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Sample records for cell wall-acting antibiotics

  1. CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects beta-lactam resistance

    DEFF Research Database (Denmark)

    Kallipolitis, Birgitte H; Ingmer, Hanne; Gahan, Cormac G;

    2003-01-01

    Listeria monocytogenes is a food-borne pathogen that can cause a variety of illnesses ranging from gastroenteritis to life-threatening septicemia. The beta-lactam antibiotic ampicillin remains the drug of choice for the treatment of listeriosis. We have previously identified a response regulator ...

  2. Antibiotics

    Science.gov (United States)

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  3. Bactericidal Antibiotics Increase Hydroxyphenyl Fluorescein Signal by Altering Cell Morphology

    DEFF Research Database (Denmark)

    Paulander, Wilhelm; Wang, Ying; Folkesson, Sven Anders;

    2014-01-01

    It was recently proposed that for bactericidal antibiotics a common killing mechanism contributes to lethality involving indirect stimulation of hydroxyl radical (OH center dot) formation. Flow cytometric detection of OH center dot by hydroxyphenyl fluorescein (HPF) probe oxidation was used...... to support this hypothesis. Here we show that increased HPF signals in antibiotics-exposed bacterial cells are explained by fluorescence associated with increased cell size, and do not reflect reactive oxygen species (ROS) concentration. Independently of antibiotics, increased fluorescence was seen...... for elongated cells expressing the oxidative insensitive green fluorescent protein (GFP). Although our data question the role of ROS in lethality of antibiotics other research approaches point to important interplays between basic bacterial metabolism and antibiotic susceptibility. To underpin...

  4. Mutations in mmpL and in the cell wall stress stimulon contribute to resistance to oxadiazole antibiotics in methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Xiao, Qiaobin; Vakulenko, Sergei; Chang, Mayland; Mobashery, Shahriar

    2014-10-01

    Staphylococcus aureus is a leading cause of hospital- and community-acquired infections, which exhibit broad resistance to various antibiotics. We recently disclosed the discovery of the oxadiazole class of antibiotics, which has in vitro and in vivo activities against methicillin-resistant S. aureus (MRSA). We report herein that MmpL, a putative member of the resistance, nodulation, and cell division (RND) family of proteins, contributes to oxadiazole resistance in the S. aureus strain COL. Through serial passages, we generated two S. aureus COL variants that showed diminished susceptibilities to an oxadiazole antibiotic. The MICs for the oxadiazole against one strain (designated S. aureus COL(I)) increased reproducibly 2-fold (to 4 μg/ml), while against the other strain (S. aureus COL(R)), they increased >4-fold (to >8 μg/ml, the limit of solubility). The COL(R) strain was derived from the COL(I) strain. Whole-genome sequencing revealed 31 mutations in S. aureus COL(R), of which 29 were shared with COL(I). Consistent with our previous finding that oxadiazole antibiotics inhibit cell wall biosynthesis, we found 13 mutations that occurred either in structural genes or in promoters of the genes of the cell wall stress stimulon. Two unique mutations in S. aureus COL(R) were substitutions in two genes that encode the putative thioredoxin (SACOL1794) and MmpL (SACOL2566). A role for mmpL in resistance to oxadiazoles was discerned from gene deletion and complementation experiments. To our knowledge, this is the first report that a cell wall-acting antibiotic selects for mutations in the cell wall stress stimulon and the first to implicate MmpL in resistance to antibiotics in S. aureus.

  5. Determination of the Antibiotic Resistance Profile of Student Cell Phones

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    Lisa Ann Blankinship

    2012-08-01

    Full Text Available Sampling of common use items (e.g., student cell phones for bacterial presence, identification, and antibiotic resistance profiling helps students to recognize the need for routine cleaning of personal items and encourages thoughtful use of currently available medications. This multilab period project can be used to teach or reinforce several methods from general microbiology including aseptic technique, isolation streak, serial dilution, spread plating, Kirby Bauer testing, unknown identification, and media production. The data generated can be saved and added to each semester, thus providing a data set that reflects a local trend of antibiotic resistance.      

  6. Bacterial cell division proteins as antibiotic targets

    NARCIS (Netherlands)

    T. den Blaauwen; J.M. Andreu; O. Monasterio

    2014-01-01

    Proteins involved in bacterial cell division often do not have a counterpart in eukaryotic cells and they are essential for the survival of the bacteria. The genetic accessibility of many bacterial species in combination with the Green Fluorescence Protein revolution to study localization of protein

  7. Antibiotic transport in resistant bacteria: synchrotron UV fluorescence microscopy to determine antibiotic accumulation with single cell resolution.

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    Slávka Kaščáková

    Full Text Available A molecular definition of the mechanism conferring bacterial multidrug resistance is clinically crucial and today methods for quantitative determination of the uptake of antimicrobial agents with single cell resolution are missing. Using the naturally occurring fluorescence of antibacterial agents after deep ultraviolet (DUV excitation, we developed a method to non-invasively monitor the quinolones uptake in single bacteria. Our approach is based on a DUV fluorescence microscope coupled to a synchrotron beamline providing tuneable excitation from 200 to 600 nm. A full spectrum was acquired at each pixel of the image, to study the DUV excited fluorescence emitted from quinolones within single bacteria. Measuring spectra allowed us to separate the antibiotic fluorescence from the autofluorescence contribution. By performing spectroscopic analysis, the quantification of the antibiotic signal was possible. To our knowledge, this is the first time that the intracellular accumulation of a clinical antibiotic could be determined and discussed in relation with the level of drug susceptibility for a multiresistant strain. This method is especially important to follow the behavior of quinolone molecules at individual cell level, to quantify the intracellular concentration of the antibiotic and develop new strategies to combat the dissemination of MDR-bacteria. In addition, this original approach also indicates the heterogeneity of bacterial population when the same strain is under environmental stress like antibiotic attack.

  8. Dielectrophoretic characterization of antibiotic-treated Mycobacterium tuberculosis complex cells.

    Science.gov (United States)

    Inoue, Shinnosuke; Lee, Hyun-Boo; Becker, Annie L; Weigel, Kris M; Kim, Jong-Hoon; Lee, Kyong-Hoon; Cangelosi, Gerard A; Chung, Jae-Hyun

    2015-10-01

    Multi-drug resistant tuberculosis (MDR-TB) has become a serious concern for proper treatment of patients. As a phenotypic method, dielectrophoresis can be useful but is yet to be attempted to evaluate Mycobacterium tuberculosis complex cells. This paper investigates the dielectrophoretic behavior of Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) cells that are treated with heat or antibiotics rifampin (RIF) or isoniazid (INH). The experimental parameters are designed on the basis of our sensitivity analysis. The medium conductivity (σ(m)) and the frequency (f) for a crossover frequency (f(xo1)) test are decided to detect the change of σ(m)-f(xo1) in conjunction with the drug mechanism. Statistical modeling is conducted to estimate the distributions of viable and nonviable cells from the discrete measurement of f (xo1). Finally, the parameters of the electrophysiology of BCG cells, C(envelope) and σ(cyto), are extracted through a sampling algorithm. This is the first evaluation of the dielectrophoresis (DEP) approach as a means to assess the effects of antimicrobial drugs on M. tuberculosis complex cells.

  9. The cell wall-targeting antibiotic stimulon of Enterococcus faecalis.

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    Jacqueline Abranches

    Full Text Available Enterococcus faecalis is an opportunistic nosocomial pathogen that is highly resistant to a variety of environmental insults, including an intrinsic tolerance to antimicrobials that target the cell wall (CW. With the goal of determining the CW-stress stimulon of E. faecalis, the global transcriptional profile of E. faecalis OG1RF exposed to ampicillin, bacitracin, cephalotin or vancomycin was obtained via microarrays. Exposure to the β-lactams ampicillin and cephalotin resulted in the fewest transcriptional changes with 50 and 192 genes differentially expressed 60 min after treatment, respectively. On the other hand, treatment with bacitracin or vancomycin for 60 min affected the expression of, respectively, 377 and 297 genes. Despite the differences in the total number of genes affected, all antibiotics induced a very similar gene expression pattern with an overrepresentation of genes encoding hypothetical proteins, followed by genes encoding proteins associated with cell envelope metabolism as well as transport and binding proteins. In particular, all drug treatments, most notably bacitracin and vancomycin, resulted in an apparent metabolic downshift based on the repression of genes involved in translation, energy metabolism, transport and binding. Only 19 genes were up-regulated by all conditions at both the 30 and 60 min time points. Among those 19 genes, 4 genes encoding hypothetical proteins (EF0026, EF0797, EF1533 and EF3245 were inactivated and the respective mutant strains characterized in relation to antibiotic tolerance and virulence in the Galleria mellonella model. The phenotypes obtained for two of these mutants, ΔEF1533 and ΔEF3245, support further characterization of these genes as potential candidates for the development of novel preventive or therapeutic approaches.

  10. Bypassing antibiotic selection: positive screening of genetically modified cells with an antigen-dependent proliferation switch

    OpenAIRE

    Kawahara, Masahiro; Ueda, Hiroshi; Morita, Sumiyo; Tsumoto, Kouhei; Kumagai, Izumi; Nagamune, Teruyuki

    2003-01-01

    While antibiotic selection has been routinely used for the selection of genetically modified cells, administration of cytotoxic drugs often leads to deleterious effects not only to inert cells but also to transfected or transduced ones. In this study, we propose an Antigen-MEdiated Genetically modified cell Amplification (AMEGA) system employing antibody/receptor chimeras without antibiotic selection. Based on a rational design where the extracellular domains of dimeric erythropoietin recepto...

  11. Unraveling the genetic driving forces enabling antibiotic resistance at the single cell level

    Science.gov (United States)

    Bos, Julia

    Bacteria are champions at finding ways to quickly respond and adapt to environments like the human gut, known as the epicentre of antibiotic resistance. How do they do it? Combining molecular biology tools to microfluidic and fluorescence microscopy technologies, we monitor the behavior of bacteria at the single cell level in the presence of non-toxic doses of antibiotics. By tracking the chromosome dynamics of Escherichia coli cells upon antibiotic treatment, we examine the changes in the number, localization and content of the chromosome copies within one cell compartment or between adjacent cells. I will discuss how our work pictures the bacterial genomic plasticity as a driving force in evolution and how it provides access to the mechanisms controlling the subtle balance between genetic diversity and stability in the development of antibiotic resistance.

  12. EFFECT OF MACROLIDE ANTIBIOTICS ON VARIOUS CELL CULTURES IN VITRO: 1. CELL MORPHOLOGY

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    Renáta Kováčová

    2012-08-01

    Full Text Available The aim of our study was to evaluate the cytotoxicity of macrolide antibiotics (tilmicosin, tylosin and spiramycin of various concentrations on different cell cultures in vitro. Cellular lines from animal tissues (VERO cells - kidney cells of Macacus rhesus, FE cells - feline embryonal cells, BHK 21 cellular line from young hamster kidneys were used. Tilmicosin effect: BHK cells are most sensitive, significant decrease in vital cells occurs already at the concentration of 50 μg.ml-1. VERO cells were most resistant, significant decrease of vital cells was observed only at the concentration of 300 μg.ml-1. Tylosin effect: BHK cells can be considered most sensitive, since at concentrations higher than 500 μg.ml-1, no vital cells were observed. At the concentration of 1000 μg.ml-1 were 3.13% of vital and 70.52% of subvital FE cells. In Vero cells, we observed a significant decrease at the concentration of 750 μg.ml-1. Spiramycin effect: Significant decrease of vital BHK cells was observed at the concentration of 150 μg.ml-1, at the concentration of 300 μg.ml-1, no vital cells and only 7.53% of subvital cells were observed. At the concentration of 500 μg.ml-1 reported 10.34% of vital FE cells. At the concentration of 500 μg.ml-1 22.48% of vital and 71.16% of subvital VERO cells were recorded.

  13. Genome-wide dynamics of a bacterial response to antibiotics that target the cell envelope

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    Tran Ngat

    2011-05-01

    Full Text Available Abstract Background A decline in the discovery of new antibacterial drugs, coupled with a persistent rise in the occurrence of drug-resistant bacteria, has highlighted antibiotics as a diminishing resource. The future development of new drugs with novel antibacterial activities requires a detailed understanding of adaptive responses to existing compounds. This study uses Streptomyces coelicolor A3(2 as a model system to determine the genome-wide transcriptional response following exposure to three antibiotics (vancomycin, moenomycin A and bacitracin that target distinct stages of cell wall biosynthesis. Results A generalised response to all three antibiotics was identified which involves activation of transcription of the cell envelope stress sigma factor σE, together with elements of the stringent response, and of the heat, osmotic and oxidative stress regulons. Attenuation of this system by deletion of genes encoding the osmotic stress sigma factor σB or the ppGpp synthetase RelA reduced resistance to both vancomycin and bacitracin. Many antibiotic-specific transcriptional changes were identified, representing cellular processes potentially important for tolerance to each antibiotic. Sensitivity studies using mutants constructed on the basis of the transcriptome profiling confirmed a role for several such genes in antibiotic resistance, validating the usefulness of the approach. Conclusions Antibiotic inhibition of bacterial cell wall biosynthesis induces both common and compound-specific transcriptional responses. Both can be exploited to increase antibiotic susceptibility. Regulatory networks known to govern responses to environmental and nutritional stresses are also at the core of the common antibiotic response, and likely help cells survive until any specific resistance mechanisms are fully functional.

  14. Induction kinetics of the Staphylococcus aureus cell wall stress stimulon in response to different cell wall active antibiotics

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    Berger-Bächi Brigitte

    2011-01-01

    Full Text Available Abstract Background Staphylococcus aureus activates a protective cell wall stress stimulon (CWSS in response to the inhibition of cell wall synthesis or cell envelope damage caused by several structurally and functionally different antibiotics. CWSS induction is coordinated by the VraSR two-component system, which senses an unknown signal triggered by diverse cell wall active agents. Results We have constructed a highly sensitive luciferase reporter gene system, using the promoter of sas016 (S. aureus N315, which detects very subtle differences in expression as well as measuring > 4 log-fold changes in CWSS activity, to compare the concentration dependence of CWSS induction kinetics of antibiotics with different cell envelope targets. We compared the effects of subinhibitory up to suprainhibitory concentrations of fosfomycin, D-cycloserine, tunicamycin, bacitracin, flavomycin, vancomycin, teicoplanin, oxacillin, lysostaphin and daptomycin. Induction kinetics were both strongly antibiotic- and concentration-dependent. Most antibiotics triggered an immediate response with induction beginning within 10 min, except for tunicamycin, D-cycloserine and fosfomycin which showed lags of up to one generation before induction commenced. Induction characteristics, such as the rate of CWSS induction once initiated and maximal induction reached, were strongly antibiotic dependent. We observed a clear correlation between the inhibitory effects of specific antibiotic concentrations on growth and corresponding increases in CWSS induction kinetics. Inactivation of VraR increased susceptibility to the antibiotics tested from 2- to 16-fold, with the exceptions of oxacillin and D-cycloserine, where no differences were detected in the methicillin susceptible S. aureus strain background analysed. There was no apparent correlation between the induction capacity of the various antibiotics and the relative importance of the CWSS for the corresponding resistance phenotypes

  15. The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells

    OpenAIRE

    Meir Djaldetti; Nimrod Nachmias; Hanna Bessler

    2016-01-01

    Context: Antibiotics belong to the powerful weapons applied against microbial infections. It is notable that in addition to their antimicrobial effect they express immunomodulatory and anti-cancer activities. Aims: To explore the effect of four antibiotics on the immune cross-talk between peripheral blood mononuclear cells (PBMC) and colon carcinoma cells from two human lines. Methods: Cefotaxime, meropenem, ampicillin and vancomycin were separately added to PBMC co-incubated with cel...

  16. Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

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    Patrick Kaiser

    2014-02-01

    Full Text Available In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN, the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.

  17. Microspectrometric insights on the uptake of antibiotics at the single bacterial cell level

    Science.gov (United States)

    Cinquin, Bertrand; Maigre, Laure; Pinet, Elizabeth; Chevalier, Jacqueline; Stavenger, Robert A.; Mills, Scott; Réfrégiers, Matthieu; Pagès, Jean-Marie

    2015-01-01

    Bacterial multidrug resistance is a significant health issue. A key challenge, particularly in Gram-negative antibacterial research, is to better understand membrane permeation of antibiotics in clinically relevant bacterial pathogens. Passing through the membrane barrier to reach the required concentration inside the bacterium is a pivotal step for most antibacterials. Spectrometric methodology has been developed to detect drugs inside bacteria and recent studies have focused on bacterial cell imaging. Ultimately, we seek to use this method to identify pharmacophoric groups which improve penetration, and therefore accumulation, of small-molecule antibiotics inside bacteria. We developed a method to quantify the time scale of antibiotic accumulation in living bacterial cells. Tunable ultraviolet excitation provided by DISCO beamline (synchrotron Soleil) combined with microscopy allows spectroscopic analysis of the antibiotic signal in individual bacterial cells. Robust controls and measurement of the crosstalk between fluorescence channels can provide real time quantification of drug. This technique represents a new method to assay drug translocation inside the cell and therefore incorporate rational drug design to impact antibiotic uptake. PMID:26656111

  18. Microspectrometric insights on the uptake of antibiotics at the single bacterial cell level.

    Science.gov (United States)

    Cinquin, Bertrand; Maigre, Laure; Pinet, Elizabeth; Chevalier, Jacqueline; Stavenger, Robert A; Mills, Scott; Réfrégiers, Matthieu; Pagès, Jean-Marie

    2015-12-11

    Bacterial multidrug resistance is a significant health issue. A key challenge, particularly in Gram-negative antibacterial research, is to better understand membrane permeation of antibiotics in clinically relevant bacterial pathogens. Passing through the membrane barrier to reach the required concentration inside the bacterium is a pivotal step for most antibacterials. Spectrometric methodology has been developed to detect drugs inside bacteria and recent studies have focused on bacterial cell imaging. Ultimately, we seek to use this method to identify pharmacophoric groups which improve penetration, and therefore accumulation, of small-molecule antibiotics inside bacteria. We developed a method to quantify the time scale of antibiotic accumulation in living bacterial cells. Tunable ultraviolet excitation provided by DISCO beamline (synchrotron Soleil) combined with microscopy allows spectroscopic analysis of the antibiotic signal in individual bacterial cells. Robust controls and measurement of the crosstalk between fluorescence channels can provide real time quantification of drug. This technique represents a new method to assay drug translocation inside the cell and therefore incorporate rational drug design to impact antibiotic uptake.

  19. Isolation of single-base genome-edited human iPS cells without antibiotic selection

    OpenAIRE

    Miyaoka, Yuichiro; Chan, Amanda H.; Luke M Judge; Yoo, Jennie; Huang, Miller; Nguyen, Trieu D.; Lizarraga, Paweena P.; So, Po-Lin; Conklin, Bruce R

    2014-01-01

    Precise editing of human genomes in pluripotent stem cells by homology-driven repair of targeted nuclease-induced cleavage has been hindered by the difficulty of isolating rare clones. We developed an efficient method to capture rare mutational events, enabling isolation of mutant lines with single-base substitutions without antibiotic selection. This method facilitates efficient induction or reversion of mutations associated with human disease in isogenic human induced pluripotent stem cells.

  20. Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility.

    Science.gov (United States)

    Aldridge, Bree B; Fernandez-Suarez, Marta; Heller, Danielle; Ambravaneswaran, Vijay; Irimia, Daniel; Toner, Mehmet; Fortune, Sarah M

    2012-01-01

    Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics. PMID:22174129

  1. Studies on penetration of antibiotic in bacterial cells in space conditions (7-IML-1)

    Science.gov (United States)

    Tixador, R.

    1992-01-01

    The Cytos 2 experiment was performed aboard Salyut 7 in order to test the antibiotic sensitivity of bacteria cultivated in vitro in space. An increase of the Minimal Inhibitory Concentration (MIC) in the inflight cultures (i.e., an increase of the antibiotic resistance) was observed. Complementary studies of the ultrastructure showed a thickening of the cell envelope. In order to confirm the results of the Cytos 2 experiment, we performed the ANTIBIO experiment during the D1 mission to try to differentiate, by means of the 1 g centrifuge in the Biorack, between the biological effects of cosmic rays and those caused by microgravity conditions. The originality of this experiment was in the fact that it was designed to test the antibiotic sensitivity of bacteria cultivated in vitro during the orbital phase of the flight. The results show an increase in resistance to Colistin in in-flight bacteria. The MIC is practically double in the in-flight cultures. A cell count of living bacteria in the cultures containing the different Colistin concentrations showed a significant difference between the cultures developed during space flight and the ground based cultures. The comparison between the 1 g and 0 g in-flight cultures show similar behavior for the two sets. Nevertheless, a small difference between the two sets of ground based control cultures was noted. The cultures developed on the ground centrifuge (1.4 g) present a slight decrease in comparison with the cultures developed in the static rack (1 g). In order to approach the mechanisms of the increase of antibiotic resistance on bacteria cultivated in vitro in space, we have proposed the study on penetration of antibiotics in bacterial cells in space conditions. This experiment was selected for the International Microgravity Laboratory 1 (IML-1) mission.

  2. The effect of antibiotics on cytokine production by mononuclear cells and the cross-talk with colon cancer cells

    Directory of Open Access Journals (Sweden)

    Meir Djaldetti

    2016-08-01

    Full Text Available Context: Antibiotics belong to the powerful weapons applied against microbial infections. It is notable that in addition to their antimicrobial effect they express immunomodulatory and anti-cancer activities. Aims: To explore the effect of four antibiotics on the immune cross-talk between peripheral blood mononuclear cells (PBMC and colon carcinoma cells from two human lines. Methods: Cefotaxime, meropenem, ampicillin and vancomycin were separately added to PBMC co-incubated with cells from two human colon carcinoma cell lines, i.e. HT-29 and RKO. After 24 hours, the level of the following cytokines produced by PBMC was evaluated: IL-6, IL-1ra, IL-1β, TNFα, IFNγ and IL-10. Results: All four antibiotics did not affect the generation of IL-6 and IL-1ra in both co-cultures. On the other hand all of them restrained the production of IL-1β by PBMC incubated with HT-29 cells. In the same incubation mixture cefotaxime, vancomycin and meropenem decreased IFNγ and IL-10 production, while ampicillin and vancomycin inhibited TNFα. As for PBMC incubated with RKO carcinoma cells, cefotaxime inhibited the production of IL-1β, IFNγ and mildly of IL-10, whereas vancomycin repressed that of IL-1β, TNFα and IFNγ. Notably, vancomycin increased the production of IL-1β and decreased that of TNFα and IFNγ. The results indicate that the four antibiotics examined exert a modulatory effect on the immune cross-talk between PBMC and human colon cancer cells from two lines expressed by a different impact on pro-and anti-inflammatory cytokines generation. Conclusions: These findings support the conception that antibiotics may express not only an anti-microbial effect, but also possess an anti-cancer activity that may be considered for integration to the therapeutic arsenal against cancer.

  3. Reducing the Level of Undecaprenyl Pyrophosphate Synthase Has Complex Effects on Susceptibility to Cell Wall Antibiotics.

    Science.gov (United States)

    Lee, Yong Heon; Helmann, John D

    2013-06-24

    Undecaprenyl pyrophosphate synthase (UppS) catalyzes the formation of the C55 lipid carrier (UPP) that is essential for bacterial peptidoglycan biosynthesis. Here we selected a vancomycin (VAN)-resistant derivative of Bacillus subtilis W168 which contains a single-point mutation in the ribosome-binding site (RBS) of the uppS gene designated uppS1. Genetic reconstruction experiments demonstrate that the uppS1 allele is sufficient to confer low-level VAN resistance and causes reduced UppS translation. The decreased level of UppS renders B. subtilis slightly more susceptible to many late-acting cell wall antibiotics including β-lactams, but significantly more resistant to fosfomycin and D-cycloserine, antibiotics that interfere with the very early steps of cell wall synthesis. We further show that the uppS1 allele leads to slightly elevated expression of the σ(M) regulon, possibly helping to compensate for the stress caused by a decrease in UPP levels. Notably, the uppS1 mutation increases resistance to VAN, fosfomycin, and D-cycloserine in wild-type cells, but this effect is greatly reduced or eliminated in a sigM mutant background. Our findings suggest that, although UppS is an attractive antibacterial target, incomplete inhibition of UppS function may lead to increased resistance to some cell wall-active antibiotics. PMID:23796923

  4. A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease

    OpenAIRE

    Duncan NA; Kronenberger WG; Hampton KC; Bloom EM; Rampersad AG; Roberson CP; Shapiro AD

    2016-01-01

    Natalie A Duncan,1 William G Kronenberger,2 Kisha C Hampton,1 Ellen M Bloom,1 Angeli G Rampersad,1 Christopher P Roberson,1 Amy D Shapiro11Department of Hematology, Indiana Hemophilia and Thrombosis Center, 2Department of Psychiatry, Indiana University School of Medicine Riley and Child Adolescent Psychiatry Clinic, Indianapolis, IN, USABackground: Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop a...

  5. Raised white cell count in renal colic: Is there a role for antibiotics?

    OpenAIRE

    Adam Alleemudder; Xin-You Tai; Anuj Goyal; Jhumur Pati

    2014-01-01

    Aims: To determine the use of antibiotics in patients with renal colic and an elevated white cell count (WCC) in the absence of other features of infection. Materials and Methods: A retrospective audit of patients presenting to an emergency department with renal colic caused by a solitary ureteric stone over a 6 month period. Statistical Analysis Used: Student′s t-test. Results: Fifty patients met the inclusion criteria for this study. In 42 patients (84%) the urinalysis showed he...

  6. Detection and Antibiotic Treatment of Mycoplasma arginini Contamination in a Mouse Epithelial Cell Line Restore Normal Cell Physiology

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    Brianna Boslett

    2014-01-01

    Full Text Available Mycoplasma contamination of cultured cell lines is difficult to detect by routine observation. Infected cells can display normal morphology and the slow growth rate of mycoplasma can delay detection for extended periods of time, compromising experimental results. Positive identification of mycoplasma typically requires cells to be either fixed and stained for DNA or processed with PCR. We present a method to detect mycoplasma using live-cell optical microscopy typically used for routine observation of cell cultures. Images of untreated mycoplasma-infected epithelial cells alongside images of infected cells treated with Plasmocin, a commercially available antibiotic targeted to mycoplasma, are shown. We found that optical imaging is an effective screening tool for detection of mycoplasma contamination. Importantly, we found that cells regained normal function after the contamination was cleared. In conclusion, we present a technique to diagnose probable mycoplasma infections in live cultures without fixation, resulting in faster response times and decreased loss of cell material.

  7. Enhanced transfection of cell lines from Atlantic salmon through nucoleofection and antibiotic selection

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    Mjaaland Siri

    2011-05-01

    Full Text Available Abstract Background Cell lines from Atlantic salmon kidney have made it possible to culture and study infectious salmon anemia virus (ISAV, an aquatic orthomyxovirus affecting farmed Atlantic salmon. However, transfection of these cells using calcium phosphate precipitation or lipid-based reagents shows very low transfection efficiency. The Amaxa Nucleofector technology™ is an electroporation technique that has been shown to be efficient for gene transfer into primary cells and hard to transfect cell lines. Findings Here we demonstrate, enhanced transfection of the head kidney cell line, TO, from Atlantic salmon using nucleofection and subsequent flow cytometry. Depending on the plasmid promoter, TO cells could be transfected transiently with an efficiency ranging from 11.6% to 90.8% with good viability, using Amaxa's cell line nucleofector solution T and program T-20. A kill curve was performed to investigate the most potent antibiotic for selection of transformed cells, and we found that blasticidin and puromycin were the most efficient for selection of TO cells. Conclusions The results show that nucleofection is an efficient way of gene transfer into Atlantic salmon cells and that stably transfected cells can be selected with blasticidin or puromycin.

  8. Multiple Roles for Enterococcus faecalis Glycosyltransferases in Biofilm-Associated Antibiotic Resistance, Cell Envelope Integrity, and Conjugative Transfer

    OpenAIRE

    Dale, Jennifer L.; Cagnazzo, Julian; Phan, Chi Q.; Barnes, Aaron M. T.; Dunny, Gary M.

    2015-01-01

    The emergence of multidrug-resistant bacteria and the limited availability of new antibiotics are of increasing clinical concern. A compounding factor is the ability of microorganisms to form biofilms (communities of cells encased in a protective extracellular matrix) that are intrinsically resistant to antibiotics. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and also has the propensity to acquire resistance determinants via horizontal gene transfer. There i...

  9. Thiazole antibiotic thiostrepton synergize with bortezomib to induce apoptosis in cancer cells.

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    Bulbul Pandit

    Full Text Available Thiazole antibiotic, thiostrepton was recently identified as proteasome inhibitor. We investigated the therapeutic potential of the combination of thiostrepton and proteasome inhibitor bortezomib (Velcade on various human tumor cell lines. Combination of sub-lethal concentrations of thiostrepton and bortezomib induced potent apoptosis and inhibition of long-term colony formation in a wide variety of human cancer cell lines. The synergistic relationship between thiostrepton and bortezomib combination was also quantitatively demonstrated by calculating their combination index values that were much lower than 1 in all studied cell lines. The synergy between these drugs was based on their proteasome inhibitory activities, because thiostrepton modification, thiostrepton methyl ester, which did not have intact quinaldic acid ring and did not inhibit proteasome activity failed to demonstrate any synergy in combination with bortezomib.

  10. Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance

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    Couto Isabel

    2011-02-01

    Full Text Available Abstract Background Active efflux systems and reduced cell-wall permeability are considered to be the main causes of mycobacterial intrinsic resistance to many antimicrobials. In this study, we have compared the Mycobacterium smegmatis wild-type strain mc2155 with knockout mutants for porins MspA (the main porin of M. smegmatis and MspC, the efflux pump LfrA (the main efflux pump system of M. smegmatis and its repressor LfrR for their ability to transport ethidium bromide (EtBr on a real-time basis. This information was then correlated with minimum inhibitory concentrations (MICs of several antibiotics in the presence or absence of the efflux inhibitors chlorpromazine, thioridazine and verapamil. Results In the absence of porins MspA and MspC, accumulation of ethidium bromide decreased and the cells became more resistant to several antibiotics, whereas the knockout mutant for the LfrA pump showed increased accumulation of EtBr and increased susceptibility to EtBr, rifampicin, ethambutol and ciprofloxacin. Moreover, the efflux inhibitors caused a reduction of the MICs of streptomycin, rifampicin, amikacin, ciprofloxacin, clarithromycin and erythromycin in most of the strains tested. Conclusions The methodology used in this study demonstrated that porin MspA plays an important role in the influx of quaternary ammonium compounds and antibiotics and that efflux via the LfrA pump is involved in low-level resistance to several antimicrobial drugs in M. smegmatis. The results obtained with this non-pathogenic mycobacterium will be used in future studies as a model for the evaluation of the activity of the same efflux inhibitors on the susceptibility of multidrug resistant strains of Mycobacterium tuberculosis to isoniazid and rifampicin.

  11. Antibiotic Resistance

    Science.gov (United States)

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  12. Pancreatic islet-cell viability, functionality and oxidative status remain unaffected at pharmacological concentrations of commonly used antibiotics in vitro

    Indian Academy of Sciences (India)

    Yogita Shewade; Suraj Tirth; R R Bhonde

    2001-09-01

    Environmental factors such as diet, physical activity, drugs, pollution and life style play an important role in the progression and/or precipitation of diseases like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate use of antibiotics to combat infectious diseases is one of the commonest forms of misuse of drugs. Antibiotics seem to have a correlation with diabetes and pancreatic function. There are controversial reports about the effect of antibiotics on the pancreatic islets; some suggesting their harmless action, some depicting a beneficial role and others indicating deleterious effect. Moreover, use of antibiotics is mandatory during islet isolation and cultivation to reduce incidences of microbial contamination. It is likely that antibiotic treatment may adversely affect islet viability and its functioning leading to failure of islet transplantation. The present in vitro study was undertaken to examine the effect of commonly used antibiotics such as gentamycin, penicillin, streptomycin, tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its functioning and induction of oxidative stress if any. The viability and insulin production data showed that none of the antibiotics used in the present study affect the viability and the functioning of the islets at their pharmacological concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal increase in lipid peroxidation with tetracycline and slight increase in NO levels with streptomycin, none of these antibiotics affect the oxidative status of the cells. Antioxidant enzymes such as superoxide dismutase and catalase remain unaffected after this treatment. Our results reveal the innocuous nature of the antibiotics used at pharmacological concentrations, suggesting their safety whenever prescribed to combat infections and also during islet isolation procedures.

  13. A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Duncan NA

    2016-06-01

    Full Text Available Natalie A Duncan,1 William G Kronenberger,2 Kisha C Hampton,1 Ellen M Bloom,1 Angeli G Rampersad,1 Christopher P Roberson,1 Amy D Shapiro11Department of Hematology, Indiana Hemophilia and Thrombosis Center, 2Department of Psychiatry, Indiana University School of Medicine Riley and Child Adolescent Psychiatry Clinic, Indianapolis, IN, USABackground: Antibiotic prophylaxis is a mainstay in sickle cell disease management. However, adherence is estimated at only 66%. This study aimed to develop and validate a Sickle Cell Antibiotic Adherence Level Evaluation (SCAALE to promote systematic and detailed adherence evaluation.Methods: A 28-item questionnaire was created, covering seven adherence areas. General Adherence Ratings from the parent and one health care provider and medication possession ratios were obtained as validation measures.Results: Internal consistency was very good to excellent for the total SCAALE (α=0.89 and four of the seven subscales. Correlations between SCAALE scores and validation measures were strong for the total SCAALE and five of the seven subscales.Conclusion: The SCAALE provides a detailed, quantitative, multidimensional, and global measurement of adherence and can promote clinical care and research. Keywords: penicillin prophylaxis, SCAALE, newborn screening program, Sickle SAFE Program, hemoglobinopathy, compliance

  14. Effect of NaCl on Heat Resistance, Antibiotic Susceptibility, and Caco-2 Cell Invasion of Salmonella

    Directory of Open Access Journals (Sweden)

    Hyunjoo Yoon

    2013-01-01

    Full Text Available This study evaluated the effects of NaCl on heat resistance, antibiotic susceptibility, and Caco-2 cell invasion of Salmonella. Salmonella typhimurium NCCP10812 and Salmonella enteritidis NCCP12243 were exposed to 0, 2, and 4% NaCl and to sequential increase of NaCl concentrations from 0 to 4% NaCl for 24 h at 35°C. The strains were then investigated for heat resistance (60°C, antibiotic susceptibility to eight antibiotics, and Caco-2 cell invasion efficiency. S. typhimurium NCCP10812 showed increased thermal resistance (P<0.05 after exposure to single NaCl concentrations. A sequential increase of NaCl concentration decreased (P<0.05 the antibiotic sensitivities of S. typhimurium NCCP10812 to chloramphenicol, gentamicin, and oxytetracycline. NaCl exposure also increased (P<0.05 Caco-2 cell invasion efficiency of S. enteritidis NCCP12243. These results indicate that NaCl in food may cause increased thermal resistance, cell invasion efficiency, and antibiotic resistance of Salmonella.

  15. Raised white cell count in renal colic: Is there a role for antibiotics?

    Directory of Open Access Journals (Sweden)

    Adam Alleemudder

    2014-01-01

    Conclusions: Over three-quarters of the patients (80.9% in this study who presented with renal colic were unjustifiably commenced on antibiotics based solely on an elevated WCC. Antibiotic use in renal colic should be reserved for when there are features of sepsis or the urinalysis is positive. Further work is required to determine the significance of the observed results and the threshold for starting antibiotics.

  16. Antibiotics Quiz

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  17. Lectin Conjugated Gold Nanoparticle-based Colorimetric Assay for Studying the Interactions of Antibiotic with Living Cell

    Institute of Scientific and Technical Information of China (English)

    WANG Jin-e; WANG Cheng-ke; LIU Dian-jun; WANG Zhen-xin

    2011-01-01

    The interactions of antibiotic with living cells were studied by iectin conjugated gold nanoparticles(GNPs)based colorimetric assay. Because of the high affinity of lectin for saccharides, the lectin conjugated GNPs are able to employ as indicators for monitoring the antibiotic induced changes of glycosyl complexes. The interactions of a well known antibiotic, tunicamycin, with two different cell lines, HeLa and SHG-44, were selected to establish this assay.In the presence of tunicamycin, the dose- and time-dependence on the decreasing of binding affinity of lectin conjugated GNPs with living cells were demonstrated by conventional microscopic and UV-Vis spectroscopic studies. The experimental result demonstrates that our approach can be used to identify antibiotic induced expression difference of glycosyl complexes on different cellular surfaces and determine drug activity quantitatively. For further confirming the capability of the GNP-based assay, the system was also studied by confocal laser scanning microscopy(CLSM)and classic flow cytometry(FCM) assay, and satisfactory results were obtained.

  18. Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco‐2 cell invasion

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Holch, Anne; Gram, Lone

    2012-01-01

    Antibiotics can act as signal molecules and affect bacterial gene expression, physiology and virulence. The purpose of this study was to determine whether subinhibitory antibiotic concentrations alter gene expression and physiology of Listeria monocytogenes. Using an agar‐based screening assay...... expression; however, altered expression could not predict changes in phenotypic behaviour. Subinhibitory concentrations of antibiotics led to increased acid sensitivity, and we speculate that this is attributed to changes in cell envelope or reduced σB‐dependent gene expression. Although subinhibitory...

  19. The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets

    Directory of Open Access Journals (Sweden)

    Yao Liu

    2016-08-01

    Full Text Available Peptidoglycan is the major component of the cell envelope of virtually all bacteria. It has structural roles and acts as a selective sieve for molecules from the outer environment. Peptidoglycan synthesis is therefore one of the most important biogenesis pathways in bacteria and has been studied extensively over the last twenty years. The pathway starts in the cytoplasm, continues in the cytoplasmic membrane and finishes in the periplasmic space, where the precursor is polymerized into the peptidoglycan layer. A number of proteins involved in this pathway, such as the Mur enzymes and the penicillin binding proteins (PBPs, have been studied and regarded as good targets for antibiotics. The present review focuses on the membrane steps of peptidoglycan synthesis that involve two enzymes, MraY and MurG, the inhibitors of these enzymes and the inhibition mechanisms. We also discuss the challenges of targeting these two cytoplasmic membrane (associated proteins in bacterial cells and the perspectives on how to overcome the issues.

  20. The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets.

    Science.gov (United States)

    Liu, Yao; Breukink, Eefjan

    2016-01-01

    Peptidoglycan is the major component of the cell envelope of virtually all bacteria. It has structural roles and acts as a selective sieve for molecules from the outer environment. Peptidoglycan synthesis is therefore one of the most important biogenesis pathways in bacteria and has been studied extensively over the last twenty years. The pathway starts in the cytoplasm, continues in the cytoplasmic membrane and finishes in the periplasmic space, where the precursor is polymerized into the peptidoglycan layer. A number of proteins involved in this pathway, such as the Mur enzymes and the penicillin binding proteins (PBPs), have been studied and regarded as good targets for antibiotics. The present review focuses on the membrane steps of peptidoglycan synthesis that involve two enzymes, MraY and MurG, the inhibitors of these enzymes and the inhibition mechanisms. We also discuss the challenges of targeting these two cytoplasmic membrane (associated) proteins in bacterial cells and the perspectives on how to overcome the issues. PMID:27571111

  1. Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro

    Directory of Open Access Journals (Sweden)

    Toshikazu Shimane

    2001-01-01

    Full Text Available Background: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood.

  2. Efficient and reproducible generation of high-expressing, stable human cell lines without need for antibiotic selection

    Directory of Open Access Journals (Sweden)

    Kewes Helmut

    2008-02-01

    Full Text Available Abstract Background Human cell lines are the most innovative choice of host cell for production of biopharmaceuticals since they allow for authentic posttranslational modification of therapeutic proteins. We present a new method for generating high and stable protein expressing cell lines based on human amniocytes without the requirement of antibiotic selection. Results Primary amniocytes from routine amniocentesis samples can be efficiently transformed with adenoviral functions resulting in stable human cell lines. Cotransfection of the primary human amniocytes with a plasmid expressing adenoviral E1 functions plus a second plasmid containing a gene of interest resulted in permanent cell lines expressing up to 30 pg/cell/day of a fully glycosylated and sialylated protein. Expression of the gene of interest is very stable for more than 90 passages and, importantly, was achieved in the absence of any antibiotic selection. Conclusion We describe an improved method for developing high protein expressing stable human cell lines. These cell lines are of non-tumor origin, they are immortalized by a function not oncogenic in human and they are from an ethically accepted and easily accessible cell source. Since the cell can be easily adapted to growth in serum-free and chemically defined medium they fulfill the requirements of biopharmaceutical production processes.

  3. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  4. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  5. Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2008-10-01

    Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.

  6. Mycobacteriophage SWU1 gp39 can potentiate multiple antibiotics against Mycobacterium via altering the cell wall permeability.

    Science.gov (United States)

    Li, Qiming; Zhou, Mingliang; Fan, Xiangyu; Yan, Jianlong; Li, Weimin; Xie, Jianping

    2016-01-01

    M. tuberculosis is intrinsically tolerant to many antibiotics largely due to the imperviousness of its unusual mycolic acid-containing cell wall to most antimicrobials. The emergence and increasingly widespread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) revitalized keen interest in phage-inspired therapy. SWU1gp39 is a novel gene from mycobacteriophage SWU1 with unknown function. SWU1gp39 expressed in M. smegmatis conferred the host cell increased susceptibility to multiple antibiotics, including isoniazid, erythromycin, norfloxacin, ampicillin, ciprofloxacin, ofloxacin, rifampicin and vancomycin, and multiple environment stresses such as H2O2, heat shock, low pH and SDS. By using EtBr/Nile red uptake assays, WT-pAL-gp39 strain showed higher cell wall permeability than control strain WT-pAL. Moreover, the WT-pAL-gp39 strain produced more reactive oxygen species and reduced NAD(+)/NADH ratio. RNA-Seq transcriptomes of the WT-pAL-gp39 and WT-pAL revealed that the transcription of 867 genes was differentially regulated, including genes associated with lipid metabolism. Taken together, our results implicated that SWU1gp39, a novel gene from mycobacteriophage, disrupted the lipid metabolism of host and increased cell wall permeability, ultimately potentiated the efficacy of multiple antibiotics and stresses against mycobacteria. PMID:27350398

  7. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nielsen, Lene Nørby; Roggenbuck, Michael; Haaber, Jakob Krause;

    2012-01-01

    ABSTRACT: BACKGROUND: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. FINDINGS: LacZ promoter fusions of genes related...... by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently...

  8. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    Science.gov (United States)

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent

  9. Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis

    Science.gov (United States)

    Chuengsaman, Piyatida

    2016-01-01

    Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value < 0.001 for all comparisons). Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter. PMID:27656294

  10. Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis

    Directory of Open Access Journals (Sweden)

    Pichaya Tantiyavarong

    2016-01-01

    Full Text Available Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7% of early response, 122 (18.9% of delayed response, and 144 (22.3% of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value < 0.001 for all comparisons. Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter.

  11. Evaluation of the use of dry cow antibiotics in low somatic cell count cows

    NARCIS (Netherlands)

    Scherpenzeel, C. G M; Den Uijl, I. E M; Van Schaik, G.; Olde Riekerink, R. G M; Keurentjes, J. M.; Lam, T. J G M

    2014-01-01

    The goal of dry cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antibiotics has become questionable. This st

  12. The multifaceted roles of antibiotics and antibiotic resistance in nature

    Directory of Open Access Journals (Sweden)

    Saswati eSengupta

    2013-03-01

    Full Text Available Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic-resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic-resistance in pathogens. In the natural milieu, antibiotics are often found to be present in subinhibitory concentrations acting as signalling molecules supporting quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host-parasite interactions (e.g., phagocytosis, adherence to the target cell and so on. The evolutionary and ecological aspects of antibiotics and antibiotic-resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behaviour of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and genes that confer resistance to antibiotics in

  13. Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Venturi Vittorio

    2009-09-01

    Full Text Available Abstract Background Burkholderia cenocepacia are opportunistic Gram-negative bacteria that can cause chronic pulmonary infections in patients with cystic fibrosis. These bacteria demonstrate a high-level of intrinsic antibiotic resistance to most clinically useful antibiotics complicating treatment. We previously identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND efflux pumps in the genome of B. cenocepacia J2315, but the contribution of these pumps to the intrinsic drug resistance of this bacterium remains unclear. Results To investigate the contribution of efflux pumps to intrinsic drug resistance of B. cenocepacia J2315, we deleted 3 operons encoding the putative RND transporters RND-1, RND-3, and RND-4 containing the genes BCAS0591-BCAS0593, BCAL1674-BCAL1676, and BCAL2822-BCAL2820. Each deletion included the genes encoding the RND transporter itself and those encoding predicted periplasmic proteins and outer membrane pores. In addition, the deletion of rnd-3 also included BCAL1672, encoding a putative TetR regulator. The B. cenocepacia rnd-3 and rnd-4 mutants demonstrated increased sensitivity to inhibitory compounds, suggesting an involvement of these proteins in drug resistance. Moreover, the rnd-3 and rnd-4 mutants demonstrated reduced accumulation of N-acyl homoserine lactones in the growth medium. In contrast, deletion of the rnd-1 operon had no detectable phenotypes under the conditions assayed. Conclusion Two of the three inactivated RND efflux pumps in B. cenocepacia J2315 contribute to the high level of intrinsic resistance of this strain to some antibiotics and other inhibitory compounds. Furthermore, these efflux systems also mediate accumulation in the growth medium of quorum sensing molecules that have been shown to contribute to infection. A systematic study of RND efflux systems in B. cenocepacia is required to provide a full picture of intrinsic antibiotic resistance in this opportunistic

  14. Bacillus subtilis as a platform for molecular characterisation of regulatory mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.

    Directory of Open Access Journals (Sweden)

    Chong Fang

    Full Text Available To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two-component system VanSB-VanRB, were produced in B. subtilis and their functions were monitored using target promoters fused to reporter genes (lacZ and luxABCDE. The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully functional in B. subtilis, both regarding regulation of bcrAB expression and resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin resistance of B. subtilis increased the sensitivity of the system. The lacZ and luxABCDE reporters were found to both offer sensitive detection of promoter induction on solid media, which is useful for screening of large mutant libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to vancomycin, but only when produced at low levels in the cell. Taken together, our data show that B. subtilis is a well-suited host for the molecular characterization of regulatory systems controlling resistance against cell wall active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful adjustment of expression levels and genetic background required for full functionality of the introduced regulators.

