala, M Joyce; Mukherjee, Amitava; Chandrasekaran, N

2013-09-01

99

Quinolones for mycobacterial infections.  

PubMed

The fluoroquinolones (FQs) are important agents for the treatment of mycobacterial infections. In leprosy, the use of FQs has enabled a dramatic shortening of formerly long and complicated therapy. Both animal and human studies support the inclusion of certain FQs as a cornerstone of leprosy therapy. In tuberculosis (TB), particularly in multidrug-resistant (MDR) infections, the place of the major antimycobacterial FQs is less clear as there is widespread resistance to these agents in areas of the world in which MDR-TB and extensively drug-resistant (XDR)-TB are prevalent, particularly in Southeast Asia. The place of the newly developed FQ-related diarylquinoline compound known as bedaquiline in the treatment of drug-resistant TB is unclear; however, human studies suggest that it might be effective for this indication. PMID:23643393

Rubinstein, Ethan; Keynan, Yoav

2013-07-01

100

Enhanced efficacy and broadening of antibacterial action of drugs via the use of capped mesoporous nanoparticles.  

PubMed

Bug busters: A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with ?-poly-L-lysine (?-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug ?-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated. PMID:23839913

Mas, Núria; Galiana, Irene; Mondragón, Laura; Aznar, Elena; Climent, Estela; Cabedo, Nuria; Sancenón, Félix; Murguía, José Ramón; Martínez-Máñez, Ramón; Marcos, María D; Amorós, Pedro

2013-08-19

101

Hepatotoxicity of Antibacterials: Pathomechanisms and Clinical Data  

Microsoft Academic Search

\\u000a Abstract\\u000a   Drug-induced hepatotoxicity is a frequent cause of liverdisease and acute liver failure, particularly in patients treatedwith\\u000a multiple drugs. Several antibacterial drugs have thepotential to cause severe liver injury and failure. This articleaims to\\u000a increase the awareness and understanding of druginducedliver injury (DILI) due to antibacterial drugs. Itreviews the pattern\\u000a of antibacterial DILI and provides detailson molecular mechanisms and toxicogenomics,

J. M. Leitner; W. Graninger; F. Thalhammer

2010-01-01

102

Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening.  

PubMed

To identify novel antibiotics against Mycobacterium tuberculosis, we performed a hierarchical structure-based drug screening (SBDS) targeting the enoyl-acyl carrier protein reductase (InhA) with a compound library of 154,118 chemicals. We then evaluated whether the candidate hit compounds exhibited inhibitory effects on the growth of two model mycobacterial strains: Mycobacterium smegmatis and Mycobacterium vanbaalenii. Two compounds (KE3 and KE4) showed potent inhibitory effects against both model mycobacterial strains. In addition, we rescreened KE4 analogs, which were identified from a compound library of 461,383 chemicals through fingerprint analysis and genetic algorithm-based docking simulations. All of the KE4 analogs (KES1-KES5) exhibited inhibitory effects on the growth of M. smegmatis and/or M. vanbaalenii. Based on the predicted binding modes, we probed the structure-activity relationships of KE4 and its analogs and found a correlative relationship between the IC50 values and the interaction residues/LogP values. The most potent inhibitor, compound KES4, strongly and stably inhibited the long-term growth of the model bacteria and showed higher inhibitory effects (IC50 = 4.8 ?M) than isoniazid (IC50 = 5.4 ?M), which is a first-line drug for tuberculosis therapy. Moreover, compound KES4 did not exhibit any toxic effects that impede cell growth in several mammalian cell lines and enterobacteria. The structural and experimental information of these novel chemical compounds will likely be useful for the development of new anti-TB drugs. Furthermore, the methodology that was used for the identification of the effective chemical compound is also likely to be effective in the SBDS of other candidate medicinal drugs. PMID:23600706

Kinjo, Tomohiro; Koseki, Yuji; Kobayashi, Maiko; Yamada, Atsumi; Morita, Koji; Yamaguchi, Kento; Tsurusawa, Ryoya; Gulten, Gulcin; Komatsu, Hideyuki; Sakamoto, Hiroshi; Sacchettini, James C; Kitamura, Mitsuru; Aoki, Shunsuke

2013-05-24

103

Prevalence of Plasmid-Mediated Quinolone Resistance  

Microsoft Academic Search

Quinolone resistance encoded by the qnr gene and mediated by plasmid pMG252 was discovered in a clinical strain of Klebsiella pneumoniae that was isolated in 1994 at the University of Alabama at Birmingham Medical Center. The gene codes for a protein that protects DNA gyrase from quinolone inhibition and that belongs to the pentapeptide repeat family of proteins. The prevalence

George A. Jacoby; Nancy Chow; Ken B. Waites

2003-01-01

104

In Vivo Diagnostic Tests in Adverse Reactions to Quinolones  

Microsoft Academic Search

? Abstract Background and objective: Contradictory reports of the sensitivity of skin tests in quinolone allergy have been reported. Our objectives were to describe the outcome of quinolone skin and challenge tests in patients consulting because of a history of adverse reaction to quinolone and to compare the outcome of quinolone skin tests and challenge tests in the subsample of

M Venturini Díaz; T Lobera Labairu; I González Mahave

105

Selection of resistant variants of respiratory pathogens by quinolones  

Microsoft Academic Search

Quinolones are widely used in the treatment of respiratory tract infections. However, some disquiet has been expressed over using quinolones for community-acquired pneumonia since their activity is generally rather poor against Streptococcus pneumoniae. In addition, it is known that resistant variants emerge at a fairly high frequency during exposure of Enterobacteriaceae to quinolones; if this also occurred during quinolone treatment

A. M Sefton; J. P Maskell; J. D Williams

1999-01-01

106

Design of Helicobacter pylori glutamate racemase inhibitors as selective antibacterial agents: A novel pro-drug approach to increase exposure  

Microsoft Academic Search

High-throughput screening uncovered a pyrazolopyrimidinedione hit as a selective, low micromolar inhibitor of Helicobacter pylori glutamate racemase (MurI). Variation of the substituents around the scaffold led to low nanomolar inhibitors and improved antibacterial activity. The challenge in this program was to translate excellent enzyme inhibition into potent antibacterial activity and pharmacokinetics suitable for oral therapy. Compounds were profiled for MurI

Gregory S. Basarab; Pamela J. Hill; Abdullah Rastagar; Peter J. H. Webborn

2008-01-01

107

Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B-ciprofloxacin conjugates with potential esterase and phosphatase triggered drug release linkers  

PubMed Central

Two desferrioxamine B-ciprofloxacin conjugates with “trimethyl-lock” based linkers that are designed to release the antibiotic after esterase or phosphatase-mediated hydrolysis were synthesized. The potential esterase-sensitive conjugate 13 displayed moderate to good antibacterial activities against selected ferrioxamine-utilizing bacteria, although the activities were lower than the parent drug ciprofloxacin. However, the potential phophatase-sensitive conjugate 23 was inactive against the same panel of organisms tested. These properties appeared to be related to the activating efficiency of the linker by the enzyme and to the outer membrane protein recognition of the chemically modified siderophore used in the conjugate.

Ji, Cheng

2012-01-01

108

Distribution of Quinolones, Sulfonamides, Tetracyclines in Aquatic Environment and Antibiotic Resistance in Indochina  

PubMed Central

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.

Suzuki, Satoru; Hoa, Phan Thi Phuong

2012-01-01

109

T cell-mediated immunity to quinolones  

Microsoft Academic Search

RationaleQuinolones, broad spectrum antibiotics widely used in the treatment of various bacterial infections, can induce immediate- and delayed-type hypersensitivity reactions, which are presumably either IgE- or T cell-mediated, in about 2 to 3% of the treated patients. To better understand the role of T cells in the pathomechanism of quinolone allergies, we analyzed patients with delayed reactions to ciprofloxacin or

D. A. Schmid

2004-01-01

110

Antibacterial activities of polyethylene glycol, tween 80 and sodium dodecyl sulphate coated silver nanoparticles in normal and multi-drug resistant bacteria.  

PubMed

Antibacterial activity of silver nanoparticles coated with different functionalizing agents i.e., polyethylene glycol, tween 80 and sodium dodecyl sulphate were evaluated on both normal and multi-drug resistant strains of bacteria. Under the same reaction conditions, these functionalizing agents were added separately to coat silver nanoparticles. Among these, polyethylene glycol coated nanoparticles were most effective in killing all the bacterial strains which includes Escherichia coli DH5a, Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus and multi-drug resistant clinical isolates of Shigella spp. (flexneri, boydii, sohnea) and Vibrio cholerae. The minimum inhibitory concentration of polyethylene glycol coated silver nanoparticles was also less compared to the other two sets of nanoparticles. Consistence with that polyethylene glycol coated nanoparticles produced more intracellular reactive oxygen species in bacteria. Moreover, when human cell lines MCF7 and Chang Liver were incubated in presence of these nanoparticles for 18 h with same concentrations as used for bacteria, no toxicity was observed. But significant increase in cell killing was observed with longer incubation time. Thus our present investigation implicates the potential therapeutic use of silver nanoparticles as antibacterial agent particularly the polyethylene glycol coated one. PMID:22755083

Bhattacharya, Debalina; Samanta, Saheli; Mukherjee, Ananda; Santra, Chitta Ranjan; Ghosh, Amar N; Niyogi, Swapan Kumar; Karmakar, Parimal

2012-03-01

111

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

PubMed

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. PMID:21820989

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

2011-10-01

112

Cytotoxic, antibacterial, DNA interaction and superoxide dismutase like activities of sparfloxacin drug based copper(II) complexes with nitrogen donor ligands.  

PubMed

The novel neutral mononuclear copper(II) complexes with fluoroquinolone antibacterial drug, sparfloxacin and nitrogen donor heterocyclic ligand have been synthesized and characterized. An antimicrobial efficiency of the complexes has been tested against five different microorganisms and showed diverse biological activity. The interaction of complex with Herring sperm (HS) DNA was investigated using viscosity titration and absorption titration techniques. The results indicate that the complexes bind to DNA by intercalative mode and have rather high DNA-binding constants. DNA cleavage study showed better cleaving ability of the complexes compare to metal salt and standard drug. All the complexes showed good cytotoxic activity with LC(50) values ranging from 4.89 to 11.94 ?g mL(-1). Complexes also exhibit SOD-like activity with their IC(50) values ranging from 0.717 to 1.848 ?M. PMID:23266675

Patel, Mohan N; Joshi, Hardik N; Patel, Chintan R

2013-03-01

113

Cytotoxic, antibacterial, DNA interaction and superoxide dismutase like activities of sparfloxacin drug based copper(II) complexes with nitrogen donor ligands  

NASA Astrophysics Data System (ADS)

The novel neutral mononuclear copper(II) complexes with fluoroquinolone antibacterial drug, sparfloxacin and nitrogen donor heterocyclic ligand have been synthesized and characterized. An antimicrobial efficiency of the complexes has been tested against five different microorganisms and showed diverse biological activity. The interaction of complex with Herring sperm (HS) DNA was investigated using viscosity titration and absorption titration techniques. The results indicate that the complexes bind to DNA by intercalative mode and have rather high DNA-binding constants. DNA cleavage study showed better cleaving ability of the complexes compare to metal salt and standard drug. All the complexes showed good cytotoxic activity with LC50 values ranging from 4.89 to 11.94 ?g mL-1. Complexes also exhibit SOD-like activity with their IC50 values ranging from 0.717 to 1.848 ?M.

Patel, Mohan N.; Joshi, Hardik N.; Patel, Chintan R.

2013-03-01

114

Characteristics of antibiotic resistance and sequence type of Acinetobacter baumannii clinical isolates in Japan and the antibacterial activity of DS-8587.  

PubMed

DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the antibacterial activity and mechanism of DS-8587 in 31 quinolone-resistant Acinetobacter baumannii clinical isolates. Efflux pump and qnr genes, mutations in quinolone resistance-determining regions of target enzymes, and sequence types determined by multilocus sequence typing were analyzed. Forty-two quinolone-susceptible clinical isolates were analyzed for comparison. For susceptibility testing, DS-8587 exhibited more effective antibacterial activity when compared with ciprofloxacin and levofloxacin. When combined with the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, the MIC of DS-8587 was less affected when compared with the MIC exhibited by combined ciprofloxacin and 1-(1-napthylmethyl)-piperazine. The efflux pump genes adeA/adeB/adeC and regulatory elements adeR/adeS were detected in 23 of 31 quinolone-resistant isolates. The qnrA/qnrB/qnrS genes were not detected in any A. baumannii isolates analyzed. Mutations in quinolone resistance-determining regions were observed in all 31 quinolone-resistant isolates. Multilocus sequence typing analyses revealed that 22 of 31 quinolone-resistant isolates belonged to ST-2, corresponding to international clonal lineage II. In conclusion, DS-8587 exhibits potent antibacterial activity against quinolone-resistant A. baumannii isolates that harbor mutations in quinolone resistance-determining regions. In the presence of the efflux pump inhibitor 1-(1-napthylmethyl)-piperazine, no significant changes were observed in the MIC for DS-8587. DS-8587 should be considered as a treatment option for A. baumannii including ST-2 strains that are predominant among the quinolone-resistant A. baumannii isolates found in Japan. PMID:24709045

Higuchi, Saito; Shikata, Mototsugu; Chiba, Megumi; Hoshino, Kazuki; Gotoh, Naomasa

2014-04-01

115

Induction of Mycobacterial Resistance to Quinolone Class Antimicrobials  

PubMed Central

An agar plate assay was developed for detecting the induction of drug-resistant mycobacterial mutants during exposure to inhibitors of DNA gyrase. When Mycobacterium smegmatis on drug-containing agar, resistant colonies arose over a period of 2 weeks. A recA deficiency reduced mutant recovery, consistent with involvement of the SOS response in mutant induction. The C-8-methoxy compounds gatifloxacin and moxifloxacin allowed the recovery of fewer resistant mutants than either ciprofloxacin or levofloxacin when present at the same multiple of the MIC; a quinolone-like 8-methoxy-quinazoline-2,4-dione was more effective at restricting the emergence of resistant mutants than its cognate fluoroquinolone. Thus, the structure of fluoroquinolone-like compounds affects mutant recovery. A spontaneous mutator mutant of M. smegmatis, obtained by growth in medium containing both isoniazid and rifampin, increased mutant induction during exposure to ciprofloxacin. Moreover, the mutator increased the size of spontaneous resistant mutant subpopulations, as detected by population analysis. Induction of ciprofloxacin resistance was also observed with Mycobacterium tuberculosis H37Rv. When measured with clinical isolates, no difference in mutant recovery was observed between multidrug-resistant (MDR) and pansusceptible isolates. This finding is consistent with at least some MDR isolates of M. tuberculosis lacking mutators detectable by the agar plate assay. Collectively, the data indicate that the use of fluoroquinolones against tuberculosis may induce resistance and that the choice of quinolone may be important for restricting the recovery of induced mutants.

Malik, Muhammad; Chavda, Kalyan; Zhao, Xilin; Shah, Nirali; Hussain, Syed; Kurepina, Natalia; Kreiswirth, Barry N.; Kerns, Robert J.

2012-01-01

116

Fluoroquinolone-Gyrase-DNA Complexes: TWO MODES OF DRUG BINDING.  

PubMed

DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 ?) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-05-01

117

Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.  

PubMed Central

Objective To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure. Methods The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound. Results Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL. Conclusions Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites.

Subramani, Ramesh; Kumar, Rohitesh; Prasad, Pritesh; Aalbersberg, William

2013-01-01

118

Antibacterial Sludge  

NSDL National Science Digital Library

Today, it's hard to find dishwashing liquids or hand soaps that don't advertise their "antibacterial" chemicals. But while it's unclear whether these chemicals actually help us, there's new reason to believe they might do more harm than good. This Science Update examines the common antibacterial agent, Triclocarban or TCC, which is found in hand soaps and other household products.

Science Update;

2004-10-04

119

Anti-bacterial performance of azithromycin nanoparticles as colloidal drug delivery system against different gram-negative and gram-positive bacteria  

PubMed Central

Purpose: Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. Methods: AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Results: Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<0.01). The enhanced antibacterial efficacy was more dominant in the gram positive species. The MIC values of NPs against the tested bacteria were reduced 8 times in comparison to those of untreated AZI. Conclusion: These results indicated an improved potency of AZI NPs which could be attributed to the modified surface characteristics as well as increased drug adsorption and uptake.

Azhdarzadeh, Morteza; Lotfipour, Farzaneh; Zakeri-Milani, Parvin; Mohammadi, Ghobad; Valizadeh, Hadi

2012-01-01

120

Extension of multi-residue methodology to include the determination of quinolones in food.  

PubMed

The multi-residue procedure for basic drugs described elsewhere by this laboratory has been evaluated for quinolone and fluoroquinolone antibiotics. The fluoroquinolones are a relatively new class of drug and an increasing number of licensed products containing these compounds are becoming available for use in animal husbandry. This, along with the possibility of the development of antibiotic resistant human pathogens, make it an important class of drug for which methodology is required for the monitoring of residues in food. Validation data are presented for a range of compounds including the quinolones; oxolinic acid and nalidixic acid, and the fluoroquinolones; flumequine, ciprofloxacin, danofloxacin, enoxacin, enrofloxacin, lomefloxacin, marbofloxacin, norfloxacin, ofloxacin and sarafloxacin. Foods for which the method was validated included poultry muscle (chicken and turkey), egg, chicken liver, honey, cattle muscle and pig muscle. This application of the multi-residue procedure further demonstrates the importance and wide-ranging usefulness of the technique. PMID:10435345

Rose, M D; Bygrave, J; Stubbings, G W

1998-12-01

121

Antibacterial and antibiotic-potentiation activities of the methanol extract of some cameroonian spices against Gram-negative multi-drug resistant phenotypes  

PubMed Central

Background The present work was designed to evaluate the antibacterial properties of the methanol extracts of eleven selected Cameroonian spices on multi-drug resistant bacteria (MDR), and their ability to potentiate the effect of some common antibiotics used in therapy. Results The extract of Cinnamomum zeylanicum against Escherichia coli ATCC 8739 and AG100 strains showed the best activities, with the lowest minimal inhibitory concentration (MIC) of 64??g/ml. The extract of Dorstenia psilurus was the most active when tested in the presence of an efflux pump inhibitor, phenylalanine Arginine-?- Naphtylamide (PA?N), a synergistic effect being observed in 56.25?% of the tested bacteria when it was combined with Erythromycin (ERY). Conclusion The present work evidently provides information on the role of some Cameroonian spices in the fight against multi-resistant bacteria.

2012-01-01

122

Plasmid-mediated quinolone resistance: an update  

Microsoft Academic Search

In 1998, the first plasmid-mediated gene involved in quinolone resistance (currently named qnrA1) was reported. Extra qnr-like plasmid-mediated genes (qnrB, qnrS, qnrC, qnrD) and their chromosomal homologues have also been characterized. These genes code for a pentapeptide repeat protein that protects\\u000a type II topoisomerases from quinolones. Since then, there have been reports of two other plasmid-mediated resistance mechanisms:\\u000a the modification

José Manuel Rodríguez-Martínez; María Eliecer Cano; Carmen Velasco; Luis Martínez-Martínez; Álvaro Pascual

2011-01-01

123

Quinolones and pregnancy: worrying animal findings, few clinical data.  

PubMed

(1) Follow-up studies of approximately 1,000 women exposed to quinolones during pregnancy show no increase in the risk of malformations, miscarriage, prematurity, intrauterine growth retardation or postnatal disorders, but there are not enough data to draw firm conclusions. (2) Teratogenic effects have been observed in animals treated with the oldest quinolones (flumequine, nalidixic acid and pipemidic acid) and also with sparfloxacin, a fluoroquinolone. (3) Cartilage damage after postnatal exposure to quinolones in animals and humans has been reported. (4) Alternatives to quinolones can almost always be found for pregnant women. (5) Accidental exposure to quinolones during pregnancy does not warrant termination. PMID:10557576

1999-02-01

124

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 2: Antibacterial and Osteoblastic Response  

PubMed Central

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time scales on bacterial and osteoblastic cell cultures. All CAP powders exhibited satisfying antibacterial performance against Staphylococcus aureus, the main causative agent of osteomyelitis. Still, owing to its highest drug adsorption efficiency, the most bacteriostatically effective phase was amorphous CAP with the minimal inhibitory concentration of less than 1 mg/ml. At the same time, the positive cell response and osteogenic effect of the antibiotic-loaded CAP particles was confirmed in vitro for all the sparsely soluble CAP phases. Adsorption of the antibiotic onto CAP particles reversed the deleterious effect that the pure antibiotic exerted on the osteogenic activity of the osteoblastic cells. The simultaneous osteogenic and antimicrobial performance of the material developed in this study, altogether with its ability to exhibit sustained drug release, may favor its consideration as a material base for alternative therapeutic approaches to prolonged antibiotic administration and surgical debridement typically prescribed in the treatment of osteomyelitis.

Uskokovic, Vuk; Desai, Tejal A.

2012-01-01

125

Transferable Quinolone Resistance in Vibrio cholerae?  

PubMed Central

Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera.

Kim, Hong Bin; Wang, Minghua; Ahmed, Sabeena; Park, Chi Hye; LaRocque, Regina C.; Faruque, Abu S. G.; Salam, Mohammed A.; Khan, Wasif A.; Qadri, Firdausi; Calderwood, Stephen B.; Jacoby, George A.; Hooper, David C.

2010-01-01

126

Role of quinolones in surgical prophylaxis  

Microsoft Academic Search

The general principles involved in the use of chemoprophylaxis in surgery, the selection of patients at risk, and the choice of antibiotic agents are reasonably well established. While a good deal of data exist regarding commonly used prophylactic regimens, very little data are available on the role of quinolones in surgical prophylaxis. The literature dealing with this area is reviewed,

L. A. Mandell

1991-01-01

127

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

PubMed Central

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.

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

2000-01-01

128

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

PubMed Central

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 control measures maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions.

Engberg, J.; Aarestrup, F. M.; Taylor, D. E.; Gerner-Smidt, P.; Nachamkin, I.

2001-01-01

129

Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate and azide ligands: Synthesis, spectroscopic studies, DFT calculations and antibacterial assays  

NASA Astrophysics Data System (ADS)

Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor ligands (thiocyanate or azide). The complexes were characterized by elemental analysis, FT-IR, 1H NMR and UV-Vis spectroscopes. The binding modes of the ligands in complexes were established by means of molecular modeling of the complexes, and calculation of their IR, NMR and absorption spectra at DFT (TDDFT)/B3LYP level were studied. The experimental and calculated data verified monodentate binding through the carboxylic oxygen atoms of anti-inflammatory drugs in the zinc complexes. The calculated 1H, FT-IR and UV-Vis data are in better agreement with the experimental results, and confirm the predicted tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level of theory. Biological studies showed the antibacterial activity of zinc complexes against Gram-positive and Gram-negative bacterial strains.

Chiniforoshan, Hossein; Tabrizi, Leila; Hadizade, Morteza; Sabzalian, Mohammad R.; Chermahini, Alireza Najafi; Rezapour, Mehdi

2014-07-01

130

Antibacterials from the Sea  

PubMed Central

The ocean contains a host of macroscopic life in a great microbial soup. Unlike the terrestrial environment, an aqueous environment provides perpetual propinquity and blurs spatial distinctions. Marine organisms are under a persistent threat of infection by resident pathogenic microbes including bacteria, and in response they have engineered complex organic compounds with antibacterial activity from a diverse set of biological precursors. The diluting effect of the ocean drives the construction of potent molecules that are stable to harsh salty conditions. Members of each class of metabolite—ribosomal and non-ribosomal peptides, alkaloids, polyketides, and terpenes—have been shown to exhibit antibacterial activity. The sophistication and diversity of these metabolites points to the ingenuity and flexibility of biosynthetic processes in Nature. Compared with their terrestrial counterparts, antibacterial marine natural products have received much less attention. Thus, a concerted effort to discover new antibacterials from marine sources has the potential to contribute significantly to the treatment of the ever increasing drug-resistant infectious diseases.

Hughes, Chambers C.; Fenical, William

2011-01-01

131

Morphology, drug release, antibacterial, cell proliferation, and histology studies of chamomile-loaded wound dressing mats based on electrospun nanofibrous poly(?-caprolactone)/polystyrene blends.  

PubMed

For the first time, it has been tried to achieve optimum conditions for electrospun poly(?-caprolactone)/polystyrene (PCL/PS) nanofibrous samples as active wound dressings containing chamomile via D-optimal design approach. In this work, systematic in vitro and in vivo studies were carried out by drug release rate, antibacterial and antifungal evaluations, cell culture, and rat wound model along with histology observation. The optimized samples were prepared under the following electrospinning conditions: PCL/PS ratio (65/35), PCL concentration 9%(w/v), PS concentration 14%(w/v), distance between the syringe needle tip and the collector 15.5 cm, applied voltage 18 kV, and solution flow rate 0.46 mL h(-1) . The FE-SEM micrographs showed electrospun PCL/PS (65/35) nanofibrous sample containing 15% chamomile had a minimum average diameter (?175 nm) compared to the neat samples (?268 nm). The drug released resulted in a gradual and high amount of chamomile from the optimized PCL/PS nanofibrous sample (?70%) in respect to PCL and PS nanofibers after 48 h. This claim was also confirmed by antibacterial and antifungal evaluations in which an inhibitory zone with a diameter of about 7.6 mm was formed. The rat wound model results also indicated that the samples loaded with 15% chamomile extract were remarkably capable to heal the wounds up to 99?±?0.5% after 14 days post-treatment periods. The adhesion of mesenchymal stem cells and their viability on the optimized samples were confirmed by MTT analysis. Also, the electrospun nanofibrous mats based on PCL/PS (65/35) showed a high efficiency in the wound closure and healing process compared to the reference sample, PCL/PS nanofibers without chamomile. Finally, the histology analysis revealed that the formation of epithelial tissues, the lack of necrosis and collagen fibers accumulation in the dermis tissues for the above optimized samples. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 977-987, 2014. PMID:24259351

Motealleh, Behrooz; Zahedi, Payam; Rezaeian, Iraj; Moghimi, Morvarid; Abdolghaffari, Amir Hossein; Zarandi, Mohammad Amin

2014-07-01

132

Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae  

Microsoft Academic Search

Although quinolone resistance results mostly from chromosomal mutations in Enterobacteriaceae, it may also be mediated by plasmid-encoded Qnr determinants. Qnr proteins protect DNA from quinolone binding and compromise the efficacy of quinolones such as nalidixic acid. Qnr proteins (QnrA-like, QnrB and QnrS) have been identified worldwide with a quite high prevalence among Asian isolates with a frequent association with clavulanic

Patrice Nordmann; Laurent Poirel

2005-01-01

133

The novel antibacterial drug XF-70 is a potent inhibitor of Staphylococcus aureus infection of the burn wound.  

PubMed

The authors report the findings of in vivo studies of XF-70 (a novel, dicationic porphyrin) against Staphylococcus aureus in a murine model of a burn wound infection. Mice received a 15% total body scald burn wound, which were inoculated with S. aureus (1.8 x 10 CFU). After 24 hours, escharectomies were performed and groups (n = 8) received single or two doses (6 hours apart) of XF-70* (100 microg/wound) or silver sulfadiazine, Acticoat, or saline applied topically. Viable bacteria were quantified from homogenized burn tissue biopsies and the spleen by plating dilutions onto agar plates and CFU determination. A single dose of XF-70 reduced bacterial burden by 98.77% (untreated: 2.78 +/- 2.96 x 10 CFU/g vs XF-70 treated: 3.4 +/- 0.19 x 10 CFU/g, P < .01). Two XF-70 doses reduced the growth of S. aureus by 99.96% (1.2 +/- 0.6 x 10 CFU/g, P < .01). These results were similar to the results obtained from commonly used topical antibacterials silver sulfadiazine and Acticoat. The spleens of mice treated with saline had a robust growth of S. aureus (7.0 +/- 1.97 x 10 CFU/g) whereas those treated with one or two XF-70 doses grew only 3.5 +/- 0.002 x 10 CFU/g and 5.7 +/- 0.002 x 10 CFU/g, respectively, a significant (P < .001) reduction in S. aureus dissemination. Single and multiple doses of XF-70 were effective in controlling S. aureus growth in burn wounds and inhibited systemic dissemination of S. aureus. Early treatment of burn wounds with XF-70 may be effective in slowing bacterial dissemination to other tissues. PMID:20453736

Hurtuk, Michael G; He, L-K; Szilagyi, Andrea; Gamelli, Richard L; Hecht, David W; Kennedy, Richard H; Rhys-Williams, William; Love, William G; Shankar, Ravi

2010-01-01

134

Challenges of Antibacterial Discovery  

PubMed Central

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

Silver, Lynn L.

2011-01-01

135

Pharmacokinetics and efficacy of the new quinolones in infections of the eye, ear, nose, and throat.  

PubMed

A review of published data indicates that the new quinolones readily penetrate the tissues and secretions of the upper respiratory tract. The concentrations of ciprofloxacin and ofloxacin in tonsillar tissue and the concentrations of ofloxacin in the mucosa of the paranasal sinuses generally exceeded the peak concentrations of these agents in serum after oral administration of the drugs. Good penetration was noted for ciprofloxacin into nasal secretions, ofloxacin into tears, and various quinolones into saliva. Penetration into ocular humors appears to be moderate. Reports in English concerning clinical trials of the new fluoroquinolones in the treatment of infections of the eyes, ears, nose, and throat are sparse, but a number of studies of ofloxacin have been published in Japanese. The data suggest that the new quinolones may be useful for the treatment of acute sinusitis and chronic suppurative otitis media. However, studies comparing these agents with more established drugs and using carefully defined criteria for diagnosis and for evaluation of the response to treatment are needed. PMID:3279497

Barza, M

1988-01-01

136

75 FR 37818 - Issues in the Design and Conduct of Clinical Trials for Antibacterial Drug Development; Public...  

Federal Register 2010, 2011, 2012, 2013

...workshop will focus on the design and conduct of non-inferiority...Drug Administration, Office of Antimicrobial Products...scientific issues in the design and conduct of clinical...various aspects of the design and conduct of clinical...Information (HFI-35), Office of Management...

2010-06-30

137

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

NASA Astrophysics Data System (ADS)

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.

Wang, Yusheng; Feng, Lin; Jiang, Chongqiu

2005-10-01

138

Electrochemical evaluation of antibacterial drugs as environment-friendly inhibitors for corrosion of carbon steel in HCl solution  

NASA Astrophysics Data System (ADS)

The effect of penicillin G, ampicillin and amoxicillin drugs on the corrosion behavior of carbon steel (ASTM 1015) in 1.0 mol L-1 hydrochloric acid solution was investigated using potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and electrochemical noise (EN) techniques. The inhibition efficiency was found to increase with increasing inhibitor concentration. The effect of temperature on the rate of corrosion in the absence and presence of these drugs was also studied. Some thermodynamic parameters were computed from the effect of temperature on corrosion and inhibition processes. Adsorption of these inhibitors was found to obey Langmuir adsorption isotherm. There was a case of mixed mode of adsorption here but while penicillin was adsorbed mainly through chemisorption, two other drugs were adsorbed mainly through physisorption. Potentiodynamic polarization measurements indicated that the inhibitors were of mixed type. In addition, this paper suggests that the electrochemical noise (EN) technique under open circuit conditions as the truly noninvasive electrochemical method can be employed for the quantitative evaluation of corrosion inhibition. This was done by using the standard deviation of partial signal (SDPS) for calculation of the amount of noise charges at the particular interval of frequency, thereby obtaining the inhibition efficiency (IE) of an inhibitor. These IE values showed a reasonable agreement with those obtained from potentiodynamic polarization and EIS measurements.

Golestani, Gh.; Shahidi, M.; Ghazanfari, D.

2014-07-01

139

Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments.  

PubMed

Fluoroquinolones are broad-spectrum antimicrobials highly effective for treatment of a variety of clinical and veterinary infections. Their antibacterial activity is due to inhibition of DNA replication. Usually resistance arises spontaneously due to point mutations that result in amino acid substitutions within the topoisomerase subunits GyrA, GyrB, ParC or ParE, decreased expression of outer membrane porins, or overexpression of multidrug efflux pumps. In addition, the recent discovery of plasmid-mediated quinolone resistance could result in horizontal transfer of fluoroquinolone resistance between strains. Acquisition of high-level resistance appears to be a multifactorial process. Care needs to taken to avoid overuse of this important class of antimicrobial in both human and veterinary medicine to prevent an increase in the occurrence of resistant zoonotic and non-zoonotic bacterial pathogens that could subsequently cause human or animal infections. PMID:15848289

Hopkins, Katie L; Davies, Robert H; Threlfall, E John

2005-05-01

140

In vitro induction of micronuclei and chromosome aberrations by quinolones: possible mechanisms.  

PubMed

The bacterial gyrase inhibitors, ciprofloxacin and PD 124816, were tested for clastogenic and aneugenic activity in V79 Chinese hamster lung cells in vitro. Cells were exposed for 3 h, washed free of drug, and subcultured for assessment of various endpoints. For structural chromosomal aberration (SCA) analysis, cells were incubated for 18 h, and treated with Colcemid for 2 h before harvest. For micronucleus (MN) analysis, treated cells were incubated with cytochalasin B (CYB) for 16 h. Aneugenicity was assessed by utilizing antikinetochore antibody to detect kinetochore-containing (K +) MN. Both quinolones induced significant increases in SCAs and MN, indicating clastogenic activity. With both compounds, however, the MN response was apparent at lower doses, and remained much higher throughout the dose range than the SCA response. The induced MN were predominantly K --, indicating that aneugenicity was not playing a major role in their induction. A possible explanation for the chromosome effects is that cross-reactivity of the gyrase inhibitors with mammalian topoisomerase II interferes with the separation of chromatids at anaphase leading to chromosome breaks and MN. Quinolones are known to inhibit resolution of the normally transient topoisomerase II-DNA cleavable complex, which may result in chromosome stickness. Thus, SCAs detected in metaphase cells may be attributed to quinolone-induced inhibition of topoisomerase II prior to mitosis while MN arise in binucleated cells as a result of this effect which interferes with chromatid separation during anaphase. PMID:8676903

Curry, P T; Kropko, M L; Garvin, J R; Fiedler, R D; Theiss, J C

1996-06-10

141

Vibrational spectra study on quinolones antibiotics  

NASA Astrophysics Data System (ADS)

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.

Wang, Yu; Yu, Ke; Wang, Sihuan

2006-09-01

142

4-Quinolone alkaloids from Melochia odorata.  

PubMed

The methanol extract of Melochia odorata yielded three 4-quinolone alkaloids including waltherione A (1) and two new alkaloids, waltherione C (2) and waltherione D (3). Waltheriones A and C showed significant activities in an in vitro anti-HIV cytoprotection assay at concentrations of 56.2 and 0.84 ?M and inhibition of HIV P24 formation of more than 50% at 1.7 and 0.95 ?M, respectively. The structures of the alkaloids were established by spectroscopic data interpretation. PMID:24392742

Jadulco, Raquel C; Pond, Christopher D; Van Wagoner, Ryan M; Koch, Michael; Gideon, Osia G; Matainaho, Teatulohi K; Piskaut, Pius; Barrows, Louis R

2014-01-24

143

Design, synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives as novel peptide deformylase inhibitors.  

