Science.gov

Sample records for antibiotic molecules bypassing

  1. New Antibiotic Molecules: Bypassing the Membrane Barrier of Gram Negative Bacteria Increases the Activity of Peptide Deformylase Inhibitors

    PubMed Central

    Mamelli, Laurent; Petit, Sylvain; Chevalier, Jacqueline; Giglione, Carmela; Lieutaud, Aurélie; Meinnel, Thierry; Artaud, Isabelle; Pagès, Jean-Marie

    2009-01-01

    Background Multi-drug resistant (MDR) bacteria have become a major concern in hospitals worldwide and urgently require the development of new antibacterial molecules. Peptide deformylase is an intracellular target now well-recognized for the design of new antibiotics. The bacterial susceptibility to such a cytoplasmic target primarily depends on the capacity of the compound to reach and accumulate in the cytosol. Methodology/Principal Findings To determine the respective involvement of penetration (influx) and pumping out (efflux) mechanisms to peptide deformylase inhibitors (PDF-I) activity, the potency of various series was determined using various genetic contexts (efflux overproducers or efflux-deleted strains) and membrane permeabilizers. Depending on the structure of the tested molecules, two behaviors could be observed: (i) for actinonin the first PDF-I characterized, the AcrAB efflux system was the main parameter involved in the bacterial susceptibility, and (ii), for the lastest PDF-Is such as the derivatives of 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide, the penetration through the membrane was a important limiting step. Conclusions/Significance Our results clearly show that the bacterial membrane plays a key role in modulating the antibacterial activity of PDF-Is. The bacterial susceptibility for these new antibacterial molecules can be improved by two unrelated ways in MDR strains: by collapsing the Acr efflux activity or by increasing the uptake rate through the bacterial membrane. The efficiency of the second method is associated with the nature of the compound. PMID:19649280

  2. [Action of antibiotics as signalling molecules].

    PubMed

    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.

  3. New antimicrobial molecules and new antibiotic strategies.

    PubMed

    Rodríguez de Castro, Felipe; Naranjo, Olga Rajas; Marco, Javier Aspa; Violán, Jordi Solé

    2009-04-01

    Drug options for treatment of infections are increasingly limited. The pharmaceutical industry has found it difficult to discover new antimicrobial agents, and only two novel classes of antibiotics, the oxazolidinones and the cyclic lipopeptides, have entered the market since the late 1960s. Few new agents have reached the market in the last decade with potential interest for community-acquired pneumonia (CAP) treatment, including linezolid (the first oxazolidinone in clinical use), new fluoroquinolones, cefditoren, ertapenem, and telithromycin. Agents currently in clinical development include other novel quinolones and ketolides, broad-spectrum cephalosporin derivatives, faropenem, several glycopeptides, and iclaprim. Other molecules are considered to be promising candidates for the future. In addition to the foregoing agents, alternative treatment approaches have also been introduced into clinical practice, which include the administration of the appropriate antimicrobials in a timely manner and the consideration of the pharmacokinetic-pharmacodynamic properties of the agent(s). PMID:19296416

  4. Bypass of genetic constraints during mutator evolution to antibiotic resistance

    PubMed Central

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

    2015-01-01

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness. PMID:25716795

  5. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

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

    2015-04-01

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

  6. RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new bioactive molecules less susceptible to bacterial resistance.

    PubMed

    Maurel, M C; Biard, B; Moulinier, C; Braz, D; Nugier, J; Chaumas, I; Reboud-Ravaux, M; Décout, J L

    2002-08-01

    During the last few years, antibiotic multiresistance has been increasing, not only in hospitals, but also, more worryingly, in general medicine. Different ways are being explored to bypass this problem. RNA-acting antibiotics such as aminosides (aminoglycosides) bind to bacterial RNA causing premature termination of proteins and mistranslation in bacteria. It is now possible to study the interactions of such antibiotics with their target by in-vitro selection of RNA molecules that recognize these antibiotics (RNA aptamers, SELEX method). The knowledge of the antibiotic-RNA interactions represents a promising way for the rational design of new bioactive compounds less susceptible to bacterial resistance.

  7. Allosteric control of the ribosome by small-molecule antibiotics

    PubMed Central

    Wang, Leyi; Pulk, Arto; Wasserman, Michael R; Feldman, Michael B; Altman, Roger B; Cate, Jamie H. Doudna; Blanchard, Scott C

    2013-01-01

    Protein synthesis is targeted by numerous, chemically distinct antibiotics that bind and inhibit key functional centers of the ribosome. Using single-molecule imaging and X-ray crystallography, we show that the aminoglycoside neomycin blocks aminoacyl–transfer RNA (aa-tRNA) selection and translocation as well as ribosome recycling by binding to helix 69 (H69) of 23S ribosomal RNA within the large subunit of the Escherichia coli ribosome. There, neomycin prevents the remodeling of intersubunit bridges that normally accompanies the process of subunit rotation to stabilize a partially rotated ribosome configuration in which peptidyl (P)-site tRNA is constrained in a previously unidentified hybrid position. Direct measurements show that this neomycin-stabilized intermediate is incompatible with the translation factor binding that is required for distinct protein synthesis reactions. These findings reveal the functional importance of reversible intersubunit rotation to the translation mechanism and shed new light on the allosteric control of ribosome functions by small-molecule antibiotics. PMID:22902368

  8. Small molecule inhibition of microbial natural product biosynthesis – An emerging antibiotic strategy

    PubMed Central

    Cisar, Justin S.; Tan, Derek S.

    2008-01-01

    A variety of natural products modulate critical biological processes in the microorganisms that produce them. Thus, inhibition of the corresponding natural product biosynthesis pathways represents a promising avenue to develop novel antibiotics. In this tutorial review, we describe several recent examples of designed small molecule inhibitors of microbial natural product biosynthesis and their use in evaluating this emerging antibiotic strategy. PMID:18568158

  9. Insights in Nanoparticle-Bacterium Interactions: New Frontiers to Bypass Bacterial Resistance to Antibiotics.

    PubMed

    Diab, Roudayna; Khameneh, Bahman; Joubert, Olivier; Duval, Raphael

    2015-01-01

    Nanotechnology has been revealed as a fundamental approach for antibiotics delivery. In this paper, recent findings demonstrating the superiority of nanocarried-antibiotics over "naked" ones and the ways by which nanoparticles can help to overwhelm bacterial drug resistance are reviewed. The second part of this paper sheds light on nanoparticle-bacterium interaction patterns. Finally, key factors affecting the effectiveness of nanoparticles interactions with bacteria are discussed.

  10. Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa.

    PubMed

    Guo, Qiaoyun; Wei, Yu; Xia, Bin; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Shi, Jing; Zhu, Feng; Li, Jinlong; Qian, Lei; Liu, Xinqi; Cheng, Zhihui; Jin, Shouguang; Lin, Jianping; Wu, Weihui

    2016-01-01

    The rising antibiotic resistance of bacteria imposes a severe threat on human health. Inhibition of bacterial virulence is an alternative approach to develop new antimicrobials. Molecules targeting antibiotic resistant enzymes have been used in combination with cognate antibiotics. It might be ideal that a molecule can simultaneously suppress virulence factors and antibiotic resistance. Here we combined genetic and computer-aided inhibitor screening to search for such molecules against the bacterial pathogen Pseudomonas aeruginosa. To identify target proteins that control both virulence and antibiotic resistance, we screened for mutants with defective cytotoxicity and biofilm formation from 93 transposon insertion mutants previously reported with increased antibiotic susceptibility. A pyrD mutant displayed defects in cytotoxicity, biofilm formation, quorum sensing and virulence in an acute mouse pneumonia model. Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis. One of the predicted inhibitors was able to suppress the enzymatic activity of PyrD as well as bacterial cytotoxicity, biofilm formation and antibiotic resistance. A single administration of the compound reduced the bacterial colonization in the acute mouse pneumonia model. Therefore, we have developed a strategy to identify novel treatment targets and antimicrobial molecules. PMID:26751736

  11. Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

    PubMed Central

    Guo, Qiaoyun; Wei, Yu; Xia, Bin; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Shi, Jing; Zhu, Feng; Li, Jinlong; Qian, Lei; Liu, Xinqi; Cheng, Zhihui; Jin, Shouguang; Lin, Jianping; Wu, Weihui

    2016-01-01

    The rising antibiotic resistance of bacteria imposes a severe threat on human health. Inhibition of bacterial virulence is an alternative approach to develop new antimicrobials. Molecules targeting antibiotic resistant enzymes have been used in combination with cognate antibiotics. It might be ideal that a molecule can simultaneously suppress virulence factors and antibiotic resistance. Here we combined genetic and computer-aided inhibitor screening to search for such molecules against the bacterial pathogen Pseudomonas aeruginosa. To identify target proteins that control both virulence and antibiotic resistance, we screened for mutants with defective cytotoxicity and biofilm formation from 93 transposon insertion mutants previously reported with increased antibiotic susceptibility. A pyrD mutant displayed defects in cytotoxicity, biofilm formation, quorum sensing and virulence in an acute mouse pneumonia model. Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis. One of the predicted inhibitors was able to suppress the enzymatic activity of PyrD as well as bacterial cytotoxicity, biofilm formation and antibiotic resistance. A single administration of the compound reduced the bacterial colonization in the acute mouse pneumonia model. Therefore, we have developed a strategy to identify novel treatment targets and antimicrobial molecules. PMID:26751736

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

    PubMed

    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.

  13. A Quorum Sensing Small Volatile Molecule Promotes Antibiotic Tolerance in Bacteria

    PubMed Central

    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. PMID:24367477

  14. Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores

    NASA Astrophysics Data System (ADS)

    Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

    2002-07-01

    Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

  15. Antibiotics

    MedlinePlus

    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 ...

  16. Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide

    PubMed Central

    Steere, Allen C.; Klitz, William; Drouin, Elise E.; Falk, Ben A.; Kwok, William W.; Nepom, Gerald T.; Baxter-Lowe, Lee Ann

    2006-01-01

    An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)–DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA163–175). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA163–175 peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic-refractory arthritis differed significantly from those in the 50 antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA163–175, whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic-refractory patients had at least one of the seven known OspA peptide–binding DR molecules compared with 46% of the antibiotic-responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease. PMID:16585267

  17. Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide.

    PubMed

    Steere, Allen C; Klitz, William; Drouin, Elise E; Falk, Ben A; Kwok, William W; Nepom, Gerald T; Baxter-Lowe, Lee Ann

    2006-04-17

    An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA163-175). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA163-175 peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic-refractory arthritis differed significantly from those in the 50 antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA163-175, whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic-refractory patients had at least one of the seven known OspA peptide-binding DR molecules compared with 46% of the antibiotic-responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease.

  18. Concise Synthesis of Spergualin-Inspired Molecules With Broad-Spectrum Antibiotic Activity

    PubMed Central

    Assimon, Victoria A.; Shao, Hao; Garneau-Tsodikova, Sylvie

    2016-01-01

    There is a growing need to identify new, broad-spectrum antibiotics. The natural product spergualin was previously shown to have promising anti-bacterial activity and a privileged structure, but its challenging synthesis had limited further exploration. For example, syntheses of spergualin and its analogs have been reported in approximately 10 linear steps, with overall yields between 0.3 and 18%. Using the Ugi multi-component reaction, we assembled spergualin-inspired molecules in a single step, dramatically improving the overall yield (20% to 96%). Using this strategy, we generated 43 new analogs and tested them for anti-bacterial activity against two Gram-negative and four Gram-positive strains. We found that the most potent analogue, compound 6, had MIC values between 4 and 32 μg/mL against the six strains, which is a significant improvement on spergualin (MIC ∼ 6.25 to 50 μg/mL). These studies provide a concise route to a broad-spectrum antibiotic with a novel chemical scaffold. PMID:27087913

  19. Towards Development of Small Molecule Lipid II Inhibitors as Novel Antibiotics

    PubMed Central

    Chauhan, Jamal; Cardinale, Steven; Fang, Lei; Huang, Jing; Kwasny, Steven M.; Pennington, M. Ross; Basi, Kelly; diTargiani, Robert; Capacio, Benedict R.; MacKerell, Alexander D.; Opperman, Timothy J.; Fletcher, Steven; de Leeuw, Erik P. H.

    2016-01-01

    Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule Lipid II inhibitor and is structurally distinct from natural agents that bind Lipid II, such as vancomycin. Here, we describe the synthesis and biological evaluation of 50 new analogs of BAS00127538 designed to explore the structure-activity relationships of the scaffold. The results of this study indicate an activity map of the scaffold, identifying regions that are critical to cytotoxicity, Lipid II binding and range of anti-bacterial action. One compound, 6jc48-1, showed significantly enhanced drug-like properties compared to BAS00127538. 6jc48-1 has reduced cytotoxicity, while retaining specific Lipid II binding and activity against Enterococcus spp. in vitro and in vivo. Further, this compound showed a markedly improved pharmacokinetic profile with a half-life of over 13 hours upon intravenous and oral administration and was stable in plasma. These results suggest that scaffolds like that of 6jc48-1 can be developed into small molecule antibiotic drugs that target Lipid II. PMID:27776124

  20. N-Heterocyclic molecule-capped gold nanoparticles as effective antibiotics against multi-drug resistant bacteria

    NASA Astrophysics Data System (ADS)

    Feng, Yan; Chen, Wenwen; Jia, Yuexiao; Tian, Yue; Zhao, Yuyun; Long, Fei; Rui, Yukui; Jiang, Xingyu

    2016-07-01

    We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs.We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03317b

  1. Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo.

    PubMed

    Hein, E; Munthe-Fog, L; Thiara, A S; Fiane, A E; Mollnes, T E; Garred, P

    2015-02-01

    The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and -3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0.0001), whereas soluble C3a and TCC in the samples were increased (P < 0.0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.

  2. A novel antibiotic-delivery system by using ovotransferrin as targeting molecule.

    PubMed

    Ibrahim, Hisham R; Tatsumoto, Sayuri; Ono, Hajime; Van Immerseel, Filip; Raspoet, Ruth; Miyata, Takeshi

    2015-01-23

    Synthetic antibiotics and antimicrobial agents, such as sulfonamide and triclosan (TCS), have provided new avenues in the treatment of bacterial infections, as they target lethal intracellular pathways. Sulfonamide antibiotics block synthesis of folic acid by inhibiting dihydrofolate reductase (DHFR) while TCS block fatty acid synthesis through inhibition of enoyl-ACP reductase (FabI). They are water-insoluble agents and high doses are toxic, limiting their therapeutic efficiency. In this study, an antibiotic drug-targeting strategy based on utilizing ovotransferrin (OTf) as a carrier to allow specific targeting of the drug to microbial or mammalian cells via the transferrin receptor (TfR) is explored, with potential to alleviate insolubility and toxicity problems. Complexation, through non-covalent interaction, with OTf turned sulfa antibiotics or TCS into completely soluble in aqueous solution. OTf complexes showed superior bactericidal activity against several bacterial strains compared to the activity of free agents. Strikingly, a multi-drug resistant Salmonella strain become susceptible to antibiotics-OTf complexes while a tolC-knockout mutant strain become susceptible to OTf and more sensitive to the complexes. The antibiotic bound to OTf was, thus exported through the multi-drug efflux pump TolC in Salmonella wild-type strain. Further, antibiotics-OTf complexes were able to efficiently kill intracellular pathogens after infecting human colon carcinoma cells (HCT-116). The results demonstrate, for the first time, that the TfR mediated endocytosis of OTf can be utilized to specifically target drugs directly to pathogens or intracellularly infected cells and highlights the potency of the antibiotic-OTf complex for the treatment of infectious diseases.

  3. A novel antibiotic-delivery system by using ovotransferrin as targeting molecule.

    PubMed

    Ibrahim, Hisham R; Tatsumoto, Sayuri; Ono, Hajime; Van Immerseel, Filip; Raspoet, Ruth; Miyata, Takeshi

    2015-01-23

    Synthetic antibiotics and antimicrobial agents, such as sulfonamide and triclosan (TCS), have provided new avenues in the treatment of bacterial infections, as they target lethal intracellular pathways. Sulfonamide antibiotics block synthesis of folic acid by inhibiting dihydrofolate reductase (DHFR) while TCS block fatty acid synthesis through inhibition of enoyl-ACP reductase (FabI). They are water-insoluble agents and high doses are toxic, limiting their therapeutic efficiency. In this study, an antibiotic drug-targeting strategy based on utilizing ovotransferrin (OTf) as a carrier to allow specific targeting of the drug to microbial or mammalian cells via the transferrin receptor (TfR) is explored, with potential to alleviate insolubility and toxicity problems. Complexation, through non-covalent interaction, with OTf turned sulfa antibiotics or TCS into completely soluble in aqueous solution. OTf complexes showed superior bactericidal activity against several bacterial strains compared to the activity of free agents. Strikingly, a multi-drug resistant Salmonella strain become susceptible to antibiotics-OTf complexes while a tolC-knockout mutant strain become susceptible to OTf and more sensitive to the complexes. The antibiotic bound to OTf was, thus exported through the multi-drug efflux pump TolC in Salmonella wild-type strain. Further, antibiotics-OTf complexes were able to efficiently kill intracellular pathogens after infecting human colon carcinoma cells (HCT-116). The results demonstrate, for the first time, that the TfR mediated endocytosis of OTf can be utilized to specifically target drugs directly to pathogens or intracellularly infected cells and highlights the potency of the antibiotic-OTf complex for the treatment of infectious diseases. PMID:25315410

  4. Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules

    PubMed Central

    2016-01-01

    ABSTRACT The Gram-negative outer membrane is an important barrier that provides protection against toxic compounds, which include antibiotics and host innate immune molecules such as cationic antimicrobial peptides. Recently, significant research progress has been made in understanding the biogenesis, regulation, and functioning of the outer membrane, including a recent paper from the laboratory of Dr. Brett Finlay at the University of British Columbia (J. van der Heijden et al., mBio 7:e01238-16, 2016, http://dx.doi.org/10.1128/mBio.01541-16). These investigators demonstrate that toxic oxygen radicals, such as those found in host tissues, regulate outer membrane permeability by altering the outer membrane porin protein channels to regulate the influx of oxygen radicals as well as β-lactam antibiotics. This commentary provides context about this interesting paper and discusses the prospects of utilizing increased knowledge of outer membrane biology to develop new antibiotics for antibiotic-resistant Gram-negative bacteria. PMID:27677793

  5. Graphene laminated gold bipyramids as sensitive detection platforms for antibiotic molecules.

    PubMed

    Lee, Seunghyun; Kumar, Prashant; Hu, Yaowu; Cheng, Gary J; Irudayaraj, Joseph

    2015-11-01

    Atomic layers of graphene were optomechanically laminated onto gold bipyramids (length of ∼95 ± 3 nm and sharp tip radius less than 10 nm) using laser induced shock pressure. The fabricated graphene-gold bipyramid hybrids were employed as surface enhanced Raman scattering (SERS)-active substrates for the detection of tetracycline, an antibiotic, at very low concentrations. PMID:26340316

  6. Intercellular adhesion molecule-1 concentration, in utero, decreases after antibiotic treatment.

    PubMed

    Hadar, Amnon; Shani-Shrem, Noa; Horowitz, Shulamith

    2005-03-01

    A parturient suffering from preterm premature rupture of membranes at 29-weeks of gestation was hospitalized and staphylococcus was detected in her amniotic fluid. After treatment with antibiotics she delivered a healthy neonate three weeks later. ICAM-1 levels decreased by 20 fold correlating with elimination of the bacteria and prolongation of the pregnancy. PMID:16147830

  7. Small Molecule Docking Supports Broad and Narrow Spectrum Potential for the Inhibition of the Novel Antibiotic Target Bacterial Pth1

    PubMed Central

    Ferguson, Paul P.; Holloway, W. Blake; Setzer, William N.; McFeeters, Hana; McFeeters, Robert L.

    2016-01-01

    Peptidyl-tRNA hydrolases (Pths) play ancillary yet essential roles in protein biosynthesis by recycling peptidyl-tRNA. In E. coli, inhibition of bacterial Pth1 leads to accumulation of peptidyl-tRNA, depletion of aminoacyl-tRNA, and cell death. Eukaryotes have multiple Pths and Pth1 knock out was shown to have no effect on viability in yeast. Thereby, bacterial Pth1 is a promising target for novel antibiotic development. With the abundance of Pth1 structural data, molecular docking was used for virtual screening of existing, commercially available antibiotics to map potential interactions with Pth enzymes. Overall, 83 compounds were docked to eight different bacterial Pth1 and three different Pth2 structures. A variety of compounds demonstrated favorable docking with Pths. Whereas, some compounds interacted favorably with all Pths (potential broad spectrum inhibition), more selective interactions were observed for Pth1 or Pth2 and even specificity for individual Pth1s. While the correlation between computational docking and experimentation still remains unknown, these findings support broad spectrum inhibition, but also point to the possibility of narrow spectrum Pth1 inhibition. Also suggested is that Pth1 can be distinguished from Pth2 by small molecule inhibitors. The findings support continued development of Pth1 as an antibiotic target. PMID:27171117

  8. Simple molecular model for the binding of antibiotic molecules to bacterial ion channels

    NASA Astrophysics Data System (ADS)

    Mafé, Salvador; Ramírez, Patricio; Alcaraz, Antonio

    2003-10-01

    A molecular model aimed at explaining recent experimental data by Nestorovich et al. [Proc. Natl. Acad. Sci. USA 99, 9789 (2002)] on the interaction of ampicillin molecules with the constriction zone in a channel of the general bacterial porin, OmpF (outer membrane protein F), is presented. The model extends T. L. Hill's theory for intermolecular interactions in a pair of binding sites [J. Am. Chem. Soc. 78, 3330 (1956)] by incorporating two binding ions and two pairs of interacting sites. The results provide new physical insights on the role of the complementary pattern of the charge distributions in the ampicillin molecule and the narrowest part of the channel pore. Charge matching of interacting sites facilitates drug binding. The dependence of the number of ampicillin binding events per second with the solution pH and salt concentration is explained qualitatively using a reduced number of fundamental concepts.

  9. Single-molecule analysis of the E. coli replisome and use of clamps to bypass replication barriers

    PubMed Central

    Georgescu, Roxana E.; Yao, Nina Y.; O’Donnell, Mike

    2010-01-01

    The process of chromosome duplication faces many obstacles. One way to circumvent blocks is to hop over them by placing a new clamp on a downstream primer. This resembles lagging strand synthesis, where the tight grip of polymerase to the clamp and DNA must be overcome upon completing each Okazaki fragment so it can transfer to new primed sites. This review focuses on recent single-molecule studies showing that E. coli Pol III can hop from one clamp to another without leaving the replication fork. This capability provides a means to circumvent obstacles like transcription or DNA lesions without fork collapse. PMID:20388515

  10. Heart bypass surgery

    MedlinePlus

    Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

  11. Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis.

    PubMed

    Seward, Robert J; Drouin, Elise E; Steere, Allen C; Costello, Catherine E

    2011-03-01

    Disease-associated HLA-DR molecules, which may present autoantigens, constitute the greatest genetic risk factor for rheumatoid arthritis (RA) and antibiotic-refractory Lyme arthritis (LA). The peptides presented by HLA-DR molecules in synovia have not previously been defined. Using tandem mass spectrometry, rigorous database searches, and manual spectral interpretation, we identified 1,427 HLA-DR-presented peptides (220-464 per patient) from the synovia of four patients, two diagnosed with RA and two diagnosed with LA. The peptides were derived from 166 source proteins, including a wide range of intracellular and plasma proteins. A few epitopes were found only in RA or LA patients. However, two patients with different diseases who had the same HLA allele had the largest number of epitopes in common. In one RA patient, peptides were identified as originating from source proteins that have been reported to undergo citrullination under other circumstances, yet neither this post-translational modification nor anti-cyclic citrullinated peptide antibodies were detected. Instead, peptides with the post-translational modification of S-cysteinylation were identified. We conclude that a wide range of proteins enter the HLA-DR pathway of antigen-presenting cells in the patients' synovial tissue, and their HLA-DR genotype, not the disease type, appears to be the primary determinant of their HLA-DR-peptide repertoire. New insights into the naturally presented HLA-DR epitope repertoire in target tissues may allow the identification of pathogenic T cell epitopes, and this could lead to innovative therapeutic interventions.

  12. Peptides Presented by HLA-DR Molecules in Synovia of Patients with Rheumatoid Arthritis or Antibiotic-Refractory Lyme Arthritis*

    PubMed Central

    Seward, Robert J.; Drouin, Elise E.; Steere, Allen C.; Costello, Catherine E.

    2011-01-01

    Disease-associated HLA-DR molecules, which may present autoantigens, constitute the greatest genetic risk factor for rheumatoid arthritis (RA) and antibiotic-refractory Lyme arthritis (LA). The peptides presented by HLA-DR molecules in synovia have not previously been defined. Using tandem mass spectrometry, rigorous database searches, and manual spectral interpretation, we identified 1,427 HLA-DR-presented peptides (220–464 per patient) from the synovia of four patients, two diagnosed with RA and two diagnosed with LA. The peptides were derived from 166 source proteins, including a wide range of intracellular and plasma proteins. A few epitopes were found only in RA or LA patients. However, two patients with different diseases who had the same HLA allele had the largest number of epitopes in common. In one RA patient, peptides were identified as originating from source proteins that have been reported to undergo citrullination under other circumstances, yet neither this post-translational modification nor anti-cyclic citrullinated peptide antibodies were detected. Instead, peptides with the post-translational modification of S-cysteinylation were identified. We conclude that a wide range of proteins enter the HLA-DR pathway of antigen-presenting cells in the patients' synovial tissue, and their HLA-DR genotype, not the disease type, appears to be the primary determinant of their HLA-DR-peptide repertoire. New insights into the naturally presented HLA-DR epitope repertoire in target tissues may allow the identification of pathogenic T cell epitopes, and this could lead to innovative therapeutic interventions. PMID:21081667

  13. Small molecule-mediated density-dependent control of gene expression in prokaryotes: bioluminescence and the biosynthesis of carbapenem antibiotics.

    PubMed

    Williams, P; Bainton, N J; Swift, S; Chhabra, S R; Winson, M K; Stewart, G S; Salmond, G P; Bycroft, B W

    1992-12-15

    Sophisticated signal transduction systems enable prokaryotes to sense their growth environment and mount an appropriate adaptive response. Signal transduction and gene regulation through the phosphorylation of two regulatory components is now recognised as one of the major global regulatory networks in bacteria. However, not all types of sensor-regulator circuits relay information via phosphoryl transfer. The Vibrio fischeri LuxR protein which has previously been characterised as a member of the response-regulator superfamily responds to a small diffusible signal molecule N-(3-oxohexanoyl)homoserine lactone (HSL). Biosynthesis of HSL in V. fischeri is dependent on the expression of the luxI gene. Until recently, the role of HSL as an 'autoinducer' was thought to be restricted to V. fischeri and a few related marine bacteria in which it controls the onset of bioluminescence. However, we have discovered that a diverse group of terrestrial bacteria: (1) produce HSL; (2) possess genes analogous to luxI; and (3) exhibit cell density-dependent induction of bioluminesence when transformed with a recombinant plasmid carrying V. fischeri lux genes but lacking luxI. In one of these, Erwinia carotovora, HSL is shown to mediate the cell density-dependent biosynthesis of a carbapenem antibiotic.

  14. Novel anti-infective molecule from innate immune cells as an antibiotic-alternative to control infections caused by Apicomplexa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With increasing needs for the global animal industry to address the regulatory restrictions on the use of antibiotic growth promoters (AGPs) in animal production, there is much interest to find alternatives to AGPs. To develop alternatives to antibiotics against the major poultry parasitic disease, ...

  15. Gastric bypass surgery

    MedlinePlus

    ... Y gastric bypass; Gastric bypass - Roux-en-Y; Weight-loss surgery - gastric bypass; Obesity surgery - gastric bypass ... Weight-loss surgery may be an option if you are very obese and have not been able to ...

  16. Gastric bypass surgery - discharge

    MedlinePlus

    ... bypass - discharge; Gastric bypass - Roux-en-Y - discharge; Obesity gastric bypass discharge; Weight loss - gastric bypass discharge ... al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised ...

  17. Thrombin during cardiopulmonary bypass.

    PubMed

    Edmunds, L Henry; Colman, Robert W

    2006-12-01

    Cardiopulmonary bypass (CPB) ignites a massive defense reaction that stimulates all blood cells and five plasma protein systems to produce a myriad of vasoactive and cytotoxic substances, cell-signaling molecules, and upregulated cellular receptors. Thrombin is the key enzyme in the thrombotic portion of the defense reaction and is only partially suppressed by heparin. During CPB, thrombin is produced by both extrinsic and intrinsic coagulation pathways and activated platelets. The routine use of a cell saver and the eventual introduction of direct thrombin inhibitors now offer the possibility of completely suppressing thrombin production and fibrinolysis during cardiac surgery with CPB. PMID:17126170

  18. [THE ROLE OF (p)ppGpp MOLECULES IN FORMATION OF "STRICT RESPONSE" IN BACTERIA AND BIOSYNTHESIS OF ANTIBIOTICS AND MORPHOLOGICAL DIFFERENTIATION IN ACTINOMYCETES].

    PubMed

    Klymyshin, D; Stephanyshyn, O; Fedorenko, V

    2016-01-01

    Strict response is a pleiotropic physiological response of cells caused by lack of aminoacetylated tRNAs. Experimentally, this response occurs due to the lack of amino acids in the environment and the limitation of tRNA aminoacylation even in the presence of the corresponding amino acids in the cell. Many features of this response indicate its dependence on the accumulation of ppGpp molecules. There is a correlation between the growth rate of actinomycetes and biosynthesis of their secondary metabolites. Introduction of additional relA gene copies of ppGpp synthetase can affect the production of antibiotics in streptomycetes. The article presents the authors' own experimental data, dedicated to the influence of heterologous relA gene expression in Streptomyces nogalater cells.