  15. Bacillus subtilis as a platform for molecular characterisation of regulatory mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.

    Science.gov (United States)

    Fang, Chong; Stiegeler, Emanuel; Cook, Gregory M; Mascher, Thorsten; Gebhard, Susanne

    2014-01-01

    To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two-component system VanSB-VanRB, were produced in B. subtilis and their functions were monitored using target promoters fused to reporter genes (lacZ and luxABCDE). The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully functional in B. subtilis, both regarding regulation of bcrAB expression and resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin resistance of B. subtilis increased the sensitivity of the system. The lacZ and luxABCDE reporters were found to both offer sensitive detection of promoter induction on solid media, which is useful for screening of large mutant libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to vancomycin, but only when produced at low levels in the cell. Taken together, our data show that B. subtilis is a well-suited host for the molecular characterization of regulatory systems controlling resistance against cell wall active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful adjustment of expression levels and genetic background required for full functionality of the introduced regulators.

  16. Combined effect of a peptide–morpholino oligonucleotide conjugate and a cell-penetrating peptide as an antibiotic

    OpenAIRE

    Wesolowski, Donna; Alonso, Dulce; Altman, Sidney

    2013-01-01

    A cell-penetrating peptide (CPP)–morpholino oligonucleotide (MO) conjugate (PMO) that has an antibiotic effect in culture had some contaminating CPPs in earlier preparations. The mixed conjugate had gene-specific and gene-nonspecific effects. An improved purification procedure separates the PMO from the free CPP and MO. The gene-specific effects are a result of the PMO, and the nonspecific effects are a result of the unlinked, unreacted CPP. The PMO and the CPP can be mixed together, as has b...

  17. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis of sensory hair cells in the mouse inner ear

    Directory of Open Access Journals (Sweden)

    Neil eSegil

    2015-05-01

    Full Text Available Aminoglycoside antibiotics are the drug of choice for treating many bacterial infections, but their administration results in hearing loss in nearly one fourth of the patients who receive them. Several biochemical pathways have been implicated in aminoglycoside antibiotic ototoxicity; however, little is known about how hair cells respond to aminoglycoside antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the aminoglycoside antibiotic gentamicin. Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from FACS-purified hair cells. Within 3 hours of gentamicin treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the JNK pathway and the NF-κB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to gentamicin share a considerable similarity with those previously observed in gentamicin-induced nephrotoxicity. Our findings suggest that previously observed early responses to gentamicin in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternative pathway regulating gentamicin-induced hair cell death. This work provides a more comprehensive view of aminoglycoside antibiotic ototoxicity, and thus contribute to identifying potential pathways or therapeutic targets to alleviate this important side effect of aminoglycoside

  18. Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria.

    Science.gov (United States)

    Hwang, In Young; Koh, Elvin; Kim, Hye Rim; Yew, Wen Shan; Chang, Matthew Wook

    2016-07-01

    The discovery of antimicrobial drugs and their subsequent use has offered an effective treatment option for bacterial infections, reducing morbidity and mortality over the past 60 years. However, the indiscriminate use of antimicrobials in the clinical, community and agricultural settings has resulted in selection for multidrug-resistant bacteria, which has led to the prediction of possible re-entrance to the pre-antibiotic era. The situation is further exacerbated by significantly reduced antimicrobial drug discovery efforts by large pharmaceutical companies, resulting in a steady decline in the number of new antimicrobial agents brought to the market in the past several decades. Consequently, there is a pressing need for new antimicrobial therapies that can be readily designed and implemented. Recently, it has become clear that the administration of broad-spectrum antibiotics can lead to collateral damage to the human commensal microbiota, which plays several key roles in host health. Advances in genetic engineering have opened the possibility of reprogramming commensal bacteria that are in symbiotic existence throughout the human body to implement antimicrobial drugs with high versatility and efficacy against pathogenic bacteria. In this review, we discuss recent advances and potentialities of engineered bacteria in providing a novel antimicrobial strategy against antibiotic resistance. PMID:27449598

  19. Selection of antibiotic resistance at very low antibiotic concentrations.

    Science.gov (United States)

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  20. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Barker Peter E

    2007-05-01

    Full Text Available Abstract Background Sulfur mustard (SM is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE cells and bronchial/tracheal epithelial (BTE cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF, and expression of inducible nitric oxide synthase (iNOS were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant. Results MTS assay and Calcein AM/ethidium homodimer (EthD-1 fluorescence staining showed that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM-stimulated overproduction of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF at both the protein level and the mRNA level, as measured by either enzyme-linked immunosorbent assay (ELISA or real-time RT-PCR. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS, as revealed by immunocytochemical analysis using quantum dots as the fluorophore. Conclusion The present study demonstrates that roxithromycin has inhibitory effects on the cytotoxicity and inflammation provoked by SM in human respiratory epithelial cells. The decreased cytotoxicity in roxithromycin-treated cells likely depends on the ability of the macrolide to down-regulate the production of proinflammatory

  1. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A;

    2012-01-01

    In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...... disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were...... available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better...

  2. Synergistic inhibition of angiogenesis and glioma cell-induced angiogenesis by the combination of temozolomide and enediyne antibiotic lidamycin.

    Science.gov (United States)

    Li, Xing-Qi; Ouyang, Zhi-Gang; Zhang, Sheng-Hua; Liu, Hong; Shang, Yue; Li, Yi; Zhen, Yong-Su

    2014-04-01

    Present work mainly evaluated the inhibitory effects of lidamycin (LDM), an enediyne antibiotic, on angiogenesis or glioma-induced angiogenesis in vitro and in vivo, especially its synergistic anti-angiogenesis with temozolomide (TMZ). LDM alone efficiently inhibited proliferations and induced apoptosis of rat brain microvessel endothelial cells (rBMEC). LDM also interrupted the tube formation of rat brain microvessel endothelial cells (rBMEC) and rat aortic ring spreading. The blockade of rBMEC invasion and C6 cell-induced rBMEC migration by LDM was associated with decrease of VEGF secretion in a co-culture system. TMZ dramatically potentiated the effects of LDM on anti-proliferation, apoptosis induction, and synergistically inhibited angiogenesis events. As determined by western blot and ELISA, the interaction of tumor cells and the rBMEC was markedly interrupted by LDM plus TMZ with synergistic regulations of VEGF induced angiogenesis signal pathway, tumor cell invasion/migration, and apoptosis signal pathway. Immunofluorohistochemistry of CD31 and VEGF showed that LDM plus TMZ resulted in synergistic decrease of microvessel density (MVD) and VEGF expression in human glioma U87 cell subcutaneous xenograft. This study indicates that the high efficacy of LDM and the synergistic effects of LDM plus TMZ against glioma are mediated, at least in part, by the potentiated anti-angiogenesis. PMID:24424202

  3. Multifunctional nanocrystalline calcium phosphates loaded with Tetracycline antibiotic combined with human adipose derived mesenchymal stromal stem cells (hASCs).

    Science.gov (United States)

    Marycz, K; Pazik, R; Zawisza, K; Wiglusz, K; Maredziak, M; Sobierajska, P; Wiglusz, R J

    2016-12-01

    Osteoconductive drug delivery system composed of nanocrystalline calcium phosphates (Ca10(PO4)6(OH)2/β-Ca3(PO4)2) co-doped with Yb(3+)/Er(3+) ions loaded with Tetracycline antibiotic (TC) was developed. Their effect on human adipose derived mesenchymal stromal stem cells (hASCs) as a potential reconstructive biomaterial for bone tissue regeneration was studied. The XRD and TEM measurements were used in order to determine the crystal structure and morphology of the final products. The characteristics of nanocomposites with the TC and hASCs as potential regenerative materials as well as the antimicrobial activity of the nanoparticles against: Staphylococcus aureus ATCC 25923 as a model of the Gram-positive bacteria, Escherichia coli ATCC 8739 of the Gram-negative bacteria, were shown. These combinations can be a promising material for theranostic due to its regenerative, antimicrobial and fluorescent properties. PMID:27612684

  4. Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Rasigade Jean

    2011-12-01

    Full Text Available Abstract Background Staphylococcus aureus is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by fnbA/B, are major pathogenesis determinants in these infections through their involvement in S. aureus adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs of antibiotics, frequently occurring in vivo because of impaired drug diffusion at the infection site, can alter S. aureus phenotype. We therefore investigated their impact on S. aureus fibronectin-mediated adhesiveness and invasiveness. Methods After in vitro challenge of S. aureus 8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored fnbA/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts. Results Oxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in fnbA/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting fnbA/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or fnbA/B transcription levels. Only oxacillin-treated S. aureus displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls. Conclusion Our findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in S. aureus in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled in vitro conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during in vivo infections is thus still uncertain and requires further investigations.

  5. Mycoplasma Suppression of THP-1 Cell TLR Responses Is Corrected with Antibiotics

    OpenAIRE

    Ekaterina Zakharova; Jaykumar Grandhi; Wewers, Mark D.; Gavrilin, Mikhail A.

    2010-01-01

    Mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. We found that chronic mycoplasma contamination of THP-1 cells suppresses responses of THP-1 cells to TLR stimuli. For example, E. coli LPS induced IL-1 beta was suppressed by 6 fold and IL-8 by 10 fold in mycoplasma positive THP-1 cells. Responses to live F. novicida challenge were suppressed by 50-fold and 40-fold respective...

  6. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity

    NARCIS (Netherlands)

    Wiedemann, [No Value; Breukink, E; van Kraaij, C; Kuipers, OP; Bierbaum, G; de Kruijff, B; Sahl, HA

    2001-01-01

    Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the Lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin

  7. Postantibiotic effect assessments for antibiotics exhibiting a wide range of bactericidal activities by using a modified total-cell-counting method.

    OpenAIRE

    Li, R. C.; S.W. Lee

    1997-01-01

    We recently described a total-cell-counting method for postantibiotic effect (PAE) assessments that performs well with weakly bactericidal antibiotics. This note presents a modified method for the study of PAE with extended capability to cover a broad range of bactericidal activities.

  8. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...... of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I...... to rationally design drug combinations that limit the evolution of antibiotic resistance due to counteracting evolutionary trajectories. My results highlight that an in-depth knowledge about the genetic responses to the individual antimicrobial compounds enables the prediction of responses to drug combinations...

  9. Aerosolized Antibiotics.

    Science.gov (United States)

    Restrepo, Marcos I; Keyt, Holly; Reyes, Luis F

    2015-06-01

    Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

  10. Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1996-06-28

    DT-Diaphorase catalyzes a two-electron reduction of mitomycin C (MC) and porfiromycin (POR) to reactive species. Many cell lines that overexpress DT-diaphorase and are sensitive to the mitomycins are protected from the aerobic cytotoxicity of these drugs by the DT-diaphorase inhibitor dicumarol. The cytoprotective properties of this relatively non-specific inhibitor, however, vanish under hypoxic conditions. To ascertain the role of DT-diaphorase in mitomycin bioactivation and cytotoxicity in living cells, a rat liver DT-diaphorase cDNA was transfected into Chinese hamster ovary cells. MC was equitoxic to the parental cells under oxygenated and hypoxic conditions. In contrast, POR was less toxic than MC to these cells under aerobic conditions, but significantly more toxic than MC under hypoxia. Two DT-diaphorase-transfected clones displayed increases in DT-diaphorase activity of 126- and 133-fold over parental cells. The activities of other oxidoreductases implicated in mitomycin bioreduction were unchanged. MC was more toxic to both DT-diaphorase-transfected lines than to parental cells; the toxicity of MC to the transfected lines was similar in air and hypoxia. POR was also more toxic to the DT-diaphorase-elevated clones than to parental cells under oxygenated conditions. Under hypoxia, however, the toxicity of POR to the transfected clones was unchanged from that of parental cells. The findings implicate DT-diaphorase in mitomycin bioactivation in living cells, but suggest that this enzyme does not contribute to the differential toxicity of MC or POR in air and hypoxia. PMID:8687482

  11. The Staphylococcus aureus Thiol/Oxidative Stress Global Regulator Spx Controls trfA, a Gene Implicated in Cell Wall Antibiotic Resistance

    Science.gov (United States)

    Jousselin, Ambre; Barras, Christine; Lew, Daniel P.

    2013-01-01

    S. aureus combats cell wall antibiotic stress by altered gene expression mediated by various environmental signal sensors. In this study, we examined the transcriptional regulation of trfA, a gene related to mecA of Bacillus subtilis encoding an adaptor protein implicated in multiple roles, notably, proteolysis and genetic competence. Despite strong sequence similarity to B. subtilis mecA, the function of S. aureus trfA remains largely unexplored; however, its deletion leads to almost complete loss of resistance to oxacillin and glycopeptide antibiotics in glycopeptide-intermediate S. aureus (GISA) derivatives of methicillin-susceptible or methicillin-resistant S. aureus (MRSA) clinical or laboratory isolates. Northern blot analysis and 5′ rapid amplification of cDNA ends (RACE) mapping revealed that trfA was expressed monocistronically by three promoters. Cell wall-active antibiotic exposure led to both increased trfA transcription and enhanced steady-state TrfA levels. trfA promoter regulation was not dependent upon the cell wall stress sentinel VraSR and other sensory stress systems, such as GraRS, WalkRK, Stk1/Stp1, and SigB. Notably, we discovered that the global oxidative-stress regulator Spx controlled trfA transcription. This finding was also confirmed using a strain with enhanced Spx levels resulting from a defect in yjbH, encoding a Spx-interacting protein governing Spx proteolytic degradation. A cohort of clinical GISA strains revealed significant steady-state upregulation of trfA compared to corresponding susceptible parental strains, further supporting a role for trfA in antibiotic resistance. These data provide strong evidence for a link between cell wall antibiotic stress and evoked responses mediated by an oxidative-stress sensor. PMID:23629700

  12. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  13. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues. PMID:25970790

  14. Antibiotics and antibiotic resistance: a bitter fight against evolution.

    Science.gov (United States)

    Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

    2013-08-01

    One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance.

  15. Efficient mineralization of the antibiotic trimethoprim by solar assisted photoelectro-Fenton process driven by a photovoltaic cell.

    Science.gov (United States)

    Zhang, Yanyu; Wang, Aimin; Tian, Xiujun; Wen, Zhenjun; Lv, Hanjiao; Li, Desheng; Li, Jiuyi

    2016-11-15

    In this study, a novel self-sustainable solar assisted photoelectro-Fenton (SPEF) system driven by a solar photovoltaic cell was developed for the efficient mineralization of antibiotic trimethoprim (TMP) in water. A comparative degradation of 200mgL(-1) TMP by RuO2/Ti anodic oxidation (AO), anodic oxidation with H2O2 electrogeneration (AO-H2O2), electro-Fenton (EF) and SPEF was investigated. SPEF was proved to exhibit the highest oxidation power, i.e., more than 80% TOC was removed after 360min SPEF treatment of 200mgL(-1) of TMP under optimal conditions at pH 3.0, 1.0mM Fe(2+) and 18mAcm(-2). Influences of current density, pH, initial Fe(2+) and initial TMP concentration on SPEF process were also studied. Ten aromatic intermediates generated from hydroxylation, carbonylation and demethylation reactions were identified using UPLC-QTOF-MS/MS system during the SPEF treatment, together with three carboxylic acids (oxamic, oxalic and formic acids) and two inorganic ions (NH4(+) and NO3(-)) measured. Therefore, a reasonable pathway of TMP degradation in SPEF process was proposed.

  16. Efficient mineralization of the antibiotic trimethoprim by solar assisted photoelectro-Fenton process driven by a photovoltaic cell.

    Science.gov (United States)

    Zhang, Yanyu; Wang, Aimin; Tian, Xiujun; Wen, Zhenjun; Lv, Hanjiao; Li, Desheng; Li, Jiuyi

    2016-11-15

    In this study, a novel self-sustainable solar assisted photoelectro-Fenton (SPEF) system driven by a solar photovoltaic cell was developed for the efficient mineralization of antibiotic trimethoprim (TMP) in water. A comparative degradation of 200mgL(-1) TMP by RuO2/Ti anodic oxidation (AO), anodic oxidation with H2O2 electrogeneration (AO-H2O2), electro-Fenton (EF) and SPEF was investigated. SPEF was proved to exhibit the highest oxidation power, i.e., more than 80% TOC was removed after 360min SPEF treatment of 200mgL(-1) of TMP under optimal conditions at pH 3.0, 1.0mM Fe(2+) and 18mAcm(-2). Influences of current density, pH, initial Fe(2+) and initial TMP concentration on SPEF process were also studied. Ten aromatic intermediates generated from hydroxylation, carbonylation and demethylation reactions were identified using UPLC-QTOF-MS/MS system during the SPEF treatment, together with three carboxylic acids (oxamic, oxalic and formic acids) and two inorganic ions (NH4(+) and NO3(-)) measured. Therefore, a reasonable pathway of TMP degradation in SPEF process was proposed. PMID:27434735

  17. Factors influencing variation of bulk milk antibiotic residue occurrence, somatic cell count, and total bacterial count in dairy sheep flocks.

    Science.gov (United States)

    Gonzalo, C; Carriedo, J A; García-Jimeno, M C; Pérez-Bilbao, M; de la Fuente, L F

    2010-04-01

    To study the variations of bulk tank milk variables in dairy ewe flocks and to identify the main target practices and flock groups to improve milk quality and safety, a total of 71,228 records of antibiotic residue (AR) and milk yield and 68,781 records of somatic cell count (SCC) and total bacterial count (TBC) were obtained over 5 yr from the same 209 dairy ewe flocks of the Assaf breed belonging to the Consortium for Ovine Promotion of Castilla-León (Spain). Based on a logistic regression model, year, month, semester, SCC, TBC, dry therapy, and milk yield significantly contributed to AR variation. High SCC was associated with increased AR violations. When antibiotic dry therapy was implemented, AR occurrence was higher than when this practice was not used. A polynomial monthly distribution throughout the year was observed for AR occurrence; the highest values were in autumn, coinciding with low milk yields per flock. Yearly occurrences drastically diminished from 2004 (1.36%) to 2008 (0.30%), probably as a result of effective educational programs. The mixed-model ANOVA of factors influencing variation in SCC and TBC indicated that year, month, AR, dry therapy group, milking type, and year interactions were significant variation factors for SCC and TBC; mathematical model accounted for 74.1 and 35.4% of total variance for each variable, respectively. Differences in management and hygiene practice caused significant SCC and TBC variations among flocks and within flocks throughout the 5-yr study. Over time, continuously dry treated flocks showed lower logSCC (5.80) and logTBC (4.92) than untreated (6.10 and 5.18, respectively) or discontinuously dry treated (6.01 and 5.05, respectively) flocks. Continuously dry treated flocks had lower AR occurrences than did discontinuously dry treated flocks. As a whole, AR occurrence and SCC and TBC bulk tank milk variables can be used for monitoring mammary health and milk hygiene and safety in dairy sheep throughout time.

  18. Ethidium bromide transport across Mycobacterium smegmatis cell-wall: correlation with antibiotic resistance

    OpenAIRE

    Couto Isabel; Ramos Jorge; Rodrigues Liliana; Amaral Leonard; Viveiros Miguel

    2011-01-01

    Abstract Background Active efflux systems and reduced cell-wall permeability are considered to be the main causes of mycobacterial intrinsic resistance to many antimicrobials. In this study, we have compared the Mycobacterium smegmatis wild-type strain mc2155 with knockout mutants for porins MspA (the main porin of M. smegmatis) and MspC, the efflux pump LfrA (the main efflux pump system of M. smegmatis) and its repressor LfrR for their ability to transport ethidium bromide (EtBr) on a real-t...

  19. Lipid II: a central component in bacterial cell wall synthesis and a target for antibiotics.

    Science.gov (United States)

    de Kruijff, Ben; van Dam, Vincent; Breukink, Eefjan

    2008-01-01

    The bacterial cell wall is mainly composed of peptidoglycan, which is a three-dimensional network of long aminosugar strands located on the exterior of the cytoplasmic membrane. These strands consist of alternating MurNAc and GlcNAc units and are interlinked to each other via peptide moieties that are attached to the MurNAc residues. Peptidoglycan subunits are assembled on the cytoplasmic side of the bacterial membrane on a polyisoprenoid anchor and one of the key components in the synthesis of peptidoglycan is Lipid II. Being essential for bacterial cell survival, it forms an attractive target for antibacterial compounds such as vancomycin and several lantibiotics. Lipid II consists of one GlcNAc-MurNAc-pentapeptide subunit linked to a polyiosoprenoid anchor 11 subunits long via a pyrophosphate linker. This review focuses on this special molecule and addresses three questions. First, why are special lipid carriers as polyprenols used in the assembly of peptidoglycan? Secondly, how is Lipid II translocated across the bacterial cytoplasmic membrane? And finally, how is Lipid II used as a receptor for lantibiotics to kill bacteria? PMID:19008088

  20. Cell wall antibiotics provoke accumulation of anchored mCherry in the cross wall of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Wenqi Yu

    Full Text Available A fluorescence microscopy method to directly follow the localization of defined proteins in Staphylococcus was hampered by the unstable fluorescence of fluorescent proteins. Here, we constructed plasmid (pCX encoded red fluorescence (RF mCherry (mCh hybrids, namely mCh-cyto (no signal peptide and no sorting sequence, mCh-sec (with signal peptide, and mCh-cw (with signal peptide and cell wall sorting sequence. The S. aureus clones targeted mCh-fusion proteins into the cytosol, the supernatant and the cell envelope respectively; in all cases mCherry exhibited bright fluorescence. In staphylococci two types of signal peptides (SP can be distinguished: the +YSIRK motif SP(lip and the -YSIRK motif SP(sasF. mCh-hybrids supplied with the +YSIRK motif SP(lip were always expressed higher than those with -YSIRK motif SP(sasF. To study the location of the anchoring process and also the influence of SP type, mCh-cw was supplied on the one hand with +YSIRK motif (mCh-cw1 and the other hand with -YSIRK motif (mCh-cw2. MCh-cw1 preferentially localized at the cross wall, while mCh-cw2 preferentially localized at the peripheral wall. Interestingly, when treated with sub-lethal concentrations of penicillin or moenomycin, both mCh-cw1 and mCh-cw2 were concentrated at the cross wall. The shift from the peripheral wall to the cross wall required Sortase A (SrtA, as in the srtA mutant this effect was blunted. The effect is most likely due to antibiotic mediated increase of free anchoring sites (Lipid II at the cross wall, the substrate of SrtA, leading to a preferential incorporation of anchored proteins at the cross wall.

  1. Inhibition of sulfur mustard-induced cytotoxicity and inflammation by the macrolide antibiotic roxithromycin in human respiratory epithelial cells

    OpenAIRE

    Barker Peter E; Xiao Yan; Ray Radharaman; Gao Xiugong; Ray Prabhati

    2007-01-01

    Abstract Background Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using ...

  2. A high speed detection platform based on surface-enhanced Raman scattering for monitoring antibiotic-induced chemical changes in bacteria cell wall.

    Directory of Open Access Journals (Sweden)

    Ting-Ting Liu

    Full Text Available Rapid and accurate diagnosis for pathogens and their antibiotic susceptibility is critical for controlling bacterial infections. Conventional methods for determining bacterium's sensitivity to antibiotic depend mostly on measuring the change of microbial proliferation in response to the drug. Such "biological assay" inevitably takes time, ranging from days for fast-growing bacteria to weeks for slow-growers. Here, a novel tool has been developed to detect the "chemical features" of bacterial cell wall that enables rapid identification of drug resistant bacteria within hours. The surface-enhanced Raman scattering (SERS technique based on our newly developed SERS-active substrate was applied to assess the fine structures of the bacterial cell wall. The SERS profiles recorded by such a platform are sensitive and stable, that could readily reflect different bacterial cell walls found in Gram-positive, Gram-negative, or mycobacteria groups. Moreover, characteristic changes in SERS profile were noticed in the drug-sensitive bacteria at the early period (i.e., approximately 1 hr of antibiotic exposure, which could be used to differentiate them from the drug-resistant ones. The SERS-based diagnosis could be applied to a single bacterium. The high-speed SERS detection represents a novel approach for microbial diagnostics. The single-bacterium detection capability of SERS makes possible analyses directly on clinical specimen instead of pure cultured bacteria.

  3. [Action of antibiotics as signalling molecules].

    Science.gov (United States)

    Bulgakova, V G; Vinogradova, K A; Orlova, T I; Kozhevin, P A; Polin, A N

    2014-01-01

    It was thought that antibiotics should be produced by soil microorganisms to inhibit the growth of competitors in natural habitats. Yet it has been shown that antibiotics at subinhibitory concentrations may have a role as signalling molecules providing cell-to-cell communication in bacteria in the environment. Antibiotics modulate gene transcription and regulate gene expression in microbial populations. Subinhibitory concentrations of antibiotics may cause a number of phenotypic and genotypic changes in microorganisms. These transcription changes are dependent on the interaction of antibiotics with macromolecular receptors such as ribosome or RNA-polymerase. Antibiotic signalling and quorum-sensing system are important regulatory mechanisms in bacteria. It was demonstrated that antibiotics interfered with quorum-sensing system.

  4. Inhibition of RNA synthesis in vitro and cell growth by anthracycline antibiotics.

    Science.gov (United States)

    Studzian, K; Wasowska, M; Piestrzeniewicz, M K; Wilmańska, D; Szmigiero, L; Oszczapowicz, I; Gniazdowski, M

    2001-01-01

    New derivatives of doxorubicin and daunorubicin with amidine group bonded to daunosamine at C-3' atom and bearing the morpholine ring attached to the amidine group have been recently synthesized. Their cytotoxic activities and effects on RNA synthesis in vitro were assayed. The drug concentrations inhibiting mouse leukaemia L1210 cell growth to 50% were about two- and three fold higher for the derivatives compared to doxorubicin and daunorubicin respectively. Inhibition of phage T7 RNA polymerase by the non-covalently interacting derivatives was also slightly lower than that by the parent compounds. As doxorubicin and daunorubicin, their amidine derivatives in the presence of dithiothreitol and Fe(III) ions are activated and covalently bind to DNA. The adducts formed affect RNA polymerase activity. Several bands corresponding to prematurely terminated RNA chains are observed by means of polyacrylamide gel electrophoresis. The patterns of bands are virtually identical for all the anthracyclines studied here and are similar to the terminations induced by actinomycin D. This observation is consistent with a notion that the adducts are formed at guanine in GpC sequences which are also binding sites of actinomycin D. A substantial difference between daunorubicin and its amidine derivative is shown by means of high performance liquid chromatography. The derivative undergoes rapid rearrangements in the presence of dithiothreitol and Fe(III) ions, while daunorubicin is stable for several hours under these conditions. The results presented here indicate that the amidine derivatives despite bulky morpholine substitution exhibit biological activity in the systems used here. PMID:11845988

  5. Beyond Antibiotics?

    Directory of Open Access Journals (Sweden)

    LE Nicolle

    2006-01-01

    Full Text Available The AMMI Canada meeting in March 2006 hosted a symposium exploring the potential alternatives to antibiotics for the prevention and treatment of infection. Four papers summarizing talks from that session are published in this issue of the Journal (1-4. These reviews address the scientific underpinnings for a number of proposed concepts, and summarize the current status of clinical use. The approaches - probiotics, bacteriophage therapy, and manipulation of innate immunity - are all intriguing but are still removed from immediate practical applications.

  6. Genotoxicity induced by drug-drug interaction between the antidepressant sertraline and the antibiotic erythromycin in micebone marrow cells.

    Directory of Open Access Journals (Sweden)

    Amany A. Tohamy

    2006-03-01

    Full Text Available Drug-drug interaction represents a widely distributed health problem. The pharmacological action and side effects of two or more drugs can act additively or antagonistically. The present study was designed to evaluate the possible genotoxicity of concurrent treatment with the antidepressant sertraline, one of the serotonin reuptake inhibitors (SSRI and the broad spectrum macrolide antibiotic erythromycin. Sertraline and erythromycin are metabolized through CYP3A4 which is one of the cytochrome P-450 enzymes in liver and are responsible for the metabolism of large number of endogenous substrates and therapeutic agents. The frequency of micronucleated polychromatic erythrocytes (MNPCEs, micronucleated normochromatic erythrocytes (MNNCEs and the ratio PCE/NCE were evaluated to measure the genotoxicity of separate and combined treatment with the tested two drugs. Clinical doses of both sertraline (0.71 mg /kg b.w. and erythromcyin strearate (14.30 mg / kg b.w. were used. Groups of animals received single separate or combined doses of either sertraline and/or erythromycin, and sacrificed after 24 hours. Other groups of mice were treated in the same way but for five consecutive days and sacrificed 24 hours after the last injection. In all treated groups, the percentage of PCEs increased significantly when compared with that of the negative control group which may indicate a stimulation of proliferative activity to an early phase of cell depletion. The genotoxicity of multiple treatment for 5 consecutive days with sertraline alone or in combination with erythromcyin was expressed in increased number of MNPCEs. The observed increased genotoxicity after multiple combined treatment with sertraline and erythromycin may indicate increased risk of toxicity-based drug-drug interaction. This toxicity may be due to the ability of sertraline and erythromycin to inhibit the activity of CYP3A4 which lead to a prolonged storage period of drugs in the body and hence

  7. Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis.

    Science.gov (United States)

    Pianta, Annalisa; Drouin, Elise E; Crowley, Jameson T; Arvikar, Sheila; Strle, Klemen; Costello, Catherine E; Steere, Allen C

    2015-10-01

    In this study, autoantibody responses to annexin A2 were found in 11-15% of 278 patients with Lyme disease, including in those with erythema migrans (EM), an early sign of the illness, and in those with antibiotic-responsive or antibiotic-refractory Lyme arthritis (LA), a late disease manifestation. In contrast, robust T cell reactivity to annexin A2 peptides was found only in patients with responsive or refractory LA. In LA patients, annexin A2 protein levels, which were higher in the refractory group, correlated with annexin A2 antibody levels in sera and synovial fluid. In addition, in patients with antibiotic-refractory LA who had anti-annexin A2 antibodies, synovial tissue had intense staining for annexin A2 protein, greater synovial fibroblast proliferation and more tissue fibrosis. Thus, a subset of LA patients had T and B cell responses to annexin A2, and in the refractory group, annexin A2 autoantibodies were associated with specific pathologic findings.

  8. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.

    Science.gov (United States)

    Shono, Yusuke; Docampo, Melissa D; Peled, Jonathan U; Perobelli, Suelen M; Velardi, Enrico; Tsai, Jennifer J; Slingerland, Ann E; Smith, Odette M; Young, Lauren F; Gupta, Jyotsna; Lieberman, Sophia R; Jay, Hillary V; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Xu, Ke; Calarfiore, Marco; Poeck, Hendrik; Caballero, Silvia; Devlin, Sean M; Rapaport, Franck; Dudakov, Jarrod A; Hanash, Alan M; Gyurkocza, Boglarka; Murphy, George F; Gomes, Camilla; Liu, Chen; Moss, Eli L; Falconer, Shannon B; Bhatt, Ami S; Taur, Ying; Pamer, Eric G; van den Brink, Marcel R M; Jenq, Robert R

    2016-05-18

    Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon. PMID:27194729

  9. Predation and selection for antibiotic resistance in natural environments

    DEFF Research Database (Denmark)

    Leisner, Jørgen; Jørgensen, Niels O. G.; Middelboe, Mathias

    2016-01-01

    Genes encoding resistance to antibiotics appear, like the antibiotics themselves, to be ancient, originating long before the rise of the era of anthropogenic antibiotics. However, detailed understanding of the specific biological advantages of antibiotic resistance in natural environments is still...... lacking, thus limiting our efforts to prevent environmental influx of resistance genes. Here, we propose that antibiotic-resistant cells not only evade predation from antibiotic producers but also take advantage of nutrients released from cells that are killed by the antibiotic-producing bacteria. Thus......, predation is potentially an important mechanism for driving antibiotic resistance during slow or stationary phase of growth when nutrients are deprived. This adds to explain the ancient nature and widespread occurrence of antibiotic resistance in natural environments unaffected by anthropogenic antibiotics...

  10. Transformation of Cowpea Vigna unguiculata Cells with an Antibiotic Resistance Gene Using a Ti-Plasmid-Derived Vector

    NARCIS (Netherlands)

    Hille, Jacques; Goldbach, Rob

    1986-01-01

    A chimaeric antibiotic resistance gene was transferred to cowpea (Vigna unguiculata), a member of the legume family. This transfer was established by inoculating cowpea leaf discs with an Agrobacterium tumefaciens strain harboring a Ti-plasmid-derived vector that contained two copies of a chimaeric

  11. The efficacy of prophylactic outpatient antibiotics for the prevention of neutropenic fever associated with high-dose etoposide (VP-16) for stem cell mobilization.

    Science.gov (United States)

    Avery, R K; Pohlman, B L; Mossad, S B; Goormastic, M; Longworth, D L; Kalaycio, M E; Sobecks, R M; Andresen, S W; Kuczkowski, E; Bernhard, L; Ostendorf, H; Wise, K; Bolwell, B J

    2002-09-01

    High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia is common. The infectious complications associated with high-dose etoposide have not been previously described. After noting a high incidence of hospitalizations for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for patients receiving high-dose etoposide plus G-CSF, attempting to reduce infectious complications. Ninety-eight patients underwent etoposide mobilization between December 1997 and June 2000. Three chronological patient groups received: (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not receiving antibiotic prophylaxis had a 68% incidence of hospitalization for neutropenic fever. In the patients receiving prophylaxis, the incidence was reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001 for comparison between prophylaxed and unprophylaxed groups). We conclude that etoposide mobilization is associated with a significant incidence of neutropenic fever, which can be substantially reduced by a vigorous antimicrobial prophylactic program. PMID:12209353

  12. Facts about Antibiotic Resistance

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  13. Antibiotic / Antimicrobial Resistance Glossary

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  14. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Sebastian, Katrin, E-mail: ksebastian@ukaachen.de [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Ott, Hagen [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany); Zwadlo-Klarwasser, Gabriele [IZKF (BIOMAT), RWTH Aachen University Hospital, D-52074 Aachen (Germany); Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F.; Baron, Jens Malte [Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen (Germany)

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  15. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte‐derived dendritic cells

    International Nuclear Information System (INIS)

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides – which are the most frequent cause of adverse drug reactions – were co-incubated with THP-1, MUTZ-LC, or primary monocyte‐derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. -- Highlights: ► We tested the sensitizing potential of small molecular weight drugs in vitro. ► In vitro assays were performed with moDCs and THP-1 cells. ► Beta-lactam antibiotics can be recognized as sensitizing compounds. ► They affect the expression of metabolic enzymes, cytokines and transcription factors. ► Sulfamethoxazole has no measurable effect on THP-1 cells and moDCs.

  16. Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway.

    Science.gov (United States)

    Esposito, Giuseppe; Gigli, Stefano; Seguella, Luisa; Nobile, Nicola; D'Alessandro, Alessandra; Pesce, Marcella; Capoccia, Elena; Steardo, Luca; Cirillo, Carla; Cuomo, Rosario; Sarnelli, Giovanni

    2016-08-01

    Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 µM) in the presence or absence of ketoconazole (10 µM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 µM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-α (HIF-1α), p70S6K and NF-κB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool. PMID:27279570

  17. Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts

    2015-04-15

    This podcast provides a brief background about antibiotics and quick tips to help prevent antibiotic resistance.  Created: 4/15/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  18. Strengthening Control of Antibiotics

    Institute of Scientific and Technical Information of China (English)

    EthelLu

    2005-01-01

    IT is a well-known fact that buy-ng guns is much easier than purchasing antibiotics in the United States. In China, however, the situation is different. According to a recent WHO survey,about 80 percent of Chinese inpatients take antibiotic medicines, and 58 percent of them are prescribed multifunctional antibiotics,

  19. Small changes in environmental parameters lead to alterations in antibiotic resistance, cell morphology and membrane fatty acid composition in Staphylococcus lugdunensis.

    Directory of Open Access Journals (Sweden)

    Marcus J Crompton

    Full Text Available Staphylococcus lugdunensis has emerged as a major cause of community-acquired and nosocomial infections. This bacterium can rapidly adapt to changing environmental conditions to survive and capitalize on opportunities to colonize and infect through wound surfaces. It was proposed that S. lugdunensis would have underlying alterations in metabolic homeostasis to provide the necessary levels of adaptive protection. The aims of this project were to examine the impacts of subtle variations in environmental conditions on growth characteristics, cell size and membrane fatty acid composition in S. lugdunensis. Liquid broth cultures of S. lugdunensis were grown under varying combinations of pH (6-8, temperature (35-39°C and osmotic pressure (0-5% sodium chloride w/w to reflect potential ranges of conditions encountered during transition from skin surfaces to invasion of wound sites. The cells were harvested at the mid-exponential phase of growth and assessed for antibiotic minimal inhibitory concentration (MIC, generation time, formation of small colony variants, cell size (by scanning electron microscopy and membrane fatty acid composition. Stress regimes with elevated NaCl concentrations resulted in significantly higher antibiotic resistance (MIC and three of the combinations with 5% NaCl had increased generation times (P<0.05. It was found that all ten experimental growth regimes, including the control and centroid cultures, yielded significantly different profiles of plasma membrane fatty acid composition (P<0.0001. Alterations in cell size (P<0.01 were also observed under the range of conditions with the most substantial reduction occurring when cells were grown at 39°C, pH 8 (514±52 nm, mean ± Standard Deviation compared with cells grown under control conditions at 37°C with pH 7 (702±76 nm, P<0.01. It was concluded that S. lugdunensis responded to slight changes in environmental conditions by altering plasma membrane fatty acid composition

  20. Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone.

    Science.gov (United States)

    Pacheco, Y; Hosni, R; Dagrosa, E E; Gormand, F; Guibert, B; Chabannes, B; Lagarde, M; Perrin-Fayolle, M

    1994-04-01

    Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis). Confluent monolayers of HBEC cultured on collagen were incubated for 24 h in a medium without study drugs (spontaneous production) or containing cefodizime or ceftriaxone at the clinically relevant concentrations of 1, 10 and 100 mg/l, with or without tumor necrosis factor alpha (TNF alpha, 100 U/ml). GM-CSF and IL-8 were measured in supernatant by ELISA technique. TNF alpha alone led to a significant (p ceftriaxone had no influence on cytokine production. This is the first report of a stimulatory effect of a beta-lactam antibiotic on cytokine production by epithelial cells. GM-CSF production by epithelial cells is an important immunological step for neutrophil and monocyte recruitment and cell priming during lung defence. Previous studies with cefodizime in immunodepressed subjects have shown activation of phagocytosis and phagocytosis-related functions in non-lung phagocytes. An indirect mechanism of action, similar to that indicated by our results, may have been responsible for these stimulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Actinolactomycin, a New 2-Oxonanonoidal Antitumor Antibiotic Produced by Streptomyces flavoretus 18522, and its Inhibitory Effect on the Proliferation of Human Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Bing HAN; Cheng Bin CUI; Bing CAI; Xiu Feng JI; Xin Sheng YAO

    2005-01-01

    Actinolactomycin 1, a new 2-oxonanonoidal antitumor antibiotic, was isolated from the fermentation broth of Streptomyces flavoretus 18522 through a bioassay-guided separation procedure. The structure of 1 was determined as 4,7-dihydroxy-3,9-dimethyl-2-oxonanone by the spectroscopic methods. Compound 1 inhibited the proliferation of A2780, K562, HCT-15, A549and HeLa cells with the IC50 values of 1.4 ± 0.4 μmol/L, 8.4 ± 4.7 μmol/L, 9.4 ± 2.2 μmol/L, 15.4± 5.6 μmol/L and 13.7 ± 2.0 μmol/L, respectively. Flow cytometric analysis indicated that 1could inhibit the cell cycle of tsFT210, A2780 and K562 cells mainly at the G0/G1 phase and could also induce apoptosis in K562 cells.

  2. Cooperative Electrostatic Polymer-Antibiotic Nanoplexes

    OpenAIRE

    Vadala, Timothy Patrick

    2010-01-01

    Many pathogenic bacteria can enter phagocytic cells and replicate in them, and these intracellular bacteria are difficult to treat because the recommended antibiotics do not transport into the cells efficiently. Examples include food-borne bacteria such as Salmonella and Listeria as well as more toxic bacteria such as Brucella and the Mycobacteria that lead to tuberculosis. Current treatments utilize aminoglycoside antibiotics that are polar and positively charged and such drugs do not ente...

  3. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo

    2016-06-01

    Full Text Available Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification.

  4. Ribosomal Antibiotics: Contemporary Challenges.

    Science.gov (United States)

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-01-01

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of "pathogen-specific antibiotics," in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID:27367739

  5. REDUCTION OF ANTIBIOTIC RESISTANCE IN BACTERIA: A REVIEW

    Directory of Open Access Journals (Sweden)

    Suresh Jaiswal et al.

    2012-03-01

    Full Text Available Drug resistant bacteria have been posing a major challenge to the effective control of bacterial infections for quite some time. One of the main causes of antibiotics drug resistance is antibiotic overuse, abuse, and in some cases, misuse, due to incorrect diagnosis. Bacterial antibiotic resistance is a significant issues faced by various industries, including the food and agricultural industries, the medical and veterinary profession and others. The potential for transfer of antibiotics resistance, or of potentially lethal antibiotic resistant bacteria, for example from a food animal to human consumer, is of particular concern. A method of controlling development and spread of antibiotic-resistant bacteria include changes in antibiotic usage and pattern of usage of different antibiotics. However, the ability of bacteria to adapt to antibiotic usage and to acquire resistance to existing and new antibiotics usage overcomes such conventional measures, and requires the continued development of alternative means of control of antibiotic resistance bacteria. Alternative means for overcoming the tendency of bacteria to acquire resistance to antibiotic control measures have taken various forms. This article explains one method evaluated for control, that is reducing or removing antibiotic resistance is so called “curing” of antibiotic resistance. Antibiotic resistance is formed in the chromosomal elements. Thus elimination of such drug-resistance plasmids results in loss of antibiotics resistance by the bacterial cell. “Curing” of a microorganism refers to the ability of the organism to spontaneously lose a resistance plasmid under the effect of particular compounds and environmental conditions, thus recovering the antibiotic sensitive state.

  6. A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2008-12-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

  7. Antibiotics: Miracle Drugs

    Centers for Disease Control (CDC) Podcasts

    2015-04-16

    The overuse of antibiotics has led to the development of resistance among bacteria, making antibiotics ineffective in treating certain conditions. This podcast discusses the importance of talking to your healthcare professional about whether or not antibiotics will be beneficial if you’ve been diagnosed with an infectious disease.  Created: 4/16/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  8. Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria.

    Science.gov (United States)

    Bennett, P M

    2008-03-01

    Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes).The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. PMID:18193080

  9. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    Science.gov (United States)

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria. PMID:22029522

  10. Update on the Management of Antibiotic Allergy

    OpenAIRE

    Thong, Bernard Yu-Hor

    2010-01-01

    Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these...

  11. Endopeptidase-Mediated Beta Lactam Tolerance

    OpenAIRE

    Dörr, Tobias; Davis, Brigid M.; Waldor, Matthew K.

    2015-01-01

    In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall (‘autolysins’) are thought to be critical. Here, we report that Vibrio cholerae, the cholera pathogen, is tolerant to antibiotics targeting cell wall synthesis. In response to a wide variety of cell wall- acting ...

  12. The future of antibiotics.

    Science.gov (United States)

    Spellberg, Brad

    2014-01-01

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on 'push' incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

  13. Metagenomics and antibiotics.

    Science.gov (United States)

    Garmendia, L; Hernandez, A; Sanchez, M B; Martinez, J L

    2012-07-01

    Most of the bacterial species that form part of the biosphere have never been cultivated. In this situation, a comprehensive study of bacterial communities requires the utilization of non-culture-based methods, which have been named metagenomics. In this paper we review the use of different metagenomic techniques for understanding the effect of antibiotics on microbial communities, to synthesize new antimicrobial compounds and to analyse the distribution of antibiotic resistance genes in different ecosystems. These techniques include functional metagenomics, which serves to find new antibiotics or new antibiotic resistance genes, and descriptive metagenomics, which serves to analyse changes in the composition of the microbiota and to track the presence and abundance of already known antibiotic resistance genes in different ecosystems.

  14. Antibiotic-loaded chitosan-Laponite films for local drug delivery by titanium implants: cell proliferation and drug release studies.