PubMed

The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated to discover SAR at P(1') and P(3') positions, and most of these derivatives exhibit better in vitro antibacterial activity than existing drugs against drug-resistant clinical isolates including MRSA, PRSP, and Haemophilus influenzae. PMID:21185180

Shi, Wei; Ma, Haikun; Duan, Yuejiao; Aubart, Kelly; Fang, Yuhong; Zonis, Rimma; Yang, Liping; Hu, Wenhao

2011-02-01

144

In vitro activities of 4-quinolones against the fish pathogen Aeromonas salmonicida.  

PubMed Central

The activities of five fluorinated 4-quinolones, namely, sarafloxacin, enrofloxacin, PD127391, PD117596, and CI934, against the fish pathogen Aeromonas salmonicida were investigated and compared with that of oxolinic acid.The results indicated that with the exception of CI934, these drugs are more active than oxolinic acid in terms of MIC. No inoculum effect was observed, but the drugs were less active at 10 degrees C than at 22 degrees C. The presence of 3% of NaCl caused an increase in drug activity. Resistance to the drugs appeared to be fairly stable, with only a small decrease in activity after 10 successive passages of the test strains on drug-free tryptone soya agar.

Barnes, A C; Lewin, C S; Hastings, T S; Amyes, S G

1990-01-01

145

Antibacterial Pollution  

NSDL National Science Digital Library

In this Science Update, from Science NetLinks, you'll hear one worrisome possibility for the potential environmental effects of common household products. A lot of household products nowadays claim to be antibacterial--containing compounds that kill viruses, bacteria, and other germs on contact. But what happens to these compounds when they get washed down the drain? Science Updates are audio interviews with scientists and are accompanied by a set of questions as well as links to related Science NetLinks lessons and other related resources.

Science Update;

2003-06-30

146

Synthetic thioamide, benzimidazole, quinolone and derivatives with carboxylic acid and ester moieties: a strategy in the design of antituberculosis agents.  

PubMed

Synthetic heterocyclic compounds have remarkable potential activity against diseases; thioamides, benzimidazoles, quinolones and derivatives with carboxylic acid and esters moieties have shown excellent activity against Mycobacterium tuberculosis. We reviewed antituberculosis activities of above compounds with reference to half maximal inhibitory concentration, minimum inhibitory concentration and structural-activity relationship which clearly indicate that electron-withdrawing groups are the main inducers of antimycobacterium activity. Comparison between clinically used drugs and new synthetic derivatives showed recent advances made in the last decade. PMID:24164193

Ashfaq, M; Shah, S S A; Najam, T; Ahmad, M M; Tabassum, R; Rivera, G

2014-03-01

147

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

PubMed Central

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. Conclusions This study shows that at least two mechanisms might explain the emerging resistance of Enterobacteriaceae to quinolones in the CAR. Beside the classical topoisomerase mutation, the cause may be acquisition of a plasmid-borne qnrA1. Clinicians and bacteriologists should be made aware of possible dissemination of ISCR1-qnrA1 among Enterobacteriacae.

2011-01-01

148

Quinolone-induced arthropathy in the neonatal mouse. Morphological analysis of articular lesions produced by pipemidic acid and ciprofloxacin.  

PubMed

Quinolone antibiotics are extensively utilized in antimicrobial chemotherapy. However, quinolone treatment in developing adolescents of several animal species is associated with acute arthropathy of the weight-bearing joints. Although arthropathy has rarely been observed following quinolone therapy in man, the toxicity observed in immature animals has resulted in restricted use of these drugs in children and pregnant women. Therefore, identification of novel quinolone antibiotics which do not cause arthropathy is highly desirable. This task would be facilitated by a bioassay of cartilage toxicity which utilizes small quantities of test material and has greater sensitivity than current toxicity assays. This study evaluated the utility of neonatal mice as a potential bioassay of quinolone-induced joint toxicity. Seven-day-old CF-1 mice (8-10/dose group) were treated subcutaneously with either pipemidic acid (50, 400, or 3150 mg/kg/day) for 7 or 14 days or ciprofloxacin (50 or 200 mg/kg/day) for 5, 7, or 14 days. Lameness was observed only after high-dose pipemidic acid treatment for 2-7 days. Histopathological assessment of the principal weight-bearing joints (knee, elbow, and multiple articulations in the fore- and hind-feet) revealed a lesion characterized by chondrocyte loss, matrix degeneration, and erosion of the articular cartilage in mice treated with pipemidic acid at 400 or 3150 mg/kg/day for 7 days or ciprofloxacin at 200 mg/kg/day for 5 days. Mice treated for 14 days with 400 mg/kg/day pipemidic acid demonstrated a lower incidence of lesions than mice treated for 7 days, suggesting the potential for reversibility during ongoing treatment. The results suggest that neonatal mice are sensitive to quinolone-induced arthropathy, but less so than previously reported for adolescent dogs. It is concluded that the neonatal mouse may be an appropriate screening system for identifying novel quinolones devoid of cartilage toxicity; however, follow-up studies with select compounds in a more sensitive species, such as the dog, are encouraged. PMID:8566484

Linseman, D A; Hampton, L A; Branstetter, D G

1995-11-01

149

Effect of new quinolones on the human gastrointestinal microflora.  

PubMed

During the last years, the effect of new quinolones--ciprofloxacin, norfloxacin, ofloxacin, and pefloxacin--on the human microflora has been studied. This review article summarizes the published data concerning these studies. The results show that the oropharyngeal flora is only slightly or not at all affected by the quinolones. All new quinolones have a similar effect on the normal intestinal flora. The gram-negative aerobic flora is strongly suppressed during administration of quinolones, while the gram-positive flora is only slightly affected. The anaerobic microflora is almost not at all affected by the administration. The emergence of resistant bacterial strains is uncommon, although one investigation showed increased MIC values for anaerobes during ciprofloxacin administration. Replacement by yeasts or other inherently resistant microorganisms does not often seem to be a problem. High concentrations of the new quinolones are reached in feces; values between 100 and 2,200 mg/kg are reported. Since the new quinolones do not cause marked ecologic disturbances in the intestinal microflora, they may be suitable for selective decontamination in immunocompromised patients and for treatment of bacterial intestinal infections. PMID:3279492

Nord, C E

1988-01-01

150

[Antibacterial and anti-algal activity if two traditional drugs in the treatment of urinary tract infection and cystitis in Mali].  

PubMed

For the treatment of the urinary infections and the cystitis, the medicinal plants constitute a source of new molecules with an antimicrobial activity and economically accessible to face the apparition of a phenomena of germ resistance to antibiotics. The urinary infections and the cystitis are very spilled and constitute a problem of public health in developing countries. About 50% of women develop a symptomatic urinary tract infection at least once in their life. The urinary infection is, by order of frequency, the first of the non epidemic infectious illnesses. The objective of our survey is to find in Malian Pharmacopoeia, plants with antibacterial and analgesic properties. Five remedies and their plants used in traditional medicine for the treatment of the urinary tract infections and the cystitis have been selected on the basis of ethnobotanic investigations results. Extracts of five remedies and their plants have been tested for their antibacterial activity on the germs responsible for the urinary infections and the cystitis. Extracts containing Stylosanthes erecta P. Beauv (Fabaceae) demonstrated an antibacterial activity against clinical strains of Escherichia coli, responsible of 75 to 80% of the urinary infections. The same extracts demonstrated an analgesic activity against the pain induced by the acetic acid in mice. The antibacterial and analgesic properties can be of great benefit in the treatment of the urinary tract infections and the cystitis. PMID:17390524

Rokia, Sanogo; Drissa, Diallo; Seydou, Diarra; Colette, Ekoumou; Flabou, Bougoudogo

2006-01-01

151

Characterization of the quinolone resistance mechanism in foodborne Salmonella isolates with high nalidixic acid resistance.  

PubMed

Sixteen Salmonella strains resistant to nalidixic acid isolated from kimbab, the most popular ready-to-eat (RTE) food in Korea, and chicken meat were selected for this study. The resistant strains were shown to have high minimal inhibitory concentrations (MICs) against nalidixic acid (512~4096 ?g/mL). Among them, 4 Salmonella enterica serovar Haardt isolates showed multi-drug resistance (MDR) patterns with reduced susceptibility to fluoroquinolone (0.5 ?g/mL of ciprofloxacin MICs). The mechanisms of quinolone resistance in the nalidixic acid resistant strains were characterized by PCR and sequence analysis. The presence of plasmid-mediated quinolone resistance (PMQR) genes and amino acid changes in the quinolone resistance determining region (QRDR) were investigated by PCR-based detection and sequencing, and the efflux pump inhibition test was also done using phe-arg-?-naphthylamide (PA?N). Although PMQR genes were not detected in any of the tested strains, the QRDR mutations were found in this study: single mutation in gyrA (Asp87Tyr, Asp87Gly, and Asp87Asn), double mutations in gyrA (Ser83Thr) and parC (Thr57Ser), and single mutation in parC (Thr57Ser). MICs of nalidixic acid were reduced by 2- to 32-folds by the efflux pump inhibitor, PA?N. Pulsed-field gel electrophoresis (PFGE) was carried out to confirm the epidemiological relationship between the nalidixic acid resistant strains. The PFGE patterns were classified into 6 groups at cutoff level of 70~100% correlation on the dendrogram. Some strains of serotype Haardt and Enteritidis showed several values of genomic identity in accordance with strains, sources, and isolation year. We suggest that point mutation on QRDR and efflux pump systems involved in antimicrobials had independent effects on drug-resistance regardless of bacterial genomic variation. PMID:21354645

Kim, Koo-Youn; Park, Jong-Hyun; Kwak, Hyo-Sun; Woo, Gun-Jo

2011-03-15

152

In vitro susceptibility of quinolone-resistant Campylobacter jejuni to new macrolide antibiotics  

Microsoft Academic Search

The MICs of erythromycin and three new macrolide antibiotics were determined for 36 quinolone-susceptible and 106 quinolone-resistantCampylobacter jejuni. The MIC90 values of azithromycin, clarithromycin, roxithromycin and erythromycin were 0.5, 4, 16 and 4 mg\\/l respectively. No difference was found between macrolide activity against the quinolone-susceptible and the quinolone-resistant strains. Clarithromycin and especially azithromycin might eventually replace erythromycin for the treatment

H. P. Endtz; M. Broeren; R. P. Mouton

1993-01-01

153

Broader Distribution of Plasmid-Mediated Quinolone Resistance in the United States  

Microsoft Academic Search

The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-suscep- tible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these

A. Robicsek; D. F. Sahm; J. Strahilevitz; G. A. Jacoby; D. C. Hooper

2005-01-01

154

Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies  

Microsoft Academic Search

Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during

G. J. Timmers; Y. Dijstelbloem; A. M. Simoons-Smit; A J van Winkelhoff; D J Touw; C. M. J. E. Vandenbroucke-Grauls; P C Huijgens

2004-01-01

155

4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-Ones Prevent the Transmission of Plasmodium falciparum to Anopheles freeborni  

PubMed Central

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.

Saenz, Fabian E.; LaCrue, Alexis N.; Cross, R. Matthew; Maignan, Jordany R.; Udenze, Kenneth O.; Manetsch, Roman

2013-01-01

156

Quinolone accumulation in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.  

PubMed Central

The accumulation of quinolones by Escherichia coli JF568, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus ATCC 29213 was measured by a modified fluorometric assay (J. S. Chapman and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:27-29, 1989). The quinolones examined were fleroxacin, pefloxacin, norfloxacin, difloxacin, A56620, ciprofloxacin, ofloxacin, and Ro 09-1168. In all three organisms, uptake was complete in less than 5 min and was proportional to extracellular quinolone concentrations between 2 and 50 micrograms/ml, which is consistent with simple diffusion. Washing cells with quinolone-free buffer decreased accumulation by up to 70% in E. coli and P. aeruginosa but not in S. aureus. Similarly, incubation with the uncouplers 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone increased accumulation up to fourfold in E. coli and P. aeruginosa, though not in S. aureus, suggesting endogenous, energy-dependent efflux. High quinolone hydrophobicity was generally associated with decreased accumulation in E. coli and P. aeruginosa (except in the case of pefloxacin) but was associated with increased accumulation in S. aureus (except in the case of difloxacin). Ciprofloxacin had the highest accumulation in E. coli and P. aeruginosa, while pefloxacin had the highest accumulation in S. aureus.

McCaffrey, C; Bertasso, A; Pace, J; Georgopapadakou, N H

1992-01-01

157

The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibrio fischeri  

Microsoft Academic Search

Quinolones are one of the most important group of synthetic antibiotics used in aquaculture. We studied the single substance and mixture toxicity of ten quinolones using a long term bioluminescence inhibition assay with the marine bacterium Vibrio fischeri as the test organism. All tested quinolones are highly toxic to the test organism with EC50 values ranging from 14 ?g\\/l for

T. Backhaus; M. Scholze; L. H. Grimme

2000-01-01

158

Plasmid-Mediated Quinolone Resistance in Clinical Isolates of Escherichia coli from Shanghai, China  

Microsoft Academic Search

Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible, qnr, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to Klebsiella pneumoniae and Escherichia coli isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai,

Minggui Wang; John H. Tran; George A. Jacoby; Yingyuan Zhang; Fu Wang; David C. Hooper

2003-01-01

159

Interaction of the Plasmid-Encoded Quinolone Resistance Protein Qnr with Escherichia coli DNA Gyrase  

Microsoft Academic Search

Quinolone resistance normally arises by mutations in the chromosomal genes for type II topoisomerases and by changes in the expression of proteins that control the accumulation of quinolones inside bacteria. A novel mechanism of plasmid-mediated quinolone resistance was recently reported that involves DNA gyrase protec- tion by a pentapeptide repeat family member called Qnr. This family includes two other members,

John H. Tran; George A. Jacoby; David C. Hooper

2005-01-01

160

Prevalence and characterisation of quinolone resistance mechanisms in Salmonella spp.  

PubMed

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. PMID:24613291

Wasyl, Dariusz; Hoszowski, Andrzej; Zaj?c, Magdalena

2014-07-16

161

Iron(III) complexes: preparation, characterization, antibacterial activity and DNA-binding.  

PubMed

Iron(III) have been combined to well known quinolones (ciprofloxacin) and some Schiff bases with the help of coordination approach. Characterization of these compounds have been done using elemental analysis, magnetic measurements, thermogravimetric analysis, IR, UV-VIS, (1)H NMR and (13)C NMR spectral investigation. Analytical studies suggest that the iron(III)-quinolone complexes assume a six-coordinated dimeric distorted octahedral geometry. All the compounds show a good antibacterial activity against broad range of bacteria like Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi and Serratia marcescens, whereas no significant inhibition towards growth of fungal strains like Aspergillus Niger, Aspergillus flavus and Lasiodiplodia theobromae. Analyses of all these compounds show effective sperm herring DNA inhibition. PMID:18343909

Pansuriya, Pramod B; Patel, M N

2008-04-01

162

Longitudinal surveillance of outpatient quinolone antimicrobial use in Canada  

PubMed Central

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important. OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time. METHODS: Antimicrobial prescribing data collected by IMS Health Canada were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements. RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year-to-year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year-to-year decreases in the DDDs per prescription were found to be significant from 2000 to 2010. DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines.

Glass-Kaastra, Shiona K; Finley, Rita; Hutchinson, Jim; Patrick, David M; Weiss, Karl; Conly, John

2014-01-01

163

Functions Required for Extracellular Quinolone Signaling by Pseudomonas aeruginosa  

Microsoft Academic Search

A set of 30 mutants exhibiting reduced production of the phenazine poison pyocyanin were isolated following transposon mutagenesis of Pseudomonas aeruginosa PAO1. The mutants could be subdivided into those with defects in the primary phenazine biosynthetic pathway and those with more pleiotropic defects. The largest set of pleiotropic mutations blocked the production of the extracellular Pseudomonas quinolone signal (PQS), a

Larry A. Gallagher; Susan L. McKnight; Marina S. Kuznetsova; Everett C. Pesci; Colin Manoil

2002-01-01

164

Salmonella enterica Serotype Typhi with nonclassical quinolone resistance phenotype.  

PubMed

We report Salmonella enterica serotype Typhi strains with a nonclassical quinolone resistance phenotype (i.e., decreased susceptibility to ciprofloxacin but with susceptibility to nalidixic acid) associated with a nonsynonymous mutation at codon 464 of the gyrB gene. These strains, not detected by the nalidixic acid disk screening test, can result in fluoroquinolone treatment failure. PMID:21749778

Accou-Demartin, Marie; Gaborieau, Valérie; Song, Yajun; Roumagnac, Philippe; Marchou, Bruno; Achtman, Mark; Weill, François-Xavier

2011-06-01

165

Design, synthesis, and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives as novel peptide deformylase inhibitors.  

PubMed

The synthesis and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated, and some of these derivatives showed better in vitro antibacterial activity than existing drugs, including penicillin, ciprofloxacin, vancomycin, and linezolid. PMID:20510610

Shi, Wei; Duan, Yuejiao; Qian, Yu; Li, Ming; Yang, Liping; Hu, Wenhao

2010-06-15

166

Evaluation of antibacterial activity of N-phosphonium chitosan as a novel polymeric antibacterial agent.  

PubMed

N-phosphonium chitosans (NPCSs) with different degrees of substitution (3%, 13% and 21%) were synthesized and evaluated as novel polymeric antibacterial agents. Their antibacterial activities compared with hydroxypropyltrimethyl ammonium chloride chitosan (HACC), parent chitosan and (5-carboxypentyl) triphenylphosphonium bromide (CTPB) were tested against Escherichia coli and two strains of drug-resistance Staphylococcus aureus by minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and biofilm prevention assays. The results show that the NPCS with 3% or 13% substitution has lower MIC and MBC values and stronger ability to inhibit biofilm formation of all the three bacteria than HACC, chitosan and CTPB. In addition, the antibacterial activity of NPCSs increases with their substitution decreasing from 21% to 3%. Overall, the antibacterial activity of NPCS with 3% or 13% substitution is better than that of NPCS with 21% substitution, HACC with 22% substitution, chitosan and CTPB. It can be considered that NPCS with appropriate degree of substitution has favorable antibacterial activity and is a potential polymeric antibacterial agent. PMID:24680902

Guo, Aijie; Wang, Feihu; Lin, Wentao; Xu, Xiaofen; Tang, Tingting; Shen, Yuanyuan; Guo, Shengrong

2014-06-01

167

Antibacterial activities of multi drug resistant Myroides odoratimimus bacteria isolated from adult flesh flies (Diptera: sarcophagidae) are independent of metallo beta-lactamase gene  

PubMed Central

Flesh flies (Diptera: Sarcophagidae) are well known cause of myiasis and their gut bacteria have never been studied for antimicrobial activity against bacteria. Antimicrobial studies of Myroides spp. are restricted to nosocomial strains. A Gram-negative bacterium, Myroides sp., was isolated from the gut of adult flesh flies (Sarcophaga sp.) and submitted to evaluation of nutritional parameters using Biolog GN, 16S rRNA gene sequencing, susceptibility to various antimicrobials by disc diffusion method and detection of metallo ?-lactamase genes (TUS/MUS). The antagonistic effects were tested on Gram-negative and Gram-positive bacteria isolated from human clinical specimens, environmental samples and insect mid gut. Bacterial species included were Aeromonas hydrophila, A. culicicola, Morganella morganii subsp. sibonii, Ochrobactrum anthropi, Weissella confusa, Escherichia coli, Ochrobactrum sp., Serratia sp., Kestersia sp., Ignatzschineria sp., Bacillus sp. The Myroides sp. strain was resistant to penicillin-G, erythromycin, streptomycin, amikacin, kanamycin, gentamycin, ampicillin, trimethoprim and tobramycin. These strain showed antibacterial action against all bacterial strains except W. confusa, Ignatzschineria sp., A. hydrophila and M. morganii subsp. sibonii. The multidrug resistance of the strain was similar to the resistance of clinical isolates, inhibiting growth of bacteria from clinical, environmental and insect gut samples. The metallo ?-lactamase (TUS/MUS) genes were absent, and resistance due to these genes was ruled out, indicating involvement of other secretion machinery.

Dharne, M.S.; Gupta, A.K.; Rangrez, A.Y.; Ghate, H.V.; Patole, M.S.; Shouche, Y.S.

2008-01-01

168

Identification of neutral 4- O-alkyl quinolone nonpeptide GnRH receptor antagonists  

Microsoft Academic Search

A series of neutral, nonbasic quinolone GnRH antagonists were prepared via Mitsunobu alkylation of protected and unprotected 4-hydroxy quinolone intermediates. The synthetic route was improved by utilization of unique reactivity and convergency afforded by the use of mono and bis-trimethylsilylethyl protected quinolones. Potent neutral GnRH antagonists were identified, including ether and lactam derivatives, that show similar in vitro binding affinity

Robert J. DeVita; Mamta Parikh; Jinlong Jiang; Jason A. Fair; Jonathan R. Young; Thomas F. Walsh; Mark T. Goulet; Jane-L. Lo; Ning Ren; Joel B. Yudkovitz; Jisong Cui; Yi T. Yang; Kang Cheng; Susan P. Rohrer; Matthew J. Wyvratt

2004-01-01

169

In vitro activities of irloxacin and E-3846, two new quinolones.  

PubMed Central

Irloxacin and E-3846 are two new fluorinated quinolones. We evaluated the activities of these antimicrobial agents, ciprofloxacin, ofloxacin, enoxacin, pefloxacin, norfloxacin, and nalidixic acid against 1,161 bacterial strains. Ciprofloxacin was the most active quinolone. Irloxacin did not show great activity. The activity of E-3846 against gram-negative bacteria was similar to those of ofloxacin and pefloxacin, and E-3846 was the most active quinolone against gram-positive bacteria and anaerobes.

Garcia-Rodriguez, J A; Garcia Sanchez, J E; Munoz Bellido, J L; Trujillano, I

1990-01-01

170

In vitro activities of irloxacin and E-3846, two new quinolones.  

PubMed

Irloxacin and E-3846 are two new fluorinated quinolones. We evaluated the activities of these antimicrobial agents, ciprofloxacin, ofloxacin, enoxacin, pefloxacin, norfloxacin, and nalidixic acid against 1,161 bacterial strains. Ciprofloxacin was the most active quinolone. Irloxacin did not show great activity. The activity of E-3846 against gram-negative bacteria was similar to those of ofloxacin and pefloxacin, and E-3846 was the most active quinolone against gram-positive bacteria and anaerobes. PMID:2393288

García-Rodríguez, J A; García Sánchez, J E; Muñoz Bellido, J L; Trujillano, I

1990-06-01

171

Antibacterial activity of thioetherhydroxyethylsulfonamide derivatives.  

PubMed

Thioetherhydroxyethylsulfonamide derivatives were synthesized and evaluated for their in vitro antibacterial activity against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923). Results have shown that compounds 8c and 9e display potent activity (MIC = 0.125 µg/mL) against E. coli when compared with the standard drug sulfamethoxazole (SMZ, MIC < 0.5 µg/mL) for this same strain. All the new compounds were fully identified and characterized by NMR ((1)H and (13)C) and X-ray crystallography (for compound 8c). This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against multi-drug bacterial resistance. PMID:24533504

Vellasco, Walcimar T; Guedes, Guilherme P; Facchinetti, Victor; Vasconcelos, Thatyana R A; Vaz, Maria G F; Cunico, Wilson; de Souza, Marcus V N; de Paula, Geraldo R; Fleming, Maria E C K; Gomes, Claudia R B

2014-05-01

172

Comparative in vitro activity of quinolones against Stenotrophomonas maltophilia.  

PubMed

The susceptibility of 109 Stenotrophomonas maltophilia isolates, all characterized by pulsed-field gel electrophoresis, to nine quinolones was studied. Grepafloxacin, trovafloxacin, and moxifloxacin displayed similar intrinsic activities (MIC90, 0.5 microg/ml), which were lower than those of ofloxacin and ciprofloxacin (MIC90, 4 microg/ml), norfloxacin (MIC90, 64 microg/ml), and nalidixic acid (MIC90, 32 microg/ml). Nalidixic acid was generally one- to twofold dilutions more active than norfloxacin. According to the criteria of the National Committee for Clinical Laboratory Standards (NCCLS), the percentage of isolates susceptible to ciprofloxacin (breakpoint < or = 1 microg/ml) was 76.1%. Using the NCCLS breakpoint for comparative purposes, the percentage of isolates susceptible to grepafloxacin, moxifloxacin, and trovafloxacin was 95.4, 96.4, and 96.4%, respectively. These results indicate that new quinolones may potentially be used for the management of Stenotrophomonas maltophilia infections. PMID:10691206

Valdezate, S; Vindel, A; Baquero, F; Cantón, R

1999-12-01

173

Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling  

NASA Astrophysics Data System (ADS)

Clay minerals are commonly used materials in pharmaceutical production both as inorganic carriers or active agents. The purpose of this study is the preparation and characterization of clay/antibacterial drug hybrids which can be further included in drug delivery systems for treatment oral infections. Novel nanocomposites with antibacterial properties were successfully prepared by ion exchange reaction from two types of kaolinite/urea intercalates and chlorhexidine diacetate. Intercalation compounds of kaolinite were prepared by reaction with solid urea in the absence of solvents (dry method) as well as with urea aqueous solution (wet method). The antibacterial activity of two prepared samples against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated by finding the minimum inhibitory concentration (MIC). Antibacterial studies of both samples showed the lowest MIC values (0.01%, w/v) after 1 day against E. faecalis, E. coli and S. aureus. A slightly worse antibacterial activity was observed against P. aeruginosa (MIC 0.12%, w/v) after 1 day. Since samples showed very good antibacterial activity, especially after 1 day of action, this means that these samples can be used as long-acting antibacterial materials. Prepared samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental data are supported by results of molecular modelling.

Holešová, Sylva; Valášková, Marta; Hlavá?, Dominik; Madejová, Jana; Samlíková, Magda; Tokarský, Jonáš; Pazdziora, Erich

2014-06-01

174

Antibacterial properties of nanoparticles.  

PubMed

Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of different NP materials. PMID:22884769

Hajipour, Mohammad J; Fromm, Katharina M; Ashkarran, Ali Akbar; Jimenez de Aberasturi, Dorleta; de Larramendi, Idoia Ruiz; Rojo, Teofilo; Serpooshan, Vahid; Parak, Wolfgang J; Mahmoudi, Morteza

2012-10-01

175

In vitro antibacterial activity of medicinal plant extracts against Escherichia coli strains from human clinical specimens and interactions with antimicrobial drugs.  

PubMed

The biological properties of medicinal plants have been documented worldwide for many centuries. We aimed to evaluate interactions between crude extracts from Psidium guajava, Zingiber officinale, Cymbopogon citratus, Caryophyllus aromaticus, Mikania glomerata and Allium sativum samples and antimicrobial drugs against Escherichia coli strains. The susceptibility test performed was disc diffusion, and crude extracts were diluted (%v/v) into Müller-Hinton agar (MHA) at one quarter of the minimal inhibitory concentration for 90% (MIC(90%)) of E. coli strains found previously. Synergistic interactions were observed between C. citratus and polymyxin, and A. sativum extracts and gentamicin. The crude A. sativum extract was the only one that did not show any antagonism with the antimicrobial drugs. The results thus showed the potential use of these medicinal plants against E. coli strains, although antagonism with antimicrobial drugs is a negative aspect in the combined therapy of infectious diseases caused by E. coli. PMID:22011190

Ushimaru, P I; Barbosa, L N; Fernandes, A A H; Di Stasi, L C; Fernandes, A

2012-01-01

176

2-Heptyl-4-Quinolone, a Precursor of the Pseudomonas Quinolone Signal Molecule, Modulates Swarming Motility in Pseudomonas aeruginosa?  

PubMed Central

Pseudomonas aeruginosa is an opportunistic pathogen capable of group behaviors, including biofilm formation and swarming motility. These group behaviors are regulated by both the intracellular signaling molecule c-di-GMP and acylhomoserine lactone quorum-sensing systems. Here, we show that the Pseudomonas quinolone signal (PQS) system also contributes to the regulation of swarming motility. Specifically, our data indicate that 2-heptyl-4-quinolone (HHQ), a precursor of PQS, likely induces the production of the phenazine-1-carboxylic acid (PCA), which in turn acts via an as-yet-unknown downstream mechanism to repress swarming motility. We show that this HHQ- and PCA-dependent swarming repression is apparently independent of changes in global levels of c-di-GMP, suggesting complex regulation of this group behavior.

Ha, Dae-Gon; Merritt, Judith H.; Hampton, Thomas H.; Hodgkinson, James T.; Janecek, Matej; Spring, David R.; Welch, Martin; O'Toole, George A.

2011-01-01

177

Y-688, a New Quinolone Active against Quinolone-Resistant Staphylococcus aureus: Lack of In Vivo Efficacy in Experimental Endocarditis  

Microsoft Academic Search

Y-688 is a new fluoroquinolone with increased activity against ciprofloxacin-resistant staphylococci. The MICs of Y-688 and other quinolones were determined for 58 isolates of ciprofloxacin-resistant and methicillin- resistant Staphylococcus aureus (MRSA). The MICs at which 50% and 90% of bacteria were inhibited were >128 and >128 mg\\/liter, respectively, for ciprofloxacin, 16 and 32 mg\\/liter, respectively, for sparfloxacin, and 0.25 and

J. M. ENTENZA; O. MARCHETTI; M. P. GLAUSER; P. MOREILLON

1998-01-01

178

Exploration of structure-based on imidazole core as antibacterial agents.  

PubMed

Imidazole, a five-membered heterocycle having three carbon atoms, and two double bonds, having efficient antibacterial Escherichia coli, Bacillus subtili, Bacillus proteus, Staphylococcus aureus, Pseudomonas aeruginosa, and Helicobacter pyloriurease etc, shows a broad-spectrum of antibacterial activities. To Search new antibacterial drugs to overcome resistance of microorganisms to antibiotics, to date hundreds of this sort of derivatives have been synthesized and possess potent antibacterial activity. As the structure of imidazole derivatives is various, the target of antibacterial is also diverse including ?-Lactamases, ?-ketoacyl-acyl carrier protein synthase III (FabH), DNA gyrase and topoisomerase, glutamate racemase and urease. In this review, we will discuss the emergence of resistance to antibiotics and attempt to summarize the main developments of imidazole derivatives in the past ten years. We hope that increasing knowledge of the structure-activity relationship (SAR) will be beneficial to the rational design of new generation of small molecule antibacterial drugs. PMID:24200359

Duan, Yong-Tao; Wang, Zhong-Chang; Sang, Ya-Li; Tao, Xiang-Xiang; Zhu, Hai-Liang

2013-01-01

179

Identification, Design and Biological Evaluation of Bisaryl Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)  

PubMed Central

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 IC50 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 bc1, and studies to determine the potential advantage of this dual-targeting effect are in progress.

2012-01-01

180

Mixed-valence Cu(II)/Cu(I) complex of quinolone ciprofloxacin isolated by a hydrothermal reaction in the presence of L-histidine: comparison of biological activities of various copper-ciprofloxacin compounds.  

PubMed

A new quinolone-metal complex was prepared by a hydrothermal reaction in the presence of L-histidine that served as a reducing agent for a metal. The title compound [Cu(II)(cfH)(2)(Cu(I)Cl(2))(2)] (1) is a mixed-valence Cu(II)-Cu(I) complex, which contains two ciprofloxacin (cfH) molecules bonded to the central copper(II) atom and two almost planar [Cu(I)Cl(2)](-) moieties. Both metal centers are connected through two bridging atoms (chloride and quinolone oxygen). The electrochemical methods (differential-pulse polarography and cyclovoltammetric measurements) confirmed the presence of various copper-ciprofloxacin complex species in aqueous solution at low concentrations used in biological activity tests and also indicated that the equilibria in this system are very complex. The biological properties of the title compound and some previously isolated copper-ciprofloxacin complexes ([Cu(cfH)(2)Cl(2)].6H(2)O (2) and [CuCl(cfH)(phen)]Cl.2H(2)O (3)) (phen=1, 10-phenantroline) were determined and compared. The DNA gyrase inhibition tests and antibacterial activity tests have shown that the effect of copper complexes is comparable to that of free quinolone. Additionally, an interesting DNA cleavage activity of the title compound was also discovered. PMID:15621275

Drevensek, Petra; Zupancic, Tatjana; Pihlar, Boris; Jerala, Roman; Kolitsch, Uwe; Plaper, Andreja; Turel, Iztok

2005-02-01

181

Differential distribution of plasmid-mediated quinolone resistance genes in clinical enterobacteria with unusual phenotypes of quinolone susceptibility from Argentina.  

PubMed

We studied a collection of 105 clinical enterobacteria with unusual phenotypes of quinolone susceptibility to analyze the occurrence of plasmid-mediated quinolone resistance (PMQR) and oqx genes and their implications for quinolone susceptibility. The oqxA and oqxB genes were found in 31/34 (91%) Klebsiella pneumoniae and 1/3 Klebsiella oxytoca isolates. However, the oqxA- and oqxB-harboring isolates lacking other known quinolone resistance determinants showed wide ranges of susceptibility to nalidixic acid and ciprofloxacin. Sixty of the 105 isolates (57%) harbored at least one PMQR gene [qnrB19, qnrB10, qnrB2, qnrB1, qnrS1, or aac(6')-Ib-cr)], belong to 8 enterobacterial species, and were disseminated throughout the country, and most of them were categorized as susceptible by the current clinical quinolone susceptibility breakpoints. We developed a disk diffusion-based method to improve the phenotypic detection of aac(6')-Ib-cr. The most common PMQR genes in our collection [qnrB19, qnrB10, and aac(6')-Ib-cr] were differentially distributed among enterobacterial species, and two different epidemiological settings were evident. First, the species associated with community-acquired infections (Salmonella spp. and Escherichia coli) mainly harbored qnrB19 (a unique PMQR gene) located in small ColE1-type plasmids that might constitute its natural reservoirs. qnrB19 was not associated with an extended-spectrum ?-lactamase phenotype. Second, the species associated with hospital-acquired infections (Enterobacter spp., Klebsiella spp., and Serratia marcescens) mainly harbored qnrB10 in ISCR1-containing class 1 integrons that may also have aac(6')-Ib-cr as a cassette within the variable region. These two PMQR genes were strongly associated with an extended-spectrum ?-lactamase phenotype. Therefore, this differential distribution of PMQR genes is strongly influenced by their linkage or lack of linkage to integrons. PMID:23478955

Andres, Patricia; Lucero, Celeste; Soler-Bistué, Alfonso; Guerriero, Leonor; Albornoz, Ezequiel; Tran, Tung; Zorreguieta, Angeles; Galas, Marcelo; Corso, Alejandra; Tolmasky, Marcelo E; Petroni, Alejandro

2013-06-01

182

Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium  

PubMed Central

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.

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

2013-01-01

183

Emergence and Dissemination of Quinolone-Resistant Escherichia coli in the Community  

Microsoft Academic Search

We studied the evolution of resistance to quinolones in Escherichia coli from 1992 to 1997 in Barcelona, Spain. An increasing proportion of quinolone-resistant E. coli (QREC) infections was observed. QREC strains were more common in patients with nosocomial infections but also increased in patients with community- acquired infections (9% in 1992 to 17% in 1996). Seventy (12%) of 572 episodes

JAVIER GARAU; MARIONA XERCAVINS; MONICA RODRIGUEZ-CARBALLEIRA; JOSEP RAMONG OMEZ-VERA; IGNACIO COLL; DOLORS VIDAL; TERESA LLOVET; ANA RUIZ-BREMON

1999-01-01

184

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

National Technical Information Service (NTIS)

The object was to synthesize and submit for antimalarial evaluation new compounds related to either endochin (2-methyl-3-heptyl-7-methoxy-4(1H)-quinolone) or the 3-carbomethoxy-4(1H)-quinolones that had shown moderate to good antimalarial activity. A tota...