  19. Heart bypass surgery

    MedlinePlus

    Heart bypass surgery begins with an incision made in the chest, with the breastbone cut exposing the heart. Next, ... of this great vein will be used to bypass the blocked arteries in the heart. The venous ...

  20. Coronary Artery Bypass Surgery

    MedlinePlus

    ... t help, you may need coronary artery bypass surgery. The surgery creates a new path for blood to flow ... more than one bypass. The results of the surgery usually are excellent. Many people remain symptom-free ...

  1. Coronary Artery Bypass

    MedlinePlus

    ... to 3 days in the Intensive Care Unit (ICU). Life After Bypass After bypass surgery, your doctor will recommend that you join a cardiac rehabilitation program. These programs help you make lifestyle changes ...

  2. Antibiotic Resistance

    MedlinePlus

    ... 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 ...

  3. MHC class I molecules with Superenhanced CD8 binding properties bypass the requirement for cognate TCR recognition and nonspecifically activate CTLs.

    PubMed

    Wooldridge, Linda; Clement, Mathew; Lissina, Anna; Edwards, Emily S J; Ladell, Kristin; Ekeruche, Julia; Hewitt, Rachel E; Laugel, Bruno; Gostick, Emma; Cole, David K; Debets, Reno; Berrevoets, Cor; Miles, John J; Burrows, Scott R; Price, David A; Sewell, Andrew K

    2010-04-01

    CD8(+) CTLs are essential for effective immune defense against intracellular microbes and neoplasia. CTLs recognize short peptide fragments presented in association with MHC class I (MHCI) molecules on the surface of infected or dysregulated cells. Ag recognition involves the binding of both TCR and CD8 coreceptor to a single ligand (peptide MHCI [pMHCI]). The TCR/pMHCI interaction confers Ag specificity, whereas the pMHCI/CD8 interaction mediates enhanced sensitivity to Ag. Striking biophysical differences exist between the TCR/pMHCI and pMHCI/CD8 interactions; indeed, the pMHCI/CD8 interaction can be >100-fold weaker than the cognate TCR/pMHCI interaction. In this study, we show that increasing the strength of the pMHCI/CD8 interaction by approximately 15-fold results in nonspecific, cognate Ag-independent pMHCI tetramer binding at the cell surface. Furthermore, pMHCI molecules with superenhanced affinity for CD8 activate CTLs in the absence of a specific TCR/pMHCI interaction to elicit a full range of effector functions, including cytokine/chemokine release, degranulation and proliferation. Thus, the low solution binding affinity of the pMHCI/CD8 interaction is essential for the maintenance of CTL Ag specificity.

  4. Antibiotic Resistance

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... these products really help. To Learn More about Antibiotic Resistance Get Smart About Antibiotics (Video) Fact Sheets and ...

  5. Laparoscopic Revision of Jejunoileal Bypass to Gastric Bypass

    ClinicalTrials.gov

    2009-12-28

    Clinically Severe Obesity; Metabolic Complications After Jejunoileal Bypass; Nutritional Complications After Jejunoileal Bypass; Obesity Recidivism; Inadequate Initial Weight Loss; Intestinal Malabsorptive Syndrome; Protein Malnutrition

  6. Flood Bypass Capacity Optimization

    NASA Astrophysics Data System (ADS)

    Siclari, A.; Hui, R.; Lund, J. R.

    2015-12-01

    Large river flows can damage adjacent flood-prone areas, by exceeding river channel and levee capacities. Particularly large floods are difficult to contain in leveed river banks alone. Flood bypasses often can efficiently reduce flood risks, where excess river flow is diverted over a weir to bypasses, that incur much less damage and cost. Additional benefits of bypasses include ecosystem protection, agriculture, groundwater recharge and recreation. Constructing or expanding an existing bypass costs in land purchase easements, and levee setbacks. Accounting for such benefits and costs, this study develops a simple mathematical model for optimizing flood bypass capacity using benefit-cost and risk analysis. Application to the Yolo Bypass, an existing bypass along the Sacramento River in California, estimates optimal capacity that economically reduces flood damage and increases various benefits, especially for agriculture. Land availability is likely to limit bypass expansion. Compensation for landowners could relax such limitations. Other economic values could affect the optimal results, which are shown by sensitivity analysis on major parameters. By including land geography into the model, location of promising capacity expansions can be identified.

  7. Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and Its Abrogation by Small Molecules.

    PubMed

    Boudreau, Marc A; Fishovitz, Jennifer; Llarrull, Leticia I; Xiao, Qiaobin; Mobashery, Shahriar

    2015-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β-lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibiotic-resistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria. PMID:27623311

  8. Phosphorylation of BlaR1 in Manifestation of Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus and its Abrogation by Small Molecules

    PubMed Central

    Boudreau, Marc A.; Fishovitz, Jennifer; Llarrull, Leticia I.; Xiao, Qiaobin; Mobashery, Shahriar

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β-lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibiotic-resistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria. PMID:27623311

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

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    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 sub-inhibitory concentrations acting as signaling molecules supporting the process of 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 behavior 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 the genes that confer resistance to antibiotics

  10. QSAR-assisted virtual screening of lead-like molecules from marine and microbial natural sources for antitumor and antibiotic drug discovery.

    PubMed

    Pereira, Florbela; Latino, Diogo A R S; Gaudêncio, Susana P

    2015-03-17

    A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors. A data set of 183 active pharmaceutical ingredients was additionally used for the external validation of the best models. The best classification models for antibiotic and antitumor activities were used to screen a data set of marine and microbial natural products from the AntiMarin database-25 and four lead compounds for antibiotic and antitumor drug design were proposed, respectively. The present work enables the presentation of a new set of possible lead like bioactive compounds and corroborates the results of our previous investigations. By other side it is shown the usefulness of quantum-chemical descriptors in the discrimination of biologically active and inactive compounds. None of the compounds suggested by our approach have assigned non-antibiotic and non-antitumor activities in the AntiMarin database and almost all were lately reported as being active in the literature.

  11. Antibiotic Safety

    MedlinePlus

    ... specific to women Antibiotics can lead to vaginal yeast infections. This happens because antibiotics kill the normal bacteria in the vagina and this causes yeast to grow rapidly. Symptoms of a yeast infection ...

  12. Antibiotic Agents

    MedlinePlus

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  13. [Antibiotic Stewardship].

    PubMed

    Lanckohr, Christian; Ellger, Björn

    2016-02-01

    The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.

  14. The expression of antibiotic resistance genes in antibiotic-producing bacteria.

    PubMed

    Mak, Stefanie; Xu, Ye; Nodwell, Justin R

    2014-08-01

    Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance.

  15. Bypass Flow Study

    SciTech Connect

    Richard Schultz

    2011-09-01

    The purpose of the fluid dynamics experiments in the MIR (Matched Index of-Refraction) flow system at Idaho National Laboratory (INL) is to develop benchmark databases for the assessment of Computational Fluid Dynamics (CFD) solutions of the momentum equations, scalar mixing, and turbulence models for the flow ratios between coolant channels and bypass gaps in the interstitial regions of typical prismatic standard fuel element (SFE) or upper reflector block geometries of typical Modular High-temperature Gas-cooled Reactors (MHTGR) in the limiting case of negligible buoyancy and constant fluid properties. The experiments use Particle Image Velocimetry (PIV) to measure the velocity fields that will populate the bypass flow study database.

  16. Hypoxaemia during cardiopulmonary bypass

    PubMed Central

    Muir, A. L.; Davidson, I. A.

    1971-01-01

    Blood oxygenation was studied in patients undergoing cardiopulmonary bypass using the Rygg-Kyvsgaard bubble oxygenator. Oxygenation was satisfactory in perfusions carried out at normothermia and during hypothermia. During the rewarming phase of hypothermic perfusions hypoxaemia occurred. This could be prevented by a ganglion blocking agent (trimetaphan) given during the cooling phase. PMID:5565791

  17. Experimental laparoscopic aortobifemoral bypass.

    PubMed

    Dion, Y M; Chin, A K; Thompson, T A

    1995-08-01

    The goal of the present study is to develop a technique for laparoscopic aortobifemoral bypass. Piglets weighing between 60 and 78 kg were anesthetized with halothane. The lateral retroperitoneal approach was preferred to the more familiar anterior transperitoneal approach and was successfully completed in 19 piglets. The piglets were placed in the right lateral decubitus position. The first port (2 cm) was inserted halfway between the tip of the 12th rib and the iliac crest. Four other trocars were placed in the retroperitoneum after balloon inflation had allowed creation of a space which permitted visualization of the aorta from the left renal artery down to the aorto-iliac junction. After evacuation of the retropneumoperitoneum, the cavity was maintained using an abdominal lift device and a retractor. Using this approach, we performed four aorto-bifemoral bypasses (end-to-end aortic anastomosis) after conventional intravenous heparinization (100 IU/kg) in less than 4 h. Blood loss did not exceed 250 ml and the hematocrit remained stable. Postmortem evaluation of the grafts revealed they were positioned as in a conventional bypass, their limbs having followed in the created retroperitoneal tunnels along the path of the native arteries. No mortality occurred before sacrifice of the animals. We believe that this first performed series of totally retroperitoneal laparoscopic aortobifemoral bypasses in the porcine model is useful in preparation for human application due to the anatomical similarities in the periaortic region.

  18. Multiple strategies to activate gold nanoparticles as antibiotics.

    PubMed

    Zhao, Yuyun; Jiang, Xingyu

    2013-09-21

    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.

  19. Multiple strategies to activate gold nanoparticles as antibiotics

    NASA Astrophysics Data System (ADS)

    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.

  20. Seal Bypass Systems (Invited)

    NASA Astrophysics Data System (ADS)

    Cartwright, J. A.

    2009-12-01

    Joe Cartwright 3DLab, School of Earth, Ocean and Planetary Sciences, Cardiff University, Main Building, Park Place, Cardiff CF10 3YE, Wales, UK (cartwrightja@cf.ac.uk) A conceptual model for the analysis of the sealing potential of caprock sequences is summarised here based on the recognition that many high quality seals are breached episodically or semi-permanently by a range of geological structures that act as seal by-pass systems (SBS). We formally define SBS as seismically resolvable geological features embedded within sealing sequences that promote cross-stratal fluid migration and allow fluids to bypass the pore network. We advance the concept that if such bypass systems exist within a given sealing sequence sequence, then predictions of sealing capacity based exclusively on rock physical properties such as capillary entry pressure/hydraulic conductivity will be largely negated by the capacity of the bypass system to breach the grain and pore network. This model is based largely on observations of sealing sequences using 3D seismic data, in which there is direct evidence of highly focused vertical or sub-vertical fluid flow from subsurface reservoirs up through the sealing sequence with leakage internally at higher levels or to the surface as seeps or pockmarks. We classify SBS into three main classes based on seismic interpretational criteria: (1) fault related, (2) intrusion-related, and (3) pipe-related. Examples are presented of each class of SBS in a relevant context of a particular sealing sequence, and where seismic evidence of hydrocarbon leakage allows the role of the bypass features to be evaluated. These include mud volcano conduits, sandstone intrusions, normal and thrust faults, blowout pipes and igneous intrusions. We show how each class exhibits different modes of behaviour with potential for different scaling relationships between flux and dimensions, and different short and long-term impacts on seal behaviour. We conclude with an analysis of

  1. Antibiotics Quiz

    MedlinePlus

    ... Viruses b) Bacteria c) Viruses and Bacteria 2. Bacteria are germs that cause colds and flu. a) ... The Flu c) Cold d) Strep Throat 4. Bacteria that cause infections can become resistant to antibiotics. ...

  2. Low-Voltage Bypass Device

    NASA Technical Reports Server (NTRS)

    Wilson, J. P.

    1994-01-01

    Improved bypass device provides low-resistance current shunt around low-voltage power cell when cell fails in open-circuit condition during operation. In comparison with older bypass devices for same application, this one weighs less, generates less heat, and has lower voltage drop (less resistance). Bypass device connected in parallel with power cell. Draws very little current during normal operation of cell.

  3. Overcoming Resistance to β-Lactam Antibiotics

    PubMed Central

    Worthington, Roberta J.; Melander, Christian

    2013-01-01

    β-Lactam antibiotics are one of the most important antibiotic classes but are plagued by problems of resistance and the development of new β-lactam antibiotics through side chain modification of existing β-lactam classes is not keeping pace with resistance development. In this perspective we summarize small molecule strategies to overcome resistance to β-lactam antibiotics. These approaches include the development of β-lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms. PMID:23530949

  4. Receptivity and Bypass Dynamics

    NASA Technical Reports Server (NTRS)

    Lasseigne, D. G.; Criminale, W. O.; Joslin, R. D.; Jackson, T. L.

    1999-01-01

    Problems concerning laminar-turbulent transition are addressed by solving a series of initial value problems. Solutions to the temporal, initial-value problem .with an inhomogeneous forcing term imposed upon the flow are sought. It is shown that: (1) A transient disturbance lying located outside of the boundary layer can lead to the growth of an unstable Tollmein-Schlicting wave; (2) A resonance with the continuous spectrum may provide a mechanism for bypass transition; and (3) The continuum modes of a disturbance feed directly into the Tollmein-Schlicting wave downstream through non-parallel effects.

  5. Your diet after gastric bypass surgery

    MedlinePlus

    Gastric bypass surgery - your diet; Obesity - diet after bypass; Weight loss - diet after bypass ... lot of calories. Avoid drinks that have sugar, fructose, or corn syrup in them. Avoid carbonated drinks ( ...

  6. Heart bypass surgery - minimally invasive - discharge

    MedlinePlus

    ... coronary artery bypass - discharge; RACAB - discharge; Keyhole heart surgery - discharge ... You had minimally invasive coronary artery bypass surgery on one ... an artery from your chest to create a detour, or bypass, around ...

  7. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    PubMed

    Vafai, Scott B; Mevers, Emily; Higgins, Kathleen W; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y; Clardy, Jon; Mootha, Vamsi K

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

  8. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors

    PubMed Central

    Mevers, Emily; Higgins, Kathleen W.; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y.; Clardy, Jon; Mootha, Vamsi K.

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as “complex I bypass.” In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

  9. Bypass Surgery for Lower Extremity Limb Salvage: Vein Bypass

    PubMed Central

    2012-01-01

    Bypass surgery for limb salvage in cases of chronic limb ischemia is a well-established treatment modality. Use of an autogenous vein provides the best conduit for infrainguinal arterial bypass procedures, particularly for bypass to the infrapopliteal arteries. In this article, we discuss infrainguinal vein bypass surgery including indications, perioperative care, and long-term follow up. We also discuss the outcomes of the procedure with regard to patient survival and limb salvage. The autogenous vein continues to be the best available conduit with the highest patency rate and the best treatment option. Compared to all other revascularization options for infrainguinal disease, the vein bypass has the best limb salvage and long-term survival in patients appropriately selected for the procedure. PMID:23342187

  10. Spiritual Bypass: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Glosoff, Harriet L.; Hammond, Cheree

    2010-01-01

    The phenomenon of spiritual bypass has received limited attention in the transpersonal psychology and counseling literature and has not been subjected to empirical inquiry. This study examines the phenomenon of spiritual bypass by considering how spirituality, mindfulness, alexithymia (emotional restrictiveness), and narcissism work together to…

  11. Aerosolized Antibiotics.

    PubMed

    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.

  12. Bypass diode integration

    NASA Technical Reports Server (NTRS)

    Shepard, N. F., Jr.

    1981-01-01

    Protective bypass diodes and mounting configurations which are applicable for use with photovoltaic modules having power dissipation requirements in the 5 to 50 watt range were investigated. Using PN silicon and Schottky diode characterization data on packaged diodes and diode chips, typical diodes were selected as representative for each range of current carrying capacity, an appropriate heat dissipating mounting concept along with its environmental enclosure was defined, and a thermal analysis relating junction temperature as a function of power dissipation was performed. In addition, the heat dissipating mounting device dimensions were varied to determine the effect on junction temperature. The results of the analysis are presented as a set of curves indicating junction temperature as a function of power dissipation for each diode package.

  13. Designing Safer and Greener Antibiotics

    PubMed Central

    Jordan, Andrew; Gathergood, Nicholas

    2013-01-01

    Since the production of the first pharmaceutically active molecules at the beginning of the 1900s, drug molecules and their metabolites have been observed in the environment in significant concentrations. In this review, the persistence of antibiotics in the environment and their associated effects on ecosystems, bacterial resistance and health effects will be examined. Solutions to these problems will also be discussed, including the pharmaceutical industries input, green chemistry, computer modeling and representative ionic liquid research. PMID:27029311

  14. The Double Life of Antibiotics

    PubMed Central

    Yap, Mee-Ngan F.

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.”~Alexander Fleming PMID:24003650

  15. Antibiotics in dentistry: Bacteremia, antibiotic prophylaxis, and antibiotic misuse.

    PubMed

    Dinsbach, Nathan A

    2012-01-01

    What is known regarding bacteremia? How effective is antibiotic prophylaxis for distant-site infections (late prosthetic joint infections and infective endocarditis)? Antibiotic resistance poses a growing danger to mankind. The misuse of antibiotics is a main cause of antibiotic resistance in bacteria. The author undertook a Medline search and a hand search of the literature regarding bacteremia, antibiotic prophylaxis for late prosthetic joint infections and infective endocarditis, antibiotic misuse, and antibiotic resistance. The findings indicate a clearer understanding of bacteremia emerging in the past 30 years, which has led to recent changes in antibiotic prophylaxis regimens. Dentists should understand how bacteremia affects their at-risk patients, the rationale for antibiotic prophylaxis, and how antibiotic misuse poses a threat to all.

  16. Heart bypass surgery - minimally invasive

    MedlinePlus

    ... MIDCAB; Robot assisted coronary artery bypass; RACAB; Keyhole heart surgery ... To perform this surgery: The heart surgeon will make a 3- to 5-inch-long surgical cut in the left part of your chest between your ribs ...

  17. Photovoltaic module bypass diode encapsulation

    NASA Technical Reports Server (NTRS)

    Shepard, N. J., Jr.

    1983-01-01

    The design and processing techniques necessary to incorporate bypass diodes within the module encapsulant are presented. The Semicon PN junction diode cells were selected. Diode junction to heat spreader thermal resistance measurements, performed on a variety of mounted diode chip types and sizes, have yielded values which are consistently below 1 deg C per watt, but show some instability when thermally cycled over the temperature range from -40 to 150 deg C. Three representative experimental modules, each incorporating integral bypass diode/heat spreader assemblies of various sizes, were designed. Thermal testing of these modules enabled the formulation of a recommended heat spreader plate sizing relationship. The production cost of three encapsulated bypass diode/heat spreader assemblies were compared with similarly rated externally mounted packaged diodes. It is concluded that, when proper designed and installed, these bypass diode devices will improve the overall reliability of a terrestrial array over a 20 year design lifetime.

  18. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. PMID:25450262

  19. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.

  20. Microbiological effects of sublethal levels of antibiotics.

    PubMed

    Andersson, Dan I; Hughes, Diarmaid

    2014-07-01

    The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.

  1. Bypass rewiring and robustness of complex networks.

    PubMed

    Park, Junsang; Hahn, Sang Geun

    2016-08-01

    A concept of bypass rewiring is introduced, and random bypass rewiring is analytically and numerically investigated with simulations. Our results show that bypass rewiring makes networks robust against removal of nodes including random failures and attacks. In particular, random bypass rewiring connects all nodes except the removed nodes on an even degree infinite network and makes the percolation threshold 0 for arbitrary occupation probabilities. In our example, the even degree network is more robust than the original network with random bypass rewiring, while the original network is more robust than the even degree networks without random bypass. We propose a greedy bypass rewiring algorithm which guarantees the maximum size of the largest component at each step, assuming which node will be removed next is unknown. The simulation result shows that the greedy bypass rewiring algorithm improves the robustness of the autonomous system of the Internet under attacks more than random bypass rewiring.

  2. Bypass rewiring and robustness of complex networks

    NASA Astrophysics Data System (ADS)

    Park, Junsang; Hahn, Sang Geun

    2016-08-01

    A concept of bypass rewiring is introduced, and random bypass rewiring is analytically and numerically investigated with simulations. Our results show that bypass rewiring makes networks robust against removal of nodes including random failures and attacks. In particular, random bypass rewiring connects all nodes except the removed nodes on an even degree infinite network and makes the percolation threshold 0 for arbitrary occupation probabilities. In our example, the even degree network is more robust than the original network with random bypass rewiring, while the original network is more robust than the even degree networks without random bypass. We propose a greedy bypass rewiring algorithm which guarantees the maximum size of the largest component at each step, assuming which node will be removed next is unknown. The simulation result shows that the greedy bypass rewiring algorithm improves the robustness of the autonomous system of the Internet under attacks more than random bypass rewiring.

  3. Bypass rewiring and robustness of complex networks.

    PubMed

    Park, Junsang; Hahn, Sang Geun

    2016-08-01

    A concept of bypass rewiring is introduced, and random bypass rewiring is analytically and numerically investigated with simulations. Our results show that bypass rewiring makes networks robust against removal of nodes including random failures and attacks. In particular, random bypass rewiring connects all nodes except the removed nodes on an even degree infinite network and makes the percolation threshold 0 for arbitrary occupation probabilities. In our example, the even degree network is more robust than the original network with random bypass rewiring, while the original network is more robust than the even degree networks without random bypass. We propose a greedy bypass rewiring algorithm which guarantees the maximum size of the largest component at each step, assuming which node will be removed next is unknown. The simulation result shows that the greedy bypass rewiring algorithm improves the robustness of the autonomous system of the Internet under attacks more than random bypass rewiring. PMID:27627320

  4. Hyperamylasemia following cardiopulmonary bypass.

    PubMed

    Chang, H; Chung, Y T; Wu, G J; Hwang, F Y; Chen, K T; Peng, W L; Hung, C R

    1992-01-01

    In order to study the occurrence of postbypass hyperamylasemia, 75 patients undergoing cardiopulmonary bypass (CPB) were studied from March 1989 to January 1990. There were 49 males and 26 females. Among them, 27 had congenital heart disease, 30 had valvular disease, and 18 had coronary artery disease. There were 27 patients with at least one elevated serum amylase sample after operation. Thus, the overall incidence of hyperamylasemia was 36%. As compared with the preoperative data (1.3%), there was a statistically significant difference in the occurrence of hyperamylasemia (p less than 0.05). Three patients had overt clinical pancreatitis postoperatively. There was no positive correlation between the serum amylase level and the occurrence of pancreatitis (p greater than 0.05). Forty-two cases had a significant elevation of the amylase creatinine clearance ratio (ACCR) after CPB. However, there was no significant difference between the groups with pulsatile and nonpulsatile CPB (p greater than 0.05). Three patients (4%) died in our series. The causes of death were heart failure in two and fulminant pancreatitis associated with low cardiac output in one. Although our experience in dealing with pancreatitis improved survival, mortality was still high (33.3%) in our series. Nevertheless, there was no apparent correlation between mortality and postbypass hyperamylasemia (p greater than 0.05). Logistic regression analysis was used to analyze the risk factors of the occurrence of hyperamylasemia, and the analysis revealed that patients with coronary artery disease were susceptible to postbypass hyperamylasemia. Our studies indicate that the use of total serum amylase or ACCR to monitor for the occurrence of pancreatitis in postbypass patients is inadequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1377742

  5. Facts about Antibiotic Resistance

    MedlinePlus

    ... Trends and Cost Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance has been called one of the world’s most ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children is of particular concern ...

  6. Heat exchanger bypass test report

    SciTech Connect

    De Vries, M.L.

    1995-01-26

    This test report documents the results that were obtained while conducting the test procedure which bypassed the heat exchangers in the HC-21C sludge stabilization process. The test was performed on November 15, 1994 using WHC-SD-CP-TC-031, ``Heat Exchanger Bypass Test Procedure.`` The primary objective of the test procedure was to determine if the heat exchangers were contributing to condensation of moisture in the off-gas line. This condensation was observed in the rotameters. Also, a secondary objective was to determine if temperatures at the rotameters would be too high and damage them or make them inaccurate without the heat exchangers in place.

  7. Psychological Effects of Intestinal Bypass Surgery.

    ERIC Educational Resources Information Center

    Wampler, Richard S.; And Others

    1980-01-01

    Preoperative and postoperative intestinal bypass patients were evaluated. Results suggest that postoperative bypass patients have improved psychological health and an increased sense of freedom and well-being but may need assistance in improving self-concepts. (Author)

  8. Secondary and College LD Bypass Strategies.

    ERIC Educational Resources Information Center

    Mosby, Robert J.

    1981-01-01

    The author describes the Developmental By-Pass (DBP) Instructional technology for teaching secondary and college learning disabled (LD) students by allowing students to bypass ordering and organizational deficits. (SB)

  9. Technology Solutions Case Study: Preventing Thermal Bypass

    SciTech Connect

    none,

    2012-10-01

    This project highlights the importance of continuous air barriers in full alignment with insulation to prevent thermal bypasses and achieve high energy performance, and recommends use of ENERGY STAR's Thermal Bypass Inspection Checklist.

  10. Perforation in the bypassed stomach following laparoscopic Roux-en-Y gastric bypass.

    PubMed

    Papasavas, Pavlos K; Yeaney, Woodrow W; Caushaj, Philip F; Keenan, Robert J; Landreneau, Rodney J; Gagné, Daniel J

    2003-10-01

    Access to the bypassed stomach is difficult following laparoscopic Roux-en-Y gastric bypass (LRYGBP). The bypassed stomach is not readily available for endoscopic or radiographic evaluation. Diagnosis and treatment of peptic ulcer disease and its complications in the excluded stomach becomes difficult. We present a case of perforation in the bypassed stomach following LRYGBP secondary to peptic ulcer disease.

  11. 34 CFR 76.672 - Bypass procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Bypass procedures. 76.672 Section 76.672 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must Be Met by the State and Its Subgrantees? Procedures for Bypass § 76.672 Bypass procedures. Sections...

  12. Antibiotics that target protein synthesis.

    PubMed

    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

  13. Bypassing shake, rattle and roll

    NASA Astrophysics Data System (ADS)

    Brun, Michele; Movchan, Alexander; Jones, Ian; McPhedran, Ross

    2013-05-01

    The Tacoma Narrows Bridge is perhaps the most famous example of a bridge that collapsed unexpectedly in response to external forces. But new "wave bypass" technology - similar to that underpinning invisibility cloaks - could help avoid such disasters, as Michele Brun, Alexander Movchan, Ian Jones and Ross McPhedran explain.

  14. Compact bypass-flow filter

    NASA Technical Reports Server (NTRS)

    Swift, W. G.; Ulanovsky, J. M.

    1979-01-01

    Annular filter consisting of stacked rings separates particulates from bypass fluid passing through it in radial direction without slowing down main flow across unimpeded flow of fluid through its center. Applications include fluidized bed reactors, equipment for catalyst operations, and water purification.

  15. 78 FR 46594 - Prospective Grant of Start-up Exclusive License: Topical Antibiotic With Immune Stimulating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... the molecular signals present in bacterial DNA that stimulate the immune system's wound healing... Antibiotic With Immune Stimulating Oligodeoxynucleotide Molecules To Speed Wound Healing; and Use of CpG... 29, 2013, each entitled ``Topical Antibiotic with Immune Stimulating oligodeoxynucleotide...

  16. Fourier transform infrared and Raman spectroscopy studies on magnetite/Ag/antibiotic nanocomposites

    NASA Astrophysics Data System (ADS)

    Ivashchenko, Olena; Jurga-Stopa, Justyna; Coy, Emerson; Peplinska, Barbara; Pietralik, Zuzanna; Jurga, Stefan

    2016-02-01

    This article presents a study on the detection of antibiotics in magnetite/Ag/antibiotic nanocomposites using Fourier transform infrared (FTIR) and Raman spectroscopy. Antibiotics with different spectra of antimicrobial activities, including rifampicin, doxycycline, cefotaxime, and ceftriaxone, were studied. Mechanical mixtures of antibiotics and magnetite/Ag nanocomposites, as well as antibiotics and magnetite nanopowder, were investigated in order to identify the origin of FTIR bands. FTIR spectroscopy was found to be an appropriate technique for this task. The spectra of the magnetite/Ag/antibiotic nanocomposites exhibited very weak (for doxycycline, cefotaxime, and ceftriaxone) or even no (for rifampicin) antibiotic bands. This FTIR "invisibility" of antibiotics is ascribed to their adsorbed state. FTIR and Raman measurements show altered Csbnd O, Cdbnd O, and Csbnd S bonds, indicating adsorption of the antibiotic molecules on the magnetite/Ag nanocomposite structure. In addition, a potential mechanism through which antibiotic molecules interact with magnetite/Ag nanoparticle surfaces is proposed.