    Science.gov (United States)

    Ordikhani, Farideh; Dehghani, Mehdi; Simchi, Arash

    2015-12-01

    In this study, chitosan-Laponite nanocomposite coatings with bone regenerative potential and controlled drug-release capacity are prepared by electrophoretic deposition technique. The controlled release of a glycopeptide drug, i.e. vancomycin, is attained by the intercalation of the polymer and drug macromolecules into silicate galleries. Fourier-transform infrared spectrometry reveals electrostatic interactions between the charged structure of clay and the amine and hydroxyl groups of chitosan and vancomycin, leading to a complex positively-charged system with high electrophoretic mobility. By applying electric field the charged particles are deposited on the surface of titanium foils and uniform chitosan films containing 25-55 wt% Laponite and 937-1655 µg/cm(2) vancomycin are obtained. Nanocomposite films exhibit improved cell attachment with higher cell viability. Alkaline phosphatase assay reveals enhanced cell proliferation due the gradual dissolution of Laponite particles into the culture medium. In-vitro drug-release studies show lower release rate through a longer period for the nanocomposite compared to pristine chitosan. PMID:26507202

  15. Solar photoelectro-Fenton degradation of the antibiotic metronidazole using a flow plant with a Pt/air-diffusion cell and a CPC photoreactor

    International Nuclear Information System (INIS)

    Highlights: • Degradation of metronidazole solutions at pH 3.0 by EF and SPEF in a flow plant. • High recalcitrance of the antibiotic and its products to be destroyed by ·OH radicals. • Only 53% mineralization by the most potent SPEF process at 55.4 mA cm−2. • 5 heterocyclic products, 12 hydroxylated derivatives and 2 carboxylic acids were found. • Release of NO3− ion and generation of persistent N-products and N-volatile species. - Abstract: The degradation of 10 dm3 of solutions of the heterocyclic antibiotic metronidazole in 0.10 mol dm−3 Na2SO4 of pH 3.0 has been comparatively studied by electro-Fenton (EF) and solar photoelectro-Fenton (SPEF). Experiments were performed in a solar flow plant equipped with a Pt/air-diffusion cell and coupled to a compound parabolic collector (CPC) photoreactor. A very weak mineralization was found for the EF process in the dark, indicating a large recalcitrance of heterocyclic compounds to be destroyed by hydroxyl radicals formed at the Pt anode from water oxidation and mainly in the bulk from Fenton's reaction between added Fe2+ and cathodically generated H2O2. The quick photolysis of intermediates by UV radiation from sunlight enhanced largely the mineralization process by SPEF. The effect of applied current density and Fe2+ and drug contents on the SPEF treatment was examined. The best process was found for 1.39 mmol dm−3 metronidazole with 0.50 mmol dm−3 Fe2+ at 55.4 mA cm−2 giving 53% mineralization, 36% mineralization current efficiency and 0.339 kWh (g DOC)−1 in 300 min. Metrodinazole was completely removed and its decay obeyed a pseudo-first-order kinetics. LC-MS analysis allowed identifying five heterocyclic products and twelve hydroxylated derivatives. Ion-exclusion HPLC analysis revealed that final oxalic and oxamic acids were practically removed at the end of electrolysis due to the efficient photolysis of their Fe(III) complexes by sunlight. The initial N of metronidazole gave NO3

  16. Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in Chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase and DT-diaphorase.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1998-01-01

    We have directly demonstrated the involvement of human NADPH: cytochrome c (P-450) reductase in the aerobic/hypoxic differential toxicity of mitomycin C and porfiromycin in living cells by varying only this enzyme in a transfected cell line. In the same manner, we have implicated rat DT-diaphorase in the aerobic and hypoxic activation of mitomycin C, but found only a minor role for this enzyme in the aerobic activation of porfiromycin. DT-Diaphorase does not cause the production of an aerobic/hypoxic differential toxicity by mitomycin C, but rather activates this agent through an oxygen insensitive pathway. The evidence suggests that DT-diaphorase activates mitomycin C more effectively than porfiromycin, with porfiromycin being preferentially activated through a one-electron reductive pathway. The therapeutic potential of mitomycin antibiotics in the treatment of cancer can be envisioned to be enhanced for those tumors containing elevated levels of the bioreductive enzymes. However, cytogenetic heterogeneity within the tumor cell population and the various environmental factors which impact on bioreductive enzyme function, including pH and oxygen tension, may subvert this approach. Moreover, if high tumor levels of a drug activating enzyme reflect high levels in the normal tissues of the patient, normal tissue damage may also be enhanced with possibly no improvement in the therapeutic ratio. Approaches utilizing gene therapy, whereby a specific bioreductive catalyst is introduced into the tumor cell population via a targeting vehicle to activate a particular prodrug, may be more effective in that not only will the prodrug of choice be specifically activated in the tumor, but the source of the catalyst, be it bacterial, rodent, or human, will not be important. In fact, in the case of DT-diaphorase and mitomycin C, the rat form of the enzyme could be advantageous because it is more effective in activating mitomycin C than is the human form of this enzyme. Assuming

  17. Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies.

    Science.gov (United States)

    Severino, Patrícia; Chaud, Marco V; Shimojo, Andrea; Antonini, Danilo; Lancelloti, Marcelo; Santana, Maria Helena A; Souto, Eliana B

    2015-05-01

    Polymyxins are a group of antibiotics with a common structure of a cyclic peptide with a long hydrophobic tail. Polymyxin B sulphate (PLX) has cationic charge, which is an obstacle for the efficient loading into Solid Lipid Nanoparticles (SLN). In the present paper, we describe an innovative method to load PLX into SLN to achieve the sustained release of the drug. PLX was firstly cross-linked with sodium alginate (SA) at different ratios (1:1, 1:2 and 1:3 SA/PLX), and loaded into SLN produced by high pressure homogenization (HPH). Optimized SLN were produced applying 500bar pressure and 5 homogenization cycles. The best results were obtained with SA/PLX (1:1), recording 99.08±1.2% for the association efficiency of the drug with SA, 0.99±10g for the loading capacity and 212.07±5.84% degree of swelling. The rheological profile of aqueous SA solution followed the typical behaviour of concentrated polymeric solutions, whereas aqueous SA/PLX solution exhibited a gel-like dynamic behaviour. Micrographs show that SA/PLX depicted a porous and discontinuous amorphous phase in different ratios. The encapsulation efficiency of SA/PLX (1:1) in SLN, the mean particle diameter, polydispersity index and zeta potential were, respectively, 82.7±5.5%; 439.5±20.42nm, 0.241±0.050 and -34.8±0.55mV. The effect of SLN on cell viability was checked in HaCat and NIH/3T3 cell lines, and the minimal inhibitory concentrations (MIC) were determined in Pseudomonas aeruginosa strains. SA/PLX-loaded SLN were shown to be less toxic than free PLX. Minimal inhibitory concentrations (MIC) showed the presence of the cross-linker polymer-drug complex, and SLN were shown to enhance MIC in the evaluated strains.

  18. Colistin : Revival of an Old Polymyxin Antibiotic

    NARCIS (Netherlands)

    Dijkmans, Anneke C.; Wilms, Erik B.; Kamerling, Ingrid M. C.; Birkhoff, Willem; Ortiz-Zacarias, Natalia V.; van Nieuwkoop, Cees; Verbrugh, Henri A.; Touw, Daan J.

    2015-01-01

    Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simul

  19. Fighting antibiotic resistance in the intensive care unit using antibiotics.

    Science.gov (United States)

    Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

  20. Antibiotic resistance in Burkholderia species.

    Science.gov (United States)

    Rhodes, Katherine A; Schweizer, Herbert P

    2016-09-01

    The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. PMID:27620956

  1. Antibiotics for uncomplicated diverticulitis

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel M; Wille-Jørgensen, Peer

    2012-01-01

    Diverticulitis is an inflammatory complication to the very common condition diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics with reference to the microbiology, extrapolation from trials on complicated intra-abdominal infections and clinical experience....

  2. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  3. Antibiotic induced meningitis.

    OpenAIRE

    1994-01-01

    Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion ...

  4. [Prophylactic antibiotics in neurosurgery].

    Science.gov (United States)

    Iacob, G; Iacob, Simona; Cojocaru, Inimioara

    2007-01-01

    Because of a low risk of infection (around 2-3%), prophylactic use of antibiotics in neurosurgery is a controversial issue. Some neurosurgeons consider that there are strong arguments against the use of antimicrobials (promotion of antibiotic-resistant strains of bacteria, superinfection and adverse drug reactions) and meticulous aseptic techniques could be more usefully than prophylactic antibiotics. On the other hand, despite of being rare, the consequences of a neurosurgical infection can be dramatic and may result in a rapid death, caused by meningitis, cerebritis, abscess formation or sepsis. Clinical studies emphasized that the most important factors influencing the choice of antibiotic prophylaxis in neurosurgery is the patient's immune status, virulence of the pathogens and the type of surgery ("clean contaminated"--procedure that crosses the cranial sinuses, "clean non-implant"--procedure that does not cross the cranial sinuses, CSF shunt surgery, skull fracture). Prophylaxis has become the standard of care for contaminated and clean-contaminated surgery, also for surgery involving insertion of artificial devices. The antibiotic (first/second generation of cephalosporins or vancomycin in allergic patients) should recover only the cutaneous possibly contaminating flora (S. aureus, S. epidermidis) and should be administrated 30' before the surgical incision, intravenously in a single dose. Most studies pointed that identification of the risk factors for infections, correct asepsis and minimal prophylactic antibiotic regimen, help neurosurgeons to improve patient care and to decrease mortality without selecting resistant bacteria. PMID:18293694

  5. [Analysis of antibiotic usage].

    Science.gov (United States)

    Balpataki, R; Balogh, J; Zelkó, R; Vincze, Z

    2001-01-01

    Economic analysis is founded on the assumption that resources are limited and that should be used in a way that maximizes the benefits gained. Pharmacoeconomics extends these assumptions to drug treatment. Therefore, a full pharmacoeconomic analysis must consider two or more alternative treatments and should be founded on measurement of incremental cost, incremental efficacy, and the value of successful outcome. Antibiotic policy based only on administrative restrictions is failed, instead of it disease formularies and infectologist consultation system are needed. Equally important are various programmes that encourage the cost-conscious use of the antibiotics chosen. Some of the methods evaluated in the literature include: streamlining from combination therapy to a single agent, early switching from parenteral to oral therapy, initiating treatment with oral agents, administering parenteral antibiotic at home from outset of therapy, and antibiotic streamlining programmes that are partnered with infectious disease physicians. The solution is the rational and adequate use of antibiotics, based on the modern theory and practice of antibiotic policy and infection control, that cannot be carried out without the activities of experts in this field. PMID:11769090

  6. Strategies to Minimize Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Sang Hee Lee

    2013-09-01

    Full Text Available Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs and various data such as pharmacokinetic (PK and pharmacodynamic (PD properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST, clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care, the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing. The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

  7. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    is considered poor compared to medicines for lifestyle diseases. According to the WHO we could be moving towards a post-antibiotic era in which previously treatable infections become fatal. Of special importance are multidrug resistant bacteria from the ESKAPE group (Enterococcus faecium, Staphylococcus aureus...... a cecropin-mellitin hybrid peptide and proved effective in killing colistin resistant Gram-negative A. baumannii in vitro. The molecule was improved with regard to toxicity, as measured by hemolytic ability. Further, this peptide is capable of specifically killing non-growing cells of colistin resistant A...

  8. Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus.

    Science.gov (United States)

    Teow, Sin-Yeang; Ali, Syed Atif

    2015-11-01

    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.

  9. Autolytic effect of the antibiotic produced by Myxococcus coralloides D.

    Science.gov (United States)

    Montoya, M D; Gálvez, A; Arias, J M; Montoya, E

    1994-12-01

    Myxococcus coralloides D secretes an antibiotic, named corallolysin, when grown on a rich medium. When a critical concentration is reached, this antibiotic lyses the producer bacterium either during vegetative growth or during morphogenesis. Corallolysin has not effect on resting cells nor on myxospores. The autolytic effect is caused by the early inhibition of RNA synthesis.

  10. Mitomycin antibiotic reductive potential and related pharmacological activities.

    Science.gov (United States)

    Pan, S S; Gonzalez, H

    1990-06-01

    Relationships of reductive potential, kinetics of enzymatic reduction, augmented oxygen consumption, and cytotoxicity were determined for seven clinically relevant mitomycin antibiotics. Potentials for one-electron reduction were obtained by cyclic voltammetry analysis in dimethyl sulfoxide with 0.1 M tetraethyl-ammonium perchlorate. These potentials were -0.55 V for N7-acetylmitomycin C, -0.61 V for mitomycin A, -0.75 V for N7-(p-hydroxyphenyl)mitomycin C, -0.79 V for N7-(dimethylamino-methylene)mitomycin C, -0.81 V for N7-(2-(4-nitrophenyldithio)-ethyl)-mitomycin C, -0.81 V for mitomycin C, and -0.89 V for porfiromycin. All seven antibiotics were reduced by xanthine oxidase and NADPH-cytochrome P450 reductase, but the rate of reduction varied for each antibiotic and each enzyme. The less negative the reductive potential of an antibiotic, the more easily that antibiotic was reduced enzymatically. These seven mitomycin antibiotics also augmented oxygen consumption by rat liver microsomes. As with their reduction by xanthine oxidase and NADPH-cytochrome P450 reductase, the less negative the reductive potential of an antibiotic, the more it augmented oxygen consumption. Cytotoxicity of each antibiotic was assessed by defining the IC50 against HCT 116 human colon carcinoma cells. A relationship between the reductive potential of these antibiotics and their cytotoxicity against HCT 116 cells was also observed. PMID:2113607

  11. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    International Nuclear Information System (INIS)

    Highlights: ► Salinomycin inhibits preadipocyte differentiation into adipocytes. ► Salinomycin inhibits transcriptional regulation of adipogenesis. ► Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  12. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  13. Patterning and lifetime of plasma membrane-localized cellulose synthase is dependent on actin organization in Arabidopsis interphase cells

    NARCIS (Netherlands)

    Sampathkumar, A.; Gutierrez, R.; McFarlane, H.E.; Bringmann, M.; Lindeboom, J.J.; Emons, A.M.C.; Samuels, L.; Ketelaar, T.; Ehrhardt, D.W.; Persson, S.

    2013-01-01

    The actin and microtubule cytoskeletons regulate cell shape across phyla, from bacteria to metazoans. In organisms with cell walls, the wall acts as a primary constraint of shape, and generation of specific cell shape depends on cytoskeletal organization for wall deposition and/or cell expansion. In

  14. High Antibiotic Consumption

    DEFF Research Database (Denmark)

    Malo, Sara; José Rabanaque, María; Feja, Cristina;

    2014-01-01

    as their exposure to antibiotics. Data on outpatient prescribing of antimicrobials (ATC J01) in 2010 were obtained from a prescription database covering Aragón (northeastern Spain). The antimicrobial consumption at the individual level was analysed both according to the volume of DDD and the number of packages...... with highest consumption) were responsible for 21% of the total DDD consumed and received ≥6 packages per year. Elderly adults (≥60 years) and small children (0-9 years) were those exposed to the highest volume of antibiotics and with the most frequent exposure, respectively. Heavy users received a high...

  15. Overdosing on Antibiotics

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Du, a Beijing resident in her 60s, believes that an antibiotic is a panacea for the maladies of her now 6-year-old grand- daughter Guoguo. Du began to take care of her granddaugh- ter since the child was merely 2 months old, for the gid's parents were busy. She is comfortable with her caretaker duties except when the girl runs high fevers. Then, the anxious grandma will feed the girl antibiotics or take her to a private child clinic nearby for intravenous infusion.

  16. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells.

    Science.gov (United States)

    Sebastian, Katrin; Ott, Hagen; Zwadlo-Klarwasser, Gabriele; Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F; Baron, Jens Malte

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. PMID:22609641

  17. Antibiotic resistance of bacterial biofilms

    DEFF Research Database (Denmark)

    Hoiby, N.; Bjarnsholt, T.; Givskov, M.;

    2010-01-01

    A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis...... and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains....... Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance...

  18. Suppression of antibiotic resistance acquisition by combined use of antibiotics.

    Science.gov (United States)

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance.

  19. [Antibiotical prophylaxy in gynecology].

    Science.gov (United States)

    Záhumenský, J; Menzlová, E; Zmrhal, J; Kučera, E

    2013-08-01

    Gynecological surgery is considered to be clear with possible contamination by gram-positive cocci from the skin, gram-negatives from the perineum or groins or polymicrobial biocenosis from vagina, depending on the surgical approach. Antibiotical prophylaxy enforces the natural mechanisms of immunity and helps to exclude present infection. There were presented many studies comparing useful effect of prophylaxis in gynecological surgery. The benefits of antibiotical prophylaxy before IUD insertion, before the cervical surgery and before hysteroscopies were not verified. On the other hand the prophylaxy of vaginal surgery including vaginal hysterectomy decreases the number of postoperative febrile complications. The positive influence of prophylaxis before the simple laparoscopy and laparoscopy without bowel injury or the opening of the vagina was not evidently verified. In abdominal hysterectomy the antibiotical prophylaxy decreases the incidence of postoperative complications significantly. The administration of 2 g of cefazolin can be recommended. In procedures taking more than 3 hours the repeated administration of cefazolin is suitable. New urogynecological procedures, using mesh implants, were not sufficiently evaluated as for postoperative infections and the posible antibiotical effect. The presence of implant in possibly non sterile area should be considered as high risc of postoperative complications. PMID:24040985

  20. Antibiotic resistance in Salmonella

    NARCIS (Netherlands)

    Vo, A.T.T.

    2007-01-01

    Immediately after their introduction in the beginning of the fourties of the previous century, the agents used to combat infectious diseases caused by bacteria were regarded with suspicion, but not long thereafter antibiotics had the status of miracle drugs. For decades mankind has lived under the i

  1. Antibiotic prophylaxis in primary immune deficiency disorders.

    Science.gov (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  2. Antibiotic-Mediated Inhibition of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV Infection: A Novel Quinolone Function Which Potentiates the Antiviral Cytokine Response in MARC-145 Cells and Pig Macrophages

    Directory of Open Access Journals (Sweden)

    William A. Cafruny

    2008-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolonecontaining compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs. Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.

  3. A study of antibiotic prescribing

    DEFF Research Database (Denmark)

    Jaruseviciene, L.; Radzeviciene-Jurgute, R.; Jurgutis, A.;

    2012-01-01

    Background. Globally, general practitioners (GPs) write more than 90% of all antibiotic prescriptions. This study examines the experiences of Lithuanian and Russian GPs in antibiotic prescription for upper respiratory tract infections, including their perceptions of when it is not indicated...... to ensure correct antibiotic use. Further, GPs should be supported in enhancing their communication skills about antibiotic use with their patients and encouraged to implement a shared decision-making model in their practices. © Versita Sp. z o.o....

  4. Investigating the Antibiotic Resistance Problem.

    Science.gov (United States)

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  5. Enhancement of antibiotic effect via gold:silver-alloy nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Moreira dos Santos, Margarida, E-mail: margarida.santos@fct.unl.pt; Queiroz, Margarida Joao; Baptista, Pedro V. [Universidade Nova de Lisboa, CIGMH, Departamento Ciencias da Vida, Faculdade de Ciencias e Tecnologia (Portugal)

    2012-05-15

    A strategy for the development of novel antimicrobials is to combine the stability and pleiotropic effects of inorganic compounds with the specificity and efficiency of organic compounds, such as antibiotics. Here we report on the use of gold:silver-alloy (Au:Ag-alloy) nanoparticles, obtained via a single-step citrate co-reduction method, combined to conventional antibiotics to enhance their antimicrobial effect on bacteria. Addition of the alloy nanoparticles considerably decreased the dose of antibiotic necessary to show antimicrobial effect, both for bacterial cells growing in rich medium in suspension and for bacterial cells resting in a physiological buffer on a humid cellulose surface. The observed effect was more pronounced than the sum of the individual effects of the nanoparticles and antibiotic. We demonstrate the enhancement effect of Au:Ag-alloy nanoparticles with a size distribution of 32.5 {+-} 7.5 nm mean diameter on the antimicrobial effect of (i) kanamycin on Escherichia coli (Gram-negative bacterium), and (ii) a {beta}-lactam antibiotic on both a sensitive and resistant strain of Staphylococcus aureus (Gram-positive bacterium). Together, these results may pave the way for the combined use of nanoparticle-antibiotic conjugates towards decreasing antibiotic resistance currently observed for certain bacteria and conventional antibiotics.

  6. Rapid determination of antibiotic resistance in E. coli using dielectrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Hoettges, Kai F [School of Engineering, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom); Dale, Jeremy W [School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom); Hughes, Michael P [School of Engineering, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)

    2007-09-21

    In recent years, infections due to antibiotic-resistant strains of bacteria such as methillicin-resistant Staphylococcus aureus and ciprofloxacin-resistant Escherichia coli are on the rise, and with them the demand for rapid antibiotic testing is also rising. Conventional tests, such as disc diffusion testing, require a primary sample to be tested in the presence of a number of antibiotics to verify which antibiotics suppress growth, which take approximately 24 h to complete and potentially place the patient at severe risk. In this paper we describe the use of dielectrophoresis as a rapid marker of cell death, by detecting changes in the electrophysiology of the cell caused by the administration of an antibiotic. In contrast to other markers, the electrophysiology of the cell changes rapidly during cell death allowing live cells to be distinguished from dead (or dying) cells without the need for culturing. Using polymyxin B as an example antibiotic, our studies indicate that significant changes in cell characteristics can be observed as soon as 1 h passes after isolating a culture from nutrient broth.

  7. Environmental pollution by antibiotics and by antibiotic resistance determinants

    International Nuclear Information System (INIS)

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  8. Environmental pollution by antibiotics and by antibiotic resistance determinants

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

    2009-11-15

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  9. Excretion of antibiotic resistance genes by dairy calves fed milk replacers with varying doses of antibiotics

    Directory of Open Access Journals (Sweden)

    Callie H. Thames

    2012-04-01

    Full Text Available Elevated levels of antibiotic resistance genes (ARGs in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning, and 12 (5 weeks after weaning. ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX, macrolide (ermB, ermF, and sulfonamide (sul1, sul2 classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies/ g wet manure of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onwards, and tetW and tetG significantly increased (P<0.10, even in control calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional

  10. Pneumococcal resistance to antibiotics.

    OpenAIRE

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumo...

  11. The role of biofilms as environmental reservoirs of antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Jose Luis eBalcazar

    2015-10-01

    Full Text Available Antibiotic resistance has become a significant and growing threat to public and environmental health. To face this problem both at local and global scales, a better understanding of the sources and mechanisms that contribute to the emergence and spread of antibiotic resistance is required. Recent studies demonstrate that aquatic ecosystems are reservoirs of resistant bacteria and antibiotic resistance genes as well as potential conduits for their transmission to human pathogens. Despite the wealth of information about antibiotic pollution and its effect on the aquatic microbial resistome, the contribution of environmental biofilms to the acquisition and spread of antibiotic resistance has not been fully explored in aquatic systems. Biofilms are structured multicellular communities embedded in a self-produced extracellular matrix that acts as a barrier to antibiotic diffusion. High population densities and proximity of cells in biofilms also increases the chances for genetic exchange among bacterial species converting biofilms in hot spots of antibiotic resistance. This review focuses on the potential effect of antibiotic pollution on biofilm microbial communities, with special emphasis on ecological and evolutionary processes underlying acquired resistance to these compounds.

  12. Optimizing Antibiotic Use in Nursing Homes Through Antibiotic Stewardship.

    Science.gov (United States)

    Sloane, Philip D; Huslage, Kirk; Kistler, Christine E; Zimmerman, Sheryl

    2016-01-01

    Antibiotic stewardship is becoming a requirement for nursing homes. Programs should be interdisciplinary and multifaceted; should have support from nursing home administrators; and should aim to promote antibiotics only when needed, not just in case. Recommended components include use of evidence-based guidelines; ongoing monitoring of antibiotic prescriptions, cultures, and study results; monitoring of health outcomes; use of nursing home-specific antibiograms; regular reporting and feedback to medical providers and nurses; and education of residents and families. PMID:27621341

  13. Lipid II as a target for antibiotics.

    Science.gov (United States)

    Breukink, Eefjan; de Kruijff, Ben

    2006-04-01

    Lipid II is a membrane-anchored cell-wall precursor that is essential for bacterial cell-wall biosynthesis. The effectiveness of targeting Lipid II as an antibacterial strategy is highlighted by the fact that it is the target for at least four different classes of antibiotic, including the clinically important glycopeptide antibiotic vancomycin. However, the growing problem of bacterial resistance to many current drugs, including vancomycin, has led to increasing interest in the therapeutic potential of other classes of compound that target Lipid II. Here, we review progress in understanding of the antibacterial activities of these compounds, which include lantibiotics, mannopeptimycins and ramoplanin, and consider factors that will be important in exploiting their potential as new treatments for bacterial infections. PMID:16531990

  14. Antibiotic susceptibility testing of the Gram-negative bacteria based on flow cytometry

    Directory of Open Access Journals (Sweden)

    Claude Saint-Ruf

    2016-07-01

    Full Text Available Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH, which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3, which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility.

  15. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

    Science.gov (United States)

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility.

  16. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

    Science.gov (United States)

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility. PMID:27507962

  17. Antibiotic prevention of postcataract endophthalmitis

    DEFF Research Database (Denmark)

    Kessel, Line; Flesner, Per; Andresen, Jens;

    2015-01-01

    Endophthalmitis is one of the most feared complications after cataract surgery. The aim of this systematic review was to evaluate the effect of intracameral and topical antibiotics on the prevention of endophthalmitis after cataract surgery. A systematic literature review in the MEDLINE, CINAHL......, Cochrane Library and EMBASE databases revealed one randomized trial and 17 observational studies concerning the prophylactic effect of intracameral antibiotic administration on the rate of endophthalmitis after cataract surgery. The effect of topical antibiotics on endophthalmitis rate was reported by one...... with the use of intracameral antibiotic administration of cefazolin, cefuroxime and moxifloxacin, whereas no effect was found with the use of topical antibiotics or intracameral vancomycin. Endophthalmitis occurred on average in one of 2855 surgeries when intracameral antibiotics were used compared to one...

  18. Antibiotics for acute maxillary sinusitis

    DEFF Research Database (Denmark)

    Ahovuo-Saloranta, Anneli; Borisenko, Oleg V; Kovanen, Niina;

    2008-01-01

    with a pooled RR of 0.74 (95% CI 0.65 to 0.84) at 7 to 15 days follow up. None of the antibiotic preparations was superior to each other. AUTHORS' CONCLUSIONS: Antibiotics have a small treatment effect in patients with uncomplicated acute sinusitis in a primary care setting with symptoms for more than seven......BACKGROUND: Expert opinions vary on the appropriate role of antibiotics for sinusitis, one of the most commonly diagnosed conditions among adults in ambulatory care. OBJECTIVES: We examined whether antibiotics are effective in treating acute sinusitis, and if so, which antibiotic classes...... or antibiotics from different classes for acute maxillary sinusitis in adults. We included trials with clinically diagnosed acute sinusitis, whether or not confirmed by radiography or bacterial culture. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened search results, extracted...

  19. Antibiotics in otorhinolaryngology practice

    Directory of Open Access Journals (Sweden)

    Stefan-Mikić Sandra

    2002-01-01

    Full Text Available Introduction This study investigated utilization of antibacterial agents at the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman and at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, in the period February - March 2001. Material and methods All antibacterial agents were classified as group J, regarding Anatomic-Therapeutic-Chemical Classification. Data on drug utilization were presented in Defined Daily Doses (DDD. Patients who were under observation were all treated with antibiotics. Results In regard to prescribed treatment in the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, most outpatients were treated with macrolide antibiotics - in 26.21%; combination of penicillin and beta-lactamase inhibitors in 20.83% and pyranosides in 16.12%. At the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, macrolides and lincosamines were most frequently used - in 20.46%; cephalosporins in 19.87% and penicillins susceptible to beta-lactamase in 18.85%. It is extremely positive and in agreement with current pharmacotherapeutic principles that in both institutions peroral ampicillins have not been prescribed. Aminoglycosides have been prescribed in less than 1% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, whereas they were much more frequently prescribed at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad - in 11.25%. Although there is a positive postantibiotic effect in regard to these antibiotics and it is recommended to use them once a day, in both examined institutions aminoglycosides were given twice a day. In regard to bacterial identification it was done in 80.76% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, while in the Ear, Nose and Throat Clinic of the Clinical Center

  20. Magnetic isotope effect of magnesium (25)Mg on E. coli resistance to antibiotics.

    Science.gov (United States)

    Letuta, U G; Vekker, A S; Kornilova, T A; Gryaznov, A A; Cheplakov, I A

    2016-07-01

    Effects of synergism and antagonism of antibacterial drugs and magnetic isotope of magnesium (25)Mg on antibiotic resistance of bacteria E. coli were discovered. Fourteen antibiotics from seven different groups were tested. The increase in antibiotic resistance in the presence of the ion (25)Mg(2+) was discovered in E. coli cells incubated with quinolones/fluoroquinolones, indicating the inhibiting effect of the magnetic moments of nuclei (25)Mg on DNA synthesis. The change in antibiotic resistance was also detected in bacteria affected by magnesium (25)Mg and certain antibiotics from aminoglycoside and lincosamide groups. PMID:27599512

  1. Probing minority population of antibiotic-resistant bacteria.

    Science.gov (United States)

    Huang, Tianxun; Zheng, Yan; Yan, Ya; Yang, Lingling; Yao, Yihui; Zheng, Jiaxin; Wu, Lina; Wang, Xu; Chen, Yuqing; Xing, Jinchun; Yan, Xiaomei

    2016-06-15

    The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies. PMID:26852201

  2. Antibiotics and oral contraceptives.

    Science.gov (United States)

    Rubin, D F

    1981-04-01

    Dermatologists often prescribe oral tetracycline for the control of acne, primarily, and to a much lesser extent, for the treatment of cutaneous infections. A number of the patients taking tetracycline are also taking birth control pills. A recent article in the British Medical Journal (1980;1:293) indicates that this combination can lead to a failure of the (OC) oral contraceptive. Such failure had been associated with ampicillin as well. It is believed that the mechanism for this was the disturbance in normal gut flora, with consequent effects on bacterial hydrolysis of steroid conjugates. This would interrupt the enterohepatic circulation of contraceptive steroids, resulting in a less than normal concentration of circulating steroids. It was recommended that women taking low-dose OCs take extra precautions against pregnancy during any cycle in which antibiotics are given. In regard to our care of and responsibilities to our patients, and in an era when malpractice suits for all types of reasons are more common, it certainly behooves dermatologists to recognize and be concerned about this potential consequence of prescribing oral antibiotics. PMID:7212735

  3. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    Science.gov (United States)

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity.

  4. Fighting antibiotic resistance in the intensive care unit using antibiotics

    NARCIS (Netherlands)

    Plantinga, Nienke L.; Wittekamp, Bastiaan H J; Van Duijn, Pleun J.; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to cl

  5. Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

    Energy Technology Data Exchange (ETDEWEB)

    Hand, W.L.; King-Thompson, N.L. (Veterans Administration Medical Center (Atlanta), Decatur, GA (USA))

    1990-06-01

    Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.

  6. Antibiotic Bactericidal Activity Is Countered by Maintaining pH Homeostasis in Mycobacterium smegmatis.

    Science.gov (United States)

    Bartek, I L; Reichlen, M J; Honaker, R W; Leistikow, R L; Clambey, E T; Scobey, M S; Hinds, A B; Born, S E; Covey, C R; Schurr, M J; Lenaerts, A J; Voskuil, M I

    2016-01-01

    Antibiotics target specific biosynthetic processes essential for bacterial growth. It is intriguing that several commonalities connect the bactericidal activity of seemingly disparate antibiotics, such as the numerous conditions that confer broad-spectrum antibiotic tolerance. Whether antibiotics kill in a manner unique to their specific targets or by a universal mechanism is a critical and contested subject. Herein, we demonstrate that the bactericidal activity of diverse antibiotics against Mycobacterium smegmatis and four evolutionarily divergent bacterial pathogens was blocked by conditions that worked to maintain intracellular pH homeostasis. Single-cell pH analysis demonstrated that antibiotics increased the cytosolic pH of M. smegmatis, while conditions that promoted proton entry into the cytosol prevented intracellular alkalization and antibiotic killing. These findings led to a hypothesis that posits antibiotic lethality occurs when antibiotics obstruct ATP-consuming biosynthetic processes while metabolically driven proton efflux is sustained despite the loss of proton influx via ATP synthase. Consequently, without a concomitant reduction in respiratory proton efflux, cell death occurs due to intracellular alkalization. Our findings indicate the effects of antibiotics on pH homeostasis should be considered a potential mechanism contributing to antibiotic lethality. IMPORTANCE Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our findings

  7. Do we need new antibiotics?

    Science.gov (United States)

    Rolain, J-M; Abat, C; Jimeno, M-T; Fournier, P-E; Raoult, D

    2016-05-01

    For several years, alarmist articles both in mass media and in the scientific community have reported an increase in antibiotic resistance, even citing an inability to treat patients infected with multidrug-resistant bacteria (MDR) responsible for high mortality worldwide. In this review we summarize and discuss the key points associated with the reality of (i) the existence of pandrug-resistant bacteria, (ii) the increase of resistance worldwide, (iii) the link between resistance and death, and (iv) the need to develop new antibiotics. Data on antibiotic resistance in Europe for the main bacteria associated with invasive infections apparently demonstrate that apart from Klebsiella pneumoniae, which is resistant to carbapenems in three countries (Romania, Italy and Greece), the level of resistance to three or more classes of antibiotics (defined as MDR phenotype) has remained low and stable over the last 5 years and that therapeutic options exist both for reference antibiotics and for old antibiotics. The clinical outcome of patients infected by MDR bacteria remains controversial and death rates attributable to MDR bacteria versus non-MDR bacteria are still debated. The arsenal of antibiotics currently available (including 'old antibiotics') suffices for facing the waves of emergence of new bacterial resistance and should be considered as a World Heritage. This heritage should be managed in a non-profit model with international regulatory approval. PMID:27021418

  8. Antibiotic Prophylaxis in Pediatric Dentistry

    OpenAIRE

    Davydova N.V.; Suyetenkov D.Ye.; Firsova I.V.; Oleynikova N.M.

    2011-01-01

    Identify options for the indications for antibiotic prophylaxis in children's dental reception. The analysis of publications shows that the basis of current trends prevention of postoperative wound infection in pediatric surgery should be measures aimed at eliminating or reducing the influence of risk factors, as well as the use of antibiotic prophylaxis

  9. Antibiotic Prophylaxis in Pediatric Dentistry

    Directory of Open Access Journals (Sweden)

    Davydova N.V.

    2011-03-01

    Full Text Available Identify options for the indications for antibiotic prophylaxis in children's dental reception. The analysis of publications shows that the basis of current trends prevention of postoperative wound infection in pediatric surgery should be measures aimed at eliminating or reducing the influence of risk factors, as well as the use of antibiotic prophylaxis

  10. The Antibiotic Resistance Problem Revisited

    Science.gov (United States)

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  11. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  12. Antibiotic prescribing for acute bronchitis

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars

    2016-01-01

    INTRODUCTION: Acute bronchitis is a self-limiting infectious disease characterized by acute cough with or without sputum but without signs of pneumonia. About 90% of cases are caused by viruses. AREAS COVERED: Antibiotics for acute bronchitis have been associated with an approximately half......-day reduction in duration of cough. However, at follow-up there are no significant differences in overall clinical improvement inpatients treated with antibiotics compared with those receiving placebo. Despite this, antibiotics are administered to approximately two thirds of these patients. This review...... discusses the reason for this antibiotic overprescription. Other therapies targeted to control symptoms have also demonstrated a marginal or no effect. EXPERT COMMENTARY: Clinicians should be aware of the marginal effectiveness of antibiotic therapy. Some strategies like the use of rapid tests, delayed...

  13. Mildiomycin: a nucleoside antibiotic that inhibits protein synthesis.

    Science.gov (United States)

    Feduchi, E; Cosín, M; Carrasco, L

    1985-03-01

    Mildiomycin, a new nucleoside antibiotic, selectively inhibits protein synthesis in HeLa cells, and is less active in the inhibition of RNA or DNA synthesis. An increased inhibition of translation by mildiomycin is observed in cultured HeLa cells when they are permeabilized by encephalomyocarditis virus. This observation suggests that this antibiotic does not easily pass through the cell membrane, as occurs with other nucleoside and aminoglycoside antibiotics. The inhibition of translation is also observed in cell-free systems, such as endogenous protein synthesis in a rabbit reticulocyte lysate or the synthesis of polyphenylalanine directed by poly (U). Finally the mode of action of mildiomycin was investigated and the results suggest that the compound blocks the peptidyl-transferase center.

  14. Comet assay with gill cells of Mytilus galloprovincialis end point tools for biomonitoring of water antibiotic contamination: Biological treatment is a reliable process for detoxification.

    Science.gov (United States)

    Mustapha, Nadia; Zouiten, Amina; Dridi, Dorra; Tahrani, Leyla; Zouiten, Dorra; Mosrati, Ridha; Cherif, Ameur; Chekir-Ghedira, Leila; Mansour, Hedi Ben

    2016-04-01

    This article investigates the ability of Pseudomonas peli to treat industrial pharmaceuticals wastewater (PW). Liquid chromatography-mass spectrometry (MS)/MS analysis revealed the presence, in this PW, of a variety of antibiotics such as sulfathiazole, sulfamoxole, norfloxacine, cloxacilline, doxycycline, and cefquinome.P. peli was very effective to be grown in PW and inducts a remarkable increase in chemical oxygen demand and biochemical oxygen demand (140.31 and 148.51%, respectively). On the other hand, genotoxicity of the studied effluent, before and after 24 h of shaking incubation with P. peli, was evaluated in vivo in the Mediterranean wild mussels Mytilus galloprovincialis using comet assay for quantification of DNA fragmentation. Results show that PW exhibited a statistically significant (p< 0.001) genotoxic effect in a dose-dependent manner; indeed, the percentage of genotoxicity was 122.6 and 49.5% after exposure to 0.66 ml/kg body weight (b.w.); 0.33 ml/kg b.w. of PW, respectively. However, genotoxicity decreased strongly when tested with the PW obtained after incubation with P. peli We can conclude that using comet assay genotoxicity end points are useful tools to biomonitor the physicochemical and biological quality of water. Also, it could be concluded that P. peli can treat and detoxify the studied PW.

  15. Assessing the antibiotic susceptibility of freshwater cyanobacteria spp.

    Directory of Open Access Journals (Sweden)

    Elsa eDias

    2015-08-01

    Full Text Available Freshwater is a vehicle for the emergence and dissemination of antibiotic resistance. Cyanobacteria are ubiquitous in freshwater, where they are exposed to antibiotics and resistant organisms, but their role on water resistome was never evaluated. Data concerning the effects of antibiotics on cyanobacteria, obtained by distinct methodologies, is often contradictory. This emphasizes the importance of developing procedures to understand the trends of antibiotic susceptibility in cyanobacteria. In this study we aimed to evaluate the susceptibility of four cyanobacterial isolates from different genera (Microcystis aeruginosa, Aphanizomenon gracile, Chrisosporum bergii, Planktothix agradhii, and among them nine isolates from the same specie (M. aeruginosa to distinct antibiotics (amoxicillin, ceftazidime, ceftriaxone, kanamycine, gentamicine, tetracycline, trimethoprim, nalidixic acid, norfloxacin. We used a method adapted from the bacteria standard broth microdilution. Cyanobacteria were exposed to serial dilution of each antibiotic (0.0015-1.6 mg/L in Z8 medium (20 ± 1 ºC; 14/10 h L/D cycle; light intensity 16 ± 4 µEm-2 s-1. Cell growth was followed overtime (OD450nm/microscopic examination and the minimum inhibitory concentrations (MICs were calculated for each antibiotic/isolate. We found that -lactams exhibited the lower MICs, aminoglycosides, tetracycline and norfloxacine presented intermediate MICs; none of the isolates were susceptible to trimethoprim and nalidixic acid. The reduced susceptibility of all tested cyanobacteria to some antibiotics suggests that they might be naturally non-susceptible to these compounds, or that that they might became non-susceptible due to antibiotic contamination pressure, or to the transfer of genes from resistant bacteria present in the environment.

  16. Antibiotic Bactericidal Activity Is Countered by Maintaining pH Homeostasis in Mycobacterium smegmatis

    Science.gov (United States)

    Bartek, I. L.; Reichlen, M. J.; Honaker, R. W.; Leistikow, R. L.; Clambey, E. T.; Scobey, M. S.; Hinds, A. B.; Born, S. E.; Covey, C. R.; Schurr, M. J.; Lenaerts, A. J.

    2016-01-01

    ABSTRACT Antibiotics target specific biosynthetic processes essential for bacterial growth. It is intriguing that several commonalities connect the bactericidal activity of seemingly disparate antibiotics, such as the numerous conditions that confer broad-spectrum antibiotic tolerance. Whether antibiotics kill in a manner unique to their specific targets or by a universal mechanism is a critical and contested subject. Herein, we demonstrate that the bactericidal activity of diverse antibiotics against Mycobacterium smegmatis and four evolutionarily divergent bacterial pathogens was blocked by conditions that worked to maintain intracellular pH homeostasis. Single-cell pH analysis demonstrated that antibiotics increased the cytosolic pH of M. smegmatis, while conditions that promoted proton entry into the cytosol prevented intracellular alkalization and antibiotic killing. These findings led to a hypothesis that posits antibiotic lethality occurs when antibiotics obstruct ATP-consuming biosynthetic processes while metabolically driven proton efflux is sustained despite the loss of proton influx via ATP synthase. Consequently, without a concomitant reduction in respiratory proton efflux, cell death occurs due to intracellular alkalization. Our findings indicate the effects of antibiotics on pH homeostasis should be considered a potential mechanism contributing to antibiotic lethality. IMPORTANCE Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our

  17. Bacterial Protein Synthesis as a Target for Antibiotic Inhibition.

    Science.gov (United States)

    Arenz, Stefan; Wilson, Daniel N

    2016-01-01

    Protein synthesis occurs on macromolecular machines, called ribosomes. Bacterial ribosomes and the translational machinery represent one of the major targets for antibiotics in the cell. Therefore, structural and biochemical investigations into ribosome-targeting antibiotics provide not only insight into the mechanism of action and resistance of antibiotics, but also insight into the fundamental process of protein synthesis. This review summarizes the recent advances in our understanding of protein synthesis, particularly with respect to X-ray and cryoelectron microscopy (cryo-EM) structures of ribosome complexes, and highlights the different steps of translation that are targeted by the diverse array of known antibiotics. Such findings will be important for the ongoing development of novel and improved antimicrobial agents to combat the rapid emergence of multidrug resistant pathogenic bacteria. PMID:27481773

  18. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    Directory of Open Access Journals (Sweden)

    Roderick I. Mackie

    2013-07-01

    Full Text Available Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  19. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    KAUST Repository

    Hong, Pei-Ying

    2013-07-31

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  20. Metagenomic Analysis of the Stool Microbiome in Patients Receiving Allogeneic Stem Cell Transplantation: Loss of Diversity Is Associated with Use of Systemic Antibiotics and More Pronounced in Gastrointestinal Graft-versus-Host Disease

    Science.gov (United States)

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E.; Ferrara, James L.; Gessner, Andre; Spang, Rainer; Oefner, Peter J.

    2016-01-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. PMID:24492144

  1. Systemic antibiotic therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anoop Kapoor

    2012-01-01

    Full Text Available Systemic antibiotics in conjunction with scaling and root planing (SRP, can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

  2. Antibiotic resistance in wild birds.

    Science.gov (United States)

    Bonnedahl, Jonas; Järhult, Josef D

    2014-05-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  3. Antibiotics and the resistant microbiome

    DEFF Research Database (Denmark)

    Sommer, Morten; Dantas, Gautam

    2011-01-01

    Since the discovery and clinical application of antibiotics, pathogens and the human microbiota have faced a near continuous exposure to these selective agents. A well-established consequence of this exposure is the evolution of multidrug-resistant pathogens, which can become virtually untreatable....... Less appreciated are the concomitant changes in the human microbiome in response to these assaults and their contribution to clinical resistance problems. Studies have shown that pervasive changes to the human microbiota result from antibiotic treatment and that resistant strains can persist for years...... expand our understanding of the interplay between antibiotics and the microbiome....

  4. Antibiotics as CECs: An Overview of the Hazards Posed by Antibiotics and Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Geoffrey Ivan Scott

    2016-04-01

    Full Text Available ABSTRACTMonitoring programs have traditionally monitored legacy contaminants but are shifting focus to Contaminants of Emerging Concern (CECs. CECs present many challenges for monitoring and assessment, because measurement methods don't always exist nor have toxicological studies been fully conducted to place results in proper context. Also some CECs affect metabolic pathways to produce adverse outcomes that are not assessed through traditional toxicological evaluations. Antibiotics are CECs that pose significant environmental risks including development of both toxic effects at high doses and antibiotic resistance at doses well below the Minimum Inhibitory Concentration (MIC which kill bacteria and have been found in nearly half of all sites monitored in the US. Antimicrobial resistance has generally been attributed to the use of antibiotics in medicine for humans and livestock as well as aquaculture operations. The objective of this study was to assess the extent and magnitude of antibiotics in the environment and estimate their potential hazards in the environment. Antibiotics concentrations were measured in a number of monitoring studies which included Waste Water Treatment Plants (WWTP effluent, surface waters, sediments and biota. A number of studies reported levels of Antibiotic Resistant Microbes (ARM in surface waters and some studies found specific ARM genes (e.g. the blaM-1 gene in E. coli which may pose additional environmental risk. High levels of this gene were found to survive WWTP disinfection and accumulated in sediment at levels 100-1000 times higher than in the sewerage effluent, posing potential risks for gene transfer to other bacteria.in aquatic and marine ecosystems. Antibiotic risk assessment approaches were developed based on the use of MICs and MIC Ratios [High (Antibiotic Resistant/Low (Antibiotic Sensitive MIC] for each antibiotic indicating the range of bacterial adaptability to each antibiotic to help define the No

  5. Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

    Directory of Open Access Journals (Sweden)

    Abedulla Khan Kayamkani

    2015-07-01

    Full Text Available Postoperative surgical site infections are a major source of illness.  Infection results in longer hospital stay and higher costs.  Uses of preoperative antibiotics have been standardized and are being used routinely in most clinical surgeries and include controversial areas like breast surgery and herniorraphy. Objective of the study is to find out the benefit of prophylactic use of antibiotics in the management of herniorraphy.This project was carried out in a multispeciality tertiary care teaching hospital from 1st-30th April in 2002. Group 1 patients were treated prophylactically half an hour before surgery with single dose of I.V. antibiotics (injection.  Ampicillin 1gm + injection.  Gentamicin 80mg. Group 2 patients were treated post surgery with capsule. Ampicillin 500mg 4 times a day for 7 days and injection. Gentamicin twice a day for first 4 days. In case of group 1 patients only one out of 20 patients (5% was infected.  Whereas in-group 2 patients 5 out of 20 patients (25% were infected. The cost of prophylactic antibiotic treatment was Rs. 25.56 per patient.  The postoperative antibiotic treatment cost was Rs. 220.4 per patient.  That means postoperative treatment is around 8.62 times costlier than prophylactic treatment.             From this study it is evident that prophylactic (preoperative treatment is better than postoperative treatment with antibiotics.

  6. An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance

    OpenAIRE

    Nadia Abed; Fatouma Saïd-Hassane; Fatima Zouhiri; Julie Mougin; Valérie Nicolas; Didier Desmaële; Ruxandra Gref; Patrick Couvreur

    2015-01-01

    The “Golden era” of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of ...

  7. Antibiotic resistance: An ethical challenge.

    Science.gov (United States)

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  8. Use of Antibiotics in Children

    DEFF Research Database (Denmark)

    Pottegård, Anton; Broe, Anne; Aabenhus, Rune;

    2015-01-01

    Background: We aimed to describe the use of systemic antibiotics among children in Denmark. Methods: National data on drug use in Denmark were extracted from the Danish National Prescription Database. We used prescription data for all children in Denmark aged 0 to 11 years from January 1, 2000...... to December 31, 2012. Results: We obtained data on 5,884,301 prescriptions for systemic antibiotics issued to 1,206,107 children. The most used single substances were phenoxymethylpenicillin (45%), amoxicillin (34%) and erythromycin (6%). The highest incidence rate of antibiotic treatment episodes......–1. There was little evidence of heavy users. Conclusion: Prescribing rate of antibiotics to children in Denmark remained stable at a high level from 2000 to 2012. An increase in the use of broad-spectrum beta-lactam penicillin was noted, but otherwise the prescribing pattern adhered well to National guidelines...