A. C. Casey

1974-01-01

185

Prevalence of Plasmid-Mediated Quinolone Resistance Determinants over a 9Year Period  

Microsoft Academic Search

Recently, several plasmid-mediated quinolone resistance (PMQR) genes conferring low levels of quinolone resistance have been discovered. To evaluate the temporal change in the prevalence of PMQR genes over a decade in a tertiary hospital in the Republic of Korea, we selected every fifth isolate of Escherichia coli and Klebsiella pneumoniae and every third isolate of Enterobacter cloacae between 1998 and

Hong Bin Kim; Chi Hye Park; Chung Jong Kim; Eui-Chong Kim; George A. Jacoby; David C. Hooper

2009-01-01

186

Structural Requirements of the Pseudomonas Quinolone Signal for Membrane Vesicle Stimulation?  

PubMed Central

Pseudomonas aeruginosa produces the quorum signal 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal), which is important for stimulating outer membrane vesicle (MV) formation. Here we describe the importance of the 3-hydroxyl and 2-alkyl chain for MV production and the length of the 2-alkyl chain for association with MVs.

Mashburn-Warren, Lauren; Howe, Jorg; Brandenburg, Klaus; Whiteley, Marvin

2009-01-01

187

Drugs.  

ERIC Educational Resources Information Center

This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

Hurst, Hunter, Ed.; And Others

1984-01-01

188

Preparation and PhysicoChemical Studies of Some Novel Mixed-Ligand Cyanonitrosyl {CrNO} Complexes of Chromium(I) with Some Antimalarial, Antibacterial and Antidyspeptic Drugs  

Microsoft Academic Search

A new series of mixed-ligand cyanonitrosyl {CrNO} complexes of chromium(I) of compositions [Cr(NO)(CN)2(L-L)(H2O)] (where L-L = primaquine diphosphate, camoquin dihydrochloride, quinine monohydrochloride, cinchonine monohydrochloride, chloroquine diphosphate or chloroquinaldol) and [Cr(NO)(CN)2(L)2(HO)](where L = bilamide) hare been synthesized by the interaction of the potassium pentacyanonitrosylchromate(I) mnnohydrate with the said drugs L-L and L. The complexes so obtained are characterized by elemental analyses,

R. C. Maurya; D. D. Mishra

1991-01-01

189

Synthesis, primary photophysical and antibacterial properties of naphthyl ester cinoxacin and nalidixic acid derivatives.  

PubMed

We have synthesized two naphthyl ester quinolone derivates and determined their ability to generate reactive oxygen species (ROS) such as (1)O(2), ()OH, H(2)O(2) upon photolysis with UV-A light. The ability of cinoxacin (1) and nalidixic acid (2), and their naphthyl ester derivatives (3 and 4) to generate a dose-dependent amount of singlet oxygen and ROS (()(-)O(2), ()OH) in cell-free systems was detected by histidine assay and by luminol-enhanced chemiluminescence (LCL), respectively. Their electronic absorption and emission spectra were quantified and their photostability was determined. Their tendency to generate peroxidic derivative species showed the following order: 3>4; in contrast, their ability to generate singlet oxygen was 4>3 and these were better sensitizers than their parent quinolones 1 and 2. The antibacterial activity in darkness and under irradiation of compounds 3 and 4 was tested on Escherichia coli and compared with that of their parent compounds. An enhanced antibacterial activity by irradiation of the naphthyl esters of cinoxacin and nalidixic acid on E. coli was observed. PMID:18562206

Vargas, Franklin; Zoltan, Tamara; Rivas, Carlos; Ramirez, Alvaro; Cordero, Tulynan; Díaz, Yrene; Izzo, Carla; Cárdenas, Ylec M; López, Verónica; Gómez, Lubimar; Ortega, Jessenia; Fuentes, Alberto

2008-08-21

190

Optical control of antibacterial activity  

NASA Astrophysics Data System (ADS)

Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism.

Velema, Willem A.; van der Berg, Jan Pieter; Hansen, Mickel J.; Szymanski, Wiktor; Driessen, Arnold J. M.; Feringa, Ben L.

2013-11-01

191

Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells.  

PubMed

Quinolones have been reported to induce adverse effects on articular cartilage, tendons and ligaments. However, the effects of quinolones on menisci have not been revealed. The present study was to test the effects of levofloxacin on meniscus cells in vitro. Rabbit meniscus cells were administrated with different concentrations of levofloxacin (0, 14, 28, 56, 112 and 224?µm) for 24 or 48?h, and cell viability and apoptosis were measured. The mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-3, Col1a1, Bcl-2, caspase-3 and inducible nitric oxide were analyzed by real-time polymerase chain reaction. Active caspase-3 was detected by immunocytochemical assay, while protein expression levels of MMP-3 and MMP-13 were measured by Western blotting assay. After treatment with levofloxacin for 48?h, cell viability was decreased from dose of 28 to 224?µm in a concentration-dependent manner. An increase of apoptotic cells was observed by flow cytometry. Active caspase-3 protein expression level was also increased. The mRNA level of Bcl-2 was decreased and levels of MMP-1, MMP-3 and MMP-13 in experimental groups were higher than those of controls. The protein levels of MMP-3 and MMP-13 were increased. Moreover, the mRNA levels of TIMP-3 and col1a1 were decreased. A dose-dependent increase of inducible nitric oxide mRNA expression level was also observed. Our results suggested the cytotoxic effects of levofloxacin on meniscus cells through induction of apoptosis and unbalanced MMPs/TIMPs expression. These side effects might result in meniscus extracellular matrix degradation and meniscal lesion. Thus, quinolones should be used cautiously on patients who perform athletic activities or undergo surgical meniscus repair. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23813946

Wang, Linlong; Wu, Yunpeng; Tan, Yang; Fei, Xi; Deng, Yu; Cao, Hong; Chen, Biao; Wang, Hui; Magdalou, Jacques; Chen, Liaobin

2014-08-01

192

Comparison of the antibacterial effect of silver sulfadiazine 1%, mupirocin 2%, Acticoat and octenidine dihydrochloride in a full-thickness rat burn model contaminated with multi drug resistant Acinetobacter baumannii.  

PubMed

In this study, our aim is to compare the efficacy of different topical antibacterial agents in a rat model contaminated with a multi drug resistant (MDR) standard Acinetobacter baumannii strain. The study was carried out on 40 Sprague-Dawley rats of 250-300 g each. For the purposes of this study, the rats were divided into 5 groups, with 8 rats in each group: Group 1 control; Group 2 silver sulfadiazine; Group 3 mupirocin; Group 4 Acticoat group; and Group 5 octenidine dihydrochloride group. Following to the formation of the full-thickness burn areas in rats, the MDR A. baumannii standard strain was inoculated into the burned area. The rats in all the groups were sacrificed at the end of the 10th day and subjected to histopathological and microbiological evaluation. In the histopathological evaluation, the lowest inflammatory cell response and bacterial density in the eschar and muscle tissues were observed in the Acticoat group. While these results were found to be statistically significant compared to the silver sulfadiazine group, only the bacterial density in the muscle tissue was found as significant in comparison to the mupirocin and octenidine groups. In the microbiological evaluation, the lowest growth in the muscle tissue culture among all the groups was observed in the Acticoat group. The growth in the eschar tissue culture was significantly lower in the Acticoat and octenidine groups in comparison to the silver sulfadiazine group. At the end of the study, it has been observed that Acticoat was effective both in eschar and muscle, while octenidine was effective in eschar tissues in a rat burn model contaminated with MDR A. baumannii. PMID:22688192

Selçuk, Caferi Tayyar; Durgun, Mustafa; Ozalp, Burhan; Tekin, Alicem; Tekin, Recep; Akçay, Cemal; Alabal?k, Ula?

2012-12-01

193

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

PubMed

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 such as aac(6')-1b-cr, might have contributed to the high quinolone resistance rates. In conclusion, not only qnr genes but all other plasmid-mediated quinolone resistance genes, should be tested for the detection of plasmid-mediated quinolone resistance and this fact should be taken into consideration when the reservoirs are being searched for. PMID:22399166

Aktepe, Orhan Cem; A??k, Gül?ah; Cetinkol, Yeliz; Biçmen, Meral; Gülay, Zeynep

2012-01-01

194

Synthesis and in vitro antibacterial activity of oxazolidine LBM-415 analogs as peptide deformylase inhibitors.  

PubMed

The drug resistant bacteria pose a severe threat to human health. The increasing resistance of those pathogens to traditional antibacterial therapy renders the identification of new antibacterial agents with novel antibacterial mechanisms an urgent need. In this study, a series of (2S)-N-substituted-1-[(formyhydroxyamino)methyl]-1-oxohexyl]-2-oxazolidinecarboxamides were designed, synthesized and evaluated for in vitro antibacterial activity. Most of these compounds displayed good activities against Gram-positive organisms comparable to reference agent LBM-415. PMID:21288715

Yu, Linliang; Zhou, Weicheng; Wang, Zhenyu

2011-03-01

195

Determinants of quinolone versus trimethoprim-sulfamethoxazole use for outpatient urinary tract infection.  

PubMed

Quinolones are increasingly favored over trimethoprim-sulfamethoxazole (TMP-SMX) for empirical treatment of uncomplicated urinary tract infection (UTI). This is associated with increasing resistance toward this broad-spectrum group of antibiotics. Our objective is to describe the prescribing patterns and identify determinants of the choice between TMP-SMX and quinolones for outpatient UTI treatment in Switzerland. An ongoing national Sentinel surveillance system was used to study 11,799 antibiotic prescriptions for UTI in adult outpatients and associated physician and patient factors between 2006 and 2008, to compare the prescription of quinolones versus that of TMP-SMX for treatment of UTI. Most UTI episodes were diagnosed as cystitis (90%). TMP-SMX was prescribed for one-fifth (22%) of UTIs. Independent predictors for prescribing quinolones were pyelonephritis and physicians with low thresholds for prescribing antibiotics for upper respiratory tract infections ("high prescribers"), whereas female patients were more likely to receive TMP-SMX. High-prescribing physicians also more often cared for patients who themselves favor antibiotic treatment (P < 0.001). Quinolones are commonly prescribed to outpatients with UTI. Nonclinical factors influence the choice of quinolones versus TMP-SMX, which may provide opportunities for interventions to improve prescribing patterns and control quinolone resistance. PMID:22232276

Stuck, Anna K; Täuber, Martin G; Schabel, Maria; Lehmann, Thomas; Suter, Herbert; Mühlemann, Kathrin

2012-03-01

196

Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections.  

PubMed

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7 %): colistin-carbapenem (CC), 69 (32.2 %): colistin-sulbactam (CS), and 43 (20.1 %: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p?=?0.97) and microbiological (p?=?0.92) outcomes and 14-day survival rates (p?=?0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p?>?0.05) and also for 14-day survival (p?>?0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p?=?0.02, p?=?0.0001, p?=?0.0001, p?=?0.02, and p?=?0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p?

Batirel, A; Balkan, I I; Karabay, O; Agalar, C; Akalin, S; Alici, O; Alp, E; Altay, F A; Altin, N; Arslan, F; Aslan, T; Bekiroglu, N; Cesur, S; Celik, A D; Dogan, M; Durdu, B; Duygu, F; Engin, A; Engin, D O; Gonen, I; Guclu, E; Guven, T; Hatipoglu, C A; Hosoglu, S; Karahocagil, M K; Kilic, A U; Ormen, B; Ozdemir, D; Ozer, S; Oztoprak, N; Sezak, N; Turhan, V; Turker, N; Yilmaz, H

2014-08-01

197

2Alkyl4(1 H )-Quinolone Signalling in Pseudomonas aeruginosa  

Microsoft Academic Search

\\u000a In addition to the las and rhl qorum sensing (QS) systems, Pseudomonas aeruginosa utilises a non-acyl homoserine lactone (AHL)-based systems which relies on the production of 2-alkyl-4(1H)-quinolone (AQ) molecules. Although this organism produces a large range of AQ derivatives, the two main AQ signal molecules\\u000a described are 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), and its immediate precursor, 2-heptyl-3-hydroxy-4(1H)-quinolone (HHQ). AQ biosynthesis and signalling in

Matthew P. Fletcher; Stephan Heeb; Siri Ram Chhabra; Stephen P. Diggle; Paul Williams; Miguel Cámara

198

gyrA mutations in quinolone-resistant isolates of the fish pathogen Aeromonas salmonicida.  

PubMed Central

gyrA mutations in quinolone-resistant isolates of Aeromonas salmonicida have been detected by using PCR to amplify the quinolone resistance-determining region of gyrA and subsequent cloning and sequencing of PCR products. Comparison of nucleotide and derived amino acid sequences of PCR products from quinolone-susceptible and -resistant bacteria revealed a serine 83-to-isoleucine substitution in the gyrase A protein of resistant isolates. One of the resistant isolates differed from the other by a two- to fourfold-higher MIC of the fluoroquinolone enrofloxacin and carried an additional alanine 67-to-glycine substitution, which may contribute to the higher level of resistance.

Oppegaard, H; S?rum, H

1994-01-01

199

Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation  

PubMed Central

Characterizing novel drugs and chemical probes of biological systems is hindered by difficulties in identifying the mechanism of action (MOA) of biologically active molecules. Here we present a metabolite suppression approach to explore the MOA of antibacterial compounds under nutrient restriction. We assembled an array of metabolites that can be screened for suppressors of inhibitory molecules. Further, we identified inhibitors of E. coli growth under nutrient limitation and charted their interactions with our metabolite array. This strategy led to the discovery and characterization of three novel antibacterial compounds, MAC168425, MAC173979 and MAC13772. We showed that MAC168425 interferes with glycine metabolism, MAC173979 is a time-dependent inhibitor of p-aminobenzoic acid biosynthesis and MAC13772 inhibits biotin biosynthesis. We conclude that metabolite suppression profiling is an effective approach to focus MOA studies on compounds impairing metabolic capabilities. Such bioactives can serve as chemical probes of bacterial physiology and as leads for antibacterial drug development.

Zlitni, S.; Ferruccio, L.F.

2014-01-01

200

Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.  

PubMed

WQ-3034 is a newly synthesized acidic fluoroquinolone. We assessed its in vitro activity against Mycobacterium tuberculosis and M. avium complex using levofloxacin (LVFX), ciprofloxacin (CPFX), sparfloxacin (SPFX), and KRM-1648 (KRM) as reference drugs. The MICs of these agents were determined by the agar dilution method with 7H11 medium. The MICs at which 50 and 90% of the test strains were inhibited (MIC(50)s, and MIC(90)s, respectively) for the test quinolones for rifampin (RMP)-susceptible M. tuberculosis strains were in the order SPFX < LVFX quinolones, while the MIC(90) of KRM for RMP-resistant M. tuberculosis strains was higher than those of the quinolones. The MIC(50)s and MIC(90)s of the test drugs for M. avium were in the order KRM < SPFX < CPFX drugs against M. tuberculosis organisms residing in cells of the Mono Mac 6 macrophage (Mphi)-like cell line (MM6-Mphis) and of the A-549 type II alveolar cell line (A-549 cells). When drugs were added at the concentration that achieves the maximum concentration in blood, progressive killing or inhibition of the M. tuberculosis organisms residing in MM6-Mphis and A-549 cells was observed in the order KRM > SPFX >/= LVFX > WQ-3034 > CPFX. The efficacies of all quinolones against intracellular M. tuberculosis organisms were significantly lower in A-549 cells than in MM6-Mphis. WQ-3034 at the MIC caused more marked growth inhibition of intramacrophage M. tuberculosis than did LVFX. These findings indicate that the in vitro anti-M. tuberculosis activity of WQ-3034 is greater than that of CPFX and is comparable to that of LVFX. PMID:10639351

Tomioka, H; Sato, K; Kajitani, H; Akaki, T; Shishido, S

2000-02-01

201

Enhanced separation of seven quinolones by capillary electrophoresis with silica nanoparticles as additive.  

PubMed

This paper describes the enhanced separation of lomefloxacin, sparfloxacin, fleroxacin, norfloxacin, ofloxacin, gatifloxacin and pazufloxacin by capillary zone electrophoresis (CZE) using silica nanoparticles (SiNPs) as running buffer additive. The impact of SiNPs concentration on the resolution and selectivity of separation was investigated and a given value of SiNPs was finally chosen under the optimum conditions. The addition of the SiNPs to the running buffer enabled electroosmotic flow (EOF) decrease and permitted full interaction between SiNPs and analytes. The influence of separation voltage, pH and buffer concentration on the separation in the presence of SiNPs was examined. Interactions between drugs and nanoparticles during the separation are discussed; the determination of interaction constants is also achieved. A good resolution of seven quinolones was obtained within 15 min in a 50 cm effective length fused-silica capillary at a separation voltage of +10 kV in a 12 mM disodium tetraborate-phosphate buffer (pH 9.08) containing 5.2 microgmL(-1) SiNPs. PMID:19159781

Wang, Yanqing; Baeyens, Willy R G; Huang, Changgang; Fei, Guangtao; He, Li; Ouyang, Jin

2009-03-15

202

Vitiquinolone--a quinolone alkaloid from Hibiscus vitifolius Linn.  

PubMed

Phytochemical investigations of the powdered root of Hibiscus vitifolius Linn. (Malvaceae) was extracted successively with n-hexane and chloroform. Analysis of the n-hexane extract by GC-MS led to the identification of twenty-six components by comparison of their mass spectra with GC-MS library data. A novel quinolone alkaloid, vitiquinolone (5) together with eight known compounds viz. ?-Amyrin acetate (1), n-octacosanol (2), ?-Amyrin (3), stigmasterol (4), xanthyletin (6), alloxanthoxyletin (7), xanthoxyletin (8) and betulinic acid (9) were isolated from chloroform extract by column chromatography over silica gel. The structure of vitiquinolone was established on the basis of spectroscopic methods including UV, IR, 1D, 2D NMR and ESI-MS. The known compounds were identified on the basis of their physical and spectroscopic data as reported in the literature. PMID:24128571

Ramasamy, D; Saraswathy, A

2014-02-15

203

Lack of effective bactericidal activity of new quinolones against Brucella spp.  

PubMed

The in vitro activities of six fluoroquinolones against 43 Brucella spp. were compared by testing three different inocula at two medium pH values. The influence of the test conditions was moderate. The activities of all quinolones were lower at pH 5 and with a high inoculum size. Results indicate the lack of effective bactericidal activity of quinolones against most strains of Brucella spp., particularly B. abortus. PMID:2069383

García-Rodriguez, J A; García Sánchez, J E; Trujillano, I

1991-04-01

204

Lack of effective bactericidal activity of new quinolones against Brucella spp.  

PubMed Central

The in vitro activities of six fluoroquinolones against 43 Brucella spp. were compared by testing three different inocula at two medium pH values. The influence of the test conditions was moderate. The activities of all quinolones were lower at pH 5 and with a high inoculum size. Results indicate the lack of effective bactericidal activity of quinolones against most strains of Brucella spp., particularly B. abortus.

Garcia-Rodriguez, J A; Garcia Sanchez, J E; Trujillano, I

1991-01-01

205

In Vitro Activities of Three Nonfluorinated Quinolones against Representative Bacterial Isolates  

Microsoft Academic Search

In vitro susceptibility tests were performed to document the inhibitory activities of three nonfluorinated quinolone (NFQ) compounds (PGE 9262932, PGE 9509924, and PGE 4175997) compared to those of cipro- floxacin, levofloxacin, and trovafloxacin against 3,030 bacterial isolates. The spectra of the NFQ agents included most gram-positive species as well as quinolone-susceptible Enterobacteriaceae. Ciprofloxacin-resis- tant, methicillin-resistant Staphylococcus aureus strains were inhibited

ARTHUR L. BARRY; PETER C. FUCHS; STEVEN D. BROWN

2001-01-01

206

Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility.  

PubMed

The quinolone resistance-determining regions (QRDRs) of topoisomerase II and IV genes from Stenotrophomonas maltophilia ATCC 13637 were sequenced and compared with the corresponding regions of 32 unrelated S. maltophilia clinical strains for which ciprofloxacin MICs ranged from 0.1 to 64 microg/ml. GyrA (Leu-55 to Gln-155, Escherichia coli numbering), GyrB (Met-391 to Phe-513), ParC (Ile-34 to Arg-124), and ParE (Leu-396 to Leu-567) fragments from strain ATCC 13637 showed high degrees of identity to the corresponding regions from the phytopathogen Xylella fastidiosa, with the degrees of identity ranging from 85.0 to 93.5%. Lower degrees of identity to the corresponding regions from Pseudomonas aeruginosa (70.9 to 88.6%) and E. coli (73.0 to 88.6%) were observed. Amino acid changes were present in GyrA fragments from 9 of the 32 strains at positions 70, 85, 90, 103, 112, 113, 119, and 124; but there was no consistent relation to higher ciprofloxacin MICs. The absence of changes at positions 83 and 87, commonly involved in quinolone resistance in gram-negative bacteria, was unexpected. The GyrB sequences were identical in all strains, and only one strain (ciprofloxacin MIC, 16 microg/ml) showed a ParC amino acid change (Ser-80-->Arg). In contrast, a high frequency (16 of 32 strains) of amino acid replacements was present in ParE. The frequencies of alterations at positions 437, 465, 477, and 485 were higher (P < 0.05) in strains from cystic fibrosis patients, but these changes were not linked with high ciprofloxacin MICs. An efflux phenotype, screened by the detection of decreases of at least twofold doubling dilutions of the ciprofloxacin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (0.5 microg/ml) or reserpine (10 microg/ml), was suspected in seven strains. These results suggest that topoisomerases II and IV may not be the primary targets involved in quinolone resistance in S. maltophilia. PMID:11850246

Valdezate, Sylvia; Vindel, Ana; Echeita, Aurora; Baquero, Fernando; Cantó, Rafael

2002-03-01

207

Topoisomerase II and IV Quinolone Resistance-Determining Regions in Stenotrophomonas maltophilia Clinical Isolates with Different Levels of Quinolone Susceptibility  

PubMed Central

The quinolone resistance-determining regions (QRDRs) of topoisomerase II and IV genes from Stenotrophomonas maltophilia ATCC 13637 were sequenced and compared with the corresponding regions of 32 unrelated S. maltophilia clinical strains for which ciprofloxacin MICs ranged from 0.1 to 64 ?g/ml. GyrA (Leu-55 to Gln-155, Escherichia coli numbering), GyrB (Met-391 to Phe-513), ParC (Ile-34 to Arg-124), and ParE (Leu-396 to Leu-567) fragments from strain ATCC 13637 showed high degrees of identity to the corresponding regions from the phytopathogen Xylella fastidiosa, with the degrees of identity ranging from 85.0 to 93.5%. Lower degrees of identity to the corresponding regions from Pseudomonas aeruginosa (70.9 to 88.6%) and E. coli (73.0 to 88.6%) were observed. Amino acid changes were present in GyrA fragments from 9 of the 32 strains at positions 70, 85, 90, 103, 112, 113, 119, and 124; but there was no consistent relation to higher ciprofloxacin MICs. The absence of changes at positions 83 and 87, commonly involved in quinolone resistance in gram-negative bacteria, was unexpected. The GyrB sequences were identical in all strains, and only one strain (ciprofloxacin MIC, 16 ?g/ml) showed a ParC amino acid change (Ser-80?Arg). In contrast, a high frequency (16 of 32 strains) of amino acid replacements was present in ParE. The frequencies of alterations at positions 437, 465, 477, and 485 were higher (P < 0.05) in strains from cystic fibrosis patients, but these changes were not linked with high ciprofloxacin MICs. An efflux phenotype, screened by the detection of decreases of at least twofold doubling dilutions of the ciprofloxacin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (0.5 ?g/ml) or reserpine (10 ?g/ml), was suspected in seven strains. These results suggest that topoisomerases II and IV may not be the primary targets involved in quinolone resistance in S. maltophilia.

Valdezate, Sylvia; Vindel, Ana; Echeita, Aurora; Baquero, Fernando; Canto, Rafael

2002-01-01

208

A review on the impact of 4-quinolones on the normal oropharyngeal and intestinal human microflora.  

PubMed

During the last few years the impact of the newer 4-quinolones, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin, on the human microflora has been studied by several investigators. This review article summarizes the published data concerning these studies. The results show that the oropharyngeal flora is affected only slightly or not at all by the 4-quinolones. All the newer 4-quinolones have a similar effect on the normal intestinal flora. The gram-negative aerobic flora is strongly suppressed during administration of 4-quinolones, while the gram-positive flora is only slightly affected. The anaerobic microflora is hardly affected at all. The emergence of resistant bacterial strains is uncommon, although one study shows increased MIC-values for anaerobes during ciprofloxacin administration. Replacement by yeasts or other inherently resistant microorganisms does not often seem to be a problem. High concentrations of the 4-quinolones are reached in faeces, values between 100-2,200 mg/kg being reported. Since the 4-quinolones do not cause marked ecological disturbances in the intestinal microflora, they may be suitable for selective decontamination in immunocompromised patients, for prophylaxis of urinary tract infections and for treatment of bacterial intestinal infections. PMID:3283041

Edlund, C; Nord, C E

1988-01-01

209

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

PubMed

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. PMID:24447641

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

2014-05-01

210

Antibacterial aminoglycoside analogs  

US Patent & Trademark Office Database

Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): ##STR00001## including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q.sub.1, Q.sub.2, Q.sub.3, R.sub.1, R.sub.2 or R.sub.3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

2014-02-25

211

Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strain and structure–activity relationship studies of 1 H-pyrazolo[3,4- b]pyridine and thieno[2,3 -b]pyridine derivatives  

Microsoft Academic Search

Antibacterial resistance is a complex problem that contributes to health and economic losses worldwide. The Staphylococcus epidermidis is an important nosocomial pathogen that affects immunocompromised patients or those with indwelling devices. Currently, there are several resistant strains including S. epidermidis that became an important medical issue mainly in hospital environment. In this work, we report the biological and theoretical evaluations

Bruno Leal; Ilídio F. Afonso; Carlos R. Rodrigues; Paula A. Abreu; Rafael Garrett; Luiz Carlos S. Pinheiro; Alexandre R. Azevedo; Julio C. Borges; Percilene F. Vegi; Cláudio C. C. Santos; Francisco C. A. da Silveira; Lúcio M. Cabral; Izabel C. P. P. Frugulhetti; Alice M. R. Bernardino; Dilvani O. Santos; Helena C. Castro

2008-01-01

212

[Antimicrobial activity of oral quinolones against clinical isolates of Bifidobacterium group and Clostridium difficile].  

PubMed

Administrations of antimicrobial agent influence human intestinal flora, and sometimes lead to cause Clostridium difficile colitis (CDC). It has been well known that antimicrobial agents, such as clindamycin (CLDM), ampicillin (ABPC) and cephems, frequently cause C. difficile colitis, however, recently some respiratory quinolones, such as garenoxacin (GRNX) and moxifloxacin (MFLX), have paid to attention. Bifidobacterium species would be highly associated with the preservation of normal intestinal flora, while C. difficile would be associated with diarrhea related with antibiotics administration. We investigated antimicrobial activity of GRNX, MFLX and levofloxacin (LVFX) by agar dilution methods based on CLSI recommendations. Forty-seven strains Bifidobacterium species isolated from healthy human intestinal flora and 51 strains of C. difficile isolated from C. difficile colitis patients between 2004 and 2006 were subjected to this study. MIC ranges of Bifidobacterium species for GRNX, MFLX and LVFX were 0.5-16, 0.06-2, and 0.5-8 microg/mL, respectively. MIC50 s of GRNX, MFLX and LVFX against Bifidobacterium species were 2, 0.5 and 4 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against Bifidobacterium species were 8, 2 and 8 microg/mL, respectively. MIC ranges of C. difficile for GRNX, MFLX and LVFX were 0.5 - > 64, 1-64, and 0.125-32 microg/mL, respectively. MIC50s of GRNX, MFLX and LVFX against C. difficile were 2, 2 and 0.5 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against C. difficile were 64, 16 and 8 microg/mL, respectively. LVFX would preserve Bifidobacterium species, and also would be bactericidal for C. difficile, which might lead to the low rate of gastrointestinal disorder in LVFX. GRNX would preserve Bifidobacterium species, however, might be lead to CDC in some cases, since antimicrobial activity for C. difficile has been weak compared with LVFX. Since MFLX would be bactericidal for Bifidobacterium species and antibacterial activity of MFLX for C. difficile would be weak compared with LVFX, we have to pay attention to antibiotics associated diarrhea in MFLX treatment. PMID:20919497

Kimura, Masao; Yamagishi, Yuka; Terada, Michinori; Ohki, Emiko; Tanaka, Kaori; Watanabe, Kunitomo; Mikamo, Hiroshige

2010-04-01

213

Synthesis and biotransformation of 2-alkyl-4(1 H )-quinolones by recombinant Pseudomonas putida KT2440  

Microsoft Academic Search

2-Alkyl-4(1H)-quinolones (AQs) and related derivatives, which exhibit a variety of biological properties, are secondary metabolites produced\\u000a by, e.g., Pseudomonas and Burkholderia spp. Due to their main role as signaling molecules in the quorum sensing system of Pseudomonas aeruginosa, 2-heptyl-4(1H)-quinolone (HHQ) and its 3-hydroxy derivative, termed the “Pseudomonas quinolone signal” (PQS), have received considerable attention. Since chemical synthesis of different AQs

Heiko Niewerth; Klaus Bergander; Siri Ram Chhabra; Paul Williams; Susanne Fetzner

214

Interaction of the Plasmid-Encoded Quinolone Resistance Protein QnrA with Escherichia coli Topoisomerase IV  

Microsoft Academic Search

The plasmid-encoded quinolone resistance protein QnrA (formerly Qnr) has been shown to protect purified Escherichia coli DNA gyrase from quinolone inhibition (4) and to bind to both the gyrase holoenzyme and its subunits (5). Protection of the second quinolone target, topoisomerase (topo) IV, how- ever, could not be established with an assay involving relax- ation of supercoiled plasmid pBR322 DNA

John H. Tran; George A. Jacoby; David C. Hooper

2005-01-01

215

Prospects for new antibacterials: can we do better?  

PubMed

Bacterial resistance to antibacterial drugs has been increasing relentlessly over the past two decades. This includes common residents of the human body: Staphylococcus aureus (methicillin resistant or MRSA) Enteroccus faecalis and E. faecium (vancomycin resistant or VRE): Enterobacteriaceae (multiresistant, carbapenems included or CRE). It also includes environmental, opportunistic, but intrinsically multiresistant species: Pseudomonas aeruginosa and Acinetobacter baumannii. Financial considerations have curtailed R&D activity in the antibacterial field in all, but a couple of large pharmaceutical companies and small biotech companies have largely been unable to fill the drug discovery gap. Antibacterials currently under development have targeted, almost exclusively, Gram-positive bacteria; hence, greater effort must be directed against Gram-negative bacteria, particularly enterobacteria. There also has to be more transparency and care in clinical development. To get ahead of the problem of resistance, we must look for first-in-class antibacterials and new targets. The need to innovate is best addressed through partnerships between drug-makers and public institutions. Such partnerships would provide a long-term view and stability to projects, but also balance the interests of corporate and public stakeholders. PMID:24205783

Georgopapadakou, Nafsika H

2014-02-01

216

Characterization of Selective Antibacterial Peptides by Polarity Index  

PubMed Central

In the recent decades, antibacterial peptides have occupied a strategic position for pharmaceutical drug applications and became subject of intense research activities since they are used to strengthen the immune system of all living organisms by protecting them from pathogenic bacteria. This work proposes a simple and easy statistical/computational method through a peptide polarity index measure by which an antibacterial peptide subgroup can be efficiently identified, that is, characterized by a high toxicity to bacterial membranes but presents a low toxicity to mammal cells. These peptides also have the feature not to adopt to an alpha-helicoidal structure in aqueous solution. The double-blind test carried out to the whole Antimicrobial Peptide Database (November 2011) showed an accuracy of 90% applying the polarity index method for the identification of such antibacterial peptide groups.

Polanco, C.; Samaniego, J. L.; Buhse, T.; Mosqueira, F. G.; Negron-Mendoza, A.; Ramos-Bernal, S.; Castanon-Gonzalez, J. A.

2012-01-01

217

Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents.  

PubMed

Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4m represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 ?g/mL and it showed the most potent activity against S. aureus TyrRS with IC50 of 0.0024 ?M. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode. PMID:24680059

Wang, She-Feng; Yin, Yong; Qiao, Fang; Wu, Xun; Sha, Shao; Zhang, Li; Zhu, Hai-Liang

2014-04-15

218

Penetration of newer quinolones in the empyema fluid.  

PubMed

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema. An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1 x 10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg.kg(-1) for both, i.v.) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC. Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUCPF/AUCblood) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (Cmax,PF) was 2.77 microg.mL(-1) and occurred at a time to maximum pleural fluid concentration (Tmax,PF) of 6 h after infusion and decreased thereafter. The peak blood concentration (Cmax,blood) was 4.81 microg.mL(-1) at 1 h after administration. With levofloxacin, the peak pleural fluid level (Cmax,PF=1.39 microg.mL(-1)) occurred at 6 h (Tmax,PF=6 h) after infusion. The Cmax,blood was 1.88 microg.mL(-1) at 1 h after administration. In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans. PMID:15358708

Liapakis, I E; Kottakis, I; Tzatzarakis, M N; Tsatsakis, A M; Pitiakoudis, M S; Ypsilantis, P; Light, R W; Simopoulos, C E; Bouros, D E

2004-09-01

219

High levels of multiresistance in quinolone resistant urinary tract isolates of Escherichia coli from Norway; a non clonal phenomen?  

PubMed Central

Background The problem of emerging ciprofloxacin resistance is compounded by its frequent association with multiresistance, the reason for which is not fully understood. In this study we compare multiresistance, clonal similarities and phylogenetic group in urinary tract isolates of Escherichia coli sensitive and resistant to the quinolone antimicrobials nalidixic acid and ciprofloxacin. Results Quinolone resistant isolates were more resistant to non-quinolone antibiotics than sensitive isolates, with resistance to ampicillin, mecillinam, sulphonamide, trimethoprim, tetracycline, kanamycin and chloramphenicol significantly increased. Fifty-one percent of quinolone-resistant isolates were multiresistant. Although multiresistance was most prevalent (63%) in isolates showing high-level ciprofloxacin resistance, it was still highly prevalent (41%) in nalidixic acid resistant isolates with low-level ciprofloxacin resistance. Multiresistance was more frequent among singleton isolates (61%) than clonal isolates (40%) of quinolone resistant Escherichia coli. Ciprofloxacin resistance was associated with certain specific clones, among them the globally distributed clonal Group A. However, there was no significant difference in the overall degree of clonality between quinolone sensitive and resistant isolates. Ciprofloxacin resistance was positively associated with phylogroup D and negatively associated with phylogroup B2. This correlation was not associated with clonal isolates. Conclusion This study supports earlier findings of association between ciprofloxacin resistance and resistance to other antibiotics. The prevalence of multiresistance in quinolone-resistant isolates that have not yet developed high-level ciprofloxacin resistance suggest that multiresistance arises early in the development of quinolone resistance. This is consistent with exposure to quinolones causing quinolone resistance by mutations and mobilization of multiresistance elements by induction of the SOS response. The spread of clones seems to be less important than previously reported in regard to emergence of quinolone resistance and multiresistance as both are associated primarily with singleton isolates.