  17. Bacteria subsisting on antibiotics.

    PubMed

    Dantas, Gautam; Sommer, Morten O A; Oluwasegun, Rantimi D; Church, George M

    2008-04-01

    Antibiotics are a crucial line of defense against bacterial infections. Nevertheless, several antibiotics are natural products of microorganisms that have as yet poorly appreciated ecological roles in the wider environment. We isolated hundreds of soil bacteria with the capacity to grow on antibiotics as a sole carbon source. Of 18 antibiotics tested, representing eight major classes of natural and synthetic origin, 13 to 17 supported the growth of clonal bacteria from each of 11 diverse soils. Bacteria subsisting on antibiotics are surprisingly phylogenetically diverse, and many are closely related to human pathogens. Furthermore, each antibiotic-consuming isolate was resistant to multiple antibiotics at clinically relevant concentrations. This phenomenon suggests that this unappreciated reservoir of antibiotic-resistance determinants can contribute to the increasing levels of multiple antibiotic resistance in pathogenic bacteria. PMID:18388292

  18. Antibiotic therapy of aortic graft infection: treatment and prevention recommendations.

    PubMed

    Hodgkiss-Harlow, Kelley D; Bandyk, Dennis F

    2011-12-01

    Surgical site infection (SSI) after aortic intervention, an uncommon but serious vascular condition, requires patient-specific antibiotic therapy. Effective treatment and prevention requires the vascular surgeon to be cognizant of changing SSI microbiology, advances in antibiotic delivery, and patient characteristics. The majority of aortic graft infections are caused by Gram-positive bacteria, with methicillin-resistant Staphylococcus aureus now the prevalent pathogen. Nasal carriage of methicillin-sensitive or methicillin-resistant S aureus strains, diabetes mellitus, recent hospitalization, a failed arterial reconstruction, and the presence of a groin incision are important SSI risk factors. Overall, the aortic SSI rate is higher than predicted by the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance risk category system; ranging from 5% after open or endovascular aortic interventions to as high as 10% to 15% after aortofemoral bypass or uni-aortoiliac grafting with femorofemoral bypass. Perioperative measures to reduce S aureus nares and skin colonization, administration of antibiotic prophylaxis, meticulous wound closure/care, and therapy directed to optimize patient host defense regulation mechanisms (eg, temperature, oxygenation, blood sugar) can minimize SSI occurrence. Antibiotic therapy for aortic graft infection should utilize bactericidal drugs that penetrate bacteria biofilms and can be delivered to the surgical site both parenterally and locally in the form of antibiotic-impregnated beads or prosthetic grafts.

  19. The jejunoileal bypass and pregnancy.

    PubMed

    Woods, J R; Brinkman, C R

    1978-11-01

    The combined experience regarding pregnancy in the jejunoileal bypass patient is too limited to draw any firm conclusions. Nevertheless, the observations made in this report suggest that: (1) Safe elapse of time from shunt procedure to pregnancy has not been established and the risk of pregnancy during the period of rapid postoperative weight loss remains speculative. Limited experience suggests that there is only a relative risk during this period of metabolic derangement. (2) Pregnancy does not appear to influence the expected clinical or metabolic changes commonly observed postoperatively in the bypass patient. Dietary supplementation should be based on the weight trend, serial laboratory chemistries, and the presence or absence of ketones in the urine. (3) Neonatal outcome appears to be good in pregnancies of patients with intestinal shunt operations. It has been suggested that small for dates babies are frequent in this group of patients. This point lacks conclusive documentation. (4) Birth control pills for contraception are not advised in intestinal bypass patients because of the uncertain intestinal absorption of the medication and the subsequent risk of an unwanted pregnancy.

  20. Antibiotics and the burn patient.

    PubMed

    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.

  1. Antibiotics and the burn patient.

    PubMed

    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

  2. Ramjet bypass duct and preburner configuration

    NASA Technical Reports Server (NTRS)

    Orlando, Robert J. (Inventor)

    1994-01-01

    A combined turbofan and ramjet aircraft engine includes a forward bypass duct which allows the engine to operate more efficiently during the turbofan mode of operation. By mounting a ramjet preburner in the forward duct and isolating this duct from the turbofan bypass air, a transition from turbofan operation to ramjet operation can take place at lower flight Mach numbers without incurring pressure losses or blockage in the turbofan bypass air.

  3. Antibiotics and Resistance: Glossary

    MedlinePlus

    ... induced by natural or human activity on the ecology and living organisms. Ecology The study of the relationships and interactions between ... antibiotics The Cost of Resistance Science of Resistance Ecology Antibiotics in Agriculture Antibacterial Agents Glossary References Web ...

  4. Combating Antibiotic Resistance

    MedlinePlus

    ... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

  5. Engineering persister-specific antibiotics with synergistic antimicrobial functions.

    PubMed

    Schmidt, Nathan W; Deshayes, Stephanie; Hawker, Sinead; Blacker, Alyssa; Kasko, Andrea M; Wong, Gerard C L

    2014-09-23

    Most antibiotics target growth processes and are ineffective against persister bacterial cells, which tolerate antibiotics due to their reduced metabolic activity. These persisters act as a genetic reservoir for resistant mutants and constitute a root cause of antibiotic resistance, a worldwide problem in human health. We re-engineer antibiotics specifically for persisters using tobramycin, an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective against persisters with low metabolic and cellular transport activity. By giving tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature via addition of 12 amino acids, we transform tobramycin itself into a transporter sequence. The resulting molecule spontaneously permeates membranes, retains the high antibiotic activity of aminoglycosides, kills E. coli and S. aureus persisters 4-6 logs better than tobramycin, but remains noncytotoxic to eukaryotes. These results suggest a promising paradigm to renovate traditional antibiotics.

  6. Reversibility of antibiotic resistance

    PubMed Central

    2014-01-01

    Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

  7. Noise analysis of antibiotic permeation through bacterial channels

    NASA Astrophysics Data System (ADS)

    Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

    2003-05-01

    Statistical analysis of high-resolution current recordings from a single ion channel reconstituted into a planar lipid membrane allows us to study transport of antibiotics at the molecular detail. Working with the general bacterial porin, OmpF, we demonstrate that addition of zwitterionic β-lactam antibiotics to the membrane-bathing solution introduces transient interruptions in the small-ion current through the channel. Time-resolved measurements reveal that one antibiotic molecule blocks one of the monomers in the OmpF trimer for characteristic times from microseconds to hundreds of microseconds. Spectral noise analysis enables us to perform measurements over a wide range of changing parameters. In all cases studied, the residence time of an antibiotic molecule in the channel exceeds the estimated time for free diffusion by orders of magnitude. This demonstrates that, in analogy to substrate-specific channels that evolved to bind specific metabolite molecules, antibiotics have 'evolved' to be channel-specific. The charge distribution of an efficient antibiotic complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a zone of attraction inside the channel and compensates the penetrating molecule's entropy loss and desolvation energy. This facilitates antibiotic translocation through the narrowest part of the channel and accounts for higher antibiotic permeability rates.

  8. Extraction and detection of antibiotics in the rhizosphere metabolome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important mechanism of natural disease suppression is the production of antibiotics by soil microbes. Antibiotics are small organic molecules of microbial origin that at low concentrations are deleterious to the growth or metabolism of other microorganisms. Soilborne pathogens are sensitive to ma...

  9. Finding alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

  10. Antibiotic resistant in microorganisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial agents are necessary for use in veterinary medicine including the production of food producing animals. Antibiotic use is indicated for the treatment of bacterial target organisms and/or disease for which the antibiotic was developed. However, an unintended consequence of antibiotic ...

  11. Biotechnology of polyketides: New breath of life for the novel antibiotic genetic pathways discovery through metagenomics

    PubMed Central

    Gomes, Elisângela Soares; Schuch, Viviane; de Macedo Lemos, Eliana Gertrudes

    2013-01-01

    The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the “goose that laid the golden egg,” the potential of this wealth is still inexorable: simply adjust the focus from “micro” to “nano”, that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms. PMID:24688489

  12. Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.

    PubMed

    Gomes, Elisângela Soares; Schuch, Viviane; de Macedo Lemos, Eliana Gertrudes

    2013-12-01

    The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the "goose that laid the golden egg," the potential of this wealth is still inexorable: simply adjust the focus from "micro" to "nano", that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

  13. Antibiotic Resistance Questions and Answers

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week Antibiotic Resistance Questions and Answers Language: English Español (Spanish) Recommend ... Many ear infections Top of Page Questions about Antibiotic Resistance Examples of How Antibiotic Resistance Spreads Click for ...

  14. Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

    PubMed Central

    Liu, Gang; Chandra, Govind; Niu, Guoqing

    2013-01-01

    SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

  15. History of cardiopulmonary bypass (CPB).

    PubMed

    Hessel, Eugene A

    2015-06-01

    The development of cardiopulmonary bypass (CPB), thereby permitting open-heart surgery, is one of the most important advances in medicine in the 20th century. Many currently practicing cardiac anesthesiologists, cardiac surgeons, and perfusionists are unaware of how recently it came into use (60 years) and how much the practice of CPB has changed during its short existence. In this paper, the development of CPB and the many changes and progress that has taken place over this brief period of time, making it a remarkably safe endeavor, are reviewed. The many as yet unresolved questions are also identified, which sets the stage for the other papers in this issue of this journal.

  16. Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy.

    PubMed

    Guillard, Thomas; Pons, Stéphanie; Roux, Damien; Pier, Gerald B; Skurnik, David

    2016-07-01

    "Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics.

  17. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Definitions. (1) Bypass means the intentional diversion of wastestreams from any portion of an Industrial User... applicable Pretreatment Standards or Requirements. An Industrial User may allow any bypass to occur which... paragraphs (c) and (d) of this section. (c) Notice. (1) If an Industrial User knows in advance of the...

  18. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Bypass. 403.17 Section 403.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND NEW SOURCES OF POLLUTION § 403.17 Bypass....

  19. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Definitions. (1) Bypass means the intentional diversion of wastestreams from any portion of an Industrial User... applicable Pretreatment Standards or Requirements. An Industrial User may allow any bypass to occur which... paragraphs (c) and (d) of this section. (c) Notice. (1) If an Industrial User knows in advance of the...

  20. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Definitions. (1) Bypass means the intentional diversion of wastestreams from any portion of an Industrial User... applicable Pretreatment Standards or Requirements. An Industrial User may allow any bypass to occur which... paragraphs (c) and (d) of this section. (c) Notice. (1) If an Industrial User knows in advance of the...

  1. Bypassing An Open-Circuit Power Cell

    NASA Technical Reports Server (NTRS)

    Wannemacher, Harry E.

    1994-01-01

    Collection of bypass circuits enables battery consisting series string of cells to continue to function when one of its cells fails in open-circuit (high-resistance) condition. Basic idea simply to shunt current around defective cell to prevent open circuit from turning off battery altogether. Bypass circuits dissipate little power and are nearly immune to false activation.

  2. Over-the-counter suboptimal dispensing of antibiotics in Uganda

    PubMed Central

    Mukonzo, Jackson K; Namuwenge, Proscovia M; Okure, Gildo; Mwesige, Benjamin; Namusisi, Olivia K; Mukanga, David

    2013-01-01

    Background Overuse and misuse of antibiotics is a serious global problem. While resistance to older antibiotics is increasing, development of newer molecules has stalled. Resistance to the existing antibiotics that is largely driven by their high-volume use is a global public health problem. Uganda is one of the countries where prescription-only drugs, including antibiotics, can be obtained over the counter. We determined the rate of antibiotic dispensing and use in Uganda. Methods The study utilized a descriptive cross-sectional study design to determine the number of antibiotic “prescribed” daily doses per 1,000 clients. Data were collected from one health center II, eight general/district hospitals, one national referral hospital, and 62 registered community pharmacies. From each study site, data were collected for five consecutive days over the months of November 2011 to January 2012. Results The overall antibiotic issue rate was 43.2%. Amoxicillin, metronidazole, ciprofloxacin, sulfamethoxazole–trimethoprim, cloxacillin, and ampicillin, belonging to the WHO anatomical therapeutic chemical classifications of penicillin with extended spectra, imidazole derivatives, fluoroquinolones, and sulfonamide–trimethoprim combinations, constituted 70% of the issued antibiotics. About 41% of antibiotics were issued over the counter. At community pharmacies, where 30% of antibiotic dispensing occurred, the number of prescribed daily doses/1,000 antibiotic clients was 4,169 compared to 6,220, 7,350 and 7,500 at general/district hospitals, the national referral hospital, and the health center, respectively. Conclusion In Uganda, at least four in every ten individuals that visit a health-care facility are treated with an antibiotic. Antibiotics are largely given as over-the-counter drugs at community pharmacies. The number of antibiotic prescribed daily doses/1,000 antibiotic clients does not significantly differ between categories of health-care facilities except at

  3. Antibiotics in Canadian poultry productions and anticipated alternatives

    PubMed Central

    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 easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  4. Antibiotics in Canadian poultry productions and anticipated alternatives.

    PubMed

    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 easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  5. Ribosomal Antibiotics: Contemporary Challenges.

    PubMed

    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

    2016-06-29

    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.

  6. Ribosomal Antibiotics: Contemporary Challenges.

    PubMed

    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

  7. Ribosomal Antibiotics: Contemporary Challenges

    PubMed Central

    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

  8. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  9. Discovery and preclinical development of new antibiotics.

    PubMed

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  10. Engineered riboswitch as a gene-regulatory platform for reducing antibiotic resistance.

    PubMed

    Liu, Libing; Wang, Shu

    2014-01-01

    Antibiotic resistance (AR), the ability of a microorganism to withstand the effects of antibiotics, is a growing and increasingly serious global public health problem. Enzymatic activation of antibiotics though the production of β-lactamase is one of the main mechanisms causing AR. Synthetic riboswitch containing aptazyme is constructed in E. coli to regulate the expression of β-lactamase through small molecule-aptamer interactions, which sharply reduces the antibiotic resistance of the engineered bacteria. PMID:24549625

  11. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  12. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is... through the cardiopulmonary bypass circuit. (b) Classification. Class II (performance standards)....

  13. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  14. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass cardiotomy return sucker... Cardiopulmonary bypass cardiotomy return sucker. (a) Identification. A cardiopulmonary bypass cardiotomy return... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  15. 21 CFR 870.4350 - Cardiopulmonary bypass oxygenator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass oxygenator. 870.4350... bypass oxygenator. (a) Identification. A cardiopulmonary bypass oxygenator is a device used to exchange... the FDA guidance document entitled “Guidance for Cardiopulmonary Bypass Oxygenators 510(k) Submissions.”...

  16. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass defoamer. 870.4230 Section... bypass defoamer. (a) Identification. A cardiopulmonary bypass defoamer is a device used in conjunction with an oxygenator during cardiopulmonary bypass surgery to remove gas bubbles from the blood....

  17. 34 CFR 76.677 - Continuation of a bypass.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Continuation of a bypass. 76.677 Section 76.677... Be Met by the State and Its Subgrantees? Procedures for Bypass § 76.677 Continuation of a bypass. The Secretary continues a bypass until the Secretary determines that the grantee or subgrantee will meet...

  18. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b)...

  19. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b)...

  20. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b)...

  1. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b)...

  2. 21 CFR 870.4205 - Cardiopulmonary bypass bubble detector.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass bubble detector. 870.4205... bypass bubble detector. (a) Identification. A cardiopulmonary bypass bubble detector is a device used to detect bubbles in the arterial return line of the cardiopulmonary bypass circuit. (b)...

  3. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  4. Exhaust gas bypass valve control for thermoelectric generator

    DOEpatents

    Reynolds, Michael G; Yang, Jihui; Meisner, Greogry P.; Stabler, Francis R.; De Bock, Hendrik Pieter Jacobus; Anderson, Todd Alan

    2012-09-04

    A method of controlling engine exhaust flow through at least one of an exhaust bypass and a thermoelectric device via a bypass valve is provided. The method includes: determining a mass flow of exhaust exiting an engine; determining a desired exhaust pressure based on the mass flow of exhaust; comparing the desired exhaust pressure to a determined exhaust pressure; and determining a bypass valve control value based on the comparing, wherein the bypass valve control value is used to control the bypass valve.

  5. Setamycin, a new antibiotic.

    PubMed

    Omura, S; Otoguro, K; Nishikiori, T; Oiwa, R; Iwai, Y

    1981-10-01

    A new antibiotic, setamycin, was extracted from the mycelia of a rare actinomycete strain KM-6054. The antibiotic, the molecular formula of which was found to be C42H61NO12 (tentative), is a yellow powder showing activity against some fungi, trichomonads and weakly against Gram-positive bacteria. PMID:7309621

  6. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  7. [Antibiotics: present and future].

    PubMed

    Bérdy, János

    2013-04-14

    The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

  8. MHD Energy Bypass Scramjet Engine

    NASA Technical Reports Server (NTRS)

    Mehta, Unmeel B.; Bogdanoff, David W.; Park, Chul; Arnold, Jim (Technical Monitor)

    2001-01-01

    Revolutionary rather than evolutionary changes in propulsion systems are most likely to decrease cost of space transportation and to provide a global range capability. Hypersonic air-breathing propulsion is a revolutionary propulsion system. The performance of scramjet engines can be improved by the AJAX energy management concept. A magneto-hydro-dynamics (MHD) generator controls the flow and extracts flow energy in the engine inlet and a MHD accelerator downstream of the combustor accelerates the nozzle flow. A progress report toward developing the MHD technology is presented herein. Recent theoretical efforts are reviewed and ongoing experimental efforts are discussed. The latter efforts also include an ongoing collaboration between NASA, the US Air Force Research Laboratory, US industry, and Russian scientific organizations. Two of the critical technologies, the ionization of the air and the MHD accelerator, are briefly discussed. Examples of limiting the combustor entrance Mach number to a low supersonic value with a MHD energy bypass scheme are presented, demonstrating an improvement in scramjet performance. The results for a simplified design of an aerospace plane show that the specific impulse of the MHD-bypass system is better than the non-MHD system and typical rocket over a narrow region of flight speeds and design parameters. Equilibrium ionization and non-equilibrium ionization are discussed. The thermodynamic condition of air at the entrance of the engine inlet determines the method of ionization. The required external power for non-equilibrium ionization is computed. There have been many experiments in which electrical power generation has successfully been achieved by magneto-hydrodynamic (MHD) means. However, relatively few experiments have been made to date for the reverse case of achieving gas acceleration by the MHD means. An experiment in a shock tunnel is described in which MHD acceleration is investigated experimentally. MHD has several

  9. Bypass diode for a solar cell

    DOEpatents

    Rim, Seung Bum; Kim, Taeseok; Smith, David D.; Cousins, Peter J.

    2012-03-13

    Bypass diodes for solar cells are described. In one embodiment, a bypass diode for a solar cell includes a substrate of the solar cell. A first conductive region is disposed above the substrate, the first conductive region of a first conductivity type. A second conductive region is disposed on the first conductive region, the second conductive region of a second conductivity type opposite the first conductivity type.

  10. Monsanto may bypass NIH in microbe test.

    PubMed

    Sun, Marjorie

    1985-01-11

    The Monsanto Company is planning to ask the Environmental Protection Agency for clearance to field test a genetically engineered microbial pesticide, bypassing the traditional approval process of the National Institutes of Health. Although only federally funded institutions are required to obtain NIH approval for genetic engineering tests, Monsanto is the first company to bypass the NIH regulatory process, which has become mired in a lawsuit brought by Jeremy Rifkin. PMID:11643692

  11. Monsanto may bypass NIH in microbe test.

    PubMed

    Sun, Marjorie

    1985-01-11

    The Monsanto Company is planning to ask the Environmental Protection Agency for clearance to field test a genetically engineered microbial pesticide, bypassing the traditional approval process of the National Institutes of Health. Although only federally funded institutions are required to obtain NIH approval for genetic engineering tests, Monsanto is the first company to bypass the NIH regulatory process, which has become mired in a lawsuit brought by Jeremy Rifkin.

  12. Metagenomics and antibiotics.

    PubMed

    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.

  13. tRNAs as Antibiotic Targets

    PubMed Central

    Chopra, Shaileja; Reader, John

    2014-01-01

    Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed. PMID:25547494

  14. Sufentanil disposition during cardiopulmonary bypass.

    PubMed

    Flezzani, P; Alvis, M J; Jacobs, J R; Schilling, M M; Bai, S; Reves, J G

    1987-11-01

    In order to investigate the ability of a computer-assisted continuous infusion (CACI) system to maintain constant plasma levels of sufentanil during cardiopulmonary bypass (CPB) using pharmacokinetic data derived from healthy surgical patients to determine the infusion rate, ten patients were anaesthetized with diazepam, enflurane and oxygen until ten minutes prior to the expected time of initiation of CPB. At that point, an infusion of sufentanil, aimed to reach a central compartment concentration of 5 ng.ml-1, was started via CACI. Plasma concentrations of sufentanil, haematocrit, total protein and albumin concentrations, and nasopharyngeal and CPB inflow temperatures were obtained at predetermined intervals before and up to 90 min after the initiation of CPB. Plasma concentrations of sufentanil reached 3.8 +/- 0.4 ng.ml-1 before CPB and approached the 5.0 ng.ml-1 set point (4.7 +/- 0.4 ng.ml-1) over the 90 min of CPB. In conclusion, our results show that it is possible to obtain stable plasma levels of sufentanil on CPB using a pharmacokinetically driven infusion scheme; however, our data suggest that use of such a system may lead to accumulation of drug during CPB. PMID:2960465

  15. Bubbles and bypass: an update.

    PubMed

    Kurusz, Mark; Butler, Bruce D

    2004-01-01

    Bubbles in the bloodstream are not a normal condition--yet they remain a fact of cardiopulmonary bypass (CPB), having been extensively studied and documented since its inception some 50 years ago. While detectable levels of gaseous microemboli (GME) have decreased significantly in recent years and gross air embolism has been nearly eliminated due to increased awareness of etiologies and technological advances, methods of use of current perfusion systems continue to elicit concerns over how best to totally eliminate GME during open-heart procedures. A few studies have correlated adverse neurocognitive manifestations associated with excessive quantities of GME. Newer techniques currently in vogue, such as vacuum-assisted venous drainage, low-prime perfusion circuits, and carbon dioxide flooding of the operative field, have, in some instances, exacerbated the problem of gas embolism or engendered secondary complications in the safe conduct of CPB. Doppler monitoring (circuit or transcranial) primarily remains a research tool to detect GME emanating from the circuit or passing into the patients' cerebral vasculature. Newer developments not yet widely available, such as multiple-frequency harmonics, may finally provide a tool to distinguish particulate microemboli from GME and further delineate the clinical significance of GME.

  16. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  17. Solving the Antibiotic Crisis.

    PubMed

    Wright, Gerard D

    2015-02-13

    Antibiotics are essential for both treating and preventing infectious diseases. Paradoxically, despite their importance as pillars of modern medicine, we are in danger of losing antibiotics because of the evolution and dissemination of resistance mechanisms throughout all pathogenic microbes. This fact, coupled with an inability to bring new drugs to market at a pace that matches resistance, has resulted in a crisis of global proportion. Solving this crisis requires the actions of many stakeholders, but chemists, chemical biologists, and microbiologists must drive the scientific innovation that is required to maintain our antibiotic arsenal. This innovation requires (1) a deep understanding of the evolution and reservoirs of resistance; (2) full knowledge of the molecular mechanisms of antibiotic action and resistance; (3) the discovery of chemical and genetic probes of antibiotic action and resistance; (4) the integration of systems biology into antibiotic discovery; and (5) the discovery of new antimicrobial chemical matter. Addressing these pressing scientific gaps will ensure that we can meet the antibiotic crisis with creativity and purpose. PMID:27622298

  18. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

    SciTech Connect

    Harvey, R.A.; Alcid, D.V.; Greco, R.S.

    1982-09-01

    Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

  19. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-11-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

  20. Oxidative stress in coronary artery bypass surgery

    PubMed Central

    Dias, Amaury Edgardo Mont’Serrat Ávila Souza; Melnikov, Petr; Cônsolo, Lourdes Zélia Zanoni

    2015-01-01

    Objective The aim of this prospective study was to assess the dynamics of oxidative stress during coronary artery bypass surgery with cardiopulmonary bypass. Methods Sixteen patients undergoing coronary artery bypass grafting were enrolled. Blood samples were collected from the systemic circulation during anesthesia induction (radial artery - A1), the systemic venous return (B1 and B2) four minutes after removal of the aortic cross-clamping, of the coronary sinus (CS1 and CS2) four minutes after removal of the aortic cross-clamping and the systemic circulation four minutes after completion of cardiopulmonary bypass (radial artery - A2). The marker of oxidative stress, malondialdehyde, was measured using spectrophotometry. Results The mean values of malondialdehyde were (ng/dl): A1 (265.1), B1 (490.0), CS1 (527.0), B2 (599.6), CS2 (685.0) and A2 (527.2). Comparisons between A1/B1, A1/CS1, A1/B2, A1/CS2, A1/A2 were significant, with ascending values (P<0.05). Comparisons between the measurements of the coronary sinus and venous reservoir after the two moments of reperfusion (B1/B2 and CS1/CS2) were higher when CS2 (P<0.05). Despite higher values ​​after the end of cardiopulmonary bypass (A2), when compared to samples of anesthesia (A1), those show a downward trend when compared to the samples of the second moment of reperfusion (CS2) (P<0.05). Conclusion The measurement of malondialdehyde shows that coronary artery bypass grafting with cardiopulmonary bypass is accompanied by increase of free radicals and this trend gradually decreases after its completion. Aortic clamping exacerbates oxidative stress but has sharper decline after reperfusion when compared to systemic metabolism. The behavior of thiobarbituric acid species indicates that oxidative stress is an inevitable pathophysiological component. PMID:27163415

  1. Robotic coronary artery bypass grafting.

    PubMed

    Folliguet, Thierry A; Dibie, Alain; Philippe, François; Larrazet, Fabrice; Slama, Michel S; Laborde, François

    2010-12-01

    Robotically assisted surgery enables coronary surgery to be performed totally or partially endoscopically. Using the Da Vinci robotic technology allows minimally invasive treatments. We report on our experience with coronary artery surgery in our department: patients requiring single or double vessel surgical revascularization were eligible. The procedure was performed without cardiopulmonary bypass on a beating heart. From April 2004 to May 2008, 55 consecutive patients were enrolled in the study, and were operated on by a single surgical team. Operative outcomes included operative time, estimated blood loss, transfusions, ventilation time, intensive care unit (ICU) and hospital length of stay. Average operative time was 270 ± 101 min with an estimated blood loss of 509 ± 328 ml, a postoperative ventilation time of 6 ± 12 h, ICU stay of 52 ± 23 h, and a hospital stay of 7 ± 3 days. Nine patients (16%) were converted to open techniques, and transfusion was required in four patients (7%). Follow-up was complete for all patients up to 1 year. There was one hospital death (1.7%) and two deaths at follow-up. Coronary anastomosis was controlled in 48 patients by either angiogram or computed tomography scan, revealing occlusion or anastomotic stenoses (>50%) in six patients. Overall permeability was 92%. Major adverse events occurred in 12 patients (21%). One-year survival was 96%. Our initial experience with robotically assisted coronary surgery is promising: it avoids sternotomy and with a methodical approach we were able to implement the procedure safely and effectively in our practice, combining minimal mortality with excellent survival. PMID:27627952

  2. Snake Venom: Any Clue for Antibiotics and CAM?

    PubMed Central

    2005-01-01

    Lately several naturally occurring peptides presenting antimicrobial activity have been described in the literature. However, snake venoms, which are an enormous source of peptides, have not been fully explored for searching such molecules. The aim of this work is to review the basis of antimicrobial mechanisms revealing snake venom as a feasible source for searching an antibiotic prototype. Therefore, it includes (i) a description of the constituents of the snake venoms involved in their main biological effects during the envenomation process; (ii) examples of snake venom molecules of commercial use; (iii) mechanisms of action of known antibiotics; and (iv) how the microorganisms can be resistant to antibiotics. This review also shows that snake venoms are not totally unexplored sources for antibiotics and complementary and alternative medicine (CAM). PMID:15841277

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

    PubMed

    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.

  4. Selective condensation of DNA by aminoglycoside antibiotics.

    PubMed

    Kopaczynska, M; Schulz, A; Fraczkowska, K; Kraszewski, S; Podbielska, H; Fuhrhop, J H

    2016-05-01

    The condensing effect of aminoglycoside antibiotics on the structure of double-stranded DNA was examined. The selective condensation of DNA by small molecules is an interesting approach in biotechnology. Here, we present the interaction between calf thymus DNA and three types of antibiotic molecules: tobramycin, kanamycin, and neomycin. Several techniques were applied to study this effect. Atomic force microscopy, transmission electron microscopy images, and nuclear magnetic resonance spectra showed that the interaction of tobramycin with double-stranded DNA caused the rod, toroid, and sphere formation and very strong condensation of DNA strands, which was not observed in the case of other aminoglycosides used in the experiment. Studies on the mechanisms by which small molecules interact with DNA are important in understanding their functioning in cells, in designing new and efficient drugs, or in minimizing their adverse side effects. Specific interactions between tobramycin and DNA double helix was modeled using molecular dynamics simulations. Simulation study shows the aminoglycoside specificity to bend DNA double helix, shedding light on the origins of toroid formation. This phenomenon may lighten the ototoxicity or nephrotoxicity issues, but also other adverse reactions of aminoglycoside antibiotics in the human body.

  5. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity.

    PubMed

    Thaker, Maulik N; Wright, Gerard D

    2015-03-20

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis.

  6. Resistance-resistant antibiotics.

    PubMed

    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.

  7. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  8. Targeting Antibiotic Resistance

    PubMed Central

    Chellat, Mathieu F.; Raguž, Luka

    2016-01-01

    Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

  9. Percutaneous Transluminal Angioplasty of Peripheral Bypass Stenoses

    SciTech Connect

    Hoksbergen, Arjan W.J.; Legemate, Dink A.; Reekers, Jim A.; Ubbink, Dirk T.; Jacobs, Michael J.H.M.