  9. Prophylactic antibiotics in orthopaedic surgery.

    Science.gov (United States)

    Prokuski, Laura; Clyburn, Terry A; Evans, Richard P; Moucha, Calin S

    2011-01-01

    The use of prophylactic antibiotics in orthopaedic surgery has been proven effective in reducing surgical site infections after hip and knee arthroplasty, spine procedures, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics, while minimizing any adverse effects, the correct antimicrobial agent must be selected, the drug must be administered just before incision, and the duration of administration should not exceed 24 hours.

  10. Systemic antibiotic therapy in periodontics

    OpenAIRE

    Anoop Kapoor; Ranjan Malhotra; Vishakha Grover; Deepak Grover

    2012-01-01

    Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, pr...

  11. Antibiotic susceptibility of Aggregatibacter actinomycetemcomitans JP2 in a biofilm

    Directory of Open Access Journals (Sweden)

    Orit Oettinger-Barak

    2013-05-01

    Full Text Available Background: Localized aggressive periodontitis (LAgP is an inflammatory disease associated with specific bacteria, particularly Aggregatibacter actinomycetemcomitans, which can result in early tooth loss. The bacteria grow as a biofilm known as subgingival plaque. Treatment includes mechanical debridement of the biofilm, often associated with empirical antibiotic treatment. Objective: The aims of this study were to test in vitro the sensitivity of A. actinomycetemcomitans JP2 during planktonic and biofilm growth to doxycycline and to the combination of metronidazole and amoxicillin, which are two antibiotic protocols commonly used in clinical practice. Design: Two in vitro biofilm models were used to test the effects of the antibiotics: a static 96-well plate assay was used to investigate the effect of these antibiotics on biofilm formation whilst a flow chamber model was used to examine the effect on established biofilms. Results: Of the antibiotics tested in this model system, doxycycline was most efficacious with a minimal inhibitory concentration (MIC against planktonic cells of 0.21 mg/L and minimal biofilm inhibitory concentration (MBIC of 2.10 mg/L. The most commonly prescribed antibiotic regimen, amoxicillin + metronidazole, was much less effective against both planktonic and biofilm cells with an MIC and MBIC of 12.0 mg/L and 20.2 mg/L, respectively. A single treatment of the clinically achievable concentration of 10 mg/L doxycycline to sparse A. actinomycetemcomitans biofilms in the flow chamber model resulted in significant decreases in biofilm thickness, biovolume, and cell viability. Dense A. actinomycetemcomitans biofilms were significantly more resistant to doxycycline treatment. Low concentrations of antibiotics enhanced biofilm formation. Conclusion: A. actinomycetemcomitans JP2 homotypic biofilms were more susceptible in vitro to doxycycline than amoxicillin + metronidazole.

  12. [Self-medication with antibiotics in Poland

    NARCIS (Netherlands)

    Olczak, A.; Grzesiowski, P.; Hryniewicz, W.; Haaijer-Ruskamp, F.M.

    2006-01-01

    Antibiotic resistance, the important public health threat, depends on antibiotic overuse/misuse. Self-medication with antibiotics is of serious medical concern. The aim of the study, as a part of SAR project (Self-medication with antibiotic in Europe) was to survey the incidence of this phenomenon.

  13. Expedient antibiotics production: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

    1988-05-01

    The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented. This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.

  14. Detection of antibiotic residues in food by Charm II test

    International Nuclear Information System (INIS)

    Antibiotics are used in food to: -therapy and prophylaxis, -increase the productivity of the food producing animals. The presence of antimicrobial residues: -constitutes a potential human health hazard. has significant impact on international food trade. has implications on technological process in dairy industry. Detection of antibiotic residues is of great interest. It helps protect humans against the effects of such residues, the more it can support the participation of our country in international trade. Charm II test is one of the methods of detection of antimicrobial residues. The tests utilize microbial or antibody receptor assay technology. The sample is incubated with a binding agent (microbial cells with specific receptor sites or with specific antibodies attached) and a tracer (the radio-labeled version of the antibiotic to be detected). The amount of tracer on the binding agent is measured using a scintillation counter and is compared to a pre-determined cut-off or control point. If contaminating antibiotic is present, it will prevent the binding of the tracer by occupying the receptors on the binding agent. The less labeled tracer detected, the more contaminating antibiotic there is present in the sample. This work, carried out at the Radiochemical Laboratory of the National Centre of Nuclear Science and Technology, has two parts: 1/ The first is reserved to a literature review provides an overview on antibiotics and the charm II method. 2/ The second is devoted to the experimental study and presentation of results.

  15. Role of porins for uptake of antibiotics by Mycobacterium smegmatis.

    Science.gov (United States)

    Danilchanka, Olga; Pavlenok, Mikhail; Niederweis, Michael

    2008-09-01

    The outer membrane of mycobacteria presents an effective permeability barrier for many antibiotics. Transport pathways across this membrane are unknown for most drugs. Here, we examined which antibiotics utilize the porin pathway across the outer membrane of the model organism Mycobacterium smegmatis. Deletion of the porins MspA and MspC drastically increased the resistance of M. smegmatis ML10 to beta-lactam antibiotics, while its beta-lactamase activity remained unchanged. These results are consistent with the ninefold-reduced outer membrane permeability of the M. smegmatis porin mutants for cephaloridine and strongly indicate that beta-lactam antibiotics rely on the porin pathway. The porin mutant ML10 accumulated less chloramphenicol and norfloxacin and was less susceptible to these antibiotics than wild-type M. smegmatis. These results demonstrated that small and hydrophilic antibiotics use the Msp porins for entering the cell. In contrast to norfloxacin, the hydrophobic moxifloxacin was 32-fold more effective in inhibiting the growth of M. smegmatis, presumably because it was able to diffuse through the lipid membrane. Structural models indicated that erythromycin, kanamycin, and vancomycin are too large to move through the MspA channel. This study presents the first experimental evidence that hydrophilic fluoroquinolones and chloramphenicol diffuse through porins in mycobacteria. Thus, mutations resulting in less efficient porins or lower porin expression levels are likely to represent a mechanism for the opportunistic pathogens M. avium, M. chelonae, and M. fortuitum, which have Msp-like porins, to acquire resistance to fluoroquinolones. PMID:18559650

  16. [Surviving Forms in Antibiotic-Treated Pseudomonas aeruginosa].

    Science.gov (United States)

    Mulyukin, A L; Kozlova, A N; Sorokin, V V; Suzina, N E; Cherdyntseva, T A; Kotova, I B; Gaponov, A M; Tutel'yan, A V; El'-Registan, G I

    2015-01-01

    Survival of bacterial populations treated with lethal doses of antibiotics is ensured by the presence of very small numbers of persister cells. Unlike antibiotic-resistant cells, antibiotic tolerance of persisters is not inheritable and reversible. The present work provides evidence supporting the hypothesis of transformation (maturation) of persisters of an opportunistic pathogen Pseudomonas aeruginosa revealed by ciprofloxacin (CF) treatment (25-100 μg/mL) into dormant cystlike cells (CLC) and non-culturable cells (NC), as was described previously for a number. of non-spore-forming bacteria. Subpopulations of type 1 and type 2 persisters, which survived antibiotic treatment and developed into dormant forms, were heterogeneous in their capacity to form colonies or microcolonies upon germination, in resistance to heating at 70 degrees C, and in cell morphology Type 1 persisters, which were formed after 1-month incubation in the stationary-phase cultures in the medium with decreased C and N concentrations, developed in several types of surviving cells, including those similar to CLC in cell morphology. In the course of 1-month incubation of type 2 persisters, which were formed in exponentially growing cultures, other types of surviving cells developed: immature CLC and L-forms. Unlike P. aeruginosa CLC formed in the control post-stationary phase cultures without antibiotic treatment, most of 1-month persisters, especially type 2 ones, were characterized by the loss of colony-forming capacity, probably due to transition into an uncultured state with relatively high numbers of live intact cells (Live/Dead test). Another survival strategy of P. aeruginosa populations was ensured by a minor subpopulation of CF-tolerant and CF-resistant cells able to grow in the form of microcolonies or regular colonies of decreased size in the presence of the antibiotic. The described P. aeruginosa dormant forms may be responsible for persistent forms in bacteria carriers and latent

  17. [Surviving Forms in Antibiotic-Treated Pseudomonas aeruginosa].

    Science.gov (United States)

    Mulyukin, A L; Kozlova, A N; Sorokin, V V; Suzina, N E; Cherdyntseva, T A; Kotova, I B; Gaponov, A M; Tutel'yan, A V; El'-Registan, G I

    2015-01-01

    Survival of bacterial populations treated with lethal doses of antibiotics is ensured by the presence of very small numbers of persister cells. Unlike antibiotic-resistant cells, antibiotic tolerance of persisters is not inheritable and reversible. The present work provides evidence supporting the hypothesis of transformation (maturation) of persisters of an opportunistic pathogen Pseudomonas aeruginosa revealed by ciprofloxacin (CF) treatment (25-100 μg/mL) into dormant cystlike cells (CLC) and non-culturable cells (NC), as was described previously for a number. of non-spore-forming bacteria. Subpopulations of type 1 and type 2 persisters, which survived antibiotic treatment and developed into dormant forms, were heterogeneous in their capacity to form colonies or microcolonies upon germination, in resistance to heating at 70 degrees C, and in cell morphology Type 1 persisters, which were formed after 1-month incubation in the stationary-phase cultures in the medium with decreased C and N concentrations, developed in several types of surviving cells, including those similar to CLC in cell morphology. In the course of 1-month incubation of type 2 persisters, which were formed in exponentially growing cultures, other types of surviving cells developed: immature CLC and L-forms. Unlike P. aeruginosa CLC formed in the control post-stationary phase cultures without antibiotic treatment, most of 1-month persisters, especially type 2 ones, were characterized by the loss of colony-forming capacity, probably due to transition into an uncultured state with relatively high numbers of live intact cells (Live/Dead test). Another survival strategy of P. aeruginosa populations was ensured by a minor subpopulation of CF-tolerant and CF-resistant cells able to grow in the form of microcolonies or regular colonies of decreased size in the presence of the antibiotic. The described P. aeruginosa dormant forms may be responsible for persistent forms in bacteria carriers and latent

  18. High Concentration of Red Clay as an Alternative for Antibiotics in Aquaculture.

    Science.gov (United States)

    Jung, Jaejoon; Jee, Seung Cheol; Sung, Jung-Suk; Park, Woojun

    2016-01-01

    The use of antibiotics in aquaculture raises environmental and food safety concerns because chronic exposure of an aquatic ecosystem to antibiotics can result in the spread of antibiotic resistance, bioaccumulation of antibiotics in the organisms, and transfer of antibiotics to humans. In an attempt to overcome these problems, high-concentration red clay was applied as an alternative antibiotic against the following common fish pathogens: Aeromonas salmonicida, Vibrio alginolyticus, and Streptococcus equinus. The growth of A. salmonicida and V. alginolyticus was retarded by red clay, whereas that of S. equinus was promoted. Phase contrast and scanning electron microscopy analyses confirmed the attachment of red clay on cell surfaces, resulting in rapid gravitational removal and cell surface damage in both A. salmonicida and V. alginolyticus, but not in S. equinus. Different cell wall properties of grampositive species may explain the unharmed cell surface of S. equinus. Significant levels of oxidative stress were generated in only the former two species, whereas significant changes in membrane permeability were found only in S. equinus, probably because of its physiological adaptation. The bacterial communities in water samples from Oncorhynchus mykiss aquacultures supplemented with red clay showed similar structure and diversity as those from oxytetracycline-treated water. Taken together, the antibiotic effects of high concentrations of red clay in aquaculture can be attributed to gravitational removal, cell surface damage, and oxidative stress production, and suggest that red clay may be used as an alternative for antibiotics in aquaculture.

  19. Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

    LENUS (Irish Health Repository)

    Murphy, D M

    2010-03-01

    The macrolides are a class of antibiotics widely prescribed in infectious disease. More recently, there has been considerable interest in potential indications for these agents, in addition to their simple antibacterial indications, in a number of lung pathophysiologies.

  20. Dielectrophoretic assay of bacterial resistance to antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Johari, Juliana [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Huebner, Yvonne [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Hull, Judith C [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Dale, Jeremy W [School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Hughes, Michael P [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom)

    2003-07-21

    The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h exposure. This method offers possibilities for the assessment of bacterial resistance to antibiotics. (note)

  1. Antibiotics: Use and misuse in pediatric dentistry

    Directory of Open Access Journals (Sweden)

    F C Peedikayil

    2011-01-01

    Full Text Available Antibiotics are commonly used in dentistry for prophylactic as well as for therapeutic purposes. Most often antibiotics are used in unwarranted situations, which may give rise to resistant bacterial strains. Dentists want to make their patients well and to prevent unpleasant complications. These desires, coupled with the belief that many oral problems are infectious, stimulate the prescribing of antibiotics. Good knowledge about the indications of antibiotics is the need of the hour in prescribing antibiotics for dental conditions.

  2. Antibiotics that target protein synthesis.

    Science.gov (United States)

    McCoy, Lisa S; Xie, Yun; Tor, Yitzhak

    2011-01-01

    The key role of the bacterial ribosome makes it an important target for antibacterial agents. Indeed, a large number of clinically useful antibiotics target this complex translational ribonucleoprotein machinery. The majority of these compounds, mostly of natural origin, bind to one of the three key ribosomal sites: the decoding (or A-site) on the 30S, the peptidyl transferase center (PTC) on the 50S, and the peptide exit tunnel on the 50S. Antibiotics that bind the A-site, such as the aminoglycosides, interfere with codon recognition and translocation. Peptide bond formation is inhibited when small molecules like oxazolidinones bind at the PTC. Finally, macrolides tend to block the growth of the amino acid chain at the peptide exit tunnel. In this article, the major classes of antibiotics that target the bacterial ribosome are discussed and classified according to their respective target. Notably, most antibiotics solely interact with the RNA components of the bacterial ribosome. The surge seen in the appearance of resistant bacteria has not been met by a parallel development of effective and broad-spectrum new antibiotics, as evident by the introduction of only two novel classes of antibiotics, the oxazolidinones and lipopeptides, in the past decades. Nevertheless, this significant health threat has revitalized the search for new antibacterial agents and novel targets. High resolution structural data of many ribosome-bound antibiotics provide unprecedented insight into their molecular contacts and mode of action and inspire the design and synthesis of new candidate drugs that target this fascinating molecular machine. PMID:21957007

  3. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    Science.gov (United States)

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  4. Background antibiotic resistance patterns in antibiotic-free pastured poultry production

    Science.gov (United States)

    Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

  5. Transmission Electron Microscopic Study of Antibiotic Action on Klebsiella pneumoniae Biofilm

    OpenAIRE

    Zahller, Jeff; Philip S. Stewart

    2002-01-01

    The penetration of ampicillin and ciprofloxacin through biofilms formed by Klebsiella pneumoniae was confirmed by transmission electron microscopic observation of antibiotic-affected cells at the distal edge of the biofilm. Because the bacteria nevertheless survived antibiotic treatment, some protective mechanism other than inadequate penetration must have been at work in the biofilm.

  6. Growth mediated feedback and the abrupt onset of antibiotic resistance

    Science.gov (United States)

    Barrett Deris, J.

    2010-03-01

    Recent results in our lab indicate that global gene expression will change in a growth-dependent manner for bacteria in sublethal antibiotic levels. We analyzed a system containing a constitutively expressed drug resistance gene and found that growth-mediated feedback provided a mechanism for bistable growth rates. That is, two identical cell-lines in the same antibiotic-infused media may respond with distinct growth rates. Our experimental work with cells carrying this resistance gene has shown that a rapid drop in growth occurs over a relatively small range of antibiotic. This result is consistent with a growth plateau arising in our analysis of the feedback mechanism. Furthermore, experiments have shown that a culture's degree of drug resistance depends on the initial growth conditions prior to exposure to high levels of antibiotics. This result is consistent with the predicted existence of a hysteretic regime near the growth plateau. The work reveals concrete mechanisms by which bacteria cope with high levels of antibiotics and illustrates the importance of considering growth-mediated feedback on gene circuits.

  7. Synergistic interaction of eugenol with antibiotics against Gram negative bacteria.

    Science.gov (United States)

    Hemaiswarya, S; Doble, M

    2009-11-01

    Eugenol, the principal chemical component of clove oil from Eugenia aromatica has been long known for its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects. The interaction of the eugenol with ten different hydrophobic and hydrophilic antibiotics was studied against five different Gram negative bacteria. The MIC of the combination was found to decrease by a factor of 5-1000 with respect to their individual MIC. This synergy is because of the membrane damaging nature of eugenol, where 1mM of its concentration is able to damage nearly 50% of the bacterial membrane. Eugenol was also able to enhance the activities of lysozyme, Triton X-100 and SDS in damaging the bacterial cell membrane. The hydrophilic antibiotics such as vancomycin and beta-lactam antibiotics which have a marginal activity on these gram negative bacteria exhibit an enhanced antibacterial activity when pretreated with eugenol. Reduced usage of antibiotics could be employed as a treatment strategy to slow down the onset of antibiotic resistance as well as decrease its toxicity. Experiments performed with human blood cells indicated that the concentration of eugenol used for the combination studies were below its cytotoxic values. Pharmacodynamic studies of the combinations need to be performed to decide on the effective dosage. PMID:19540744

  8. A non-polyene antifungal antibiotic from Streptomyces albidoflavus PU 23

    Indian Academy of Sciences (India)

    S K Augustine; S P Bhavsar; B P Kapadnis

    2005-03-01

    In all 312 actinomycete strains were isolated from water and soil samples from different regions. All these isolates were purified and screened for their antifungal activity against pathogenic fungi. Out of these, 22% of the isolates exhibited activity against fungi. One promising strain, Streptomyces albidoflavus PU 23 with strong antifungal activity against pathogenic fungi was selected for further studies. Antibiotic was extracted and purified from the isolate. Aspergillus spp. was most sensitive to the antibiotic followed by other molds and yeasts. The antibiotic was stable at different temperatures and pH tested and there was no significant loss of the antifungal activity after treatment with various detergents and enzymes. Synergistic effect was observed when the antibiotic was used in combination with hamycin. The antibiotic was fairly stable for a period of 12 months at 4°C. The mode of action of the antibiotic seems to be by binding to the ergosterol present in the fungal cell membrane resulting in the leakage of intracellular material and eventually death of the cell. The structure of the antibiotic was determined by elemental analysis and by ultraviolet (UV), Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and liquid chromatography mass spectra (LCMS). The antibiotic was found to be a straight chain polyhydroxy, polyether, non-proteinic compound with a single double bond, indicating a nonpolyene antifungal antibiotic.

  9. A new approach for the discovery of antibiotics by targeting non-multiplying bacteria: a novel topical antibiotic for staphylococcal infections.

    Directory of Open Access Journals (Sweden)

    Yanmin Hu

    Full Text Available In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates.

  10. Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs)

    Science.gov (United States)

    Fiorillo, Marco; Lamb, Rebecca; Tanowitz, Herbert B.; Cappello, Anna Rita; Martinez-Outschoorn, Ubaldo E.; Sotgia, Federica; Lisanti, Michael P.

    2016-01-01

    Bedaquiline (a.k.a., Sirturo) is an anti-microbial agent, which is approved by the FDA for the treatment of multi-drug resistant pulmonary tuberculosis (TB). Bedaquiline is a first-in-class diaryl-quinoline compound, that mechanistically inhibits the bacterial ATP-synthase, and shows potent activity against both drug-sensitive and drug-resistant TB. Interestingly, eukaryotic mitochondria originally evolved from engulfed aerobic bacteria. Thus, we hypothesized that, in mammalian cells, bedaquiline might also target the mitochondrial ATP-synthase, leading to mitochondrial dysfunction and ATP depletion. Here, we show that bedaquiline has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs). More specifically, we demonstrate that bedaquiline treatment of MCF7 breast cancer cells inhibits mitochondrial oxygen-consumption, as well as glycolysis, but induces oxidative stress. Importantly, bedaquiline significantly blocks the propagation and expansion of MCF7-derived CSCs, with an IC-50 of approx. 1-μM, as determined using the mammosphere assay. Similarly, bedaquiline also reduces both the CD44+/CD24low/− CSC and ALDH+ CSC populations, under anchorage-independent growth conditions. In striking contrast, bedaquiline significantly increases oxygen consumption in normal human fibroblasts, consistent with the fact that it is well-tolerated in patients treated for TB infections. As such, future pre-clinical studies and human clinical trials in cancer patients may be warranted. Interestingly, we also highlight that bedaquiline shares certain structural similarities with trans-piceatannol and trans-resveratrol, which are known natural flavonoid inhibitors of the mitochondrial ATP-synthase (complex V) and show anti-aging properties. PMID:27344270

  11. Fungal Biotransformation of Tetracycline Antibiotics.

    Science.gov (United States)

    Shang, Zhuo; Salim, Angela A; Khalil, Zeinab; Bernhardt, Paul V; Capon, Robert J

    2016-08-01

    The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation. PMID:27419475

  12. Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing

    OpenAIRE

    Zhang, Qi; Wang, Shanshan; Yang, Dexuan; PAN, KEVIN; Li, Linna; Yuan, Shoujun

    2016-01-01

    The established urinary antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking cancer cell invasion. These features make nitroxoline an excellent candidate for anticancer drug repurposing. To rapidly advance nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazo...

  13. Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure

    Directory of Open Access Journals (Sweden)

    Jessica Z. Kubicek-Sutherland

    2015-09-01

    Full Text Available Current antibiotic testing does not include the potential influence of host cell environment on microbial susceptibility and antibiotic resistance, hindering appropriate therapeutic intervention. We devised a strategy to identify the presence of host–pathogen interactions that alter antibiotic efficacy in vivo. Our findings revealed a bacterial mechanism that promotes antibiotic resistance in vivo at concentrations of drug that far exceed dosages determined by standardized antimicrobial testing. This mechanism has escaped prior detection because it is reversible and operates within a subset of host tissues and cells. Bacterial pathogens are thereby protected while their survival promotes the emergence of permanent drug resistance. This host-dependent mechanism of transient antibiotic resistance is applicable to multiple pathogens and has implications for the development of more effective antimicrobial therapies.

  14. Mycobacteriophage putative GTPase-activating protein can potentiate antibiotics.

    Science.gov (United States)

    Yan, Shuangquan; Xu, Mengmeng; Duan, Xiangke; Yu, Zhaoxiao; Li, Qiming; Xie, Longxiang; Fan, Xiangyu; Xie, Jianping

    2016-09-01

    The soaring incidences of infection by antimicrobial resistant (AR) pathogens and shortage of effective antibiotics with new mechanisms of action have renewed interest in phage therapy. This scenario is exemplified by resistant tuberculosis (TB), caused by resistant Mycobacterium tuberculosis. Mycobacteriophage SWU1 A321_gp67 encodes a putative GTPase-activating protein. Mycobacterium smegmatis with gp67 overexpression showed changed colony formation and biofilm morphology and supports the efficacy of streptomycin and capreomycin against Mycobacterium. gp67 down-regulated the transcription of genes involved in cell wall and biofilm development. To our knowledge, this is the first report to show that phage protein in addition to lysin or recombination components can synergize with existing antibiotics. Phage components might represent a promising new clue for better antibiotic potentiators. PMID:27345061

  15. An Antibiotic Selection System For Protein Overproducing Bacteria

    DEFF Research Database (Denmark)

    Rennig, Maja; Nørholm, Morten

    2015-01-01

    Introduction: Protein overproduction is a major bottleneck for analyses of membrane proteins and for the construction of cell factories. Screening for optimized protein production can be very time consuming. In this study we show that the coupling of antibiotic resistance to poorly produced...... membrane proteins of Escherichia coli can be used as a fast and simple selection system for protein overproduction.Methods: We designed an expression plasmid encoding the gene of interest and an additional, inducible antibiotic resistance marker. Both genes were linked by a hairpin structure...... that translationally couples the genes. Consequently, high expressing gene variants also allow for higher production of the coupled antibiotic resistance marker. Therefore, high expressing gene variants in a library can be determined either by plating the expression library on selection plates or by growing...

  16. Antibiotic treatment of verocytotoxin-producing Escherichia coli (VTEC) infection

    DEFF Research Database (Denmark)

    Agger, Morten; Scheutz, Flemming; Villumsen, Steen;

    2015-01-01

    OBJECTIVES: A consensus has existed on not to treat verocytotoxin-producing Escherichia coli (VTEC)-infected individuals with antibiotics because of possible subsequent increased risk of developing haemolytic uraemic syndrome (HUS). The aim of this systematic review is to clarify the risk...... associated with antibiotic treatment during acute VTEC infection and in chronic VTEC carrier states. METHODS: A systematic search in PubMed identified 1 meta-analysis, 10 clinical studies and 22 in vitro/in vivo studies. RESULTS: Four clinical studies found an increased risk of HUS, four studies found...... no altered risk of HUS and two studies found a protective effect of antibiotics. In vitro and clinical studies suggest that DNA synthesis inhibitors should be avoided, whereas evidence from in vitro studies indicates that certain protein and cell wall synthesis inhibitors reduce the release of toxins from...

  17. Antibodies: an alternative for antibiotics?

    Science.gov (United States)

    Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C

    2005-04-01

    In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases. PMID:15844826

  18. Antibiotics and the burn patient.

    Science.gov (United States)

    Ravat, François; Le-Floch, Ronan; Vinsonneau, Christophe; Ainaud, Pierre; Bertin-Maghit, Marc; Carsin, Hervé; Perro, Gérard

    2011-02-01

    Infection is a major problem in burn care and especially when it is due to bacteria with hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-negative organisms, the most effective molecules are 20 years old and there is little hope of any new product available even in the distant future. Therefore, it is obvious that currently available antibiotics should not be misused. With this aim in mind, the following review was conducted by a group of experts from the French Society for Burn Injuries (SFETB). It examined key points addressing the management of antibiotics for burn patients: when to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The authors also considered antibioprophylaxis and some other key points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French guidelines for the use of antibiotics in burn patients have been designed up from this work. PMID:20510518

  19. Antibiotic resistance pattern in uropathogens

    OpenAIRE

    Gupta V; Yadav A; Joshi R

    2002-01-01

    Uropathogenic strains from inpatient and outpatient departments were studied from April 1997 to March 1999 for their susceptibility profiles. The various isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii and Enterococcus faecalis. Antibiotic susceptibility pattern of these isolates revealed that for outpatients, first generation cephalosporins, nitrofurantoin, norfloxacin/ciprofloxacin were effective for treatment of urina...

  20. ANTIBIOTIC THERAPY FOR ENT INFECTIONS

    Directory of Open Access Journals (Sweden)

    A. B. Turovsky

    2014-07-01

    Full Text Available The paper outlines basic principles of and new approaches to antibiotic therapy for ENT and upper respiratory tract infections, from point of view of the authors, on the basis of the data available in Russian and foreign literature.

  1. Antibiotic associated diarrhoea: Infectious causes

    Directory of Open Access Journals (Sweden)

    Ayyagari A

    2003-01-01

    Full Text Available Nearly 25% of antibiotic associated diarrhoeas (AAD is caused by Clostridium difficile, making it the commonest identified and treatable pathogen. Other pathogens implicated infrequently include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp. and Salmonella spp. Most mild cases of AAD are due to non-infectious causes which include reduced break down of primary bile acids and decrease metabolism of carbohydrates, allergic or toxic effects of antibiotic on intestinal mucosa and pharmacological effect on gut motility. The antibiotics most frequently associated with C. difficile associated diarrhoea are clindamycin, cephalosporin, ampicillin and amoxicillin. Clinical presentation may vary from mild diarrhoea to severe colitis and pseudomembranous colitis associated with high morbidity and mortality. The most sensitive and specific diagnostic test for C. difficile infection is tissue culture assay for cytotoxicity of toxin B. Commercial ELISA kits are available. Though less sensitive, they are easy to perform and are rapid. Withdrawal of precipitating antibiotic is all that is needed for control of mild to moderate cases. For severe cases of AAD, oral metronidazole is the first line of treatment, and oral vancomycin is the second choice. Probiotics have been used for recurrent cases.

  2. Antibiotic resistance in probiotic bacteria

    Directory of Open Access Journals (Sweden)

    Miguel eGueimonde

    2013-07-01

    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue.

  3. The ABC of Ribosome-Related Antibiotic Resistance

    Science.gov (United States)

    Wilson, Daniel N.

    2016-01-01

    ABSTRACT The increase in multidrug-resistant pathogenic bacteria is limiting the utility of our current arsenal of antimicrobial agents. Mechanistically understanding how bacteria obtain antibiotic resistance is a critical first step to the development of improved inhibitors. One common mechanism for bacteria to obtain antibiotic resistance is by employing ATP-binding cassette (ABC) transporters to actively pump the drug from the cell. The ABC-F family includes proteins conferring resistance to a variety of clinically important ribosome-targeting antibiotics; however, controversy remains as to whether resistance is conferred via efflux like other ABC transporters or whether another mechanism, such as ribosome protection, is at play. A recent study by Sharkey and coworkers (L. K. Sharkey, T. A. Edwards, and A. J. O’Neill, mBio 7:e01975-15, 2016, http://dx.doi.org/10.1128/mBio.01975-15) provides strong evidence that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosome and displacing the drug from its binding site, thus revealing a novel role for ABC-F proteins in antibiotic resistance. PMID:27143393

  4. Antibiotics, Formula Feeding Might Change Baby's 'Microbiome'

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159392.html Antibiotics, Formula Feeding Might Change Baby's 'Microbiome' C-section birth ... microbiomes" are altered by cesarean births, antibiotics and formula feeding. "The microbiome is really important in how ...

  5. Antibiotic and Antimicrobial Resistance: Threat Report 2013

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Antibiotic Resistance Threats in the United States, 2013 Recommend on Facebook Tweet Share Compartir This report, Antibiotic resistance threats in the United States, 2013 gives a first- ...

  6. Antibiotic 'Report Card' Drills Guidelines into Dentists

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160702.html Antibiotic 'Report Card' Drills Guidelines Into Dentists Seeing their ... HealthDay News) -- Dentists are less likely to prescribe antibiotics for patients after seeing a "report card" on ...

  7. Influence of the Charge State on the Structures and Interactions of Vancomycin Antibiotics with Cell-Wall Analogue Peptides: Experimental and Theoretical Studies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2009-02-16

    In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the non-covalent complex between the vancomycin and the cell wall peptide analogue Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac2KDADA). The binding energies between the vancomycin and the peptide were obtained from the RRKM modeling of the time- and energy resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex toward fragmentation increases in the order: [V+Ac2KDADA+H]+2 < [V+Ac2KDADA+H]+ < [V+Ac2KDADA-H]-. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects indicating substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of 1.75 eV and 1.34 eV obtained for the [V+Ac2KDADA-H]- and [V+Ac2KDADA+H]+ , respectively, are in excellent agreement with the results of density functional theory (DFT) calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex as compared to only one charged site in the singly protonated complex. The low binding energy of 0.93 eV obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.

  8. Squalamine: an aminosterol antibiotic from the shark.

    OpenAIRE

    Moore, K.S.; Wehrli, S; Roder, H; Rogers, M.; Forrest, J N; McCrimmon, D; Zasloff, M.

    1993-01-01

    In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bact...

  9. Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics

    NARCIS (Netherlands)

    Kimpen, JLL; van Houten, M.A.

    1998-01-01

    In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies

  10. Antibiotic susceptibility profiles of oral pathogens

    NARCIS (Netherlands)

    Veloo, A. C. M.; Seme, K.; Raangs, E.; Rurenga, P.; Singadji, Z.; Wekema-Mulder, G.; van Winkelhoff, A. J.

    2012-01-01

    Periodontitis is a bacterial disease that can be treated with systemic antibiotics. The aim of this study was to establish the antibiotic susceptibility profiles of five periodontal pathogens to six commonly used antibiotics in periodontics. A total of 247 periodontal bacterial isolates were tested

  11. New business models for antibiotic innovation.

    Science.gov (United States)

    So, Anthony D; Shah, Tejen A

    2014-05-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards.

  12. Influence of population density on antibiotic resistance

    NARCIS (Netherlands)

    Bruinsma, N; Hutchinson, JM; van den Bogaard, AE; Giamarellou, H; Degener, J; Stobberingh, EE

    2003-01-01

    Antibiotic consumption and population density as a measure of crowding in the community were related to the prevalence of antibiotic resistance of three cities in three different countries: St Johns in Newfoundland (Canada), Athens in Greece and Groningen in The Netherlands. Antibiotic consumption w

  13. The global problem of antibiotic resistance.

    Science.gov (United States)

    Gootz, Thomas D

    2010-01-01

    . These determinants confer a complex resistance phenotype that is often superimposed on mutations in the primary drug target in the cell. The continued evolution of such a complex array of antibiotic-resistance genes presents a formidable challenge at a time when large pharmaceutical companies have scaled down their presence in the anti-infectives arena. PMID:20370622

  14. [Mechanism of action of antibiotics:some examples].

    Science.gov (United States)

    Michel-Briand, Y

    1978-01-01

    Antibiotics are very commonly used substances to eradicate bacterial infections by bacteriostatic or even bactericid effect. They act at a very specific stage (target), although other less important or secondary interactions can occur. We studied the interaction of three antibiotic families (beta-lactamins, aminosides, rifampicin) with bacterial cell. Penicillin disturbs the cell wall synthesis and more accurately the glycopeptide (or murein) formation, a substance giving rigidity or shape to bacteria. It acts in the late phase of murein-biosynthesis, when N-acetyl glucosamin -- N-acetyl muramic acid L ala -D glu M-DAP (L lys) -D ala -D ala are linked together by the peptide part, under the effect of several enzymes, particularly transpeptidase and DD-carboxy-peptidase. It would appear that beta-lactame-thiazolidine rings have a steric analogy with dipeptide D-alanyl D-alanine. The result would be that the enzyme would act on the antibiotic instead of peptide: the consequence would be inhibition of the peptidic link, giving an abnormal murein, and an incomplete cell wall i.e. fragile bacteria. Aminosides, particularly Streptomycin, link themselves to 30 S subunit of bacterial ribosome. In this case, it seems that it is a 3''OH function which reacts with lysine (from S 12 protein part of 30 S subunit). The consequence is an alteration in the RNA messager lecture, and a false traduction and consequently protein biosynthesis stops with a decrease of polyribosomes and of the formation of inert 70 S ribosome. Rifamycins, and particularly Rifampicin act by inhibition of RNA messager synthesis. One molecule of antibiotic links itself to one molecule of RNA messager : hydroxyl and cetone function in C1 Cs C21 C23 and "ansa" bridge link to beta subunit of RNA polymerase. This linkage gives a conformational change to the RNA polymerase-DNA complex, inhibiting the catalytic action of this enzyme, and consequently stopping RNA messager and protein synthesis. The study of the

  15. A mathematical model for expected time to extinction of pathogenic bacteria through antibiotic

    Science.gov (United States)

    Ghosh, M. K.; Nandi, S.; Roy, P. K.

    2016-04-01

    Application of antibiotics in human system to prevent bacterial diseases like Gastritis, Ulcers, Meningitis, Pneumonia and Gonorrhea are indispensable. Antibiotics saved innumerable lives and continue to be a strong support for therapeutic application against pathogenic bacteria. In human system, bacterial diseases occur when pathogenic bacteria gets into the body and begin to reproduce and crowd out healthy bacteria. In this process, immature bacteria releases enzyme which is essential for bacterial cell-wall biosynthesis. After complete formation of cell wall, immature bacteria are converted to mature or virulent bacteria which are harmful to us during bacterial infections. Use of antibiotics as drug inhibits the bacterial cell wall formation. After application of antibiotics within body, the released bacterial enzyme binds with antibiotic molecule instead of its functional site during the cell wall synthesis in a competitive inhibition approach. As a consequence, the bacterial cell-wall formation as well as maturation process of pathogenic bacteria is halted and the disease is cured with lysis of bacterial cells. With this idea, a mathematical model has been developed in the present research investigation to review the inhibition of biosynthesis of bacterial cell wall by the application of antibiotics as drug in the light of enzyme kinetics. This approach helps to estimate the expected time to extinction of the pathogenic bacteria. Our mathematical approach based on the enzyme kinetic model for finding out expected time to extinction contributes favorable results for understanding of disease dynamics. Analytical and numerical results based on simulated findings validate our mathematical model.

  16. A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria.

    Directory of Open Access Journals (Sweden)

    Yok-Ai Que

    Full Text Available Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Amino-acetophenone (2-AA, a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes.

  17. A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria.

    Science.gov (United States)

    Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Giddey, Marlyse; Wilhelmy, Julie; Mindrinos, Michael N; Rahme, Laurence G

    2013-01-01

    Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Amino-acetophenone (2-AA), a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS) signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes.

  18. Biosynthesis of Enediyne Antitumor Antibiotics

    OpenAIRE

    Van Lanen, Steven G.; Shen, Ben

    2008-01-01

    The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been...

  19. Uncialamycin, a new enediyne antibiotic.

    Science.gov (United States)

    Davies, Julian; Wang, Hao; Taylor, Terry; Warabi, Kaoru; Huang, Xin-Hui; Andersen, Raymond J

    2005-11-10

    [structure: see text] Laboratory cultures of an undescribed streptomycete obtained from the surface of a British Columbia lichen produce uncialamycin (1), a new enediyne antibiotic. The structure of uncialamycin (1) has been elucidated by analysis of spectroscopic data. Uncialamycin (1) exhibits potent in vitro antibacterial activity against gram-positive and gram-negative human pathogens, including Burkholderia cepacia, a major cause of morbidity and mortality in patients with cystic fibrosis. PMID:16268546

  20. Minocycline: far beyond an antibiotic

    OpenAIRE

    Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

    2013-01-01

    Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic acti...

  1. Metabolic engineering of an industrial polyoxin producer for the targeted overproduction of designer nucleoside antibiotics.

    Science.gov (United States)

    Qi, Jianzhao; Liu, Jin; Wan, Dan; Cai, You-Sheng; Wang, Yinghu; Li, Shunying; Wu, Pan; Feng, Xuan; Qiu, Guofu; Yang, Sheng-Ping; Chen, Wenqing; Deng, Zixin

    2015-09-01

    Polyoxin and nikkomycin are naturally occurring peptidyl nucleoside antibiotics with potent antifungal bioactivity. Both exhibit similar structural features, having a nucleoside skeleton and one or two peptidyl moieties. Combining the refactoring of the polyoxin producer Streptomyces aureochromogenes with import of the hydroxypyridylhomothreonine pathway of nikkomycin allows the targeted production of three designer nucleoside antibiotics designated as nikkoxin E, F, and G. These structures were determined by NMR and/or high resolution mass spectrometry. Remarkably, the introduction of an extra copy of the nikS gene encoding an ATP-dependent ligase significantly enhanced the production of the designer antibiotics. Moreover, all three nikkoxins displayed improved bioactivity against several pathogenic fungi as compared with the naturally-occurring antibiotics. These data provide a feasible model for high efficiency generation of nucleoside antibiotics related to polyoxins and nikkomycins in a polyoxin cell factory via synthetic biology strategy.

  2. A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S.

    Science.gov (United States)

    Shiver, Anthony L; Osadnik, Hendrik; Kritikos, George; Li, Bo; Krogan, Nevan; Typas, Athanasios; Gross, Carol A

    2016-06-01

    Fighting antibiotic resistance requires a deeper understanding of the genetic factors that determine the antibiotic susceptibility of bacteria. Here we describe a chemical-genomic screen in Escherichia coli K-12 that was designed to discover new aspects of antibiotic resistance by focusing on a set of 26 antibiotics and other stresses with poorly characterized mode-of-action and determinants of resistance. We show that the screen identifies new resistance determinants for these antibiotics including a common signature from two antimicrobials, kasugamycin and blasticidin S, used to treat crop diseases like rice blast and fire blight. Following this signature, we further investigated the mechanistic basis for susceptibility to kasugamycin and blasticidin S in E. coli using both genetic and biochemical approaches. We provide evidence that these compounds hijack an overlapping set of peptide ABC-importers to enter the bacterial cell. Loss of uptake may be an underappreciated mechanism for the development of kasugamycin resistance in bacterial plant pathogens. PMID:27355376

  3. A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S.

    Directory of Open Access Journals (Sweden)

    Anthony L Shiver

    2016-06-01

    Full Text Available Fighting antibiotic resistance requires a deeper understanding of the genetic factors that determine the antibiotic susceptibility of bacteria. Here we describe a chemical-genomic screen in Escherichia coli K-12 that was designed to discover new aspects of antibiotic resistance by focusing on a set of 26 antibiotics and other stresses with poorly characterized mode-of-action and determinants of resistance. We show that the screen identifies new resistance determinants for these antibiotics including a common signature from two antimicrobials, kasugamycin and blasticidin S, used to treat crop diseases like rice blast and fire blight. Following this signature, we further investigated the mechanistic basis for susceptibility to kasugamycin and blasticidin S in E. coli using both genetic and biochemical approaches. We provide evidence that these compounds hijack an overlapping set of peptide ABC-importers to enter the bacterial cell. Loss of uptake may be an underappreciated mechanism for the development of kasugamycin resistance in bacterial plant pathogens.

  4. Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung

    Science.gov (United States)

    Jansen, Gunther; Mahrt, Niels; Tueffers, Leif; Barbosa, Camilo; Harjes, Malte; Adolph, Gernot; Friedrichs, Anette; Krenz-Weinreich, Annegret; Rosenstiel, Philip; Schulenburg, Hinrich

    2016-01-01

    Background and objectives: Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung. Methodology: Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci. Result: Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and β-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype. Conclusions and implications: Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. PMID:27193199

  5. Evaluation of the antibiotic properties of glutathione.

    Science.gov (United States)

    Schairer, David O; Chouake, Jason S; Kutner, Allison J; Makdisi, Joy; Nosanchuk, Josh D; Friedman, Adam J

    2013-11-01

    Skin and soft tissue infections (SSTIs) are growing in prevalence in both the outpatient and inpatient settings and are some of the most common diseases seen by dermatologists, who are often the first point of care for these patients. Microbial resistance to antibiotics continues to rise as more virulent strains evolve, and strains predominantly found in the hospital setting are now being seen in the community. Therefore, innovative approaches to combat this trend are needed. Glutathione (GSH) is a well-described and established antioxidant. It participates in detoxification of xenobiotics, regulation of cellular growth, modulation of immune response, and maintenance of the thiol status of proteins and cellular cysteine levels. GSH is also known to have a regulatory effect on immune cells and even inherent antibacterial properties have been reported. To this end, the value of GSH as an antibiotic was evaluated by growing methicillin resistant S. aureus, E. coli, K. pneumoniae and P. aeruginosa strains isolated from human skin and soft tissue infection in the presence of GSH. At a physiologic concentration of 10 mM, GSH had no effect on bacterial growth. At concentrations above 50 mM, which created acidic conditions (pH < 4), bacterial growth was completely inhibited. When adjusted to physiologic pH, GSH exhibited a bacteriostatic effect in a concentration-dependent manner. Additionally, the cytotoxicity of GSH was evaluated in a murine cell line. GSH was relatively non-toxic to murine macrophages, even at the highest concentration tested (160 mM). These results suggest the potential utility of GSH for the prevention and/or as adjunctive treatment of infection, most significantly in disease states associated with GSH deficiency. PMID:24196336

  6. Antibiotics as CECs: An Overview of the Hazards Posed by Antibiotics and Antibiotic Resistance

    OpenAIRE

    Geoffrey Ivan Scott; Porter, Dwayne E.; R. Sean Norman; C. Hart Scott; Miguel Ignacio Uyaguari-Diaz; Keith eMaruya; Steve B. Weisberg; Fulton, Michael H.; Ed F. Wirth; Janet eMooore; Pennington , Paul L.; Daniel eSchlenk; Cobb, George P.; Denslow, Nancy D.

    2016-01-01

    ABSTRACTMonitoring programs have traditionally monitored legacy contaminants but are shifting focus to Contaminants of Emerging Concern (CECs). CECs present many challenges for monitoring and assessment, because measurement methods don't always exist nor have toxicological studies been fully conducted to place results in proper context. Also some CECs affect metabolic pathways to produce adverse outcomes that are not assessed through traditional toxicological evaluations. Antibiotics are CEC...

  7. Antibiotic Modification of Native Grafts: Improving upon nature's scaffolds

    Science.gov (United States)

    Ketonis, Constantinos

    -like cells with no increased toxicity. Furthermore, the antibiotic-modified allograft incorporated well into tibial defects in the rat. Finally, this construct was efficacious in decreasing the severity of infection and host reaction when impacted in an in vivo model of allograft-associated infection. Thus, our proposed modification in surface design serves as a starting point for the development of a new generation of bone grafts that are biologically active at sites of physiological importance.

  8. Antibiotic Susceptibility and Immunomodulatory Potential of Chosen Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    M. Sujatha

    2010-01-01

    Full Text Available Problem statement: Antibiotic susceptibility is still the best way for bacterial pathogen escape mechanism against immunity. Approach: In the present investigation, bacterial pathogens like Staphylococcus aureus, Escherichia coli, Aeromonas hydrophila, Klebsiella and Pseudomonas aeruginosa were used to screen antibiotic susceptibility and immunomodulatory potential. Results: All the test pathogens were sensitive to all the test antibiotics 11±2 mm except penicillin. The conditions for the preparation of antigens of intact natural composition and conformation from pathogens (whole cell and heat killed, were determined using Swiss albino mice (Balb/C as experimental species. Immunomodulatory potential of test pathogens were screened using animal model. Test pathogen decreases the body weight comparing that of normal mice, some notable changes were also noted in activity, growth, water consumption, feed consumption. Antibody titre level in animal serum decreased upto 50% in whole cell pathogen and heat killed pathogen treated animals. Conclusion: The five pathogens administered animals, decrement in B-lymphocyte was much pronounced in Pseudomonas aeruginosa followed by Escherichia coli, Staphylococcus aureus, Klebsiella sp., Aeromonas hydrophila in the 5 week. Pathogen treated mice showed an IgG suppressive effect. It is found to be suppressive to T cell production, so induction in cell mediated immunity has confirmed pathogenic potential of test pathogens. All these test pathogenic strains were remarkably suppressing immune system of pathogen exposed animals.

  9. Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment

    DEFF Research Database (Denmark)

    Pruden, Amy; Larsson, D.G. Joakim; Amézquita, Alejandro;

    2013-01-01

    Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic resistance...... of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little...... associated with antibiotic resistance strongly indicate the need for action....