2014-01-01

220

Antibacterial polyelectrolyte-coated Mg alloys for biomedical applications  

NASA Astrophysics Data System (ADS)

This study deals with two biomedical subjects: corrosion rates of polyelectrolyte-coated magnesium (Mg) alloys, mainly used for biomedical purposes, and antibacterial properties of these alloys. Thin sheets of Mg alloys were coated with cationic polyelectrolyte chitosan (CHI) and anionic polyelectrolyte carboxymethyl cellulose (CMC) using a layer-by-layer coating method and then embedded with antibacterial agents under vacuum. Electrochemical impedance spectroscopy was employed to analyze these samples in order to detect their corrosion properties at different conditions. In the electrochemical analysis section, a corrosion rate of 72 mille inches per year was found in a salt solution for the sample coated with a 12 phosphonic acid self-assembled monolayer and 9 CHI/CMC multilayers. In the antibacterial tests, gentamicin was used to investigate the effects of the drug embedded with the coated surfaces against the Escherichia coli (E. coli) bacteria. Antibacterial studies were tested using the disk diffusion method. Based on the standard diameter of the zone of inhibition chart, the antibacterial diffusion from the surface strongly inhibited bacterial growth in the regions. The largest recorded diameter of the zone of inhibition was 50 mm for the pre-UV treated and gentamicin-loaded sample, which is more than three times the standard diameter.

Seraz, Md. S.; Asmatulu, R.; Chen, Z.; Ceylan, M.; Mahapatro, A.; Yang, S. Y.

2014-04-01

221

Novel Antibacterial Nanofibrous PLLA Scaffolds  

PubMed Central

In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NS-scaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy.

Feng, Kai; Sun, Hongli; Bradley, Mark A.; Dupler, Ellen J.; Giannobile, William V.; Ma, Peter X.

2010-01-01

222

Use of quinolones for treatment of ear and eye infections.  

PubMed

Malignant otitis externa is a severe, necrotizing infection of the external auditory canal which is sometimes fatal. The traditional antimicrobial treatment has usually been the combination of an antipseudomonal beta-lactam and an aminoglycoside, given intravenously for 4 to 8 weeks. Over 100 patients have been treated with a fluoroquinolone alone, most commonly ciprofloxacin given by mouth in a dosage of 750 mg b.i.d. for 6 to 12 weeks. About 90% of patients have been cured. Treatment with a quinolone has the advantage over older treatments that it can be given orally and has a low rate of side-effects. The ocular penetration of the fluoroquinolones has been studied in patients with unifected eyes. After the administration of a single dose of ciprofloxacin, pefloxacin, ofloxacin or norfloxacin, penetration into the aqueous humor, expressed as the ratio of the peak concentration in the aqueous humor to that in the serum, is about 20%. The penetration of ciprofloxacin into the vitreous humor, based primarily on the data from one report, is about 20%. The concentrations are likely to be higher after repeated doses or in the inflamed eye. Whether the concentrations achieved will be adequate for therapeutic or prophylactic purposes has not been determined. PMID:1864290

Barza, M

1991-04-01

223

Magnesium Deficiency Induces Joint Cartilage Lesions in Juvenile Rats Which Are Identical to Quinolone-Induced Arthropathy  

Microsoft Academic Search

Quinolones accumulate in cartilage, and because they form chelate complexes with divalent cations, they possess the potential to induce a deficiency of functionally available magnesium. To test the hypothesis that quinolone-induced arthropathy is caused (or aggravated) by magnesium deficiency in cartilage, we induced magnesium deficiency by feeding juvenile rats a magnesium-deficient diet for 9 days and treated the rats with

RALF STAHLMANN; CHRISTIAN FORSTER; MEHDI SHAKIBAEI; JURGEN VORMANN; THEODOR GUNTHER; ANDHANS-JOACHIM MERKER

1995-01-01

224

Negativity of the Basophil Activation Test in Quinolone Hypersensitivity: A Breakthrough for Provocation Test Decision-Making  

Microsoft Academic Search

Background: Quinolone hypersensitivity reactions are being more frequently reported. Skin tests in investigations of patients are known to not be fully reliable. The provocation test thus remains the gold standard in the definitive diagnosis of allergy, despite the risks involved. The aim of this study was to evaluate basophil activation tests (BATs) in the diagnosis of immediate-type reactions to quinolones.

Paul Rouzaire; Audrey Nosbaum; Laure Denis; Françoise Bienvenu; Frédéric Bérard; Grégoire Cozon; Jacques Bienvenu

2012-01-01

225

A copper-mediated cross-coupling approach for the synthesis of 3-heteroaryl quinolone and related analogues.  

PubMed

An efficient and practical method for the direct cross-coupling between quinolones and a range of azoles was developed via copper-mediated C-H functionalization. This synthetic strategy provides a convenient access to a variety of C3-heteroaryl quinolones, quinolinone, nalidixic acid, uracil, pyridone and chromone derivatives, which are prominent structural motifs in many biologically active compounds. PMID:24968218

Shin, Sanghye; Kim, Yechan; Kim, Kiho; Hong, Sungwoo

2014-08-14

226

[The rapid microbiological control of the efficacy of the antibacterial therapy of bacteremia and septicemia].  

PubMed

No previous isolation of the agent on the media is needed in using a new microbiological express-method of automatic control over antibacterial therapy of bacteremia and septicemia. The method is efficient in determination of sensitivity to the drug of the whole heterogeneous population of bacteria. It does not predict efficacy of antibacterial therapy but states the presence or absence of the effect in vivo. The method is integral, evaluates antibacterial plasma titer suggesting adequate correction. The duration of the test is maximum 12 h that is 3-4 times less than other methods. PMID:9245063

Kotliarova, G A; Lopatkin, N A; Kondrat'eva, E M; Perepanova, T S

1997-01-01

227

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

PubMed

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. PMID:22118907

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

2012-02-01

228

Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers  

PubMed Central

The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.

2014-01-01

229

Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers.  

PubMed

The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone. PMID:24720377

Nilsen, Aaron; Miley, Galen P; Forquer, Isaac P; Mather, Michael W; Katneni, Kasiram; Li, Yuexin; Pou, Sovitj; Pershing, April M; Stickles, Allison M; Ryan, Eileen; Kelly, Jane Xu; Doggett, J Stone; White, Karen L; Hinrichs, David J; Winter, Rolf W; Charman, Susan A; Zakharov, Lev N; Bathurst, Ian; Burrows, Jeremy N; Vaidya, Akhil B; Riscoe, Michael K

2014-05-01

230

Mechanisms of Resistance in Nontyphoidal Salmonella enterica Strains Exhibiting a Nonclassical Quinolone Resistance Phenotype?  

PubMed Central

Nontyphoidal Salmonella enterica strains with a nonclassical quinolone resistance phenotype were isolated from patients returning from Thailand or Malaysia to Finland. A total of 10 isolates of seven serovars were studied in detail, all of which had reduced susceptibility (MIC ? 0.125 ?g/ml) to ciprofloxacin but were either susceptible or showed only low-level resistance (MIC ? 32 ?g/ml) to nalidixic acid. Phenotypic characterization included susceptibility testing by the agar dilution method and investigation of efflux activity. Genotypic characterization included the screening of mutations in the quinolone resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE by PCR and denaturing high-pressure liquid chromatography and the amplification of plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, qnrS, qnrD, aac(6?)-Ib-cr, and qepA by PCR. PMQR was confirmed by plasmid analysis, Southern hybridization, and plasmid transfer. No mutations in the QRDRs of gyrA, gyrB, parC, or parE were detected with the exception of a Thr57-Ser substitution within ParC seen in all but the S. enterica serovar Typhimurium strains. The qnrA and qnrS genes were the only PMQR determinants detected. Plasmids carrying qnr alleles were transferable in vitro, and the resistance phenotype was reproducible in Escherichia coli DH5? transformants. These data demonstrate the emergence of a highly mobile qnr genotype that, in the absence of mutation within topoisomerase genes, confers the nontypical quinolone resistance phenotype in S. enterica isolates. The qnr resistance mechanism enables bacteria to survive elevated quinolone concentrations, and therefore, strains carrying qnr alleles may be able to expand during fluoroquinolone treatment. This is of concern since nonclassical quinolone resistance is plasmid mediated and therefore mobilizable.

Gunell, Marianne; Webber, Mark A.; Kotilainen, Pirkko; Lilly, Andrew J.; Caddick, Jonathan M.; Jalava, Jari; Huovinen, Pentti; Siitonen, Anja; Hakanen, Antti J.; Piddock, Laura J. V.

2009-01-01

231

Community acquired quinolone-resistant Escherichia coli pyelonephritis complicated with multiple renal abscesses: a case report.  

PubMed

Acute pyelonephritis is a potentially organ-damaging and life-threatening infection. A 37-year old woman was admitted to Intensive Care Unit in septic shock and multi-organ failure due to acute pyelonephritis with systemic bacterial dissemination caused by a quinolone-resistant Escherichia coli. The patient, a previously healthy woman, reported recurrent episodes of urinary tract infection in the previous 3 years, which were treated with quinolones. Treatment course with broad-spectrum antimicrobial agents reversed her septic shock and multi-organ failure. However, pyelonephritis progressed to intrarenal and perirenal abscesses formation. The patient fully recovered after surgical removal of the infected kidney. PMID:23935324

Katsiari, M; Nikolaou, C; Roussou, Z; Triantopoulou, C; Apessou, D; Platsouka, Ed; Maguina, A

2012-10-01

232

Cytotoxic dimeric quinolone-terpene alkaloids from the root bark of Zanthoxylum rhetsa.  

PubMed

Four quinolone-terpene alkaloids, chelerybulgarine (1), 2'-episimulanoquinoline (3), 2,11-didemethoxyvepridimerine B (4), and rhetsidimerine (5) were isolated from the root bark of Zanthoxylum rhetsa DC. Chelerybulgarine (1) is a C-C linked terpene alkaloid where the C-6 of dihydrochelerythrine is linked to C-11 of the sesquiterpenoid 10?-methoxybulgarene. 2'-Episimulanoquinoline is a dimeric alkaloid containing dihydrochelerythrine and 8-methoxy-N-methylflindersine moieties, whereas 2,11-didemethoxyvepridimerine B and rhetsidimerine are dimeric prenylated quinolone alkaloids. Seven of the isolated compounds exhibited weak cytotoxicity when tested against a panel of six human stomach-cancer cell lines. PMID:24768324

Ahsan, Monira; Haque, Mohammad Rashedul; Hossain, Md Belayet; Islam, Sheikh Nazrul; Gray, Alexander I; Hasan, Choudhury Mahmood

2014-07-01

233

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

PubMed Central

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.

Cruz, Giovanna Rincon; Radice, Marcela; Sennati, Samantha; Pallecchi, Lucia; Rossolini, Gian Maria; Gutkind, Gabriel; Conza, Jose Alejandro Di

2013-01-01

234

Multi-residue method for the detection of veterinary drugs in distillers grains by liquid chromatography-Orbitrap high resolution mass spectrometry.  

PubMed

Distillers Grain (DG) is an important by-product of ethanol production. The ethanol production process uses only the starch portion of the plant and all the remaining nutrients, protein, fat, minerals, and vitamins remain in DGs, a valuable feed material for livestock. The use of antimicrobial drugs is helpful to limit harmful bacterial growth during the early part of the fermentation process. This can lead to the possible presence of contaminants in the by-products that are used in the food and feed industries, resulting in a major concern for the development of bacterial resistance in both humans and animals. To facilitate the detection of antimicrobial and other commonly used veterinary drugs in DGs, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed targeting a wide range of 12 chemical classes of anti-bacterial substances and drugs, such as ionophore and non-ionophore authorized coccidiostats, banned coccidiostats, macrolides, tetracyclines, nitroimidazoles, amphenicols, quinolones, sulphonamides, tranquilizers, non-steroidal anti-inflammatory drugs and benzimidazoles. Following a simple and fast extraction step with a mixture of organic solvents, the extract was directly injected into the LC coupled to an Orbitrap mass analyzer. The identification of residues is based on accurate mass measurement. The high mass resolution of 50,000 full width at half maximum (FWHM) and corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in such a complex matrix. A single-laboratory validation procedure was carried out evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance for precision and trueness, and allowed the determination of the compounds at low concentration. The proposed multi-method demonstrated that liquid chromatography coupled to an Orbitrap mass spectrometer is a promising analytical technique, suitable for official residue control of a variety of veterinary drugs in DGs supporting feed safety policies. PMID:24239439

Kaklamanos, George; Vincent, Ursula; von Holst, Christoph

2013-12-27

235

Quinolone Resistance Due to Reduced Target Enzyme Expression  

PubMed Central

We report for the first time low-level quinolone resistance mediated by decreased expression of topoisomerase IV in Staphylococcus aureus. A single-step mutant of wild-type S. aureus strain ISP794, P18 selected by using twice the MIC of premafloxacin, had four- and four- to eightfold greater MICs of premafloxacin and ciprofloxacin, respectively, than the wild type. Sequencing of parEC and gyrBA with their promoter regions revealed a point mutation (G?A) 13 bp upstream of the start codon of parE. Genetic linkage studies showed that there was a high level of correlation between the mutation and the resistance phenotype, and allelic exchange confirmed the contribution of the mutation to resistance. Decreased expression of ParE and decreased steady-state levels of parEC transcripts in P18 and in resistant allelic exchange mutants were observed. The steady-state levels of gyrBA and topB transcripts were increased in P18 but not in two resistant allelic exchange mutants, and sequencing upstream of either gene did not reveal a difference between ISP794 and P18. The steady-state levels of topA transcripts were similar in the various strains. Growth competition experiments performed at 30, 37, and 41°C with a susceptible allelic exchange strain and a resistant allelic exchange strain suggested that loss of fitness was associated with reduced levels of ParE at 41°C. However, P18 had a growth advantage over ISP794 at all temperatures, suggesting that a compensatory mechanism was associated with the increased levels of gyrBA and topB transcripts. Thus, reduced levels of ParE appear to be compatible with cell survival, although there may be a fitness cost during rapid cell multiplication, which might be overcome by compensatory mechanisms without reversion of the resistance phenotype.

Ince, Dilek; Hooper, David C.

2003-01-01

236

3-Aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration.  

PubMed

Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC(50) index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents. PMID:12036363

Joseph, Benoît; Darro, Francis; Béhard, Aurélie; Lesur, Brigitte; Collignon, Françoise; Decaestecker, Christine; Frydman, Armand; Guillaumet, Gérald; Kiss, Robert

2002-06-01

237

The Toxoplasma gondii type-II NADH dehydrogenase TgNDH2-I is inhibited by 1-hydroxy-2-alkyl-4(1H)quinolones.  

PubMed

The apicomplexan parasite Toxoplasma gondii does not possess complex I of the mitochondrial respiratory chain, but has two genes encoding rotenone-insensitive, non-proton pumping type-II NADH dehydrogenases (NDH2s). The absence of such "alternative" NADH dehydrogenases in the human host defines these enzymes as potential drug targets. TgNDH2-I and TgNDH2-II are constitutively expressed in tachyzoites and bradyzoites and are localized to the mitochondrion as shown by epitope tagging. Functional expression of TgNDH2-I in the yeast Yarrowia lipolytica as an internal enzyme, with the active site facing the mitochondrial matrix, permitted growth in the presence of the complex I inhibitor DQA. Bisubstrate kinetics of TgNDH2-I measured within Y. lipolytica mitochondrial membrane preparations were in accordance with a ping-pong mechanism. Using inhibition kinetics we demonstrate here that 1-hydroxy-2-alkyl-4(1)quinolones with long alkyl chains of C(12) (HDQ) and C(14) are high affinity inhibitors for TgNDH2-I, while compounds with shorter side chains (C(5) and C(6)) displayed significantly higher IC(50) values. The efficiency of the various quinolone derivatives to inhibit TgNDH2-I enzyme activity mirrors their inhibitory potency in vivo, suggesting that a long acyl site chain is critical for the inhibitory potential of these compounds. PMID:18786503

Lin, San San; Kerscher, Stefan; Saleh, Ahmad; Brandt, Ulrich; Gross, Uwe; Bohne, Wolfgang

2008-11-01

238

EmmdR, a New Member of the MATE Family of Multidrug Transporters, Extrudes Quinolones from Enterobacter cloacae  

PubMed Central

We cloned a gene, ECL_03329, from the chromosome of Enterobacter cloacae ATCC13047, using a drug-hypersensitive Escherichia coli KAM32 cell as the host. We show here that this gene, designated emmdR, is responsible for multidrug resistance in E. cloacae. E. coli KAM32 host cells containing the cloned emmdR gene (KAM32/pEMMDR28) showed decreased susceptibilities to benzalkonium chloride, norfloxacin, ciprofloxacin, levofloxacin, ethidium bromide, acriflavine, rhodamine6G, and trimethoprim. emmdR-deficient E. cloacae cells (Ec?emmdR) showed increased susceptibilities to several of the antimicrobial agents tested. EmmdR has twelve predicted transmembrane segments and some shared identity with members of the Multidrug and Toxic Compound Extrusion (MATE) family of transporters. Study of the antimicrobial agent efflux activities revealed that EmmdR is an H+-drug antiporter but not a Na+ driven efflux pump. These results indicate that EmmdR is responsible for multidrug resistance and pumps out quinolones from E. cloacae.

He, Gui-Xin; Thorpe, Conner; Wash, Dennis; Crow, Robert; Chen, Hui-Zhong; Kumar, Sanath; Varela, Manuel F.

2011-01-01

239

Escherichia coli resistant to cephalosporins and quinolones is still susceptible to the cephalosporin-quinolone ester Ro 23-9424.  

PubMed Central

Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin (desacetylcefotaxime) linked through an ester bond to a fluoroquinolone (fleroxacin). Its activity against mutants of Escherichia coli TE18 resistant to both antibacterial components was examined. E. coli TE18 overproduces the AmpC beta-lactamase and is resistant to several cephalosporins, including desacetylcefotaxime (MIC, 50 micrograms/ml), although it is still susceptible to Ro 23-9424 (MIC, 0.2 microgram/ml). Thirty-five spontaneous, two-step mutants of E. coli TE18 which were resistant to fleroxacin (MIC, 50 micrograms/ml) were isolated. In the mutants, replicative DNA biosynthesis (permeabilized cells) was resistant to fleroxacin, and some mutants had porin abnormalities. However, all remained susceptible to Ro 23-9424 (MIC, 0.5 microgram/ml). Examination of beta-lactamase activity in the parent strain revealed that it hydrolyzes desacetylcefotaxime more rapidly than it does Ro 23-9424. Thus, Ro 23-9424 may be less susceptible to the gram-negative, chromosomal beta-lactamases that hydrolyze several broad-spectrum cephalosporins and may be effective in cases in which neither of its two components is active. Images

Pace, J; Bertasso, A; Georgopapadakou, N H

1991-01-01

240

Detection of Quinolone-Resistance Mutations In Salmonella Spp. Strains of Epidemic and Poultry Origin  

PubMed Central

Mutations into codons Aspartate-87 (62%) and Serine-83 (38%) in QRDR of gyrA were identified in 105 Salmonella strains resistant to nalidixic acid (94 epidemic and 11 of poultry origin). The results show a high incidence of mutations associated to quinolone resistance but suggest association with others mechanisms of resistance.

de Souza, Roberta Barreiros; Magnani, Marciane; Ferrari, Rafaela Gomes; Kottwitz, Luciana Bill Mikito; Sartori, Daniele; Tognim, Maria Cristina Bronharo; de Oliveira, Tereza Cristina R. M.

2011-01-01

241

Synthesis of Some 4-Quinolones and Related Structures for Evaluation as Potential Anti-Malarial Agents.  

National Technical Information Service (NTIS)

The need for effective prophylactic agents in plasmodial infections in humans made it desirable to explore the antimalarial effect of a series of compounds chemically related to endochin (2-methyl-3-n-heptyl-7-methoxy-4(1H)-quinolone). The authors have sy...

A. C. Casey

1973-01-01

242

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

SciTech Connect

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.

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

1990-05-01

243

Two new 3-methoxy-4-quinolone alkaloids from the bark of Sarcomelicope megistophylla.  

PubMed

Two new alkaloids, megistonine I (1) and megistonine II (2), were isolated from the bark of Sarcomelelicope megistophylla. Their structures, which are derived from the 3-methoxy-4-quinolone basic skeleton, were elucidated on the basis of MS and extensive NMR studies. PMID:11145161

Fokialakis, N; Magiatis, P; Mitaku, S; Tillequin, F; Sévenet, T

2000-12-01

244

Prevalence and characterization of quinolone resistance in Laribacter hongkongensis from grass carp and Chinese tiger frog.  

PubMed

Laribacter hongkongensis is a food-borne bacterium associated with community-acquired gastroenteritis and diarrhoea. Quinolone resistance was recently reported in bacterial isolates from aquatic products, but the molecular mechanisms for resistance were still unknown. In this study, a total of 157 L. hongkongensis strains were isolated from grass carps (n = 443) and Chinese tiger frogs (n = 171). Twenty-one ciprofloxacin-resistant strains were analysed for mutations in quinolone resistance-determining regions (QRDR), acquired quinolone resistance (AQR) genes and the role of efflux pumps in resistance. All QRDR mutations in gyrA (codons 85 and 89) and parC (codons 83 and 231) were found to be closely associated with ciprofloxacin resistance. The AQR gene aac(6')-Ib-cr was found in 42.9% (9/21) of the resistant strains, but qnrA, qnrB, qnrC, qnrD, qnrS and qepA were not detected. No significant change of MICs to ciprofloxacin was observed in the presence of an efflux pump inhibitor, indicating the role of efflux pump was probably absent. All 21 ciprofloxacin-resistant strains showed different electrophoretic patterns, which suggested they were not genetically related. These data highlight the importance of QRDR mutations and the AQR gene aac(6')-Ib-cr during the development of quinolone resistance in a heterogeneous population of L. hongkongensis. PMID:23906590

Chen, Ding-Qiang; Yang, Ling; Luo, Yu-Ting; Mao, Min-Jie; Lin, Yong-Ping; Wu, Ai-Wu

2013-10-01

245

Screening of antibacterial activities of twenty-one oxygenated monoterpenes.  

PubMed

Plant essential oils are widely used as fragrances and flavours in the cosmetic, perfume, drug and food industries. Oxygenated monoterpenes are widespread components of the essential oils, usually occurring in high amount. In this paper, the antibacterial activities of twenty-one oxygenated monoterpenes (borneol, borneol acetate, camphor, carvone, 1,8-cineole, citronellal, beta-citronellol, dihydrocarvone, fenchol, fenchone, geraniol acetate, isomenthol, limonene oxide, linalool, linalool acetate, nerol, nerol acetate, terpinen-4-ol, alpha-terpineol, menthol and menthone) and penicillin (standard antibiotic) were determined using a disc diffusion method (in vitro) against 63 bacterial strains, belonging to 37 different genera and 54 species (plant, food and clinic origins). The results showed that the oxygenated monoterpenes exhibited a variable degree of antibacterial activities. These compounds also inhibited the growth of bacterial strains by producing a weak zone of inhibition from 7 to 11 mm in diameter, depending on the susceptibility of the tested bacteria. Among the tested compounds, nerol, linalool alpha-terpineol, fenchol and terpinen-4-ol showed antibacterial activity at a broad spectrum. However, their antibacterial activities were lower than those of penicillin. In contrast to these compounds, camphor and 1,8-cineole exhibited no inhibition effects on the growth of all tested bacteria. PMID:17913064

Kotan, Recep; Kordali, Saban; Cakir, Ahmet

2007-01-01

246

Evaluation of the Antibacterial Activity of Patchouli Oil  

PubMed Central

In the present study, the antimicrobial tests of patchouli oil were studied by using molecular docking technology and antimicrobial test in vitro. Five biological macromolecule enzymes, required by the bacteria in the process of biosynthesis were selected as target molecules. Five antibiotics benzylpenicillin, sulfadiazine, trimethoprim, rifampicin and ciprofloxacin, which are generally acknowledged as antibacterial drugs, were selected as reference compounds. The 3 three-dimensional (3D) structures of the 5 reference compounds and 26 compounds from patchouli oil were established by using surflex-dock software (8.1). And the 3D structures of five biological macromolecule enzymes derived from Protein Data Bank (PDB). Molecular docking was carried out between the 31 chemical compounds (ligands) and the 5 enzymes (receptors) by using surflex-dock function. Furthermore, the antibacterial effects of 31 chemical compounds were investigated by the scoring function after molecular docking was completed. By comparing the scoring result of 26 compounds in patchouli oil with 5 compared components, we inferred antibacterial activity in about 26 compounds in patchouli oil. On the other hand, six frequently-used pathogenic bacteria were selected for antimicrobial test in vitro, patchouli oil and its two major compounds: (-)-patchouli alcohol and pogostone, which their contents exceeded 60% in patchouli oil samples, were selected antibacterial agents. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined. Molecular docking technology and antimicrobial test in vitro proved that patchouli oil had strong antimicrobial effects. Particularly, pogostone and (-)-patchouli alcohol have potent antimicrobial activity.

Yang, Xian; Zhang, Xue; Yang, Shui-Ping; Liu, Wei-Qi

2013-01-01

247

Synthesis and chromatographic enantioresolution of anti-HIV quinolone derivatives.  

PubMed

The successful enantioseparation of five 6-desfluoroquinolones with three polysaccharide-based stationary phases (namely, the cellulose-based Chiralpak IB and the two amylose-based Chiralpak AD-H and Lux Amylose-2) is herein described. The investigated species differ for the nature of substituents and/or the position of the stereogenic centre on the quinolone scaffold. The effect on the enantioseparation performance exerted by the different morphology of the cellulose-based and amylose-based polymers, was systematically evaluated for all compounds. In this frame, the impact of alternative alcoholic (ethanol, 2-ethoxyethanol, methanol, 2-propanol) and acidic (acetic, methanesulfonic and trifluoroacetic acid) modifiers as well as of a "non-standard" solvent (chloroform), was investigated in normal phase conditions along with the stereo-electronic peculiarities of the selected polymers. While 7-[4-(1,3-benzothiazol-2-yl)-2-methyl-1-piperazinyl]-1-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (1) was enantioresolved with conventional normal-phase conditions by means of the largely employed amylose-based Chiralpak AD-H column, the recruitment of a bulky alcohol (2-ethoxyethanol) succeeded in the enantioresolution of 6-amino-1-methyl-7-[2-methyl-4-(2-pyridinyl)-1-piperazinyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (2) and 6-amino-1-[1-(hydroxymethyl)propyl]-4-oxo-7-(4-pyridin-2-ylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (3) with the same column. The use of the amylose-based Lux Amylose-2 column, carrying both an electro-withdrawing (chlorine) and an electro-donating (methyl) group on the carbamate residue, allowed to get 6-amino-1-methyl-4-oxo-7-[3-(2-pyridinyl)-1-pyrrolidinyl]-1,4-dihydro-3-quinolinecarboxylic acid hydrochloride (4) enanantioresolved, and 6-amino-1-methyl-4-oxo-7-(3-pyridin-2-ylpiperidin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (5) enantioseparated. PMID:21807200

Natalini, Benedetto; Sardella, Roccaldo; Massari, Serena; Ianni, Federica; Tabarrini, Oriana; Cecchetti, Violetta

2011-09-15

248

Synthesis of methoxy-2-quinolones via pummerer-type cyclization of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides.  

PubMed

The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the synthesis of methoxy-2-quinolones. PMID:11145131

Toda, J; Sakagami, M; Goan, Y; Simakata, M; Saitoh, T; Horiguchi, Y; Sano, T

2000-12-01

249

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

PubMed

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 ?g/kg. The precision for determining the quinolones was <19.39%. The proposed method was successfully developed for the determination of quinolones in real cosmetic samples. PMID:24610829

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

2014-05-01

250

Synthesis and antibacterial activity of doxycycline neoglycosides.  

PubMed

A set of 37 doxycycline neoglycosides were prepared, mediated via a C-9 alkoxyamino-glycyl-based spacer reminiscent of that of tigecycline. Subsequent in vitro antibacterial assays against representative drug-resistant Gram negative and Gram positive strains revealed a sugar-dependent activity profile and one doxycycline neoglycoside, the 2'-amino-?-D-glucoside conjugate, to rival that of the parent pharmacophore. In contrast, the representative tetracycline-susceptible strain E. coli 25922 was found to be relatively responsive to a range of doxycycline neoglycosides. This study also extends the use of aminosugars in the context of neoglycosylation via a simple two-step strategy anticipated to be broadly applicable for neoglycorandomization. PMID:23987662

Zhang, Jianjun; Ponomareva, Larissa V; Marchillo, Karen; Zhou, Maoquan; Andes, David R; Thorson, Jon S

2013-09-27

251

Substituted Hydroxyapatites with Antibacterial Properties  

PubMed Central

Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.

Kolmas, Joanna; Groszyk, Ewa; Kwiatkowska-Rozycka, Dagmara

2014-01-01

252

Antibacterial Biomimetic Hybrid Films  

PubMed Central

In this work, we present a novel method to prepare a hybrid coating based on dextran grafted to a substrate and embedded with silver nanoparticles (Ag NPs). First, the Ag NPs are synthesized in situ in the presence of oxidized dextran in solution. Second, the oxidized dextran is exposed to an amine functionalized surface resulting in the simultaneous grafting of dextran and the trapping of Ag NPs within the layer. The NP loading is controlled by the concentration of silver nitrate, which is 2 mM (DEX-Ag2) and 5 mM (DEX-Ag5). The dried film thickness increases with silver nitrate concentration from 2 nm for dextran to 7 nm and 12 nm for DEX-Ag2 and DEX-Ag5, respectively. The grafted dextran film displays features with a diameter and height of ~ 50 nm and 2 nm, respectively. For the DEX-Ag2 and DEX-Ag5, the dextran features as well as individual Ag NPs (~ 5 nm) and aggregates of Ag NPs are observed. Larger and more irregular aggregates are observed for DEX-Ag5. Overall, the Ag NPs are embedded in the dextran film as suggested by AFM and UVO studies. In terms of its antimicrobial activity, DEX-Ag2 resists bacterial adhesion to a greater extent than DEX-Ag5, which in turn is better than dextran and silicon. Because these antibacterial hybrid coatings can be grafted to a variety of surfaces, many biomedical applications can be envisioned, ranging from coating implants to catheters.

Ferrer, M. Carme Coll; Hickok, Noreen J.; Eckmann, David M.; Composto, Russell J.

2012-01-01

253

Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs  

PubMed Central

Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus.

Viswanathan, V.; Phadatare, A. G.; Mukne, Alka

2014-01-01

254

Single-Nucleotide Polymorphism Mutation Spectra and Resistance to Quinolones in Salmonella enterica Serovar Enteritidis with a Mutator Phenotype  

Microsoft Academic Search

Resistance to quinolone antibiotics has been associated with single-nucleotide polymorphisms (SNPs) in the quinolone resistance-determining region (QRDR) of gyrA. Mutations in the gyrA gene were compared by using mutant populations derived from wild-type Salmonella enterica serovar Enteritidis and its isogenic mutS::Tn10 mutator counterpart. Spontaneous mutants arising during nonselective growth were isolated by selection with either nalidixic acid, enrofloxacin, or ciprofloxacin.

Dan D. Levy; Bhavana Sharma; Thomas A. Cebula

2004-01-01

255

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

PubMed

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. PMID:21646485

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

2011-08-01

256

Comparison of drug utilization of most commonly used drugs in Poland and Czech Republic.  

PubMed

Utilization of drugs from the following groups: antibacterial, cardiovascular, gastrointestinal and respiratory tract diseases in Poland and Czech Republic was analyzed. The most commonly sold drugs were among antibacterial drugs, viz., doxycycline (4.5DDD/1000 inh./day in Poland; 3.3 in Czech Republic), co-trimoxazole (Poland-2.9; Czech Republic 2.5), ampicilline and amoxicilline; among gastrointestinal drugs, ascorbic acid (Poland 42.2; Czech Republic 59.3), among respiratory drugs, sodium cromoglicate in Poland and bromhexine in Czech Republic, and among cardiovascular drugs, enalapril in Poland and diuretics with potasium sparing drug in Czech Republic. In general, the leading drugs in Poland and Czech Republic, were the same. All drugs with highest utilization were on the Essential Drug List. Some differences in drug utilization between these two countries could result from the prevalence of particular diseases in each population and physician's prescribing patterns. PMID:9821399

Ruszczy?ska, E; Biba, V; Stika, L; Czarnecki, A

1998-01-01

257

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

PubMed

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. PMID:24570454

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

2014-02-01

258

Plasmid-Related Quinolone Resistance Determinants in Epidemic Vibrio parahaemolyticus, Uropathogenic Escherichia coli, and Marine Bacteria from an Aquaculture Area in Chile.  

PubMed

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. PMID:24760167

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

2014-08-01

259

Probenecid and the antibacterial activity of cephradine in vivo.  

PubMed

The influence of probenecid on the concentrations in blood and antibacterial efficacy of cephradine was studied in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the thighs of irradiated, granulocytopenic mice. Probenecid was given 1 hr later, just before the administration of cephradine. The control animals received only the vehicle. Concentrations of cephradine in blood were determined for 2 hr; the antibacterial activity was estimated from bacterial counts made in the homogenized individual thighs. The blood concentrations of cephradine were 1.77 times higher in the probenecid-treated animals than in the controls. The potency ratio for doses was 2.41, the potency ratio for the areas under the drug concentration in blood vs. time curves was 1.34, and that for the peak blood concentrations was 1.43. PMID:351091

Kunst, M W; Mattie, H

1978-06-01

260

Interaction of vanadium (IV) solvates (L) with second-generation fluoroquinolone antibacterial drug ciprofloxacin: Spectroscopic, structure, thermal analyses, kinetics and biological evaluation (L = An, DMF, Py and Et3N)  

NASA Astrophysics Data System (ADS)

The preparation and characterization of the new solid complexes [VO(CIP)2L]SO4?nH2O, where L = aniline (An), dimethylformamide (DMF), pyridine (Py) and triethylamine (Et3N) in the reaction of ciprofloxacin (CIP) with VO(SO4)2·2H2O in ethanol. The isolated complexes have been characterized with their melting points, elemental analysis, IR spectroscopy, magnetic properties, conductance measurements, UV-Vis. and 1H NMR spectroscopic methods and thermal analyses. The results supported the formation of the complexes and indicated that ciprofloxacin reacts as a bidentate ligand bound to the vanadium ion through the pyridone oxygen and one carboxylato oxygen. The activation energies, E*; entropies, ?S*; enthalpies, ?H*; Gibbs free energies, ?G*, of the thermal decomposition reactions have been derived from thermo gravimetric (TGA) and differential thermo gravimetric (DTG) curves, using Coats-Redfern and Horowitz-Metzeger methods. The lowest energy model structure of each complex has been proposed by using the density functional theory (DFT) at the B3LYP/CEP-31G level of theory. The ligand and their metal complexes were also evaluated for their antibacterial activity against several bacterial species, such as Bacillus Subtilis (B. Subtilis), Staphylococcus aureus (S. aureus), Nesseria Gonorrhoeae (N. Gonorrhoeae), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli).

Zordok, Wael A.

2014-08-01

261

Interaction of vanadium (IV) solvates (L) with second-generation fluoroquinolone antibacterial drug ciprofloxacin: Spectroscopic, structure, thermal analyses, kinetics and biological evaluation (L=An, DMF, Py and Et3N).  