    1999-07-15

    Purpose: To assess the success of percutaneous transluminal angioplasty (PTA) in treating peripheral bypass stenoses. Methods: Patients who received a femoropopliteal or femorocrural bypass graft for limb ischemia were included in a duplex surveillance program. If duplex ultrasound revealed a short (<2 cm) severe (peak systolic velocity ratio {>=} 4.5) stenosis, patients were scheduled for arteriography and PTA. Fifty-eight peripheral bypass stenoses in 39 grafts in 37 patients were treated with PTA. The cumulative primary patency of treated stenoses was calculated. Results: During the first year after PTA 31 (53%) treated lesions remained patent, 15 (26%) lesions restenosed at a median interval of 5.0 (range 1-12) months and 4 (7%) bypasses occluded. The cumulative primary patency of 58 treated graft stenoses at 1 year was 60% [95% confidence interval (CI) 46%-74%] and 55% (95% CI 41%-70%) at 2 years. Graft body stenoses showed a better 2-year cumulative primary patency (86%; 95% CI 68%-100%) compared with juxta-anastomotic lesions (45%; 95% CI 29%-62%; p < 0.05). Conclusion: PTA is justifiable as the initial treatment of peripheral bypass stenoses. Nevertheless, the restenosis rate is rather high, especially in juxta-anastomotic lesions. Continuation of duplex surveillance after PTA and timely reintervention is recommended.

  10. [Antibiotic therapy in psittacines].

    PubMed

    Krautwald, M E

    1989-01-01

    The use of different antibiotics in psittacines is described. Among other aspects especially the anatomy of the bird and its consequence for the application of medicaments is taken into account. The use of antibiotics in psittacines often turns out to be difficult because of missing data about their pharmacokinetics, dosage, period of application and their compatibility. In order to deal with the increasing number of pet-birds in the veterinary practice, further examinations have to be conducted. PMID:2655172

  11. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases. PMID:24326504

  12. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases.

  13. Clinical experimentation with aerosol antibiotics: current and future methods of administration

    PubMed Central

    Zarogoulidis, Paul; Kioumis, Ioannis; Porpodis, Konstantinos; Spyratos, Dionysios; Tsakiridis, Kosmas; Huang, Haidong; Li, Qiang; Turner, J Francis; Browning, Robert; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos

    2013-01-01

    Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed. PMID:24115836

  14. Natural and engineered biosynthesis of nucleoside antibiotics in Actinomycetes.

    PubMed

    Chen, Wenqing; Qi, Jianzhao; Wu, Pan; Wan, Dan; Liu, Jin; Feng, Xuan; Deng, Zixin

    2016-03-01

    Nucleoside antibiotics constitute an important family of microbial natural products bearing diverse bioactivities and unusual structural features. Their biosynthetic logics are unique with involvement of complex multi-enzymatic reactions leading to the intricate molecules from simple building blocks. Understanding how nature builds this family of antibiotics in post-genomic era sets the stage for rational enhancement of their production, and also paves the way for targeted persuasion of the cell factories to make artificial designer nucleoside drugs and leads via synthetic biology approaches. In this review, we discuss the recent progress and perspectives on the natural and engineered biosynthesis of nucleoside antibiotics.

  15. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    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. PMID:24036486

  16. [Simplified laparoscopic gastric bypass. Initial experience].

    PubMed

    Hernández-Miguelena, Luis; Maldonado-Vázquez, Angélica; Cortes-Romano, Pablo; Ríos-Cruz, Daniel; Marín-Domínguez, Raúl; Castillo-González, Armando

    2014-01-01

    Antecedentes: la cirugía de la obesidad comprende diversos procedimientos gastrointestinales. El bypass gástrico en Y de Roux es el prototipo de los procedimientos mixtos y el más practicado en el mundo en sus diversas variedades. Una técnica similar y novedosa es la adoptada por Cardoso-Ramos y Galvao denominada "bypass simplificado" que rápidamente se aceptó por la mayor facilidad y resultados muy parecidos a la técnica convencional. Objetivo: describir los resultados a un año del bypass gástrico simplificado para el tratamiento de la obesidad mórbida. Material y métodos: estudio retrospectivo y descriptivo de todos los pacientes a quienes se realizó bypass gástrico de enero de 2008 a julio de 2012, en la clínica de obesidad de un hospital privado de la Ciudad de México. Resultados: se estudiaron 90 pacientes con diagnóstico de obesidad mórbida, con límites de edad de 18 y 65 años, operados para bypass gástrico simplificado. En 10% de los pacientes hubo complicaciones, las más frecuentes fueron: hemorragia y hernia interna. Durante el periodo de estudio la mortalidad fue de 0%. La pérdida de peso promedio a los 12 meses fue de 72.7%. Conclusión: el bypass gástrico simplificado laparoscópico es una cirugía segura, con buenos resultados a mediano plazo, y con una pérdida del exceso de peso adecuada en 71% de los casos.

  17. Battery Cell By-Pass Circuit

    NASA Technical Reports Server (NTRS)

    Evers, Jeffrey (Inventor); Gelger, Ronald V. (Inventor)

    2001-01-01

    The invention is a circuit and method of limiting the charging current voltage from a power supply net work applied to an individual cell of a plurality of cells making up a battery being charged in series. It is particularly designed for use with batteries that can be damaged by overcharging, such as Lithium-ion type batteries. In detail. the method includes the following steps: 1) sensing the actual voltage level of the individual cell; 2) comparing the actual voltage level of the individual cell with a reference value and providing an error signal representative thereof; and 3) by-passing the charging current around individual cell necessary to keep the individual cell voltage level generally equal a specific voltage level while continuing to charge the remaining cells. Preferably this is accomplished by by-passing the charging current around the individual cell if said actual voltage level is above the specific voltage level and allowing the charging current to the individual cell if the actual voltage level is equal or less than the specific voltage level. In the step of bypassing the charging current, the by-passed current is transferred at a proper voltage level to the power supply. The by-pass circuit a voltage comparison circuit is used to compare the actual voltage level of the individual cell with a reference value and to provide an error signal representative thereof. A third circuit, designed to be responsive to the error signal, is provided for maintaining the individual cell voltage level generally equal to the specific voltage level. Circuitry is provided in the third circuit for bypassing charging current around the individual cell if the actual voltage level is above the specific voltage level and transfers the excess charging current to the power supply net work. The circuitry also allows charging of the individual cell if the actual voltage level is equal or less than the specific voltage level.

  18. [Evolution in the antibiotic susceptibility and resistance].

    PubMed

    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

  19. Coronary artery bypass surgery without cardiopulmonary bypass: short- and mid-term results.

    PubMed

    Mishra, Y; Mehta, Y; Kohli, V M; Kohli, V; Mairal, M; Mishra, A; Bapna, R K; Trehan, N

    1997-01-01

    From March 1994 to April 1997, 433 patients had undergone coronary artery bypass grafting without cardiopulmonary bypass in our institute. Sixty-eight patients had various organ dysfunctions and/or aortic atheroma or calcification and were regarded as high risk for cardiopulmonary bypass. In 277 patients surgery was performed through midline sternotomy, while in 156 minithoracotomy approach was used. In 361 patients single coronary artery bypass grafting was done, and in 72 two-coronary arteries were bypassed. In 63 patients who had graftable vessels in anterior wall and diffusely diseased ungraftable vessels in posterolateral and/or inferior wall, transmyocardial laser revascularisation was also done along with coronary artery bypass grafting to achieve complete myocardial revascularisation. Nine patients in this series were also subjected to simultaneous carotid endarterectomy along with myocardial revascularisation. In two patients complementary percutaneous transluminal coronary angioplasty of left circumflex coronary artery was done five days after minithoracotomy and left internal mammary artery to left anterior descending coronary artery bypass grafting. Forty-two cases were extubated in operating room. Average blood loss was 260 ml. Six patients were reexplored for postoperative bleeding. Seven patients had perioperative myocardial infarction. One developed neurological complication. Hospital mortality was 2.3 percent (10/433 cases) and four deaths were due to malignant ventricular arrhythmias. Nine patients developed chest wound complications. Average hospital stay after operation was six days, 423 patients were discharged from hospital and all of them were asymptomatic. During three years follow-up (range 3 to 38 months) there were three known cardiac deaths. Ninety percent (391) patients reported to the follow-up clinic and 91 percent of them were angina-free. In patients who were subjected to transmyocardial laser revascularisation along with coronary

  20. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted. PMID:24646082

  1. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Valves § 56.20-20 Valve bypasses. (a) Sizes of bypasses shall be in accordance with MSS SP-45 (incorporated by reference; see 46 CFR 56.01-2). (b) Pipe for bypasses should be at least Schedule 80 seamless... 46 Shipping 2 2011-10-01 2011-10-01 false Valve bypasses. 56.20-20 Section 56.20-20 Shipping...

  2. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Valves § 56.20-20 Valve bypasses. (a) Sizes of bypasses shall be in accordance with MSS SP-45 (incorporated by reference; see 46 CFR 56.01-2). (b) Pipe for bypasses should be at least Schedule 80 seamless... 46 Shipping 2 2010-10-01 2010-10-01 false Valve bypasses. 56.20-20 Section 56.20-20 Shipping...

  3. [Sepsis management -- antibiotic therapy].

    PubMed

    Welte, T

    2004-11-26

    Sepsis is one of the most frequent infectious problems at Intensive Care Units, and sepsis is associated with significant mortality. The latter could not be markedly reduced in the last years, despite a number of advances in the field of volume substitution, catecholamines, and endocrinologic therapy. The reason might be that important steps towards overcoming of sepsis are the surgical resection of infectious foci and an adequate antibiotic treatment. A critical role plays the growing resistance of pathogens against the common antibiotics. Since no major progress in the development of new antibiotics can be expected for the next years, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad and high dose initial treatment, a de-escalation strategy according to the clinical course, and -with exceptions- a limitation of treatment to 7 to 10 days. Rotation of antibiotics should be performed, if problems with resistances exist or no specialist for infectious diseases is available on the Intensive Care Unit.

  4. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass temperature controller. 870.4250 Section 870.4250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature...

  5. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the...

  6. 21 CFR 870.4300 - Cardiopulmonary bypass gas control unit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass gas control unit. 870.4300 Section 870.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... bypass gas control unit. (a) Identification. A cardiopulmonary bypass gas control unit is a device...

  7. 21 CFR 870.3545 - Ventricular bypass (assist) device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3545 Ventricular bypass (assist) device. (a) Identification. A ventricular bypass (assist) device is a device that assists... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ventricular bypass (assist) device....

  8. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the...

  9. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the...

  10. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the...

  11. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the...

  12. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger....

  13. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger....

  14. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger....

  15. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger....

  16. Bypass apparatus and method for series connected energy storage devices

    DOEpatents

    Rouillard, Jean; Comte, Christophe; Daigle, Dominik

    2000-01-01

    A bypass apparatus and method for series connected energy storage devices. Each of the energy storage devices coupled to a common series connection has an associated bypass unit connected thereto in parallel. A current bypass unit includes a sensor which is coupled in parallel with an associated energy storage device or cell and senses an energy parameter indicative of an energy state of the cell, such as cell voltage. A bypass switch is coupled in parallel with the energy storage cell and operable between a non-activated state and an activated state. The bypass switch, when in the non-activated state, is substantially non-conductive with respect to current passing through the energy storage cell and, when in the activated state, provides a bypass current path for passing current to the series connection so as to bypass the associated cell. A controller controls activation of the bypass switch in response to the voltage of the cell deviating from a pre-established voltage setpoint. The controller may be included within the bypass unit or be disposed on a control platform external to the bypass unit. The bypass switch may, when activated, establish a permanent or a temporary bypass current path.

  17. 21 CFR 870.4300 - Cardiopulmonary bypass gas control unit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... gas. (b) Classification. Class II (performance standards). ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass gas control unit. 870.4300... bypass gas control unit. (a) Identification. A cardiopulmonary bypass gas control unit is a device...

  18. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  19. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  20. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  1. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  2. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  3. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  4. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  5. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  6. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow....

  7. Quinolones: from antibiotics to autoinducers

    PubMed Central

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

    2011-01-01

    Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc1 complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression. PMID:20738404

  8. Analysis of macrolide antibiotics.

    PubMed

    Kanfer, I; Skinner, M F; Walker, R B

    1998-07-01

    The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included.

  9. Antibiotic Precautions in Athletes

    PubMed Central

    Fayock, Kristopher; Voltz, Matthew; Sandella, Bradley; Close, Jeremy; Lunser, Matthew; Okon, Joshua

    2014-01-01

    Context: Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. Evidence Acquisition: Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website was utilized. Study Design: Clinical review. Level of Evidence: Level 3. Results: The team physician should consider alternative medications in place of the “drug of choice” when adverse drug effects are a concern for an athlete’s health or performance. If alternative medications cannot be selected, secondary preventative measures, including sunscreen or probiotics, may be needed. Conclusion: Physicians choose medications based on a variety of factors to help ensure infection resolution while limiting potential side effects. Extra precautions are indicated when treating athletes with certain antibiotics. PMID:24982704

  10. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon.

  11. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon. PMID:3569006

  12. Gastric infarction following gastric bypass surgery

    PubMed Central

    Do, Patrick H; Kang, Young S; Cahill, Peter

    2016-01-01

    Gastric infarction is an extremely rare occurrence owing to the stomach’s extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID:27200168

  13. Antibiotic prophylaxis in otolaryngologic surgery

    PubMed Central

    Ottoline, Ana Carolina Xavier; Tomita, Shiro; Marques, Marise da Penha Costa; Felix, Felippe; Ferraiolo, Priscila Novaes; Laurindo, Roberta Silveira Santos

    2013-01-01

    Summary Aim: Antibiotic prophylaxis aims to prevent infection of surgical sites before contamination or infection occurs. Prolonged antibiotic prophylaxis does not enhance the prevention of surgical infection and is associated with higher rates of antibiotic-resistant microorganisms. This review of the literature concerning antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery in order to reduce the numbers of complications stemming from the indiscriminate use of antibiotics. PMID:25991999

  14. Tackling antibiotic resistance.

    PubMed

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A; Kishony, Roy; Kreiswirth, Barry N; Kutter, Elizabeth; Lerner, Stephen A; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H; Mobashery, Shahriar; Piddock, Laura J V; Projan, Steven; Thomas, Christopher M; Tomasz, Alexander; Tulkens, Paul M; Walsh, Timothy R; Watson, James D; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I

    2011-11-02

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.

  15. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  16. Antibiotic drug discovery.

    PubMed

    Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. PMID:27470984

  17. Antibiotics in Animal Products

    NASA Astrophysics Data System (ADS)

    Falcão, Amílcar C.

    The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

  18. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  19. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  20. Interstellar molecules

    NASA Astrophysics Data System (ADS)

    Smith, D.

    1987-09-01

    Some 70 different molecular species have so far been detected variously in diffuse interstellar clouds, dense interstellar clouds, and circumstellar shells. Only simple (diatomic and triatomic) species exist in diffuse clouds because of the penetration of destructive UV radiations, whereas more complex (polyatomic) molecules survive in dense clouds as a result of the shielding against this UV radiation provided by dust grains. A current list of interstellar molecules is given together with a few other molecular species that have so far been detected only in circumstellar shells. Also listed are those interstellar species that contain rare isotopes of several elements. The gas phase ion chemistry is outlined via which the observed molecules are synthesized, and the process by which enrichment of the rare isotopes occurs in some interstellar molecules is described.

  1. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  2. Antibiotics and antibiotic resistance in agroecosystems: State of the science

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review article proposes a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal ...

  3. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

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

    PubMed

    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.

  5. Discovery research: the scientific challenge of finding new antibiotics.

    PubMed

    Livermore, David M

    2011-09-01

    The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to permeate bacteria, evade efflux and avoid mutational resistance; moreover, the compound libraries were systematically biased against antibiotics. The sorry result is that no antibiotic found by this strategy has yet entered clinical use and many major pharmaceutical companies have abandoned antibiotic discovery. Although a raft of start-up companies-variously financed by venture capital, charity or public money--are now finding new antibiotic compounds (some of them very promising in vitro or in early trials), their development through Phase III depends on financial commitments from large pharmaceutical companies, where the discouraging regulatory environment and the poor likely return on investment remain paramount issues.

  6. Fever of unknown origin: Importance of 18F-FDG PET/CT in the diagnosis of a late infectious complication after aneurysm bypass.

    PubMed

    Goudard, Y; Pierret, C; Dusaud, M; Falzone, E; Tourtier, J P; de Kerangal, X

    2011-09-01

    Persistent blood flow in aneurysmal sac after bypass-exclusion is well documented in the literature. Aneurysm enlargement, local compressive symptoms and even sac rupture are commonly described complications. Late secondary infection of popliteal artery aneurysm (PAA) following ligation and venous bypass is exceptional. We report the case of late PAA infection six years after bypass-exclusion in a 75 year-old man which was diagnosed by 18F-FDG PET/CT. The patient was successfully treated by aneurysm resection and antibiotics. The diagnosis of popliteal aneurysm infection is often clinical, echographic and sonographic, but computed tomography scan can be false negative in chronic low-grade infection. 18F-FDG PET/CT is able to accurately diagnose and localize infection with high sensibility and specificity.

  7. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  8. [Antibiotical prophylaxy in gynecology].

    PubMed

    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

  9. Mechanisms of Antibiotic Resistance.

    PubMed

    Munita, Jose M; Arias, Cesar A

    2016-04-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens. PMID:27227291

  10. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target 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 due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target 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. PMID:25458541

  11. Antibiotics before surgery.

    PubMed

    Kaatz, B

    1996-01-01

    The antimicrobial era (along with greater surgical skill and precision) has brought us relative safety for procedures that previously were fraught with danger. Civil War amputation surgeries, for example, had an extraordinarily high incidence of infections and mortality. Staying aware of and avoiding the small, but real, risks associated with surgical antibiotic prophylaxis will help sustain the advances we enjoy today. PMID:8650524

  12. Antibiotics, pediatric dysbiosis, and disease.

    PubMed

    Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S; Knights, Dan

    2015-05-13

    Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.

  13. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

  14. A new strategy to fight antimicrobial resistance: the revival of old antibiotics

    PubMed Central

    Cassir, Nadim; Rolain, Jean-Marc; Brouqui, Philippe

    2014-01-01

    The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice. PMID:25368610

  15. Detection of Antibiotics Produced by Soil and Rhizosphere Microbes In Situ

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are small organic molecules of microbial origin that at low concentrations, are deleterious to the growth or metabolism of other microorganisms. More broadly, antibiotics constitute a functionally defined subset of the diverse array of bioactive metabolites produced by microorganisms in ...

  16. Novel TPP-riboswitch activators bypass metabolic enzyme dependency

    NASA Astrophysics Data System (ADS)

    Mayer, Günter; Lünse, Christina; Suckling, Colin; Scott, Fraser

    2014-07-01

    Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antibacterial targets. Here, we describe thiamine analogs containing a central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent gene expression in different E. coli strains. Additionally, we show that compound activation is dependent on proteins involved in the metabolic pathways of thiamine uptake and synthesis. The most promising molecule, triazolethiamine (TT), shows concentration dependent reporter gene repression that is dependent on the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a known TPP-riboswitch modulator, is ThiK independent. We further show that this dependence can be bypassed by triazolethiamine-derivatives that bear phosphate-mimicking moieties. As triazolethiamine reveals superior activity compared to pyrithiamine, it represents a very promising starting point for developing novel antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting compounds engage diverse endogenous mechanisms to attain in vivo activity. These findings are of importance for the understanding of compounds that require metabolic activation to achieve effective riboswitch modulation and they enable the design of novel compound generations that are independent of endogenous activation mechanisms.

  17. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    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)

  18. What Can Be Done about Antibiotic Resistance?

    MedlinePlus

    ... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

  19. Specialised metabolites regulating antibiotic biosynthesis in Streptomyces spp.

    PubMed

    Niu, Guoqing; Chater, Keith F; Tian, Yuqing; Zhang, Jihui; Tan, Huarong

    2016-07-01

    Streptomyces bacteria are the major source of antibiotics and other secondary metabolites. Various environmental and physiological conditions affect the onset and level of production of each antibiotic by influencing concentrations of the ligands for conserved global regulatory proteins. In addition, as reviewed here, well-known autoregulators such as γ-butyrolactones, themselves products of secondary metabolism, accumulate late in growth to concentrations allowing their effective interaction with cognate binding proteins, in a necessary prelude to antibiotic biosynthesis. Most autoregulator binding proteins target the conserved global regulatory gene adpA, and/or regulatory genes for 'cluster-situated regulators' (CSRs) linked to antibiotic biosynthetic gene clusters. It now appears that some CSRs bind intermediates and end products of antibiotic biosynthesis, with regulatory effects interwoven with those of autoregulators. These ligands can exert cross-pathway effects within producers of more than one antibiotic, and when excreted into the extracellular environment may have population-wide effects on production, and mediate interactions with neighbouring microorganisms in natural communities, influencing speciation. Greater understanding of these autoregulatory and cross-regulatory activities may aid the discovery of new signalling molecules and their use in activating cryptic antibiotic biosynthetic pathways. PMID:27288284

  20. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

  1. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed Central

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

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

    PubMed

    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.

  3. 'Escentric' molecules.

    PubMed

    Schön, Geza

    2008-06-01

    Can a fragrance be revolutionary? In this commentary, the creation of two unusual, extravagant fine fragrances, 'escentric01' and 'molecule01', is described. In response to the fantasy components found in release notes of many recent perfume launches, both center around a single real fragrance raw material, the transparent woody aroma chemical 'Iso E Super' (1+2). The perfume 'escentric01' contains 65% of it, accompanied by Trisamber (3), red pepper, lime oil, incense and musks, while 'molecule01' consists exclusively of 'Iso E Super' (1+2). The elegant woody note lives here its own eccentric life--the revolution starts.

  4. [Cardiac rehabilitation after coronary artery bypass surgery].

    PubMed

    Dayan, Victor; Ricca, Roberto

    2014-01-01

    Ischemic heart disease is the leading cause of death worldwide with an increase in the incidence in younger populations. Today revascularization strategies are capable of alleviating acute ischemia and/or chronic ischemia. These can be performed percutaneously or through surgery. Even if we improve myocardial perfusion by these methods, the main determinant in maintaining patency of coronary arteries and bypass is a correctly instituted secondary prevention. This is the main focus of cardiac rehabilitation proposals. Although much has been published about the role of cardiac rehabilitation after percutaneous revascularization, there is little work able to synthesize the current state of cardiac rehabilitation in patients undergoing coronary artery bypass surgery. The aim of this paper is to review the effect of rehabilitation in the return to work, survival, functional capacity, depression and anxiety, as well as compare centralized vs. home rehabilitation in this patient population.

  5. The Golden bypass landslide, Golden, Colorado

    USGS Publications Warehouse

    Highland, L.M.; Brown, W. M.

    1993-01-01

    Slope instability along a new highway bypass in Golden, Colorado, became a major concern in 1993. Rains and snowmelt accelerated movement of a landslide that had begun to develop before the bypass was opened to traffic in July of 1991. The downslope movement of earth materials increased significantly in 1993. During the first few months of the year, the landslide pushed onto the west shoulder of the road and crumpled the pavement beneath the south-bound lane. As we prepare this article (September, 1993), the slide continues to encroach onto the highway, posing a persistent problem despite repeated efforts to slow or stop its movement. As this article will show, permanent solutions to landslide problems of this kind are difficult to obtain. 

  6. Temporary extracorporeal bypass modalities during aortic surgery.

    PubMed

    Bassin, Levi; Bell, David

    2016-09-01

    The key to aortic surgery is protection of the brain, heart, spinal cord, and viscera. For operations involving the aortic arch, the focus is on cerebral protection, while for pathology involving the descending thoracic aorta, the focus is on spinal protection. Optimal cerebral and spinal protection requires an extensive knowledge of the operative steps and an understanding of the cardiopulmonary bypass modalities that are possible. A bloodless field is required when operating on the aorta. As a result, periods of ischemia to the central nervous system and end-organ viscera are often unavoidable. The main techniques to mitigate ischemia include hypothermia and selective perfusion of the ischemic organ in question. This chapter will first briefly review bypass modalities and then describe how they can be used for various aortic scenarios. PMID:27650344

  7. TRAS principles blight arterial bypass and plasty.

    PubMed

    Kothari, M V; Mehta, L A; Kothari, V M

    1997-01-01

    A new concept--Tissue Requisitions (Principle I)/Relinquishes (Principle II) Arterial Supply--of TRAS principles is introduced to help appreciate the failures/successes of modern medicine's attempts at restoring arterial flow in luminally compromised coronary/carotid fields, an invasive branch rightly called vascular ReRheology, which comprises diagnosing/treating arterial blocks. The technical wizardry of arterial reconstruction (bypass) or lumen--restoration (plasty) has to reckon with the TRAS principles all the time. PMID:10740714

  8. [ECG-gated bypass CT angiography--application in imaging arterial bypasses].

    PubMed

    Wintersperger, B J; Bastarrika, G; Nikolaou, K; Rist, C; Huber, A; Knez, A; Reiser, M F; Becker, C R; Vicol, C

    2004-02-01

    Nowadays coronary artery bypass grafting is increasingly performed using arterial grafts. Purpose of the study was the evaluation of a appropriate 16 detector-row CT angiography protocol in patients after predominantly arterial bypass grafting. Fourteen patients after bypass grafting were including into the study and CT angiography carried out in the early postoperative period using a 16 detector-row CT system. To reduce cardiac pulsation artifacts data acquisition was implemented using ECG-gating algorithms. Overall 43 grafts (37 arterial, 6 venous) were examined. In 13 patients surgery had been performed using composite grafts with T or TY configuration. The mean heart rate was 74.1 bpm and showed a negative correlation to the image quality (r=-0.65; p=0.01). However, all data sets were diagnostic. Contrast injection protocol allowed for a homogeneous opacification throughout the vessels of interest. All non-delineationable grafts (5) showed a close proximity to the heart (T or Y grafts). Cardiac surgery is increasingly focusing on arterial revascularisation in bypass grafting and therefore leading to new demands for non-invasive bypass graft imaging. 16 detector-row CT allows a reliable visualization of even composite arterial grafts. However, for detection of grafts in the proximity of the heart a reduction of the heart rate (<65-70) still seems to be necessary. PMID:14991132

  9. [Prophylactic antibiotics in plastic surgery].

    PubMed

    Sabovcík, R; Kyslan, K

    2006-06-01

    There is no consensus on the use of prophylactic antibiotics in plastic surgery to prevent postoperative infection. This study was performed to investigate whether the use of prophylactic antibiotics has an effect on postoperative infection rate. A total of 500 patients were classified into 3 groups based on their diagnosis. Approximately half of the cases received amoxicilin/clavulanate combination the other half had no antibiotics. Wound infection was observed in the post operative period. According to our clinical findings, antibiotic prophylaxis is not necessary in plastic surgery in all patients. We did not find significant difference between the antibiotic prophylaxis and placebo group.

  10. [Robot-assisted Coronary Artery Bypass Grafting].

    PubMed

    Ishikawa, Norihiko; Watanabe, Go

    2016-07-01

    The application for robot-assisted coronary surgery ranges from internal thoracic artery (ITA) harvesting with hand-sewn anastomoses to totally endoscopic coronary artery bypass grafting (TECAB), either on- or off-pump. The bilateral IMA can be harvested with the aid of a surgical robot and then multivessel bypass grafting can follow. Such robot-assisted minimally invasive direct coronary artery bypass grafting is called "ThoraCAB". Surgical robots cannot only endoscopically harvest the ITA but they can also anastomose the coronary artery in TECAB. But TECAB still has the difficulties, such as narrow surgical field in Japanese patients. Both procedures have the significant advantages of minimizing surgical trauma, such as reduced comlications, faster return back to normal activities and being improved cosmesis, and which have resulted in the development of minimally invasive surgery. Robot-assisted cardiac surgery for structural heart disease has been approved by the Ministry of Health, Labour and Welfare (MHLW) since December 2015, however, robot-assisted cardiac surgery for TECAB has not been approved yet in Japan. PMID:27440015

  11. Reviving old antibiotics.

    PubMed

    Theuretzbacher, Ursula; Van Bambeke, Françoise; Cantón, Rafael; Giske, Christian G; Mouton, Johan W; Nation, Roger L; Paul, Mical; Turnidge, John D; Kahlmeter, Gunnar

    2015-08-01

    In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections.

  12. When antibiotics are unnecessary.

    PubMed

    Hirschmann, J V

    2009-01-01

    Dermatologists can decrease unnecessary use of antimicrobial agents by avoiding them in situations wherein good evidence indicates that they are ineffective. Controlled trials indicate that antimicrobial agents are unhelpful in treating cutaneous abscesses, inflamed epidermal cysts, uninfected atopic eczema, and cutaneous ulcers caused by venous insufficiency or diabetes in the absence of significant contiguous soft-tissue inflammation. Prophylactic antibiotics are rarely appropriate for routine dermatologic surgery and are not indicated for patients who have prosthetic joints or vascular grafts. They are recommended only for a small group of patients who have abnormal cardiac valves, and then only with surgery involving clearly infected skin or soft-tissue. Topical antibiotics are no better than white petrolatum in covering sutured wounds, and with moist occlusive dressings, no ointment is necessary. PMID:18984370

  13. Bacterial gasotransmitters: an innate defense against antibiotics.

    PubMed

    Luhachack, Lyly; Nudler, Evgeny

    2014-10-01

    In recent decades, there has been growing interest in the field of gasotransmitters, endogenous gaseous signaling molecules (NO, H2S, and CO), as regulators of a multitude of biochemical pathways and physiological processes. Most of the concerted effort has been on eukaryotic gasotransmitters until the subsequent discovery of bacterial counterparts. While the fundamental aspects of bacterial gasotransmitters remain undefined and necessitate further research, we will discuss a known specific role they play in defense against antibiotics. Considering the current dilemma of multidrug-resistant bacteria we consider it particularly prudent to exploring novel targets and approaches, of which the bacterial gasotransmitters, nitric oxide and hydrogen sulfide represent.