  10. Antibiotic persistence: the role of spontaneous DNA repair response.

    Science.gov (United States)

    Debbia, E A; Roveta, S; Schito, A M; Gualco, L; Marchese, A

    2001-01-01

    Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics. To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis. To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+. In several cases, the number of colony-forming units decreased below the limit of assay. This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin). The same experiments were repeated using E. coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control. In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control. The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90%. These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3. Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.

  11. Laser based enhancement of susceptibility of bacteria to antibiotic

    Science.gov (United States)

    Reznick, Yana; Banin, Ehud; Lipovsky, Anat; Lubart, Rachel; Zalevsky, Zeev

    2012-03-01

    Our objective is to test the effect of pulsed (Q-switched) and continuous wave (CW) laser light at wavelength of 532nm on the viability of free-living stationary phase bacteria with and without gentamicin (an antibiotic) treatment. Free living stationary phase gram negative bacteria (Pseudomonas aeruginosa strain PAO1) was immersed in Luria Broth (LB) solution and exposed to Q-switched and CW lasers with and without the addition of the antibiotic gentamicin. Cell viability was determined at different time points. Laser treatment alone did not reduce cell viability compared to untreated control and the gentamicin treatment alone only resulted in a 0.5 log reduction in the viable count for P. aeruginosa. The combined laser and gentamicin treatment, however, resulted in a synergistic effect and viability was reduced by 8 log's for P. aeruginosa PAO1.

  12. Affinities and in-plane stress forces between glycopeptide antibiotics and biomimetic bacterial membranes

    Directory of Open Access Journals (Sweden)

    Sisi Bi

    2015-03-01

    Full Text Available Understanding the molecular basis of interactions between antibiotics affecting bacterial cell wall biosynthesis and cellular membranes is important in rational drug design of new drugs to overcome resistance. However, a precise understanding of how bacteriostatic antibiotics effect action often neglects the effect of biophysical forces involved following antibiotic-receptor binding events. We have employed a combination of a label-free binding biosensor (surface plasmon resonance, SPR and a force biosensor (in-plane stress cantilever, together with model membrane systems to study the complex interplay between glycopeptide antibiotics, their cognate ligands and different model membranes. Bacterial cell wall precursor analogue N-α-Docosanoyl-ε-acetyl-Lys-d-Alanine-d-Alanine (doc-KAA was inserted into lipid layers comprised of zwitterionic or anionic lipids then exposed to either vancomycin or the membrane-anchored glycopeptide antibiotic teicoplanin. Binding affinities and kinetics of the antibiotics to these model membranes were influenced by electrostatic interactions with the different lipid backgrounds, in addition to ligand affinities. In addition, cantilever sensors coated with model membranes showed that planar surface stress changes were induced by glycopeptide antibiotics adsorption and caused compressive surface stress generation in a ligand-dependent manner.

  13. Allantoin catabolism influences the production of antibiotics in Streptomyces coelicolor.

    Science.gov (United States)

    Navone, Laura; Casati, Paula; Licona-Cassani, Cuauhtémoc; Marcellin, Esteban; Nielsen, Lars K; Rodriguez, Eduardo; Gramajo, Hugo

    2014-01-01

    Purines are a primary source of carbon and nitrogen in soil; however, their metabolism is poorly understood in Streptomyces. Using a combination of proteomics, metabolomics, and metabolic engineering, we characterized the allantoin pathway in Streptomyces coelicolor. When cells grew in glucose minimal medium with allantoin as the sole nitrogen source, quantitative proteomics identified 38 enzymes upregulated and 28 downregulated. This allowed identifying six new functional enzymes involved in allantoin metabolism in S. coelicolor. From those, using a combination of biochemical and genetic engineering tools, it was found that allantoinase (EC 3.5.2.5) and allantoicase (EC 3.5.3.4) are essential for allantoin metabolism in S. coelicolor. Metabolomics showed that under these growth conditions, there is a significant intracellular accumulation of urea and amino acids, which eventually results in urea and ammonium release into the culture medium. Antibiotic production of a urease mutant strain showed that the catabolism of allantoin, and the subsequent release of ammonium, inhibits antibiotic production. These observations link the antibiotic production impairment with an imbalance in nitrogen metabolism and provide the first evidence of an interaction between purine metabolism and antibiotic biosynthesis.

  14. Influence of antibiotics on indirect organogenesis of Teak

    Directory of Open Access Journals (Sweden)

    Evandro Vagner Tambarussi

    2015-04-01

    Full Text Available Agrobacterium is the largest method employed to transform woody plants. The bacterium is required to introduce the transgene into the plant nuclear genome. After transferring T-DNA to the plant cell, the bacteria affect plant growth negatively and have to be eliminated from plant tissue culture medium through the use of antibiotics. The effect of different antibiotics (timentin, cefotaxime and carbenicillin on in vitro shoot regeneration of teak (Tectona grandis L. f. was compared in hypocotyl, mature cotyledon and cotyledonary segments explants. Timentin and cefotaxime (100-300 mg l-1 did not affect shoot regeneration and the number of shoots per explant. Moreover, at these concentrations, the two antibiotics seem to stimulate shoot regeneration. Carbenicillin at a dosage of 300 mg l-1 as well as cefotaxime and timentin at a dosage of 500 mg l-1 induced abundant calli formation and inhibited regeneration. Our data show that cefotaxime and timentin (300 mg l-1 can be harmless to teak regeneration and can be used as bactericide agents during Agrobacterium-mediated transformation of Tectona grandis. Furthermore, we discuss the effect of antibiotic degradation on plant morphogenesis and its effect on regeneration from different explants.

  15. Partial recovery of microbiomes after antibiotic treatment.

    Science.gov (United States)

    Raymond, Frédéric; Déraspe, Maxime; Boissinot, Maurice; Bergeron, Michel G; Corbeil, Jacques

    2016-09-01

    Antibiotics profoundly affect the gut microbiome and modulate microbial communities. We recently observed that antimicrobial drugs also impact the abundance and distribution of antibiotic resistance genes. In this addendum, we reanalyze our ∼1 trillion nucleotide shotgun metagenomic dataset to quantify comprehensive genomic differences at the sequence level before and after antibiotic treatment. We show that 7 day exposure to cefprozil leads to a statistically significant loss of metagenome sequences. Recovery of gut microbiomes 3 months after antibiotherapy was characterized by the emergence of new genome sequences not observed prior to antibiotic exposure. Participants with low initial gut microbiome diversity had an increased amount of sequences related to antibiotic resistance. Therefore, we suggest that while the taxonomical composition of microbiomes is partially affected by the antibiotic, the genomic content and population structure of bacterial communities is noticeably impacted. PMID:27494088

  16. Response to "Antibiotic Use and Resistance"

    DEFF Research Database (Denmark)

    Malo, Sara; Rabanaque, María José; Feja, Christina;

    2014-01-01

    As mentioned, antibiotic consumption in heavy users, especially in children, is really striking. Certainly, our results revealed an antibiotic use in this age group higher than published in previous studies, and in line with different reports repeatedly presenting the high antibiotic consumption...... existing in Spain compared with other European countries (1). Determinants involved in antibiotic prescribing are numerous and varied. It is true that therapeutic failures lead to repeated courses of antibiotic treatment. However, it is not probably the only reason. Frequent and high consumption...... of antibiotics, as observed in heavy users, could also be due to factors related to the GP, patient and parents' expectations or the influence exerted by the pharmaceutical industry (2). This article is protected by copyright. All rights reserved....

  17. Factors Affecting the Cost Effectiveness of Antibiotics

    Directory of Open Access Journals (Sweden)

    Steven Simoens

    2011-01-01

    Full Text Available In an era of spiraling health care costs and limited resources, policy makers and health care payers are concerned about the cost effectiveness of antibiotics. The aim of this study is to draw on published economic evaluations with a view to identify and illustrate the factors affecting the cost effectiveness of antibiotic treatment of bacterial infections. The findings indicate that the cost effectiveness of antibiotics is influenced by factors relating to the characteristics and the use of antibiotics (i.e., diagnosis, comparative costs and comparative effectiveness, resistance, patient compliance with treatment, and treatment failure and by external factors (i.e., funding source, clinical pharmacy interventions, and guideline implementation interventions. Physicians need to take into account these factors when prescribing an antibiotic and assess whether a specific antibiotic treatment adds sufficient value to justify its costs.

  18. Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.

    Science.gov (United States)

    Arenz, Stefan; Wilson, Daniel N

    2016-01-01

    Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes. Recent structural studies have characterized a number of antibiotics discovered decades ago that have unique chemical scaffolds and/or utilize novel modes of action to interact with the ribosome and inhibit translation. Additionally, structures of eukaryotic cytoplasmic and mitochondrial ribosomes have provided further structural insight into the basis for specificity and toxicity of antibiotics. Together with our increased understanding of bacterial resistance mechanisms, revisiting our treasure trove of "forgotten" antibiotics could pave the way for the next generation of antimicrobial agents.

  19. Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.

    Science.gov (United States)

    Arenz, Stefan; Wilson, Daniel N

    2016-01-01

    Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes. Recent structural studies have characterized a number of antibiotics discovered decades ago that have unique chemical scaffolds and/or utilize novel modes of action to interact with the ribosome and inhibit translation. Additionally, structures of eukaryotic cytoplasmic and mitochondrial ribosomes have provided further structural insight into the basis for specificity and toxicity of antibiotics. Together with our increased understanding of bacterial resistance mechanisms, revisiting our treasure trove of "forgotten" antibiotics could pave the way for the next generation of antimicrobial agents. PMID:26585390

  20. Antibiotic Resistance in Childhood with Pneumococcal Infection

    OpenAIRE

    Ali Gunes

    2013-01-01

    Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with me...

  1. Superbugs and antibiotics in the newborn

    OpenAIRE

    Alessandro Borghesi; Mauro Stronati

    2015-01-01

    Antibiotic resistance has become an urgent and global issue, with 700,000 deaths attributable to multidrug-resistance occurring each year worldwide. The overuse of antibiotics, both in animal industry and in clinical settings, and the generated selective pressure, are the main factors implicated in the emergence of resistant strains. The Centers for Disease Control and Prevention (CDC) have pointed out that more than half of hospital patients receive an antibiotic during their stay, and nearl...

  2. Coping with antibiotic resistance: contributions from genomics

    OpenAIRE

    Rossolini, Gian Maria; Thaller, Maria Cristina

    2010-01-01

    Antibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will further current knowledge on antibiotic resistance and help to tackle the problem. Bacterial genomics and transcriptomics can inf...

  3. Antibiotic resistance - the interplay between antibiotic use in animals and human beings

    DEFF Research Database (Denmark)

    Singer, R.S.; Finch, R.; Wegener, Henrik Caspar;

    2003-01-01

    Antibiotic-resistant bacteria were first identified in the 1940s, but while new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. Today, the excessive use of antibiotics compounded by the paucity of new agents on the market has...... meant the problem of antibiotic resistance is fast escalating into a global health crisis. There is no doubt that misuse of these drugs in human beings has contributed to the increasing rates of resistance, but recently the use of antibiotics in food animals and its consequent effect on resistance...... of antibiotics in animals-whether therapeutic or as growth promoters-pales by comparison with human use, and that efforts should be concentrated on the misuse of antibiotics in people. Others warn of the dangers of unregulated and unnecessary use of antibiotics, especially growth promoters in animal husbandry...

  4. Antibiotic research and development: business as usual?

    Science.gov (United States)

    Harbarth, S; Theuretzbacher, U; Hackett, J

    2015-01-01

    The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public-private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents. PMID:25673635

  5. Antibiotic treatments and microbes in the gut.

    Science.gov (United States)

    Macfarlane, Sandra

    2014-04-01

    Antibiotic therapies are important in combating disease-causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi-drug-resistant disease-causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long-term antibiotic-associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.

  6. Design of dual action antibiotics as an approach to search for new promising drugs

    International Nuclear Information System (INIS)

    The review is devoted to the latest achievements in the design of dual action antibiotics — heterodimeric (chimeric) structures based on antibacterial agents of different classes (fluoroquinolones, anthracyclines, oxazolidines, macrolides and so on). Covalent binding can make the pharmacokinetic characteristics of these molecules more predictable and improve the penetration of each component into the cell. Consequently, not only does the drug efficacy increase owing to inhibition of two targets but also the resistance to one or both antibiotics can be overcome. The theoretical grounds of elaboration, design principles and methods for the synthesis of dual action antibiotics are considered. The structures are classified according to the type of covalent spacer (cleavable or not) connecting the moieties of two agents. Dual action antibiotics with a spacer that can be cleaved in a living cell are considered as dual action prodrugs. Data on the biological action of heterodimeric compounds are presented and structure–activity relationships are analyzed. The bibliography includes 225 references

  7. Design of dual action antibiotics as an approach to search for new promising drugs

    Science.gov (United States)

    Tevyashova, A. N.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2015-01-01

    The review is devoted to the latest achievements in the design of dual action antibiotics — heterodimeric (chimeric) structures based on antibacterial agents of different classes (fluoroquinolones, anthracyclines, oxazolidines, macrolides and so on). Covalent binding can make the pharmacokinetic characteristics of these molecules more predictable and improve the penetration of each component into the cell. Consequently, not only does the drug efficacy increase owing to inhibition of two targets but also the resistance to one or both antibiotics can be overcome. The theoretical grounds of elaboration, design principles and methods for the synthesis of dual action antibiotics are considered. The structures are classified according to the type of covalent spacer (cleavable or not) connecting the moieties of two agents. Dual action antibiotics with a spacer that can be cleaved in a living cell are considered as dual action prodrugs. Data on the biological action of heterodimeric compounds are presented and structure-activity relationships are analyzed. The bibliography includes 225 references.

  8. Where antibiotic resistance mutations meet quorum-sensing

    Directory of Open Access Journals (Sweden)

    Rok Krašovec

    2014-06-01

    Full Text Available We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014, 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress. Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1. Why this novel density-dependent ‘mutation rate plasticity’ (DD-MRP occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.

  9. Deliberations on the impact of antibiotic contamination on dissemination of antibiotic resistance genes in aquatic environments

    OpenAIRE

    Berglund, Björn

    2014-01-01

    The great success of antibiotics in treating bacterial infectious diseases has been hampered by the increasing prevalence of antibiotic resistant bacteria. Not only does antibiotic resistance threaten to increase the difficulty in treating bacterial infectious diseases, but it could also make medical procedures such as routine surgery and organ transplantations very dangerous to perform. Traditionally, antibiotic resistance has been regarded as a strictly clinical problem and studies of the p...

  10. [Health economics and antibiotic therapy].

    Science.gov (United States)

    Leclercq, P; Bigdéli, M

    1995-01-01

    In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation. An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria. The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician. PMID:7481251

  11. Molecular modelling of betalactamic antibiotic

    Directory of Open Access Journals (Sweden)

    Elso Manuel Cruz Cruz

    2010-02-01

    Full Text Available Background: The antibacterial properties of a compound are the result of its molecular structure. To establish the structural and electronic characteristics makes possible to understand the mechanisms of its action and becomes paramount for the rational design new drugs. Objective: To model some of the molecular properties of betalactamic antibiotics and inhibitors of the betalactamases and to relate them with their pharmacological actions. Method: The molecular structures were optimized with PM3• semiempiric calculus. The structure of the betalactamic ring in the different compounds was compared. The molecular properties were calculated according to the Density Functional Theory at a B3LYP/6-31G(d level. The density of the atomic charges and the frontier orbitals were analyzed. Results There are variations in the calculated properties that make possible to define two groups of compounds: one for the monobactams and the inhibitors of the betalactamases, with less planarity in the ring and less reactivity and another one with the penicillins, cephalosporins and carbapenems, planer, more structurally stable and reactive. Conclusions: The modelled molecular properties of the betalactamic antibiotics and inhibitors of the betalactamases show agreement with its pharmacological action.

  12. Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection.

    OpenAIRE

    Oh, Y. K.; Nix, D E; Straubinger, R M

    1995-01-01

    Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial system. Current therapy is not highly effective. Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more efficiently to M. avium-infected cells. We investigated the formulation of the antibiotics ciprofloxacin and azithromycin in liposomes and tested their antibacterial activities in vitro against M. a...

  13. Analytical strategy for the detection of antibiotic residues in milk from small ruminants

    OpenAIRE

    Beltrán Martínez, Mª Carmen

    2015-01-01

    In Mediterranean countries, sheep and goat’s milk production has traditionally been destined for the manufacture of cheese, often as raw milk. Cheese quality is closely related to milk composition but also to hygienic aspects such as somatic cell count, bacteriology or presence of antibiotic residues, currently regulated by European legislation. The implications of the presence of antibiotic residues in milk as a result of veterinary treatments include negative effects on consumer’s health...

  14. Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

    OpenAIRE

    Ndieyira, J. W.; Watari, M.; Barrera, A. Donoso; Zhou, D; Vögtli, M; Batchelor, M.; Cooper, M. A.; Strunz, T; Horton, M. A.; Abell, C; Rayment, T.; Aeppli, G.; McKendry, R. A.

    2008-01-01

    The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements...

  15. Bacteriophages as potential treatment option for antibiotic resistant bacteria.

    Science.gov (United States)

    Bragg, Robert; van der Westhuizen, Wouter; Lee, Ji-Yun; Coetsee, Elke; Boucher, Charlotte

    2014-01-01

    The world is facing an ever-increasing problem with antibiotic resistant bacteria and we are rapidly heading for a post-antibiotic era. There is an urgent need to investigate alterative treatment options while there are still a few antibiotics left. Bacteriophages are viruses that specifically target bacteria. Before the development of antibiotics, some efforts were made to use bacteriophages as a treatment option, but most of this research stopped soon after the discovery of antibiotics. There are two different replication options which bacteriophages employ. These are the lytic and lysogenic life cycles. Both these life cycles have potential as treatment options. There are various advantages and disadvantages to the use of bacteriophages as treatment options. The main advantage is the specificity of bacteriophages and treatments can be designed to specifically target pathogenic bacteria while not negatively affecting the normal microbiota. There are various advantages to this. However, the high level of specificity also creates potential problems, the main being the requirement of highly specific diagnostic procedures. Another potential problem with phage therapy includes the development of immunity and limitations with the registration of phage therapy options. The latter is driving research toward the expression of phage genes which break the bacterial cell wall, which could then be used as a treatment option. Various aspects of phage therapy have been investigated in studies undertaken by our research group. We have investigated specificity of phages to various avian pathogenic E. coli isolates. Furthermore, the exciting NanoSAM technology has been employed to investigate bacteriophage replication and aspects of this will be discussed.

  16. Bacteriophages as potential treatment option for antibiotic resistant bacteria.

    Science.gov (United States)

    Bragg, Robert; van der Westhuizen, Wouter; Lee, Ji-Yun; Coetsee, Elke; Boucher, Charlotte

    2014-01-01

    The world is facing an ever-increasing problem with antibiotic resistant bacteria and we are rapidly heading for a post-antibiotic era. There is an urgent need to investigate alterative treatment options while there are still a few antibiotics left. Bacteriophages are viruses that specifically target bacteria. Before the development of antibiotics, some efforts were made to use bacteriophages as a treatment option, but most of this research stopped soon after the discovery of antibiotics. There are two different replication options which bacteriophages employ. These are the lytic and lysogenic life cycles. Both these life cycles have potential as treatment options. There are various advantages and disadvantages to the use of bacteriophages as treatment options. The main advantage is the specificity of bacteriophages and treatments can be designed to specifically target pathogenic bacteria while not negatively affecting the normal microbiota. There are various advantages to this. However, the high level of specificity also creates potential problems, the main being the requirement of highly specific diagnostic procedures. Another potential problem with phage therapy includes the development of immunity and limitations with the registration of phage therapy options. The latter is driving research toward the expression of phage genes which break the bacterial cell wall, which could then be used as a treatment option. Various aspects of phage therapy have been investigated in studies undertaken by our research group. We have investigated specificity of phages to various avian pathogenic E. coli isolates. Furthermore, the exciting NanoSAM technology has been employed to investigate bacteriophage replication and aspects of this will be discussed. PMID:24619620

  17. Superbugs and antibiotics in the newborn

    Directory of Open Access Journals (Sweden)

    Alessandro Borghesi

    2015-10-01

    Full Text Available Antibiotic resistance has become an urgent and global issue, with 700,000 deaths attributable to multidrug-resistance occurring each year worldwide. The overuse of antibiotics, both in animal industry and in clinical settings, and the generated selective pressure, are the main factors implicated in the emergence of resistant strains. The Centers for Disease Control and Prevention (CDC have pointed out that more than half of hospital patients receive an antibiotic during their stay, and nearly a third receive a broad-spectrum antibiotic. In neonatal units, previous antibiotic exposure to third-generation cephalosporin and carbapenem were identified as independent risk factors for infection caused by multi-drug resistant strains. While resistant ‘superbugs’ emerge, the arsenal to fight these microorganisms is progressively shrinking, as the number of newly discovered antibiotics approved by the Food and Drug administration each year is dropping. In face of global spread of antibiotic resistance and of the limited development of new drugs, policies and rules are under study by agencies (CDC, World Health Organization and governments, in order to: i facilitate and foster the discovery of new antibiotic compounds; ii develop new, alternative therapies able to potentiate or modulate the host immune response or to abrogate the resistance and virulence factors in the microorganisms; and iii prevent the emergence of resistance through antibiotic stewardship programs, educational programs, and reduction of antibiotic use in livestock; the field of neonatal medicine will need its own, newborn-tailored, antibiotic stewardship programs to be implemented in the NICUs. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai

  18. Optimizing antibiotic selection in treating COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  19. Cell surface hydrophobicity and adherence of a strain of group B streptococci during the post-antibiotic effect of penicillin Hidrofobicidade de superfície celular e aderência de uma estirpe de estreptococos do grupo B durante o efeito pós-antibiótico da penicilina

    Directory of Open Access Journals (Sweden)

    Ângela Maria Mendes Araújo

    2008-08-01

    Full Text Available The minimum inhibitory concentration and post-antibiotic effects of an antimicrobial agent are parameters to be taken into consideration when determining its dosage schedules. The in vitro post-antibiotic effects on cell surface hydrophobicity and bacterial adherence were examined in one strain of group B streptococci. Exposure of the microorganism for 2 h at 37 °C to 1 x MIC of penicillin induced a PAE of 1.1 h. The cell surface charge of the Streptococcus was altered significantly during the post-antibiotic phase as shown by its ability to bind to xylene: hydrophobicity was decreased. Bacterial adherence to human buccal epithelial cells was also reduced. The results of the present investigation indicate that studies designed to determine therapeutic regimens should evaluate the clinical significance of aspects of bacterial physiology during the post-antibiotic period.A concentração mínima inibitória e os efeitos pós-antibióticos (EPA de um agente antimicrobiano são parâmetros que devem ser levados em consideração quando da determinação do esquema de dosagem. Os efeitos pós-antibióticos in vitro na hidrofobicidade de superfície celular e na aderência foram pesquisados em uma amostra de estreptococos do grupo B. A exposição do microrganismo por 2 h a 37 °C a 1 x CMI de penicilina induziu um EPA de 1,1 h. A carga da superfície celular da bactéria foi alterada significativamente durante a fase pós-antibiótica revelada através da capacidade de ligação ao xileno, indicada pela diminuição da hidrofobicidade. A aderência bacteriana às células epiteliais bucais humanas também foi reduzida. Os resultados da investigação demonstram que estudos clínicos destinados a determinar regimes terapêuticos deveriam incluir o conhecimento da fisiologia bacteriana durante o período pós-antibiótico.

  20. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.

    Science.gov (United States)

    Pienaar, Elsje; Cilfone, Nicholas A; Lin, Philana Ling; Dartois, Véronique; Mattila, Joshua T; Butler, J Russell; Flynn, JoAnne L; Kirschner, Denise E; Linderman, Jennifer J

    2015-02-21

    While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome.

  1. An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance.

    Science.gov (United States)

    Abed, Nadia; Saïd-Hassane, Fatouma; Zouhiri, Fatima; Mougin, Julie; Nicolas, Valérie; Desmaële, Didier; Gref, Ruxandra; Couvreur, Patrick

    2015-01-01

    The "Golden era" of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of two natural terpenes (farnesyl and geranyl) to design nanodevices for an efficient intracellular delivery of penicillin G. The covalent linkage between the terpene moieties and the antibiotic leads to formation of prodrugs that self-assemble to form nanoparticles with a high drug payload between 55-63%. Futhermore, the addition of an environmentally-sensitive bond between the antibiotic and the terpene led to an efficient antibacterial activity against the intracellular pathogen Staphylococcus aureus with reduced intracellular replication of about 99.9% compared to untreated infected cells. Using HPLC analysis, we demonstrated and quantified the intracellular release of PenG when this sensitive-bond (SB) was present on the prodrug, showing the success of this technology to deliver antibiotics directly into cells.

  2. Studies on the purification, characterization and structure of antibiotics from centipede using RI labelled compound

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Key Seung; Lee, Sang Min; Choi, Jin Sung; Hong, Sa Weon [Hanyang University, Seoul (Korea, Republic of)

    1997-07-01

    The substance which has antibiotic properties was extracted by diethyl ether and purified from a centipede S. subspinipes by the silicic acid and high S column chromatography. This antibiotics named {sup C}entipedin{sup h}as exhibited a significant antibiotic activity against a variety of microorganism, such as Gram{sup +}, Gram{sup -}, fungi etc. In connection with the antibiotic property, it was confirmed that its inhibitory effect on the growth of Staphylococcus aureus was related with the transcriptional level of DNA and RNA polymerase. The centipedin was measured quantitatively by GC methods and molecular weight was confirmed as 162 Da by mass-spec. Also, molecular formular was identified to C{sub 9}O{sub 3}H{sub 6} by the method of UV, IR and NMR. Antibiotics from centipede did not exhibit any significant cytotoxicity against cancer cell lines, such as HL-60 cell and myeloma cell. It was confirmed that centipedin antibiotics was biosynthesized from {sup 14}C-acetate in vivo experiment. 12 refs., 23 figs. (author)

  3. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use.

    Science.gov (United States)

    Del Rosso, James Q; Webster, Guy F; Rosen, Ted; Thiboutot, Diane; Leyden, James J; Gallo, Richard; Walker, Clay; Zhanel, George; Eichenfield, Lawrence

    2016-04-01

    Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology. PMID:27462384

  4. Topical and oral antibiotics for acne vulgaris.

    Science.gov (United States)

    Del Rosso, James Q

    2016-06-01

    Antibiotics, both oral and topical, have been an integral component of the management of acne vulgaris (AV) for approximately 6 decades. Originally thought to be effective for AV due to their ability to inhibit proliferation of Propionibacterium acnes, it is now believed that at least some antibiotics also exert anti-inflammatory effects that provide additional therapeutic benefit. To add, an increase in strains of P acnes and other exposed bacteria that are less sensitive to antibiotics used to treat AV have emerged, with resistance directly correlated geographically with the magnitude of antibiotic use. Although antibiotics still remain part of the therapeutic armamentarium for AV treatment, current recommendations support the following when used to treat AV: 1) monotherapy use should be avoided; 2) use benzoyl peroxide concomitantly to reduce emergence of resistant P acnes strains; 3) oral antibiotics should be used in combination with a topical regimen for moderate-to-severe inflammatory AV; and 4) use oral antibiotics over a limited duration to achieve control of inflammatory AV with an exit plan in place to discontinue their use as soon as possible. When selecting an oral antibiotic to treat AV, potential adverse effects are important to consider. PMID:27416309

  5. [Modification of antibiotic resistance in microbial symbiosis].

    Science.gov (United States)

    Aznabaeva, L M; Usviatsov, B Ia; Bukharin, O V

    2010-01-01

    In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554). PMID:21033469

  6. Antibiotics: Pharmacists Can Make the Difference

    Centers for Disease Control (CDC) Podcasts

    2015-04-16

    In this podcast, a pharmacist counsels a frustrated father about appropriate antibiotic use and symptomatic relief options for his son's cold.  Created: 4/16/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  7. Antibiotic RX in Hospitals: Proceed with Caution

    Centers for Disease Control (CDC) Podcasts

    2014-03-04

    This podcast is based on the March 2014 CDC Vital Signs report. Antibiotics save lives, but poor prescribing practices can put patients at risk for health problems. Learn how to protect patients by protecting antibiotics.  Created: 3/4/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/4/2014.

  8. Analysis of antibiotic consumption in burn patients.

    Science.gov (United States)

    Soleymanzadeh-Moghadam, Somayeh; Azimi, Leila; Amani, Laleh; Rastegar Lari, Aida; Alinejad, Faranak; Rastegar Lari, Abdolaziz

    2015-01-01

    Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used. The results indicated that P. aeruginosa is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR) microorganisms, but it can also decrease the cost of treatment. PMID:26124986

  9. Topical and oral antibiotics for acne vulgaris.

    Science.gov (United States)

    Del Rosso, James Q

    2016-06-01

    Antibiotics, both oral and topical, have been an integral component of the management of acne vulgaris (AV) for approximately 6 decades. Originally thought to be effective for AV due to their ability to inhibit proliferation of Propionibacterium acnes, it is now believed that at least some antibiotics also exert anti-inflammatory effects that provide additional therapeutic benefit. To add, an increase in strains of P acnes and other exposed bacteria that are less sensitive to antibiotics used to treat AV have emerged, with resistance directly correlated geographically with the magnitude of antibiotic use. Although antibiotics still remain part of the therapeutic armamentarium for AV treatment, current recommendations support the following when used to treat AV: 1) monotherapy use should be avoided; 2) use benzoyl peroxide concomitantly to reduce emergence of resistant P acnes strains; 3) oral antibiotics should be used in combination with a topical regimen for moderate-to-severe inflammatory AV; and 4) use oral antibiotics over a limited duration to achieve control of inflammatory AV with an exit plan in place to discontinue their use as soon as possible. When selecting an oral antibiotic to treat AV, potential adverse effects are important to consider.

  10. Antibiotic resistance: a physicist’s view

    Science.gov (United States)

    Allen, Rosalind; Waclaw, Bartłomiej

    2016-08-01

    The problem of antibiotic resistance poses challenges across many disciplines. One such challenge is to understand the fundamental science of how antibiotics work, and how resistance to them can emerge. This is an area where physicists can make important contributions. Here, we highlight cases where this is already happening, and suggest directions for further physics involvement in antimicrobial research.

  11. Antibiotic information application offers nurses quick support

    NARCIS (Netherlands)

    Wentzel, Jobke; Drie-Pierik, Regine; Nijdam, Lars; Geesing, Jos; Sanderman, Robbert; Gemert-Pijnen, van Julia E.W.C.

    2016-01-01

    Background Nurses can be crucial contributors to antibiotic stewardship programs (ASPs), interventions aimed at improving antibiotic use, but nurse empowerment in ASPs adds to their job complexity. Nurses work in complex settings with high cognitive loads, which ask for easily accessible information

  12. Antibiotic information application offers nurses quick support

    NARCIS (Netherlands)

    Wentzel, Jobke; van Drie-Pierik, Regine; Nijdam, Lars; Geesing, Jos; Sanderman, Robbert; van Gemert-Pijnen, Julia E. W. C.

    2016-01-01

    Background: Nurses can be crucial contributors to antibiotic stewardship programs (ASPs), interventions aimed at improving antibiotic use, but nurse empowerment in ASPs adds to their job complexity. Nurses work in complex settings with high cognitive loads, which ask for easily accessible informatio

  13. Antibiotic prophylaxis in craniotomy : a review

    NARCIS (Netherlands)

    Liu, Weiming; Ni, Ming; Zhang, Yuewei; Groen, Rob J. M.

    2014-01-01

    The effectiveness of antibiotic prophylaxis (AP) in craniotomies has been clarified through the accumulation of evidence and increased antibiotic knowledge. This paper focuses on the use of AP in craniotomies during different historical periods and collects highly relevant evidence on this issue. Th

  14. Antibiotic research and development: business as usual?

    NARCIS (Netherlands)

    Harbarth, S.; Theuretzbacher, U.; Hackett, J.; Hulscher, M.

    2015-01-01

    The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is

  15. Snort Sniffle Sneeze: No Antibiotics Please

    Centers for Disease Control (CDC) Podcasts

    2009-09-29

    Antibiotics aren't always the answer for sneezes or sore throats. This podcast discusses ways to feel better without antibiotics.  Created: 9/29/2009 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2009.

  16. Genetic architecture of intrinsic antibiotic susceptibility.

    Directory of Open Access Journals (Sweden)

    Hany S Girgis

    Full Text Available BACKGROUND: Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. METHODOLOGY/PRINCIPAL FINDINGS: To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. CONCLUSIONS/SIGNIFICANCE: Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

  17. Analysis of antibiotic consumption in burn patients

    Directory of Open Access Journals (Sweden)

    Soleymanzadeh-Moghadam, Somayeh

    2015-06-01

    Full Text Available Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of and were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used.The results indicated that is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR microorganisms, but it can also decrease the cost of treatment.

  18. Transport and transformation of genetic information in the critical zone: The case of antibiotic resistance genes

    Science.gov (United States)

    Zhu, Y. G.

    2015-12-01

    In addition to material and energy flows, the dynamics and functions of the Earth's critical zone are intensively mediated by biological actions performed by diverse organisms. These biological actions are modulated by the expression of functional genes and their translation into enzymes that catalyze geochemical reactions, such as nutrient turnover and pollutant biodegradation. Although geobiology, as an interdisciplinary research area, is playing and vital role in linking biological and geochemical processes at different temporal and spatial scales, the distribution and transport of functional genes have rarely been investigated from the Earth's critical zone perspectives. To illustrate the framework of studies on the transport and transformation of genetic information in the critical zone, antibiotic resistance is taken as an example. Antibiotic resistance genes are considered as a group of emerging contaminants, and their emergence and spread within the critical zone on one hand are induced by anthropogenic activities, and on other hand are threatening human health worldwide. The transport and transformation of antibiotic resistance genes are controlled by both horizontal gene transfer between bacterial cells and the movement of bacteria harboring antibiotic resistance genes. In this paper, the fate and behavior of antibiotic resistance genes will be discussed in the following aspects: 1) general overview of environmental antibiotic resistance; 2) high through quantification of the resistome in various environmental media; 3) pathways of resistance gene flow within the critical zone; and 4) potential strategies in mitigating antibiotic resistance, particularly from the critical zone perspectives.

  19. A novel approach for assessing the susceptibility of Escherichia coli to antibiotics

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The dynamic growth process of Escherichia coli CVCC249 under different concentrations of antibiotics was analyzed. The results suggested that the main reason that definitive results cannot be obtained by antibiotic susceptibility testing (AST) is that the ratio of drug concentration to the population of bacteria and the combined effect of drug concentration and action time cannot be completely determined with the methods used. Based on the analysis of the growth process with a series of concentrations of gentamicin acting for a certain time, and according to the forward difference method, a novel method for AST was proposed. The net increase in turbidity of the bacterial population was used to eliminate the existing effects of resting cells, and then the recurrent coefficient for a growing sequence was used to characterize the effect of antibiotics on bacterial division, and the contour plot was used to display and analyze the combined effect of drug concentration and action time. The inhibition rate of the antibiotics can be characterized as the dynamic change in the composite function of the antibiotic concentration and action time, which indicated that the inhibition rate was dependent on the combined effect of time and concentration of antibiotics. The effectiveness of this new method has been verified with different kinds of antibiotics, such as enrofloxacin, levofloxacin, and ceftriaxone, having different antibacterial mechanisms.

  20. A role for the bacterial GATC methylome in antibiotic stress survival.

    Science.gov (United States)

    Cohen, Nadia R; Ross, Christian A; Jain, Saloni; Shapiro, Rebecca S; Gutierrez, Arnaud; Belenky, Peter; Li, Hu; Collins, James J

    2016-05-01

    Antibiotic resistance is an increasingly serious public health threat. Understanding pathways allowing bacteria to survive antibiotic stress may unveil new therapeutic targets. We explore the role of the bacterial epigenome in antibiotic stress survival using classical genetic tools and single-molecule real-time sequencing to characterize genomic methylation kinetics. We find that Escherichia coli survival under antibiotic pressure is severely compromised without adenine methylation at GATC sites. Although the adenine methylome remains stable during drug stress, without GATC methylation, methyl-dependent mismatch repair (MMR) is deleterious and, fueled by the drug-induced error-prone polymerase Pol IV, overwhelms cells with toxic DNA breaks. In multiple E. coli strains, including pathogenic and drug-resistant clinical isolates, DNA adenine methyltransferase deficiency potentiates antibiotics from the β-lactam and quinolone classes. This work indicates that the GATC methylome provides structural support for bacterial survival during antibiotic stress and suggests targeting bacterial DNA methylation as a viable approach to enhancing antibiotic activity. PMID:26998690

  1. Penetration barrier contributes to bacterial biofilm-associated resistance against only select antibiotics, and exhibits genus-, strain- and antibiotic-specific differences.

    Science.gov (United States)

    Singh, Rachna; Sahore, Simmi; Kaur, Preetinder; Rani, Alka; Ray, Pallab

    2016-08-01

    Bacterial biofilms are implicated in a wide range of implant-based and chronic infections. These infections are often associated with adverse therapeutic outcomes, owing to the decreased antibiotic susceptibility of biofilms compared with their planktonic counterparts. This altered biofilm susceptibility has been attributed to multiple factors, including a reduced antibiotic penetration. Although several studies have addressed the role of penetration barrier in biofilm-associated drug resistance, it remains inconclusive. This study was done to elucidate antibiotic penetration through biofilms formed by Staphylococcus aureus, S. epidermidis, Escherichia coli and Klebsiella pneumoniae, using an agar disk diffusion assay. Penetration capacity of six antimicrobial drugs from different classes (β-lactams, aminoglycosides, tetracyclines, phenicols, fluoroquinolones and glycopeptides) through biofilms formed by standard strains and clinical isolates from catheter-related bloodstream infections (CRBSI) was elucidated by measuring their growth-inhibition zones in lawn cultures on Mueller-Hinton agar, following diffusion of an antibiotic from an overlying disk through their biofilm to the agar medium. Penetration of only select antimicrobials (vancomycin and chloramphenicol) was hindered through biofilms. There was considerable variation in biofilm-permeating capacity depending upon the genus, strain/CRBSI isolate and antibiotic tested. Furthermore, antibiotics failed to kill the biofilm cells independent of penetration, indicating that other factors contributed substantially to biofilm resistance. PMID:27402781

  2. Penetration barrier contributes to bacterial biofilm-associated resistance against only select antibiotics, and exhibits genus-, strain- and antibiotic-specific differences.

    Science.gov (United States)

    Singh, Rachna; Sahore, Simmi; Kaur, Preetinder; Rani, Alka; Ray, Pallab

    2016-08-01

    Bacterial biofilms are implicated in a wide range of implant-based and chronic infections. These infections are often associated with adverse therapeutic outcomes, owing to the decreased antibiotic susceptibility of biofilms compared with their planktonic counterparts. This altered biofilm susceptibility has been attributed to multiple factors, including a reduced antibiotic penetration. Although several studies have addressed the role of penetration barrier in biofilm-associated drug resistance, it remains inconclusive. This study was done to elucidate antibiotic penetration through biofilms formed by Staphylococcus aureus, S. epidermidis, Escherichia coli and Klebsiella pneumoniae, using an agar disk diffusion assay. Penetration capacity of six antimicrobial drugs from different classes (β-lactams, aminoglycosides, tetracyclines, phenicols, fluoroquinolones and glycopeptides) through biofilms formed by standard strains and clinical isolates from catheter-related bloodstream infections (CRBSI) was elucidated by measuring their growth-inhibition zones in lawn cultures on Mueller-Hinton agar, following diffusion of an antibiotic from an overlying disk through their biofilm to the agar medium. Penetration of only select antimicrobials (vancomycin and chloramphenicol) was hindered through biofilms. There was considerable variation in biofilm-permeating capacity depending upon the genus, strain/CRBSI isolate and antibiotic tested. Furthermore, antibiotics failed to kill the biofilm cells independent of penetration, indicating that other factors contributed substantially to biofilm resistance.

  3. General principles of antibiotic resistance in bacteria.

    Science.gov (United States)

    Martinez, Jose L

    2014-03-01

    Given the impact of antibiotic resistance on human health, its study is of great interest from a clinical view- point. In addition, antibiotic resistance is one of the few examples of evolution that can be studied in real time. Knowing the general principles involved in the acquisition of antibiotic resistance is therefore of interest to clinicians, evolutionary biologists and ecologists. The origin of antibiotic resistance genes now possessed by human pathogens can be traced back to environmental microorganisms. Consequently, a full understanding of the evolution of antibiotic resistance requires the study of natural environments as well as clinical ecosystems. Updated information on the evolutionary mechanisms behind resistance, indicates that ecological connectivity, founder effect and fitness costs are important bottle- necks that modulate the transfer of resistance from environmental microorganisms to pathogens. PMID:24847651

  4. The 'liaisons dangereuses' between iron and antibiotics.

    Science.gov (United States)

    Ezraty, Benjamin; Barras, Frédéric

    2016-05-01

    The decline in the rate of new antibiotic discovery is of growing concern, and new antibacterial strategies must now be explored. This review brings together research in two fields (metals in biology and antibiotics) in the hope that collaboration between scientists working in these two areas will lead to major advances in understanding and the development of new approaches to tackling microbial pathogens. Metals have been used as antiseptics for centuries. In this review, we focus on iron, an essential trace element that can nevertheless be toxic to bacteria. We review the many situations in which iron and antibiotics have combinatorial effects when used together. Understanding the molecular relationships between iron and antibiotics, from pure chemistry to gene reprogramming via biochemical competition, is important not only to increase basic knowledge, but also for the development of treatments against pathogens, with a view to optimizing antibiotic efficacy. PMID:26945776

  5. Innovation of novel antibiotics: an economic perspective.

    Science.gov (United States)

    McKellar, Michael R; Fendrick, A Mark

    2014-10-15

    Despite the public attention to antibiotic overuse and the specter of antimicrobial-resistant pathogens, current infections necessitate the use of antibiotics. Yet, patients and providers may not fully consider the societal cost associated with inappropriate antimicrobial use and subsequent resistance. Policies intended to limit use to minimize resistance must be balanced with the competing concern of underutilization. It is difficult to determine whether research and development incentives or reducing the costs of bringing new antibiotics through expedited review will be sufficient. Likely, the most effective method would be allowing higher prices for use deemed to be clinically appropriate. The ultimate policy goal is to ensure that antibiotics are used appropriately, with the right patients receiving the right medication at the right time, and that the world has a steady stream of future antibiotics to effectively treat the resistant organisms that will inevitably emerge.

  6. The 'liaisons dangereuses' between iron and antibiotics.

    Science.gov (United States)

    Ezraty, Benjamin; Barras, Frédéric

    2016-05-01

    The decline in the rate of new antibiotic discovery is of growing concern, and new antibacterial strategies must now be explored. This review brings together research in two fields (metals in biology and antibiotics) in the hope that collaboration between scientists working in these two areas will lead to major advances in understanding and the development of new approaches to tackling microbial pathogens. Metals have been used as antiseptics for centuries. In this review, we focus on iron, an essential trace element that can nevertheless be toxic to bacteria. We review the many situations in which iron and antibiotics have combinatorial effects when used together. Understanding the molecular relationships between iron and antibiotics, from pure chemistry to gene reprogramming via biochemical competition, is important not only to increase basic knowledge, but also for the development of treatments against pathogens, with a view to optimizing antibiotic efficacy.

  7. Biosynthesis of enediyne antitumor antibiotics.

    Science.gov (United States)

    Van Lanen, Steven G; Shen, Ben

    2008-01-01

    The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures' means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027. PMID:18397168

  8. Antibiotic resistance pattern in uropathogens

    Directory of Open Access Journals (Sweden)

    Gupta V

    2002-01-01

    Full Text Available Uropathogenic strains from inpatient and outpatient departments were studied from April 1997 to March 1999 for their susceptibility profiles. The various isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii and Enterococcus faecalis. Antibiotic susceptibility pattern of these isolates revealed that for outpatients, first generation cephalosporins, nitrofurantoin, norfloxacin/ciprofloxacin were effective for treatment of urinary tract infection but for inpatients, parenteral therapy with newer aminoglycosides and third generation cephalosporins need to be advocated as the organisms for nosocomial UTI exhibit a high degree of drug resistance. Trimethoprim and sulphamethoxazole combination was not found to be effective for the treatment of urinary tract infections as all the uropathogens from inpatients and outpatients showed high degree of resistance to co-trimoxazole. Culture and sensitivity of the isolates from urine samples should be done as a routine before advocating the therapy.

  9. Inhibition of Bacterial Adhesion by Subinhibitory Concentrations of Antibiotics

    Directory of Open Access Journals (Sweden)

    Vidya K

    2005-01-01

    Full Text Available Background: Urinary Tract Infections (UTIs due to Escherichia coli is one of the most common diseases encountered in clinical practice. Most common recognised pathogenic factor in E.coli is adhesion. There is accumulating evidence that through subinhibitory concentrations (sub - MICs of many antibiotics do not kill bacteria, they are able to interfere with some important aspects of bacterial cell function. Materials and Methods: A study was conducted to investigate the effect of sub MICs (1/2-1/8 MIC of ciprofloxacin, ceftazidime, gentamicin, ampicillin and co - trimoxazole on E. coli adhesiveness to human vaginal epithelial cells using three strains ATCC 25922, MTCC 729 and U 105. Results: The 1/2 MIC of all the antibiotics tested produced the greatest inhibition of bacterial adhesion. Morphological changes were observed with ciprofloxacin, ceftazidime and ampicillin at 1/2 MIC and to a lesser extent at 1/4 and 1/8 MIC. Co-trimoxazole caused the greatest suppression of adhesion at 1/2 MIC of E. coli strain MTCC 729 when compared with the controls, followed by ceftazidime. Conclusion: These results suggest that co - trimoxazole is the most effective antibiotic in the treatment of urinary tract infections caused by uropathogenic E. coli.