PubMed

The preparation and characterization of the new solid complexes [VO(CIP)2L]SO4?nH2O, where L=aniline (An), dimethylformamide (DMF), pyridine (Py) and triethylamine (Et3N) in the reaction of ciprofloxacin (CIP) with VO(SO4)2·2H2O in ethanol. The isolated complexes have been characterized with their melting points, elemental analysis, IR spectroscopy, magnetic properties, conductance measurements, UV-Vis. and (1)H NMR spectroscopic methods and thermal analyses. The results supported the formation of the complexes and indicated that ciprofloxacin reacts as a bidentate ligand bound to the vanadium ion through the pyridone oxygen and one carboxylato oxygen. The activation energies, E(*); entropies, ?S(*); enthalpies, ?H(*); Gibbs free energies, ?G(*), of the thermal decomposition reactions have been derived from thermo gravimetric (TGA) and differential thermo gravimetric (DTG) curves, using Coats-Redfern and Horowitz-Metzeger methods. The lowest energy model structure of each complex has been proposed by using the density functional theory (DFT) at the B3LYP/CEP-31G level of theory. The ligand and their metal complexes were also evaluated for their antibacterial activity against several bacterial species, such as Bacillus Subtilis (B. Subtilis), Staphylococcus aureus (S. aureus), Nesseria Gonorrhoeae (N. Gonorrhoeae), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). PMID:24762540

Zordok, Wael A

2014-08-14

262

Antibacterial polyphenol from Erodium glaucophyllum.  

PubMed

Geraniin and gallic acid were isolated from the alcohol extract of the aerial parts of Erodium glaucophyllum (Geraniaceae). The identity of the compounds was verified through different physical and spectrometric methods. The antibacterial and antifungal activity of geraniin is presented. PMID:14577629

Gohar, Ahmed A; Lahloub, Mohammed E; Niwa, Masatake

2003-01-01

263

Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.  

PubMed

Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains. PMID:21831637

Li, Xiaoming; Hilgers, Mark; Cunningham, Mark; Chen, Zhiyong; Trzoss, Michael; Zhang, Junhu; Kohnen, Lucy; Lam, Thanh; Creighton, Chris; G C, Kedar; Nelson, Kirk; Kwan, Bryan; Stidham, Mark; Brown-Driver, Vickie; Shaw, Karen J; Finn, John

2011-09-15

264

Identification and Evolution of Drug Efflux Pump in Clinical Enterobacter aerogenes Strains Isolated in 1995 and 2003  

PubMed Central

Background The high mortality impact of infectious diseases will increase due to accelerated evolution of antibiotic resistance in important human pathogens. Development of antibiotic resistance is a evolutionary process inducing the erosion of the effectiveness of our arsenal of antibiotics. Resistance is not necessarily limited to a single class of antibacterial agents but may affect many unrelated compounds; this is termed ‘multidrug resistance’ (MDR). The major mechanism of MDR is the active expulsion of drugs by bacterial pumps; the treatment of Gram negative bacterial infections is compromised due to resistance mechanisms including the expression of efflux pumps that actively expel various usual antibiotics (ß-lactams, quinolones, …). Methodology/Principal Findings Enterobacter aerogenes has emerged among Enterobacteriaceae associated hospital infections during the last twenty years due to its faculty of adaptation to antibiotic stresses. Clinical isolates of E. aerogenes belonging to two strain collections isolated in 1995 and 2003 respectively, were screened to assess the involvement of efflux pumps in antibiotic resistance. Drug susceptibility assays were performed on all bacterial isolates and an efflux pump inhibitor (PAßN) previously characterized allowed to decipher the role of efflux in the resistance. Accumulation of labelled chloramphenicol was monitored in the presence of an energy poison to determine the involvement of active efflux on the antibiotic intracellular concentrations. The presence of the PAßN-susceptible efflux system was also identified in resistant E. aerogenes strains. Conclusions/Significance For the first time a noticeable increase in clinical isolates containing an efflux mechanism susceptible to pump inhibitor is report within an 8 year period. After the emergence of extended spectrum ß-lactamases in E. aerogenes and the recent characterisation of porin mutations in clinical isolates, this study describing an increase in inhibitor-susceptible efflux throws light on a new step in the evolution of mechanism in E. aerogenes.

Garnotel, Eric; Nicolas, Pierre; Davin-Regli, Anne; Pages, Jean-Marie

2008-01-01

265

4(1H)-Quinolones with Liver Stage Activity against Plasmodium berghei  

PubMed Central

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-Luccon) 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.

LaCrue, Alexis N.; Saenz, Fabian E.; Cross, R. Matthew; Udenze, Kenneth O.; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S.; Manetsch, Roman

2013-01-01

266

Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli.  

PubMed Central

The gene parC encodes the A subunit of topoisomerase IV of Escherichia coli. Mutations in the parC region analogous to those in the quinolone resistance-determining region of gyrA were investigated in 27 clinical isolates of E. coli for which ciprofloxacin MICs were 0.0007 to 128 micrograms/ml. Of 15 isolates for which ciprofloxacin MICs were > or = 1 microgram/ml, 8 showed a change in the serine residue at position 80 (Ser-80), 4 showed a change in Glu-84, and 3 showed changes in both amino acids. No mutations were detected in 12 clinical isolates for which ciprofloxacin MICs were < or = 0.25 micrograms/ml. These findings suggest that ParC from E. coli may be another target for quinolones and that mutations at residues Ser-80 and Glu-84 may contribute to decreased fluoroquinolone susceptibility.

Vila, J; Ruiz, J; Goni, P; De Anta, M T

1996-01-01

267

Comparative activities of eight quinolones against members of the Bacteroides fragilis group.  

PubMed Central

The in vitro activities of five new quinolones (clinafloxacin [CI-960 or PD-127391], BAY Y 3118, E-4868, E-5065, and E-5068) against 100 Bacteroides fragilis group bacterial isolates were compared with those of ciprofloxacin, ofloxacin, and sparfloxacin. Overall, E-5068 was the most active in vitro (MIC for 90% of isolates tested [MIC90], 0.25 microgram/ml); this was followed by clinafloxacin and BAY Y 3118 (MIC90, 0.5 microgram/ml). Ciprofloxacin, sparfloxacin, and ofloxacin were the least active (MIC90s, 64, 16, and 16 micrograms/ml, respectively). B. fragilis and Bacteroides caccae were more susceptible than the other members of the B. fragilis group to all of the quinolones tested.

Borobio, M V; Conejo, M; Ramirez, E; Suarez, A I; Perea, E J

1994-01-01

268

Xenobiotic biotransformation of 4-methoxy-N-methyl-2-quinolone, isolated from Zanthoxylum monophyllum.  

PubMed

Phytochemical evaluation of Zanthoxylum monophyllum has led to the isolation of the alkaloid 4-methoxy-N-methyl-2-quinolone (1) with a significant activity against methicillin-resistant Staphylococcus aureus (MRSA), with an IC50 value of 1.5 microg/mL. Xenobiotic biotransformation of 1 has been conducted with the general goal of increasing the bioactivity of the compound and contributing new leads for further pharmacological research. Twenty-nine microorganisms were used for screening and two (Aspergillus flavus and Cunninghamella echinulata var. echinulata) were able to transform compound 1 to 4-methoxy-2-quinolone (2). Structural identification of the compounds was based on NMR, IR, and MS data. PMID:20923009

Rodríguez-Guzmán, Raquel; Radwan, Mohamed M; Burandt, Charles L; Williamson, John S; Ross, Samir A

2010-09-01

269

[Investigation of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae: a multicenter study].  

PubMed

Fluoroquinolones which are in use since 1986, are effective agents both against gram-positive and gram-negative bacteria. Quinolones show bactericidal effect as a result of inhibition of DNA gyrase and topoisomerase IV enzymes. Main quinolone resistance mechanisms are chromosomal mutations in these enzymes and decreased intracellular accumulation due to efflux pumps or decreased membrane uptake. Recently a new quinolone resistance mechanism mediated by plasmids has been defined. These plasmids carry genes called as qnr. Qnr genes do not cause quinolone resistance but they cause decreased quinolone susceptibility and lead to higher minimum inhibitory concentrations. Currently there are qnrA, qnrB, qnrC, qnrD and qnrS genes. This study was aimed to investigate the presence of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae isolates collected from four different centers in Turkey. A total of 647 isolates (387 from Trabzon, Black Sea region; 82 from Canakkale, Trace region; 96 from Ankara, Central Anatolia region; 82 from Tokat, Black Sea region) belonging to the Enterobacteriaceae family collected between May-July 2009, were included in the study. Presence of qnrA, qnrB, qnrS and qnrC genes were investigated by multiplex polymerase chain reaction (PCR) method and confirmed by gene sequencing. The results of the PCR amplification revealed that 2 isolates were positive for qnrA, 12 isolates were positive for qnrB, 4 isolates were positive for qnrC and 10 isolates were positive for qnrS. However, the number of positive strains decreased with the use of gene sequencing, and this method led to the identification of qnrA1 in two isolates [Enterobacter cloacae (code. 796), Salmonella group B (code. 491)], qnrB1 in two isolates [Salmonella group B (code. 491), Citrobacter freundii (code. 768)], qnrB6 in one isolate [Escherichia coli (code. CC1800)], qnrB9 in one isolate [E.coli (code. CC1873)], qnrB24 in one isolate [Citrobacter koseri (code. MP5200)], qnrB27 in one isolate [C.freundii (code. 842)], qnrS1 in two isolates [E.coli (code. CC1705), E.coli (code.159)] and qnrB2 in one isolate [E.coli (code. 843)]. One of the isolates that carried the qnr gene was ciprofloxacin-resistant and two isolates were nalidixic-acid resistant. Transferable quinolone resistance due to the dissemination of qnr genes may have important impacts in terms of infection control and treatment problems. Survey of plasmid mediated quinolone resistance will help to determine the size of the issue and guide the measures that should be taken to avoid escalation of resistance and dissemination problem. PMID:22951649

Coban, Ahmet Y?lmaz; Nohut, Okan Kadir; Tanr?verdi Çayc?, Yeliz; Bayramo?lu, Gülçin; Pirinççiler, Müjgan; Cetinkaya, Ebru; Cekiç Cihan, Ci?dem; Bozdo?an, Bülent; Durup?nar, Belma

2012-07-01

270

Recent Advances in Drugs and Prodrugs Design of Chitosan  

Microsoft Academic Search

The aim of this review is to outline the recent advances in chitosan molecular modeling, especially its usage as a prodrug or drug in a field of antibacterial, anticarcinogenic and antioxidant activity. Polymeric materials like peptides, polysaccharides and other natural products have recently attracted attention as biodegradabile drug car- riers. They can optimize clinical drug application, minimize the undesirable drug

J. Vinsova; E. Vavrikova

271

Induction of plasmid-carried qnrS1 in Escherichia coli by naturally occurring quinolones and quorum-sensing signal molecules.  

PubMed

Naturally occurring quinolone and quinolone-like compounds, such as quinine, 2-hydroxyquinoline, 4-hydroxyquinoline, and 2-heptyl-3-hydroxy-4(1H)-quinolone, increased expression of qnrS1 in Escherichia coli 2.3- to 11.2-fold, similar to the synthetic quinolone ciprofloxacin. In contrast, chromosomal qnrVS1 of Vibrio splendidus was not induced by these compounds. Molecules associated with quorum sensing, such as N-3-hydroxybutyryl-homoserine lactone (HSL), N-hexanoyl-HSL, and N-3-(oxododecanoyl)-HSL, did not show an induction effect on either qnrS1 or qnrVS1 at the tested concentrations. PMID:23689721

Kwak, Yee Gyung; Jacoby, George A; Hooper, David C

2013-08-01

272

Effects of cyclic lipodepsipeptide structural modulation on stability, antibacterial activity and human cell toxicity  

PubMed Central

Bacterial infections are becoming increasingly difficult to treat due to the development and spread of antibiotic resistance. Therefore, identifying novel antibacterial targets and new antibacterial agents capable of treating infections from drug-resistant bacteria is of vital importance. Structurally simple, yet potent fusaricidin or LI-F class of natural products represents a particularly attractive source of candidates for the development of new antibacterial agents. We have synthesized eighteen fusaricidin/LI-F analogs and investigated the effect of their structure modification on conformation, serum stability, antibacterial activity and human cell toxicity. Our findings show that substitution of an ester bond in depsipeptides with an amide bond may afford equally potent analogs with improved stability and greatly decreased cytotoxicity. Lower overall hydrophobicity/amphiphilicity of amide analogs in comparison to their parent depsipeptides, as indicated by the HPLC retention times, may explain dissociation of antibacterial activity and human cell cytotoxicity. These results indicate that amide analogs may have significant advantages over fusaricidin/LI-F natural products and their depsipeptide analogs as lead structures for the development of new antibacterial agents.

Bionda, Nina; Stawikowski, Maciej; Stawikowska, Roma; Cudic, Mare; Lopez-Vallejo, Fabian; Treitl, Daniela; Medina-Franco, Jose

2012-01-01

273

Quinolones for the treatment of skin, soft tissue, bone and prosthetic joint infections  

Microsoft Academic Search

\\u000a The antimicrobial spectrum of activity of the early quinolones (i.e., norfloxacin, ofloxacin, ciprofloxacin) favor potency\\u000a against Gram-negative microorganisms [1, 2]. The newer agents (levofloxacin, gatifloxacin, moxifloxacin) have expanded activity against the Gram-positive microorganisms\\u000a [3, 4] and some of these newer agents which are currently available or in clinical trial (moxifloxacin, gatifloxacin, garenoxacin)\\u000a also demonstrate excellent in vitro activity against the

John M. Embil

274

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.  

PubMed

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions. PMID:2088195

Boeckh, M; Lode, H; Deppermann, K M; Grineisen, S; Shokry, F; Held, R; Wernicke, K; Koeppe, P; Wagner, J; Krasemann, C

1990-12-01

275

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.  

PubMed Central

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.

Boeckh, M; Lode, H; Deppermann, K M; Grineisen, S; Shokry, F; Held, R; Wernicke, K; Koeppe, P; Wagner, J; Krasemann, C

1990-01-01

276

Development of resistance to quinolones in five patients with campylobacteriosis treated with norfloxacin or ciprofloxacin  

Microsoft Academic Search

Development of resistance to nalidixic acid, norfloxacin and ciprofloxacin was observed in five patients withCampylobacter jejuni orCampylobacter coli infection. From all these patients nalidixic acid- and quinolone-susceptible strains were isolated initially, whereas after therapy with norfloxacin or ciprofloxacin strains resistant to these antibiotics were found.Campylobacter strains from the same patient always belonged to the same species and, with the exception

H. Adler-Mosca; J. Lüthy-Hottenstein; G. Martinetti Lucchini; A. Burnens; M. Altwegg

1991-01-01

277

qnrB, Another Plasmid-Mediated Gene for Quinolone Resistance  

Microsoft Academic Search

A novel plasmid-mediated quinolone resistance gene, qnrB, has been discovered in a plasmid encoding the CTX-M-15 -lactamase from a Klebsiella pneumoniae strain isolated in South India. It has less than 40% amino acid identity with the original qnr (now qnrA) gene or with the recently described qnrS but, like them, codes for a protein belonging to the pentapeptide repeat family.

George A. Jacoby; Kelley E. Walsh; Debra M. Mills; Victoria J. Walker; Herin Oh; Ari Robicsek; David C. Hooper

2006-01-01

278

Quinolone-resistant mutations of the gyrA gene of Escherichia coli  

Microsoft Academic Search

DNA fragments of 8.5 kb containing the gyrA gene were cloned from Escherichia coli KL-16 and from four spontaneous gyrA mutants which showed various levels of resistance to quinolones. The gyrA gene was situated at about 4 kb in front of the nrdA gene and transcribed counterclockwise on the E. coli chromosome. It encoded a polypeptide of 875 amino acids

Hiroaki Yoshida; Tsuyoshi Kojima; Jun-ichi Yamagishi; Shinichi Nakamura

1988-01-01

279

Light-induced cleavage of model phenylalanine conjugates based on coumarins and quinolones  

Microsoft Academic Search

In order to evaluate the application of quinolone as a new photocleavable protecting group, in comparison with coumarin, a\\u000a series of model phenylalanine conjugates were prepared by reaction with chloromethylated O and N heterocycles. The photophysical\\u000a properties of the resulting ester conjugates were evaluated as well as the photosensitivity under irradiation at 250, 300,\\u000a 350, and 419 nm. The results obtained

Andrea S. C. Fonseca; M. Sameiro T. Gonçalves; Susana P. G. Costa

2010-01-01

280

Comparative activity of the quinolones against anaerobic bacteria isolated at community hospitals.  

PubMed Central

The in vitro activity of five quinolone compounds, amoxicillin, and clindamycin against 118 strains of anaerobic bacteria isolated at community hospitals was determined by an agar dilution method. Nalidixic acid and cinoxacin had poor activity, and norfloxacin and enoxacin showed relatively poor activity. Ciprofloxacin was active against Bacteroides fragilis, Fusobacterium species, Clostridium perfringens, and gram-positive cocci. At peak levels achievable in the feces, norfloxacin and enoxacin had moderate activity.

Goldstein, E J; Citron, D M

1985-01-01

281

Characterization of ESBLs and associated quinolone resistance in Escherichia coli and Klebsiella pneumoniae isolates from an urban wastewater treatment plant in Algeria.  

PubMed

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. PMID:23952363

Alouache, Souhila; Estepa, Vanesa; Messai, Yamina; Ruiz, Elena; Torres, Carmen; Bakour, Rabah

2014-02-01

282

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

NASA Astrophysics Data System (ADS)

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)(?2-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.

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

283

Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues.  

PubMed

Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinolone (BSTFA 1% TMCS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-l were obtained in 40-77% yields. The esters 2a-j and 2l were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 microM, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7+/-0.04 and 0.8+/-0.09 microM, respectively. Both compounds were not toxic towards the Vero cell line. PMID:16321530

Lucero, Bianca d'A; Gomes, Claudia Regina B; Frugulhetti, Izabel Christina de P P; Faro, Letícia V; Alvarenga, Lise; de Souza, Maria Cecília B V; de Souza, Thiago M L; Ferreira, Vitor F

2006-02-15

284

Simple and sensitive determination of five quinolones in food by liquid chromatography with fluorescence detection.  

PubMed

A simple and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the determination of five different quinolones: enrofloxacin, ciprofloxacin, sarafloxacin, oxolinic acid and flumequine in pork and salmon muscle. The method includes one extraction and clean-up step for the five quinolones together which are detected in two separated HPLC runs by means of their fluorescence. The proposed analytical method involves homogenizing of the tissue sample with 0.05 M phosphate buffer, pH 7.4 and clean-up by Discovery DS-18 cartridges. For chromatographic separation a Symmetry C(18) column is used in two different runs: (1) ciprofloxacin, enrofloxacin and sarafloxacin with acetonitrile-0.02 M phosphate buffer pH 3.0 (18:82) as mobile phase and the detector at excitation wavelength: 280 nm and emission wavelength 450 nm; and (2) oxolinic acid and flumequine with acetonitrile-0.02 M phosphate buffer pH 3.0 (34:66) as mobile phase and excitation wavelength: 312 nm and emission wavelength: 366 nm. Detection limit was as low as 5 ng g(-1), except for sarafloxacin which had a limit of 10 ng g(-1). Standard curves using blank muscle tissues spiked at different levels showed a good linear correlation coefficient, r(2) higher than 0.999 for all quinolones. PMID:12742128

Ramos, Macarena; Aranda, Angela; Garcia, Elena; Reuvers, Thea; Hooghuis, Henny

2003-06-15

285

Molecular characterization of tetracycline- and quinolone-resistant Aeromonas salmonicida isolated in Korea  

PubMed Central

The antibiotic resistance of 16 Aeromonas (A.) salmonicida strains isolated from diseased fish and environmental samples in Korea from 2006 to 2009 were investigated in this study. Tetracycline or quinolone resistance was observed in eight and 16 of the isolates, respectively, based on the measured minimal inhibitory concentrations. Among the tetracycline-resistant strains, seven of the isolates harbored tetA gene and one isolate harbored tetE gene. Additionally, quinolone-resistance determining regions (QRDRs) consisting of the gyrA and parC genes were amplified and sequenced. Among the quinolone-resistant A. salmonicida strains, 15 harbored point mutations in the gyrA codon 83 which were responsible for the corresponding amino acid substitutions of Ser83?Arg83 or Ser83?Asn83. We detected no point mutations in other QRDRs, such as gyrA codons 87 and 92, and parC codons 80 and 84. Genetic similarity was assessed via pulsed-field gel electrophoresis, and the results indicated high clonality among the Korean antibiotic-resistant strains of A. salmonicida.

Kim, Ji Hyung; Hwang, Sun Young; Son, Jee Soo; Han, Jee Eun; Jun, Jin Woo; Shin, Sang Phil; Choresca, Casiano; Choi, Yun Jaie; Park, Yong Ho

2011-01-01

286

Molecular characterization of tetracycline- and quinolone-resistant Aeromonas salmonicida isolated in Korea.  

PubMed

The antibiotic resistance of 16 Aeromonas (A.) salmonicida strains isolated from diseased fish and environmental samples in Korea from 2006 to 2009 were investigated in this study. Tetracycline or quinolone resistance was observed in eight and 16 of the isolates, respectively, based on the measured minimal inhibitory concentrations. Among the tetracycline-resistant strains, seven of the isolates harbored tetA gene and one isolate harbored tetE gene. Additionally, quinolone-resistance determining regions (QRDRs) consisting of the gyrA and parC genes were amplified and sequenced. Among the quinolone-resistant A. salmonicida strains, 15 harbored point mutations in the gyrA codon 83 which were responsible for the corresponding amino acid substitutions of Ser(83)?Arg(83) or Ser(83)?Asn(83). We detected no point mutations in other QRDRs, such as gyrA codons 87 and 92, and parC codons 80 and 84. Genetic similarity was assessed via pulsed-field gel electrophoresis, and the results indicated high clonality among the Korean antibiotic-resistant strains of A. salmonicida. PMID:21368562

Kim, Ji Hyung; Hwang, Sun Young; Son, Jee Soo; Han, Jee Eun; Jun, Jin Woo; Shin, Sang Phil; Choresca, Casiano; Choi, Yun Jaie; Park, Yong Ho; Park, Se Chang

2011-03-01

287

Antibacterial Activity of Some Medicinal Plants Used by Tribals Against Uti Causing Pathogens  

Microsoft Academic Search

Bacterial pathogens have evolved numerous defense mechanisms against antimicrobial agents; hence resistance to old and newly produced drugs is on the rise. The phenomenon of antibiotic resistance exhibited by the pathogenic microorganisms have led to the need for screening of several medicinal plants for their potential antimicrobial activity. Thus the present study was undertaken to investigate the antibacterial activity of

Anjana Sharma; Rani Verm; Padmini Ramteke

288

Screening of anti-bacterial activity of medicinal plants from Belize (Central America)  

Microsoft Academic Search

Twenty-one extracts from seven herbal drugs, Aristolochia trilobata (Aristolochiaceae) leaves and bark, Bursera simaruba (Burseraceae) bark, Guazuma ulmifolia (Sterculiaceae) bark, Hamelia patens (Rubiaceae) leaves and Syngonium podophyllum (Araceae) leaves and bark, used in traditional medicine of Belize (Central America) as deep and superficial wound healers, were evaluated for their anti-bacterial properties. Activity was tested against standard strains of Escherichia coli

A. Camporese; M. J. Balick; R. Arvigo; R. G. Esposito; N. Morsellino; F. De Simone; A. Tubaro

2003-01-01

289

Graphene oxide-based antibacterial cotton fabrics.  

PubMed

Graphene oxide (GO) is an excellent bacteria-killing nanomaterial. In this work, macroscopic applications of this promising nanomaterial by fixing GO sheets onto cotton fabrics, which possess strong antibacterial property and great laundering durability, are reported. The GO-based antibacterial cotton fabrics are prepared in three ways: direct adsorption, radiation-induced crosslinking, and chemical crosslinking. Antibacterial tests show that all these GO-containing fabrics possess strong antibacterial property and could inactivate 98% of bacteria. Most significantly, these fabrics can still kill >90% bacteria even after being washed for 100 times. Also importantly, animal tests show that GO-modified cotton fabrics cause no irritation to rabbit skin. Hence, it is believed that these flexible, foldable, and re-usable GO-based antibacterial cotton fabrics have high promise as a type of new nano-engineered antibacterial materials for a wide range of applications. PMID:23483725

Zhao, Jinming; Deng, Bo; Lv, Min; Li, Jingye; Zhang, Yujie; Jiang, Haiqing; Peng, Cheng; Li, Jiang; Shi, Jiye; Huang, Qing; Fan, Chunhai

2013-09-01

290

Recombinant bacteriophage lysins as antibacterials  

PubMed Central

With the increasing worldwide prevalence of antibiotic resistant bacteria, bacteriophage endolysins (lysins) represent a very promising novel alternative class of antibacterial in the fight against infectious disease. Lysins are phage-encoded peptidoglycan hydrolases which, when applied exogenously (as purified recombinant proteins) to Gram-positive bacteria, bring about rapid lysis and death of the bacterial cell. A number of studies have recently demonstrated the strong potential of these enzymes in human and veterinary medicine to control and treat pathogens on mucosal surfaces and in systemic infections. They also have potential in diagnostics and detection, bio-defence, elimination of food pathogens and control of phytopathogens. This review discusses the extensive research on recombinant bacteriophage lysins in the context of antibacterials, and looks forward to future development and potential.

Fenton, Mark; Ross, Paul; McAuliffe, Olivia; O'Mahony, Jim

2010-01-01

291

Characterization of antibacterial silver coated yarns  

Microsoft Academic Search

Surface treatments of textile fibers and fabrics significantly increase their performances for specific biomedical applications.\\u000a Nowadays, silver is the most used antibacterial agent with a number of advantages. Among them, it is worth to note the high\\u000a degree of biocompatibility, an excellent resistance to sterilization conditions, antibacterial properties with respect to\\u000a different bacteria associated with a long-term of antibacterial efficiency.

M. Pollini; M. Russo; A. Licciulli; A. Sannino; A. Maffezzoli

2009-01-01

292

Drugs against superbugs: private lessons from bacteriophages.  

PubMed

Bacterial genomics has provided a plethora of potential targets for antibacterial drug discovery, however, success in the hunt for new antibiotics will hinge on selecting targets with the highest potential. A recent paper by Liu and coworkers describes a new approach to target selection that uncovers strategies used by bacteriophage to disable bacteria. The method uses key phage proteins to identify and validate vulnerable targets and exploits them further in the identification of new antibacterial leads. PMID:15331220

Brown, Eric D

2004-09-01

293

Antibacterial compounds from Zanthoxylum rhetsa.  

PubMed

A new amide, zanthorhetsamide (1), along with nine known compounds (2-10) was isolated from the roots and stem barks of Zanthoxylum rhetsa. The structure was characterized by spectroscopic methods. In addition, the antibacterial activity of the isolates was evaluated. Dihydrochelerythrine (4) exhibited strong activity against methicillin-resistant Staphylococcus aureus SK1 and moderate activity against Escherichia coli TISTR 780 with MIC values of 8 and 16 ?g/mL, respectively. PMID:22864735

Tantapakul, Cholpisut; Phakhodee, Wong; Ritthiwigrom, Thunwadee; Yossathera, Kulsiri; Deachathai, Suwanna; Laphookhieo, Surat

2012-07-01

294

Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens  

PubMed Central

We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis.

King, Ada; Watkins, Derrick; Kumar, Sunil; Ranjan, Nihar; Gong, Changjun; Whitlock, Jarred

2013-01-01

295

Rapid screening method for quinolone residues in livestock and fishery products using immobilised metal chelate affinity chromatographic clean-up and liquid chromatography-fluorescence detection  

Microsoft Academic Search

An efficient LC method was developed for screening the presence of quinolones (QLs) – comprising fluoroquinolones (FQs) and acidic quinolones (AQs) – residues in various livestock and fishery products. Targeted analytes were for nine FQs of marbofloxacin (MAR), ofloxacin (OFL), norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), danofloxacin (DAN), orbifloxacin (ORB), difloxacin (DIF) and sarafloxacin (SAR), and three AQs of oxolinic

N. Takeda; M. Gotoh; T. Matsuoka

2011-01-01

296

Activity of Gemifloxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model  

PubMed Central

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 105 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 107 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 (AUC24)/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 AUC24/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.

Azoulay-Dupuis, E.; Bedos, J. P.; Mohler, J.; Moine, P.; Cherbuliez, C.; Peytavin, G.; Fantin, B.; Kohler, T.

2005-01-01

297

Investigation of sulfonamide, tetracycline, and quinolone antibiotics in vegetable farmland soil in the Pearl River Delta area, southern China.  

PubMed

Thirteen antibiotics in soil from vegetable farmlands of the Pearl River Delta, southern China, were investigated. At least three antibiotics were detected in each sample. Six antibiotics including four quinolones, tetracycline, and sulfamethoxazole were detected in >94% of the samples. The total contents of three tetracyclines, eight sulfonamides, and four quinolones were not detected-242.6, 33.3-321.4, and 27.8-1537.4 ?g/kg, respectively. The highest antibiotic concentrations were observed mainly in vegetable farmlands affiliated with livestock farms. Chlortetracycline, sulfameter, and quinolones in some samples exceed the ecotoxic effect trigger value (100 ?g/kg) set by the Steering Committee of Veterinary International Committee on Harmonization. The composition and concentration of antibiotics in soil were correlated with vegetable species. This study has revealed an alarming condition of antibiotics in vegetable farmland soil. Further investigation including environmental fate, plant uptake, and human exposure to antibiotics by plant-derived food should be conducted. PMID:21623636

Li, Yan-Wen; Wu, Xiao-Lian; Mo, Ce-Hui; Tai, Yi-Ping; Huang, Xian-Pei; Xiang, Lei

2011-07-13

298

Resistance of M. leprae to Quinolones: A Question of Relativity?  

PubMed Central

Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin. Methodology/Principal Findings We used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1nu/Foxn1nu) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5×103, 5×102, 5×101, and 5×100 M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5×10?1 bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin. Conclusion/Significance DNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae.

Veziris, Nicolas; Chauffour, Aurelie; Escolano, Sylvie; Henquet, Sarah; Matsuoka, Masanori; Jarlier, Vincent; Aubry, Alexandra

2013-01-01

299

Oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad spectrum antibacterial agents.  

PubMed

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs with reduced off-target activity (hERG IC50 > 18 ?M) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 ?M) and topo IV (IC50 = 10.4 ?M). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker. PMID:24900889

Singh, Sheo B; Kaelin, David E; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Meinke, Peter T; Olsen, David; Lagrutta, Armando; Bradley, Prudence; Lu, Jun; Patel, Sangita; Rickert, Keith W; Smith, Robert F; Soisson, Stephen; Wei, Changqing; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Fukuda, Yasumichi

2014-05-01

300

Antibacterial mesh sling: a prospective outcome analysis  

Microsoft Academic Search

Objectives. To prospectively assess the outcome results of the Gore-Tex antibacterial mesh sling in women with pelvic prolapse and stress incontinence.Methods. Between July 1997 and November 1998, 30 women with stress incontinence and vaginal prolapse underwent vaginal reconstruction with the antibacterial mesh sling. All patients had documented stress incontinence by preoperative urodynamic evaluation. Postoperatively, we conducted an outcome analysis on

Jong M Choe; Kenneth Ogan; Stephen Bennett

2000-01-01

301

A new antibacterial compound from Ibicella lutea  

Microsoft Academic Search

Ibicella lutea is a ‘quasi-carnivorous’ plant that grows wild in Uruguay where it is used in popular medicine as an antiseptic for eye and skin infections. In an earlier screening, it showed a broad antibacterial spectrum. From the chloroform extract of the plant the main antibacterial compound has now been isolated and identified by several MS and NMR methods as

M. P Cerdeiras; J Fernández; M Soubes; S Vero; F Ferreira; P Moyna; I Olano; A Vázquez

2000-01-01

302

Multi-targeting by monotherapeutic antibacterials  

Microsoft Academic Search

Antibacterial discovery research has been driven, medically, commercially and intellectually, by the need for new therapeutics that are not subject to the resistance mechanisms that have evolved to combat previous generations of antibacterial agents. This need has often been equated with the identification and exploitation of novel targets. But efforts towards discovery and development of inhibitors of novel targets have

Lynn L Silver

2006-01-01

303

EVALUATION OF ANTIBACTERIAL ACTIVITY OF BERGENIA CILIATA  

Microsoft Academic Search

Bergenia ciliata was subjected to antibacterial analysis. A battery of assays were performed on different extracts of Bergenia ciliata for antibacterialactivities. Antibacterial effects of ethanol, hexane, ethyl acetate, chloroform, butanol and aqueous extracts of the roots and leaves extract of Bergenia ciliata exhibited various degree of inhibition activity. It was observed that root and leaves extract were promising against gram

IQBAL AZHAR; FARAH MAZHAR; KHAN USMANGHANI; MUHAMMAD ASLAM GILL; AFZAL AHMAD

304

Antibacterial activity of some lichen extracts  

Microsoft Academic Search

The aqueous and ethanol extracts prepared from some lichens species were evaluated for antibacterial activity against six standard strains (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumoniae, Staphylococcus aureus and Staphylococcus epidermidis) and two environmental strains (Aeromonas) that were isolated from different lakes. The aqueous and ethanol extracts showed a variable range of antibacterial activity to both standard strains and

Ali Karagöz; Nihal Doruöz; Zuhal Zeybek; Ali Aslan

2009-01-01

305

Antibacterial properties of tuftsin and its analogs.  

PubMed Central

The antibacterial properties of tuftsin and its 11 analogs on 20 bacterial strains were investigated. Tuftsin showed a definite antibacterial effect at a minimal effective concentration of 62.5 micrograms/ml. All analogs were either less effective or lacked any activity. The bacteria used included some highly pathogenic organisms.

Blok-Perkowska, D; Muzalewski, F; Konopinska, D

1984-01-01

306

Antibacterial Activity of Leaf Extracts of Baeckea frutescens against Methicillin-Resistant Staphylococcus aureus  

PubMed Central

This study was based on screening antibacterial activity of the ethanol extract of Baeckea frutescens L. against MRSA clinical isolates, analyzes the potential antibacterial compound, and assesses the cytotoxicity effect of the extract in tissue culture. Leaves of Baeckea frutescens L. were shade dried, powdered, and extracted using solvent ethanol. Preliminary phytochemical screening of the crude extracts revealed the presence of alkaloids, flavonoids, steroids, terpenoids, phenols, and carbohydrates. The presence of these bioactive constituents is related to the antibacterial activity of the plant. Disc diffusion method revealed a high degree of activity against microorganisms. The results confirm that Baeckea frutescens L. can be used as a source of drugs to fight infections caused by susceptible bacteria.

Razmavar, Somayeh; Abdulla, Mahmood Ameen; Ismail, Salmah Binti; Hassandarvish, Pouya

2014-01-01

307

Antibacterial Activity of Leaf Extracts of Baeckea frutescens against Methicillin-Resistant Staphylococcus aureus.  