  14. Understanding and manipulating antibiotic production in actinomycetes.

    PubMed

    Bibb, Mervyn J

    2013-12-01

    Actinomycetes are prolific producers of natural products with a wide range of biological activities. Many of the compounds that they make (and derivatives thereof) are used extensively in medicine, most notably as clinically important antibiotics, and in agriculture. Moreover, these organisms remain a source of novel and potentially useful molecules, but maximizing their biosynthetic potential requires a better understanding of natural product biosynthesis. Recent developments in genome sequencing have greatly facilitated the identification of natural product biosynthetic gene clusters. In the present article, I summarize the recent contributions of our laboratory in applying genomic technologies to better understand and manipulate natural product biosynthesis in a range of different actinomycetes.

  15. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  16. Pneumococcal resistance to antibiotics.

    PubMed Central

    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 pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  17. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  18. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass... cardiopulmonary bypass circuit during bypass surgery. (b) Classification. Class II (performance standards)....

  19. Antibiotic resistance: an ecological imbalance.

    PubMed

    Levy, S B

    1997-01-01

    Antibiotic resistance thwarts the treatment of infectious diseases worldwide. Although a number of factors can be identified which contribute to the problem, clearly the antibiotic as a selective agent and the resistance gene as the vehicle of resistance are the two most important, making up a 'drug resistance equation'. Both are needed in order for a clinical problem to arise. Given sufficient time and quantity of antibiotic, drug resistance will eventually appear. But a public health problem is not inevitable if the two components of the drug resistance equation are kept in check. Enhancing the emergence of resistance is the case by which resistance determinants and resistant bacteria can spread locally and globally, selected by widespread use of the same antibiotics in people, animal husbandry and agriculture. Antibiotics are societal drugs. Each individual use contributes to the sum total of society's antibiotic exposure. In a broader sense, the resistance problem is ecological. In the framework of natural competition between susceptible and resistant bacteria, antibiotic use has encouraged growth of the resistant strains, leading to an imbalance in prior relationships between susceptible and resistant bacteria. To restore efficacy to earlier antibiotics and to maintain the success of new antibiotics that are introduced, we need to use antibiotics in a way which assures an ecological balance that favours the predominance of susceptible bacterial flora.

  20. Colistin: Revival of an Old Polymyxin Antibiotic.

    PubMed

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

    2015-08-01

    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 simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.

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

    PubMed

    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

  2. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  3. Heat exchanger bypass system for an absorption refrigeration system

    DOEpatents

    Reimann, Robert C.

    1984-01-01

    A heat exchanger bypass system for an absorption refrigeration system is disclosed. The bypass system operates to pass strong solution from the generator around the heat exchanger to the absorber of the absorption refrigeration system when strong solution builds up in the generator above a selected level indicative of solidification of strong solution in the heat exchanger or other such blockage. The bypass system includes a bypass line with a gooseneck located in the generator for controlling flow of strong solution into the bypass line and for preventing refrigerant vapor in the generator from entering the bypass line during normal operation of the refrigeration system. Also, the bypass line includes a trap section filled with liquid for providing a barrier to maintain the normal pressure difference between the generator and the absorber even when the gooseneck of the bypass line is exposed to refrigerant vapor in the generator. Strong solution, which may accumulate in the trap section of the bypass line, is diluted, to prevent solidification, by supplying weak solution to the trap section from a purge system for the absorption refrigeration system.

  4. Endovascular exclusion of aortoesophageal fistula after coarctation extraanatomical bypass.

    PubMed

    Myers, Patrick O; Gemayel, Gino; Mugnai, Damiano; Murith, Nicolas; Kalangos, Afksendiyos

    2014-07-01

    Extraanatomical bypass has been advocated as the primary technique in adolescents or adults presenting with aortic coarctation. This approach carries significant morbidity, and graft-related complications may be more important in the young patient population. A 52-year-old man who had previously undergone extraanatomical bypass of aortic coarctation was diagnosed with a distal anastomotic pseudoaneurysm and aortoesophageal fistula. This was managed by proximal bypass plugging with an occluder, endovascular exclusion with a stent-graft in the thoracic descending aorta covering the pseudoaneurysm, and coarctation balloon dilation. Aortoesophageal fistula is a late complication observed after extraanatomical bypass for coarctation. This case illustrates this rare complication.

  5. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4230 Cardiopulmonary... with an oxygenator during cardiopulmonary bypass surgery to remove gas bubbles from the blood....

  6. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4420... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  7. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4230 Cardiopulmonary... with an oxygenator during cardiopulmonary bypass surgery to remove gas bubbles from the blood....

  8. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4230 Cardiopulmonary... with an oxygenator during cardiopulmonary bypass surgery to remove gas bubbles from the blood....

  9. Antibiotic resistance in pediatric urology

    PubMed Central

    Copp, Hillary L.

    2014-01-01

    Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

  10. Walking molecules.

    PubMed

    von Delius, Max; Leigh, David A

    2011-07-01

    Movement is intrinsic to life. Biologists have established that most forms of directed nanoscopic, microscopic and, ultimately, macroscopic movements are powered by molecular motors from the dynein, myosin and kinesin superfamilies. These motor proteins literally walk, step by step, along polymeric filaments, carrying out essential tasks such as organelle transport. In the last few years biological molecular walkers have inspired the development of artificial systems that mimic aspects of their dynamics. Several DNA-based molecular walkers have been synthesised and shown to walk directionally along a track upon sequential addition of appropriate chemical fuels. In other studies, autonomous operation--i.e. DNA-walker migration that continues as long as a complex DNA fuel is present--has been demonstrated and sophisticated tasks performed, such as moving gold nanoparticles from place-to-place and assistance in sequential chemical synthesis. Small-molecule systems, an order of magnitude smaller in each dimension and 1000× smaller in molecular weight than biological motor proteins or the walker systems constructed from DNA, have also been designed and operated such that molecular fragments can be progressively transported directionally along short molecular tracks. The small-molecule systems can be powered by light or chemical fuels. In this critical review the biological motor proteins from the kinesin, myosin and dynein families are analysed as systems from which the designers of synthetic systems can learn, ratchet concepts for transporting Brownian substrates are discussed as the mechanisms by which molecular motors need to operate, and the progress made with synthetic DNA and small-molecule walker systems reviewed (142 references). PMID:21416072

  11. Antibiotics as intermicrobial signaling agents instead of weapons

    PubMed Central

    Linares, J. F.; Gustafsson, I.; Baquero, F.; Martinez, J. L.

    2006-01-01

    It has been widely assumed that the ecological function of antibiotics in nature is fighting against competitors. This made them a good example of the Darwinian struggle-for-life in the microbial world. Based on this idea, it also has been believed that antibiotics, even at subinhibitory concentrations, reduce virulence of bacterial pathogens. Herein, using a combination of genomic and functional assays, we demonstrate that specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunistic bacterial pathogen Pseudomonas aeruginosa. All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of P. aeruginosa type III secretion system and consequently bacterial cytotoxicity. Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial species in natural, nonclinical environments, either by favoring colonization of surfaces (biofilm, motility) or for fighting against eukaryotic predators (cytotoxicity). Our results support the notion that antibiotics are not only bacterial weapons for fighting competitors but also signaling molecules that may regulate the homeostasis of microbial communities. At low concentrations, they can even be beneficial for the behavior of susceptible bacteria in natural environments. This is a complete change on our vision on the ecological function of antibiotics with clear implications both for the treatment of infectious diseases and for the understanding of the microbial relationships in the biosphere. PMID:17148599

  12. Antibiotics from predatory bacteria

    PubMed Central

    Korp, Juliane; Vela Gurovic, María S

    2016-01-01

    Summary Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism. PMID:27340451

  13. Antibiotics from predatory bacteria.

    PubMed

    Korp, Juliane; Vela Gurovic, María S; Nett, Markus

    2016-01-01

    Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism. PMID:27340451

  14. Treating appendicitis with antibiotics.

    PubMed

    Brook, Itzhak

    2016-03-01

    A nonsurgical approach using antimicrobial agents has been advocated as the initial treatment of uncomplicated appendicitis. Several studies and meta-analyses explored this approach. Because many of these studies included individuals with resolving appendicitis, their results were biased. Antimicrobials, however, are warranted and needed for the management of surgical high-risk patients with perforated appendicitis and those with localized abscess or phlegmon. Randomized placebo-controlled trials that focus on early identification of complicated acute appendicitis patients needing surgery and that prospectively evaluate the optimal use of antibiotic treatment in patients with uncomplicated acute appendicitis are warranted.

  15. A β-Lactamase-Imprinted Responsive Hydrogel for the Treatment of Antibiotic-Resistant Bacteria.

    PubMed

    Li, Wen; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

    2016-07-01

    Antibiotics play important roles in infection treatment and prevention. However, the effectiveness of antibiotics is now threatened by the prevalence of drug-resistant bacteria. Furthermore, antibiotic abuse and residues in the environment cause serious health issues. In this study, a stimuli-responsive imprinted hydrogel was fabricated by using β-lactamase produced by bacteria for deactivating antibiotics as the template molecule. The imprinted hydrogel could initially trap β-lactamase excreted by drug-resistant bacteria, thus making bacteria sensitive to antibiotics. After the bactericidal treatment, the "imprinted sites" on the hydrogel could be reversibly abolished with a temperature stimulus, which resulted in the reactivation of β-lactamase to degrade antibiotic residues. We also present an example of the use of this antibacterial design to treat wound infection. PMID:27159893

  16. Preoperative graft assessment in aortocoronary bypass surgery

    PubMed Central

    Tinica, Grigore; Vartic, Cristina Luca; Mocanu, Veronica; Baran, Dana; Butcovan, Doina

    2016-01-01

    Coronary artery bypass graft (CABG) is a surgical procedure able to improve the blood supply to the myocardium. In the present study, the distal segments of grafts taken from the internal thoracic artery (ITA), radial artery (RA) and saphenous vein (SV) for use in aortocoronary bypass surgery were examined. The morphologies of the grafts were investigated in order to draw conclusions concerning their patency and viability. In addition, clinical and laboratory risk factors considered to be significant predictors of lesion severity in graft vessels used in CABGs were investigated. In total, 54 distal graft segments of ITAs, RAs and SVs from 20 men and 6 women aged between 42 and 78 years, were evaluated. Histological analyses were used to visualize graft lesions. Morphometrically, the intimal thickness index (ITI) and luminal narrowing were assessed as an indication of graft patency. The histological changes observed in the graft vessel walls included the presence of distinct atheromatous plaques (fatty streaks in 2 cases) or thickening of the intima (20 cases) and media (17 cases). Morphometric analysis showed that the mean ITI of the vessel conduits was 0.37 in the SVs, 0.95 in the RAs, and 1.66 in the ITAs. No patient had >50% conduit stenosis. By assessing the association between risk factors and graft lesions, it was found that all the patients showed risk factors for atherosclerosis, such as age (61.54%), arterial hypertension (65.38%), hyperlipidemia (65.38%), smoking (34.61%), diabetes mellitus (38.46%) and obesity (15.38%). The presence of pre-existing lesions in bypass grafts may contribute to a reduction in their viability, particularly in the case of venous grafts. Further long-term follow-ups are mandatory to evaluate the consequences of such lesions upon the patency of the grafts. PMID:27446279

  17. A new antitumor antibiotic, kazusamycin.

    PubMed

    Umezawa, I; Komiyama, K; Oka, H; Okada, K; Tomisaka, S; Miyano, T; Takano, S

    1984-07-01

    A new antibiotic kazusamycin, was isolated from the culture broth of Streptomyces sp. No. 81-484, which shows antitumor activity against experimental murine tumors. This antibiotic did not possess antibacterial activity against Gram-positive and Gram-negative bacteria, but showed strong cytotoxic activity against HeLa cells in vitro. The chemical and physico-chemical properties of kazusamycin suggest that the molecular formula of this antibiotic is C33H48O7 (MW 556). PMID:6432763

  18. Prothracarcin, a novel antitumor antibiotic.

    PubMed

    Shimizu, K; Kawamoto, I; Tomita, F; Morimoto, M; Fujimoto, K

    1982-08-01

    A novel antibiotic, prothracarcin was isolated from the culture broth of Streptomyces umbrosus subsp. raffinophilus DO-62. The antibiotic has the molecular formula of C14H14N2O and belongs to the pyrrolo [1,4]benzodiazepine antibiotics. Its structure has been elucidated by mass and NMR spectra. It is active against Gram-positive and Gram-negative bacteria and experimental murine tumor sarcoma 180 and leukemia P388. PMID:7142014

  19. Bypass diode for a solar cell

    DOEpatents

    Rim, Seung Bum; Kim, Taeseok; Smith, David D; Cousins, Peter J

    2013-11-12

    Methods of fabricating bypass diodes for solar cells are described. In once embodiment, a method includes forming a first conductive region of a first conductivity type above a substrate of a solar cell. A second conductive region of a second conductivity type is formed on the first conductive region. In another embodiment, a method includes forming a first conductive region of a first conductivity type above a substrate of a solar cell. A second conductive region of a second conductivity type is formed within, and surrounded by, an uppermost portion of the first conductive region but is not formed in a lowermost portion of the first conductive region.

  20. Bypass and monitoring circuit for refrigeration system

    SciTech Connect

    Kyzer, G.; Smollon, J.

    1987-05-19

    A bypass and monitoring circuit is described for use with a refrigeration system having means to sense a need to initiate a defrost cycle and means to reset the defrost cycle upon sensing the defrosting of the refrigeration system. The circuit comprises: first means to sense whether the duration of each defrost cycle exceeds a certain period; and second means, responsive to the first means sensing that the duration of a given cycle exceeded the certain period, for electrically decoupling the reset means from the refrigeration system, for resetting the given defrost cycle and for enabling the occurrence of and controlling the duration of subsequent defrost cycle.

  1. Flow characteristics in narrowed coronary bypass graft

    NASA Astrophysics Data System (ADS)

    Bernad, S. I.; Bosioc, A.; Bernad, E. S.; Petre, I.; Totorean, A. F.

    2016-06-01

    Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

  2. Conduits for Coronary Bypass: Vein Grafts

    PubMed Central

    Farkas, Emily A

    2012-01-01

    The saphenous vein has been the principal conduit for coronary bypass grafting from the beginning, circa 1970. This report briefly traces this history and concomitantly presents one surgeons experience and personal views on use of the vein graft. As such it is not exhaustive but meant to be practical with a modest number of references. The focus is that of providing guidance and perspective which may be at variance with that of others and recognizing that there may be many ways to accomplish the task at hand. Hopefully the surgeon in training/early career may find this instructive on the journey to surgical maturity. PMID:23130300

  3. Conduits for coronary bypass: vein grafts.

    PubMed

    Barner, Hendrick B; Farkas, Emily A

    2012-10-01

    The saphenous vein has been the principal conduit for coronary bypass grafting from the beginning, circa 1970. This report briefly traces this history and concomitantly presents one surgeons experience and personal views on use of the vein graft. As such it is not exhaustive but meant to be practical with a modest number of references. The focus is that of providing guidance and perspective which may be at variance with that of others and recognizing that there may be many ways to accomplish the task at hand. Hopefully the surgeon in training/early career may find this instructive on the journey to surgical maturity. PMID:23130300

  4. Reservoirs of antibiotic resistance genes.

    PubMed

    Salyers, Abigail; Shoemaker, Nadja B

    2006-01-01

    A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating the risk of agricultural use of antibiotics are assessed critically. In addition, the potential benefits of applying new technology and using new insights from the field of microbial ecology are explained.

  5. Ionomycin, a new polyether antibiotic.

    PubMed

    Liu, W C; Slusarchyk, D S; Astle, G; Trejo, W H; Brown, W E; Meyers, E

    1978-09-01

    Ionomycin, a new polyether antibiotic with a high affinity for calcium ions, is obtained in pure form from fermentation broths of Streptomyces conglobatus sp. nov. Trejo by solvent extraction. It is unique amongst known polyether antibiotics in that it has a UV absorption maximum at 300 nm. thereby distinguishing it from other antibiotics of its class. The Ca salt has the molecular formula C41H70O9Ca. Ionomycin is a narrow spectrum antibiotic being active against Gram-positive bacteria. PMID:711623

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

    PubMed

    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.

  7. At 1050 Gallery, Block 65, view of coaster gate bypass ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    At 1050 Gallery, Block 65, view of coaster gate bypass valve (for turbine-generator unit G-10, this bypass-valve unit manufactured by Western Koppers Co., Fort Wayne, Ind., 1938), looking southeast. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  8. 21 CFR 870.4430 - Cardiopulmonary bypass intracardiac suction control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass intracardiac suction control. 870.4430 Section 870.4430 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....4430 Cardiopulmonary bypass intracardiac suction control. (a) Identification. A cardiopulmonary...

  9. 40 CFR 57.304 - Bypass, excess emissions and malfunctions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... construction had not commenced (as defined in 40 CFR 60.2 (g) and (i)) as of August 7, 1977 and which the... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Bypass, excess emissions and... Bypass, excess emissions and malfunctions. (a) Definition of excess emissions. For the purposes of...

  10. Reverse bias protected solar array with integrated bypass battery

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A (Inventor)

    2012-01-01

    A method for protecting the photovoltaic cells in a photovoltaic (PV) array from reverse bias damage by utilizing a rechargeable battery for bypassing current from a shaded photovoltaic cell or group of cells, avoiding the need for a bypass diode. Further, the method mitigates the voltage degradation of a PV array caused by shaded cells.

  11. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed...

  12. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed...

  13. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  14. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  15. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  16. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed...

  17. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed...

  18. Arterial ketone body ratio during and after cardiopulmonary bypass.

    PubMed

    Nomoto, S; Shimahara, Y; Kumada, K; Ogino, H; Okamoto, Y; Ban, T

    1992-06-01

    This study is the first to investigate the alteration in hepatic function during and after cardiopulmonary bypass in 30 patients by measuring the arterial ketone body ratio, an index of mitochondrial redox potential (oxidized nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide). Although the preoperative arterial ketone body ratio was within normal limits (1.24 +/- 0.63), it decreased markedly 5 minutes after the start of cardiopulmonary bypass to 0.35 +/- 0.12 and remained at this low level throughout bypass. After bypass it continued to rise in a time-dependent fashion, returning to its preoperative level by the morning of the second postoperative day in normal convalescent patients. However, the ratio recovered more slowly in patients who required prolonged circulatory or respiratory support than in other patients. Thus we suggest that cardiopulmonary bypass had deleterious effects on the hepatic mitochondrial redox potential, which may contribute to homeostatic derangements and metabolic abnormalities.

  19. Cardiopulmonary bypass: development of John Gibbon's heart-lung machine

    PubMed Central

    Passaroni, Andréia Cristina; Silva, Marcos Augusto de Moraes; Yoshida, Winston Bonetti

    2015-01-01

    Objective To provide a brief review of the development of cardiopulmonary bypass. Methods A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation. Results The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies. Conclusion Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function. PMID:26107456

  20. Focal brain atrophy in gastric bypass patients with cognitive complaints.

    PubMed

    Graff-Radford, Jonathan; Whitwell, Jennifer L; Trenerry, Max R; Ahlskog, J Eric; Jensen, Michael D; Jack, Clifford R; Josephs, Keith A

    2011-12-01

    Recently, we have identified a series of patients presenting with cognitive complaints after gastric bypass, without any identifiable etiology. We aimed to determine if focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass who had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to 10 age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass surgery at a median age of 54 (range: 46-64). Cognitive complaints developed at a median age of 57 (52-69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery may have focal thalamic brain atrophy that could result in cognitive impairment.

  1. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    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…

  2. Do we need new antibiotics?

    PubMed

    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

  3. Antibiotic use in livestock production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

  4. Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions.

    PubMed

    Chen, Jin; Coakley, Arthur; O'Connor, Michelle; Petrov, Alexey; O'Leary, Seán E; Atkins, John F; Puglisi, Joseph D

    2015-11-19

    Nearly half of the ribosomes translating a particular bacteriophage T4 mRNA bypass a region of 50 nt, resuming translation 3' of this gap. How this large-scale, specific hop occurs and what determines whether a ribosome bypasses remain unclear. We apply single-molecule fluorescence with zero-mode waveguides to track individual Escherichia coli ribosomes during translation of T4's gene 60 mRNA. Ribosomes that bypass are characterized by a 10- to 20-fold longer pause in a non-canonical rotated state at the take-off codon. During the pause, mRNA secondary structure rearrangements are coupled to ribosome forward movement, facilitated by nascent peptide interactions that disengage the ribosome anticodon-codon interactions for slippage. Close to the landing site, the ribosome then scans mRNA in search of optimal base-pairing interactions. Our results provide a mechanistic and conformational framework for bypassing, highlighting a non-canonical ribosomal state to allow for mRNA structure refolding to drive large-scale ribosome movements. PMID:26590426

  5. [Antibiotic resistance: A global crisis].

    PubMed

    Alós, Juan-Ignacio

    2015-12-01

    The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics.

  6. Antibiotics, microbiota, and immune defense.

    PubMed

    Ubeda, Carles; Pamer, Eric G

    2012-09-01

    The gastrointestinal tract microbiota contributes to the development and differentiation of the mammalian immune system. The composition of the microbiota affects immune responses and affects susceptibility to infection by intestinal pathogens and development of allergic and inflammatory bowel diseases. Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities and decreases host resistance to antibiotic-resistant microbes. Here, we review recent advances that begin to define the interactions between complex intestinal microbial populations and the mammalian immune system and how this relation is perturbed by antibiotic administration. We further discuss how antibiotic-induced disruption of the microbiota and immune homeostasis can lead to disease and we review strategies to restore immune defenses during antibiotic administration.

  7. The Prehistory of Antibiotic Resistance.

    PubMed

    Perry, Julie; Waglechner, Nicholas; Wright, Gerard

    2016-01-01

    Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. PMID:27252395

  8. Haemodynamic analysis of vessel remodelling in STA-MCA bypass for Moyamoya disease and its impact on bypass patency.

    PubMed

    Zhu, Feng-Ping; Zhang, Yu; Higurashi, Masakazu; Xu, Bin; Gu, Yu-Xiang; Mao, Ying; Morgan, Michael Kerin; Qian, Yi

    2014-06-01

    The purpose of this study is to estimate the remodelling characteristics of STA-MCA bypass and its influence on patency via the use of computational fluid dynamic (CFD) technology. The reconstructed three-dimensional geometries from MRA were segmented to create computational domains for CFD simulations. Eleven patients, who underwent regular MRA both immediately following surgery and at the six months follow-up, were studied. The flow velocities at STA were measured via the use of quantitative MRA (QMRA) to validate simulation results. STA-MCA bypass patency was confirmed for each patient immediately following surgery. The simulation indicated that the remodelling of the arterial pedicle in nine patients was associated with a reduction in the resistance to flow through the bypass. For these cases, the modelling of a driving pressure of 10mmHg through the bypass at 6 months post-surgery resulted in a 50% greater blood flow than those found immediately following surgery. However, two patients were found to exhibit contradictory patterns of remodelling, in which a highly curved bending at the bypass immediately post-surgery underwent progression, with increased resistance to flow through the bypass at 6 months follow-up, thereby resulting in a modelled flow rate reduction of 50% and 25%, respectively. This study revealed that STA-MCA bypass has a characteristic remodelling that usually reduces flow resistance. The initial morphology of the bypass may have had a significant effect on the outcome of vessel remodelling.

  9. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... Register on September 9, 2009 (74 FR 46453). This revised proposal would include measures for the... Bureau of Reclamation San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and Structural Improvements Project, Merced County, CA AGENCY: Bureau of...

  10. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics.

  11. Antibiotics and Bacterial Resistance in the 21st Century

    PubMed Central

    Fair, Richard J; Tor, Yitzhak

    2014-01-01

    Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed. PMID:25232278

  12. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics. PMID:26025191

  13. Approval and withdrawal of new antibiotics and other antiinfectives in the U.S., 1980-2009.

    PubMed

    Outterson, Kevin; Powers, John H; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Kesselheim, Aaron S

    2013-01-01

    Numerous reports have noted decreasing numbers of antibiotic approvals. To determine the context for this decline, we examined all new molecule entities (NMEs) and new biologic licenses (NBLs) approved by the FDA from 1980-2009, and compared approval rates of the 61 approved antibiotics to trends in other drug classes. We also tracked withdrawals of approved drugs and found more withdrawals for antibiotics than other drug classes. After adjusting for drugs subsequently withdrawn, the record for antibiotic innovation is less dire than previously reported. We also report problems with the quality of the approved antibiotics studied. Future policies providing incentives for new antibiotic development should not be based on simple numerical targets and key provisions should ensure appropriate quality as well as quantity of antibiotic drug innovation. PMID:24088160

  14. A survey on antibiotic therapy knowledge among physicians of a tertiary care and university hospital.

    PubMed

    Gentile, Ivan; Landolfo, Danilo; Buonomo, Antonio Riccardo; Crispo, Manuel; Iula, Vita Dora; Minei, Giuseppina; Catania, Maria Rosaria; Borgia, Guglielmo

    2015-03-01

    Antibiotic therapy has resulted in major progress in the fight against infectious diseases and is associated with an improved quality of life and increased survival. However, the emergence of resistant bacterial strains represents an inevitable consequence of antibiotic treatment and yields a loss of beneficial effects. Due to the scarce availability of new molecules in the near future, physicians have to learn how to best use currently available molecules. The aim of the present study was to evaluate the criteria that physicians use in choosing targeted antibiotic therapy. To achieve this goal, we used a questionnaire comprising seven questions. The questionnaire was administered, with the guarantee of anonymity, to a pool of physicians at the Federico II University Hospital of Naples who could prescribe antibiotics. Of the physicians interviewed, 68% chose antibiotic therapy autonomously or in cooperation with other doctors of the same structure, whereas 30% of interviewees referred to the infectious diseases consultant (8% after the first bacterial isolation and 22% after antibiotic therapy failure). The definition and meaning of minimum inhibitory concentration (MIC) were known to the vast majority of physicians (82% and 83%, respectively). In contrast, few of the interviewees knew the definition or meaning of breakpoint (16% and 17%, respectively). The key question of the questionnaire focused on the main criterion for antibiotic choice: 68% of interviewees gave an incorrect answer, most interviewees considering only the lowest MIC value for the isolated bacterium as the fundamental parameter in antibiotic choice. Our study shows that antibiotic therapy in a teaching hospital is often chosen using inappropriate criteria. Due to the well-known effects of the wrong antibiotic choice on therapeutic failure rate and on healthcare cost, information and training programmes for physicians who prescribe antibiotics are urgently needed.

  15. Curing bacteria of antibiotic resistance: reverse antibiotics, a novel class of antibiotics in nature.

    PubMed

    Hiramatsu, Keiichi; Igarashi, Masayuki; Morimoto, Yuh; Baba, Tadashi; Umekita, Maya; Akamatsu, Yuzuru

    2012-06-01

    By screening cultures of soil bacteria, we re-discovered an old antibiotic (nybomycin) as an antibiotic with a novel feature. Nybomycin is active against quinolone-resistant Staphylococcus aureus strains with mutated gyrA genes but not against those with intact gyrA genes against which quinolone antibiotics are effective. Nybomycin-resistant mutant strains were generated from a quinolone-resistant, nybomycin-susceptible, vancomycin-intermediate S. aureus (VISA) strain Mu 50. The mutants, occurring at an extremely low rate (<1 × 10(-11)/generation), were found to have their gyrA genes back-mutated and to have lost quinolone resistance. Here we describe nybomycin as the first member of a novel class of antibiotics designated 'reverse antibiotics'. PMID:22534508

  16. Factor V Leiden and Cardiopulmonary Bypass

    PubMed Central

    Uppal, Victor; Rosin, Mark; Marcoux, Jo-Anne; Olson, Marnie; Bezaire, Jennifer; Dalshaug, Gregory

    2015-01-01

    Abstract: We present a case of a patient with factor V Leiden with an antithrombin III activity of 67% who received a successful aortic valve replacement supported by cardiopulmonary bypass (CPB). A safe level of anticoagulation was achieved by monitoring activated clotting time (ACT) and heparin concentration ensuring adequate anticoagulation throughout the procedure. Results from ACT, heparin dose response, heparin protamine titration, and thrombelastography are given. Factor V Leiden patients can be safely anti-coagulated using heparin for CPB procedures when monitored with ACT, heparin protamine titration, and thrombelastography. Postoperative chest tube losses were 360 mL, less than half our institutional average. Anticoagulation for the pre-and post-operative phase is also discussed. PMID:26834284

  17. Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

    PubMed

    Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

    2015-04-01

    Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

  18. Decline in the frequencies of Borrelia burgdorferi OspA161 175-specific T cells after antibiotic therapy in HLA-DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory lyme arthritis.

    PubMed

    Kannian, Priya; Drouin, Elise E; Glickstein, Lisa; Kwok, William W; Nepom, Gerald T; Steere, Allen C

    2007-11-01

    Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated with T cell recognition of Borrelia burgdorferi outer surface protein A (OspA(161-175)) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA(161-175)-specific T cells in samples of PBMC and synovial fluid mononuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibiotic-refractory arthritis had frequencies of OspA(161-175)-specific CD4(+) T cells in peripheral blood above the cutoff value of 4 per 10(5) cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 10(5) cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA(161-175)-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA(161-175)-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells.