  10. Identification of Antibiotic Use Pattern as an Effort to Control Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Ivan S. Pradipta

    2012-03-01

    Full Text Available The objective of this study is to determine quantity and pattern of antibiotic use in hospitalized patients at one of Bandung’s private hospital that can give benefit in control of antibiotic resistance and procurement planning of antibiotic. Data of antibiotic consumption were obtained from hospital pharmacy department on February–September 2011. Data were processed using the ATC/DDD and DU90% method. There were 390,98 DDD/100 bed days and 381,34 DDD/100 bed days total of an-tbiotic use in 2009 and 2010. Thirty nine antibiotic were consumed in 2009 within 11 kind of antibiotics in DU90% segment (ceftriaxone, amoxicillin, cefotaxime, ciprofloxacin, levofloxacin, metronidazole, cefixime, doxycycline, thiamphenicol, cefodoxime, cefalexin and 44 antibiotic were consumed in 2010 within 18 kind of antibiotics in DU90% segment (ceftriaxone, ciprofloxacin, amoxicillin, cefixime, levofloxacin, cefadroxil, cefotaxime, metronidazole, thiamphenicol, doxycycline, clindamycin, chloramphenicol, amikacin, sulbactam, gentamycin, streptomycin, cefoperazone, canamycin. There were decline of antibiotic use that followed decline number of bed days/year in 2009–2010, but in both antibiotic kind and quantity of DU90% antibiotic group were increased.

  11. Antibiotics in Animal Feed Contribute to Drug-Resistant Germs

    Science.gov (United States)

    ... medlineplus/news/fullstory_158316.html Antibiotics in Animal Feed Contribute to Drug-Resistant Germs: Study Individual farm ... HealthDay News) -- Use of antibiotics in farm animal feed is helping drive the worldwide increase in antibiotic- ...

  12. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

    Science.gov (United States)

    Brogan, David M; Mossialos, Elias

    2016-02-01

    Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. PMID:26808335

  13. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

    Science.gov (United States)

    Brogan, David M; Mossialos, Elias

    2016-02-01

    Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development.

  14. Antibiotic susceptibility of different lactic acid bacteria strains.

    Science.gov (United States)

    Karapetkov, N; Georgieva, R; Rumyan, N; Karaivanova, E

    2011-12-01

    Five lactic acid bacteria (LAB) strains belonging to species Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus delbrueckii subsp. lactis and Streptococcus thermophilus were tested for their susceptibility to 27 antibiotics. The minimum inhibitory concentrations of each antimicrobial were determined using a microdilution test. Among the strains a high susceptibility was detected for most of the cell-wall synthesis inhibitors (penicillins, cefoxitin and vancomycin) and resistance toward inhibitors of DNA synthesis (trimethoprim/sulfonamides and fluoroquinolones). Generally, the Lactobacillus strains were inhibited by antibiotics such as chloramphenicol, erythromycin and tetracycline at breakpoint levels lower or equal to the levels defined by the European Food Safety Authority. Despite the very similar profile of S. thermophilus LC201 to lactobacilli, the detection of resistance toward erythromycin necessitates the performance of additional tests in order to prove the absence of transferable resistance genes.

  15. Membrane depolarization-triggered responsive diversification leads to antibiotic tolerance

    Directory of Open Access Journals (Sweden)

    Natalie Verstraeten

    2015-07-01

    Full Text Available Bacterial populations are known to harbor a small fraction of so-called persister cells that have the remarkable ability to survive treatment with very high doses of antibiotics. Recent studies underscore the importance of persistence in chronic infections, yet the nature of persisters remains poorly understood. We recently showed that the universally conserved GTPase Obg modulates persistence via a (pppGpp-dependent mechanism that proceeds through expression of hokB. HokB is a membrane-bound toxin that causes the membrane potential to collapse. The resulting drop in cellular energy levels triggers a switch to the persistent state, yielding protection from antibiotic attack. Obg-mediated persistence is conserved in the human pathogen Pseudomonas aeruginosa, making Obg a promising target for therapies directed against bacterial persistence.

  16. Time lapse investigation of antibiotic susceptibility using a microfluidic linear gradient 3D culture device.

    Science.gov (United States)

    Hou, Zining; An, Yu; Hjort, Karin; Hjort, Klas; Sandegren, Linus; Wu, Zhigang

    2014-09-01

    This study reports a novel approach to quantitatively investigate the antibacterial effect of antibiotics on bacteria using a three-dimensional microfluidic culture device. In particular, our approach is suitable for studying the pharmacodynamics effects of antibiotics on bacterial cells temporally and with a continuous range of concentrations in a single experiment. The responses of bacterial cells to a linear concentration gradient of antibiotics were observed using time-lapse photography, by encapsulating bacterial cells in an agarose-based gel located in a commercially available microfluidics chamber. This approach generates dynamic information with high resolution, in a single operation, e.g., growth curves and antibiotic pharmacodynamics, in a well-controlled environment. No pre-labelling of the cells is needed and therefore any bacterial sample can be tested in this setup. It also provides static information comparable to that of standard techniques for measuring minimum inhibitory concentration (MIC). Five antibiotics with different mechanisms were analysed against wild-type Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. The entire process, including data analysis, took 2.5-4 h and from the same analysis, high-resolution growth curves were obtained. As a proof of principle, a pharmacodynamic model of streptomycin against Salmonella Typhimurium was built based on the maximal effect model, which agreed well with the experimental results. Our approach has the potential to be a simple and flexible solution to study responding behaviours of microbial cells under different selection pressures both temporally and in a range of concentrations.

  17. Multi-bacteria multi-antibiotic testing using surface enhanced Raman spectroscopy (SERS) for urinary tract infection (UTI) diagnosis

    Science.gov (United States)

    Hadjigeorgiou, Katerina; Kastanos, Evdokia; Pitris, Costas

    2013-06-01

    The inappropriate use of antibiotics leads to antibiotic resistance, which is a major health care problem. The current method for determination of bacterial susceptibility to antibiotics requires overnight cultures. However most of the infections cannot wait for the results to receive treatment, so physicians administer general spectrum antibiotics. This results in ineffective treatments and aggravates the rising problem of antibiotic resistance. In this work, a rapid method for diagnosis and antibiogram for a bacterial infection was developed using Surface Enhanced Raman Spectroscopy (SERS) with silver nanoparticles. The advantages of this novel method include its rapidness and efficiency which will potentially allow doctors to prescribe the most appropriate antibiotic for an infection. SERS spectra of three species of gram negative bacteria, Escherichia coli, Proteus spp., and Klebsiella spp. were obtained after 0 and 4 hour exposure to the seven different antibiotics. Bacterial strains were diluted in order to reach the concentration of (2x105 cfu/ml), cells/ml which is equivalent to the minimum concentration found in urine samples from UTIs. Even though the concentration of bacteria was low, species classification was achieved with 94% accuracy using spectra obtained at 0 hours. Sensitivity or resistance to antibiotics was predicted with 81%-100% accuracy from spectra obtained after 4 hours of exposure to the different antibiotics. This technique can be applied directly to urine samples, and with the enhancement provided by SERS, this method has the potential to be developed into a rapid method for same day UTI diagnosis and antibiogram.

  18. Do antibiotics have environmental side-effects? Impact of synthetic antibiotics on biogeochemical processes.

    Science.gov (United States)

    Roose-Amsaleg, Céline; Laverman, Anniet M

    2016-03-01

    Antibiotic use in the early 1900 vastly improved human health but at the same time started an arms race of antibiotic resistance. The widespread use of antibiotics has resulted in ubiquitous trace concentrations of many antibiotics in most environments. Little is known about the impact of these antibiotics on microbial processes or "non-target" organisms. This mini-review summarizes our knowledge of the effect of synthetically produced antibiotics on microorganisms involved in biogeochemical cycling. We found only 31 articles that dealt with the effects of antibiotics on such processes in soil, sediment, or freshwater. We compare the processes, antibiotics, concentration range, source, environment, and experimental approach of these studies. Examining the effects of antibiotics on biogeochemical processes should involve environmentally relevant concentrations (instead of therapeutic), chronic exposure (versus acute), and monitoring of the administered antibiotics. Furthermore, the lack of standardized tests hinders generalizations regarding the effects of antibiotics on biogeochemical processes. We investigated the effects of antibiotics on biogeochemical N cycling, specifically nitrification, denitrification, and anammox. We found that environmentally relevant concentrations of fluoroquinolones and sulfonamides could partially inhibit denitrification. So far, the only documented effects of antibiotic inhibitions were at therapeutic doses on anammox activities. The most studied and inhibited was nitrification (25-100 %) mainly at therapeutic doses and rarely environmentally relevant. We recommend that firm conclusions regarding inhibition of antibiotics at environmentally relevant concentrations remain difficult due to the lack of studies testing low concentrations at chronic exposure. There is thus a need to test the effects of these environmental concentrations on biogeochemical processes to further establish the possible effects on ecosystem functioning.

  19. No apparent costs for facultative antibiotic production by the soil bacterium Pseudomonas fluorescens Pf0-1.

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    Paolina Garbeva

    Full Text Available BACKGROUND: Many soil-inhabiting bacteria are known to produce secondary metabolites that can suppress microorganisms competing for the same resources. The production of antimicrobial compounds is expected to incur fitness costs for the producing bacteria. Such costs form the basis for models on the co-existence of antibiotic-producing and non-antibiotic producing strains. However, so far studies quantifying the costs of antibiotic production by bacteria are scarce. The current study reports on possible costs, for antibiotic production by Pseudomonas fluorescens Pf0-1, a soil bacterium that is induced to produce a broad-spectrum antibiotic when it is confronted with non-related bacterial competitors or supernatants of their cultures. METHODOLOGY AND PRINCIPAL FINDINGS: We measured the possible cost of antibiotic production for Pseudomonas fluorescens Pf0-1 by monitoring changes in growth rate with and without induction of antibiotic production by supernatant of a bacterial competitor, namely Pedobacter sp.. Experiments were performed in liquid as well as on semi-solid media under nutrient-limited conditions that are expected to most clearly reveal fitness costs. Our results did not reveal any significant costs for production of antibiotics by Pseudomonas fluorescens Pf0-1. Comparison of growth rates of the antibiotic-producing wild-type cells with those of non-antibiotic producing mutants did not reveal costs of antibiotic production either. SIGNIFICANCE: Based on our findings we propose that the facultative production of antibiotics might not be selected to mitigate metabolic costs, but instead might be advantageous because it limits the risk of competitors evolving resistance, or even the risk of competitors feeding on the compounds produced.

  20. Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

    Directory of Open Access Journals (Sweden)

    Marothi Yogyata

    2010-07-01

    Full Text Available Abstract Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in

  1. Phenotypic and gene expression responses of E. coli to antibiotics during spaceflight

    Science.gov (United States)

    Zea, Luis

    Bacterial susceptibility to antibiotics has been shown in vitro to be reduced during spaceflight; however, the underlying mechanisms responsible for this outcome are not fully understood. In particular, it is not yet clear whether this observed response is due to increased drug resistance (a microbial defense response) or decreased drug efficacy (a microgravity biophysical mass transport effect). To gain insight into the differentiation between these two potential causes, an investigation was undertaken onboard the International Space Station (ISS) in 2014 termed Antibiotic Effectiveness in Space-1 (AES-1). For this purpose, E. coli was challenged with two antibiotics, Gentamicin Sulfate and Colistin Sulfate, at concentrations higher than those needed to inhibit growth on Earth. Phenotypic parameters (cell size, cell envelope thickness, population density and lag phase duration) and gene expression were compared between the spaceflight samples and ground controls cultured in varying levels of drug concentration. It was observed that flight samples proliferated in antibiotic concentrations that were inhibitory on Earth, growing on average to a 13-fold greater concentration than matched 1g controls. Furthermore, at the highest drug concentrations in space, E. coli cells were observed to aggregate into visible clusters. In spaceflight, cell size was significantly reduced, translating to a decrease in cell surface area to about one half of the ground controls. Smaller cell surface area can in turn proportionally reduce the rate of antibiotic molecules reaching the cell. Additionally, it was observed that genes --- in some cases more than 2000 --- were overexpressed in space with respect to ground controls. Up-regulated genes include poxB, which helps catabolize glucose into organic acids that alter acidity around and inside the cell, and the gadABC family genes, which confer resistance to extreme acid conditions. The next step is to characterize the mechanisms behind

  2. Get Smart: Know When Antibiotics Work - Sinus Infection (Sinusitis)

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  3. Get Smart: Know When Antibiotics Work - Influenza (Flu)

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  4. Get Smart: Know When Antibiotics Work - Ear Infections

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  5. Get Smart: Know When Antibiotics Work - Urinary Tract Infection

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  6. Get Smart: Know When Antibiotics Work - Sore Throat

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  7. Get Smart: Know When Antibiotics Work - Symptom Relief

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  8. Get Smart: Know When Antibiotics Work - What You Can Do

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  9. A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics.

    Science.gov (United States)

    Dörr, Tobias; Delgado, Fernanda; Umans, Benjamin D; Gerding, Matthew A; Davis, Brigid M; Waldor, Matthew K

    2016-08-01

    Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated vigA (for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The vigA open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the vigA mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions. PMID:27216069

  10. Effects of osmotic pressure, acid, or cold stresses on antibiotic susceptibility of Listeria monocytogenes.

    Science.gov (United States)

    Al-Nabulsi, Anas A; Osaili, Tareq M; Shaker, Reyad R; Olaimat, Amin N; Jaradat, Ziad W; Zain Elabedeen, Noor A; Holley, Richard A

    2015-04-01

    Prevalence of antibiotic resistance of Listeria monocytogenes isolated from a variety of foods has increased in many countries. L. monocytogenes has many physiological adaptations that enable survival under a wide range of environmental stresses. The objective of this study was to evaluate effects of osmotic (2, 4, 6, 12% NaC), pH (6, 5.5, 5.0) and cold (4 °C) stresses on susceptibility of three isolates of L. monocytogenes towards different antibiotics. The minimal inhibitory concentrations (MICs) of tested antibiotics against unstressed (control), stressed or post-stressed L. monocytogenes isolates (an ATCC strain and a meat and dairy isolate) were determined using the broth microdilution method. Unstressed cells of L. monocytogenes were sensitive to all tested antibiotics. In general, when L. monocytogenes cells were exposed to salt, cold and pH stresses, their antibiotic resistance increased as salt concentration increased to 6 or 12%, as pH was reduced to pH 5 or as temperature was decreased to 10 °C. Results showed that both meat and dairy isolates were more resistant than the ATCC reference strain. Use of sub-lethal stresses in food preservation systems may stimulate antibiotic resistance responses in L. monocytogenes strains. PMID:25475279

  11. Treatment with antibiotics that interfere with peptidoglycan biosynthesis inhibits chloroplast division in the desmid Closterium.

    Directory of Open Access Journals (Sweden)

    Hiroko Matsumoto

    Full Text Available Charophytes is a green algal group closely related to land plants. We investigated the effects of antibiotics that interfere with peptidoglycan biosynthesis on chloroplast division in the desmid Closterium peracerosum-strigosum-littorale complex. To detect cells just after division, we used colchicine, which inhibits Closterium cell elongation after division. Although normal Closterium cells had two chloroplasts before and after cell division, cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division. The antibiotics bacitracin and vancomycin showed no obvious effect. Electron microscopic observation showed that irregular-shaped chloroplasts existed in ampicillin-treated Closterium cells. Because antibiotic treatments resulted in the appearance of long cells with irregular chloroplasts and cell death, we counted cell types in the culture. The results suggested that cells with one chloroplast appeared first and then a huge chloroplast was generated that inhibited cell division, causing elongation followed by cell death.

  12. "Practical knowledge" and perceptions of antibiotics and antibiotic resistance among drugsellers in Tanzanian private drugstores

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    Tomson Göran

    2010-09-01

    Full Text Available Abstract Background Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Methods Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Results Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85% said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic

  13. Chitin stimulates production of the antibiotic andrimid in a Vibrio corallilyticus strain

    DEFF Research Database (Denmark)

    Wietz, Matthias; Månsson, Maria; Gram, Lone

    2011-01-01

    per cell was twofold higher. In cultures with Artemia as live chitin model system, S2052 reached up to 108 cells ml-1, produced andrimid and showed attachment to the exoskeleton and chitinous exuviae. The metabolic focus on andrimid production with chitin indicates that the antibiotic could serve...

  14. Antibiotic prescribing practices by dentists: a review

    Directory of Open Access Journals (Sweden)

    Najla Saeed Dar-Odeh

    2010-06-01

    Full Text Available Najla Saeed Dar-Odeh1, Osama Abdalla Abu-Hammad1, Mahmoud Khaled Al-Omiri1, Ameen Sameh Khraisat1, Asem Ata Shehabi21Faculty of Dentistry, University of Jordan, Amman, Jordan; 2Faculty of Medicine, University of Jordan, Amman, JordanAbstract: Antibiotics are prescribed by dentists for treatment as well as prevention of infection. Indications for the use of systemic antibiotics in dentistry are limited, since most dental and periodontal diseases are best managed by operative intervention and oral hygiene measures. However, the literature provides evidence of inadequate prescribing practices by dentists, due to a number of factors ranging from inadequate knowledge to social factors. Here we review studies that investigated the pattern of antibiotic use by dentists worldwide. The main defects in the knowledge of antibiotic prescribing are outlined. The main conclusion is that, unfortunately, the prescribing practices of dentists are inadequate and this is manifested by over-prescribing. Recommendations to improve antibiotic prescribing practices are presented in an attempt to curb the increasing incidence of antibiotic resistance and other side effects of antibiotic abuse.Keywords: over-prescribing, antimicrobial resistance, recommended practice, penicillin

  15. Antibiotic resistance in ocular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Bacterial infections of the eye are common and ophthalmologists are spoilt for choice with a variety of antibiotics available in the market. Antibiotics can be administered in the eye by a number of routes; topical, subconjunctival, subtenon and intraocular. Apart from a gamut of eye drops available, ophthalmologists also have the option of preparing fortified eye drops from parenteral formulations, thereby, achieving high concentrations; often much above the minimum inhibitory concentration (MIC, of antibiotics in ocular tissues during therapy. Antibiotic resistance among ocular pathogens is increasing in parallel with the increase seen over the years in bacteria associated with systemic infections. Although it is believed that the rise in resistant ocular bacterial isolates is linked to the rise in resistant systemic pathogens, recent evidence has correlated the emergence of resistant bacteria in the eye to prior topical antibiotic therapy. One would like to believe that either of these contributes to the emergence of resistance to antibiotics among ocular pathogens. Until recently, ocular pathogens resistant to fluoroquinolones have been minimal but the pattern is currently alarming. The new 8-fluoroquinolone on the scene-besifloxacin, is developed exclusively for ophthalmic use and it is hoped that it will escape the selective pressure for resistance because of lack of systemic use. In addition to development of new antibacterial agents, the strategies to halt or control further development of resistant ocular pathogens should always include judicious use of antibiotics in the treatment of human, animal or plant diseases.

  16. [Antibiotic resistance of bacteria to 6 antibiotics in secondary effluents of municipal wastewater treatment plants].

    Science.gov (United States)

    Lu, Sun-Qin; Li, Yi; Huang, Jing-Jing; Wei, Bin; Hu, Hong-Ying

    2011-11-01

    Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate antibiotic resistance in secondary effluents of municipal wastewater treatment plants, antibiotic tolerance of heterotrophic bacteria, proportion of antibiotic-resistant bacteria and hemi-inhibitory concentrations of six antibiotics (penicillin, ampicillin, cefalexin, chloramphenicol, tetracycline and rifampicin) were determined at two wastewater treatment plants (WWTPs) in Beijing. The results showed that proportions of ampicillin-resistant bacteria in WWTP-G and chloramphenicol-resistant bacteria in WWTP-Q were highest to 59% and 44%, respectively. The concentrations of ampicillin-resistant bacteria in the effluents of WWTP-G and WWTP-Q were as high as 4.0 x 10(3) CFU x mL(-1) and 3.5 x 10(4) CFU x mL(-1), respectively; the concentrations of chloramphenicol-resistant bacteria were 4.9 x 10(2) CFU x mL(-1) and 4.6 x 10(4) CFU x mL(-1), respectively. The data also indicated that the hemi-inhibitory concentrations of heterotrophic bacteria to 6 antibiotics were much higher than common concentrations of antibiotics in sewages, which suggested that antibiotic-resistant bacteria could exist over a long period in the effluents with low concentrations of antibiotics. Antibiotic-resistant bacteria could be a potential microbial risk during sewage effluent reuse or emission into environmental waters. PMID:22295644

  17. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci.

    Science.gov (United States)

    McMurray, Claire L; Hardy, Katherine J; Verlander, Neville Q; Hawkey, Peter M

    2015-12-01

    Staphylococci are a significant cause of hospital-acquired infection. Nasal carriage of Staphylococcus aureus is an important risk factor for infection in surgical patients and coagulase-negative staphylococci (CNS) are a major cause of prosthetic joint infections. The impact that antibiotic surgical prophylaxis has on the nasal carriage of staphylococci has not been studied. Daily nasal swabs were taken from 63 patients who received antibiotic surgical prophylaxis and 16 patients who received no antibiotics. Total aerobic bacterial count, S. aureus and CNS were enumerated by culture from nasal swabs. Representative isolates were typed by staphylococcal interspersed repeat units (SIRU) typing and PFGE, and MICs to nine antibiotics were determined. After antibiotic administration, there was a reduction in S. aureus counts (median - 2.3 log(10)c.f.u. ml(- 1)) in 64.0 % of S. aureus carriers, compared with only a 0.89 log(10)c.f.u. ml(- 1) reduction in 75.0 % of S. aureus carriers who did not receive antibiotics. A greater increase in the nasal carriage rate of meticillin-resistant CNS was observed after antibiotic surgical prophylaxis compared with hospitalization alone, with increases of 16.4 and 4.6 %, respectively. Antibiotic-resistant S. epidermidis carriage rate increased by 16.6 % after antibiotic administration compared with 7.5 % with hospitalization alone. Antibiotic surgical prophylaxis impacts the nasal carriage of both S. aureus and CNS.

  18. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens.

    Science.gov (United States)

    Goneau, Lee W; Yeoh, Nigel S; MacDonald, Kyle W; Cadieux, Peter A; Burton, Jeremy P; Razvi, Hassan; Reid, Gregor

    2014-01-01

    Persister cells represent a multidrug-tolerant (MDT), physiologically distinct subpopulation of bacteria. The ability of these organisms to survive lethal antibiotic doses raises concern over their potential role in chronic disease, such as recurrent urinary tract infection (RUTI). Persistence is believed to be conveyed through global metabolic dormancy, which yields organisms unresponsive to external stimuli. However, recent studies have contested this stance. Here, various antibiotics that target different cellular processes were used to dissect the activity of transcription, translation, and peptidoglycan turnover in persister cells. Differential susceptibility patterns were found in type I and type II persisters, and responses differed between Staphylococcus saprophyticus and Escherichia coli uropathogens. Further, SOS-deficient strains were sensitized to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the importance of active DNA repair systems for ciprofloxacin tolerance. These results indicate that global dormancy per se cannot sufficiently account for antibiotic tolerance. Rather, the activity of individual cellular processes dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the susceptibility patterns of persisters depended on their mechanisms of onset, with subinhibitory antibiotic pretreatments selectively shutting down cognate targets and increasing the persister fraction against the same agent. Interestingly, antibiotics targeting transcription and translation enhanced persistence against multiple agents indirectly related to these processes. Conducting these assays with uropathogenic E. coli isolated from RUTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy. This finding suggests that persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure. PMID:24449771

  19. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  20. Alliance for the Prudent Use of Antibiotics

    Science.gov (United States)

    ... strains Novel innovations offer promise in infection control Harvard chemists use novel platform to create new antibiotics ... M., professor at the Boston University School of Law and Boston University School of Public Health, as ...

  1. Antibiotic Prescription in Danish General Practice

    DEFF Research Database (Denmark)

    Sydenham, Rikke Vognbjerg; Plejdrup Hansen, Malene; Pedersen, Line Bjørnskov;

    2016-01-01

    factors (microbiological diagnostics, point-of-care tests, patients’ expectations) in the management of infectious diseases. 3. Results This PhD project is scheduled to be carried out in 2016-2019. The hypotheses and anticipated perspectives will be discussed at the conference. 4. Conclusions The project......1. Background & Aim The overall aim of the project is to describe antibiotic consumption in Danish general practice with emphasis on specific types of antibiotics. The project will shed light on the impact of microbiological diagnostic methods (MDM) on the choice of antibiotic and the project...... will assess and quantify the usage of MDM prior to antibiotic prescription. Furthermore we will investigate associations between GP characteristics, use of MDM and description patterns. A questionnaire comprising a discrete choice experiment will allow us to investigate the relative importance of selected...

  2. Controlling antibiotic resistance in the ICU

    NARCIS (Netherlands)

    Derde, L.P.G.

    2013-01-01

    Patients admitted to intensive care units (ICUs) are frequently colonized with (antibiotic-resistant) bacteria, which may lead to healthcare associated infections. Antimicrobial-resistant bacteria (AMRB), such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (V

  3. Antibiotic stewardship in the intensive care unit.

    Science.gov (United States)

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial infections in these critically ill patients, based on pharmacokinetic-pharmacodynamic characteristics, but also improving our ability to avoid administering unnecessary broad-spectrum antibiotics, shortening the duration of their administration, and reducing the numbers of patients receiving undue antibiotic therapy. Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens.

  4. What Can Be Done about Antibiotic Resistance?

    Science.gov (United States)

    ... WHO issued its Global Strategy for Containment of Antimicrobial Resistance , a document aimed at policy-makers that urges ... of existing antibiotics by modifying them so the bacterial enzymes that cause resistance cannot attack them. Alternately, "decoy" molecules can be ...

  5. Do antibiotics decrease effectiveness of oral contraceptives?

    Science.gov (United States)

    Cottet, C

    1996-09-01

    The number of accidental pregnancies occurring in oral contraceptive (OC) users who are concurrently taking certain antibiotics and antifungal agents exceeds the 1% failure rate associated with OCs, suggesting some form of drug interaction. Two mechanisms of action have been proposed to explain this phenomenon. First, drugs such as rifampin and griseofulvin induce liver enzymes that break down the estrogen and progestin contained in OCs, reducing plasma hormone levels. Second, changes in the intestinal bacterial flora induced by penicillin and tetracycline may reduce the gut's absorption of hormones, also compromising efficacy. Since rifampin and griseofulvin are the medications most frequently implicated in accidental pregnancies in OC users, the induction of liver enzymes is the more probable, potent cause of failure. Although the risk of pregnancy due to OC-antibiotic interactions is extremely small, OC users prescribed antibiotics should be warned to use condoms or spermicides until the antibiotics are discontinued. PMID:9006212

  6. Antibiotics May Blunt Breast-Feeding's Benefits

    Science.gov (United States)

    ... fighting infection because of the immunity offered in mother's milk," said Dr. William Muinos, a pediatric gastroenterologist at Nicklaus Children's Hospital in Miami. Antibiotics kill the bacteria in the gut, he said. "If ...

  7. Metagenomic exploration of antibiotic resistance in soil.

    Science.gov (United States)

    Monier, Jean-Michel; Demanèche, Sandrine; Delmont, Tom O; Mathieu, Alban; Vogel, Timothy M; Simonet, Pascal

    2011-06-01

    The ongoing development of metagenomic approaches is providing the means to explore antibiotic resistance in nature and address questions that could not be answered previously with conventional culture-based strategies. The number of available environmental metagenomic sequence datasets is rapidly expanding and henceforth offer the ability to gain a more comprehensive understanding of antibiotic resistance at the global scale. Although there is now evidence that the environment constitutes a vast reservoir of antibiotic resistance gene determinants (ARGDs) and that the majority of ARGDs acquired by human pathogens may have an environmental origin, a better understanding of their diversity, prevalence and ecological significance may help predict the emergence and spreading of newly acquired resistances. Recent applications of metagenomic approaches to the study of ARGDs in natural environments such as soil should help overcome challenges concerning expanding antibiotic resistances. PMID:21601510

  8. Race against time to develop new antibiotics

    OpenAIRE

    2011-01-01

    The second part of a series of three news features on antimicrobial resistance looks at how the antibiotics pipeline is drying up while resistance to existing drugs is increasing. Theresa Braine reports.

  9. Priorities for antibiotic resistance surveillance in Europe

    DEFF Research Database (Denmark)

    Fluit, A. C.; van der Bruggen, J. T.; Aarestrup, Frank Møller;

    2006-01-01

    Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitud......Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies...... to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during...... of antibiotic resistance....

  10. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    -day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post...

  11. Get Smart: Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts

    2008-09-10

    This podcast answers questions from the public about appropriate antibiotic use.  Created: 9/10/2008 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/15/2008.

  12. Structures and Properties of Naturally Occurring Polyether Antibiotics

    Directory of Open Access Journals (Sweden)

    Jacek Rutkowski

    2013-01-01

    Full Text Available Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

  13. Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic resistance genes in water and wastewater.

    Science.gov (United States)

    McKinney, Chad W; Pruden, Amy

    2012-12-18

    Disinfection of wastewater treatment plant effluent may be an important barrier for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). While ideally disinfection should destroy ARGs, to prevent horizontal gene transfer to downstream bacteria, little is known about the effect of conventional water disinfection technologies on ARGs. This study examined the potential of UV disinfection to damage four ARGs, mec(A), van(A), tet(A), and amp(C), both in extracellular form and present within a host ARBs: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa 01, respectively. An extended amplicon-length quantitative polymerase chain reaction assay was developed to enhance capture of ARG damage events and also to normalize to an equivalent length of target DNA (∼1000 bp) for comparison. It was found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two Gram-positive organisms also possessed smaller total genome sizes, which could also have reduced their susceptibility to UV because of fewer potential pyrimidine dimer targets. An effect of cell type on damage to ARGs was only observed in VRE and P. aeruginosa, the latter potentially because of extracellular polymeric substances. In general, damage of ARGs required much greater UV doses (200-400 mJ/cm² for 3- to 4-log reduction) than ARB inactivation (10-20 mJ/cm² for 4- to 5-log reduction). The proportion of amplifiable ARGs following UV treatment exhibited a strong negative correlation with the number of adjacent thymines (Pearson r 0.85; p disinfection technologies should be explored.

  14. Antibiotics Cure Anthrax in Animal Models▿

    OpenAIRE

    Weiss, Shay; Kobiler, David; Levy, Haim; Pass, Avi; Ophir, Yakir; Rothschild, Nili; Tal, Arnon; Schlomovitz, Josef; Altboum, Zeev

    2011-01-01

    Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combi...

  15. Antibiotic tolerance and resistance in biofilms

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim

    2010-01-01

    One of the most important features of microbial biofilms is their tolerance to antimicrobial agents and components of the host immune system. The difficulty of treating biofilm infections with antibiotics is a major clinical problem. Although antibiotics may decrease the number of bacteria...... in biofilms, they will not completely eradicate the bacteria in vivo which may have important clinical consequences in form of relapses of the infection....

  16. DNA-Aptamers Binding Aminoglycoside Antibiotics

    OpenAIRE

    Nadia Nikolaus; Beate Strehlitz

    2014-01-01

    Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminog...

  17. Antibiotic stewardship in the intensive care unit

    OpenAIRE

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    International audience; The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial...

  18. Intensive Care Unit Infections and Antibiotic Use

    OpenAIRE

    Ayşegül Yeşilkaya; Hande Arslan

    2011-01-01

    Burn wound infections is the leading cause of morbidity and mortality in burn trauma patients. Although burn wound is sterile at the beginning, because of risk factors such as prolonged hospital stay, immunesuppression and burn affecting large body surface area, colonisation firstly with Staphylococcus aureus and then Pseudomonas aeruginosa will occur later. Delay in wound closure and treatment with broad-spectrum antibiotic will result wound colonisation with antibiotic-resistant bacteria. T...

  19. Multiple antibiotic resistance in Stenotrophomonas maltophilia.

    OpenAIRE

    Alonso, A.; Martínez, J L

    1997-01-01

    A cryptic multidrug resistance (MDR) system in Stenotrophomonas maltophilia, the expression of which is selectable by tetracycline, is described. Tetracycline resistance was the consequence of active efflux of the antibiotic, and it was associated with resistance to quinolones and chloramphenicol, but not to aminoglycosides or beta-lactam antibiotics. MDR is linked to the expression of an outer membrane protein (OMP54) both in a model system and in multidrug-resistant clinical isolates.

  20. Identification of Antibiotic Use Pattern as an Effort to Control Antibiotic Resistance

    OpenAIRE

    Ivan S. Pradipta; Ellin Febrina; Muhammad H. Ridwan; Rani Ratnawati

    2012-01-01

    The objective of this study is to determine quantity and pattern of antibiotic use in hospitalized patients at one of Bandung’s private hospital that can give benefit in control of antibiotic resistance and procurement planning of antibiotic. Data of antibiotic consumption were obtained from hospital pharmacy department on February–September 2011. Data were processed using the ATC/DDD and DU90% method. There were 390,98 DDD/100 bed days and 381,34 DDD/100 bed days total of an-tbiotic use i...

  1. Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance.

    Science.gov (United States)

    Omoto, Charlotte K.; Malm, Kirstin

    2003-01-01

    Describes a microbiology laboratory experiment in which students test their own microbial flora of Staphylococcus for antibiotic resistance. Provides directions on how to conduct the experiment. (YDS)

  2. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$

    Institute of Scientific and Technical Information of China (English)

    Nishant A. Dafale n; Uttam P. Semwal; Rupak K. Rajput; G.N. Singh

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  3. Antibiotics in agroecosystems: Introduction to the special section

    Science.gov (United States)

    The presence of antibiotic drug residues, antibiotic resistant bacteria, and antibiotic resistance genes in agroecosystems has become a significant area of research in recent years, and is a growing public health concern. While antibiotics are utilized for human medicine and agricultural practices, ...

  4. Reducing Parental Demand for Antibiotics by Promoting Communication Skills

    Science.gov (United States)

    Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.

    2005-01-01

    Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics…

  5. Patterns of antibiotic use in the community in Denmark

    NARCIS (Netherlands)

    Muscat, Mark; Monnet, Dominique L.; Klemmensen, Thomas; Grigoryan, Larissa; Jensen, Maria Hummelshoj; Andersen, Morten; Haaijer-Ruskamp, Flora M.

    2006-01-01

    A cross-sectional descriptive population survey was conducted in 2003 to examine epidemiological characteristics of antibiotic use in the community in Denmark and particularly in the area of self-medication with antibiotics. Self-medication with antibiotics was rare in Denmark. 97% of antibiotics us

  6. Trends in Antibiotic Prescribing in Adults in Dutch General Practice

    NARCIS (Netherlands)

    M.B. Haeseker (Michiel); N.H.T.M. Dukers-Muijrers (Nicole); C.J.P.A. Hoebe (Christian); C.A. Bruggeman (Cathrien); J.W.L. Cals (Jochen); A. Verbon (Annelies)

    2012-01-01

    textabstractBackground: Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this stud

  7. Multiple strategies to activate gold nanoparticles as antibiotics

    Science.gov (United States)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  8. Squalamine: an aminosterol antibiotic from the shark.

    Science.gov (United States)

    Moore, K S; Wehrli, S; Roder, H; Rogers, M; Forrest, J N; McCrimmon, D; Zasloff, M

    1993-02-15

    In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bactericidal activity against both Gram-negative and Gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. The chemical structure of the antibiotic 3 beta-N-1-(N-[3-(4-aminobutyl)]- 1,3-diaminopropane)-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate has been determined by fast atom bombardment mass spectroscopy and NMR. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with spermidine. The discovery of squalamine in the shark implicates a steroid as a potential host-defense agent in vertebrates and provides insights into the chemical design of a family of broad-spectrum antibiotics. PMID:8433993

  9. Active controlled studies in antibiotic drug development.

    Science.gov (United States)

    Dane, Aaron

    2011-01-01

    The increasing concern of antibacterial resistance has been well documented, as has the relative lack of antibiotic development. This paradox is in part due to challenges with clinical development of antibiotics. Because of their rapid progression, untreated bacterial infections are associated with significant morbidity and mortality. As a consequence, placebo-controlled studies of new agents are unethical. Rather, pivotal development studies are mostly conducted using non-inferiority designs versus an active comparator. Further, infections because of comparator-resistant isolates must usually be excluded from the trial programme. Unfortunately, the placebo-controlled data classically used in support of non-inferiority designs are largely unavailable for antibiotics. The only available data are from the 1930s and 1940s and their use is associated with significant concerns regarding constancy and assay sensitivity. Extended public debate on this challenge has led to proposed solutions by some in which these concerns are addressed by using very conservative approaches to trial design, endpoints and non-inferiority margins, in some cases leading to potentially impractical studies. To compound this challenge, different Regulatory Authorities seem to be taking different approaches to these key issues. If harmonisation does not occur, antibiotic development will become increasingly challenging, with the risk of further decreases in the amount of antibiotic drug development. However with clarity on Regulatory requirements and an ability to feasibly conduct global development programmes, it should be possible to bring much needed additional antibiotics to patients.

  10. SELF MEDICATION PATTERN AMONG DENTISTS WITH ANTIBIOTICS

    Directory of Open Access Journals (Sweden)

    Shubha

    2013-11-01

    Full Text Available Self medication with antibiotics has become a common practice among people, and more so among those with medical background. Dentists are one group who have kno wledge and accessibility to antibiotics. Hence this study was aimed at knowing the prevalence of self medication with antibiotics among dentists reasons for not visiting the physician. RESULT: Prevalence rate of self medication among dentist was 78.18%. Mo st common cause for self medication were common cold, tooth ache and sore throat. Most common antibiotic used was azithromycin next to ampicillin. Most common reason for not visiting doctor was that participants were themselves a doctor. CONCLUSION: Though dentists have knowledge about antibiotics, knowledge on appropriate usage of antibiotics is poor. This may have a bad impact on practice. Hence they have to overcome the ego and take proper advice from physician which may help the community in curbing ant ibiotic resistance The only limitation of the study was small sample size as dentists from only two colleges were considered. There is a need for study in large number of population.

  11. DNA-Aptamers Binding Aminoglycoside Antibiotics

    Directory of Open Access Journals (Sweden)

    Nadia Nikolaus

    2014-02-01

    Full Text Available Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

  12. Antibiotic prescribing policy and Clostridium difficile diarrhoea.

    LENUS (Irish Health Repository)

    O'Connor, K A

    2012-02-03

    BACKGROUND: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients. AIM: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients. DESIGN: Retrospective analysis. METHODS: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data. RESULTS: Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03). DISCUSSION: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.

  13. Antibiotic use: how to improve it?

    Science.gov (United States)

    Hulscher, Marlies E J L; van der Meer, Jos W M; Grol, Richard P T M

    2010-08-01

    Antibiotics are an extremely important weapon in the fight against infections. However, antimicrobial resistance is a growing problem. That is why the appropriate use of antibiotics is of great importance. A proper analysis of factors influencing appropriate antibiotic use is at the heart of an effective improvement programme, as interventions can only result in improved medical behaviour if they are well attuned to the problems, the target group, and the setting in which the change is to take place. Determinants of appropriate and inappropriate prescribing are not only found in patient knowledge and behaviour, in the way medical professionals think and act, and in the way in which patient care is organised, but also in the wider, socio-cultural environment of doctors and their patients. We present several relevant factors at each of these 4 levels and various possible measures that could be an effective response to them. The reasons why antibiotic use is inappropriate are complex. This means that any programme to rationalise antibiotic use - if it is to be effective - will have to include activities at all 4 levels discussed above. A national programme for 'appropriate antibiotic use' could be considered, including patient, professional and organisational-oriented activities. In addition, close international cooperation is required involving international guidelines, agreements, monitoring and feedback of information, and implementation programmes. PMID:20434950

  14. A novel method for imaging the pharmacological effects of antibiotic treatment on Clostridium difficile.

    Science.gov (United States)

    Endres, Bradley T; Bassères, Eugénie; Memariani, Ali; Chang, Long; Alam, M Jahangir; Vickers, Richard J; Kakadiaris, Ioannis A; Garey, Kevin W

    2016-08-01

    Clostridium difficile is a significant cause of nosocomial-acquired infection that results in severe diarrhea and can lead to mortality. Treatment options for C. difficile infection (CDI) are limited, however, new antibiotics are being developed. Current methods for determining efficacy of experimental antibiotics on C. difficile involve antibiotic killing rates and do not give insight into the drug's pharmacologic effects. Considering this, we hypothesized that by using scanning electron microscopy (SEM) in tandem to drug killing curves, we would be able to determine efficacy and visualize the phenotypic response to drug treatment. To test this hypothesis, supraMIC kill curves were conducted using vancomycin, metronidazole, fidaxomicin, and ridinilazole. Following collection, cells were either plated or imaged using a scanning electron microscope (SEM). Consistent with previous reports, we found that the tested antibiotics had significant bactericidal activity at supraMIC concentrations. By SEM imaging and using a semi-automatic pipeline for image analysis, we were able to determine that vancomycin and to a lesser extent fidaxomicin and ridinilazole significantly affected the cell wall, whereas metronidazole, fidaxomicin, and ridinilazole had significant effects on cell length suggesting a metabolic effect. While the phenotypic response to drug treatment has not been documented previously in this manner, the results observed are consistent with the drug's mechanism of action. These techniques demonstrate the versatility and reliability of imaging and measurements that could be applied to other experimental compounds. We believe the strategies laid out here are vital for characterizing new antibiotics in development for treating CDI. PMID:27108094

  15. Photodynamic inactivation of antibiotic-resistant bacteria and biofilms by hematoporphyrin monomethyl ether.

    Science.gov (United States)

    Liu, Chengcheng; Hu, Min; Ma, Dandan; Lei, Jin'e; Xu, Jiru

    2016-02-01

    The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. A promising approach to killing antibiotic-resistant bacteria is photodynamic antimicrobial chemotherapy, which uses light in combination with a photosensitizer to induce a phototoxic reaction. We evaluated the photodynamic inactivation (PDI) efficiency of hematoporphyrin monomethyl ether (HMME) on antibiotic-resistant bacteria and biofilms. HMME exhibited no significant dark toxicity and provided dose-dependent inactivation of antibiotic-resistant bacteria and biofilms. After incubation with 100-μM HMME and irradiation with 72-J cm(-2) white light, 4.19-7.59 log10 reductions in survival were achieved in planktonic suspension. Antibiotic-resistant strains were as susceptible to PDI in biofilms as in planktonic suspensions, but the inactivation of bacterial cells in biofilms was attenuated. In addition, gram-positive bacterial strains and biofilms were more susceptible than gram-negative strains and biofilms to the PDI effect of HMME. Thus, HMME is a promising photosensitizer for the treatment of infectious diseases caused by antibiotic-resistant bacteria, especially gram-positive bacteria.

  16. Effect of physiological heterogeneity of E. coli population on antibiotic susceptivity test

    Institute of Scientific and Technical Information of China (English)

    LIU; YuQing; ZHANG; HuaiQiang; SHEN; JianZhong; GAO; PeiJi

    2007-01-01

    According to the instantaneous growth rate (dN/dt) of E. coli CVCC249 growing in batch culture, the entire growth progress was distinguished into four phases: accelerating growth phase, constant growth phase, decelerating growth phase and declining phase, in each of which obvious variation in physiological and biochemical properties was detected, including total DNA, total protein, and MTT-dehydrogenase activity, etc., that led to difference in their antibiotic susceptivity. Antibiotic susceptivity of the population sampled from each phase was tested by Concentration-killing Curve (CKC) approach following the formula N=N0/{1+exp[r((x-BC50)]}, showing as normal distribution at the individual cell level for an internal population, in which the median bactericidal concentration BC50 represents the mean level of susceptivity, while the bactericidal span BC1-99=(2lnN0)/r indicates the variation degree of the antibiotic susceptivity. Furthermore, tested by CKC approach, the antibiotic susceptivity of E. coli CVCC249 population in each physiological phase to gentamicin or enoxacin was various: susceptivity of the population in the constant growth phase and declining phase all increased compared with that in the accelerating growth phase for gentamicin but declined for enoxacin. The primary investigations revealed that the physiological phase should be taken into account in the context of antibiotic susceptivity and research into antimicrobial mechanism. However there are few reports concerned with this study. Further research using different kinds of antibiotics with synchronized continuous culture of different bacterial strains is required.

  17. High-resolution structure of the antibiotic resistance protein NimA from Deinococcus radiodurans

    International Nuclear Information System (INIS)

    In this paper, the 1.2 Å atomic resolution crystal structure of the 5-nitroimidazole antibiotic resistance protein NimA from Deinococcus radiodurans (DrNimA) is presented. Many anaerobic human pathogenic bacteria are treated using 5-nitroimidazole-based (5-Ni) antibiotics, a class of inactive prodrugs that contain a nitro group. The nitro group must be activated in an anaerobic one-electron reduction and is therefore dependent on the redox system in the target cells. Antibiotic resistance towards 5-Ni drugs is found to be related to the nim genes (nimA, nimB, nimC, nimD, nimE and nimF), which are proposed to encode a reductase that is responsible for converting the nitro group of the antibiotic into a nonbactericidal amine. A mechanism for the Nim enzyme has been proposed in which two-electron reduction of the nitro group leads to the generation of nontoxic derivatives and confers resistance against these antibiotics. The cofactor was found to be important in the mechanism and was found to be covalently linked to the reactive His71. In this paper, the 1.2 Å atomic resolution crystal structure of the 5-nitroimidazole antibiotic resistance protein NimA from Deinococcus radiodurans (DrNimA) is presented. A planar cofactor is clearly visible and well defined in the electron-density map adjacent to His71, the identification of the cofactor and its properties are discussed

  18. Detection of residues antibiotics in food using a microbiological method

    International Nuclear Information System (INIS)

    Antibiotics are effective therapeutic agents because of their property of selective bacterial toxicity which helps controlling infections. Animals, just like humans, can be treated with antibiotics. This use of antibiotics can lead to the development of resistance. Resistant strains may cause severe infections in humans and animals. In addition, antibiotic residues might represent a problem for human health. Our objective is to develop a microbiological method for the detection of antibiotic residues in poultry(muscle, liver,...). For this purpose, antibiotic sensitive bacteria and selective agar media were used. An inhibition growth zone surrounds each of the food samples containing antibiotic residues after a prescribed incubation time. (Author). 23 refs

  19. Magnetic separation of antibiotics by electrochemical magnetic seeding

    International Nuclear Information System (INIS)

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  20. Magnetic separation of antibiotics by electrochemical magnetic seeding

    Energy Technology Data Exchange (ETDEWEB)

    Ihara, I; Toyoda, K [Department of Agricultural Engineering and Socio Economics, Kobe University, Nada, Kobe 657-8501 (Japan); Beneragama, N; Umetsu, K [Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan)], E-mail: ihara@port.kobe-u.ac.jp

    2009-03-01

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  1. Emergence and dissemination of antibiotic resistance: a global problem.

    Science.gov (United States)

    Choudhury, R; Panda, S; Singh, D V

    2012-01-01

    Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure. PMID:23183460

  2. Influence of electromagnetic signal of antibiotics excited by low-frequency pulsed electromagnetic fields on growth of Escherichia coli.