PubMed

This study was based on screening antibacterial activity of the ethanol extract of Baeckea frutescens L. against MRSA clinical isolates, analyzes the potential antibacterial compound, and assesses the cytotoxicity effect of the extract in tissue culture. Leaves of Baeckea frutescens L. were shade dried, powdered, and extracted using solvent ethanol. Preliminary phytochemical screening of the crude extracts revealed the presence of alkaloids, flavonoids, steroids, terpenoids, phenols, and carbohydrates. The presence of these bioactive constituents is related to the antibacterial activity of the plant. Disc diffusion method revealed a high degree of activity against microorganisms. The results confirm that Baeckea frutescens L. can be used as a source of drugs to fight infections caused by susceptible bacteria. PMID:25028658

Razmavar, Somayeh; Abdulla, Mahmood Ameen; Ismail, Salmah Binti; Hassandarvish, Pouya

2014-01-01

308

Mesoporous TiO2 implants for loading high dosage of antibacterial agent  

NASA Astrophysics Data System (ADS)

We have fabricated mesoporous thin films composed of TiO2 nanoparticles on anodized titanium implant surfaces for loading drugs at high doses. Surface anodization followed by treatment with TiO2 paste leads to the formation of mechanically stable mesoporous thin films with controllable thickness. A series of antibacterial agents (silver nanoparticles, cephalothin, minocycline, and amoxicillin) were loaded into the mesoporous thin films and their antibacterial activities were evaluated against five bacterial species including three oral pathogens. Additionally, two agents (silver nanoparticles and minocycline) were loaded together on the thin film and tested for antibacterial effectiveness. The combination of silver nanoparticles and minocycline was found to display a wide range of effectiveness against all tested bacteria.

Park, Se Woong; Lee, Donghyun; Choi, Yong Suk; Jeon, Hoon Bong; Lee, Chang-Hoon; Moon, Ji-Hoi; Kwon, Il Keun

2014-06-01

309

Proteolytically activated anti-bacterial hydrogel microspheres.  

PubMed

Hydrogels are finding increased clinical utility as advances continue to exploit their favorable material properties. Hydrogels can be adapted for many applications, including surface coatings and drug delivery. Anti-infectious surfaces and delivery systems that actively destroy invading organisms are alternative ways to exploit the favorable material properties offered by hydrogels. Sterilization techniques are commonly employed to ensure the materials are non-infectious upon placement, but sterilization is not absolute and infections are still expected. Natural, anti-bacterial proteins have been discovered which have the potential to act as anti-infectious agents; however, the proteins are toxic and need localized release to have therapeutic efficacy without toxicity. In these studies, we explore the use of the glutathione s-transferase (GST) to anchor the bactericidal peptide, melittin, to the surface of poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We show that therapeutic levels of protein can be anchored to the surface of the microspheres using the GST anchor. We compared the therapeutic efficacy of recombinant melittin released from PEGDA microspheres to melittin. We found that, when released by an activating enzyme, thrombin, recombinant melittin efficiently inhibits growth of the pathogenic bacterium Streptococcus pyogenes as effectively as melittin created by solid phase peptide synthesis. We conclude that a GST protein anchor can be used to immobilize functional protein to PEGDA microspheres and the protein will remain immobilized under physiological conditions until the protein is enzymatically released. PMID:23816641

Buhrman, Jason S; Cook, Laura C; Rayahin, Jamie E; Federle, Michael J; Gemeinhart, Richard A

2013-11-10

310

Role of protein D2 and lipopolysaccharide in diffusion of quinolones through the outer membrane of Pseudomonas aeruginosa.  

PubMed Central

Routes of quinolone permeation in Pseudomonas aeruginosa were investigated by using sparfloxacin as a prototype compound. [14C]sparfloxacin cell labeling was 13 to 28% lower in three protein D2-deficient mutants resistant to imipenem than in their imipenem-susceptible counterparts. In four impermeability-type quinolone-resistant strains isolated from pefloxacin-treated animals, we observed two- to fourfold-greater resistance to imipenem, reduced protein D2 expression in the outer membrane according to Western blotting (immunoblotting), and 25 to 29% decreased cell labeling with imipenem. In a protein D2-producing strain but not in its protein D2-deficient isogenic mutant, uptake of [14C]sparfloxacin was strongly inhibited by L-lysine and imipenem, which act as substrates for protein D2. Conversely, binding of [14C]imipenem in a porin D2-positive strain was reduced by sparfloxacin but not by the nonamphoteric quinolone nalidixic acid. Sparfloxacin, imipenem, and lysine possess a carboxyl group and a potentially protonated nitrogen separated from each other by 0.64 to 1.07 nm as calculated by computer. Hence, protein D2 may catalyze facilitated diffusion for sparfloxacin, as it does for imipenem. In addition, pefloxacin-selected isolates contained 41 to 113% more 3-deoxy-D-mannooctulosonic acid than their quinolone-susceptible counterparts, with MIC increases of 2- to 4-fold for WIN-57273 (n-octanol-phosphate buffer partition coefficient, 13.139), 4- to 8-fold for difloxacin (partition coefficient, 3.093) and sparfloxacin (partition coefficient, 0.431), and 8- to 16-fold for norfloxacin (partition coefficient, 0.059) and ciprofloxacin (partition coefficient, 0.056). Thus, we hypothetize that in quinolone-selected strains, increased amounts of lipopolysaccharide form a permeability barrier that acts preferentially against hydrophilic quinolones. Images

Michea-Hamzehpour, M; Furet, Y X; Pechere, J C

1991-01-01

311

Antibacterial activities of Sesbania grandiflora extracts.  

PubMed

In this study, Sesbania grandiflora, a plant in the Leguminosae family, was investigated for its antibacterial activities. The agar well diffusion assay as well as the agar and broth dilution assays were used for determination of antibacterial activities. The crude ethanolic extracts obtained from different parts of this plant exhibited different potent activities. The stem bark has the most potential to yield an extract with the highest antibacterial action. The fractionation of the stem bark with different solvents indicated that the fractionated extracts obtained from ethyl acetate or butanol possessed the most pronounced antibacterial activity. The kinetic study of bactericidal activities revealed that the butanol fractionated extract of the stem bark was effective against Gram negative bacteria. This study suggests that the stem bark of S. grandiflora contains promising antibacterial substances for clinical purposes. PMID:22466091

Anantaworasakul, P; Klayraung, S; Okonogi, S

2011-02-01

312

In vitro antibacterial effect of wasp (Vespa orientalis) venom  

PubMed Central

Background The emergence of antibacterial resistance against several classes of antibiotics is an inevitable consequence of drug overuse. As antimicrobial resistance spreads throughout the globe, new substances will always be necessary to fight against multidrug-resistant microorganisms. Venoms of many animals have recently gained attention in the search for new antimicrobials to treat infectious diseases. Thefore, the present study aimed to study the antibacterial effects of wasp (Vespa orientalis) crude venom. Two gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two gram-negative ones (Escherichia coli and Klesiella pneumonia) were compared for their sensitivity to the venom by determining the inhibition zone (Kirby-Bauer method) and minimum inhibitory concentration (MIC). A microbroth kinetic system based on continuous monitoring of changes in the optical density of bacterial growth was also used for determination of antimicrobial activity. Results The venom exhibited a well-recognized antimicrobial property against the tested bacterial strains. The inhibition zones were determined to be 12.6, 22.7, 22.4 and 10.2 mm for S. aureus, B. subtilis, E. coli and K. pneumonia, respectively. The corresponding MIC values were determined to be 64, 8, 64 and 128 ?g/mL, respectively. The MIC50 and MIC90 values of the venom were respectively determined to be 63.6 and 107 ?g/mL for S. aureus, 4.3 and 7.0 ?g/mL for B. subtilis, 45.3 and 65.7 ?g/mL for E. coli and 74.4 and 119.2 ?g/mL for K. pneumonia. Gram-positive bacteria were generally more sensitive to the venom than gram-negative ones. Conclusions Results revealed that the venom markedly inhibits the growth of both gram-positive and gram-negative bacteria and could be considered a potential source for developing new antibacterial drugs.

2014-01-01

313

Quinolone-benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer disease.  

PubMed

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds show effective AchE inhibitions, high selectivities over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of quinolone derivatives to serve in the design of N-benzylpiperidine linked multipotent molecules for the treatment of Alzheimer Disease has been established. PMID:24657052

Pudlo, Marc; Luzet, Vincent; Ismaïli, Lhassane; Tomassoli, Isabelle; Iutzeler, Anne; Refouvelet, Bernard

2014-04-15

314

Cytotoxic quinolines (part 1). Azolylalkyloxy quinolines and 1-azolylalkyl-4(1H)-quinolones.  

PubMed

A series of 4-azolylalkyloxyquinolines and 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for cytotoxicity against various cancer cell lines. 1-Phenyl-1,2,3-triazole and 1-methylpyrazole were found to be the most effective azoles. The length of the alkyl chain was critical, with 8 to 10 carbon atoms being optimal. Several of the compounds were found to be very cytotoxic in vitro towards various cancer cells. Compounds 9o, 10k, and 10r were evaluated in vivo, but were ineffective and exhibited acute general toxicity at higher dosages. PMID:8854042

Abel, M D; Ha, C M; Luu, H T; Micetich, R G; Nguyen, D Q; Nukatsuka, M; Oreski, A B; Tempest, M L; Daneshtalab, M

1996-03-01

315

Antibacterial activity of baking soda.  

PubMed

The antibacterial activity of baking soda (sodium bicarbonate) was assessed using three different experimental approaches. Standard minimum inhibitory concentration analyses revealed substantial inhibitory activity against Streptococcus mutans that was not due to ionic strength or high osmolarity. Short-term exposure assays showed significant killing of bacterial suspensions when baking soda was combined with the detergent sodium dodecylsulfate. Multiple, brief exposures of sucrose-colonized S mutans to baking soda and sodium dodecylsulfate caused statistically significant decreases in numbers of viable cells. Use of oral health care products with high concentrations of baking soda could conceivably result in decreased levels of cariogenic S mutans in saliva and plaque. PMID:12017929

Drake, D

1997-01-01

316

Antibacterial activity of baking soda.  

PubMed

The antibacterial activity of baking soda (sodium bicarbonate) was assessed using three different experimental approaches. Standard minimum inhibitory concentration analyses revealed substantial inhibitory activity against Streptococcus mutans that was not due to ionic strength or high osmolarity. Short-term exposure assays showed significant killing of bacterial suspensions when baking soda was combined with the detergent sodium dodecylsulfate. Multiple, brief exposures of sucrose-colonized S mutans to baking soda and sodium dodecylsulfate caused statistically significant decreases in numbers of viable cells. Use of oral health care products with high concentrations of baking soda could conceivably result in decreased levels of cariogenic S mutans in saliva and plaque. PMID:11524862

Drake, D

1996-01-01

317

Toxicity and antibacterial assessment of chitosancoated silver nanoparticles on human pathogens and macrophage cells  

PubMed Central

Background Pathogenic bacteria are able to develop various strategies to counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs) have emerged as a potential alternative to conventional antibiotics because of their potent antimicrobial properties. The purpose of this study was to synthesize chitosan-stabilized AgNPs (CS-AgNPs) and test for their cytotoxic, genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities. Methods AgNPs were synthesized using chitosan as both a stabilizing and a reducing agent. Antibacterial activity was determined by colony-forming unit assay and scanning electron microscopy. Genotoxic and cytotoxic activity were determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Cellular uptake and intracellular antibacterial activity were tested on macrophages. Results CS-AgNPs exhibited potent antibacterial activity against different human pathogens and also impeded bacterial biofilm formation. Scanning electron microscopy analysis indicated that CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no significant cytotoxic or DNA damage effect on macrophages at the bactericidal dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs resulting in reduced intracellular bacterial survival in macrophages. Conclusion The present study concludes that at a specific dose, chitosan-based AgNPs kill bacteria without harming the host cells, thus representing a potential template for the design of antibacterial agents to decrease bacterial colonization and to overcome the problem of drug resistance.

Jena, Prajna; Mohanty, Soumitra; Mallick, Rojee; Jacob, Biju; Sonawane, Avinash

2012-01-01

318

Random Mutagenesis of the Aspergillus oryzae Genome Results in Fungal Antibacterial Activity.  

PubMed

Multidrug-resistant bacteria cause severe infections in hospitals and communities. Development of new drugs to combat resistant microorganisms is needed. Natural products of microbial origin are the source of most currently available antibiotics. We hypothesized that random mutagenesis of Aspergillus oryzae would result in secretion of antibacterial compounds. To address this hypothesis, we developed a screen to identify individual A. oryzae mutants that inhibit the growth of Methicillin-resistant Staphylococcus aureus (MRSA) in vitro. To randomly generate A. oryzae mutant strains, spores were treated with ethyl methanesulfonate (EMS). Over 3000 EMS-treated A. oryzae cultures were tested in the screen, and one isolate, CAL220, exhibited altered morphology and antibacterial activity. Culture supernatant from this isolate showed antibacterial activity against Methicillin-sensitive Staphylococcus aureus, MRSA, and Pseudomonas aeruginosa, but not Klebsiella pneumonia or Proteus vulgaris. The results of this study support our hypothesis and suggest that the screen used is sufficient and appropriate to detect secreted antibacterial fungal compounds resulting from mutagenesis of A. oryzae. Because the genome of A. oryzae has been sequenced and systems are available for genetic transformation of this organism, targeted as well as random mutations may be introduced to facilitate the discovery of novel antibacterial compounds using this system. PMID:23983696

Leonard, Cory A; Brown, Stacy D; Hayman, J Russell

2013-01-01

319

Overcoming scientific and structural bottlenecks in antibacterial discovery and development  

PubMed Central

Antibiotic resistance is becoming an increasing threat, with too few novel antibiotics coming to market to replace those lost due to resistance development. Efforts by the pharmaceutical industry to screen for and design novel antibacterials have not been successful, with several companies minimizing or closing down their antibacterial research units, leading to a loss of skills and know-how. At the same time, antibiotic innovation in academia is not filling the void due to misaligned incentive structures and lack of vital knowledge of drug discovery. The scientific and structural difficulties in discovering new antibiotics have only begun to be appreciated in the latest years. Part of the problem has been a paradigm shift within both industry and academia to focus on ‘rational’ drug development with an emphasis on single targets and high-throughput screening of large chemical libraries, which may not be suited to target bacteria. The very particular aspects of ‘targeting an organism inside another organism’ have not been given enough attention. In this paper, researcher interviews have complemented literature studies to delve deeper into the specifics of the different scientific and structural barriers, and some potential solutions are offered.

2014-01-01

320

Optimization of antibacterial peptides by genetic algorithms and cheminformatics.  

PubMed

Pathogens resistant to available drug therapies are a pressing global health problem. Short, cationic peptides represent a novel class of agents that have lower rates of drug resistance than derivatives of current antibiotics. Previously, we created a software system utilizing artificial neural networks that were trained on quantitative structure-activity relationship descriptors calculated for a total of 1400 synthetic peptides for which antibacterial activity was determined. Using the trained system, we correctly identified additional peptides with activity of 94% accuracy; active peptides were 47 of the top rated 50 peptides chosen from an in silico library of nearly 100,000 sequences. Here, we report a method of generating candidate peptide sequences using the heuristic evolutionary programming method of genetic algorithms (GA), which provided a large (19-fold) improvement in identification of novel antibacterial peptides. Approximately 0.50% of peptides evaluated during the GA method were classified as highly active, while only 0.026% of the nearly 100,000 sequences we previously screened were classified as highly active. A selection of these peptides was tested in vitro and activities reported here. While GA significantly improves the possibility of identifying candidate peptides, we encountered important pitfalls to this method that should be considered when using GA. PMID:20942839

Fjell, Christopher D; Jenssen, Håvard; Cheung, Warren A; Hancock, Robert E W; Cherkasov, Artem

2011-01-01

321

Overcoming scientific and structural bottlenecks in antibacterial discovery and development.  

PubMed

Abstract Antibiotic resistance is becoming an increasing threat, with too few novel antibiotics coming to market to replace those lost due to resistance development. Efforts by the pharmaceutical industry to screen for and design novel antibacterials have not been successful, with several companies minimizing or closing down their antibacterial research units, leading to a loss of skills and know-how. At the same time, antibiotic innovation in academia is not filling the void due to misaligned incentive structures and lack of vital knowledge of drug discovery. The scientific and structural difficulties in discovering new antibiotics have only begun to be appreciated in the latest years. Part of the problem has been a paradigm shift within both industry and academia to focus on 'rational' drug development with an emphasis on single targets and high-throughput screening of large chemical libraries, which may not be suited to target bacteria. The very particular aspects of 'targeting an organism inside another organism' have not been given enough attention. In this paper, researcher interviews have complemented literature studies to delve deeper into the specifics of the different scientific and structural barriers, and some potential solutions are offered. PMID:24646118

Zorzet, Anna

2014-05-01

322

[Drugs renal toxicity].  

PubMed

Drug-induced renal dysfunction is frequent in clinical practice. Outcomes may be severe, with increased morbidity and mortality. Kidneys are particularly vulnerable to drug toxicity, especially since they are highly vascularized, thus receiving about 25% of cardiac output. Furthermore, interstitial accumulation of toxic agents in papilla and the medulla often occurs due to the existence of a corticomedullary osmotic gradient. Moreover, the key role played by the renal tubule in the reabsorption processes of a number of endogenous and exogenous substances further increases the exposure of the kidney to high concentrations of potentially toxic agents, both in the tubular lumen and cells. As a result, drugs may be toxic to all of the four structures of the kidney: glomerulus, tubule, interstitium, and blood vessels. This chapter reviews the main mechanisms of drug-induced renal toxicity and then focuses on the nephrotoxicity of anti-infectious drugs: antibacterial drugs, antifungal agents, antimalariae, and antiviral drugs. NSAID and anticancer drugs renal toxicity are detailed elsewhere in this textbook. Methods used to prevent drug-induced nephrotoxicity, when known, are detailed. Risk factors are also listed, such as high-risk populations, identification and elimination of risk factors, and drug dosage adjustment in patients with baseline abnormal renal function. PMID:19345176

Karie, Svetlana; Launay-Vacher, Vincent; Deray, Gilbert; Isnard-Bagnis, Corinne

2010-02-01

323

Association of plasmid-mediated quinolone resistance and virulence markers in Escherichia coli isolated from water.  

PubMed

This work aimed to investigate the association of the carriage of plasmid-mediated quinolone resistance (PMQR) genes, the virulence potential encoded in pathogenicity islands (PAIs) and the phylogenetic background in Escherichia coli strains isolated from waters of diverse origin. Antimicrobial susceptibilities were determined by the disc diffusion method. Screening for PMQR (qnr, aac(6')-Ib-variant and qepA) genes, PAIs and the determination of phylogroup was performed by PCR. Nineteen percent of strains were resistant to nalidixic acid, 11% to ciprofloxacin and 5% to gentamicin. qnrA was the only PMQR detected in 16% of strains, susceptible to quinolones and grouped in phylogenetic lineage B1. Sixty-seven percent of the isolates were assigned to the less-virulent groups A and B1. PAIs IV(536) and II(CFT073) were detected in 16 and 3% of the isolates, respectively. All PAIs were detected in the phylogroups D and B1. The presence of PAIs in isolates from waters may represent an increased risk for public health, as they were isolated from samples collected from surface and drinking waters. As E. coli is an important indicator of microbiological water quality, and also a potential pathogen, routine analysis for its detection could be complemented by screening for virulence factors and antimicrobial genes. PMID:22717754

Mendonça, Nuno; Ramalho, Joana; Vieira, Pedro; Da Silva, Gabriela Jorge

2012-06-01

324

Ornamental fish as a source of plasmid-mediated quinolone resistance genes and antibiotic resistance plasmids.  

PubMed

Growing ornamental fish industry is associated with public health concerns including extensive antibiotic use accompanied by increasing antibiotic resistance. The aim of this study was to analyze Aeromonas isolates from imported tropical ornamental fish and coldwater koi carps bred in the Czech Republic to assess the potential risk of ornamental fish as a source of plasmid-mediated quinolone resistance genes (PMQR) and antibiotic resistance plasmids. A collection of Aeromonas spp. with reduced susceptibility to ciprofloxacin (MIC?0.05mg/L) was selected for the detection of PMQR genes. Isolates harbouring PMQR genes were further analyzed for the additional antibiotic resistance, integron content, clonality, biofilm production and transferability of PMQR genes by conjugation and transformation. Comparative analysis of plasmids carrying PMQR genes was performed. Fifteen (19%, n=80) isolates from koi carps and 18 (24%, n=76) isolates from imported ornamental fish were positive for qnrS2, aac(6')-Ib-cr or qnrB17 genes. PMQR-positive isolates from imported ornamental fish showed higher MIC levels to quinolones, multiresistance and diverse content of antibiotic resistance genes and integrons compared to the isolates from the carps. Related IncU plasmids harbouring qnrS2 and aac(6')-Ib-cr genes were found in Aeromonas spp. from imported ornamental fish and koi carps from various geographical areas. Ornamental fish may represent a potential source of multiresistant bacteria and mobile genetic elements for the environment and for humans. PMID:24629900

Dobiasova, Hana; Kutilova, Iva; Piackova, Veronika; Vesely, Tomas; Cizek, Alois; Dolejska, Monika

2014-07-16

325

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

PubMed

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 ?L 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%. PMID:22517642

Wang, Mi-Hung; Wang, Shu-Ping

2012-03-01

326

Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe River Basin, China.  

PubMed

The occurrence and transport of 12 antibiotics (from the tetracycline, sulfonamide, quinolone, and macrolide families) was studied in a 72-km stretch of the Haihe River, China, and in six of its tributaries. Aqueous and sediment samples were analyzed by HPLC-MS/MS. Sulfonamides were detected at the highest concentrations (24-385 ng/L) and highest frequencies (76-100%). Eight of the 12 antibiotics likely originated from veterinary applications in swine farms and fishponds, and concentrations at these sources (0.12-47 ?g/L) were 1-2 orders of magnitude higher than in the effluent of local wastewater treatment plants. Sulfachloropyridazine (SCP) was detected in all swine farm and fishpond samples (maximum concentration 47 ?g/L), which suggests its potential usefulness to indicate livestock source pollution in the Haihe River basin. Hydrological and chemical factors that may influence antibiotic distribution in the Haihe River were considered by multiple regression analysis. River flow rate exerted the most significant effect on the first-order attenuation coefficient (K) for sulfonamides, quinolones, and macrolides, with higher flow rates resulting in higher K, probably due to dilution. For tetracyclines, sediment total organic matter and cation exchange capacity exerted a greater impact on K than flow rate, indicating that adsorption to sediments plays an important role in attenuating tetracycline migration. Overall, the predominance of sulfonamides in the Haihe River underscores the need to consider regulating their veterinary use and improving the management and treatment of associated releases. PMID:21309601

Luo, Yi; Xu, Lin; Rysz, Michal; Wang, Yuqiu; Zhang, Hao; Alvarez, Pedro J J

2011-03-01

327

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

PubMed Central

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.

Baucheron, Sylvie; Monchaux, Isabelle; Le Hello, Simon; Weill, Francois-Xavier; Cloeckaert, Axel

2014-01-01

328

Structure-guided discovery of 1,3,5-triazine-pyrazole conjugates as antibacterial and antibiofilm agent against pathogens causing human diseases with favorable metabolic fate.  

PubMed

Impressed by the exceptional antibacterial activity exhibited by our earlier designed molecules originating from 1,3,5-triazine, the present study was undertaken to synthesize a novel series of 1,3,5-triazine-pyrazole conjugates to bring diversity around the core skeleton. The target analogues showed potent antibacterial activity against tested Gram-positive and Gram-negative microorganisms. The toxicity and metabolic site prediction studies were also held out to set an effective lead candidate for the future antibacterial drug discovery initiatives. PMID:24961639

Singh, Babita; Bhat, Hans Raj; Kumawat, Mukesh Kumar; Singh, Udaya Pratap

2014-08-01

329

Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I.  

PubMed

Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In principle, it shows remarkable antibacterial activities against laboratory and clinically isolated Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further expanded its antibacterial spectrum into against Gram-negative bacteria with the assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate through the bacterial outer membrane. Finally, the therapeutic effect of haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit model. With distinctive structural difference from the antibiotics we used, the haloemodins are of value as promising antibacterial pharmacophore, especially for combat the infections caused by drug-resistant pathogens. PMID:24588790

Duan, Feixia; Li, Xiaohong; Cai, Suping; Xin, Guang; Wang, Yanyan; Du, Dan; He, Shiliang; Huang, Baozhan; Guo, Xiurong; Zhao, Hang; Zhang, Rui; Ma, Limei; Liu, Yan; Du, Qigen; Wei, Zeliang; Xing, Zhihua; Liang, Yong; Wu, Xiaohua; Fan, Chengzhong; Ji, Chengjie; Zeng, Dequan; Chen, Qianming; He, Yang; Liu, Xuyang; Huang, Wen

2014-05-01

330

Antibacterial phenylpropanoid glycosides from Paulownia tomentosa Steud.  

PubMed

The butanol extract of Paulownia tomentosa stem showed antibacterial activity against Staphylococcus aureus (SG511, 285 and 503), Streptococcus pyogenes (A308 and A77) and Streptococcus faecium MD8b etc. The most active compound of the extract was identified to be campneoside I, which had a minimal inhibitory concentration (MIC) of 150 micrograms/ml against Streptococcus and Staphylococcus species. From such antibacterial activity, the methoxy group of campneoside I was postulated to be the essential element for the antibacterial activity. PMID:10319161

Kang, K H; Jang, S K; Kim, B K; Park, M K

1994-12-01

331

Antibacterial Activity of Polyphenols of Garcinia Indica  

PubMed Central

The aim of present work is to study the antibacterial activity of polyphenols isolated from the ethyl acetate soluble of methanol extract of stem bark of Garcinia indica against Staphylococcus aureus, Salmonella typhi and Escherichia coli by paper disc method. The results showed good antibacterial activity against S. aureus at higher concentrations, moderate at lower concentrations, against S. typhi moderate at higher concentrations but no activity against E. coli even at higher concentration for flavononylflavone. With proauthocyanin S. Aureus, S. Typhi and E. coli showed good antibacterial activity at higher concentration only.

Lakshmi, C.; Kumar, K. Akshaya; Dennis, T. J.; Kumar, T. S. S. P. N. S. Sanath

2011-01-01

332

The inducible antibacterial peptides of insects.  

PubMed

Insects respond to bacterial challenge by the rapid and transient synthesis of a large number of potent antibacterial peptides that are active against many different bacteria. Two families of inducible antibacterial peptides are well characterized: the cecropins and the insect defensins. A rapidly increasing number of proline- and glycine-rich peptides are reported from various insect species together with cecropins and insect defensins. In this review, Stéphane Cociancich, Philippe Bulet, Charles Hetru and Jules A. Hoffmann give an update of our current information on the induced antibacterial peptides. PMID:15275477

Cociancich, S; Bulet, P; Hetru, C; Hoffmann, J A

1994-04-01

333

Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus  

Microsoft Academic Search

Staphylococcus aureus remains an important human pathogen affecting both outpatients and those hospitalized. Increasing antimicrobial resistance is global but prevalence rates are variable for different geographical areas. Fluoroquinolones have been used to treat S. aureus infections and the newer quinolones have enhanced in vitro activity against this organism. The mutant prevention concentration (MPC) defines the antimicrobial drug concentration threshold that

K. Metzler; G. M. Hansen; Peter Hedlin; Elizabeth Harding; Karl Drlica; J. M. Blondeau

2004-01-01

334

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

PubMed

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?g/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?g/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. PMID:24797736

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

335

Emerging Plasmid-Mediated Quinolone Resistance Associated with the qnr Gene in Klebsiella pneumoniae Clinical Isolates in the United States  

Microsoft Academic Search

Although quinolone resistance commonly results from chromosomal mutation, recent studies indicate that such resistance can also be transferred on plasmids carrying the gene responsible, qnr. One hundred ten ciprofloxacin-resistant clinical isolates of Klebsiella pneumoniae and Escherichia coli from the United States were screened for the qnr gene by PCR and Southern hybridization of plasmid DNA. Conjugation experiments were done with

Minggui Wang; Daniel F. Sahm; George A. Jacoby; David C. Hooper

2004-01-01

336

Increase in Quinolone Resistance in a Haemophilus influenzae Strain Isolated from a Patient with Recurrent Respiratory Infections Treated with Ofloxacin  

Microsoft Academic Search

The increase in the level of quinolone resistance of Haemophilus influenzae clinical isolates during ofloxacin therapy of a patient with recurrent respiratory infections was investigated. The first isolate (MIC of cipro- floxacin of 2 mg\\/ml) and the second isolate (MIC of 32 mg\\/ml) belonged to the same clone, as shown by pulsed- field gel electrophoresis, and the increase in the

JORDI VILA; JOAQUIM RUIZ; FERRAN SANCHEZ; FERRAN NAVARRO; BEATRIZ MIRELIS; M. TERESA JIMENEZ DE ANTA; GUILLEM PRATS

337

Vitek2® system: a reliable tool to detect qnr determinants in Enterobacteriaceae without quinolone resistance-determining region modifications  

Microsoft Academic Search

Qnr determinants have now been found worldwide. In 2008, among 6150 Enterobacteriaceae, 12 isolates belonging to different bacterial species showing an unusual quinolone resistance pattern on Vitek2® system were investigated. Of 12, 11 harbored a qnr gene. Without QRDR modifications, qnr genes can be detected based on a Vitek2® resistance phenotype.

Stéphane Corvec; Lise Crémet; Alain Reynaud; Didier Lepelletier; Nathalie Caroff

2009-01-01

338

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

PubMed

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(?)), detection capability (CC(?)), 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. PMID:21085936

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

2011-05-01

339

Characterization of Mutations in DNA Gyrase and Topoisomerase IV Involved in Quinolone Resistance of Mycoplasma gallisepticum Mutants Obtained In Vitro  

Microsoft Academic Search

Mycoplasma gallisepticum is responsible for chronic respira- tory diseases of chickens and sinusitis of turkeys (17). Control by antimicrobials is sometimes necessary to minimize its trans- mission in case of an outbreak. M. gallisepticum is known to be susceptible to several antimicrobials (10, 17) but can develop resistance against some of the quinolones used in veterinary medicine (14). Unlike human

A. K. Reinhardt; C. M. Bebear; M. Kobisch; I. Kempf; A. V. Gautier-Bouchardon

2002-01-01

340

Solidphase synthesis and antibacterial activity of hydroxycinnamic acid amides and analogues against methicillin-resistant Staphylococcus aureus and vancomycin-resistant S. aureus  

Microsoft Academic Search

A library of hydroxycinnamic acid amides (HCAAs) and analogues were synthesized using solid-phase synthesis technique. These compounds were screened for antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Dihydrocaffeoyl analogues showed activity against VRSA which were better than the reference drugs, vancomycin and oxacillin. These compounds also exhibited antibacterial activity against MRSA, which

Boon-ek Yingyongnarongkul; Nuttapon Apiratikul; Nuntana Aroonrerk; Apichart Suksamrarn

2006-01-01

341

Antibacterial hydroperoxysterols from Xanthosoma robustum.  

PubMed

Three new hydroperoxysterols, 24-hydroperoxy-4 alpha, 14 alpha- dimethylcholesta-8,25-dien-3 beta-ol, 25-hydroperoxy-4 alpha, 14 alpha-dimethylcholesta-8,23-dien-3 beta-ol and 25-hydroperoxycycloart-23-en- 3 beta-ol, have been isolated from the aerial parts of Xanthosoma robustum, besides 24-hydroperoxycycloart-25-en-3 beta-ol, 4 alpha, 14 alpha-dimethylcholesta-8,24-dien-3 beta-ol and cycloartenol. Additionally, the two new diols, 4 alpha, 14 alpha-dimethylcholesta-8,25-dien-3 beta, 24-diol and 4 alpha, 14 alpha-dimethylcholesta-8,23-dien-3 beta, 25-diol were obtained from the first two hydroperoxysterols, respectively, by reduction with triphenylphosphine. The structures have been defined by chemical and spectroscopic studies. The four hydroperoxysterols exhibited antibacterial activities against Escherichia coli, Bacillus subtilis and Micrococcus luteus. PMID:8728719

Kato, T; Frei, B; Heinrich, M; Sticher, O

1996-03-01

342

Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from Citrus microcarpa.  

PubMed

Two novel type III polyketide synthases, quinolone synthase (QNS) and acridone synthase (ACS), were cloned from Citrus microcarpa (Rutaceae). The deduced amino acid sequence of C. microcarpa QNS is unique, and it shared only 56-60% identities with C. microcarpa ACS, Medicago sativa chalcone synthase (CHS), and the previously reported Aegle marmelos QNS. In contrast to the quinolone- and acridone-producing A. marmelos QNS, C. microcarpa QNS produces 4-hydroxy-N-methylquinolone as the "single product" by the one-step condensation of N-methylanthraniloyl-CoA and malonyl-CoA. However, C. microcarpa ACS shows broad substrate specificities and produces not only acridone and quinolone but also chalcone, benzophenone, and phloroglucinol from 4-coumaroyl-CoA, benzoyl-CoA, and hexanoyl-CoA, respectively. Furthermore, the x-ray crystal structures of C. microcarpa QNS and ACS, solved at 2.47- and 2.35-? resolutions, respectively, revealed wide active site entrances in both enzymes. The wide active site entrances thus provide sufficient space to facilitate the binding of the bulky N-methylanthraniloyl-CoA within the catalytic centers. However, the active site cavity volume of C. microcarpa ACS (760 ?(3)) is almost as large as that of M. sativa CHS (750 ?(3)), and ACS produces acridone by employing an active site cavity and catalytic machinery similar to those of CHS. In contrast, the cavity of C. microcarpa QNS (290 ?(3)) is significantly smaller, which makes this enzyme produce the diketide quinolone. These results as well as mutagenesis analyses provided the first structural bases for the anthranilate-derived production of the quinolone and acridone alkaloid by type III polyketide synthases. PMID:23963450

Mori, Takahiro; Shimokawa, Yoshihiko; Matsui, Takashi; Kinjo, Keishi; Kato, Ryohei; Noguchi, Hiroshi; Sugio, Shigetoshi; Morita, Hiroyuki; Abe, Ikuro

2013-10-01

343

Prospects for developing new antibacterials targeting bacterial type IIA topoisomerases.  

PubMed

The modulation of DNA topology by DNA gyrase and topoisomerase IV, both of which are type IIA topoisomerases and found in most bacteria, is a function vital to DNA replication, repair and decatenation. Despite the potential for resistance development, DNA gyrase and/or topoisomerase IV have been proven to be and remain highly attractive targets in antibacterial drug discovery due to their potential for dual targeting. The search for new GyrA and/or ParC inhibitors that can overcome the increasing spread of multidrug-resistant bacteria has been successfully focused in the last decades on the modification of the known fluoroquinolone scaffold as primarily guided by ligand-based design via classical structure-activity relationship studies and the optimisation of physicochemical properties. This focus has resulted in several novel fluoroquinolones that have been introduced into clinical practice since 2000, and several of these new compounds are currently in different phases of clinical trials. Due to increasing resistance to fluoroquinolones, a significant part of DNA gyrase research has shifted to the discovery of new GyrB and/or ParE inhibitors, which are commonly identified through fragment-based design as well as virtual screening techniques and structure-based hit optimisation programs. This research often results in lead compounds with potent inhibitory activity and promising antibacterial activity profiles. Nevertheless, it is important to understand how different physicochemical properties (e.g., logD and total polar surface area) and different structural motifs influence the compounds' permeability to ensure the efficient discovery of potent, small-molecule antibacterials particularly against Gram-negative strains. PMID:24236722

Tomaši?, Tihomir; Maši?, Lucija Peterlin

2014-01-01

344

Prioritized current unmet needs for antibacterial therapies.  