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

    PubMed

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I

    2013-01-01

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

    PubMed Central

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

    2013-01-01

    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. PMID:27029309

  1. CFD Analysis of Core Bypass Phenomena

    SciTech Connect

    Richard W. Johnson; Hiroyuki Sato; Richard R. Schultz

    2010-03-01

    The U.S. Department of Energy is exploring the potential for the VHTR which will be either of a prismatic or a pebble-bed type. One important design consideration for the reactor core of a prismatic VHTR is coolant bypass flow which occurs in the interstitial regions between fuel blocks. Such gaps are an inherent presence in the reactor core because of tolerances in manufacturing the blocks and the inexact nature of their installation. Furthermore, the geometry of the graphite blocks changes over the lifetime of the reactor because of thermal expansion and irradiation damage. The existence of the gaps induces a flow bias in the fuel blocks and results in unexpected increase of maximum fuel temperature. Traditionally, simplified methods such as flow network calculations employing experimental correlations are used to estimate flow and temperature distributions in the core design. However, the distribution of temperature in the fuel pins and graphite blocks as well as coolant outlet temperatures are strongly coupled with the local heat generation rate within fuel blocks which is not uniformly distributed in the core. Hence, it is crucial to establish mechanistic based methods which can be applied to the reactor core thermal hydraulic design and safety analysis. Computational Fluid Dynamics (CFD) codes, which have a capability of local physics based simulation, are widely used in various industrial fields. This study investigates core bypass flow phenomena with the assistance of commercial CFD codes and establishes a baseline for evaluation methods. A one-twelfth sector of the hexagonal block surface is modeled and extruded down to whole core length of 10.704m. The computational domain is divided vertically with an upper reflector, a fuel section and a lower reflector. Each side of the sector grid can be set as a symmetry boundary

  2. CFD Analysis of Core Bypass Phenomena

    SciTech Connect

    Richard W. Johnson; Hiroyuki Sato; Richard R. Schultz

    2009-11-01

    The U.S. Department of Energy is exploring the potential for the VHTR which will be either of a prismatic or a pebble-bed type. One important design consideration for the reactor core of a prismatic VHTR is coolant bypass flow which occurs in the interstitial regions between fuel blocks. Such gaps are an inherent presence in the reactor core because of tolerances in manufacturing the blocks and the inexact nature of their installation. Furthermore, the geometry of the graphite blocks changes over the lifetime of the reactor because of thermal expansion and irradiation damage. The existence of the gaps induces a flow bias in the fuel blocks and results in unexpected increase of maximum fuel temperature. Traditionally, simplified methods such as flow network calculations employing experimental correlations are used to estimate flow and temperature distributions in the core design. However, the distribution of temperature in the fuel pins and graphite blocks as well as coolant outlet temperatures are strongly coupled with the local heat generation rate within fuel blocks which is not uniformly distributed in the core. Hence, it is crucial to establish mechanistic based methods which can be applied to the reactor core thermal hydraulic design and safety analysis. Computational Fluid Dynamics (CFD) codes, which have a capability of local physics based simulation, are widely used in various industrial fields. This study investigates core bypass flow phenomena with the assistance of commercial CFD codes and establishes a baseline for evaluation methods. A one-twelfth sector of the hexagonal block surface is modeled and extruded down to whole core length of 10.704m. The computational domain is divided vertically with an upper reflector, a fuel section and a lower reflector. Each side of the one-twelfth grid can be set as a symmetry boundary

  3. Myocardial revascularization in 1997: angioplasty versus bypass surgery.

    PubMed

    Faxon, D P

    1997-10-01

    In patients with coronary artery disease and severe ischemia, angioplasty and coronary artery bypass surgery have been shown to reduce symptoms, improve functional capacity and, in some patients, prolong life. Six major randomized trials have recently been reported comparing bypass surgery with angioplasty in patients with multivessel coronary disease. Uniformly, these studies demonstrate an equal mortality and reinfarction rate over five years of follow-up. Patients with angioplasties needed a repeat procedure during follow-up far more frequently than patients with bypass needed an additional bypass procedure (30 to 40 percent versus 5 to 10 percent). Although angioplasty was initially less costly, over five years the costs for the two procedures were similar. Mortality rates decreased by twofold when patients with diabetes mellitus were treated with bypass surgery rather than angioplasty. These studies confirm that in nondiabetic patients, bypass surgery and angioplasty are equally effective in the treatment of severe coronary disease. In diabetic patients with severe disease, however, bypass surgery is favored.

  4. Alongshore sediment bypassing as a control on river mouth morphodynamics

    NASA Astrophysics Data System (ADS)

    Nienhuis, Jaap H.; Ashton, Andrew D.; Nardin, William; Fagherazzi, Sergio; Giosan, Liviu

    2016-04-01

    River mouths, shoreline locations where fluvial and coastal sediments are partitioned via erosion, trapping, and redistribution, are responsible for the ultimate sedimentary architecture of deltas and, because of their dynamic nature, also pose great management and engineering challenges. To investigate the interaction between fluvial and littoral processes at wave-dominated river mouths, we modeled their morphologic evolution using the coupled hydrodynamic and morphodynamic model Delft3D-SWAN. Model experiments replicate alongshore migration of river mouths, river mouth spit development, and eventual spit breaching, suggesting that these are emergent phenomena that can develop even under constant fluvial and wave conditions. Furthermore, we find that sediment bypassing of a river mouth develops though feedbacks between waves and river mouth morphology, resulting in either continuous bypassing pathways or episodic bar bypassing pathways. Model results demonstrate that waves refracting into the river mouth bar create a zone of low alongshore sediment transport updrift of the river mouth, which reduces sediment bypassing. Sediment bypassing, in turn, controls the river mouth migration rate and the size of the river mouth spit. As a result, an intermediate amount of river discharge maximizes river mouth migration. The fraction of alongshore sediment bypassing can be predicted from the balance between the jet and the wave momentum flux. Quantitative comparisons show a match between our modeled predictions of river mouth bypassing and migration rates observed in natural settings.

  5. Diagnostic tools for post-gastric bypass hypoglycaemia.

    PubMed

    Emous, M; Ubels, F L; van Beek, A P

    2015-10-01

    In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature.

  6. [When the antibiotic miracle turns into a nightmare].

    PubMed

    Trémolières, François

    2010-11-01

    Antibiotics have been a true miracle. Would it end in a nightmare? Possibly. Since 1941, the antibiotic treatment of bacterial infections has been a revolution. The golden age lasted half a century, a period during which infectious diseases were considered definitely defeated. And although from the beginning some kind of bacterial resistance was observed, a strong long-lasting belief was that continuous innovation and invention of new molecules would keep providing a step ahead in the war waged between the human and microbes. For twenty years the resistances became each year a greater concern. Having first hit the hospital, they now affect the community. New effective antibiotics are scarce, and innovation once thought endless, stopped. Today, to escape the nightmare of a return to the pre-antibiotic era, we must find a way to curb the spread of resistant bacteria, change radically our irresponsible squander of antibiotics, and give ways to new treatments effective against future resistant pathogens. These topics are developed in the present paper dealing with the real risk that these 20th century wonder of the medical science, become an object of memory. PMID:21106173

  7. Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors

    PubMed Central

    Cocozaki, Alexis I.; Altman, Roger B.; Huang, Jian; Buurman, Ed T.; Kazmirski, Steven L.; Doig, Peter; Prince, D. Bryan; Blanchard, Scott C.; Cate, Jamie H. D.; Ferguson, Andrew D.

    2016-01-01

    Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future. PMID:27382179

  8. Antibiotic resistance in wild birds

    PubMed Central

    Bonnedahl, Jonas

    2014-01-01

    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

  9. Systemic antibiotic therapy in periodontics

    PubMed Central

    Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak

    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, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy. PMID:23559912

  10. Antibiotic Treatment of Hidradenitis Suppurativa.

    PubMed

    Bettoli, Vincenzo; Join-Lambert, Olivier; Nassif, Aude

    2016-01-01

    Although hidradenitis suppurativa (HS) is not primarily an infectious disease, antibiotics are widely used to treat HS. Recent microbiological data show that HS suppurating lesions are associated with a polymorphous anaerobic flora, including actinomycetes and milleri group streptococci, and can therefore be considered as polymicrobial soft tissue and skin infections. Analysis of the literature provides little information on the efficacy of antibiotics in HS but suggests a beneficial effect of certain antimicrobial treatments, depending on the clinical severity of the disease. Patients must be informed and should agree with the treatment strategy before starting antibiotic treatments.

  11. Antibiotic resistance in wild birds.

    PubMed

    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

  12. Aortocarotid bypass for hemispheric hypoperfusion in a child.

    PubMed

    Sanai, Nader; Fullerton, Heather; Karl, Tom R; Lawton, Michael T

    2008-04-01

    Large-vessel vasculitis syndromes in the pediatric population are rare and highly morbid. The authors here report on the microsurgical revascularization of a unique case of presumed vasculitis with aortitis and severe obliterative arteriopathy in a 10-month-old child with symptomatic hemispheric hypoperfusion. Using a cryopreserved saphenous vein, this unilateral aortocarotid bypass restored normal intracranial perfusion bilaterally and led to a resolution of the patient's ischemic symptoms. The aortocarotid bypass is clinically effective and technically feasible in young children when a saphenous vein allograft is used. The bypass graft is amenable to angioplasty with or without stenting if delayed stenosis becomes an issue later in life.

  13. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line... entitled “Guidance for Cardiopulmonary Bypass Arterial Line Blood Filter 510(k) Submissions.”...

  14. β-Lactam Antibiotics Renaissance

    PubMed Central

    Qin, Wenling; Panunzio, Mauro; Biondi, Stefano

    2014-01-01

    Since the 1940s β-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of β-lactam resistance has reached the point where many marketed β-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel β-lactam antibiotics and β-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel β-lactam antibiotics and β-lactamase inhibitors. PMID:27025744

  15. Antibiotic resistance: An ethical challenge.

    PubMed

    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.

  16. Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication

    PubMed Central

    Fröhlich, Esther E.; Farzi, Aitak; Mayerhofer, Raphaela; Reichmann, Florian; Jačan, Angela; Wagner, Bernhard; Zinser, Erwin; Bordag, Natalie; Magnes, Christoph; Fröhlich, Eleonore; Kashofer, Karl; Gorkiewicz, Gregor; Holzer, Peter

    2016-01-01

    Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis. PMID:26923630

  17. Cyclic lipopeptides as antibacterial agents - potent antibiotic activity mediated by intriguing mode of actions.

    PubMed

    Schneider, Tanja; Müller, Anna; Miess, Henrike; Gross, Harald

    2014-01-01

    Cyclic lipopeptides (CLPs) are a promising class of natural products with antibiotic properties. CLPs are amphiphilic molecules, composed of a fatty acid tail linked to a short oligopeptide which form a macrocylic ring structure. This review presents an overview of this class of antibiotics, focusing on the current and potential therapeutic applications and placing particular emphasis on the molecular modes of action of these compounds.

  18. Prophylactic antibiotics in orthopaedic surgery.

    PubMed

    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.

  19. Expedient antibiotics production: Final report

    SciTech Connect

    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.

  20. 1. PLENUM INTERIOR, SHOWING HEATING COILS AND BYPASS Hot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PLENUM INTERIOR, SHOWING HEATING COILS AND BY-PASS - Hot Springs National Park, Bathhouse Row, Fordyce Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

  1. Bypass graft imaging and coronary anomalies in MDCT.

    PubMed

    Fernandez, Gabriel C

    2005-02-01

    Coronary artery bypass graft (CABG) is used to restore the blood flow in an ischemic area of myocardium using conduits bypassing a diseased coronary artery. Until now, conventional angiography has been the recognized technique to study patients with bypass grafts. Nowadays, non-invasive methods such as multi-detector CT (MDCT) emerge as reliable imaging methods in the study of CABG. Thus, radiologists play an important role in this field, not only to define if the bypass graft is occluded or stenosed but also to report further information such as CABG technique performed, type of conduit used or pre-operative findings. This paper analyzes the most practical information that the radiologist must know in a study of CABG. Another theme which will be briefly described is the use of MDCT in coronary anomalies studies, with particular emphasis on the course of the abnormal vessel and its relation to great vessels. PMID:15801059

  2. Oil Bypass Filter Technology Performance Evaluation - First Quarterly Report

    SciTech Connect

    Zirker, L.R.; Francfort, J.E.

    2003-01-31

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  3. 14. DRAGLINE BEGINNING CONSTRUCTION OF THE BYPASS CHANNEL CONNECTING THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. DRAGLINE BEGINNING CONSTRUCTION OF THE BY-PASS CHANNEL CONNECTING THE DIVERSION GATE ALONG THE OUTLET CHANNEL WITH THE ORIGINAL CHANNEL OF THE SOURIS RIVER - Upper Souris National Wildlife Refuge, Dam 83, Souris River Basin, Foxholm, Surrey (England), ND

  4. 21 CFR 870.4230 - Cardiopulmonary bypass defoamer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... with an oxygenator during cardiopulmonary bypass surgery to remove gas bubbles from the blood. (b) Classification. Class II (special controls). The special control for this device is the FDA guidance...

  5. Left Subclavian Artery Occlusion: Femoro-Axillary Artery Retrograde Bypass

    PubMed Central

    Nakashima, Masaya; Kobayashi, Hideaki; Kobayashi, Masayoshi

    2016-01-01

    The treatment tactics for subclavian artery occlusion include the more commonly used endovascular therapy rather than surgical intervention. We present a case of a 61-year-old woman with dialysis-dependent chronic renal failure who experienced left finger necrosis in the left upper extremity. To salvage the limb, we performed femoro-axillary (fem-ax) artery bypass using an autologous saphenous vein graft. However, 10 months later, she experienced coldness in the left forearm. Angiography revealed chronic total occlusion of the venous bypass. Despite emergent thrombectomy, redo fem-ax artery bypass operation was performed using a prosthetic graft. Upper limb salvage can be achieved by fem-ax artery retrograde bypass. PMID:27386454

  6. Oil Bypass Filter Technology Performance Evaluation - January 2003 Quarterly Report

    SciTech Connect

    Laurence R. Zirker; James E. Francfort

    2003-01-01

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  7. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4310... gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  8. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4310... gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  9. A Large Refilling Cystic Lesion In A Gastric Bypass Patient

    PubMed Central

    Tewari, Deepali; Antunez, Daylem; Iqbal, Shahzad; Williams, Susan

    2015-01-01

    We describe a patient with a history of gastric bypass and chronic alcoholism suffering from a rare Peterson's hernia resulting from her surgery. There are a few case reports in which afferent loop obstruction was misdiagnosed as pancreatic pseudocyst after Billroth II gastrectomy. Ours is the first in which Peterson's hernia was initially misdiagnosed as a pancreatic pseudocyst in a gastric bypass patient. PMID:26203456

  10. Electrical failure during cardiopulmonary bypass: a critical moment.

    PubMed

    Durukan, Ahmet Baris; Gurbuz, Hasan Alper; Ozcelik, Gokhan; Yorgancioglu, Cem

    2016-06-01

    Electrical failure during cardiopulmonary bypass is a crisis situation for the cardiac surgical team. Fortunately, it has a low incidence with low morbidity and mortality rates. Notwithstanding, institutional preventative and management measures should be taken. Here, we report a case of electrical failure during cardiopulmonary bypass, which was successfully managed during the surgery, allowing the patient to recover uneventfully. These unwanted complications can only be managed by promoting awareness and putting in place strategies against them. PMID:27516788

  11. Electrical failure during cardiopulmonary bypass: a critical moment

    PubMed Central

    Gurbuz, Hasan Alper; Ozcelik, Gokhan; Yorgancioglu, Cem

    2016-01-01

    Electrical failure during cardiopulmonary bypass is a crisis situation for the cardiac surgical team. Fortunately, it has a low incidence with low morbidity and mortality rates. Notwithstanding, institutional preventative and management measures should be taken. Here, we report a case of electrical failure during cardiopulmonary bypass, which was successfully managed during the surgery, allowing the patient to recover uneventfully. These unwanted complications can only be managed by promoting awareness and putting in place strategies against them. PMID:27516788

  12. Carburetor by-pass and fuel control system

    SciTech Connect

    Deboynton, W.L.

    1983-01-04

    A fuel-saving and emission reduction system for internal combustion engines includes electronic carburetor controlling circuitry and a carburetor by-pass system which stops fuel flow to the engine when power from combustion is not required. A normally open by-pass control butterfly valve in the fuel/air passage between the throttle valve and the engine intake manifold is operated by a motor, such as a solenoid or the like, under control of the controlling circuitry and is closed only upon release of the engine throttle and during the period that the vehicle has sufficient speed to assure restart upon reapplication of the fuel/air flow. A carburetor by-pass valve is held in a normally closed position by the combined effects of spring bias and the normal vacuum in the fuel/air passage. When the normally open by-pass control butterfly is closed, the fuel/air vacuum is reduced to permit the spring biased normally closed selfregulating carburetor by-pass valve to admit filtered air at a predetermined reduced vacuum to the engine manifold for continued operation of vacuum accessories and also for reducing the amount of oil drawn past combustion chamber seals and valve guides. Associated with the carburetor by-pass valve is a carburetor vent valve which is simultaneously opened to admit filtered air to the fuel/air passage between the throttle valve and the by-pass control butterfly to thereby eliminate all vacuum that will draw fuel from the carburetor. As a further feature, the electronic controlling circuitry operates to close the by-pass control butterfly for about one-half second upon the opening of the ignition switch to thereby eliminate self-ignition or dieseling and reduced hydrocarbon emissions.

  13. Derivatization of Aminoglycoside Antibiotics with Tris(2,6-dimethoxyphenyl)carbenium Ion

    PubMed Central

    Topolyan, A.P.; Belyaeva, M.A.; Bykov, E.E.; Coodan, P.V.; Rogozhin, E.A.; Strizhevskaya, D.A.; Ivanova, O.M.; Ustinov, A.V.; Mikhura, I.V.; Prokhorenko, I.A.; Korshun, V.A.; Formanovsky, A.A.

    2016-01-01

    Detection of aminoglycoside antibiotics by MS or HPLC is complicated, because a) carbohydrate molecules have low ionization ability in comparison with other organic molecules (particularly in MALDI-MS), and b) the lack of aromatics and/or amide bonds in the molecules makes common HPLC UV-detectors useless. Here, we report on the application of a previously developed method for amine derivatization with tris(2,6- dimethoxyphenyl)carbenium ion to selective modification of aminoglycoside antibiotics. Only amino groups bound to primary carbons get modified. The attached aromatic residue carries a permanent positive charge. This makes it easy to detect aminoglycoside antibiotics by MS-methods and HPLC, both as individual compounds and in mixtures. PMID:27795853

  14. Bypass flow computations on the LOFA transient in a VHTR

    SciTech Connect

    Tung, Yu-Hsin; Johnson, Richard W.; Ferng, Yuh-Ming; Chieng, Ching-Chang

    2014-01-01

    Bypass flow in the prismatic gas-cooled very high temperature reactor (VHTR) is not intentionally designed to occur, but is present in the gaps between graphite blocks. Previous studies of the bypass flow in the core indicated that the cooling provided by flow in the bypass gaps had a significant effect on temperature and flow distributions for normal operating conditions. However, the flow and heat transports in the core are changed significantly after a Loss of Flow Accident (LOFA). This study aims to study the effect and role of the bypass flow after a LOFA in terms of the temperature and flow distributions and for the heat transport out of the core by natural convection of the coolant for a 1/12 symmetric section of the active core which is composed of images and mirror images of two sub-region models. The two sub-region models, 9 x 1/12 and 15 x 1/12 symmetric sectors of the active core, are employed as the CFD flow models using computational grid systems of 70.2 million and 117 million nodes, respectively. It is concluded that the effect of bypass flow is significant for the initial conditions and the beginning of LOFA, but the bypass flow has little effect after a long period of time in the transient computation of natural circulation.

  15. Progress on Complications of Direct Bypass for Moyamoya Disease.

    PubMed

    Yu, Jinlu; Shi, Lei; Guo, Yunbao; Xu, Baofeng; Xu, Kan

    2016-01-01

    Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD.

  16. Progress on Complications of Direct Bypass for Moyamoya Disease.

    PubMed

    Yu, Jinlu; Shi, Lei; Guo, Yunbao; Xu, Baofeng; Xu, Kan

    2016-01-01

    Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD. PMID:27499690

  17. Progress on Complications of Direct Bypass for Moyamoya Disease

    PubMed Central

    Yu, Jinlu; Shi, Lei; Guo, Yunbao; Xu, Baofeng; Xu, Kan

    2016-01-01

    Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD. PMID:27499690

  18. The determinants of the antibiotic resistance process

    PubMed Central

    Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

    2009-01-01

    Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

  19. [Coronary revascularization by arterial bypasses: advantages, disadvantages].

    PubMed

    Bical, O; Deleuze, P; Sousa Uva, M

    1997-01-01

    Coronary vein grafts are frequently become occluded or develop atherosclerotic lesions in the long-term. In contrast, the internal mammary artery has a very satisfactory long-term patency rate. The use of an internal mammary artery on the LAD consequently increases the benefit of coronary surgery. The benefit of using 2 internal mammary arteries or other arterial grafts for coronary artery bypass surgery is more controversial. The advantages and disadvantages of the various coronary artery grafts are reported together with the clinical experience of several teams in this area. Coronary artery surgery should be reserved to patients with a good general condition, who are likely to benefit from this type of revascularization. The right internal mammary artery is unsuitable for revascularization of the right coronary network and the two internal mammary arteries must be used to revascularize the left coronary network, in order to obtain a good result. However, surgeons must be aware of the limitations of coronary artery surgery and these techniques should be used cautiously.

  20. Ultra-High Bypass Ratio Jet Noise

    NASA Technical Reports Server (NTRS)

    Low, John K. C.

    1994-01-01

    The jet noise from a 1/15 scale model of a Pratt and Whitney Advanced Ducted Propulsor (ADP) was measured in the United Technology Research Center anechoic research tunnel (ART) under a range of operating conditions. Conditions were chosen to match engine operating conditions. Data were obtained at static conditions and at wind tunnel Mach numbers of 0.2, 0.27, and 0.35 to simulate inflight effects on jet noise. Due to a temperature dependence of the secondary nozzle area, the model nozzle secondary to primary area ratio varied from 7.12 at 100 percent thrust to 7.39 at 30 percent thrust. The bypass ratio varied from 10.2 to 11.8 respectively. Comparison of the data with predictions using the current Society of Automotive Engineers (SAE) Jet Noise Prediction Method showed that the current prediction method overpredicted the ADP jet noise by 6 decibels. The data suggest that a simple method of subtracting 6 decibels from the SAE Coaxial Jet Noise Prediction for the merged and secondary flow source components would result in good agreement between predicted and measured levels. The simulated jet noise flight effects with wind tunnel Mach numbers up to 0.35 produced jet noise inflight noise reductions up to 12 decibels. The reductions in jet noise levels were across the entire jet noise spectra, suggesting that the inflight effects affected all source noise components.

  1. Conduits for Coronary Bypass: Internal Thoracic Artery

    PubMed Central

    2012-01-01

    This second report in the series on coronary artery bypass presents the authors experience and personal views on the internal thoracic artery (ITA) which date to 1966. There has been a very gradual evolution in the acceptance of this conduit which was initially compared with the saphenous vein and viewed as an improbable alternative to it. As is common with concepts and techniques which are 'outside the box' there was skepticism and criticism of this new conduit which was more difficult and time consuming to harvest for the surgeon who had to do it all. It was viewed as small, fragile, spastic and its flow capacity was questioned. Only a few surgeons employed it because of these issues and some of them would frequently graft it to the diagonal artery as it was thought not to supply adequate flow for the left anterior descending unless it was small. After a decade, angiographic data revealed superior patency to vein grafts. Even this evidence and survival benefit reported a few years later did not convince many surgeons that their concerns about limitations justified its use. Thus widespread adaption of the ITA as the conduit of choice for the anterior descending required another decade and bilateral use is only now expanding to more than 5% of patients in the US and somewhat faster in other countries. PMID:23275918

  2. Ultra-high bypass ratio jet noise

    NASA Astrophysics Data System (ADS)

    Low, John K. C.

    1994-10-01

    The jet noise from a 1/15 scale model of a Pratt and Whitney Advanced Ducted Propulsor (ADP) was measured in the United Technology Research Center anechoic research tunnel (ART) under a range of operating conditions. Conditions were chosen to match engine operating conditions. Data were obtained at static conditions and at wind tunnel Mach numbers of 0.2, 0.27, and 0.35 to simulate inflight effects on jet noise. Due to a temperature dependence of the secondary nozzle area, the model nozzle secondary to primary area ratio varied from 7.12 at 100 percent thrust to 7.39 at 30 percent thrust. The bypass ratio varied from 10.2 to 11.8 respectively. Comparison of the data with predictions using the current Society of Automotive Engineers (SAE) Jet Noise Prediction Method showed that the current prediction method overpredicted the ADP jet noise by 6 decibels. The data suggest that a simple method of subtracting 6 decibels from the SAE Coaxial Jet Noise Prediction for the merged and secondary flow source components would result in good agreement between predicted and measured levels. The simulated jet noise flight effects with wind tunnel Mach numbers up to 0.35 produced jet noise inflight noise reductions up to 12 decibels. The reductions in jet noise levels were across the entire jet noise spectra, suggesting that the inflight effects affected all source noise components.

  3. Post-gastric bypass hypoglycaemia: a review.

    PubMed

    Shantavasinkul, Prapimporn C; Torquati, Alfonso; Corsino, Leonor

    2016-07-01

    Bariatric surgery is a highly effective treatment for severe obesity, resulting in substantial weight loss and normalizing obesity-related comorbidities. However, long-term consequences can occur, such as postbariatric surgery hypoglycaemia. This is a challenging medical problem, and the number of patients presenting with it has been increasing. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it is the surgery most commonly associated with the development of postbariatric surgery hypoglycaemia. To date, the pathogenesis of this condition has not been completely established. However, various factors - particularly increased postprandial glucagon-like peptide (GLP)-1 secretion - have been considered as crucial mediator. The mechanisms responsible for diabetic remission after bariatric surgery may be responsible for the development of hypoglycaemia, which typically occurs 1-3 h after a meal and is concurrent with inappropriate hyperinsulinaemia. Carbohydrate-rich foods usually provoke hypoglycaemic symptoms, which can typically be alleviated by strict dietary modifications, including carbohydrate restriction and avoidance of high glycaemic index foods and simple sugars. Few patients require further medical intervention, such as medications, but some patients have required a pancreatectomy. Because this option is not always successful, it is no longer routinely recommended. Clinical trials are needed to further determine the pathophysiology of this condition as well as the best diagnostic and treatment approaches for these patients.

  4. Current status of mini-gastric bypass

    PubMed Central

    Mahawar, Kamal K.; Kumar, Parveen; Carr, William RJ; Jennings, Neil; Schroeder, Norbert; Balupuri, Shlok; Small, Peter K.

    2016-01-01

    Mini-gastric bypass (MGP) is a promising bariatric procedure. Tens of thousands of this procedure have been performed throughout the world since Rutledge performed the first procedure in the United States of America in 1997. Several thousands of these have even been documented in the published scientific literature. Despite a proven track record over nearly two decades, this operation continues to polarise the bariatric community. A large number of surgeons across the world have strong objections to this procedure and do not perform it. The risk of symptomatic (bile) reflux, marginal ulceration, severe malnutrition, and long-term risk of gastric and oesophageal cancers are some of the commonly voiced concerns. Despite these expressed fears, several advantages such as technical simplicity, shorter learning curve, ease of revision and reversal, non-inferior weight loss and comorbidity resolution outcomes have prompted some surgeons to advocate a wider adoption of this procedure. This review examines the current status of these controversial aspects in the light of the published academic literature in English. PMID:27251826

  5. The use of platensimycin and platencin to fight antibiotic resistance

    PubMed Central

    Allahverdiyev, Adil M; Bagirova, Melahat; Abamor, Emrah Sefik; Ates, Sezen Canim; Koc, Rabia Cakir; Miraloglu, Meral; Elcicek, Serhat; Yaman, Serkan; Unal, Gokce

    2013-01-01

    Infectious diseases are known as one of the most life-threatening disabilities worldwide. Approximately 13 million deaths related to infectious diseases are reported each year. The only way to combat infectious diseases is by chemotherapy using antimicrobial agents and antibiotics. However, due to uncontrolled and unnecessary use of antibiotics in particular, surviving bacteria have evolved resistance against several antibiotics. Emergence of multidrug resistance in bacteria over the past several decades has resulted in one of the most important clinical health problems in modern medicine. For instance, approximately 440,000 new cases of multidrug-resistant tuberculosis are reported every year leading to the deaths of 150,000 people worldwide. Management of multidrug resistance requires understanding its molecular basis and the evolution and dissemination of resistance; development of new antibiotic compounds in place of traditional antibiotics; and innovative strategies for extending the life of antibiotic molecules. Researchers have begun to develop new antimicrobials for overcoming this important problem. Recently, platensimycin – isolated from extracts of Streptomyces platensis – and its analog platencin have been defined as promising agents for fighting multidrug resistance. In vitro and in vivo studies have shown that these new antimicrobials have great potential to inhibit methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in bacteria. Showing strong efficacy without any observed in vivo toxicity increases the significance of these antimicrobial agents for their use in humans. However, at the present time, clinical trials are insufficient and require more research. The strong antibacterial efficacies of platensimycin and platencin may be established in clinical trials and their use in humans for coping with multidrug resistance may be

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

    EPA Science Inventory

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. [The correlation between flow pattern during cardiopulmonary bypass and patency of the coronary artery bypass grafts].