    Science.gov (United States)

    Ke, Yin-Lung; Chang, Fu-Yu; Chen, Ming-Kun; Li, Shun-Lai; Jang, Ling-Sheng

    2013-01-01

    Energy medicine (EM) provides a new medical choice for patients, and its advantages are the noninvasive detection and nondrug treatment. An electromagnetic signal, a kind of EM, induced from antibiotic coupling with weak, extremely low-frequency pulsed electromagnetic fields (PEMFs) is utilized for investigating the growth speed of Escherichia coli (E. coli). PEMFs are produced by solenoidal coils for coupling the electromagnetic signal of antibiotics (penicillin). The growth retardation rate (GRR) of E. coli is used to investigate the efficacy of the electromagnetic signal of antibiotics. The E. coli is cultivated in the exposure of PEMFs coupling with the electromagnetic signal of antibiotics. The maximum GRR of PEMFs with and without the electromagnetic signal of antibiotics on the growth of E. coli cells in the logarithmic is 17.4 and 9.08%, respectively. The electromagnetic signal of antibiotics is successfully coupled by the electromagnetic signal coupling instrument to affect the growth of E. coli. In addition, the retardation effect on E. coli growth can be improved of by changing the carrier frequency of PEMFs coupling with the electromagnetic signal of antibiotics. GRR caused by the electromagnetic signal of antibiotics can be fixed by a different carrier frequency in a different phase of E. coli growth.

  3. Self-defensive layer-by-layer films with bacteria-triggered antibiotic release.

    Science.gov (United States)

    Zhuk, Iryna; Jariwala, Freneil; Attygalle, Athula B; Wu, Yong; Libera, Matthew R; Sukhishvili, Svetlana A

    2014-08-26

    We report on highly efficient, bioresponsive, controlled-release antibacterial coatings constructed by direct assembly of tannic acid (TA) with one of several cationic antibiotics (tobromycin, gentamicin, and polymyxin B) using the layer-by-layer (LbL) technique. These films exhibit a distinct “self-defense” behavior triggered by acidification of the immediate environment by pathogenic bacteria, such as Staphylococcus epidermidis (S. epidermidis) or Escherichia coli (E. coli). Films assembled using spin-assisted and dip-assisted techniques show drastically different morphology, thickness and pH-/bacteria-triggered antibiotic release characteristics. While dip-deposited films have rough surfaces with island-like, granular structures regardless of the film thickness, spin-assisted LbL assemblies demonstrate a transition from linear deposition of uniform 2D films to a highly developed 3D morphology for films thicker than ∼45 nm. Ellipsometry, UV–vis and mass spectrometry confirm that all coatings do not release antibiotics in phosphate buffered saline at pH 7.4 for as long as one month in the absence of bacteria and therefore do not contribute to the development of antibiotic resistance. These films do, however, release antibiotics upon pH lowering. The rate of triggered release can be controlled through the choice of assembled antibiotic and the assembly technique (spin- vs dip-deposition) and by the spinning rate used during deposition, which all affect the strength of TA–antibiotic binding. TA/antibiotic coatings as thin as 40 nm strongly inhibit S. epidermidis and E. coli bacterial growth both at surfaces and in surrounding medium, but support adhesion and proliferation of murine osteoblast cells. These coatings thus present a promising way to incorporate antibacterial agents at surfaces to prevent bacterial colonization of implanted biomedical devices.

  4. A new naphthaquinone antibiotic from a new species of yeast.

    Science.gov (United States)

    Flegel, T W; Meevootisom, V; Thebtaranonth, Y; Qi-Tai, Z; Clardy, J

    1984-04-01

    A fusiform yeast producing limited pseudomycelium and limited true mycelium on malt extract agar has been isolated. This non-fermentative yeast has hyaline cell walls but produces a thick, black oily exudate which is water insoluble and gives the colony a smooth black lacquered appearance. On the basis of morphology and physiology, this organism is distinctive enough to warrant the designation of a new genus. During stationary phase of cultures on chemically defined medium, a deep red substance is produced which has strong antibiotic activity against Staphylococcus aureus in vitro. The substance has been identified as a new natural naphthaquinone of the empirical formula C16H16O7 . PMID:6725143

  5. Epidemiology of antibiotic resistance in Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Simpore J; Zeba B; Karou D; Ilboudo D; Pignatelli S; Nacoulma OG; Musumeci S

    2008-01-01

    Burkina Faso (West Africa)is a tropical country with a high incidence of infectious diseases.The uncontrolled use of antibiotics against bacterial pathogens has given rise to the emergence of antibiotic resistance in this country.The aims of this study were.i)to determine the prevalences of the most important pathogenic bacteri-a,isolated in the town of Ouagadougou.ii)to identify the bacterial species which have acquired resistance as a result of antibiotic selection.iii)to compare antibiotic-resistances ofEscherichia coli isolated from stool cul-ture in the present study,with results obtained in 2002 from strains collected in the same structure in Burkina Faso.iv)to determine the trend of antibiotic resistance in Burkina Faso in order to give local advice on the most appropriate empiric antibiotic therapy.Six thousand two hundred and sixty four samples of blood,stools, urine,sputum,pus and vaginal secretion were collected and analyzed in Saint Camille Medical Center (SC-MC)laboratory from May 2001 to May 2006.Out of the 6264 samples tested no pathogen was identified in 1583 (25.31%),whilst 4681 (74.73%)were positive,with the incidence of the microrganisms isolated be-ing as follows:Escherichia coli 1291 (27.6%),Staphylococcus aureus 922 (19.7%),Salmonella spp 561 (12.0%),Streptococcus spp 499 (10.7%),Klebsiella spp 359 (7.7%),Shigella spp (6.3%),Acineto-bacter spp 266 (5.7%)and others 783 (16.7%).Among the isolated pathogens,the highest resistance was found to Amoxycillin:Proteus spp 95.6%,Escherichia coli 78.2%,Salmonella spp 62.2%,Shigella spp 73. 4% and Klebsiella spp 89.9%,followed by resistance to Ampicillin and cotrimoxazole.Comparing the preva-lence of antibiotic resistance of Escherichia coli from stool cultures isolated during 1999-2000 to that of 2001-2006,a significant reduction was found,which could be due to the improved use of antibiotics in recent years. The reduced antibiotic-resistance observed in pathogens isolated in Burkina Faso during this

  6. Antibiotics in Canadian poultry productions and anticipated alternatives

    OpenAIRE

    Diarra, Moussa S.; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can ea...

  7. Antibiotics in Canadian poultry productions and anticipated alternatives

    OpenAIRE

    Moussa Sory Diarra; Francois eMalouin

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics in feed (growth promoters) need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can ea...

  8. Antibiotic use and resistance in long term care facilities.

    OpenAIRE

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Benthem, B.H.B. van; Natsch, S.; Hertogh, C.M.P.M.

    2012-01-01

    Introduction: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available on antibiotic use, antibiotic resistance, and strategies to reduce antibiotic resistance. Methods: Relevant literature was identified by conducting a systematic search in the MEDLINE and EMBASE dat...

  9. Antibiotic efficacy is linked to bacterial cellular respiration

    OpenAIRE

    Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J; Khalil, Ahmad S.; James J Collins

    2015-01-01

    The global burden of antibiotic resistance has created a demand to better understand the basic mechanisms of existing antibiotics. Of significant interest is how antibiotics may perturb bacterial metabolism, and how bacterial metabolism may influence antibiotic activity. Here, we study the interaction of bacteriostatic and bactericidal antibiotics, the two major phenotypic drug classes. Interestingly, the two classes differentially perturb bacterial cellular respiration, with major consequenc...

  10. Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics.

    Science.gov (United States)

    Pritsos, C A; Sartorelli, A C

    1986-07-01

    Mitomycin C (MC) is a naturally occurring anticancer agent which has been shown to be more cytotoxic to hypoxic tumor cells than to their aerobic counterparts. The mechanism of action of this agent is thought to involve biological reductive activation, to a species that alkylates DNA. A comparison of the cytotoxicity of MC to EMT6 tumor cells with that of the structural analogues porfiromycin (PM), N-(N',N'-dimethylaminomethylene)amine analogue of mitomycin C (BMY-25282), and N-(N',N'-dimethylaminomethylene)amine analogue of porfiromycin (BL-6783) has demonstrated that PM is considerably less cytotoxic to aerobic EMT6 cells than MC, whereas BMY-25282 and BL-6783 are significantly more toxic. The relative abilities of each of these compounds to generate oxygen free radicals following biological activation were measured. Tumor cell sonicates, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, xanthine oxidase, and mitochondria were used as the biological reducing systems. All four mitomycin antibiotics produced oxygen radicals following biological reduction, a process that may account for the aerobic cytotoxicity of agents of this class. The generation of relative amounts of superoxide and hydroxyl radical were also measured in EMT6 cell sonicates. BMY-25282 and BL-6783 produced significantly greater quantities of oxygen free radicals with the EMT6 cell sonicate, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, and mitochondria than did MC and PM. In contrast, BMY-25282 and BL-6783 did not generate detectable levels of free radicals in the presence of xanthine oxidase, whereas this enzyme was capable of generating free radicals with MC and PM as substrates. MC consistently produced greater amounts of free radicals than PM with all of the reducing systems. BMY-25282, BL-6783, and MC all generated hydroxyl radicals, while PM did not appear to form these radicals. The findings indicate that a correlation exists between

  11. Autoinducer-2 analogs and electric fields - an antibiotic-free bacterial biofilm combination treatment.

    Science.gov (United States)

    Subramanian, Sowmya; Gerasopoulos, Konstantinos; Guo, Min; Sintim, Herman O; Bentley, William E; Ghodssi, Reza

    2016-10-01

    Bacterial biofilms are a common cause of chronic medical implant infections. Treatment and eradication of biofilms by conventional antibiotic therapy has major drawbacks including toxicity and side effects associated with high-dosage antibiotics. Additionally, administration of high doses of antibiotics may facilitate the emergence of antibiotic resistant bacteria. Thus, there is an urgent need for the development of treatments that are not based on conventional antibiotic therapies. Presented herein is a novel bacterial biofilm combination treatment independent of traditional antibiotics, by using low electric fields in combination with small molecule inhibitors of bacterial quorum sensing - autoinducer-2 analogs. We investigate the effect of this treatment on mature Escherichia coli biofilms by application of an alternating and offset electric potential in combination with the small molecule inhibitor for 24 h using both macro and micro-scale devices. Crystal violet staining of the macro-scale biofilms shows a 46 % decrease in biomass compared to the untreated control. We demonstrate enhanced treatment efficacy of the combination therapy using a high-throughput polydimethylsiloxane-based microfluidic biofilm analysis platform. This microfluidic flow cell is designed to reduce the growth variance of in vitro biofilms while providing an integrated control, and thus allows for a more reliable comparison and evaluation of new biofilm treatments on a single device. We utilize linear array charge-coupled devices to perform real-time tracking of biomass by monitoring changes in optical density. End-point confocal microscopy measurements of biofilms treated with the autoinducer analog and electric fields in the microfluidic device show a 78 % decrease in average biofilm thickness in comparison to the negative controls and demonstrate good correlation with real-time optical density measurements. Additionally, the combination treatment showed 76 % better treatment

  12. Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang;

    2016-01-01

    acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm...... subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance...... development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates...

  13. Nouws antibiotics test: Validation of a post-screening method for antibiotic residues in kidney

    NARCIS (Netherlands)

    Pikkemaat, M.G.; Oostra-van Dijk, S.; Schouten, J.; Rapallini, M.; Kortenhoeven, L.; Egmond, van H.J.

    2009-01-01

    Anticipating the rise in ‘suspect’ samples caused by the introduction of a more sensitive screening test for the presence of antibiotic residues in slaughter animals, an additional microbial post-screening method was developed. The test comprises four antibiotic group specific test plates, optimized

  14. Characterization of Antibiotics and Antibiotic Resistance Genes on an Ecological Farm System

    Directory of Open Access Journals (Sweden)

    Songhe Zhang

    2015-01-01

    Full Text Available There is a growing concern worldwide about the prevalence of antibiotics and antibiotic resistance genes (ARGs on the farm. In this study, we investigated the distribution of seven antibiotics and ten ARGs in fresh and dried pig feces, in biogas slurry, and in grape-planting soil from an ecological farm. Antibiotics including sulfamethazine, norfloxacin, ofloxacin, tetracycline, oxytetracycline, and chlortetracycline were detected in these samples (except for sulfamethoxazole in dried feces. In general, antibiotics levels in samples were in the sequence: biogas slurry > fresh feces > soil or dried feces. Results of ecological risk assessments revealed that among the seven antibiotics chlortetracycline showed the highest ecological risk. Among the ten ARGs, sulI and tetO were the most prevalent on this ecological farm. There were positive correlations between certain ARGs and the corresponding antibiotics on this ecological farm. Therefore, continuous monitoring of antibiotics and their corresponding ARGs should be conducted in the agroecosystem near the concentrated animal farming operation systems.

  15. Effects of combination of antibiotic-resistant bifidobacteria and corresponding antibiotics on survival of irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal' tsev, V.N.

    1982-05-01

    Broad-spectrum antibiotics are used to treat intestinal dysbacteriosis of diverse etiology, including postradiation dysbacteriosis. Antibiotic therapy is instrumental in decontaminating the intestine. In addition to pathogenic microorganisms, there is disappearance of lactobacilli and bifidobacteria which perform several important and useful functions. For this reason, in addition to antibiotics, bifidobacterial preparations are used to restore the microbial cenosis and administration thereof is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bididobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. On the other hand, use of antibiotics alone could, in turn, be the cause of intestinal dysbacteriosis. Our objective was to eliminate intestinal dysbacteriosis in irradiated animals by means of combining antibiotics and preparations of bifidobacteria resistant to these antibiotics, and thus prolong the life of these animals.

  16. Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

    Science.gov (United States)

    Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

    2016-06-01

    Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture. PMID:27038482

  17. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance.

    NARCIS (Netherlands)

    Bell, B.G.; Schellevis, F.; Stobberingh, E.; Goossen, H.; Pringle, M.

    2014-01-01

    Background: Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substant

  18. [Acute otitis media and antibiotics. Evidence-based guidelines for antibiotic therapy?].

    Science.gov (United States)

    Thorøe, J; Lous, J

    1999-09-27

    Antibiotic treatment of acute otitis media is controversial. The questions are when to treat, with which antibiotic, and for how long? Within the last years three reviews attempting to discuss these questions have been published. All three found only a marginal effect of antibiotic treatment. The effect was less earache after the first day. The meta-analyses showed that between eight and 22 children had to be treated before one had any benefit of the treatment. The randomized studies did not find a greater effect of amoxicillin than of penicillin. The marginal effect of antibiotics on acute otitis media supports watchful waiting and individualized care and follow-up. There is a need for well-organized, randomized, placebo-controlled trials including the youngest children and the more severe cases of acute otitis media where the effect of antibiotic treatment may turn out to be most beneficial.

  19. Development and comparison of four methods for the extraction of antibiotics from a vegetative matrix.

    Science.gov (United States)

    Sallach, J Brett; Snow, Daniel; Hodges, Laurie; Li, Xu; Bartelt-Hunt, Shannon

    2016-04-01

    Studies have shown the potential for antibiotic uptake into food crops from irrigation water and soils containing pharmaceuticals. The objective of the present study was to develop and compare methods quantifying uptake of antibiotics in food crops. Four methods were evaluated: freeze-and-thaw cell lysing, mechanical maceration, tissue sonication, and microwave-assisted solvent extraction. Four antibiotics (ciprofloxacin, lincomycin, oxytetracycline, and sulfamethoxazole) were tested representing 4 classes of antibiotics. The methods were evaluated based on method detection limits, analyte recoveries, and sample preparation time. The 2 most viable methods, freeze-and-thaw lysing and mechanical maceration, were used on replicate lettuce (Lactuca sativa) samples grown using irrigation water spiked with 3 of the antibiotic contaminants. Only lincomycin and sulfamethoxazole were detected in lettuce samples at concentrations as high as 1757 ng/g and 425 ng/g, with detection limits of 57 ng/g and 35 ng/g, respectively. Freeze-and-thaw cell lysing provided the highest level of extraction efficiency on environmental samples and required the least amount of sample preparation while providing adequate detection limits and reproducible analyte recovery. PMID:26291062

  20. Toxicity of three antibiotics used in aquaculture on the marine microalgae Tetraselmis suecica (Kylin Butch.

    Directory of Open Access Journals (Sweden)

    Marta Seoane

    2014-06-01

    Full Text Available Aquaculture facilities are a potential source of antibiotics to the aquatic ecosystems. The presence of these compounds in the environment may have deleterious effects on non-target aquatic organisms such as microalgae, which are often used as biological indicators of pollution. Therefore, the aim of the present study was to evaluate the toxicity induced by chloramphenicol (CHL, florfenicol (FLO and oxytetracycline (OTC, three antibiotics widely used in aquaculture, on the marine microalgae Tetraselmis suecica, a species also used in aquacultural practices. Toxicity was evaluated taking into account alterations on growth and cellular viability and activity, being these parameters monitored using flow cytometry technique. Results showed that all three antibiotics assayed inhibit growth of T. suecica with 96 h IC50 values of 11.16, 9.03 and 17.25 mg l-1 for CHL, FLO and OTC, respectively. After 24 hours of exposure, the integrity of the cell membrane, related with cellular viability and assessed by propidium iodide staining (PI, was not altered; therefore cells remained viable. However, FLO and OTC were found to significant reduce the metabolic activity at higher concentrations assayed, as indicated the fluorescein diacetate assay (FDA. Since growth inhibition and significant physiological alterations were observed, it can be concluded that T. suecica was sensitive to the three antibiotics tested, thus the use of these antibiotics should be carefully monitored to reduce the potential risk of contamination of the marine environment.

  1. Recycling Antibiotics into GUMBOS: A New Combination Strategy to Combat Multi-Drug-Resistant Bacteria

    Directory of Open Access Journals (Sweden)

    Marsha R. Cole

    2015-04-01

    Full Text Available The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin and a well-known antiseptic (chlorhexidine di-acetate were fashioned into a group of uniform materials based on organic salts (GUMBOS as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics, GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.

  2. Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to β-lactam antibiotics.

    Science.gov (United States)

    Pensinger, Daniel A; Aliota, Matthew T; Schaenzer, Adam J; Boldon, Kyle M; Ansari, Israr-ul H; Vincent, William J B; Knight, Benjamin; Reniere, Michelle L; Striker, Rob; Sauer, John-Demian

    2014-08-01

    While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.

  3. Recycling antibiotics into GUMBOS: a new combination strategy to combat multi-drug-resistant bacteria.

    Science.gov (United States)

    Cole, Marsha R; Hobden, Jeffery A; Warner, Isiah M

    2015-01-01

    The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin) and a well-known antiseptic (chlorhexidine di-acetate) were fashioned into a group of uniform materials based on organic salts (GUMBOS) as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics), GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.

  4. ANTIMICROBIAL PEPTIDES: AN EFFECTIVE ALTERNATIVE FOR ANTIBIOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    KK PULICHERLA

    2013-01-01

    Full Text Available Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence has suggested that cationic antimicrobial peptides (AMP’s are of greatest potential to represent a new class of antibiotics. These peptides have a good scope in current antibiotic research. During the past two decades several AMPs have been isolated from a wide variety of animals (both vertebrates and invertebrates, and plants as well as from bacteria and fungi. These are relatively small (<10kDa, cationic and amphipathic peptides of variable length, sequence and structure. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, protozoa, yeast, fungi and viruses. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. Antimicrobial peptides encompass a wide variety of structural motifs such as α -helical peptides, β -sheet peptides, looped peptides and extended peptides. Preparations enriched by a specific protein are rarely easily obtained from natural host cells. Hence, recombinant protein production is frequently the sole applicable procedure. Several fusion strategies have been developed for the expression and purification of small antimicrobial peptides (AMPs in recombinant bacterial expression systems which were produced by cloning. This article aims to review in brief the sources of antimicrobial peptides, diversity in structural features, mode of action, production strategies and insight into the current data on their antimicrobial activity followed by a brief comment on the peptides that have entered clinical trials.

  5. Antibiotics in development targeting protein synthesis.

    Science.gov (United States)

    Sutcliffe, Joyce A

    2011-12-01

    The resolution of antibiotic-ribosomal subunit complexes and antibacterial-protein complexes at the atomic level has provided new insights into modifications of clinically relevant antimicrobials and provided new classes that target the protein cellular apparatus. New chemistry platforms that use fragment-based drug design or allow novel modifications in known structural classes are being used to design new antibiotics that overcome known resistance mechanisms and extend spectrum and potency by circumventing ubiquitous efflux pumps. This review provides details on seven antibiotics in development for treatment of moderate-to-severe community-acquired bacterial pneumonia and/or acute bacterial skin and skin structure infections: solithromycin, cethromycin, omadacycline, CEM-102, GSK1322322, radezolid, and tedizolid. Two antibiotics of the oxazolidinone class, PF-02341272 and AZD5847, are being developed as antituberculosis agents. Only three antibiotics that target the protein cellular machinery, TP-434, GSK2251052, and plazomicin, have a spectrum that encompasses multidrug-resistant Gram-negative pathogens. These compounds provide hope for treating key pathogens that cause serious disease in both the community and the hospital. PMID:22191530

  6. BIOSYNTHESIS AND PROPERTIES OF ANTIBIOTIC BATUMIN

    Directory of Open Access Journals (Sweden)

    V. V. Klochko

    2014-12-01

    Full Text Available Biosynthesis of antistaphylococcal antibiotic batumin under periodic conditions of Pseudomonas batumici growth has been studied. Antibiotic synthesis in fermenter occurred across the culture growth and achieved its maximal value after 50–55 hours. The active oxygen utilization by the producing strain was observed during 20–55 hours of fermentation with maximum after 40–45 hours. Antibiotic yield was 175–180 mg/l and depended on intensity of aeration. contrast to «freshly isolated» antibiotic after fermentation the long-term kept batumin has shown two identical by molecular mass peaks according to the chromato-mass spectrometric analysis. Taking into account of batumin molecule structure the conclusion has been made that the most probable isomerization type is keto-enolic tautomerism. At the same time batumin is diastereoisomer of kalimantacin A which has the same chemical structure. The optic rotation angle is [α]d25 = +56.3° for kalimantacin and [α]d25 = –13.5° for batumin. The simultaneous P. batumici growth and antibiotic biosynthesis and the ability of this molecule to optical isomerisation and keto-enolic forms formation allow us to suppose that batumin plays a certain role in metabolism of the producing strain.

  7. Antibiotic resistance: are we all doomed?

    Science.gov (United States)

    Collignon, P

    2015-11-01

    Antibiotic resistance is a growing and worrying problem associated with increased deaths and suffering for people. Overall, there are only two factors that drive antimicrobial resistance, and both can be controlled. These factors are the volumes of antimicrobials used and the spread of resistant micro-organisms and/or the genes encoding for resistance. The One Health concept is important if we want to understand better and control antimicrobial resistance. There are many things we can do to better control antimicrobial resistance. We need to prevent infections. We need to have better surveillance with good data on usage patterns and resistance patterns available across all sectors, both human and agriculture, locally and internationally. We need to act on these results when we see either inappropriate usage or resistance levels rising in bacteria that are of concern for people. We need to ensure that food and water sources do not spread multi-resistant micro-organisms or resistance genes. We need better approaches to restrict successfully what and how antibiotics are used in people. We need to restrict the use of 'critically important' antibiotics in food animals and the entry of these drugs into the environment. We need to ensure that 'One Health' concept is not just a buzz word but implemented. We need to look at all sectors and control not only antibiotic use but also the spread and development of antibiotic resistant bacteria - both locally and internationally. PMID:26563691

  8. Utilisation of antibiotic therapy in community practice.

    LENUS (Irish Health Repository)

    McGowan, B

    2008-10-01

    The aim of the study was to identify outpatient antibiotic consumption between Jan 2000 and Dec 2005 through analysis of the HSE-Primary Care Reimbursement Services (PCRS) database as part of the Surveillance of Antimicrobial Resistance in Ireland (SARI) project. Total antibiotic consumption on the PCRS scheme between January 2000 and December 2005 expressed in Defined Daily Dose per 1000 PCRS inhabitants per day increased by 26%. The penicillin group represents the highest consumption accounting for approximately 50% of the total outpatient antibiotic use. Total DIDs for this group increased by 25% between 2000 and 2005. Co-amoxiclav and amoxicillin account for 80% of the total consumption of this group of anti-infectives. With the exception of aminoglycosides and sulfonamides which demonstrated a decrease in DID consumption of 47% and 8% respectively, all other groups of anti-infectives had an increase in DID consumption of greater than 25% during the study period. Antibiotic prescribing data is a valuable tool for assessing public health strategies aiming to optimise antibiotic prescribing.

  9. Medical Treatment of Diverticular Disease: Antibiotics.

    Science.gov (United States)

    Lué, Alberto; Laredo, Viviana; Lanas, Angel

    2016-10-01

    Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients. PMID:27622367

  10. New techniques in antibiotic discovery and resistance: Raman spectroscopy.

    Science.gov (United States)

    Carey, Paul R; Heidari-Torkabadi, Hossein

    2015-09-01

    Raman spectroscopy can play a role in both antibiotic discovery and understanding the molecular basis of resistance. A major challenge in drug development is to measure the population of the drug molecules inside a cell line and to follow the chemistry of their reactions with intracellular targets. Recently, a protocol based on Raman microscopy has been developed that achieves these goals. Drug candidates are soaked into live bacterial cells and subsequently the cells are frozen and freeze-dried. The samples yield exemplary (nonresonance) Raman data that provide a measure of the number of drug molecules within each cell, as well as details of drug-target interactions. Results are discussed for two classes of compounds inhibiting either β-lactamase or dihydrofolate reductase enzymes in a number of Gram-positive or Gram-negative cell lines. The advantages of the present protocol are that it does not use labels and it can measure the kinetics of cell-compound uptake on the time scale of minutes. Spectroscopic interpretation is supported by in vitro Raman experiments. Studying drug-target interactions in aqueous solution and in single crystals can provide molecular level insights into drug-target interactions, which, in turn, provide the underpinnings of our understanding of data from bacterial cells. Thus, the applicability of X-ray crystallographic-derived data to in-cell chemistry can be tested. PMID:26275225

  11. Patents, antibiotics, and autarky in Spain.

    Science.gov (United States)

    Romero De Pablos, Ana

    2014-01-01

    Patents on antibiotics were introduced in Spain in 1949. Preliminary research reveals diversification in the types of antibiotics: patents relating to penicillin were followed by those relating to streptomycin, erythromycin and tetracycline. There was also diversification in the firms that applied for patents: while Merck & Co. Incorporated and Schenley Industries Inc. were the main partners with Spanish antibiotics manufacturers in the late 1940s, this industrial space also included many others, such as Eli Lilly & Company, Abbott Laboratories, Chas. Pfizer & Co. Incorporated, and American Cyanamid Company in the mid-1970s. The introduction of these drugs in Spain adds new elements to a re-evaluation of the autarkic politics of the early years of the Franco dictatorship. PMID:26054209

  12. Antibiotic resistance genes in the environment

    Directory of Open Access Journals (Sweden)

    Jianqiang Su

    2013-07-01

    Full Text Available Antibiotic resistance and its spread in bacteria are topics of great importance in global research. In this paper, we review recent progress in understanding sources, dissemination, distribution and discovery of novel antibiotics resistance genes (ARGs in the environment. Bacteria exhibiting intrinsic resistance and antibiotic resistant bacteria in feces from humans and animals are the major sources of ARGs occurring in the environment. A variety of novel ARGs have been discovered using functional metagenomics. Recently, the long-term overuse of antibotics in drug therapy and animal husbandry has led to an increase in diversity and abundance of ARGs, causing the environmental dissemination of ARGs in aquatic water, sewage treatmentplants, rivers, sediment and soil. Future research should focus on dissemination mechanisms of ARGs, the discovery of novel ARGs and their resistant mechanisms, and the establishment of environmental risk assessment systems for ARGs.

  13. Antibiotics for the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-12-01

    Full Text Available Mesut OgrendikDivision Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: Antibiotic treatment for rheumatoid arthritis (RA commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment.Keywords: oral bacteria, treatment, disease-modifying antirheumatic drugs, periodontitis

  14. Tolerance of staphylococci to bactericidal antibiotics.

    Science.gov (United States)

    Vaudaux, Pierre; Lew, Daniel P

    2006-05-01

    Antibiotic therapy for deep-seated staphylococcal infections, especially when they are associated with artificial devices used for orthopedic surgery is often associated with failure. Standard anti-staphylococcal bactericidal antibiotics, such as semi-synthetic penicillins, cephalosporins, or glycopeptides, are effective when given prophylactically in clinical conditions or experimental trials of implant-related infections. However, the efficacy of all anti-staphylococcal agents is seriously diminished on already established implant-related deep-seated infections, which then frequently require surgical implant removal to obtain a cure. The failure of antibiotic therapy to cure established staphylococcal foreign-body infections may arise in part from a broad-spectrum phenotypic tolerance expressed in vivo to different classes of antimicrobial agents. The molecular and physiological mechanisms of this in vivo tolerance remain poorly understood. PMID:16651066

  15. Antibiotics for acute otitis media in children.

    Science.gov (United States)

    Nitsche, María Pía; Carreño, Monica

    2015-10-29

    Acute otitis media is one of the most common infectious diseases diagnosed in children. Antibiotic treatment use remains controversial. This summary aims to evaluate the effectiveness and safety of antibiotics in children with acute otitis media. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 18 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforations in children with acute otitis media, but they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).

  16. Martinomycin, a new polyether antibiotic produced by Streptomyces salvialis. I. Taxonomy, fermentation and biological activity.

    Science.gov (United States)

    Bernan, V S; Montenegro, D A; Goodman, J J; Alluri, M R; Carter, G T; Abbanat, D R; Pearce, C J; Maiese, W M; Greenstein, M

    1994-12-01

    Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin. Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria. PMID:7844037

  17. A Pseudo-tRNA Modulates Antibiotic Resistance in Bacillus cereus

    DEFF Research Database (Denmark)

    Rogers, Theresa E; Ataide, Sandro F; Dare, Kiley;

    2012-01-01

    . Deletion of tRNA(Other) led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding t...

  18. beta-Lactam and glycopeptide antibiotics: first and last line of defense?

    NARCIS (Netherlands)

    Jovetic, S.; Yang Zhu, Yang; Marcone, G.L.; Marinelli, F.; Tramper, J.

    2010-01-01

    Most infections are caused by bacteria, many of which are ever-evolving and resistant to nearly all available antibiotics beta-Lactams and glycopeptides are used to combat these infections by inhibiting bacterial cell-wall synthesis This mechanism remains an interesting target in the search for new

  19. β-Lactam and glycopeptide antibiotics: First and last line of defense?

    NARCIS (Netherlands)

    Jovetic, S.; Zhu, Y.; Marcone, G.L.; Marinelli, F.; Tramper, J.

    2010-01-01

    Most infections are caused by bacteria, many of which are ever-evolving and resistant to nearly all available antibiotics. β-Lactams and glycopeptides are used to combat these infections by inhibiting bacterial cell-wall synthesis. This mechanism remains an interesting target in the search for new a

  20. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    Science.gov (United States)

    Surawicz, Christina M.

    Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

  1. Polyphosphate Kinase Mediates Antibiotic Tolerance in Extraintestinal Pathogenic Escherichia coli PCN033.

    Science.gov (United States)

    Chen, Jing; Su, Lijie; Wang, Xiangru; Zhang, Tao; Liu, Feng; Chen, Huanchun; Tan, Chen

    2016-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. Therefore, it is necessary to explore new drug targets to control E. coli epidemics. Previous studies have reported that ppk mutants of Burkholderia pseudomallei and Mycobacterium tuberculosis are more susceptible than the wild types (WTs) to stress. Therefore, we investigated the stress response to antibiotics mediated by polyphosphate kinase (PPK) in ExPEC strain PCN033. We observed that planktonic cells of a ppk knockout strain (Δppk) were more susceptible to antibiotics than was WT. However, biofilm-grown Δppk cells showed similar susceptibility to that of the WT and were more tolerant than the planktonic cells. During the planktonic lifestyle, the expression of genes involved in antibiotic tolerance (including resistance-conferring genes, and antibiotic influx, and efflux genes) did not change in the Δppk mutant without antibiotic treatment. However, the resistance-conferring gene bla and efflux genes were upregulated more in the WT than in the Δppk mutant by treatment with tazobactam. After treatment with gentamycin, the efflux genes and influx genes were upregulated and downregulated, respectively, more in the WT than in the Δppk mutant. The expression of genes involved in biofilm regulation also changed after treatment with tazobactam or gentamycin, and which is consistent with the results of the biofilm formation. Together, these observations indicate that PPK is important for the antibiotic stress response during the planktonic growth of ExPEC and might be a potential drug target in bacteria. PMID:27242742

  2. Polyphosphate Kinase Mediates Antibiotic Tolerance in Extraintestinal Pathogenic Escherichia coli PCN033

    Directory of Open Access Journals (Sweden)

    Jing eChen

    2016-05-01

    Full Text Available Extraintestinal pathogenic Escherichia coli (ExPEC causes a variety of acute infections in its hosts, and multidrug-resistant strains present significant challenges to public health and animal husbandry. Therefore, it is necessary to explore new drug targets to control E. coli epidemics. Previous studies have reported that ppk mutants of Burkholderia pseudomallei and Mycobacterium tuberculosis are more susceptible than the wild types (WTs to stress. Therefore, we investigated the stress response to antibiotics mediated by polyphosphate kinase (PPK in ExPEC strain PCN033. We observed that planktonic cells of a ppk knockout strain (Δppk were more susceptible to antibiotics than was WT. However, biofilm-grown Δppk cells showed similar susceptibility to that of the WT and were more tolerant than the planktonic cells. During the planktonic lifestyle, the expression of genes involved in antibiotic tolerance (including resistance-conferring genes,and antibiotic influx and efflux genes did not change in the Δppk mutant without antibiotic treatment. However, the resistance-conferring gene bla and efflux genes were upregulated more in the WT than in the Δppk mutant by treatment with tazobactam. After treatment with gentamycin, the efflux genes and influx genes were upregulated and downregulated, respectively, more in the WT than in the Δppk mutant. The expression of genes involved in biofilm regulation also changed after treatment with tazobactam or gentamycin, and which is consistent with the results of the biofilm formation. Together, these observations indicate that PPK is important for the antibiotic stress response during the planktonic growth of ExPEC and might be a potential drug target in bacteria.

  3. Sublethal Concentrations of Antibiotics Cause Shift to Anaerobic Metabolism in Listeria monocytogenes and Induce Phenotypes Linked to Antibiotic Tolerance

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Fromberg, Arvid; Ng, Yin;

    2016-01-01

    antibiotic concentrations would affect the bacterial physiology and induce antibiotic tolerance. Transcriptomic analyses demonstrated that each of the four antibiotics tested caused an antibiotic-specific gene expression pattern related to mode-of-action of the particular antibiotic. All four antibiotics...... caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism and higher ethanol production. A mutant in the bifunctional acetaldehyde-CoA/alcohol dehydrogenase encoded by Imo1634 did not have altered antibiotic tolerance. However, a mutant...... in Imo1179 (eutE) encoding an aldehyde oxidoreductase where rerouting caused increased ethanol production was tolerant to three of four antibiotics tested. This shift in metabolism could be a survival strategy in response to antibiotics to avoid generation of ROS production from respiration by oxidation...

  4. Efforts to slacken antibiotic resistance: Labeling meat products from animals raised without antibiotics in the United States.

    Science.gov (United States)

    Centner, Terence J

    2016-09-01

    As bacteria and diseases spread due to climatic change, greater amounts of antibiotics will be used thereby exacerbating the problem of antibiotic resistance. To help slacken the development of resistant bacteria, the medical community is attempting to reduce unnecessary and excessive usage of antibiotics. One of the targets is the use of antibiotics for enhancing animal growth and promoting feed efficiency in the production of food animals. While governments can adopt regulations prohibiting nontherapeutic uses of antibiotics in food animals and strategies to reduce antibiotic usage, another idea is to publicize when antibiotics are used in food animal production by allowing labeled meat products. This paper builds upon existing labeling and marketing efforts in the United States to show how a government can develop a verified antibiotic-free labeling program that would allow consumers to purchase meat products from animals that had never received antibiotics. PMID:27236477

  5. How to Fight Back Against Antibiotic Resistance

    DEFF Research Database (Denmark)

    Dantas, Gautam; Sommer, Morten

    2014-01-01

    Mapping the exchange of genes between pathogens and nonpathogens offers new ways to understand and manage the spread of drug-resistant strains. In reality, the development of new antibiotics is only part of the solution, as pathogens will inevitably develop resistance to even the most promising new...... compounds. To save the era of antibiotics, scientists must figure out what it is about bacterial pathogens that makes resistance inevitable. Although most studies on drug resistance have focused on disease causing pathogens, recent efforts have shifted attention to the resistomes of nonpathogenic bacteria...

  6. Effects of probiotics and antibiotics on biofilms

    OpenAIRE

    Pradeep, B.; Pandey, P K; S. Ayyappan

    2003-01-01

    Experiments were conducted to study the effects of probiotics and antibiotics on 3-months old biofilms formed on three different substrates, namely glass, granite and fiberglass reinforced plastic. The variations in heterotrophic bacterial populations associated with biofilms were monitored for a period of one month after one-time application of the probiotic Biogreen (Gee Key Marine Pvt. Ltd, Chennai) at 0.2 mg lˉ¹ and the antibiotic tetracycline at 1.0 mg lˉ¹. The variations in heterotrophi...

  7. Antibiotics, probiotics and prebiotics in IBD.

    Science.gov (United States)

    Bernstein, Charles N

    2014-01-01

    The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause

  8. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone.

    Science.gov (United States)

    Heß, Stefanie; Gallert, Claudia

    2015-12-01

    Tolerance of antibiotic susceptible and antibiotic resistant Escherichia coli, Enterococcus and Staphylococcus strains from clinical and wastewater samples against ozone was tested to investigate if ozone, a strong oxidant applied for advanced wastewater treatment, will affect the release of antibiotic resistant bacteria into the aquatic environment. For this purpose, the resistance pattern against antibiotics of the mentioned isolates and their survival after exposure to 4 mg/L ozone was determined. Antibiotic resistance (AR) of the isolates was not correlating with higher tolerance against ozone. Except for ampicillin resistant E. coli strains, which showed a trend towards increased resistance, E. coli strains that were also resistant against cotrimoxazol, ciprofloxacin or a combination of the three antibiotics were similarly or less resistant against ozone than antibiotic sensitive strains. Pigment-producing Enterococcus casseliflavus and Staphylococcus aureus seemed to be more resistant against ozone than non-pigmented species of these genera. Furthermore, aggregation or biofilm formation apparently protected bacteria in subsurface layers from inactivation by ozone. The relatively large variance of tolerance against ozone may indicate that resistance to ozone inactivation most probably depends on several factors, where AR, if at all, does not play a major role.

  9. Removal of antibiotics and antibiotic resistance genes in rural wastewater by an integrated constructed wetland.

    Science.gov (United States)

    Chen, Jun; Liu, You-Sheng; Su, Hao-Chang; Ying, Guang-Guo; Liu, Feng; Liu, Shuang-Shuang; He, Liang-Ying; Chen, Zhi-Feng; Yang, Yong-Qiang; Chen, Fan-Rong

    2015-02-01

    Integrated constructed wetlands (ICWs) are regarded as one of the most important removal technology for pollutants in rural domestic wastewaters. This study investigated the efficiency of an ICW consisting of a regulating pool, four surface and subsurface flow-constructed wetlands, and a stabilization unit for removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic wastewaters. The results showed that antibiotics leucomycin, ofloxacin, lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the predominant antibiotics and ARGs in the influent, respectively. The ICW system could significantly reduce most of the detected antibiotics and ARGs with their aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the measured concentrations, the total pollution loadings of antibiotics were 3,479 μg/day in the influent and 199 μg/day in the final effluent. Therefore, constructed wetlands could be a promising technology for rural wastewater in removing contaminants such as antibiotics and ARGs.

  10. Antibiotics in Drinking Water in Shanghai and Their Contribution to Antibiotic Exposure of School Children.

    Science.gov (United States)

    Wang, Hexing; Wang, Na; Wang, Bin; Zhao, Qi; Fang, Hong; Fu, Chaowei; Tang, Chuanxi; Jiang, Feng; Zhou, Ying; Chen, Yue; Jiang, Qingwu

    2016-03-01

    A variety of antibiotics have been found in aquatic environments, but antibiotics in drinking water and their contribution to antibiotic exposure in human are not well-explored. For this, representative drinking water samples and 530 urine samples from schoolchildren were selected in Shanghai, and 21 common antibiotics (five macrolides, two β-lactams, three tetracyclines, four fluoquinolones, four sulfonamides, and three phenicols) were measured in water samples and urines by isotope dilution two-dimensional ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. Drinking water included 46 terminal tap water samples from different spots in the distribution system of the city, 45 bottled water samples from 14 common brands, and eight barreled water samples of different brands. Of 21 antibiotics, only florfenicol and thiamphenicol were found in tap water, with the median concentrations of 0.0089 ng/mL and 0.0064 ng/mL, respectively; only florfenicol was found in three bottled water samples from a same brand, with the concentrations ranging from 0.00060 to 0.0010 ng/mL; no antibiotics were found in barreled water. In contrast, besides florfenicol and thiamphenicol, an additional 17 antibiotics were detected in urine samples, and the total daily exposure doses and detection frequencies of florfenicol and thiamphenicol based on urine samples were significantly and substantially higher than their predicted daily exposure doses and detection frequencies from drinking water by Monte Carlo Simulation. These data indicated that drinking water was contaminated by some antibiotics in Shanghai, but played a limited role in antibiotic exposure of children.

  11. Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.

    Science.gov (United States)

    Yap, Polly Soo Xi; Lim, Swee Hua Erin; Hu, Cai Ping; Yiap, Beow Chin

    2013-06-15

    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance. PMID:23537749

  12. Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China.

    Science.gov (United States)

    Wu, Dong; Huang, Zhiting; Yang, Kai; Graham, David; Xie, Bing

    2015-04-01

    Many studies have quantified antibiotics and antibiotic resistance gene (ARG) levels in soils, surface waters, and waste treatment plants (WTPs). However, similar work on municipal solid waste (MSW) landfill leachates is limited, which is concerning because antibiotics disposal is often in the MSW stream. Here we quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM, ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014. Antibiotic levels were higher in TS than LR leachates (985 ± 1965 ng/L vs 345 ± 932 ng/L, n = 40), which was because of very high levels in the HL leachates (averaging at 1676 ± 5175 ng/L, n = 40). The mean MLs (3561 ± 8377 ng/L, n = 12), FQs (975 ± 1608 ng/L, n = 24), and SAs (402 ± 704 ng/L, n = 42) classes of antibiotics were highest across all samples. ARGs were detected in all leachate samples with normalized sul2 and ermB levels being especially elevated (-1.37 ± 1.2 and -1.76 ± 1.6 log (copies/16S-rDNA), respectively). However, ARG abundances did not correlate with detected antibiotic levels, except for tetW and tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured ARGs did significantly correlate with heavy metal levels (p antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment.

  13. Value addition in the efficacy of conventional antibiotics by Nisin against Salmonella.

    Science.gov (United States)

    Singh, Aman Preet; Prabha, Vijay; Rishi, Praveen

    2013-01-01

    Frequent and indiscriminate use of existing battery of antibiotics has led to the development of multi drug resistant (MDR) strains of pathogens. As decreasing the concentration of the antibiotic required to treat Salmonellosis might help in combating the development of resistant strains, the present study was designed to assess the synergistic effects, if any, of nisin, in combination with conventional anti-Salmonella antibiotics against Salmonella enterica serovar Typhimurium. Minimum inhibitory concentrations (MICs) of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by radial diffusion assay, fractional inhibitory concentration (FIC) index (checkerboard test) and time-kill assay. Scanning electron microscopy (SEM) was also performed to substantiate the effect of the combinations. In-vivo synergistic efficacy of the combinations selected on the basis of in-vitro results was also evaluated in the murine model, in terms of reduction in the number of Salmonellae in liver, spleen and intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have additive effects, whereas the combinations of nisin-ceftriaxone and nisin-cefotaxime were found to be highly synergistic against serovar Typhimurium as evident by checkerboard test and time-kill assay. SEM results revealed marked changes on the outer membrane of the bacterial cells treated with various combinations. In-vivo synergy was evident from the larger log unit decreases in all the target organs of mice treated with the combinations than in those treated with drugs alone. This study thus highlights that nisin has the potential to act in conjunction with conventional antibiotics at much lower MICs. These observations seem to be significant, as reducing the therapeutic concentrations of antibiotics may be a valuable strategy for avoiding/reducing the development of emerging antibiotic resistance. Value added

  14. Value addition in the efficacy of conventional antibiotics by Nisin against Salmonella.

    Directory of Open Access Journals (Sweden)

    Aman Preet Singh

    Full Text Available Frequent and indiscriminate use of existing battery of antibiotics has led to the development of multi drug resistant (MDR strains of pathogens. As decreasing the concentration of the antibiotic required to treat Salmonellosis might help in combating the development of resistant strains, the present study was designed to assess the synergistic effects, if any, of nisin, in combination with conventional anti-Salmonella antibiotics against Salmonella enterica serovar Typhimurium. Minimum inhibitory concentrations (MICs of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by radial diffusion assay, fractional inhibitory concentration (FIC index (checkerboard test and time-kill assay. Scanning electron microscopy (SEM was also performed to substantiate the effect of the combinations. In-vivo synergistic efficacy of the combinations selected on the basis of in-vitro results was also evaluated in the murine model, in terms of reduction in the number of Salmonellae in liver, spleen and intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have additive effects, whereas the combinations of nisin-ceftriaxone and nisin-cefotaxime were found to be highly synergistic against serovar Typhimurium as evident by checkerboard test and time-kill assay. SEM results revealed marked changes on the outer membrane of the bacterial cells treated with various combinations. In-vivo synergy was evident from the larger log unit decreases in all the target organs of mice treated with the combinations than in those treated with drugs alone. This study thus highlights that nisin has the potential to act in conjunction with conventional antibiotics at much lower MICs. These observations seem to be significant, as reducing the therapeutic concentrations of antibiotics may be a valuable strategy for avoiding/reducing the development of emerging antibiotic resistance

  15. The Agricultural Antibiotic Carbadox Induces Phage-mediated Gene Transfer in Salmonella

    Directory of Open Access Journals (Sweden)

    Bradley L. Bearson

    2014-02-01

    Full Text Available Antibiotics are used for disease therapeutic or preventative effects in humans and animals, as well as for enhanced feed conversion efficiency in livestock. Antibiotics can also cause undesirable effects in microbial populations, including selection for antibiotic resistance, enhanced pathogen invasion, and stimulation of horizontal gene transfer. Carbadox is a veterinary antibiotic used in the U.S. during the starter phase of swine production for improved feed efficiency and control of swine dysentery and bacterial swine enteritis. Carbadox has been shown in vitro to induce phage-encoded Shiga toxin in Shiga toxin-producing Escherichia coli and a phage-like element transferring antibiotic resistance genes in Brachyspira hyodysenteriae, but the effect of carbadox on prophages in other bacteria is unknown. This study examined carbadox exposure on prophage induction and genetic transfer in Salmonella enterica serovar Typhimurium, a human foodborne pathogen that frequently colonizes swine without causing disease. S. Typhimurium LT2 exposed to carbadox induced prophage production, resulting in bacterial cell lysis and release of virions that were visible by electron microscopy. Carbadox induction of phage-mediated gene transfer was confirmed by monitoring the transduction of a sodCIII::neo cassette in the Fels-1 prophage from LT2 to a recipient Salmonella strain. Furthermore, carbadox frequently induced generalized transducing phages in multidrug-resistant phage type DT104 and DT120 isolates, resulting in the transfer of chromosomal and plasmid DNA that included antibiotic resistance genes. Our research indicates that exposure of Salmonella to carbadox induces prophages that can transfer virulence and antibiotic resistance genes to susceptible bacterial hosts. Carbadox-induced, phage-mediated gene transfer could serve as a contributing factor in bacterial evolution during animal production, with prophages being a reservoir for bacterial fitness

  16. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

    Directory of Open Access Journals (Sweden)

    Sibylle Schirm

    Full Text Available Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

  17. Emerging antibiotic resistance in bacteria with special reference to India

    Indian Academy of Sciences (India)

    D Raghunath

    2008-11-01

    The antibiotic era started in the 1940s and changed the profile of infectious diseases and human demography. The burgeoning classes and numbers promised much and elimination of this major cause of human (and animal) morbidity appeared possible. Bacterial antibiotic resistance which was observed soon after antibiotic introduction has been studied extensively. Diverse mechanisms have been demonstrated and the genetic basis elucidated. The resilience of the prokaryote ecosystems to antibiotic stress has been realized. The paper presents these subjects briefly to afford an overview. The epidemiology of antibiotic resistance is dealt with and community practices in different countries are described. The role of high antibiotic usage environments is indicated. The implication of the wide use of antibiotics in animals has been pointed out. Steadily increasing antibiotic resistance and decreasing numbers of newer antibiotics appear to point to a post-antibiotic period during which treatment of infections would become increasingly difficult. This article attempts to review the global antimicrobial resistance scene and juxtaposes it to the Indian experience. The prevalence in India of antibiotic resistance among major groups of pathogens is described. The factors that determine the prevalent high antibiotic resistance rates have been highlighted. The future research activity to ensure continued utility of antibiotics in the control of infections has been indicated.