PubMed

As a result of declining new antibacterial approvals and rising antibiotic resistance, society clearly needs new treatments for bacterial infections. Specific areas of unmet need evolve over time owing to changes in resistance patterns and treatment strategies. Our goal here is to describe and prioritize the current areas of greatest unmet need for new antibacterial development based on an understanding of the most serious treatment challenges facing patients and their providers today. PMID:25056396

Spellberg, B; Shlaes, D

2014-08-01

345

Antibacterial efficacy of triclosan-incorporated polymers  

Microsoft Academic Search

Triclosan (2, 4, 4’-trichloro-2’-hydroxydiphenyl ether) is a broad-spectrum antimicrobial agent, routinely used in various personal care products.1 It is also incorporated into polymers through melt-mixing, with the aim of providing persistent antibacterial action on the surface of the polymer.2,3 Such triclosan-incorporated polymers can be promoted for hospital use as fabric seat covers, tables, chairs, and clothing. We assessed the antibacterial

Bilgé D. Kalyon; Ugursoy Olgun

2001-01-01

346

Antibacterial activity of selected glass ionomer cements.  

PubMed

Introduction: The aim of the paper was to determine the antibacterial activity of four glass ionomer cements against bacteria of the genera Streptococcus and Lactobacillus. Material and methods: Four capsulated glass ionomer cements were applied in the study: Fuji Triage (GC), Fuji IX (GC), Ketac Molar (3M Espe) and Ketac Silver (3M Espe). Four standard bacterial strains were used to assess the antibacterial activity of the studied cements: Streptococcus mutans, S. sanguis, S. salivarius and Lactobacillus casei. The antibacterial activity was determined by the agar diffusion method. The bacterial suspension was spread with a cotton swab on TSA plates. For each material six wells (7 mm diameter, 5 mm deep) were made with a cork borer. Each well was then filled with freshly prepared cements. The results were obtained by measuring the bacterial growth inhibition zone after 1, 2, 3 and 7 days. Results: Fuji Triage cement inhibited the growth of all bacterial strains. Fuji IX cement demonstrated the most potent antibacterial activity against S. sanguis. Ketac Molar showed antibacterial activity against S. sanguis and S. salivarius, whereas Ketac Silver was efficient against S. mutans as well. Neither of the Ketac cements inhibited growth of the standard L. casei strain. Discussion: Antibacterial activity of glass ionomer cements has attracted the interest of scientists in recent years. Most authors, including us, carried out experiments using the agar diffusion method and demonstrated antibacterial activity of glass ionomer cements. Different antibacterial activity of glass ionomer cements, observed in our study and studies of other authors, depended on the evaluated cement, bacterial strain and period of evaluation. PMID:24491892

Luczaj-Cepowicz, El?bieta; Marczuk-Kolada, Gra?yna; Zalewska, Anna; Pawi?ska, Ma?gorzata; Leszczy?ska, Katarzyna

2014-01-01

347

A new antibacterial compound from Ibicella lutea.  

PubMed

Ibicella lutea is a 'quasi-carnivorous' plant that grows wild in Uruguay where it is used in popular medicine as an antiseptic for eye and skin infections. In an earlier screening, it showed a broad antibacterial spectrum. From the chloroform extract of the plant the main antibacterial compound has now been isolated and identified by several MS and NMR methods as a new compound, 11-O-(6'-O-acetyl-beta-D-glucopyranosyl)-stearic acid. PMID:11091008

Cerdeiras, M P; Fernández, J; Soubes, M; Vero, S; Ferreira, F; Moyna, P; Olano, I; Vázquez, A

2000-12-01

348

Isoflavones as potentiators of antibacterial activity.  

PubMed

Isoflavones isolated from Lupinus argenteus were found to potentiate the antibacterial activity of alpha-linolenic acid, also found in the same plant. The isoflavones also potentiated the activity of the natural plant antibiotic berberine and the synthetic fluoroquinoline antibiotic norfloxacin. The isoflavones increased the uptake of berberine into Staphylococcus aureus cells, indicating that they may be inhibiting a multidrug resistance pump (MDR). Thus, L. argenteus contains a weak antibacterial and also MDR pump inhibitors, which increase its potency. PMID:12952418

Morel, Cécile; Stermitz, Frank R; Tegos, George; Lewis, Kim

2003-09-10

349

ANTIBACTERIAL ACTIVITY OF THYMUS DAENENSIS METHANOLIC EXTRACT  

Microsoft Academic Search

Medicinal plants are potential of antimicrobial compounds. The present study deals with the antibacterial activity of methanolic extract of Thymus daenensis. Aerial parts of the plant were collected from Alvand mountainside (Hamadan, Iran) in May 2005, air-dried and extracted by methanol. The dried extract was redissolved in methanol to make a 100mg\\/ml solution and then filtered. Antibacterial activity of the

FARAZ MOJAB; MAHSHID POURSAEED; HADI MEHRGAN; SHIMA PAKDAMAN

2008-01-01

350

A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore  

SciTech Connect

As the need for novel antibiotic classes to combat bacterial drug resistance increases, the paucity of leads resulting from target-based antibacterial screening of pharmaceutical compound libraries is of major concern. One explanation for this lack of success is that antibacterial screening efforts have not leveraged the eukaryotic bias resulting from more extensive chemistry efforts targeting eukaryotic gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on antibacterial target space resembling these eukaryotic targets, we used whole-cell screening to identify a series of antibacterial pyridopyrimidines derived from a protein kinase inhibitor pharmacophore. In bacteria, the pyridopyrimidines target the ATP-binding site of biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid biosynthesis. These inhibitors are effective in vitro and in vivo against fastidious Gram-negative pathogens including Haemophilus influenzae. Although the BC active site has architectural similarity to those of eukaryotic protein kinases, inhibitor binding to the BC ATP-binding site is distinct from the protein kinase-binding mode, such that the inhibitors are selective for bacterial BC. In summary, we have discovered a promising class of potent antibacterials with a previously undescribed mechanism of action. In consideration of the eukaryotic bias of pharmaceutical libraries, our findings also suggest that pursuit of a novel inhibitor leads for antibacterial targets with active-site structural similarity to known human targets will likely be more fruitful than the traditional focus on unique bacterial target space, particularly when structure-based and computational methodologies are applied to ensure bacterial selectivity.

Miller, J. Richard; Dunham, Steve; Mochalkin, Igor; Banotai, Craig; Bowman, Matthew; Buist, Susan; Dunkle, Bill; Hanna, Debra; Harwood, H. James; Huband, Michael D.; Karnovsky, Alla; Kuhn, Michael; Limberakis, Chris; Liu, Jia Y.; Mehrens, Shawn; Mueller, W. Thomas; Narasimhan, Lakshmi; Ogden, Adam; Ohren, Jeff; Prasad, J.V.N. Vara; Shelly, John A.; Skerlos, Laura; Sulavik, Mark; Thomas, V. Hayden; VanderRoest, Steve; Wang, LiAnn; Wang, Zhigang; Whitton, Amy; Zhu, Tong; Stover, C. Kendall; (Pfizer)

2009-06-25

351

In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae)  

Microsoft Academic Search

BACKGROUND: Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of

Assam Assam JP; JP Dzoyem; CA Pieme; VB Penlap

2010-01-01

352

Contamination of honey by the herbicide asulam and its antibacterial active metabolite sulfanilamide.  

PubMed

A number of antibacterial drugs (antibiotics) like sulfonamides, tetracyclines and streptomycin are used for the treatment of bacterial diseases in beehives. Yet, the finding of sulfanilamide residues in some 15 Swiss honeys out of some 350 samples could not be explained by such apicultural practice. Bees occasionally collect nectar from meadows treated with the herbicide asulam. Such honey is not only contaminated by asulam, but also by its degradation product sulfanilamide. This is the first report that the use of a herbicide causes the appearance of residues of an antibacterial active metabolite belonging to the category of sulfonamide drugs in food. The relevance of this finding lies in the fact that the use of the herbicide asulam might cause unacceptable residue levels of sulfanilamide in a product fbr human consumption. PMID:15204534

Kaufmann, A; Kaenzig, A

2004-06-01

353

Biotin Analogues with Antibacterial Activity Are Potent Inhibitors of Biotin Protein Ligase  

PubMed Central

There is a desperate need to develop new antibiotic agents to combat the rise of drug-resistant bacteria, such as clinically important Staphylococcus aureus. The essential multifunctional enzyme, biotin protein ligase (BPL), is one potential drug target for new antibiotics. We report the synthesis and characterization of a series of biotin analogues with activity against BPLs from S. aureus, Escherichia coli, and Homo sapiens. Two potent inhibitors with Ki < 100 nM were identified with antibacterial activity against a panel of clinical isolates of S. aureus (MIC 2–16 ?g/mL). Compounds with high ligand efficiency and >20-fold selectivity between the isozymes were identified and characterized. The antibacterial mode of action was shown to be via inhibition of BPL. The bimolecular interactions between the BPL and the inhibitors were defined by surface plasmon resonance studies and X-ray crystallography. These findings pave the way for second-generation inhibitors and antibiotics with greater potency and selectivity.

2012-01-01

354

The Cyclic Cystine Ladder in ?-Defensins Is Important for Structure and Stability, but Not Antibacterial Activity*  

PubMed Central

?-Defensins are ribosomally synthesized cyclic peptides found in the leukocytes of some primate species and have promising applications as antimicrobial agents and scaffolds for peptide drugs. The cyclic cystine ladder motif, comprising a cyclic peptide backbone and three parallel disulfide bonds, is characteristic of ?-defensins. In this study, we explore the role of the cyclic peptide backbone and cystine ladder in the structure, stability, and activity of ?-defensins. ?-Defensin analogues with different numbers and combinations of disulfide bonds were synthesized and characterized in terms of their NMR solution structures, serum and thermal stabilities, and their antibacterial and membrane-binding activities. Whereas the structures and stabilities of the peptides were primarily dependent on the number and position of the disulfide bonds, their antibacterial and membrane-binding properties were dependent on the cyclic backbone. The results provide insights into the mechanism of action of ?-defensins and illustrate the potential of ?-defensin analogues as scaffolds for peptide drug design.

Conibear, Anne C.; Rosengren, K. Johan; Daly, Norelle L.; Henriques, Sonia Troeira; Craik, David J.

2013-01-01

355

Supramolecular photochemistry of drugs in biomolecular environments.  

PubMed

In this tutorial review we illustrate how the interaction of photoactive drugs/potential drugs with proteins or DNA in supramolecular complexes can determine the course of the reactions initiated by the drug absorbed photons, evidencing the mechanistic differences with respect to the solution conditions. We focus on photoprocesses, independent of oxygen, that lead to chemical modification of the biomolecules, with formation of new covalent bonds or cleavage of existing bonds. Representative systems are mainly selected from the literature of the last decade. The photoreactivity of some aryl propionic acids, (fluoro)quinolones, furocoumarins, metal coordination complexes, quinine-like compounds, naphthaleneimides and pyrenyl-peptides with proteins or DNA is discussed. The use of light for biomolecule photomodification, historically relevant to biological photosensitization processes and some forms of photochemotherapy, is nowadays becoming more and more important in the development of innovative methods in nanomedicine and biotechnology. PMID:24464275

Monti, Sandra; Manet, Ilse

2014-05-27

356

Bacteriophages as twenty-first century antibacterial tools for food and medicine  

Microsoft Academic Search

Antibiotic-resistant bacteria are an increasing source of concern in all environments in which these drugs have been used.\\u000a More stringent regulations have led to a slow but sure decrease in antibiotic use in the food industry worldwide, but have\\u000a also stimulated the search for alternative antibacterial agents. In medicine, the number of people infected with pan-resistant\\u000a bacteria is driving research

Damien Maura; Laurent Debarbieux

2011-01-01

357

Evaluation of antibacterial, antifungal, and antioxidant properties of some food dyes  

Microsoft Academic Search

Natural dyes find use in the coloring of textiles, drugs, cosmetics, etc. Owing to their nontoxic effects, they are also used\\u000a for coloring various food products. In the present study antimicrobial properties of 8 food dyes against 10 bacteria and 5\\u000a fungal organisms were investigated. It was observed that red dyes showed best antibacterial activity while yellow dyes showed\\u000a better

Ramamoorthy Siva; Meera George Palackan; Lubaina Maimoon; T. Geetha; Dipita Bhakta; P. Balamurugan; S. Rajanarayanan

2011-01-01

358

Proarrhythmic Effects of Fluoroquinolone Antibacterial Agents: In Vivo Effects as Physiologic Substrate for Torsades  

Microsoft Academic Search

Drug-induced prolongation of the QT interval is often associated with the onset of Torsades de Pointes (TdP) resulting in a life-threatening ventricular arrhythmia. The potential of the proarrhythmic effects of the new fluoroquinolone antibacterial agents, levofloxacin and sparfloxacin, was examined in the chronic complete atrioventricular block dogs with stable idioventricular automaticity using Holter ECG monitoring in conscious state (Experiment 1).

Katsuyoshi Chiba; Atsushi Sugiyama; Yoshioki Satoh; Hiroyuki Shiina; Keitaro Hashimoto

2000-01-01

359

Development of azithromycin-PLGA nanoparticles: physicochemical characterization and antibacterial effect against Salmonella typhi.  

PubMed

The objective of the present research was to formulate poly(lactide-co-glycolide) nanoparticles loaded with azithromycin with appropriate physicochemical properties and antimicrobial activity. Azithromycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared in three different ratios of drug to polymer by nanoprecipitation technique. Antibacterial activity of these nanoparticles was examined against gram-negative intra cellular microorganism Salmonella typhi. The antibacterial effect was investigated using serial dilution technique to achieve the minimum inhibitory concentration (MIC) of nanoparticles. The results showed that physicochemical properties were affected by drug to polymer ratio. The results showed that nanoscale size particles ranging from 212 to 252nm were achieved. Physicochemical properties were affected by drug to polymer ratio. The highest entrapment efficiency (78.5+/-4.2%) was obtained when the ratio of drug to polymer was 1:3. Zeta (zeta) potential of the nanoparticles was fairly negative. The DSC thermograms and X-ray diffraction patterns revealed that the drug in the nanoparticles was in amorphous state. FT-IR spectroscopy demonstrated no detectable interactions between the drug and polymer in molecular level. In vitro release study showed two phases: an initial burst for 4h followed by a very slow release pattern during a period of 24h. The results of antimicrobial activity test showed that the nanoparticles were more effective than pure azithromycin against S. typhi with the nanoparticles showing equal antibacterial effect at 1/8 concentration of the intact drug. In conclusion, the azithromycin nanoparticle preparations showed appropriate physicochemical and improved antimicrobial properties which can be useful for oral administration. PMID:20558048

Mohammadi, Ghobad; Valizadeh, Hadi; Barzegar-Jalali, Mohammad; Lotfipour, Farzaneh; Adibkia, Khosro; Milani, Morteza; Azhdarzadeh, Morteza; Kiafar, Farhad; Nokhodchi, Ali

2010-10-01

360

Rapid test for distinguishing membrane-active antibacterial agents.  

PubMed

In the search for antibacterial agents with a novel mode-of-action (MOA) many targeted cellular and cell-free assays are developed and used to screen chemical and natural product libraries. Frequently, hits identified by the primary screens include compounds with nonspecific activities that can affect the integrity and function of bacterial membrane. For a rapid dereplication of membrane-active compounds, a simple method was established using a commercially available Live/Dead(R) Bacterial Viability Kit. This method utilized two fluorescent nucleic acid stains, SYTO9 (stains all cells green) and propidium iodide (stains cells with damaged membrane red) for the drug-treated bacterial cells. The cells were then either examined visually by fluorescence microscopy or their fluorescence emissions were recorded using a multi-label plate reader set to measure emissions at two different wavelengths. The ratio of green versus red was compared to a standard curve indicating the percentage of live versus dead bacteria. Nine known antibiotics and 14 lead compounds from various antibacterial screens were tested with results consistent with their MOA. PMID:16631264

Prakash Singh, Maya

2006-10-01

361

4-Quinolones as Noncovalent Inhibitors of High Molecular Mass Penicillin-Binding Proteins  

PubMed Central

Penicillin-binding proteins (PBPs) are important bacterial enzymes that carry out the final steps of bacterial cell wall assembly. Their DD-transpeptidase activity accomplishes the essential peptide cross-linking step of the cell wall. To date, all attempts to discover effective inhibitors of PBPs, apart from ?-lactams, have not led to new antibiotics. Therefore, the need for new classes of efficient inhibitors of these enzymes remains. Guided by a computational fragment-based docking procedure, carried out on Escherichia coli PBP5, we have designed and synthesized a series of 4-quinolones as potential inhibitors of PBPs. We describe their binding to the PBPs of E. coli and Bacillus subtilis. Notably, these compounds bind quite tightly to the essential high molecular mass PBPs.

2012-01-01

362

An imported enteric fever caused by a quinolone-resistant Salmonella typhi  

PubMed Central

Recent reports indicate that nalidixic acid susceptibility correlates well with the clinical outcome of patients with Salmonella Typhi infection treated with quinolones. We report a case of enteric fever caused by S Typhi in which the isolate was resistant to nalidixic acid, but showed in vitro susceptibility to ciprofloxacin. Following treatment with ciprofloxacin, the clinical outcome was not satisfactory and the patient had a relapse. However, after using a higher dose of ciprofloxacin, the patient was cured. We recommend that all Salmonella systemic infections resistant to nalidixic acid with in vitro but decreased susceptibility to fluoroquinolones be treated with other antibiotics like third-generation cephalosporins or azithromycin. These patients should be closely followed up and observed for further relapse.

Somily, Ali M.

2010-01-01

363

The SOS response promotes qnrB quinolone-resistance determinant expression  

PubMed Central

The qnr genes are plasmid-borne fluoroquinolone-resistance determinants widespread in Enterobacteriaceae. Three families of qnr determinants (qnrA, B and S) have been described, but little is known about their expression and regulation. Two new determinants, qnrC and qnrD, have been found recently. Here, we describe the characterization of the qnrB2 promoter and the identification of a LexA-binding site in the promoter region of all qnrB alleles. LexA is the central regulator of the SOS response to DNA damage. We show that qnrB2 expression is regulated through the SOS response in a LexA/RecA-dependent manner, and that it can be induced by the quinolone ciprofloxacin, a known inducer of the SOS system. This is the first description of direct SOS-dependent regulation of an antibiotic-resistance mechanism in response to the antibiotic itself.

Da Re, Sandra; Garnier, Fabien; Guerin, Emilie; Campoy, Susana; Denis, Francois; Ploy, Marie-Cecile

2009-01-01

364

A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis  

Microsoft Academic Search

BACKGROUND: The first report on the transferable, plasmid-mediated quinolone-resistance determinant qnrA1 was in 1998. Since then, qnr alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP) family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural

Qinglan Guo; Jingwei Weng; Xiaogang Xu; Minghua Wang; Xiaoying Wang; Xinyu Ye; Wenning Wang; Minggui Wang

2010-01-01

365

Mobilizable IncQ-Related Plasmid Carrying a New Quinolone Resistance Gene, qnrS2, Isolated from the Bacterial Community of a Wastewater Treatment Plant  

Microsoft Academic Search

Plasmid-encoded quinolone resistance was previously reported for different bacteria isolated from patients not only in the United States and Asia but also in Europe. Here we describe the isolation, by applying a new selection strategy, of the quinolone resistance plasmid pGNB2 from an activated sludge bacterial community of a wastewater treatment plant in Germany. The hypersensitive Escherichia coli strain KAM3

Gabriele Bonemann; Michael Stiens; Alfred Puhler; Andreas Schluter

2006-01-01

366

Characteristics of Plasmid-Mediated Quinolone Resistance Genes in Extended-Spectrum Cephalosporin-Resistant Isolates of Klebsiella pneumoniae and Escherichia coli in Korea  

Microsoft Academic Search

Background: Quinolone resistance is frequently associated with extended-spectrum cephalosporin resistance in Enterobacteriaceae. Methods: The characteristics of plasmid-mediated quinolone resistance (PMQR) genes [qnr genes, aac(6?)-Ib-cr and qepA] in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to extended-spectrum cephalosporin were studied. Results: 5 and 4 of 95 E. coli isolates but 46 (86\\/187) and 6% (12\\/187) of K. pneumoniae had

Mi-Ran Seo; Yoon Soo Park; Hyunjoo Pai

2010-01-01

367

Detection of plasmid-mediated quinolone resistance determinant QnrS1 in an extended-spectrum ?-lactamase-producing Enterobacter cloacae in Tunisia  

Microsoft Academic Search

A clinical isolate of Enterobacter cloacae BF280 showing a multidrug resistance phenotype including resistance to ?-lactams and quinolones is the subject of this study.\\u000a This strain was isolated from a patient at the intensive care unit of a military hospital (hôpital Militaire de Tunis). By\\u000a polymerase chain reaction amplification and sequencing, this isolate was found to produce quinolone resistance determinant

Amel Bourouis; Véronique Dubois; Hella Chihi; Chérifa Beladj; Mohamed Ben Moussa; Claudine Quentin; Omrane Belhadj

2010-01-01

368

High Prevalence of Plasmid-Mediated Quinolone Resistance Genes qnr and aac(6')-Ib-cr in Clinical Isolates of Enterobacteriaceae from Nine Teaching Hospitals in China  

Microsoft Academic Search

Quinolone resistance is an emerging problem in China. To investigate the prevalence of the plasmid- mediated quinolone resistance genes qnr and aac(6)-Ib-cr, a total of 265 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Enterobacter cloacae with ciprofloxacin MICs of >0.25 g\\/ml were screened at nine teaching hospitals in China. The qnrA, qnrB, qnrS, and aac(6)-Ib genes were

Hong Yang; Hongbin Chen; Qiwen Yang; Minjun Chen; Hui Wang

2008-01-01

369

High-resolution melting assay for the detection of gyrA mutations causing quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi.  

PubMed

We developed a novel rapid assay to detect the gyrA mutations that cause quinolone resistance in typhoid and paratyphoid fever Salmonella spp. using high-resolution melting (Idaho Technology, Salt Lake City, UT) analysis of polymerase chain reaction amplicons. The presence of gyrA mutations led to small but consistent changes in amplicon melting temperatures that allowed quinolone-resistant isolates to be differentiated from susceptible ones. PMID:17156963

Slinger, Robert; Bellfoy, Deana; Desjardins, Marc; Chan, Francis

2007-04-01

370

Quinolones induce partial or total loss of pathogenicity islands in uropathogenic Escherichia coli by SOS-dependent or -independent pathways, respectively.  

PubMed

Escherichia coli is the most common microorganism causing urinary tract infections. Quinolone-resistant E. coli strains have fewer virulence factors than quinolone-susceptible strains. Several urovirulence genes are located in pathogenicity islands (PAIs). We investigated the capacity of quinolones to induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor 1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic E. coli strains. In a multistep selection, all strains lost hemolytic capacity at between 1 and 4 passages when they were incubated with subinhibitory concentrations of ciprofloxacin, showing a partial or total loss of the PAI containing the hly (hemolysin) and cnf-1 (cytotoxic necrotizing factor 1) genes. RecA(-) mutants were obtained from the two E. coli strains with partial or total loss of the PAI. The inactivation of the RecA protein affected only the partial loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed on incubation in the absence of quinolones in either the wild-type or mutant E. coli strains. Quinolones induce partial or total loss of PAIs in vitro in uropathogenic E. coli by SOS-dependent or -independent pathways, respectively. PMID:16436722

Soto, S M; Jimenez de Anta, M T; Vila, J

2006-02-01

371

In vitro antibacterial activity of Hibiscus rosa-sinensis flower extract against human pathogens  

PubMed Central

Objective To access the in vitro antibacterial activity of Hibiscus rosa-sinensis (H. rosa- sinensis) flower extract against human pathogens. Methods Antibacterial activity was evaluated by using disc and agar diffusion methods. The protein was run through poly acrylmide gel electrophoresis to view their protein profile. Results The results showed that the cold extraction illustrates a maximum zone of inhibition against Bacillus subtillis (B. subtillis), Escherichia coli (E. coli) viz., (17.00 ± 2.91), (14.50 ± 1.71) mm, followed by hot extraction against, E. coli, Salmonella sp. as (11.66 ± 3.14), (10.60 ± 3.09) mm. In methanol extraction showed a highest zone of inhibition recorded against B. subtillis, E. coli as (18.86 ± 0.18), (18.00 ± 1.63) mm pursued by ethanol extraction showed utmost zone of inhibition recorded against Salmonella sp. at (20.40 ± 1.54) mm. The crude protein from flower showed a maximum inhibitory zone observed against Salmonella sp., E. coli viz., (16.55 ± 1.16), (14.30 ± 2.86) mm. The flower material can be taken as an alternative source of antibacterial agent against the human pathogens. Conclusions The extracts of the H. rosa-sinensis are proved to have potential antibacterial activity, further studies are highly need for the drug development.

Ruban, P; Gajalakshmi, K

2012-01-01

372

A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity.  

PubMed

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G; McAdam, Alexander J; Husson, Robert N; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I

2012-01-01

373

A novel antibacterial resin composite for improved dental restoratives.  

PubMed

A novel furanone-containing antibacterial resin composite has been prepared and evaluated. compressive strength (CS) and Streptococcus mutans viability were used to evaluate the mechanical strength and antibacterial activity of the composites. The modified resin composites showed a significant antibacterial activity without substantially decreasing the mechanical strengths. With 5-30 % addition of the furanone derivative, the composite kept its original CS unchanged but showed a significant antibacterial activity with a 16-68 % reduction in the S. mutans viability. Further, the antibacterial function of the new composite was not affected by human saliva. The aging study indicates that the composite may have a long-lasting antibacterial function. Within the limitations of this study, it appears that the experimental antibacterial resin composite may potentially be developed into a clinically attractive dental restorative due to its high mechanical strength and antibacterial function. PMID:22466818

Weng, Yiming; Howard, Leah; Guo, Xia; Chong, Voon Joe; Gregory, Richard L; Xie, Dong

2012-06-01

374

Antibacterial activity of the essential oil from Ferula gummosa seed.  

PubMed

Antibacterial activity of Ferula gummosa essential oil was studied against bacterial laboratory ATCC standards using the disk diffusion method. The results showed activity against Gram(+) bacteria and Escherichia coli. Little antibacterial activity was found against Pseudomonas aeruginosa. PMID:15567258

Eftekhar, Fereshteh; Yousefzadi, Morteza; Borhani, K

2004-12-01

375

76 FR 59406 - Anti-Infective Drugs Advisory Committee; Notice of Meeting  

Federal Register 2010, 2011, 2012, 2013

...antibacterials for the treatment of community-acquired bacterial pneumonia and the draft document entitled ``Guidance for Industry: Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment,'' published March 2009...

2011-09-26

376

77 FR 61417 - Guidance for Industry on Acute Bacterial Sinusitis: Developing Drugs for Treatment; Availability  

Federal Register 2010, 2011, 2012, 2013

...Administration Safety and Innovation Act that FDA review guidances for the conduct of clinical trials with respect to antibacterial and antifungal drugs, and revise such guidances as appropriate.\\2\\...

2012-10-09

377

Alterations in the GyrA Subunit of DNA Gyrase and the ParC Subunit of Topoisomerase IV in Quinolone-Resistant Clinical Isolates ofKlebsiella pneumoniae  

Microsoft Academic Search

We determined a partial sequence of theKlebsiella pneumoniae parCgene, including the region analogous to the quinolone resistance-determining region of theEscherichia coli gyrAgene, and examined 26 clinical strains ofK. pneumoniae for an association of alterations in GyrA and ParC with susceptibilities to quinolones. The study suggests that inK. pneumoniaeDNA gyrase is a primary target of quinolones and that ParC alterations play

TAKASHI DEGUCHI; AKIHISA FUKUOKA; MITSURU YASUDA; MASAHIRO NAKANO; SHIGEHIKO OZEKI; EMIKO KANEMATSU; YOSHINORI NISHINO; SATOSHI ISHIHARA; YOSHIHITO BAN; ANDYUKIMICHI KAWADA

378

A new antibacterial titanium-copper sintered alloy: preparation and antibacterial property.  

PubMed

Copper element was added in pure titanium by a powder metallurgy to produce a new antibacterial titanium-copper alloy (Ti-Cu alloy). This paper reported the very early stage results, emphasizing on the preparation, mechanical property and antibacterial activity. The phase constitution was analyzed by XRD and the microstructure was observed under SEM equipped with EDS. The hardness, the compressive strength and the corrosion resistance of Ti-Cu alloy were tested in comparison with cp-Ti. The antibacterial property of the Ti-Cu alloy was assessed by two methods: agar diffusion assay and plate-count method, in which Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were used. XRD and SEM results showed that Ti2Cu phase and Cu-rich phase were synthesized in the Ti-Cu sintered alloy, which significantly increases the hardness and the compressive strength compared with cp-Ti and slightly improves the corrosion resistance. No antibacterial activity was detected by the agar diffusion assay on the Ti-Cu alloy, but the plate-count results indicated that the Ti-Cu alloy exhibited strong antibacterial property against both bacteria even after three polishing treatments, which demonstrates strongly that the whole alloy is of antibacterial activity. The antibacterial mechanism was thought to be in associated with the Cu ion released from the Ti-Cu alloy. PMID:23910344

Zhang, Erlin; Li, Fangbing; Wang, Hongying; Liu, Jie; Wang, Chunmin; Li, Muqin; Yang, Ke

2013-10-01

379

Quinolone resistance is associated with increased risk of invasive illness or death during infection with Salmonella serotype Typhimurium.  

PubMed

In a registry-based cohort study, we determined the risk of invasive illness or death associated with infection with quinolone-resistant Salmonella serotype Typhimurium. We linked data from the Danish surveillance registry of enteric pathogens with data from the Danish civil registration system and 2 national health registries. Of 1323 patients infected with Salmonella Typhimurium, 46 (3.5%) were hospitalized due an invasive illness within 90 days of infection, and 16 (1.2%) died within 90 days of infection. After adjustment for age, sex, and comorbidity, infection with quinolone-resistant Salmonella Typhimurium was associated with a 3.15-fold (95% confidence interval, 1.39-7.10-fold) higher risk of invasive illness or death within 90 days of infection, compared with that observed for infection with pansusceptible strains. PMID:15478071

Helms, Morten; Simonsen, Jacob; Molbak, Kare

2004-11-01

380

Room temperature ionic liquid-mediated molecularly imprinted polymer monolith for the selective recognition of quinolones in pork samples.  

PubMed

A novel molecularly imprinted polymer monolith was prepared by the room temperature ionic liquid-mediated in situ molecular imprinting technique, using norfloxacin (NOR) as the template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker. The optimal synthesis conditions and recognition properties of NOR-imprinted monolithic column were investigated. The results indicated that the imprinted monoliths exhibited good ability of selective recognition against the template and its structural analog. Using the fabricated material as solid-phase extraction sorbent, a sample pre-treatment procedure of molecularly imprinted solid-phase extraction coupling with HPLC was developed for determination of trace quinolone residues in animal tissues samples. The recoveries ranging from 78.16 to 93.50% for eight quinolones antibiotics such as marbofloxacin, NOR, ciprofloxacin, danofloxacin, difloxacin, oxolinic acid, flumequine and enrofloxacin were obtained. PMID:21082676

Sun, Xiangli; He, Jia; Cai, Guorui; Lin, Anqing; Zheng, Wenjie; Liu, Xuan; Chen, Langxing; He, Xiwen; Zhang, Yukui

2010-12-01

381

Validation of an enzyme-linked immunosorbent assay screening for quinolones in egg, poultry muscle and feed samples.  

PubMed

Quinolones are a group of chemotherapeutic agents with an excellent efficiency against poultry pathogens. Two commercial enzyme-linked immunosorbent assay (ELISA) tests have been applied in parallel for the qualitative screening analysis of several quinolones in eggs, poultry muscle and feeds at the required levels. During the validation study, carried out according to the Commission Decision 2002/657/EC criteria, two different sample treatments were compared in foods: the simple and fast procedure suggested by the kit producer (Euro-Diagnostica) and a more complex solid-phase extraction (SPE) sample preparation. The results demonstrated that the method based on SPE clean up exhibited better characteristic performances, particularly in eggs for which lower detection levels are required. Despite the fact that screening methods should be rapid and cheap, the use of non-chromatographic techniques such as ELISA for multiresidual detection of a class of substances involves some additional attention to sample preparation. PMID:19286040

Scortichini, Giampiero; Annunziata, Loredana; Di Girolamo, Valeria; Buratti, Roberta; Galarini, Roberta

2009-04-01

382

Synergy of non-antibiotic drugs and pyrimidinethiol on gold nanoparticles against superbugs.  

PubMed

Co-presenting non-antibiotic drugs and pyrimidinethiol on gold nanoparticles (NPs) can generate broad-spectrum antibacterial and bactericidal activities against superbugs. Dimethylbiguanide (metformin), an anti-hyperglycemic drug, shows the best enhanced activity via increasing the ability to compromise bacterial cell walls. Synergistic effects are also reflected in the eradicating biofilm cells. Our findings suggest a large chemical space to develop new antibacterial materials to treat superbugs. PMID:23957534

Zhao, Yuyun; Chen, Zeliang; Chen, Yanfen; Xu, Jie; Li, Jinghong; Jiang, Xingyu

2013-09-01

383

A Comparison between Antibacterial Activity of Propolis and Aloe vera on Enterococcus faecalis (an In Vitro Study)  

PubMed Central

Removing the bacteria, including Enterococcus faecalis, from the root canal is one of the important aims in endodontic treatment.We aimed to compare the antibacterial activity of Chlorhexidine with two natural drugs. The antibacterial activities of three different propolis extracts (alcohol concentrations: 0, 15, 40%) and Aloe vera gel on E. faecalis were compared using three methods: disk diffusion, microdilution and direct contact test. In addition to the above bacterium, the Aloe vera gel effect on Staphylococcus aureus and Streptococcus mutans was evaluated. Disk diffusion test revealed that propolis ethanolic extracts (the alcohol concentration of 15 and 40%) and Aloe vera gel have antibacterial activities but aqueous extract of propolis did not show any effect in this test. The MICs for propolis ethanolic extracts, Aloe vera gel and aqueous extract of propolis (0% alcohol) were 313 µg/ml, 750 µg/ml, 2250 µg/ml, and ? 500 µg/ml respectively, much higher than the Chlorhexidine one. In direct contact test, contrary to Aloe vera, all three propolis extracts showed antibacterial effects on E. faecalis. The Aloe vera gel also showed significant antibacterial effect on S.aureus and S.mutans. The hydroalcoholic extracts of propolis and Aloe vera gel had antibacterial effects on E. faecalis, however, propolis is more potent than Aloe vera. The antibacterial effect of Aloe vera on S. aureus and S. mutans is low (MIC ? 2250 µg/ml). Appropriate concentrations of alcoholic extracts of propolis and some fractions of Aloe vera gel might be good choices for disinfecting the root canal in endodontic treatments.

Ehsani, Maryam; Amin Marashi, Mahmood; Zabihi, Ebrahim; Issazadeh, Maryam; Khafri, Soraya

2013-01-01

384

A Comparison between Antibacterial Activity of Propolis and Aloe vera on Enterococcus faecalis (an In Vitro Study).  