    PubMed

    Hagiwara, H; Shirakawa, M; Nakayama, T; Asai, T; Nakayama, M; Ito, T; Yano, Y

    2005-07-01

    Recently the availability of transit time flow measurement (TTFM) is reported especially in off-pump coronary artery bypass grafting (CABG). But little is known about TTFM findings in on-pump CABG. We examined the correlation between the TTFM flow pattern and the angiography findings in on-pump CABG. The subjects consisted of 52 patients who underwent on-pump CABG and angiography early after operation. In these patients, 55 internal thoracic artery (ITA), 17 gastroepiploic artery (GEA), 13 saphenous vein graft (SVG) and 41 radial artery (RA) were tested with TTFM during cardiopulmonary bypass (CPB). TTFM demonstrated a diastolic filling pattern in 53 ITA, 16 GEA, 13 SVG and 36 RA. The angiography revealed that all these grafts were perfectly patent with the exception of a GEA with a flow competition pattern. TTFM revealed an abnormal flow pattern in 2 ITA (these 2 grafts were revised during CPB and the angiography demonstrated their perfect patency), 1 GEA (to and fro pattern), 0 SVG and 5 RA (the abnormal pattern was due to graft spasm in 3 of 5, and the angiography revealed their perfect patency, however, the angiography detected stenosis in the remaining 2 grafts). The present study found that the TTFM flow pattern during CPB correlated well with the angiography findings. TTFM during CPB was useful to detect graft failure, and grafts were revised safely during CPB. PMID:16004331

  9. Cofactor bypass variants reveal a conformational control mechanism governing cell wall polymerase activity.

    PubMed

    Markovski, Monica; Bohrhunter, Jessica L; Lupoli, Tania J; Uehara, Tsuyoshi; Walker, Suzanne; Kahne, Daniel E; Bernhardt, Thomas G

    2016-04-26

    To fortify their cytoplasmic membrane and protect it from osmotic rupture, most bacteria surround themselves with a peptidoglycan (PG) exoskeleton synthesized by the penicillin-binding proteins (PBPs). As their name implies, these proteins are the targets of penicillin and related antibiotics. We and others have shown that the PG synthases PBP1b and PBP1a of Escherichia coli require the outer membrane lipoproteins LpoA and LpoB, respectively, for their in vivo function. Although it has been demonstrated that LpoB activates the PG polymerization activity of PBP1b in vitro, the mechanism of activation and its physiological relevance have remained unclear. We therefore selected for variants of PBP1b (PBP1b*) that bypass the LpoB requirement for in vivo function, reasoning that they would shed light on LpoB function and its activation mechanism. Several of these PBP1b variants were isolated and displayed elevated polymerization activity in vitro, indicating that the activation of glycan polymer growth is indeed one of the relevant functions of LpoB in vivo. Moreover, the location of amino acid substitutions causing the bypass phenotype on the PBP1b structure support a model in which polymerization activation proceeds via the induction of a conformational change in PBP1b initiated by LpoB binding to its UB2H domain, followed by its transmission to the glycosyl transferase active site. Finally, phenotypic analysis of strains carrying a PBP1b* variant revealed that the PBP1b-LpoB complex is most likely not providing an important physical link between the inner and outer membranes at the division site, as has been previously proposed. PMID:27071112

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

    PubMed

    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

  11. Replication fork bypass of a pyrimidine dimer blocking leading strand DNA synthesis.

    PubMed

    Cordeiro-Stone, M; Zaritskaya, L S; Price, L K; Kaufmann, W K

    1997-05-23

    We constructed a double-stranded plasmid containing a single cis, syn-cyclobutane thymine dimer (T[c,s]T) 385 base pairs from the center of the SV40 origin of replication. This circular DNA was replicated in vitro by extracts from several types of human cells. The dimer was placed on the leading strand template of the first replication fork to encounter the lesion. Two-dimensional gel electrophoresis of replication intermediates documented the transient arrest of the replication fork by the dimer. Movement of the replication fork beyond the dimer was recognized by the appearance of a single fork arc in DNA sequences located between the T[c,s]T and the half-way point around the circular template (180 degrees from the origin). Upon completion of plasmid replication, the T[c,s]T was detected by T4 endonuclease V in about one-half (46 +/- 9%) of the closed circular daughter molecules. Our results demonstrate that extracts prepared from HeLa cells and SV40-transformed human fibroblasts (SV80, IDH4), including a cell line defective in nucleotide-excision repair (XPA), were competent for leading strand DNA synthesis opposite the pyrimidine dimer and replication fork bypass. In contrast, dimer bypass was severely impaired in otherwise replication-competent extracts from two different xeroderma pigmentosum variant cell lines.

  12. [Alliance against MDRO: safeguarding antibiotics].

    PubMed

    Carlet, J; Rambaud, C; Pulcini, C

    2012-09-01

    Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the 5 next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practitioners, and veterinarians.

  13. Bypass transition in compressible boundary layers

    NASA Technical Reports Server (NTRS)

    Vandervegt, J. J.

    1992-01-01

    Transition to turbulence in aerospace applications usually occurs in a strongly disturbed environment. For instance, the effects of free-stream turbulence, roughness and obstacles in the boundary layer strongly influence transition. Proper understanding of the mechanisms leading to transition is crucial in the design of aircraft wings and gas turbine blades, because lift, drag and heat transfer strongly depend on the state of the boundary layer, laminar or turbulent. Unfortunately, most of the transition research, both theoretical and experimental, has focused on natural transition. Many practical flows, however, defy any theoretical analysis and are extremely difficult to measure. Morkovin introduced in his review paper the concept of bypass transition as those forms of transition which bypass the known mechanisms of linear and non-linear transition theories and are currently not understood by experiments. In an effort to better understand the mechanisms leading to transition in a disturbed environment, experiments are conducted studying simpler cases, viz. the effects of free stream turbulence on transition on a flat plate. It turns out that these experiments are very difficult to conduct, because generation of free stream turbulence with sufficiently high fluctuation levels and reasonable homogeneity is non trivial. For a discussion see Morkovin. Serious problems also appear due to the fact that at high Reynolds numbers the boundary layers are very thin, especially in the nose region of the plate where the transition occurs, which makes the use of very small probes necessary. The effects of free-stream turbulence on transition are the subject of this research and are especially important in a gas turbine environment, where turbulence intensities are measured between 5 and 20 percent, Wang et al. Due to the fact that the Reynolds number for turbine blades is considerably lower than for aircraft wings, generally a larger portion of the blade will be in a laminar

  14. A Snapshot of Coagulopathy After Cardiopulmonary Bypass.

    PubMed

    Höfer, Judith; Fries, Dietmar; Solomon, Cristina; Velik-Salchner, Corinna; Ausserer, Julia

    2016-09-01

    Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the data available on patients' coagulation status at the end of CPB in order to provide relevant information for the development of tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and 17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most appropriate to guide hemostatic therapy.

  15. Annular MHD Physics for Turbojet Energy Bypass

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.

    2011-01-01

    The use of annular Hall type MHD generator/accelerator ducts for turbojet energy bypass is evaluated assuming weakly ionized flows obtained from pulsed nanosecond discharges. The equations for a 1-D, axisymmetric MHD generator/accelerator are derived and numerically integrated to determine the generator/accelerator performance characteristics. The concept offers a shockless means of interacting with high speed inlet flows and potentially offers variable inlet geometry performance without the complexity of moving parts simply by varying the generator loading parameter. The cycle analysis conducted iteratively with a spike inlet and turbojet flying at M = 7 at 30 km altitude is estimated to have a positive thrust per unit mass flow of 185 N-s/kg. The turbojet allowable combustor temperature is set at an aggressive 2200 deg K. The annular MHD Hall generator/accelerator is L = 3 m in length with a B(sub r) = 5 Tesla magnetic field and a conductivity of sigma = 5 mho/m for the generator and sigma= 1.0 mho/m for the accelerator. The calculated isentropic efficiency for the generator is eta(sub sg) = 84 percent at an enthalpy extraction ratio, eta(sub Ng) = 0.63. The calculated isentropic efficiency for the accelerator is eta(sub sa) = 81 percent at an enthalpy addition ratio, eta(sub Na) = 0.62. An assessment of the ionization fraction necessary to achieve a conductivity of sigma = 1.0 mho/m is n(sub e)/n = 1.90 X 10(exp -6), and for sigma = 5.0 mho/m is n(sub e)/n = 9.52 X 10(exp -6).

  16. A Snapshot of Coagulopathy After Cardiopulmonary Bypass.

    PubMed

    Höfer, Judith; Fries, Dietmar; Solomon, Cristina; Velik-Salchner, Corinna; Ausserer, Julia

    2016-09-01

    Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the data available on patients' coagulation status at the end of CPB in order to provide relevant information for the development of tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and 17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most appropriate to guide hemostatic therapy. PMID:27268940

  17. Hypogammaglobulinemia After Cardiopulmonary Bypass in Infants

    PubMed Central

    Rhodes, Leslie A; Robert, Stephen M; Atkinson, T. Prescott; Dabal, Robert J; Mahdi, Alla M.; Alten, Jeffrey A

    2014-01-01

    Background Hypogammaglobulinemia has been reported after cardiac surgery and may be associated with adverse outcomes. We sought to define baseline immunoglobulin (Ig) concentration in neonates and infants with congenital heart disease, determine its course following cardiopulmonary bypass (CPB), and determine if post-CPB hypogammaglobulinemia was associated with increased morbidity. Methods Single center, retrospective analysis of infants who underwent cardiac surgery with CPB between June 2010 and December 2011. Ig concentration obtained from banked plasma of 47 patients from a prior study (pre-CPB, immediately post-CPB, and 24- and 48-hours post-CPB). Additionally, any Ig levels drawn for clinical purposes after CPB were included. Ig levels were excluded if drawn after chylothorax diagnosis or intravenous immunoglobulin G administration. Results Median age was 7 days. Preoperative Ig concentration was similar to that described in healthy children. IgG level fell to less than 50% of preoperative concentration by 24-hr post-CPB and failed to recover by 7 days. 25/47 (53%) patients had low IgG after CPB (<248 mg/dl). Despite no difference in demographics or risk factors between patients with low and normal IgG, low IgG patients had more positive fluid balance at 24-hours, increased pro-inflammatory plasma cytokine levels, duration of mechanical ventilation, and CICU length of stay. Additionally, low IgG patients had increased incidence of post-operative infections (40% vs. 14%, p=0.056). Conclusions Hypogammaglobulinemia occurs in half of infants after CPB. Its association with fluid overload and increased inflammatory cytokines suggests it may result from capillary leak. Postoperative hypogammaglobulinemia is associated with increased morbidity, including more secondary infections. PMID:24035378

  18. Antibiotic treatment for Helicobacter pylori: Is the end coming?

    PubMed Central

    Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

    2015-01-01

    Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

  19. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.

    PubMed

    Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi

    2015-04-01

    The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

  20. Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity.

    PubMed

    Capeletti, Larissa Brentano; de Oliveira, Luciane França; Gonçalves, Kaliandra de Almeida; de Oliveira, Jessica Fernanda Affonso; Saito, Ângela; Kobarg, Jörg; dos Santos, João Henrique Zimnoch; Cardoso, Mateus Borba

    2014-07-01

    New and more aggressive antibiotic resistant bacteria arise at an alarming rate and represent an ever-growing challenge to global health care systems. Consequently, the development of new antimicrobial agents is required to overcome the inefficiency of conventional antibiotics and bypass treatment limitations related to these pathologies. In this study, we present a synthesis protocol, which was able to entrap tetracycline antibiotic into silica nanospheres. Bactericidal efficacy of these structures was tested against bacteria that were susceptible and resistant to antibiotics. For nonresistant bacteria, our composite had bactericidal efficiency comparable to that of free-tetracycline. On the other hand, the synthesized composites were able to avoid bacterial growth of resistant bacteria while free-tetracycline has shown no significant bactericidal effect. Finally, we have investigated the cytotoxicity of these nanoparticles against mammalian cells to check any possible poisoning effect. It was found that these nanospheres are not apoptosis-inducers and only a reduction on the cell replication rate was seen when compared to the control without nanoparticles.

  1. The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

    PubMed Central

    Plésiat, Patrick

    2015-01-01

    SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps. PMID:25788514

  2. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

    PubMed

    Niu, Guoqing; Tan, Huarong

    2015-02-01

    The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics.

  3. Applications of Local Antibiotics in Orthopedic Trauma.

    PubMed

    Cancienne, Jourdan M; Burrus, M Tyrrell; Weiss, David B; Yarboro, Seth R

    2015-10-01

    Local antibiotics have a role in orthopedic trauma for both infection prophylaxis and treatment. They provide the advantage of high local antibiotic concentration without excessive systemic levels. Nonabsorbable polymethylmethacrylate (PMMA) is a popular antibiotic carrier, but absorbable options including bone graft, bone graft substitutes, and polymers have gained acceptance. Simple aqueous antibiotic solutions continue to be investigated and appear to be clinically effective. For established infections, such as osteomyelitis, a combination of surgical debridement with local and systemic antibiotics seems to represent the most effective treatment at this time. Further investigation of more effective local antibiotic utilization is ongoing.

  4. Antibacterial properties of cationic steroid antibiotics.

    PubMed

    Savage, Paul B; Li, Chunhong; Taotafa, Uale; Ding, Bangwei; Guan, Qunying

    2002-11-19

    Cationic steroid antibiotics have been developed that display broad-spectrum antibacterial activity. These compounds are comprised of steroids appended with amine groups arranged to yield facially amphiphilic morphology. Examples of these antibiotics are highly bactericidal, while related compounds effectively permeabilize the outer membranes of Gram-negative bacteria sensitizing these organisms to hydrophobic antibiotics. Cationic steroid antibiotics exhibit various levels of eukaryote vs. prokaryote cell selectivity, and cell selectivity can be increased via charge recognition of prokaryotic cells. Studies of the mechanism of action of these antibiotics suggest that they share mechanistic aspects with cationic peptide antibiotics. PMID:12445638

  5. Small Molecules Take A Big Step Against Clostridium difficile.

    PubMed

    Beilhartz, Greg L; Tam, John; Melnyk, Roman A

    2015-12-01

    Effective treatment of Clostridium difficile infections demands a shift away from antibiotics towards toxin-neutralizing agents. Work by Bender et al., using a drug that attenuates toxin action in vivo without affecting bacterial survival, demonstrates the exciting potential of small molecules as a new modality in the fight against C. difficile. PMID:26547239

  6. Helping Chemists Discover New Antibiotics.

    PubMed

    Blaskovich, Mark A T; Zuegg, Johannes; Elliott, Alysha G; Cooper, Matthew A

    2015-07-10

    The world is facing a crisis in treating infectious diseases, with a scarcity of new antibiotics in development to treat the growing threat of drug-resistant "superbugs". We need new strategies to reinvigorate the antibiotic pipeline. In this Viewpoint we discuss one such approach, encouraging the community of synthetic chemists to participate in testing chemical diversity from their laboratories for antimicrobial potential. CO-ADD, the Community for Open Antimicrobial Drug Discovery, offers free screening against five bacteria and two fungi with follow up hit confirmation and validation, all with no strings attached. PMID:27622818

  7. [Mercurimetric determination of cephalosporin antibiotics].

    PubMed

    Pospísilová, B; Kubes, J

    1988-04-01

    The conditions for a potenciometric estimation of cefuroxime, cefsulodin, cefotaxime and ceftriaxon with mercury(II) perchlorate after the previous reaction of the antibiotics with hydroxylamine were established. The mercurimetric determination was well reproducible with the relative error of the mean ranging up to 1% and the results are identical with the spectrometric and microbiological determination. There is no need to use a standard. With this technique only the content of effective antibiotic with an intact beta-lactam ring can be estimated. The method did not provide objective results for cefoperazone and cefoxitin. The direct determination of cephalosporin degradation products was verified for cefalexin, cefalothin, cefuroxime, cefsulodin and ceftriaxon.

  8. Cefuroxime - a new cephalosporin antibiotic.

    PubMed

    O'Callaghan, C H; Sykes, R B; Ryan, D M; Foord, R D; Muggleton, P W

    1976-01-01

    Cefuroxime is a new broad spectrum cephalosporin antibiotic for administration by injection. It is stable to most beta-lactamases. It is active against gram-positive organisms, including penicillinase-producing staphylococci, and has wide activity against gram-negative bacilli including Enterobacter and many strains of indole-positive Proteus spp. The substance is also highly active against Haemophilus influenzae and Neisseria gonorrhoeae. Studies on human volunteers showed that it produced high, long-lasting blood levels with virtually complete recovery of unchanged antibiotic in the urine. No evidence of toxicity due to cefuroxime was found. Slight, short-lived pain followed intramuscular injection, and the compound was well tolerated intravenously.

  9. Focal brain atrophy in gastric bypass patients with cognitive complaints

    PubMed Central

    Graff-Radford, Jonathan; Whitwell, Jennifer L.; Trenerry, Max R.; Ahlskog, J. Eric; Jensen, Michael D.; Jack, Clifford R.; Josephs, Keith A.

    2012-01-01

    Recently, we have noticed a series of patients presenting for cognitive complaints after gastric bypass, without any identifiable etiology. We set out to determine whether any focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass that had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to ten age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass at a median age of 54 (range: 46–64). Cognitive complaints began at a median age of 57 (52–69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery have focal thalamic brain atrophy that could account for the cognitive impairment. PMID:22088949

  10. Entry overload, emergency department overcrowding, and ambulance bypass

    PubMed Central

    Fatovich, D; Hirsch, R

    2003-01-01

    Objectives: To describe an experience of emergency department (ED) overcrowding and ambulance bypass. Methods: A prospective observational study at Royal Perth Hospital, a major teaching hospital. Episodes of ambulance bypass and their characteristics were recorded. Results: From 1 July 1999 to 30 June 2001, there were 141 episodes of ambulance bypass (mean duration 187 min, range 35–995). Monday was the most common day with 39 (28%) episodes. Entry block alone was the most common reason bypass was activated (n=38, 30.4%). The mean number of patients in ED at these times was 40 (occupancy 174%), including nine in the corridor, seven awaiting admission, and 14 waiting to be seen. Episodes attributable to entry block were typically preceded by a presentation rate of ⩾10 patients per hour for ⩾2 hours (OR 6.2, 95% CI 4.3 to 8.5). Mid-afternoon to early evening was the most common time for activation. Ambulance bypass is increasing in frequency and duration. Conclusions: Entry overload resulting in entry block results from overwhelming numbers of patients presenting to the ED in a short space of time. Entry block impairs access to emergency care. Unless something is done in the near future, the general public may no longer be able to rely on EDs for quality and timely emergency care. A "whole of system" approach is necessary to tackle the problem. PMID:12954675

  11. Antibiotic Transport in Resistant Bacteria: Synchrotron UV Fluorescence Microscopy to Determine Antibiotic Accumulation with Single Cell Resolution

    PubMed Central

    Kaščáková, Slávka; Maigre, Laure; Chevalier, Jacqueline; Réfrégiers, Matthieu; Pagès, Jean-Marie

    2012-01-01

    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 antibitiotic 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. PMID:22719907

  12. Probiotic approach to prevent antibiotic resistance.

    PubMed

    Ouwehand, Arthur C; Forssten, Sofia; Hibberd, Ashley A; Lyra, Anna; Stahl, Buffy

    2016-01-01

    Probiotics are live microorganisms, mainly belonging to the genera Lactobacillus and Bifidobacterium, although also strain of other species are commercialized, that have a beneficial effect on the host. From the perspective of antibiotic use, probiotics have been observed to reduce the risk of certain infectious disease such as certain types of diarrhea and respiratory tract infection. This may be accompanied with a reduced need of antibiotics for secondary infections. Antibiotics tend to be effective against most common diseases, but increasingly resistance is being observed among pathogens. Probiotics are specifically selected to not contribute to the spread of antibiotic resistance and not carry transferable antibiotic resistance. Concomitant use of probiotics with antibiotics has been observed to reduce the incidence, duration and/or severity of antibiotic-associated diarrhea. This contributes to better adherence to the antibiotic prescription and thereby reduces the evolution of resistance. To what extent probiotics directly reduce the spread of antibiotic resistance is still much under investigation; but maintaining a balanced microbiota during antibiotic use may certainly provide opportunities for reducing the spread of resistances. Key messages Probiotics may reduce the risk for certain infectious diseases and thereby reduce the need for antibiotics. Probiotics may reduce the risk for antibiotic-associated diarrhea Probiotics do not contribute to the spread of antibiotic resistance and may even reduce it.

  13. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  14. Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis: example of coronary artery bypass surgery.

    PubMed Central

    Zanetti, G.; Goldie, S. J.; Platt, R.

    2001-01-01

    Routine us of vancomycin for perioperative prophylaxis is discouraged, principally to minimize microbial resistance to it. However, outcomes and costs of this recommendation have not been assessed. We used decision-analytic models to compare clinical results and cost-effectiveness of no prophylaxis, cefazolin, and vancomycin, in coronary artery bypass graft surgery. In the base case, vancomycin resulted in 7% fewer surgical site infections and 1% lower all-cause mortality and saved $117 per procedure, compared with cefazolin. Cefazolin, in turn, resulted in substantially fewer infections and deaths and lower costs than no prophylaxis. We conclude that perioperative antibiotic prophylaxis with vancomycin is usually more effective and less expensive than cefazolin. Data on vancomycin's impact on resistance are needed to quantify the trade-off between individual patients' improved clinical outcomes and lower costs and the future long-term consequences to society. PMID:11747694

  15. Antibodies: an alternative for antibiotics?

    PubMed

    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

  16. Antibiotic resistance in probiotic bacteria

    PubMed Central

    Gueimonde, Miguel; Sánchez, Borja; G. de los Reyes-Gavilán, Clara; Margolles, Abelardo

    2013-01-01

    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. PMID:23882264

  17. Spatial mapping of antibiotic resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serious concern for modern animal production is the fear that feed antimicrobials, such as monensin, increase the potential for high levels of antibiotic resistant (AR) gene prevalence in the manure, which may subsequently be shared with soil communities and eventually be taken up by human pathoge...

  18. Antibiotics May Blunt Breast-Feeding's Benefits

    MedlinePlus

    ... how it helps a baby develop intestinal bacteria (microbiota), and that antibiotics disturb that development, she said. ... the mother guides the development of the infant's microbiota," she said. "Antibiotic use disrupts the natural microbiota ...

  19. Origins and Evolution of Antibiotic Resistance

    PubMed Central

    Davies, Julian; Davies, Dorothy

    2010-01-01

    Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

  20. Antibiotics Overprescribed for Possible STDs: Study

    MedlinePlus

    ... There is a tricky balance between not furthering antibiotic resistance by over-prescribing, but also still getting people ... a national and international priority to help prevent antibiotic resistance, which would threaten our ability to treat even ...

  1. Alliance for the Prudent Use of Antibiotics

    MedlinePlus

    ... Competencies Current Projects Completed Projects The Center for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance ... visit our partner lab at the Center for Adaptation Genetics and Drug Resistance . Antibiotic Resistance in the ...

  2. When and How to Take Antibiotics

    MedlinePlus

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  3. Antibiotic stewardship programmes and the surgeon's role.

    PubMed

    Çakmakçi, M

    2015-04-01

    Inappropriate antibiotic use is a frequent occurrence, especially in surgical units. Among the unnecessary costs of such usage are unfavourable outcomes for patients and the emergence and spread of resistant bacteria. Antibiotic stewardship programmes aim to limit the spread of antibiotic resistance by promoting thoughtful prescribing of antibiotics. Such programmes usually try to control inappropriate use of antibiotics; to optimize the choice of drug, dosing, route, and duration of therapy; to maximize clinical cure or prevention of infection; and to limit unwanted effects and excess cost. In this paper, I discuss the impact of improper use of antibiotics and outline why I believe that antibiotic stewardship is likely to be the best way of dealing with it. Engagement of surgeons in antibiotic stewardship programmes is crucial to their success.

  4. FDA Bolsters Warnings about Class of Antibiotics

    MedlinePlus

    ... 160078.html FDA Bolsters Warnings About Class of Antibiotics Fluoroquinolones such as Cipro, Levaquin should be reserved ... it's strengthening label warnings on a class of antibiotics called fluoroquinolones because the drugs can lead to ...

  5. Collective antibiotic tolerance: Mechanisms, dynamics, and intervention

    PubMed Central

    Meredith, Hannah R.; Srimani, Jaydeep K.; Lee, Anna J.; Lopatkin, Allison J.; You, Lingchong

    2016-01-01

    Bacteria have developed resistance against every antibiotic at an alarming rate, considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics, and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. In contrast, a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming, and inter-population interactions. These strategies can enable rapid population recovery after antibiotic treatment, and provide a time window for otherwise susceptible bacteria to acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy. PMID:25689336

  6. Rapid electrochemical phenotypic profiling of antibiotic-resistant bacteria.

    PubMed

    Besant, Justin D; Sargent, Edward H; Kelley, Shana O

    2015-07-01

    Rapid phenotyping of bacteria to identify drug-resistant strains is an important capability for the treatment and management of infectious disease. At present, the rapid determination of antibiotic susceptibility is hindered by the requirement that, in existing devices, bacteria must be pre-cultured for 2-3 days to reach detectable levels. Here we report a novel electrochemical approach that achieves rapid readout of the antibiotic susceptibility profile of a bacterial infection within one hour. The electrochemical reduction of a redox-active molecule is monitored that reports on levels of metabolically-active bacteria. Bacteria are captured in miniaturized wells, incubated with antimicrobials and monitored for resistance. This electrochemical phenotyping approach is effective with clinically-relevant levels of bacteria, and provides results comparable to culture-based analysis. Results, however, are delivered on a much faster timescale, with resistance profiles available after a one hour incubation period.

  7. Enhanced Antimicrobial Activity Of Antibiotics Mixed With Metal Nanoparticles

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep; Kumar, Neeraj; Bhanjana, Gaurav; Thakur, Rajesh; Dilbaghi, Neeraj

    2011-12-01

    Current producers of antimicrobial technology have a long lasting, environmentally safe, non-leaching, water soluble solution that will eventually replace all poisons and heavy metals. The transition metal ions inevitably exist as metal complexes in biological systems by interaction with the numerous molecules possessing groupings capable of complexation or chelation. Nanoparticles of metal oxides offer a wide variety of potential applications in medicine due to the unprecedented advances in nanobiotechnology research. the bacterial action of antibiotics like penicillin, erythryomycin, ampicillin, streptomycin, kanamycin etc. and that of a mixture of antibiotics and metal and metal oxide nanoparticles like zinc oxide, zirconium, silver and gold on microbes was examined by the agar-well-diffusion method, enumeration of colony-forming units (CFU) and turbidimetry.

  8. Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives

    PubMed Central

    Garneau-Tsodikova, Sylvie

    2015-01-01

    Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance. PMID:26877861

  9. New and alternative approaches to tackling antibiotic resistance

    PubMed Central

    Theriault, Nicolette

    2013-01-01

    Multidrug-resistant bacteria are becoming more common and due to their multiplicity of mechanisms, they are frequently resistant to many if not all of the current antibiotics. This daunting spectre has been the target of many research efforts into conventional antibiotics and alternative approaches. This review focuses on the more recent advances in these fields with an overview on peptidomimetics, nanoparticles and their derivatives, FimH inhibitors, quorum sensing inhibition molecules, neoglycosides and phage therapies. These various approaches are at different stages of development, some are closer to the clinic than others, but recent regulatory guidance and re-awakened interest from the pharmaceutical companies gives us some optimism for the future. PMID:24381727

  10. Proposal of bypass in heat recovery system with sucking air

    NASA Astrophysics Data System (ADS)

    Siažik, Ján; Malcho, Milan; Rezničák, Štefan

    2016-06-01

    Waste heat is utilized in a wide variety of technologies for a number of reasons. But the significant one such reason is use of the energy contained for example in waste water or waste heat that would otherwise left unused. Other considerable reason it is also reduces primary costs to operate the technology. The article deals with the arrangement section of the unit in heat recovery systems where the entry of waste gases into defluorinastion device. The technologies re-use heat often use the bypass. Bypass fulfill their duty in equipment failures, for example heat exchanger where it is not possible to stop the operationimmediately and the hot combustion gases can flow bypass without interrupting operation.

  11. Rankine cycle load limiting through use of a recuperator bypass

    DOEpatents

    Ernst, Timothy C.

    2011-08-16

    A system for converting heat from an engine into work includes a boiler coupled to a heat source for transferring heat to a working fluid, a turbine that transforms the heat into work, a condenser that transforms the working fluid into liquid, a recuperator with one flow path that routes working fluid from the turbine to the condenser, and another flow path that routes liquid working fluid from the condenser to the boiler, the recuperator being configured to transfer heat to the liquid working fluid, and a bypass valve in parallel with the second flow path. The bypass valve is movable between a closed position, permitting flow through the second flow path and an opened position, under high engine load conditions, bypassing the second flow path.

  12. Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

    PubMed

    Koning, Nick J; de Lange, Fellery; Vonk, Alexander B A; Ahmed, Yunus; van den Brom, Charissa E; Bogaards, Sylvia; van Meurs, Matijs; Jongman, Rianne M; Schalkwijk, Casper G; Begieneman, Mark P V; Niessen, Hans W; Baufreton, Christophe; Boer, Christa

    2016-03-01

    Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

  13. Experimental laparoscopic aortobifemoral bypass for occlusive aortoiliac disease

    PubMed Central

    Dion, Yves-Marie; Gaillard, Félix; Demalsy, Jean-Claude; Gracia, Carlos R.