  18. Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect

    Directory of Open Access Journals (Sweden)

    Aleš Panáček

    2015-12-01

    Full Text Available The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

  19. Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect.

    Science.gov (United States)

    Panáček, Aleš; Smékalová, Monika; Kilianová, Martina; Prucek, Robert; Bogdanová, Kateřina; Večeřová, Renata; Kolář, Milan; Havrdová, Markéta; Płaza, Grażyna Anna; Chojniak, Joanna; Zbořil, Radek; Kvítek, Libor

    2015-12-28

    The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

  20. Gramicidin A: A New Mission for an Old Antibiotic

    Directory of Open Access Journals (Sweden)

    Justin M David

    2015-01-01

    Full Text Available Gramicidin A (GA is a channel-forming ionophore that renders biological membranes permeable to specific cations which disrupts cellular ionic homeostasis.  It is a well-known antibiotic, however it’s potential as a therapeutic agent for cancer has not been widely evaluated.  In two recently published studies, we showed that GA treatment is toxic to cell lines and tumor xenografts derived from renal cell carcinoma (RCC, a devastating disease that is highly resistant to conventional therapy.  GA was found to possess the qualities of both a cytotoxic drug and a targeted angiogenesis inhibitor, and this combination significantly compromised RCC growth in vitro and in vivo.  In this review, we summarize our recent research on GA, discuss the possible mechanisms whereby it exerts its anti-tumor effects, and share our perspectives on the future opportunities and challenges to the use of GA as a new anticancer agent.

  1. Antibiotic resistances of intestinal lactobacilli isolated from wild boars.

    Science.gov (United States)

    Klose, Viviana; Bayer, Katharina; Kern, Corinna; Goelß, Florian; Fibi, Silvia; Wegl, Gertrude

    2014-01-10

    Acquired antibiotic resistances have been reported in lactobacilli of various animal and food sources, but there are no data from wild boar. The objective was a preliminary examination of the antibiotic resistance prevalence of intrinsically vancomycin-resistant lactobacilli isolated from wild boar intestines and analysis of the genetic determinants implicated. Out of three wild boars, 121 lactobacilli were recovered and grouped according to their whole cell protein patterns. Initial phenotypic screening revealed that all were susceptible to erythromycin (2 μg/ml), but 30 were resistant to tetracycline (32 μg/ml). Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were selected as representative genotypes for identification and minimum inhibitory concentration (MIC) determination. Partial 16S rRNA gene sequencing identified four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of heterofermentative strains, as well as the aph(3')-III kanamycin gene in L. murinus. This is the first report showing acquired antibiotic resistance determinants in intestinal lactobacilli of wild boar origin.

  2. Antibiotic resistances of intestinal lactobacilli isolated from wild boars.

    Science.gov (United States)

    Klose, Viviana; Bayer, Katharina; Kern, Corinna; Goelß, Florian; Fibi, Silvia; Wegl, Gertrude

    2014-01-10

    Acquired antibiotic resistances have been reported in lactobacilli of various animal and food sources, but there are no data from wild boar. The objective was a preliminary examination of the antibiotic resistance prevalence of intrinsically vancomycin-resistant lactobacilli isolated from wild boar intestines and analysis of the genetic determinants implicated. Out of three wild boars, 121 lactobacilli were recovered and grouped according to their whole cell protein patterns. Initial phenotypic screening revealed that all were susceptible to erythromycin (2 μg/ml), but 30 were resistant to tetracycline (32 μg/ml). Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were selected as representative genotypes for identification and minimum inhibitory concentration (MIC) determination. Partial 16S rRNA gene sequencing identified four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of heterofermentative strains, as well as the aph(3')-III kanamycin gene in L. murinus. This is the first report showing acquired antibiotic resistance determinants in intestinal lactobacilli of wild boar origin. PMID:24326231

  3. Role of tetracycline speciation in the bioavailability to Escherichia coli for uptake and expression of antibiotic resistance.

    Science.gov (United States)

    Zhang, Yingjie; Boyd, Stephen A; Teppen, Brian J; Tiedje, James M; Li, Hui

    2014-05-01

    Tetracycline contains ionizable functional groups that manifest several species with charges at different locales and differing net charge; the fractional distribution of each species depends on pH-pKa relationship in the aqueous phase. In nature, these species interact with naturally abundant cations (e.g., Ca(2+) and Mg(2+)) to form metal-tetracycline complexes in water. In this study, we used Escherichia coli MC4100/pTGM whole-cell bioreporter to investigate tetracycline uptake from solution under varying conditions of pH, salt composition and concentration by quantifying the corresponding expression of antibiotic resistance gene. The expression of antibiotic resistance gene in the E. coli bioreporter responded linearly to intracellular tetracycline concentration. Less tetracycline entered E. coli cells at solution pH of 8.0 than at pH 6.0 or 7.0 indicating reduced bioavailability of the antibiotic at higher pH. Both Mg(2+) and Ca(2+) in solution formed metal-tetracycline complexes which reduced uptake of tetracycline by E. coli hence diminishing the bioresponse. Among the various tetracycline species present in solution, including both metal-complexed and free (noncomplexed) species, zwitterionic tetracycline was identified as the predominant species that most readily passed through the cell membrane eliciting activation of the antibiotic resistance gene in E. coli. The results indicate that the same total concentration of tetracycline in ambient solution can evoke very different expression of antibiotic resistance gene in the exposed bacteria due to differential antibiotic uptake. Accordingly, geochemical factors such as pH and metal cations can modulate the selective pressure exerted by tetracycline for development and enrichment of antibiotic resistant bacteria. We suggest that tetracycline speciation analysis should be incorporated into the risk assessment framework for evaluating environmental exposure and the corresponding development of antibiotic

  4. Effects of Subminimum Inhibitory Concentrations of Antibiotics on the Pasteurella multocida Proteome: A Systems Approach

    Directory of Open Access Journals (Sweden)

    Bindu Nanduri

    2008-01-01

    Full Text Available To identify key regulators of subminimum inhibitory concentration (sub-MIC antibiotic response in the Pasteurella multocida proteome, we applied systems approaches. Using 2D-LC-ESI-MS2, we achieved 53% proteome coverage. To study the differential protein expression in response to sub-MIC antibiotics in the context of protein interaction networks, we inferred P. multocida Pm70 protein interaction network from orthologous proteins. We then overlaid the differential protein expression data onto the P. multocida protein interaction network to study the bacterial response. We identified proteins that could enhance antimicrobial activity. Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.

  5. Methodology in improving antibiotic implementation policies.

    Science.gov (United States)

    Özgenç, Onur

    2016-06-26

    The basic requirements of antibiotic prescribing are components of methodology; knowledge, logical reasoning, and analysis. Antimicrobial drugs are valuable but limited resources, different from other drugs and they are among the most commonly prescribed drugs all over the world. They are the only drugs which do not intentionally affect the patient. They affect the pathogens which invade the host. The emergence and spread of antibiotic-resistant pathogens are accelerated by heavy antibiotic usage. The effective antimicrobial stewardship and infection control program have been shown to limit the emergence of antimicrobial-resistant bacteria. In this respect, education for antibiotic prescribing could be designed by going through the steps of scientific methodology. A defined leadership and a coordinated multidisciplinary approach are necessary for optimizing the indication, selection, dosing, route of administration, and duration of antimicrobial therapy. In scenarios, knowledge is also as important as experience for critical decision making as is designated. In this setting, the prevalence and resistance mechanisms of antimicrobials, and their interactions with other drugs need to be observed. In this respect, infectious disease service should play an important role in improving antimicrobial use by giving advice on the appropriate use of antimicrobial agents, and implementing evidence-based guidelines. PMID:27376019

  6. Antibiotic Resistance in Children with Bloody Diarrhea

    Directory of Open Access Journals (Sweden)

    Hamedi Abdolkarim

    2009-05-01

    Full Text Available Shigellosis is an important public health problem, especially in developing countries. Antibiotic treatment of bacterial dysentery, aimed at resolving diarrhea or reducing its duration is especially indicated whenever malnutrition is present. First-line drugs include ampicillin and trimethoprim sulfamethoxazole(TMP-SMX; however multidrug-resistance has occurred and careful antibiotic selection must be considered in prescribing .When epidemiologic data indicate a rise in resistancy, fluoroquinolones may be used in adults and oral third-generation cephalosporins and nalidixic acid in children. All children (n=2400 with acute diarrhea who were admitted to the Pediatric department of Dr.sheykh Hospital Mashhad, Iran from March 2004 to March 2005 were selected and their stool culture were obtained, then positive cultures (312 cases,13% were evaluated by antibiogram. This study showed that in heavily populated areas of IRAN like Mashhad, 97% shigella strain isolated from children with bloody diarrhea were sensitive to nalidixic acid, ciprofloxacin and cefixime and rarely susceptible to ampicillin and cotrimoxazole. There is increasing resistance of Shigella to most of the antibiotics in use, and for this reason, careful selection of antibiotics must use considered in each area. Development and use of new drugs are expensive and have severe limitations in the third world. Simple prophylactic alternatives are therefore, required, such as awareness of hygienic child care practices and early promotion of breast feeding. For treatment of shigellosis in infants Ceftriaxon, and in children Nalidixic Acid is recommended.

  7. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari

    2001-10-01

    Full Text Available Abstract Background Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. Presentation We hypothesize that aminoglycoside antibiotics could a trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. Testing Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children and the onset of autism symptoms (hypothesis "a", or between amino glycoside use and improvement of these symptoms (hypothesis "b". Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". Implications It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

  8. Physics and the Production of Antibiotics: 2

    Science.gov (United States)

    Fairbrother, Robert; Riddle, Wendy; Fairbrother, Neil

    2006-01-01

    In an article in the preceding issue we discussed the design and construction of fermenters in which antibiotics are cultured. For industrial purposes these fermenters can range in size up to 500 m[cube]. They have to be sterilized, filled with sterile culture medium and the culture itself and supplied with oxygen continuously. In some cases they…

  9. Towards new β-lactam antibiotics

    NARCIS (Netherlands)

    Andersson, I.; Terwisscha van Scheltinga, A.C.; Valegård, K.

    2001-01-01

    Antibiotics have had a profound impact on human health and belong to one of the largest-selling classes of drugs worldwide. Introduced into industrial production only some half century ago, these miracle drugs have been the main contributors to the recent increase in human life expectancy. However,

  10. Polyene antibiotic that inhibits membrane transport proteins.

    Science.gov (United States)

    te Welscher, Yvonne Maria; van Leeuwen, Martin Richard; de Kruijff, Ben; Dijksterhuis, Jan; Breukink, Eefjan

    2012-07-10

    The limited therapeutic arsenal and the increase in reports of fungal resistance to multiple antifungal agents have made fungal infections a major therapeutic challenge. The polyene antibiotics are the only group of antifungal antibiotics that directly target the plasma membrane via a specific interaction with the main fungal sterol, ergosterol, often resulting in membrane permeabilization. In contrast to other polyene antibiotics that form pores in the membrane, the mode of action of natamycin has remained obscure but is not related to membrane permeabilization. Here, we demonstrate that natamycin inhibits growth of yeasts and fungi via the immediate inhibition of amino acid and glucose transport across the plasma membrane. This is attributable to ergosterol-specific and reversible inhibition of membrane transport proteins. It is proposed that ergosterol-dependent inhibition of membrane proteins is a general mode of action of all the polyene antibiotics, of which some have been shown additionally to permeabilize the plasma membrane. Our results imply that sterol-protein interactions are fundamentally important for protein function even for those proteins that are not known to reside in sterol-rich domains. PMID:22733749

  11. Respiratory infection and antibiotic prescription rates.

    NARCIS (Netherlands)

    Otters, H.; Wouden, J. van der; Schellevis, F.

    2004-01-01

    In the October issue of the BJGP, Fleming et al showed that a decrease in antibiotic prescription rates is directly related to a decrease in respiratory infections presented in general practice. We compliment the authors for their interesting study and the clear presentation of their results.

  12. Proficiency test for antibiotics in beef

    NARCIS (Netherlands)

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

    2009-01-01

    The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of antibiotics in bovine tissues, including the screening analysis. This study also provided an evaluation of the methods applied for screening and quantitative and

  13. A Review of Antibiotic Use in Pregnancy.

    Science.gov (United States)

    Bookstaver, P Brandon; Bland, Christopher M; Griffin, Brooke; Stover, Kayla R; Eiland, Lea S; McLaughlin, Milena

    2015-11-01

    During pregnancy, untreated sexually transmitted or urinary tract infections are associated with significant morbidity, including low birth weight, preterm birth, and spontaneous abortion. Approximately one in four women will be prescribed an antibiotic during pregnancy, accounting for nearly 80% of prescription medications in pregnant women. Antibiotic exposures during pregnancy have been associated with both short-term (e.g., congenital abnormalities) and long-term effects (e.g., changes in gut microbiome, asthma, atopic dermatitis) in the newborn. However, it is estimated that only 10% of medications have sufficient data related to safe and effective use in pregnancy. Antibiotics such as beta-lactams, vancomycin, nitrofurantoin, metronidazole, clindamycin, and fosfomycin are generally considered safe and effective in pregnancy. Fluoroquinolones and tetracyclines are generally avoided in pregnancy. Physiologic changes in pregnancy lead to an increase in glomerular filtration rate, increase in total body volume, and enhanced cardiac output. These changes may lead to pharmacokinetic alterations in antibiotics that require dose adjustment or careful monitoring and assessment. PMID:26598097

  14. New antibiotic agents for bloodstream infections.

    Science.gov (United States)

    Vergidis, Paschalis I; Falagas, Matthew E

    2008-11-01

    Infections due to multidrug-resistant pathogens have shown a dramatic worldwide increase in prevalence. Bloodstream infections (BSIs) represent an important cause of morbidity and mortality in hospitalised patients. Research in the field led to the introduction of several novel antibiotic agents in the fight against bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas and Acinetobacter isolates are of particular concern. Doripenem is a recently approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a novel cephalosporin under investigation, have activity both against Gram-positive and Gram-negative organisms. In addition to the above agents, alternative treatment approaches that require further investigation have also been introduced into clinical practice. These include antibiotic lock therapy and continuous intravenous administration of antibiotics. In this article, we review the above treatment options for BSIs based on current clinical evidence. Comparative trials specifically focusing on patients with bacteraemia were generally not performed; however, a proportion of patients from the reported studies did have bacteraemia. PMID:18723329

  15. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    1995-01-01

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibi

  16. Audiological Management of Patients Receiving Aminoglycoside Antibiotics

    Science.gov (United States)

    Konrad-Martin, Dawn; Wilmington, Debra J.; Gordon, Jane S.; Reavis, Kelly M.; Fausti, Stephen A.

    2005-01-01

    Aminoglycoside antibiotics, commonly prescribed for adults and children to treat a wide range of bacterial infections, are potentially ototoxic, often causing irreversible damage to the auditory and vestibular systems. Ototoxic hearing loss usually begins at the higher frequencies and can progress to lower frequencies necessary for understanding…

  17. Antibiotics for acute otitis media in children

    NARCIS (Netherlands)

    Venekamp, Roderick P.; Sanders, Sharon L.; Glasziou, Paul P.; Del Mar, Chris B.; Rovers, Maroeska M.

    2015-01-01

    BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 a

  18. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    Science.gov (United States)

    Ye, Jianzhong; Zhou, Hao; Chen, Hongxia

    2016-01-01

    Polyprenol (GBP) from Ginkgo biloba Leaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm) combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro. PMID:27642597

  19. High-resolution structure of the antibiotic resistance protein NimA from Deinococcus radiodurans.

    Science.gov (United States)

    Leiros, Hanna Kirsti S; Tedesco, Consiglia; McSweeney, Seán M

    2008-06-01

    Many anaerobic human pathogenic bacteria are treated using 5-nitroimidazole-based (5-Ni) antibiotics, a class of inactive prodrugs that contain a nitro group. The nitro group must be activated in an anaerobic one-electron reduction and is therefore dependent on the redox system in the target cells. Antibiotic resistance towards 5-Ni drugs is found to be related to the nim genes (nimA, nimB, nimC, nimD, nimE and nimF), which are proposed to encode a reductase that is responsible for converting the nitro group of the antibiotic into a nonbactericidal amine. A mechanism for the Nim enzyme has been proposed in which two-electron reduction of the nitro group leads to the generation of nontoxic derivatives and confers resistance against these antibiotics. The cofactor was found to be important in the mechanism and was found to be covalently linked to the reactive His71. In this paper, the 1.2 A atomic resolution crystal structure of the 5-nitroimidazole antibiotic resistance protein NimA from Deinococcus radiodurans (DrNimA) is presented. A planar cofactor is clearly visible and well defined in the electron-density map adjacent to His71, the identification of the cofactor and its properties are discussed.

  20. Antibiotics are not needed during tube thoracostomy for spontaneous pneumothorax: an observational case study

    Directory of Open Access Journals (Sweden)

    Mulazimoglu Lutfiye

    2006-11-01

    Full Text Available Abstract Background Usefulness of prophylactic antibiotics following tube thoracostomy remains controversial in the literature. In this study, we aimed to investigate the consequences of closed tube thoracostomy for primary spontaneous pneumothorax without the use of antibiotics. Methods One-hundred and nineteen patients underwent tube thoracostomy for primary spontaneous pneumothorax. None of them received prophylactic antibiotic treatment. Eight patients with prolonged air leak undergoing either video assisted thoracoscopic surgery or thoracotomy were excluded. Results Of the remaining 111 (104 male and 7 female, 28 (25% patients developed some induration around the entry site of chest tube that settled without further treatment. White blood cell count was high without any other evidence of infection in 12 (11% patients and returned to its normal levels before discharge home in all. There was also some degree of fever not lasting for more than 48 hours in 8 (7% patients. Bacterial cultures from suspected sites did not reveal any significant growth in these patients. Conclusion Prophylactic antibiotic treatment seems avoidable during closed tube thoracostomy for primary spontaneous pneumothorax. This policy was not only cost-effective but also prevented our patients from detrimental properties of unnecessary antibiotic use, such as development of drug resistance and undesirable side effects.

  1. Distribution of multiple antibiotic resistant Vibrio spp across Palk Bay

    Digital Repository Service at National Institute of Oceanography (India)

    Sneha, K.G.; Anas, A.; Jayalakshmy, K.V.; Jasmin, C.; VipinDas, P.V.; Pai, S.S.; Pappu, S.; Nair, M.; Muraleedharan, K.R.; Sudheesh, K.; Nair, S.

    Presence of multiple antibiotic resistant microorganisms in marine systems is increasingly a focus of concern as they pose potential health risk to humans and animals. The present study reports the distribution, diversity, antibiotic resistance...

  2. Many Adults Use Antibiotics without Consulting Doctor, Survey Finds

    Science.gov (United States)

    ... gov/news/fullstory_159803.html Many Adults Use Antibiotics Without Consulting Doctor, Survey Finds 1 in 20 ... News) -- Adding to fears about the overuse of antibiotics, a new Texas study finds that one in ...

  3. U.K. Case of Throat Gonorrhea Resists Antibiotics

    Science.gov (United States)

    ... html U.K. Case of Throat Gonorrhea Resists Antibiotics U.S. officials concerned about potential danger of untreatable ... throat gonorrhea that proved untreatable with the standard antibiotic regimen. The patient, a heterosexual man who had ...

  4. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

    DEFF Research Database (Denmark)

    Wollenberger, Leah; Halling-Sørensen, B.; Kusk, Kresten Ole

    2000-01-01

    The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC...

  5. Antibiotic use and resistance in long term care facilities

    NARCIS (Netherlands)

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Benthem, B.H. van; Natsch, S.S.; Hertogh, C.M.P.M.

    2012-01-01

    INTRODUCTION: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available

  6. Antibiotic-Resistant Bacteria Detected in Sewage Spill

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_160031.html Antibiotic-Resistant Bacteria Detected in Sewage Spill 'People need to be ... News) -- Sewer line breaks can release antibiotic-resistant bacteria that pose a public health threat, a new ...

  7. Prevalence and Predictors of Antibiotic Administration during Pregnancy and Birth

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Schjørring, Susanne; Pedersen, Louise;

    2013-01-01

    Antibiotic treatment during pregnancy and birth is very common. In this study, we describe the estimated prevalence of antibiotic administration during pregnancy and birth in the COPSAC2010 pregnancy cohort, and analyze dependence on social and lifestyle-related factors....

  8. Dilemmas in primary care: antibiotic treatment of acute otitis media.

    Science.gov (United States)

    True, B L; Helling, D K

    1986-09-01

    Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

  9. CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

    Science.gov (United States)

    Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

  10. Doctors' Decision-Making Tool Could Cut Unnecessary Antibiotic Use

    Science.gov (United States)

    ... html Doctors' Decision-Making Tool Could Cut Unnecessary Antibiotic Use A drop of about 10 percent is ... for doctors may help reduce unnecessary use of antibiotics in children with respiratory tract infections and cough, ...

  11. 2nd Antibiotic Halves C-Section Infection Rate

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161230.html 2nd Antibiotic Halves C-Section Infection Rate: Study Two medications ... 29, 2016 (HealthDay News) -- Doctors routinely give an antibiotic before a cesarean-section, the surgical delivery of ...

  12. Antibiotic use and resistance in long term care facilities.

    NARCIS (Netherlands)

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Benthem, B.H.B. van; Natsch, S.; Hertogh, C.M.P.M.

    2012-01-01

    Introduction: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available

  13. Antibiotic resistance: from Darwin to Lederberg to Keynes.

    Science.gov (United States)

    Amábile-Cuevas, Carlos F

    2013-04-01

    The emergence and spread of antibiotic-resistant bacteria reflects both, a gradual, completely Darwinian evolution, which mostly yields slight decreases in antibiotic susceptibility, along with phenotypes that are not precisely characterized as "resistance"; and sudden changes, from full susceptibility to full resistance, which are driven by a vast array of horizontal gene transfer mechanisms. Antibiotics select for more than just antibiotic resistance (i.e., increased virulence and enhanced gene exchange abilities); and many non-antibiotic agents or conditions select for or maintain antibiotic resistance traits as a result of a complex network of underlying and often overlapping mechanisms. Thus, the development of new antibiotics and thoughtful, integrated anti-infective strategies is needed to address the immediate and long-term threat of antibiotic resistance. Since the biology of resistance is complex, these new drugs and strategies will not come from free-market forces, or from "incentives" for pharmaceutical companies.

  14. Antibiotic Residues - A Global Health Hazard

    Directory of Open Access Journals (Sweden)

    Nisha A.R.

    Full Text Available Use of Antibiotic that might result in deposition of residues in meat, milk and eggs must not be permitted in food intended for human consumption. If use of antibiotics is necessary as in prevention and treatment of animal diseases, a withholding period must be observed until the residues are negligible or no longer detected. The use of antibiotics to bring about improved performance in growth and feed efficiency, to synchronize or control of reproductive cycle and breeding performance also often lead to harmful residual effects. Concern over antibiotic residues in food of animal origin occurs in two times; one which produces potential threat to direct toxicity in human, second is whether the low levels of antibiotic exposure would result in alteration of microflora, cause disease and the possible development of resistant strains which cause failure of antibiotic therapy in clinical situations. A withdrawal period is established to safeguard human from exposure of antibiotic added food. The withdrawal time is the time required for the residue of toxicological concern to reach safe concentration as defined by tolerance. It is the interval from the time an animal is removed from medication until permitted time of slaughter. Heavy responsibility is placed on the veterinarian and livestock producer to observe the period for a withdrawal of a drug prior to slaughter to assure that illegal concentration of drug residue in meat, milk and egg do not occur. Use of food additives may improve feed efficiency 17% in beef cattle, 10% in lambs, 15% in poultry and 15% in swine. But their indiscriminate use will produce toxicity in consumers. WHO and FAO establish tolerances for a drug, pesticide or other chemical in the relevant tissues of food producing animals. The tolerance is the tissue concentration below, which a marker residue for the drug or chemical must fall in the target tissue before that animal edible tissues are considered safe for human

  15. Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal Microbiome and Antiviral Immunity.

    Science.gov (United States)

    Gonzalez-Perez, Gabriela; Hicks, Allison L; Tekieli, Tessa M; Radens, Caleb M; Williams, Brent L; Lamousé-Smith, Esi S N

    2016-05-01

    Microbial colonization of the infant gastrointestinal tract (GIT) begins at birth, is shaped by the maternal microbiota, and is profoundly altered by antibiotic treatment. Antibiotic treatment of mothers during pregnancy influences colonization of the GIT microbiota of their infants. The role of the GIT microbiota in regulating adaptive immune function against systemic viral infections during infancy remains undefined. We used a mouse model of perinatal antibiotic exposure to examine the effect of GIT microbial dysbiosis on infant CD8(+) T cell-mediated antiviral immunity. Maternal antibiotic treatment/treated (MAT) during pregnancy and lactation resulted in profound alterations in the composition of the GIT microbiota in mothers and infants. Streptococcus spp. dominated the GIT microbiota of MAT mothers, whereas Enterococcus faecalis predominated within the MAT infant GIT. MAT infant mice subsequently exhibited increased and accelerated mortality following vaccinia virus infection. Ag-specific IFN-γ-producing CD8(+) T cells were reduced in sublethally infected MAT infant mice. MAT CD8(+) T cells from uninfected infant mice also demonstrated a reduced capacity to sustain IFN-γ production following in vitro activation. We additionally determined that control infant mice became more susceptible to infection if they were born in an animal facility using stricter standards of hygiene. These data indicate that undisturbed colonization and progression of the GIT microbiota during infancy are necessary to promote robust adaptive antiviral immune responses. PMID:27036912

  16. Escherichia coli adhesion, biofilm development and antibiotic susceptibility on biomedical materials.

    Science.gov (United States)

    Gomes, L C; Silva, L N; Simões, M; Melo, L F; Mergulhão, F J

    2015-04-01

    The aim of this work was to test materials typically used in the construction of medical devices regarding their influence in the initial adhesion, biofilm development and antibiotic susceptibility of Escherichia coli biofilms. Adhesion and biofilm development was monitored in 12-well microtiter plates containing coupons of different biomedical materials--silicone (SIL), stainless steel (SS) and polyvinyl chloride (PVC)--and glass (GLA) as control. The susceptibility of biofilms to ciprofloxacin and ampicillin was assessed, and the antibiotic effect in cell morphology was observed by scanning electron microscopy. The surface hydrophobicity of the bacterial strain and materials was also evaluated from contact angle measurements. Surface hydrophobicity was related with initial E. coli adhesion and subsequent biofilm development. Hydrophobic materials, such as SIL, SS, and PVC, showed higher bacterial colonization than the hydrophilic GLA. Silicone was the surface with the greatest number of adhered cells and the biofilms formed on this material were also less susceptible to both antibiotics. It was found that different antibiotics induced different levels of elongation on E. coli sessile cells. Results revealed that, by affecting the initial adhesion, the surface properties of a given material can modulate biofilm buildup and interfere with the outcome of antimicrobial therapy. These findings raise the possibility of fine-tuning surface properties as a strategy to reach higher therapeutic efficacy.

  17. Metabolic engineering of antibiotic factories: New tools for antibiotic production in actinomycetes

    DEFF Research Database (Denmark)

    Weber, Tilmann; Charusanti, Pep; Musiol-Kroll, Ewa Maria;

    2015-01-01

    Actinomycetes are excellent sources for novel bioactive compounds, which serve as potential drug candidates for antibiotics development. While industrial efforts to find and develop novel antimicrobials have been severely reduced during the past two decades, the increasing threat of multidrug...

  18. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption

    DEFF Research Database (Denmark)

    Megraud, Francis; Coenen, Samuel; Versporten, Ann;

    2013-01-01

    OBJECTIVE: Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection. A study was conducted to assess prospectively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels...... in different countries. DESIGN: Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries. Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001-8 were expressed in Defined Daily...... Doses (DDD) per 1000 inhabitants per day. The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models. RESULTS: Of 2204 patients included, H pylori resistance rates for adults were 17.5% for clarithromycin, 14...

  19. [Evolution in the antibiotic susceptibility and resistance].

    Science.gov (United States)

    Stefani, S

    2009-07-01

    Over the last decade the proliferation of antibiotic-resistant pathogens has been a growing problem, especially in some geographic areas, making useless most of the classical antibiotic therapies. The rapid emergence of resistant bacteria is the result of different factors as the intrinsic microbial complexity, the growing attitude to travel of humans, animals and goods, the use of antibiotics outside hospitals, and the lack of precise therapeutic chooses for high risk group of patients. The antibiotic-resistance becomes certainly a serious problem when a resistant pathogen, and often multi-resistant today, is present in an infective site. In fact in a recent estimate of the Centre for Disease Control and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to bacterial infections and in particular to resistant pathogens. It appears clear that the clinic relevance of this problem is the decimation of the sensible germs of the normal flora that leads to the upper hand of the only resistant bacteria. The antibiotic therapy, in fact, select the resistance and each bacteria has developed a particular strategy to survive: mutations of the genetic content or acquisition of resistance genes from the external. Among the Gram positive bacteria, besides methicillin resistant Staphyloccocus aureus, there are other pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium and Enterococcus faecalis, some species of streptococci and multiresistant Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus, are recognized as new important nosocomial pathogens and are not only responsible of invasive infections but have become in few years resistant to oxacillin (more than 60%) and multiresistant. The unsuspected fragility of glycopeptides, which for 40 years have been the most important treatment against infections due to Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among the therapeutic

  20. Intensive Care Unit Infections and Antibiotic Use

    Directory of Open Access Journals (Sweden)

    Ayşegül Yeşilkaya

    2011-07-01

    Full Text Available Burn wound infections is the leading cause of morbidity and mortality in burn trauma patients. Although burn wound is sterile at the beginning, because of risk factors such as prolonged hospital stay, immunesuppression and burn affecting large body surface area, colonisation firstly with Staphylococcus aureus and then Pseudomonas aeruginosa will occur later. Delay in wound closure and treatment with broad-spectrum antibiotic will result wound colonisation with antibiotic-resistant bacteria. To control colonization and to prevent burn wound infection topical antimicrobial dressings are used. The criteria used for the diagnosis of sepsis and wound infections are different in burn victims. Surface swabs from burn wounds must be cultured for the early assestment of infection. Although histopathological examination and quantitative culture of wound tissue biopsy has been known as the gold standard for the verification of invasive burn wound infection, many burn centers cannot do histopathological examination. When the traditional treatment modalities such as debridement of necrotic tissue, cleaning of wound and topical antimicrobial dressing application fails in the management of burn patient, cultures must be taken from possible foci of infection for the early diagnosis. After specimen collection, empirical bactericidal systemic antibiotic treatment should be started promptly. Inappropriate utilization of antibiotics may cause selection of resistant bacteria in the flora of the patient and of the burn unit which facilitates an infection or an outbreak at the end. Infection control in the burn unit includes surveillance cultures, cohort patient care staff, standard isolation precautions, strict hand hygiene compliance and appropariate antibiotic utilization. (Journal of the Turkish Society Intensive Care 2011; 9 Suppl: 55-61

  1. Trends in antibiotic use among outpatients in New Delhi, India

    Directory of Open Access Journals (Sweden)

    Holloway Kathleen

    2011-04-01

    Full Text Available Abstract Background The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices. Methods This study surveyed antibiotic use in the community (December 2007-November 2008 using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC classification and the Defined Daily Dose (DDD measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic. Results During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed

  2. Widespread antibiotic resistance of diarrheagenic Escherichia coli and Shigella species

    OpenAIRE

    Azam Fatahi Sadeghabadi; Ali Ajami; Reza Fadaei; Masoud Zandieh; Elham Heidari; Mahmoud Sadeghi; Behrooz Ataei; Shervin Ghaffari Hoseini

    2014-01-01

    Background: Antibiotic resistance of enteric pathogens particularly Shigella species, is a critical world-wide problem and monitoring their resistant pattern is essential, because the choice of antibiotics is absolutely dependent on regional antibiotic susceptibility patterns. During summer 2013, an unusual increase in number of diarrheal diseases was noticed in Isfahan, a central province of Iran. Therefore, the antibiotic resistance of diarrheagenic Escherichia coli and Shigella species iso...

  3. Functional metagenomics for the investigation of antibiotic resistance

    OpenAIRE

    Mullany, Peter

    2014-01-01

    Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in thes...

  4. Messages about Antibiotic Resistance in Different Newspaper Genres

    OpenAIRE

    Marwa Nasr; Krina Amin; Rachel Virgo; Sochima Okafor; Parastou Donyai

    2013-01-01

    Poorer people are more likely to use antibiotics; inappropriate antibiotic use causes resistance, and health campaigns attempt to change behaviour through education. However, fuelled by the media, the public think antibiotic resistance is outside their control. Differences in the attribution of blame for antibiotic resistance in two genres of UK newspapers, targeting distinct socioeconomic groups, were examined using a mixed methods approach. Firstly, depiction of blame was categorised as eit...

  5. Sensitivity of ribosomes of the hyperthermophilic bacterium Aquifex pyrophilus to aminoglycoside antibiotics.

    OpenAIRE

    Bocchetta, M; Huber, R.; Cammarano, P

    1996-01-01

    A poly(U)-programmed cell-free system from the hyperthermophilic bacterium Aquifex pyrophilus has been developed, and the susceptibility of Aquifex ribosomes to the miscoding-inducing and inhibitory actions of all known classes of aminoglycoside antibiotics has been assayed at temperatures (75 to 80 degrees C) close to the physiological optimum for cell growth. Unlike Thermotoga maritima ribosomes, which are systematically refractory to all known classes of aminoglycoside compounds (P. Londei...

  6. The Shared Antibiotic Resistome of Soil Bacteria and Human Pathogens

    DEFF Research Database (Denmark)

    Forsberg, Kevin J.; Reyes, Alejandro; Wang, Bin;

    2012-01-01

    From Farm to Clinic?Soil organisms have long been assumed to be an important source of antibiotic resistance genes, in part because of antibiotic-treated livestock and in part because of the natural ecology of antibiotic production in the soil. Forsberg et al. (p. 1107) developed a metagenomic...

  7. Quality indicators to measure appropriate antibiotic use in hospitalized adults

    NARCIS (Netherlands)

    Bosch, C.M.A. van den; Geerlings, S.E.; Natsch, S.S.; Prins, J.M.; Hulscher, M.

    2015-01-01

    BACKGROUND: An important requirement for an effective antibiotic stewardship program is the ability to measure appropriateness of antibiotic use. The aim of this study was to develop quality indicators (QIs) that can be used to measure appropriateness of antibiotic use in the treatment of all bacter

  8. Identifying targets for quality improvement in hospital antibiotic prescribing

    NARCIS (Netherlands)

    Spreuwel, P.C. van; Blok, H.; Langelaar, M.F.; Kullberg, B.J.; Mouton, J.W.; Natsch, S.S.

    2015-01-01

    OBJECTIVES: To audit antibiotic use in a university hospital and to identify targets for quality improvement in a setting with low antibiotic use and resistance rates. METHODOLOGY: A point-prevalence survey (PPS), using a patient-based audit tool for antibiotic use, was executed in the Radboud Unive

  9. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    Science.gov (United States)

    ... age. It’s important to only take antibiotics for bacterial infections since they can put you or your child at risk for harmful side effects and antibiotic-resistant infections. Top of Page Related Links Antibiotic/Antimicrobial Resistance Get Smart for Healthcare Get Smart: Know When ...

  10. Outpatient antibiotic prescriptions from 1992 to 2001 in The Netherlands

    NARCIS (Netherlands)

    Kuyvenhoven, MM; van Balen, FAM; Verheij, TJM

    2003-01-01

    Objectives: Although Dutch outpatient antibiotic prescription rates are low compared with other European countries, continuing to scrutinize trends in outpatient antibiotic use is important in order to identify possible increases in antibiotic use or inappropriate increases in the use of particular

  11. Improving antibiotic use for complicated urinary tract infections

    NARCIS (Netherlands)

    V. Spoorenberg

    2014-01-01

    Guidelines for antimicrobial treatment are important in the process of improving antibiotic use, because they describe appropriate antibiotic use. In this thesis, we demonstrated the value of appropriate antibiotic use (i.e. guideline adherence) in patients with a complicated urinary tract infection

  12. Evaluation of antibiotic use in a Lebanese hospital

    OpenAIRE

    Ibrahim, Mohamad

    2016-01-01

    Antimicrobial resistance is a significant global health problem. Misuse of antibiotics is associated with antimicrobial resistance which presents clinicians with treatment challenges and increases the complexity of the decision making process related to the selection of appropriate antibiotic therapy. Antibiotic resistant organisms can often lead to nosocomial infections (NIs) and undoubtedly causes patient harm and increases healthcare costs. According to the National Insti...

  13. Occurrence and reservoirs of antibiotic resistance genes in the environment

    NARCIS (Netherlands)

    Seveno, N.; Kallifidas, D.; Smalla, K.; Elsas, van J.D.; Collard, J.M.; Karagouni, A.; Wellington, E.M.H.

    2002-01-01

    Antibiotic resistance genes have become highly mobile since the development of antibiotic chemotherapy. A considerable body of evidence exists proving the link between antibiotic use and the significant increase in drug-resistant human bacterial pathogens. The application of molecular detection and

  14. 9 CFR 114.10 - Antibiotics as preservatives.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Antibiotics as preservatives. 114.10... BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use as preservatives for biological products if used within the limitations as to kinds and amounts prescribed in...

  15. Oral antibiotics for perforated appendicitis is not recommended

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg, Jacob; Alamili, Mahdi

    2010-01-01

    In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this paper...

  16. Antibiotic concentration and antibiotic-resistant bacteria in two shallow urban lakes after stormwater event.

    Science.gov (United States)

    Zhang, Songhe; Pang, Si; Wang, PeiFang; Wang, Chao; Han, Nini; Liu, Bin; Han, Bing; Li, Yi; Anim-Larbi, Kwaku

    2016-05-01

    Stormwater runoff is generally characterized as non-point source pollution. In the present study, antibiotic concentration and antibiotic susceptibilities of cultivable heterotrophic bacteria were investigated in two small shallow urban lakes before and after strong storm event. Several antibiotics, lactose-fermenting bacteria and cultivable heterotrophic bacteria concentrations increased in surface water and/or surface sediment of two small urban lakes (Lake Xuanwu and Wulongtan) after strong storm event. In general, the frequencies of bacteria showing resistance to nine antibiotics increased after storm event. Based on the 16S rRNA genes of 50 randomly selected isolates from each water sample of two lakes, Aeromonas and Bacillus were dominant genera in samples from two lakes, while genera Proteus and Lysinibacillus were the third abundant genera in Lake Xuanwu and Wulongtu, respectively. Presences of nine antibiotic resistance genes (ARGs) in the 100 isolates were detected and most of these isolates harbored at least two ARGs with different functions. The detection frequency of ARGs in Gram-negative isolates was higher than that in Gram-positive isolates. The most prevalent integron in 100 isolates was int(II) (n = 28), followed by int(I) (n = 17) and int(III) (n = 17). Our results indicate that strong storm events potentially contribute to the transfer of ARGs and antibiotic-resistant bacteria from land-sewer system to the urban Lakes. PMID:26865482

  17. COMPARISON OF SINGLE DOSE PROPHYLACTIC ANTIBIOTICS VERSUS FIVE DAYS ANTIBIOTIC IN CESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Zeel

    2014-03-01

    Full Text Available AIMS AND OBJECTIVES: To compare if single dose antibiotic is as effective as multiple doses in prevention of post-operative infection in caesarean section. To compare the cost effectiveness of drugs in both the groups. MATERIAL AND METHOD: This prospective randomized controlled study was carried out to evaluate the effectiveness of single dose antibiotic versus multiple doses in caesarean section. The study population consisted of 600 patients that were randomly allocated to single or multiple dose groups. All potentially infected cases were excluded from this study. All patients received inj Cefotaxime IV half hour before surgery. In addition the multiple dose group received antibiotics for five days post-operatively. Each patient in the study was observed till discharge for presence of any morbidity like endometritis, urinary tract infections, and wound infections. STATISTICAL ANALYSISIS: Fischer exact test, unpaired t test used for analysis. RESULTS: There was no statistically significance in the rate of infections in both the groups. The rate of febrile morbidity, endometritis, urinary tract infection and wound infections were statistically not significant. However the difference in cost of antibiotic in both the groups was significant. CONCLUSIONS: Single dose antibiotics are effective as multiple doses in prevention of post-operative infections in caesarean sections Careful periodic surveillance of antibiotic prophylaxis is necessary to detect the emergence of drug resistant strains of bacteria in our institution because it caters to the needs of local population.

  18. Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh; Fuglsang, Eva; Jiang, Pingping;

    2016-01-01

    Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis, while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and...... delay gut bacterial colonization and thereby protect preterm neonates against both NEC and bacteremia in the immediate postnatal period. Preterm pigs were given formula and administered saline (CON) or broad-spectrum antibiotics orally (ORA) or systemically (SYS) for 5 d after birth. Temporal changes in...... blood parameters and bacterial composition in the intestine, blood and immune organs were analyzed. Newborn preterm pigs had few blood neutrophils and a high frequency of progenitor cells. Neutrophils gradually matured after preterm birth with increasing CD14 and decreasing CD172a expressions. Preterm...

  19. Efflux Pump Blockers in Gram-Negative Bacteria: The New Generation of Hydantoin Based-Modulators to Improve Antibiotic Activity.

    Science.gov (United States)

    Otręebska-Machaj, Ewa; Chevalier, Jacqueline; Handzlik, Jadwiga; Szymańska, Ewa; Schabikowski, Jakub; Boyer, Gérard; Bolla, Jean-Michel; Kieć-Kononowicz, Katarzyna; Pagès, Jean-Marie; Alibert, Sandrine

    2016-01-01

    Multidrug resistant (MDR) bacteria are an increasing health problem with the shortage of new active antibiotic agents. Among effective mechanisms that contribute to the spread of MDR Gram-negative bacteria are drug efflux pumps that expel clinically important antibiotic classes out of the cell. Drug pumps are attractive targets to restore the susceptibility toward the expelled antibiotics by impairing their efflux activity. Arylhydantoin derivatives were investigated for their potentiation of activities of selected antibiotics described as efflux substrates in Enterobacter aerogenes expressing or not AcrAB pump. Several compounds increased the bacterial susceptibility toward nalidixic acid, chloramphenicol and sparfloxacin and were further pharmacomodulated to obtain a better activity against the AcrAB producing bacteria. PMID:27199950

  20. Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation.

    Directory of Open Access Journals (Sweden)

    Markus Arnoldini

    2014-08-01

    Full Text Available Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide labor during S. typhimurium infections. Here, we show that heterogeneous virulence gene expression in this organism also promotes survival against exposure to antibiotics through a bet-hedging mechanism. Using microfluidic devices in combination with fluorescence time-lapse microscopy and quantitative image analysis, we analyzed the expression of virulence genes at the single cell level and related it to survival when exposed to antibiotics. We found that, across different types of antibiotics and under concentrations that are clinically relevant, the subpopulation of bacterial cells that express virulence genes shows increased survival after exposure to antibiotics. Intriguingly, there is an interplay between the two consequences of phenotypic heterogeneity. The bet-hedging effect that arises through heterogeneity in virulence gene expression can protect clonal populations against avirulent mutants that exploit and subvert the division of labor within these populations. We conclude that bet-hedging and the division of labor can arise through variation in a single trait and interact with each other. This reveals a new degree of functional complexity of phenotypic heterogeneity. In addition, our results suggest a general principle of how pathogens can evade antibiotics: Expression of virulence factors often entails metabolic costs and the resulting growth retardation could generally increase tolerance against antibiotics and thus compromise treatment.