PubMed

Removing the bacteria, including Enterococcus faecalis, from the root canal is one of the important aims in endodontic treatment.We aimed to compare the antibacterial activity of Chlorhexidine with two natural drugs. The antibacterial activities of three different propolis extracts (alcohol concentrations: 0, 15, 40%) and Aloe vera gel on E. faecalis were compared using three methods: disk diffusion, microdilution and direct contact test. In addition to the above bacterium, the Aloe vera gel effect on Staphylococcus aureus and Streptococcus mutans was evaluated. Disk diffusion test revealed that propolis ethanolic extracts (the alcohol concentration of 15 and 40%) and Aloe vera gel have antibacterial activities but aqueous extract of propolis did not show any effect in this test. The MICs for propolis ethanolic extracts, Aloe vera gel and aqueous extract of propolis (0% alcohol) were 313 µg/ml, 750 µg/ml, 2250 µg/ml, and ? 500 µg/ml respectively, much higher than the Chlorhexidine one. In direct contact test, contrary to Aloe vera, all three propolis extracts showed antibacterial effects on E. faecalis. The Aloe vera gel also showed significant antibacterial effect on S.aureus and S.mutans. The hydroalcoholic extracts of propolis and Aloe vera gel had antibacterial effects on E. faecalis, however, propolis is more potent than Aloe vera. The antibacterial effect of Aloe vera on S. aureus and S. mutans is low (MIC ? 2250 µg/ml). Appropriate concentrations of alcoholic extracts of propolis and some fractions of Aloe vera gel might be good choices for disinfecting the root canal in endodontic treatments. PMID:24551800

Ehsani, Maryam; Amin Marashi, Mahmood; Zabihi, Ebrahim; Issazadeh, Maryam; Khafri, Soraya

2013-01-01

385

In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens.  

PubMed

The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml). PMID:3101590

Liebowitz, L D; Saunders, J; Fehler, G; Ballard, R C; Koornhof, H J

1986-12-01

386

Susceptibility and bactericidal activity of 8 oral quinolones against conventional-fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates.  

PubMed

We evaluated the pharmacokinetic/pharmacodynamic parameters of 8 oral quinolones (ciprofloxacin, garenoxacin [GRNX], gatifloxacin, levofloxacin, moxifloxacin, prulifloxacin, sitafloxacin, and sparfloxacin) on 11 fluoroquinolone-resistant Streptococcus pneumoniae strains, screened from 780 strains isolated from various clinical sources in Japan. GRNX showed the highest area under the blood concentration time curve/MIC ratios, which exceeded the target values for bacterial eradication against all fluoroquinolone-resistant S. pneumoniae strains. PMID:19679241

Yokota, Shin-ichi; Ohkoshi, Yasuo; Fujii, Nobuhiro

2009-09-01

387

SIMULTANEOUS DETERMINATION OF 14 QUINOLONES IN ROYAL JELLY BY LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY USING ANIONEXCHANGE SOLIDPHASE EXTRACTION  

Microsoft Academic Search

A new method based on liquid chromatography-tandem mass spectrometry has been developed for simultaneous determination of 14 quinolones (QNs) residues, including ciprofloxacin, danofloxacin, difloxacin, enoxacin, enrofloxacin, flumequine, lomefloxacin, marbofloxacin, norfloxacin, orbifloxacin, ofloxacin, pipemidic acid, pefloxacin, and sarafloxacin in royal jelly. The proposed analytical procedure involves extraction of the QNs from samples by 0.1 M sodium hydroxide aqueous solution, a step for

Chong-yu Shen; Dong-xu Shen; Tao Ding; Jin-zhong Xu; Yuan Jiang; Bin Wu; Hong-zhen Lian

2011-01-01

388

Contribution of the ATP Binding Site of ParE to Susceptibility to Novobiocin and Quinolones in Streptococcus pneumoniae  

Microsoft Academic Search

In Streptococcus pneumoniae, an H103Y substitution in the ATP binding site of the ParE subunit of topo- isomerase IV was shown to confer quinolone resistance and hypersensitivity to novobiocin when associated with an S84F change in the A subunit of DNA gyrase. We reconstituted in vitro the wild-type topoisomerase IV and its ParE mutant. The ParE mutant enzyme showed a

Philippe Dupont; Alexandra Aubry; Emmanuelle Cambau; Laurent Gutmann

2005-01-01

389

Prevalence and risk factors for quinolone resistance among Escherichia coli strains isolated from males with community febrile urinary tract infection  

Microsoft Academic Search

The purpose of this study was to evaluate the prevalence and clinical risk factors for quinolone resistance (QR) in E. coli strains from males with febrile urinary tract infection (FUTI). An ambispective cross-sectional study was performed in which\\u000a we evaluated 153 males with a community FUTI caused by E. coli. Among the 153 FUTI episodes, 101 (66%) were due to

A. Smithson; C. Chico; J. Ramos; C. Netto; M. Sanchez; J. Ruiz; R. Porron; M. T. Bastida

390

New Plasmid-Mediated Quinolone Resistance Gene, qnrC, Found in a Clinical Isolate of Proteus mirabilis  

Microsoft Academic Search

Since the discovery of qnrA in 1998, two additional qnr genes, qnrB and qnrS, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of Proteus mirabilis was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10,

Minghua Wang; Qinglan Guo; Xiaogang Xu; Xiaoying Wang; Xinyu Ye; Shi Wu; David C. Hooper; Minggui Wang

2009-01-01

391

Rapid detection of qnr and qepA plasmid-mediated quinolone resistance genes using real-time PCR  

Microsoft Academic Search

Plasmid-mediated quinolone resistance genes in clinical strains cannot be detected by phenotypic traits but require gene detection. We developed a multiplex real-time polymerase chain reaction (PCR) assay using high-resolution melting master mix with ResoLight dye to detect qnr genes and a simplex real-time PCR assay using SYBR Green I to detect qepA genes. Using qnr-positive and qepA1-positive control strains, the

Thomas Guillard; Hélène Moret; Lucien Brasme; Antoine Carlier; Véronique Vernet-Garnier; Emmanuelle Cambau; Christophe de Champs

2011-01-01

392

Single and Multiple-Dose Pharmacokinetics of AM1155, a New 6-Fluoro-8Methoxy Quinolone, in Humans  

Microsoft Academic Search

The pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, was examined in healthy male volunteers after the oral administration of a single dose of 100, 200, 400, or 600 mg and multiple doses of 300 mg twice daily for 6.5 days (13 total doses). Throughout the whole study period, AM-1155 was well tolerated in every subject. In the single-dose study, the

MITSUYOSHI NAKASHIMA; TOSHIHIKO UEMATSU; KAZUHIRO KOSUGE; HISAO KUSAJIMA; TSUYOSHI OOIE; YUICHI MASUDA; RYOZO ISHIDA; ANDHIROSHI UCHIDA

1995-01-01

393

Mutations in Topoisomerase IV and DNA Gyrase of Staphylococcus aureus: Novel Pleiotropic Effects on Quinolone and Coumarin Activity  

Microsoft Academic Search

Previous studies have shown that topoisomerase IV and DNA gyrase interact with quinolones and coumarins in different ways. The MICs of coumarins (novobiocin and coumermycin) for MT5, a Staphylococcus aureus nov mutant, are higher than those for wild-type strains. Sequencing the gyrB gene encoding one subunit of the DNA gyrase revealed the presence of a double mutation likely to be

BENEDICTE FOURNIER; DAVID C. HOOPER

1998-01-01

394

Relationship between clinical efficacy of treatment of pulmonary Mycobacterium avium complex disease and drug-sensitivity testing of Mycobacterium avium complex isolates  

Microsoft Academic Search

We prospectively investigated the relationship between the clinical efficacy of treatment of pulmonary Mycobacterium avium complex (MAC) disease and drug-sensitivity testing of MAC isolates for antituberculous drugs, new quinolone antibiotics,\\u000a and clarithromycin (CAM). Fifty-two patients who satisfied the diagnostic criteria of the American Thoracic Society (ATS)\\u000a and who received treatment between April 1998 and December 2005, using combined therapy of

Yoshihiro Kobashi; Kouichiro Yoshida; Naoyuki Miyashita; Yoshihito Niki; Mikio Oka

2006-01-01

395

Effects of AntiBacterial Agents, Sample Preparation and Contact Time on AntiBacterial Efficacy in MDPE Film  

Microsoft Academic Search

The anti-bacterial efficacy of medium-density polyethylene (MDPE) with various contents of different anti-bacterial agents was studied with respect to the effects of the anti-bacterial concentration, size and form of MDPE test-specimen, and the contact time. The three anti-bacterial agents used were carbendazim and zinc dimethyl dithiocarbamate (TROYSAN-S88), 2-hydroxypropyl3-piperazinyl-quinoline carboxylic acid methacrylate (HPQM), and silver substituted zeolite (ZEOMIC). The halo and

Pakawat Chammanee; Kwannate Sombatsompop; Apisit Kositchaiyong; Narongrit Sombatsompop

2009-01-01

396

Antibacterial resistance leadership group: open for business.  

PubMed

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance. PMID:24610430

Chambers, Henry F; Bartlett, John G; Bonomo, Robert A; Chiou, Christine; Cosgrove, Sara E; Cross, Heather R; Daum, Robert S; Downing, Michele; Evans, Scott R; Knisely, Jane; Kreiswirth, Barry N; Lautenbach, Ebbing; Mickley, Brenda S; Patel, Robin; Pettigrew, Melinda M; Rodvold, Keith A; Spellberg, Brad; Fowler, Vance G

2014-06-01

397

Antibacterial activity of eight Brazilian annonaceae plants.  

PubMed

Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X. amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A. cherimolia. Amongst the investigated extracts, six showed antibacterial activity against at least one of the tested organisms at the concentration of 100 microg/mL. The most active extracts were those prepared from X. frutescens, X. amazonica, and A. ambotay. A phytochemical screening showed the presence of anonaceus acetogenins in some active extracts. Eleven diterpenoids were also tested for comparison purposes. Six were natural products, previously isolated from Xylopia sp. (kaurenoic, frutoic, xylopic, 15beta-hydroxy-kaurenoic and trachylobanic acids plus kaurenol) and five were derivatives of such compounds, obtained by esterification or reduction reactions. Trachylobanic acid showed antibacterial activity against B. subtilis and S. aureus. PMID:16286303

Takahashi, Jacqueline A; Pereira, Cássia R; Pimenta, Lúcia P S; Boaventura, Maria Amélia D; Silva, Luiz G F E

2006-01-01

398

Cytotoxic and antibacterial effects of orthodontic appliances.  

PubMed

The cytotoxic and antibacterial effects of orthodontic appliances were assessed. Metallic devices used in orthodontics, such as molar bands, brackets, and archwires were tested by the agar overlay cytotoxicity test with mouse fibroblast cells. The same devices were tested for antibacterial effect with Streptococcus mutans and S. sanguis. The multicomponent devices, which are bonded with silver- and copper-based brazing alloys, were more cytotoxic than the single-component devices, probably because copper is more cytotoxic than nickel. The devices had a definite, but low, antibacterial effect, as compared with the 0.05% chlorhexidine positive control. A cytotoxic effect of the devices per se might contribute to a localized gingivitis. It is uncertain whether orthodontic devices have any significant inhibitory effect on dental plaque viability. PMID:8362202

Grimsdottir, M R; Hensten-Pettersen, A

1993-08-01

399

Antibacterial household products: cause for concern.  

PubMed Central

The recent entry of products containing antibacterial agents into healthy households has escalated from a few dozen products in the mid-1990s to more than 700 today. Antibacterial products were developed and have been successfully used to prevent transmission of disease-causing microorganisms among patients, particularly in hospitals. They are now being added to products used in healthy households, even though an added health benefit has not been demonstrated. Scientists are concerned that the antibacterial agents will select bacteria resistant to them and cross-resistant to antibiotics. Moreover, if they alter a person's microflora, they may negatively affect the normal maturation of the T helper cell response of the immune system to commensal flora antigens; this change could lead to a greater chance of allergies in children. As with antibiotics, prudent use of these products is urged. Their designated purpose is to protect vulnerable patients.

Levy, S. B.

2001-01-01

400

Actinopyga lecanora Hydrolysates as Natural Antibacterial Agents  

PubMed Central

Actinopyga lecanora, a type of sea cucumber commonly known as stone fish with relatively high protein content, was explored as raw material for bioactive peptides production. Six proteolytic enzymes, namely alcalase, papain, pepsin, trypsin, bromelain and flavourzyme were used to hydrolyze A. lecanora at different times and their respective degrees of hydrolysis (DH) were calculated. Subsequently, antibacterial activity of the A. lecanora hydrolysates, against some common pathogenic Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas sp.) were evaluated. Papain hydrolysis showed the highest DH value (89.44%), followed by alcalase hydrolysis (83.35%). Bromelain hydrolysate after one and seven hours of hydrolysis exhibited the highest antibacterial activities against Pseudomonas sp., P. aeruginosa and E. coli at 51.85%, 30.07% and 30.45%, respectively compared to the other hydrolysates. Protein hydrolysate generated by papain after 8 h hydrolysis showed maximum antibacterial activity against S. aureus at 20.19%. The potent hydrolysates were further fractionated using RP-HPLC and antibacterial activity of the collected fractions from each hydrolysate were evaluated, wherein among them only three fractions from the bromelain hydrolysates exhibited inhibitory activities against Pseudomonas sp., P. aeruginosa and E. coli at 24%, 25.5% and 27.1%, respectively and one fraction of papain hydrolysate showed antibacterial activity of 33.1% against S. aureus. The evaluation of the relationship between DH and antibacterial activities of papain and bromelain hydrolysates revealed a meaningful correlation of four and six order functions.

Ghanbari, Raheleh; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

2012-01-01

401

Actinopyga lecanora Hydrolysates as Natural Antibacterial Agents.  

PubMed

Actinopyga lecanora, a type of sea cucumber commonly known as stone fish with relatively high protein content, was explored as raw material for bioactive peptides production. Six proteolytic enzymes, namely alcalase, papain, pepsin, trypsin, bromelain and flavourzyme were used to hydrolyze A. lecanora at different times and their respective degrees of hydrolysis (DH) were calculated. Subsequently, antibacterial activity of the A. lecanora hydrolysates, against some common pathogenic Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas sp.) were evaluated. Papain hydrolysis showed the highest DH value (89.44%), followed by alcalase hydrolysis (83.35%). Bromelain hydrolysate after one and seven hours of hydrolysis exhibited the highest antibacterial activities against Pseudomonas sp., P. aeruginosa and E. coli at 51.85%, 30.07% and 30.45%, respectively compared to the other hydrolysates. Protein hydrolysate generated by papain after 8 h hydrolysis showed maximum antibacterial activity against S. aureus at 20.19%. The potent hydrolysates were further fractionated using RP-HPLC and antibacterial activity of the collected fractions from each hydrolysate were evaluated, wherein among them only three fractions from the bromelain hydrolysates exhibited inhibitory activities against Pseudomonas sp., P. aeruginosa and E. coli at 24%, 25.5% and 27.1%, respectively and one fraction of papain hydrolysate showed antibacterial activity of 33.1% against S. aureus. The evaluation of the relationship between DH and antibacterial activities of papain and bromelain hydrolysates revealed a meaningful correlation of four and six order functions. PMID:23222684

Ghanbari, Raheleh; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

2012-01-01

402

Antiviral and antibacterial polyurethanes of various modalities.  

PubMed

We have prepared and characterized a new polyurethane-based antimicrobial material, N,N-dodecyl,methyl-polyurethane (Quat-12-PU). It exhibits strong antiviral and antibacterial activities when coated (as an organic solution or an aqueous nanosuspension) onto surfaces and antibacterial activity when electrospun into nanofibers. Quat-12-PU surfaces are able to kill airborne Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, as well as inactivate the enveloped influenza virus (but not the non-enveloped poliovirus). PMID:23306899

Park, Daewon; Larson, Alyssa M; Klibanov, Alexander M; Wang, Yadong

2013-02-01

403

Injectable bioadhesive hydrogels with innate antibacterial properties.  

PubMed

Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5?wt% oxidized dextran and 6.9?wt% polyethylenimine sets within seconds forming a mechanically rigid (~\

Giano, Michael C; Ibrahim, Zuhaib; Medina, Scott H; Sarhane, Karim A; Christensen, Joani M; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P

2014-01-01

404

Peptoid analogues of anoplin show antibacterial activity.  

PubMed

We have synthesised nine analogues of the antibacterial peptide anoplin with a peptoid residue at position 5 (H-GLLKXIKTLL-NH(2)). The most active compounds showed MIC-values of 12.5 and 25 microM against E.coli and S.aureus. These MIC-values are comparable with anoplin which showed 23 microM and 11 microM against E. coli and S.aureus. However, the selectivity was reversed. Our results indicate that peptoid analogues of anoplin are promising lead structures for developing new antibacterial agents. PMID:19799550

Meinike, K; Hansen, P R

2009-01-01

405

Mechanisms of quinolone resistance in Escherichia coli and Salmonella: Recent developments  

Microsoft Academic Search

Fluoroquinolones are broad-spectrum antimicrobials highly effective for treatment of a variety of clinical and veterinary infections. Their antibacterial activity is due to inhibition of DNA replication. Usually resistance arises spontaneously due to point mutations that result in amino acid substitutions within the topoisomerase subunits GyrA, GyrB, ParC or ParE, decreased expression of outer membrane porins, or overexpression of multidrug efflux

Katie L. Hopkins; Robert H. Davies; E. John Threlfall

2005-01-01

406

Controlled release and antibacterial activity of antibiotic-loaded electrospun halloysite/poly(lactic-co-glycolic acid) composite nanofibers.  

PubMed

Fabrication of nanofiber-based drug delivery system with controlled release property is of general interest in biomedical sciences. In this study, we prepared an antibiotic drug tetracycline hydrochloride (TCH)-loaded halloysite nanotubes/poly(lactic-co-glycolic acid) composite nanofibers (TCH/HNTs/PLGA), and evaluated the drug release and antibacterial activity of this drug delivery system. The structure, morphology, and mechanical properties of the formed electrospun TCH/HNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. We show that the incorporation of TCH-loaded HNTs within the PLGA nanofibers is able to improve the tensile strength and maintain the three-dimensional structure of the nanofibrous mats. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the fibrous scaffolds demonstrate that the developed TCH/HNTs/PLGA composite nanofibers are cytocompatible. More importantly, the TCH/HNTs/PLGA composite nanofibers are able to release the antibacterial drug TCH in a sustained manner for 42 days and display antimicrobial activity solely associated with the encapsulated TCH drug. With the improved mechanical durability, sustained drug release profile, good cytocompatibility, and non-compromised therapeutic efficacy, the developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for tissue engineering and drug delivery applications. PMID:23711785

Qi, Ruiling; Guo, Rui; Zheng, Fuyin; Liu, Hui; Yu, Jianyong; Shi, Xiangyang

2013-10-01

407

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?  

PubMed Central

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.

Labro, Marie-Therese

2000-01-01

408

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification  

PubMed Central

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 ?M (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

Ballester, Pedro J.; Mangold, Martina; Howard, Nigel I.; Robinson, Richard L. Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B. O.

2012-01-01

409

Type II NADH Dehydrogenase Inhibitor 1-Hydroxy-2-Dodecyl- 4(1H)Quinolone Leads to Collapse of Mitochondrial Inner- Membrane Potential and ATP Depletion in Toxoplasma gondii?  

PubMed Central

The apicomplexan parasite Toxoplasma gondii expresses type II NADH dehydrogenases (NDH2s) instead of canonical complex I at the inner mitochondrial membrane. These non-proton-pumping enzymes are considered to be promising drug targets due to their absence in mammalian cells. We recently showed by inhibition kinetics that T. gondii NDH2-I is a target of the quinolone-like compound 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ), which inhibits T. gondii replication in the nanomolar range. In this study, the cationic fluorescent probes Mitotracker and DiOC6(3) (3,3?-dihexyloxacarbocyanine iodine) were used to monitor the influence of HDQ on the mitochondrial inner membrane potential (??m) in T. gondii. Real-time imaging revealed that nanomolar HDQ concentrations led to a ??m collapse within minutes, which is followed by severe ATP depletions of 30% after 1 h and 70% after 24 h. ??m depolarization was attenuated when substrates for other dehydrogenases that can donate electrons to ubiquinone were added to digitonin-permeabilized cells or when infected cultures were treated with the Fo-ATPase inhibitor oligomycin. A prolonged treatment with sublethal concentrations of HDQ induced differentiation into bradyzoites. This dormant stage is likely to be less dependent on the ??m, since ??m-positive parasites were found at a significantly lower frequency in alkaline-pH-induced bradyzoites than in tachyzoites. Together, our studies reveal that oxidative phosphorylation is essential for maintaining the ATP level in the fast-growing tachyzoite stage and that HDQ interferes with this pathway by inhibiting the electron transport chain at the level of ubiquinone reduction.

Lin, San San; Gross, Uwe; Bohne, Wolfgang

2009-01-01

410

Type II NADH dehydrogenase inhibitor 1-hydroxy-2-dodecyl-4(1H)quinolone leads to collapse of mitochondrial inner-membrane potential and ATP depletion in Toxoplasma gondii.  

PubMed

The apicomplexan parasite Toxoplasma gondii expresses type II NADH dehydrogenases (NDH2s) instead of canonical complex I at the inner mitochondrial membrane. These non-proton-pumping enzymes are considered to be promising drug targets due to their absence in mammalian cells. We recently showed by inhibition kinetics that T. gondii NDH2-I is a target of the quinolone-like compound 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ), which inhibits T. gondii replication in the nanomolar range. In this study, the cationic fluorescent probes Mitotracker and DiOC(6)(3) (3,3'-dihexyloxacarbocyanine iodine) were used to monitor the influence of HDQ on the mitochondrial inner membrane potential (Delta Psi m) in T. gondii. Real-time imaging revealed that nanomolar HDQ concentrations led to a Delta Psi m collapse within minutes, which is followed by severe ATP depletions of 30% after 1 h and 70% after 24 h. Delta Psi m depolarization was attenuated when substrates for other dehydrogenases that can donate electrons to ubiquinone were added to digitonin-permeabilized cells or when infected cultures were treated with the F(o)-ATPase inhibitor oligomycin. A prolonged treatment with sublethal concentrations of HDQ induced differentiation into bradyzoites. This dormant stage is likely to be less dependent on the Delta Psi m, since Delta Psi m-positive parasites were found at a significantly lower frequency in alkaline-pH-induced bradyzoites than in tachyzoites. Together, our studies reveal that oxidative phosphorylation is essential for maintaining the ATP level in the fast-growing tachyzoite stage and that HDQ interferes with this pathway by inhibiting the electron transport chain at the level of ubiquinone reduction. PMID:19286986

Lin, San San; Gross, Uwe; Bohne, Wolfgang

2009-06-01

411

Growth inhibition of Toxoplasma gondii and Plasmodium falciparum by nanomolar concentrations of 1-hydroxy-2-dodecyl-4(1H)quinolone, a high-affinity inhibitor of alternative (type II) NADH dehydrogenases.  

PubMed

Both apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum lack type I NADH dehydrogenases (complex I) but instead carry alternative (type II) NADH dehydrogenases, which are absent in mammalian cells and are thus considered promising antimicrobial drug targets. The quinolone-like compound 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ) was recently described as a high-affinity inhibitor of fungal alternative NADH dehydrogenases in enzymatic assays, probably by interfering with the ubiquinol binding site of the enzyme. We describe here that HDQ effectively inhibits the replication rates of P. falciparum and T. gondii in tissue culture. The 50% inhibitory concentration (IC50) of HDQ for T. gondii was determined to be 2.4+/-0.3 nM with a growth assay based on vacuole sizes and 3.7+/-1.4 nM with a growth assay based on beta-galactosidase activity. Quantification of the P. falciparum replication rate using a fluorometric assay revealed an IC50 of 14.0+/-1.9 nM. An important feature of the HDQ structure is the length of the alkyl side chain at position 2. Derivatives with alkyl side chains of C6, C8, C12 (HDQ), and C14 all displayed excellent anti-T. gondii activity, while a C5 derivative completely failed to inhibit parasite replication. A combined treatment of T. gondii-infected cells with HDQ and the antimalarial agent atovaquone, which blocks the ubiquinol oxidation site of cytochrome b in complex III, resulted in synergism, with a calculated fractional inhibitory concentration of 0.16 nM. Interference of the mitochondrial ubiquinone/ubiquinol cycle at two different locations thus appears to be a highly effective strategy for inhibiting parasite replication. HDQ and its derivatives, particularly in combination with atovaquone, represent promising compounds with a high potential for antimalarial and antitoxoplasmal therapy. PMID:17242151

Saleh, Ahmad; Friesen, Johannes; Baumeister, Stefan; Gross, Uwe; Bohne, Wolfgang

2007-04-01

412

Trend of plasmid-mediated quinolone resistance genes at the Children's Hospital in Tunisia.  

PubMed

The prevalence of plasmid-mediated quinolone resistance genes [qnr, aac(6')-Ib-cr and qepA] was sought among Enterobacteriaceae strains obtained from the Children's Hospital of Tunis (Tunisia). Non-duplicate isolates (n?=?278) with resistance to extended-spectrum cephalosporins and collected in 2003, 2007, 2008 and 2009 were screened for qnr genes. Forty (14.4?%) isolates were qnr positive and were screened for the presence of the aac(6')-Ib-cr and qepA genes. qnrB was detected in 21 Klebsiella pneumoniae, 11 Escherichia coli and 6 Enterobacter cloacae isolates. Sequence analysis of the qnrB amplicons revealed variants including 24 qnrB1, 11 qnrB2 and 3 qnrB6. qnrS (qnrS1 allele) was detected only in K. pneumoniae isolates, either alone (two isolates) or with the qnrB gene (one isolate). The qnrA, qnrC and qnrD genes were not found in any of the 278 isolates. No qnr-positive isolates carried the qepA gene. Pyrosequencing results showed that aac(6')-Ib-cr, a variant of the aac(6')-Ib gene, was present in 31 qnr-positive isolates (21 K. pneumoniae isolates, seven Escherichia coli isolates and three Enterobacter cloacae isolates). aac(6')-Ib was also found either alone (two isolates) or in association with aac(6')-Ib-cr (one isolate). Of the 40 qnr-positive isolates, 92.5, 82.5, 57.5, 85 and 82.5?% were non-susceptible to nalidixic acid, ciprofloxacin, levofloxacin, ofloxacin and norfloxacin, respectively, and all were extended-spectrum ?-lactamase producers. Random amplified polymorphic DNA-PCR typing of these isolates showed 16, 8 and 5 different genotypes in K. pneumoniae, Escherichia coli and Enterobacter cloacae isolates, respectively. Our study highlights the high prevalence of qnr in association with aac(6')-Ib-cr among Enterobacteriaceae isolates, even from children, who are patients not overtreated with quinolones. PMID:24194556

Jlili, Nour El-Houda; Réjiba, Samia; Smaoui, Hanen; Guillard, Thomas; Chau, Françoise; Kechrid, Amel; Cambau, Emmanuelle

2014-02-01

413

Synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro  

Microsoft Academic Search

Human cytomegalovirus (HCMV) causes severe morbidity and mortality in immunocompromised patients. Treatment of HCMV infections with conventional antiviral drugs like ganciclovir and cidofovir has major drawbacks (i.e. serious side effects). Therefore, combination therapies using drugs with different antiviral mechanisms should be envisaged. Potential synergy between lactoferrin (LF), an antibacterial, antimycotic and antiviral protein, and the antiviral drugs acyclovir, ganciclovir, foscarnet

Froukje M. De Boer; Hester I. Bakker; Dirk K. F. Meijer; Grietje Molema; Martin C. Harmsen

2003-01-01

414

[Infectious diseases caused by carbapenemase-producing Enterobacteriaceae--a particular challenge for antibacterial therapy].  

PubMed

Enterobacteriaceae species such as Escherichia coli and Klebsiella pneumoniae are among the most common human pathogens. They are responsible for a wide range of community-acquired and nosocomial diseases. Many of the illnesses caused by these bacteria could be treated with beta-lactams for several decades. The increasing use of carbapenems for the treatment of diseases caused by Enterobacteriaceae expressing extended spectrum beta-lactamases, however, lead to the selection and spread of carbapenemase-producing pathogens. Such bacteria are not only resistant to virtually all beta-lactams, but also to numerous other antibiotics such as quinolones, co-trimoxazole, nitrofurantoin, tetracyclines and most aminoglycosides. During the last years, carbapenemase-producing Enterobacteriaceae have spread into almost all regions of the world. Klebsiella pneumoniae carbapenemases (KPC, belonging to Ambler class A), OXA-48 enzymes and their derivatives (belonging to Ambler class D) as well as some metallo-beta-lactamases (Ambler class B) such as NDM, VIM and IMP are the most important carbapenemases produced by Enterobacteriaceae strains. In Germany, the metallo-carbapenemase GIM-1, which has never been proven in bacteria outside Germany, is also of clinical significance. There is no established antibacterial therapy for these difficult-to-treat diseases. For the treatment of severe diseases caused by carbapenemase-producing bacteria, fosfomycin, gentamicin and tigecycline, polymyxins such as polymyxin B or colistin as well as carbapenems, are frequently applied. Combination antibiotic treatment may be more effective than monotherapy for severe ill patients with serious diseases. The most promising new treatment options arise with the development of avibactam. This non-beta-lactam beta-lactamase inhibitor shows good activity against (nearly) all class A and class C beta-lactamases (including strains expressing class A carbapenemases and/or derepressed AmpC enzymes) as well as OXA-48 carbapenemases. It may be used successfully in combination with ceftazidime, ceftaroline or aztreonam. PMID:24908928

Stock, Ingo

2014-05-01

415

Sesbania grandiflora leaf extract mediated green synthesis of antibacterial silver nanoparticles against selected human pathogens  

NASA Astrophysics Data System (ADS)

Simple, effective and rapid approach for the green synthesis of silver nanoparticles (AgNPs) using leaf extract of Sesbania grandiflora and their in vitro antibacterial activity against selected human pathogens has been demonstrated in the study. Various instrumental techniques were adopted to characterize the synthesized AgNPs viz. UV-Vis, FTIR, XRD, TEM, EDX and AFM. Surface Plasmon spectra for AgNPs are centered at 422 nm with dark brown color. The synthesized AgNPs were found to be spherical in shape with size in the range of 10-25 nm. The presence of water soluble proteins in the leaf extract was identified by FTIR which were found to be responsible for the reduction of silver ions (Ag+) to AgNPs. Moreover, the synthesized AgNPs showed potent antibacterial activity against multi-drug resistant (MDR) bacteria such as Salmonella enterica and Staphylococcus aureus.

Das, J.; Paul Das, M.; Velusamy, P.

2013-03-01

416

Antibacterial Activity of Fistulin: A Protease Inhibitor Purified from the Leaves of Cassia fistula.  

PubMed

Plant protease inhibitors (PPIs) are one of the important components of a plant's defense machinery. PPIs are active against the insects and microbes which invade the plant. Cassia species possess anti-insecticidal and antimicrobial properties and this study was aimed at investigating the antibacterial efficacy of a PPI present in the leaves of Cassia fistula. A PPI, fistulin, was isolated from the leaves of C. fistula and purified by gel filtration chromatography. The antibacterial activity of the purified fistulin was studied against five bacterial strains, namely, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli. The PPI was found to be very active against S. aureus, E. coli, B. subtilis, and K. pneumonia, and its efficacy was comparable to the standard drug, streptomycin sulphate. PMID:22779011

Arulpandi, I; Sangeetha, R

2012-01-01

417

Antibacterial Activity of Fistulin: A Protease Inhibitor Purified from the Leaves of Cassia fistula  

PubMed Central

Plant protease inhibitors (PPIs) are one of the important components of a plant's defense machinery. PPIs are active against the insects and microbes which invade the plant. Cassia species possess anti-insecticidal and antimicrobial properties and this study was aimed at investigating the antibacterial efficacy of a PPI present in the leaves of Cassia fistula. A PPI, fistulin, was isolated from the leaves of C. fistula and purified by gel filtration chromatography. The antibacterial activity of the purified fistulin was studied against five bacterial strains, namely, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli. The PPI was found to be very active against S. aureus, E. coli, B. subtilis, and K. pneumonia, and its efficacy was comparable to the standard drug, streptomycin sulphate.

Arulpandi, I.; Sangeetha, R.

2012-01-01

418

Sesbania grandiflora leaf extract mediated green synthesis of antibacterial silver nanoparticles against selected human pathogens.  

PubMed

Simple, effective and rapid approach for the green synthesis of silver nanoparticles (AgNPs) using leaf extract of Sesbania grandiflora and their in vitro antibacterial activity against selected human pathogens has been demonstrated in the study. Various instrumental techniques were adopted to characterize the synthesized AgNPs viz. UV-Vis, FTIR, XRD, TEM, EDX and AFM. Surface Plasmon spectra for AgNPs are centered at 422 nm with dark brown color. The synthesized AgNPs were found to be spherical in shape with size in the range of 10-25 nm. The presence of water soluble proteins in the leaf extract was identified by FTIR which were found to be responsible for the reduction of silver ions (Ag(+)) to AgNPs. Moreover, the synthesized AgNPs showed potent antibacterial activity against multi-drug resistant (MDR) bacteria such as Salmonella enterica and Staphylococcus aureus. PMID:23270884

Das, J; Paul Das, M; Velusamy, P

2013-03-01

419

Antibacterial activity and bonding ability of an adhesive incorporating an antibacterial monomer DMAE-CB.  

PubMed

This study evaluated the antibacterial effect and microtensile bond strength of a resin-based adhesive containing an antibacterial monomer DMAE-CB (methacryloxylethyl cetyl dimethyl ammonium chloride). Cured specimens of 1, 2, and 3% DMAE-CB-containing Single Bond 2 (crosslinking monomer: Bis-GMA, dimethacrylates; functional monomer: HEMA) were prepared, and their antibacterial effects on Streptococcus mutans ATCC 25175 were investigated. Antibacterial property after 0, 30, 90, and 180 days of aging was also tested. Bonding ability of the experimental adhesive incorporating 3% DMAE-CB was evaluated by microtensile bond strength test. The cured experimental adhesive exhibited an inhibitory effect on S. mutans growth, and the adhesive containing 3% DMAE-CB showed higher antibacterial efficiency compared with those incorporating 1 or 2% anibacterial monomer. Antibacterial activities of the specimens lasted for at least 180 days. Microtensile bond strength test revealed that the bonding ability of the experimental adhesive was not significantly adversely affected by the incorporation of DMAE-CB. Therefore, dental adhesives with strong and long-lasting bacteriostatic property could be achieved by incorporating DMAE-CB without negatively influencing bonding ability. PMID:19280645

Xiao, Yu-Hong; Ma, Sai; Chen, Ji-Hua; Chai, Zhi-Guo; Li, Fang; Wang, Ying-Jie

2009-08-01

420

Antibacterial prophylaxis in neutropenic children with cancer  

PubMed Central

During the period of neutropenia induced by chemotherapy, patients have a high risk of infection. The use of antibiotic prophylaxis to reduce neutropenia-related complications in patients with cancer is still disputed. Recent meta-analysis and clinical trials demonstrated that antibiotic prophylaxis with quinolones reduces febrile episodes, bacterial infections and mortality in adult oncological patients with neutropenia induced by chemotherapy in acute leukaemia. In paediatric patients, the only randomized, double-blind, prospective study until now suggests that amoxicillin/clavulanate may represent an effective prophylactic treatment in reducing fever and infections in oncological children with neutropenia, with an efficacy that is statistically demonstrated only in patients with acute leukaemia. Considering the risk of resistances, antibiotic-prophylaxis should be used only in selected patients.

Barone, Angelic