    1996-01-01

    Objective To describe a totally laparoscopic technique for aortobifemoral bypass to treat aortoiliac atheromatous occlusive disease. Design A feasibility study. Setting A university teaching hospital. Subjects Six piglets weighing between 70 and 80 kg were submitted to a totally laparoscopic retroperitoneal aortobifemoral bypass, performed through six trocar sites, with abdominal suspension and a gasless technique. No minilaparotomy was performed. After systemic heparinization, the infrarenal aorta was cross-clamped and the aortic bifurcation stapled. An end-to-end aorto–prosthetic anastomosis was performed. Retroperitoneal tunnels were created to allow each limb of the graft to join its corresponding femoral artery by a conventional anastomosis. Intervention Totally laparoscopic aortobifemoral bypass. Main Outcome Measures Duration of the procedure, intraoperative blood loss and operative complications, bleeding in the immediate postoperative period. Evaluation of the aortic anastomosis at autopsy. Results All aortobifemoral bypasses were completed in less than 4 hours. Intraoperative blood loss did not exceed 250 mL. No intraoperative complication was encountered except occasional bleeding at the aortic anastomosis upon releasing the arterial clamp. This was controlled with a collagen sponge (three cases) or extra stitches (two cases). The animals were observed for 15 minutes before sacrifice. Autopsy revealed a normal aortic anastomosis in all cases and a normal progression of the limbs of the graft under the ureters in the retroperitoneal tunnels. Conclusions This animal model demonstrates the feasibility of the aortobifemoral bypass through a laparoscopic approach. The retroperitoneal anatomy of the piglet is similar to that of man. Aortic surgery can be conducted as for the standard technique. We used a similar approach to perform the first human, totally laparoscopic aortobifemoral bypass with an end-to-end anastomosis. PMID:8956809

  14. A call for antibiotic alternatives research.

    PubMed

    Stanton, Thaddeus B

    2013-03-01

    The persistence and spread of antibiotic resistance, in conjunction with decreased profitability of new antibiotics, have created the dangerous prospect of ineffective therapies against bacterial diseases. National strategies aimed at discovery, development, and definition of the mechanisms of effective antibiotic alternatives, especially for agricultural applications, should be encouraged. PMID:23473628

  15. Pipeline of Known Chemical Classes of Antibiotics

    PubMed Central

    d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

    2013-01-01

    Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. PMID:27029317

  16. Overcoming the current deadlock in antibiotic research.

    PubMed

    Schäberle, Till F; Hack, Ingrid M

    2014-04-01

    Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. PMID:24698433

  17. Delivery of antibiotics with polymeric particles.

    PubMed

    Xiong, Meng-Hua; Bao, Yan; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun

    2014-11-30

    Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection.

  18. Overcoming the current deadlock in antibiotic research.

    PubMed

    Schäberle, Till F; Hack, Ingrid M

    2014-04-01

    Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward.

  19. New business models for antibiotic innovation.

    PubMed

    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.

  20. Surgical cartographic navigation system for endoscopic bypass grafting.

    PubMed

    Voruganti, Arun; Mayoral, Rafael; Jacobs, Stephan; Grunert, Ronny; Moeckel, Hendrik; Korb, Werner

    2007-01-01

    Endoscopic bypass grafting with the da Vinci system is still challenging and needs high level of experience and skill of the surgeon. Therefore, it is necessary to support the surgeon with enhanced vision and augmented reality. The augmentation of the patient model into the view of the endoscope is a direct approach to enhance support. The results of a preclinical study are shown in this paper. The method applied is suitable for endoscopic bypass grafting and in general applicable to minimal invasive surgery. The system was designed as an open architecture to facilitate easy transfer of the methodology into other surgical domain applications. PMID:18002243

  1. Dextrocardia with situs inversus totalis: coronary artery bypass grafting.

    PubMed

    Hashmi, Salila; Anis, Mariam; Darr, Umer

    2012-01-01

    Dextrocardia with situs inversus is a rare congenital abnormality involving a left-handed mal rotation of the visceral organs. The incidence of coronary artery disease is the same as that in the general population. Performing coronary artery bypass surgery on patients with dextrocardia poses a more challenging task. It is recommended that the right internal mammary artery be the first choice of graft for the anterior descending artery for a "situs inversus" situation. We report 2 cases of patients with Dextrocardia who developed coronary artery disease and underwent coronary artery bypass grafting. Also mentioned is the slight difference in our technique.

  2. Assessment of coronary bypass surgery and percutaneous transluminal coronary angioplasty.

    PubMed

    Preston, T A

    1989-01-01

    Coronary bypass surgery developed as another in a line of surgical procedures dating back more than 60 years. The medical profession at first assessed this procedure with time-honored anecdotal techniques. Gradually, for a variety of reasons, improved methods of comparisons worked their way into assessments of bypass surgery. Randomized controlled trials met resistance but have been very influential. Assessment of percutaneous transluminal coronary angioplasty has benefited from the knowledge generated during the last 25 years, but clinicians have been slower to apply the most advanced techniques.

  3. Narcotic addiction following gastric bypass surgery--a case study.

    PubMed

    Wendling, Andrea; Wudyka, Andrea

    2011-05-01

    Addictive behavior following gastric bypass surgery is widely discussed in the lay press, but published reports provide conflicting evidence regarding the prevalence of postoperative substance abuse among bariatric surgery patients. We present a case report of a Roux-en-Y gastric bypass patient who presented with recurrent and various pain and nausea complaints postoperatively. These symptoms resulted in multiple radiological and operative procedures before her narcotic addiction was identified. Physicians caring for bariatric surgical patients postoperatively need to be aware of this risk and need to be able to identify early signs of potential postoperative addictions. PMID:20473721

  4. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    MedlinePlus

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Nanocarriers for antibiotics: a promising solution to treat intracellular bacterial infections.

    PubMed

    Abed, Nadia; Couvreur, Patrick

    2014-06-01

    In the field of antibiotherapy, intracellular infections remain difficult to eradicate mainly due to the poor intracellular penetration of most of the commonly used antibiotics. Bacteria have quickly understood that their intracellular localisation allows them to be protected from the host immune system, but also from the action of antimicrobial agents. In addition, in most cases pathogens nestle in professional phagocytic cells, and can even use them as a 'Trojan horse' to induce a secondary site of infection thereby causing persistent or recurrent infections. Thus, new strategies had to be considered in order to counteract these problems. Amongst them, nanocarriers loaded with antibiotics represent a promising approach. Nowadays, it is possible to encapsulate, incorporate or even conjugate biologically active molecules into different families of nanocarriers such as liposomes or nanoparticles in order to deliver antibiotics intracellularly and hence to treat infections. This review gives an overview of the variety of nanocarriers developed to deliver antibiotics directly into infected cells.

  7. [The role of the pharmaceutical industry. Why aren't new antibiotics being marketed?].

    PubMed

    García-Rey, César

    2010-11-01

    The lack or absence of social and political interest in the problem of antibiotic resistance, the difficulty in identifying active molecules against new targets, and above all, low profitability in comparison to other types of drugs, as well as uncertainty and the arbitrary nature of regulatory authorities in terms of assessing effectiveness, all contribute to a significant slowdown in the marketing of new antibiotics. Current conditions do not favor investment in new antibiotics by the pharmaceutical industry, which has available therapeutic areas with far greater profit potential, and other problems of its own to handle. Since we cannot force the industry to develop antibiotics, it is necessary to implement policies as soon as possible that stimulate interest in developing them, or find a way for the states and regulatory authorities to replace the pharmaceutical industry in this task. PMID:21458701

  8. Carbohydrate-Based Antibiotics: A New Approach to Tackling the Problem of Resistance.

    PubMed

    Ritter, Thomas K.; Wong, Chi-Huey

    2001-10-01

    Recent interest in the problem of antibiotic resistance has led to the identification of new targets and strategies for antibiotic discovery. Among these efforts, the development of small molecules as antibiotics to target carbohydrate receptors or carbohydrate-modifying enzymes represents a new direction. This review covers recent work in this regard and discusses the impact of each strategy on the development of drug resistance. Particularly interesting targets include unique cell-surface carbohydrates, the transglycosylase involved in peptidoglycan biosynthesis, and bacterial RNA. With a greater understanding of the genome of different bacteria as well as advances in functional genomics and proteomics, we can expect the discovery of a variety of targets for the development of novel antibiotics.

  9. A Bypass Program of Supportive Instruction for Secondary Students with Learning Disabilities.

    ERIC Educational Resources Information Center

    Mosby, Robert J.

    1979-01-01

    The developmental bypass teaching technique (which provides students an opportunity to bypass their learning deficits) was studied with regard to social studies achievement and classroom behaviors in 50 learning disabled junior high school students. (Author/PHR)

  10. Off-pump coronary artery bypass grafting in patients with mirror-imaging dextrocardia.

    PubMed

    Yuan, Xin; Sun, Hansong; Wang, Xianqiang

    2015-08-01

    Dextrocardia requires alterations in techniques during coronary artery bypass graft (CABG) surgery. We report two cases undergoing off-pump coronary artery bypass graft (OPCAB) surgery and discuss techniques for the operative management of these patients.

  11. Antibiotic resistance differentiates Echinacea purpurea endophytic bacterial communities with respect to plant organs.

    PubMed

    Mengoni, Alessio; Maida, Isabel; Chiellini, Carolina; Emiliani, Giovanni; Mocali, Stefano; Fabiani, Arturo; Fondi, Marco; Firenzuoli, Fabio; Fani, Renato

    2014-10-01

    Recent findings have shown that antibiotic resistance is widespread in multiple environments and multicellular organisms, as plants, harboring rich and complex bacterial communities, could be hot spot for emergence of antibiotic resistances as a response to bioactive molecules production by members of the same community. Here, we investigated a panel of 137 bacterial isolates present in different organs of the medicinal plant Echinacea purpurea, aiming to evaluate if different plant organs harbor strains with different antibiotic resistance profiles, implying then the presence of different biological interactions in the communities inhabiting different plant organs. Data obtained showed a large antibiotic resistance variability among strains, which was strongly related to the different plant organs (26% of total variance, P < 0.0001). Interestingly this uneven antibiotic resistance pattern was present also when a single genus (Pseudomonas), ubiquitous in all organs, was analyzed and no correlation of antibiotic resistance pattern with genomic relatedness among strains was found. In conclusion, we speculate that antibiotic resistance patterns are tightly linked to the type of plant organ under investigation, suggesting the presence of differential forms of biological interaction in stem/leaves, roots and rhizosphere. PMID:25283726

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

    PubMed

    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

  13. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.

    PubMed

    Arenz, Stefan; Juette, Manuel F; Graf, Michael; Nguyen, Fabian; Huter, Paul; Polikanov, Yury S; Blanchard, Scott C; Wilson, Daniel N

    2016-07-01

    The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis. PMID:27330110

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

    PubMed Central

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

    2016-01-01

    Antibiotic resistance is an increasingly serious public health threat1. Understanding pathways allowing bacteria to survive antibiotic stress may unveil new therapeutic targets2–8. 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. While 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 PolIV, 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 antibiotics stress and suggests targeting bacterial DNA methylation as a viable approach to enhancing antibiotic activity. PMID:26998690

  15. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

    PubMed Central

    Arenz, Stefan; Graf, Michael; Nguyen, Fabian; Huter, Paul; Polikanov, Yury S.; Blanchard, Scott C.; Wilson, Daniel N.

    2016-01-01

    The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis. PMID:27330110

  16. Antibiotic resistance differentiates Echinacea purpurea endophytic bacterial communities with respect to plant organs.

    PubMed

    Mengoni, Alessio; Maida, Isabel; Chiellini, Carolina; Emiliani, Giovanni; Mocali, Stefano; Fabiani, Arturo; Fondi, Marco; Firenzuoli, Fabio; Fani, Renato

    2014-10-01

    Recent findings have shown that antibiotic resistance is widespread in multiple environments and multicellular organisms, as plants, harboring rich and complex bacterial communities, could be hot spot for emergence of antibiotic resistances as a response to bioactive molecules production by members of the same community. Here, we investigated a panel of 137 bacterial isolates present in different organs of the medicinal plant Echinacea purpurea, aiming to evaluate if different plant organs harbor strains with different antibiotic resistance profiles, implying then the presence of different biological interactions in the communities inhabiting different plant organs. Data obtained showed a large antibiotic resistance variability among strains, which was strongly related to the different plant organs (26% of total variance, P < 0.0001). Interestingly this uneven antibiotic resistance pattern was present also when a single genus (Pseudomonas), ubiquitous in all organs, was analyzed and no correlation of antibiotic resistance pattern with genomic relatedness among strains was found. In conclusion, we speculate that antibiotic resistance patterns are tightly linked to the type of plant organ under investigation, suggesting the presence of differential forms of biological interaction in stem/leaves, roots and rhizosphere.

  17. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    PubMed

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.

  18. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    PubMed

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation. PMID:26493767

  19. On Pump Coronary Artery Bypass Graft Surgery Versus Off Pump Coronary Artery Bypass Graft Surgery: A Review

    PubMed Central

    Islam, Mohammad Yousuf-ul; Ahmed, Muhammad Umer; Khan, Muhammad Shahzeb; Bawany, Faizan Imran; Khan, Asadullah; Arshad, Mohammad Hussham

    2014-01-01

    There are two basic ways of performing coronary artery bypass graft surgery (CABG): on pump CABG and off pump CABG. Off pump CABG is relatively a newer procedure to on-pump CABG and does not require the use of the cardiopulmonary bypass machine. On pump CABG is the more traditional method of performing bypass surgery. However its resultant inflammatory effects cause renal dysfunction, gastrointestinal distress and cardiac abnormalities which have forced the surgeons to look for alternatives to the procedure. An extensive literature search revealed that on pump CABG causes better revascularization as compared to off pump CABG while off pump CABG has a much lower post operative morbidity and mortality especially in high risk patients. We suggest that the technique used should depend on the ease of the surgeon doing the operation as both the methods seem almost equally efficient according to the review. PMID:24762361

  20. Total Synthesis and Structural Revision of Antibiotic CJ-16,264**

    PubMed Central

    Nicolaou, K. C.; Shah, Akshay A.; Korman, Henry; Khan, Tabrez; Shi, Lei; Worawalai, Wisuttaya; Theodorakis, Emmanuel A.

    2015-01-01

    The total synthesis and structural revision of antibiotic CJ-16,264 is described. Starting with citronellal, the quest for the target molecule featured a novel bis-transannular Diels–Alder reaction that casted stereoselectively the decalin system and included the synthesis of six isomers before demystification of its true structure. PMID:26096055

  1. Surface modeling of soil antibiotics.

    PubMed

    Shi, Wen-jiao; Yue, Tian-xiang; Du, Zheng-ping; Wang, Zong; Li, Xue-wen

    2016-02-01

    Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints.

  2. Surface modeling of soil antibiotics.

    PubMed

    Shi, Wen-jiao; Yue, Tian-xiang; Du, Zheng-ping; Wang, Zong; Li, Xue-wen

    2016-02-01

    Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. PMID:26613514

  3. Infection, antibiotics, and preterm delivery.

    PubMed

    Locksmith, G; Duff, P

    2001-10-01

    The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor

  4. Use of antibiotic-loaded cement in total knee arthroplasty

    PubMed Central

    Hinarejos, Pedro; Guirro, Pau; Puig-Verdie, Lluis; Torres-Claramunt, Raul; Leal-Blanquet, Joan; Sanchez-Soler, Juan; Monllau, Joan Carles

    2015-01-01

    Bone cement has the capacity to release antibiotic molecules if any antibiotic is included in it, and these elution properties are improved as cement porosity is increased. In vitro studies have shown high local antibiotic concentration for many hours or few days after its use. Antibiotic loaded bone cement (ALBC) is helpful when treating an infection in total knee arthroplasty (TKA) revision surgery. The purpose of this paper was to review the evidence for the routine use of ALBC in TKA in the literature, its pros and cons. Many authors have recommended the use of ALBC also in primary TKA for infection prophylaxis, but the evidence based on data from National Registries, randomized clinical trials and meta-analysis suggest a protective effect of ALBC against infection when used in hips, but not (or only mild) in knees. A possible explanation to this finding is that the duration and quantity of locally elevated antibiotic levels after surgery are smaller in TKA, due to the smaller amount of cement used for fixation in TKA-only a layer in the bone surface. There are some concerns about the routine use of ALBC in primary TKA as prophylaxis against infection: Firstly, there is a risk of hypersensivity or toxicity even when the chance is highly improbable. Secondly, there is a reduction in the mechanical properties of the cement, but this can be probably neglected if the antibiotic is used in low doses, not more than 1 g per 40 g cement package. Another significant concern is the increased economic cost, which could be overlooked if there were enough savings in treating fewer prosthetic infections. Finally, there is also a risk of selection of antibiotic-resistant strains of bacteria and this could be the main concern. If used, the choice of the antibiotic mixed in ALBC should consider microbiological aspects (broad antimicrobial spectrum and low rate of resistant bacteria), physical and chemical aspects (thermal stability, high water solubility), pharmacological

  5. 21 CFR 870.4290 - Cardiopulmonary bypass adaptor, stopcock, manifold, or fitting.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass adaptor, stopcock, manifold... Devices § 870.4290 Cardiopulmonary bypass adaptor, stopcock, manifold, or fitting. (a) Identification. A cardiopulmonary bypass adaptor, stopcock, manifold, or fitting is a device used in cardiovascular...

  6. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood...

  7. 75 FR 26320 - Notice of Intent To Prepare an Environmental Impact Statement; West Waukesha Bypass, Waukesha...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... Waukesha Bypass, Waukesha County, WI AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of... improvements in the planned West Waukesha Bypass corridor in Waukesha County, Wisconsin. The EIS is being... Bypass. Participation by the public, local officials, state and federal regulatory agencies,...

  8. 40 CFR 63.1569 - What are my requirements for HAP emissions from bypass lines?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... emissions from bypass lines? 63.1569 Section 63.1569 Protection of Environment ENVIRONMENTAL PROTECTION..., Catalytic Reforming Units, Sulfur Recovery Units, and Bypass Lines § 63.1569 What are my requirements for HAP emissions from bypass lines? (a) What work practice standards must I meet? (1) You must meet...

  9. Patient Bypass Behavior and Critical Access Hospitals: Implications for Patient Retention

    ERIC Educational Resources Information Center

    Liu, Jiexin (Jason); Bellamy, Gail R.; McCormick, Melissa

    2007-01-01

    Purpose: To assess the extent of bypass for inpatient care among patients living in Critical Access Hospital (CAH) service areas, and to determine factors associated with bypass, the reasons for bypass, and what CAHs can do to retain patients locally. Methods: Six hundred and forty-seven subjects, aged 18 years and older, who had been admitted to…

  10. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass on-line blood gas monitor. 870.4330 Section 870.4330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood...

  11. 21 CFR 870.4340 - Cardiopulmonary bypass level sensing monitor and/or control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass level sensing monitor and... Devices § 870.4340 Cardiopulmonary bypass level sensing monitor and/or control. (a) Identification. A cardiopulmonary bypass level sensing monitor and/or control is a device used to monitor and/or control the...

  12. 21 CFR 870.4210 - Cardiopulmonary bypass vascular catheter, cannula, or tubing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass vascular catheter, cannula... Devices § 870.4210 Cardiopulmonary bypass vascular catheter, cannula, or tubing. (a) Identification. A cardiopulmonary bypass vascular catheter, cannula, or tubing is a device used in cardiopulmonary surgery...

  13. 34 CFR 76.676 - Judicial review of a bypass action.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Judicial review of a bypass action. 76.676 Section 76... Conditions Must Be Met by the State and Its Subgrantees? Procedures for Bypass § 76.676 Judicial review of a bypass action. If a grantee or subgrantee is dissatisfied with the Secretary's final action after...

  14. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through...

  15. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through...

  16. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line blood filter is a device used as part of a gas exchange (oxygenator) system to filter...

  17. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line blood filter is a device used as part of a gas exchange (oxygenator) system to filter...

  18. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood...

  19. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass on-line blood gas monitor... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood gas monitor is a device used in conjunction with a blood gas sensor to measure the level of gases in the...

  20. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass on-line blood gas monitor... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood gas monitor is a device used in conjunction with a blood gas sensor to measure the level of gases in the...

  1. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through...

  2. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line blood filter is a device used as part of a gas exchange (oxygenator) system to filter...

  3. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line blood filter is a device used as part of a gas exchange (oxygenator) system to filter...

  4. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood...

  5. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood...

  6. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass on-line blood gas monitor... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood gas monitor is a device used in conjunction with a blood gas sensor to measure the level of gases in the...

  7. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through...

  8. 21 CFR 870.4330 - Cardiopulmonary bypass on-line blood gas monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass on-line blood gas monitor... Cardiopulmonary bypass on-line blood gas monitor. (a) Identification. A cardiopulmonary bypass on-line blood gas monitor is a device used in conjunction with a blood gas sensor to measure the level of gases in the...

  9. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood...

  10. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass heart-lung machine console... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine... heart-lung machine. The console is designed to interface with the basic units used in a gas...

  11. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass heart-lung machine console... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine... heart-lung machine. The console is designed to interface with the basic units used in a gas...

  12. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass heart-lung machine console... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine... heart-lung machine. The console is designed to interface with the basic units used in a gas...

  13. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass heart-lung machine console... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine... heart-lung machine. The console is designed to interface with the basic units used in a gas...

  14. 21 CFR 870.4220 - Cardiopulmonary bypass heart-lung machine console.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass heart-lung machine console... Cardiopulmonary bypass heart-lung machine console. (a) Identification. A cardiopulmonary bypass heart-lung machine... heart-lung machine. The console is designed to interface with the basic units used in a gas...

  15. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class...

  16. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class...

  17. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class...

  18. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class...

  19. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class...

  20. 21 CFR 870.4340 - Cardiopulmonary bypass level sensing monitor and/or control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass level sensing monitor and... Devices § 870.4340 Cardiopulmonary bypass level sensing monitor and/or control. (a) Identification. A cardiopulmonary bypass level sensing monitor and/or control is a device used to monitor and/or control the...

  1. Antibiotic resistance: a growing and multifaceted problem.

    PubMed

    Clark, L

    Antibiotic resistance is an increasing problem worldwide that is exacerbated by the overuse and misuse of antibiotics. Patients, pharmaceutical marketing, and the use of antibiotics in veterinary medicine and animal husbandry are important factors to consider in the emergence of resistance. Infection control measures to prevent the spread of antibiotic-resistant bacteria are compromised by poor compliance to basic measures such as handwashing and standards of environmental cleanliness. Wider epidemiological factors such as global travel and complacency towards public health must also be considered. This article aims to improve understanding of antibiotic resistance and suggests ways in which nurses can contribute towards the strategy to address the problem.

  2. Review of antibiotics and indications for prophylaxis.

    PubMed

    Weiss, Adam; Dym, Harry

    2012-01-01

    Antibiotic prophylaxis to prevent infective endocarditis has been controversial through the years, with various changes made to recommendations provided to treating physicians and dentists. The dentist must always use his or her best judgment when applying any guideline. However, it is important to remember that the guidelines may be cited in any malpractice litigation as evidence of the standard of care. Early diagnosis with prompt treatment with effective antimicrobial therapy is the best way to lower the mortality and morbidity. When prescribing antibiotics, the clinician must realize that the overprescription of antibiotics has led to resistance to antibiotic regimens and the rise of antibiotic-resistant bacteria.

  3. Antibiotic overuse and resistance in dermatology.

    PubMed

    Chon, Susan Y; Doan, Hung Q; Mays, Rana Majd; Singh, Selina M; Gordon, Rachel A; Tyring, Stephen K

    2012-01-01

    Antibiotics have a significant role in dermatology, treating a wide range of diseases, including acne, rosacea, inflammatory skin conditions and skin structure infections, such as cellulitis, folliculitis, carbuncles, and furuncles. Because of their consistent use, utility, and availability, antibiotics are susceptible to overuse within the medical practice, and, specific to this discussion, in the dermatologic setting. The issue of continuously increasing risk of antibiotic resistance remains an important concern to the dermatologist. The scope of this review will be to provide an overview of the common antibiotics used in the dermatologic setting with an emphasis on identifying areas of overuse, reported bacterial resistance, and discussion of clinical management aimed at decreasing antibiotic resistance.

  4. [Searching for new antibiotics--inhibitors of bacterial chromosome replication].

    PubMed

    Trojanowski, Damian; Skut, Patrycja; Hołówka, Joanna; Szafran, Marcin Jan

    2014-01-01

    The excessive and often unreasonable use of antibacterial drugs leads to rise of antibioticresistant strains. To overcome this problem, new antibiotics are searched and the new drug targets are investigated. The proteins involved in replication of bacterial chromosomes seem to be promising candidates for drug targets since they are involved in crucial life pathways and are structurally and/or functionally different from the eukaryotic homologues. Within last few years, a large number of newly developed methods allowed to search among thousands of molecules for the ones that specifically inhibit DNA synthesis in the prokaryotic cell. In this review, we present some of these methods.

  5. Use of antibiotics in plant agriculture.

    PubMed

    Stockwell, V O; Duffy, B

    2012-04-01

    Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment. PMID:22849276

  6. Resistance to Antibiotics Mediated by Target Alterations

    NASA Astrophysics Data System (ADS)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  7. Use of antibiotics in plant agriculture.

    PubMed

    Stockwell, V O; Duffy, B

    2012-04-01

    Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment.

  8. Outer Membrane Permeability and Antibiotic Resistance

    PubMed Central

    Delcour, Anne H.

    2009-01-01

    Summary To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of Gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways. PMID:19100346

  9. Severe hypoxaemia after weaning from cardiopulmonary bypass: a case report.

    PubMed

    Simon, Caterina; Cavarretta, Elena; Capuano, Fabio; Bianchini, Roberto; Roscitano, Antonio; Tonelli, Euclide; Sinatra, Riccardo

    2007-11-01

    Persistence of patent foramen ovale is frequent in adults and usually asymptomatic. We report the case of a patient in whom a patent foramen ovale was diagnosed after weaning from cardiopulmonary bypass and was not recognised preoperatively. Intraoperative transoesophageal echocardiography is pivotal for surgical decision-making and should be performed in all patients undergoing cardiac surgery. PMID:17906486

  10. Thermal Reliability Study of Bypass Diodes in Photovoltaic Modules (Poster)

    SciTech Connect

    Zhang, Z.; Wohlgemuth, J.; Kurtz, S.

    2013-05-01

    This paper presents the result of high-temperature durability and thermal cycling testing and analysis for the selected diodes to study the detail of the thermal design and relative long-term reliability of the bypass diodes used to limit the detrimental effects of module hot-spot susceptibility.

  11. Brachiocephalic vein bypass with sternal reconstruction for symptomatic occlusion.

    PubMed

    O'Donnell, Mark E; Jaroszewski, Dawn E; Coan, Kathryn; Kazmier, Francis J; Money, Samuel R

    2014-11-01

    Complications attributed to central venous stenosis and subsequent thrombosis are increasing in frequency and are most commonly associated with neointimal fibroplasia as well as neoplastic, fibrotic, and traumatic pathologies. We present the successful venous bypass and thoracic wall reconstruction of a 58-year-old female with chronic atypical symptoms secondary to brachiocephalic vein occlusion from congenital thoracic dystrophy.

  12. Cycling firing method for bypass operation of bridge converters

    DOEpatents

    Zabar, Zivan

    1982-01-01

    The bridge converter comprises a number of switching elements and an electronic logic system which regulated the electric power levels by controlling the firing, i.e., the initiation of the conduction period of the switching elements. Cyclic firing of said elements allows the direct current to bypass the alternating current system with high power factor and negligible losses.

  13. Bypassing the Local Rural Hospital for Outpatient Procedures

    ERIC Educational Resources Information Center

    Saunders, Charles; Bellamy, Gail R.; Menachemi, Nir; Chukmaitov, Askar S.; Brooks, Robert G.

    2009-01-01

    Purpose: To assess the amount of local rural hospital outpatient department (HOPD) bypass for outpatient procedures. Methods: We analyzed data on colonoscopies and upper gastrointestinal endoscopies performed in the state of Florida over the period 1997-2004. Findings: Approximately, 53% of colonoscopy and 45% of upper gastrointestinal endoscopy…

  14. Step by Step: Avoiding Spiritual Bypass in 12-Step Work

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Clarke, Philip B.; Graves, Elizabeth G.

    2009-01-01

    With spirituality as a cornerstone, 12-step groups serve a vital role in the recovery community. It is important for counselors to be mindful, however, of the potential for clients to be in spiritual bypass, which likely will undermine the recovery process.

  15. Integral bypass diodes in an amorphous silicon alloy photovoltaic module

    NASA Technical Reports Server (NTRS)

    Hanak, J. J.; Flaisher, H.

    1991-01-01

    Thin-film, tandem-junction, amorphous silicon (a-Si) photovoltaic modules were constructed in which a part of the a-Si alloy cell material is used to form bypass protection diodes. This integral design circumvents the need for incorporating external, conventional diodes, thus simplifying the manufacturing process and reducing module weight.

  16. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES... (incorporated by reference; see 46 CFR 56.01-2). (b) Pipe for bypasses should be at least Schedule 80 seamless, and of a material of the same nominal chemical composition and physical properties as that used...

  17. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES... (incorporated by reference; see 46 CFR 56.01-2). (b) Pipe for bypasses should be at least Schedule 80 seamless, and of a material of the same nominal chemical composition and physical properties as that used...

  18. 21 CFR 870.4350 - Cardiopulmonary bypass oxygenator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass oxygenator. 870.4350 Section 870.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-heart surgery. (b) Classification. Class II (special controls). The special control for this device...

  19. 21 CFR 870.4350 - Cardiopulmonary bypass oxygenator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass oxygenator. 870.4350 Section 870.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-heart surgery. (b) Classification. Class II (special controls). The special control for this device...

  20. 21 CFR 870.3545 - Ventricular bypass (assist) device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ventricular bypass (assist) device. 870.3545 Section 870.3545 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3545...