Relevant bibliographies by topics / Polymyxin E

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Academic literature on the topic 'Polymyxin E'

Author: Grafiati
Published: 4 June 2021
Last updated: 2 February 2022

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Journal articles on the topic "Polymyxin E"

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Choi, Soo-Keun, Soo-Young Park, Rumi Kim, Seong-Bin Kim, Choong-Hwan Lee, Jihyun F. Kim, and Seung-Hwan Park. "Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis." Journal of Bacteriology 191, no. 10 (May 15, 2009): 3350–58. http://dx.doi.org/10.1128/jb.01728-08.

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ABSTRACT Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added l-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis.
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Lenhard, Bulman, Tsuji, and Kaye. "Shifting Gears: The Future of Polymyxin Antibiotics." Antibiotics 8, no. 2 (April 12, 2019): 42. http://dx.doi.org/10.3390/antibiotics8020042.

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The manuscripts contained in this special edition of Antibiotics represent a current review of the polymyxins as well as highlights from the 3rd International Polymyxin Conference, which was held in Madrid, Spain, April 25 to 26, 2018. The role of the polymyxin antibiotics has evolved over time based on the availability of alternative agents. After high rates of nephrotoxicity caused the drug class to fall out of favor, polymyxins were once against utilized in the 21st century to combat drug-resistant pathogens. However, the introduction of safer agents with activity against drug-resistant organisms has brought the future utility of polymyxins into question. The present review investigates the future niche of polymyxins by evaluating currently available and future treatment options for difficult-to-treat pathogens. The introduction of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin are likely to decrease polymyxin utilization for infections caused by Enterobacteriaceae. Similarly, the availability of ceftolozane-tazobactam will reduce the use of polymyxins to counter multidrug-resistant Pseudomonas aeruginosa. In contrast, polymyxins will likely continue be an important option for combatting carbapenem-resistant Acinetobacter baumannii until better options become commercially available. Measuring polymyxin concentrations in patients and individualizing therapy may be a future strategy to optimize clinical outcomes while minimizing nephrotoxicity. Inhaled polymyxins will continue to be an adjunctive option for pulmonary infections but further clinical trials are needed to clarify the efficacy of inhaled polymyxins. Lastly, safer polymyxin analogs will potentially be an important addition to the antimicrobial armamentarium.
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Dai, Chongshan, Yang Wang, Gaurav Sharma, Jianzhong Shen, Tony Velkov, and Xilong Xiao. "Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment." Antioxidants 9, no. 6 (June 9, 2020): 506. http://dx.doi.org/10.3390/antiox9060506.

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The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens.
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Yun, Bo, Mohammad A. K. Azad, Cameron J. Nowell, Roger L. Nation, Philip E. Thompson, Kade D. Roberts, Tony Velkov, and Jian Li. "Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes." Antimicrobial Agents and Chemotherapy 59, no. 12 (September 21, 2015): 7489–96. http://dx.doi.org/10.1128/aac.01216-15.

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ABSTRACTPolymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity.
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Poirel, Laurent, Aurélie Jayol, and Patrice Nordmann. "Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes." Clinical Microbiology Reviews 30, no. 2 (March 8, 2017): 557–96. http://dx.doi.org/10.1128/cmr.00064-16.

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SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.
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Barth, Natália, Vanessa B. Ribeiro, and Alexandre P. Zavascki. "In VitroActivity of Polymyxin B plus Imipenem, Meropenem, or Tigecycline against KPC-2-Producing Enterobacteriaceae with High MICs for These Antimicrobials." Antimicrobial Agents and Chemotherapy 59, no. 6 (March 23, 2015): 3596–97. http://dx.doi.org/10.1128/aac.00365-15.

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ABSTRACTWe evaluated thein vitroactivity of polymyxin B plus imipenem, meropenem, or tigecycline against six KPC-2-producingEnterobacteriaceaestrains with high MICs for these antimicrobial agents. Polymyxin B with carbapenems, especially meropenem, were the most active combinations forKlebsiella pneumoniaeandEnterobacter cloacaeregardless of the polymyxin B concentration used in the time-kill assay. This combination was also synergistic against twoSerratia marcescensstrains that are intrinsically resistant to polymyxins. Polymyxin B and tigecycline also presented synergistic activity in most experiments.
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Cho, Hyejin, Atanu Naskar, Sohee Lee, Semi Kim, and Kwang-Sun Kim. "A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-Resistant Escherichia coli." Pharmaceutics 13, no. 2 (February 11, 2021): 250. http://dx.doi.org/10.3390/pharmaceutics13020250.

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Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance (mcr-1) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli. The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.
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Jiang, Xukai, Kai Yang, Bing Yuan, Meiling Han, Yan Zhu, Kade D. Roberts, Nitin A. Patil, et al. "Molecular dynamics simulations informed by membrane lipidomics reveal the structure–interaction relationship of polymyxins with the lipid A-based outer membrane of Acinetobacter baumannii." Journal of Antimicrobial Chemotherapy 75, no. 12 (September 10, 2020): 3534–43. http://dx.doi.org/10.1093/jac/dkaa376.

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Abstract Background MDR bacteria represent an urgent threat to human health globally. Polymyxins are a last-line therapy against life-threatening Gram-negative ‘superbugs’, including Acinetobacter baumannii. Polymyxins exert antimicrobial activity primarily via permeabilizing the bacterial outer membrane (OM); however, the mechanism of interaction between polymyxins and the OM remains unclear at the atomic level. Methods We constructed a lipid A-based OM model of A. baumannii using quantitative membrane lipidomics data and employed all-atom molecular dynamics simulations with umbrella sampling techniques to elucidate the structure–interaction relationship and thermodynamics governing the penetration of polymyxins [B1 and E1 (i.e. colistin A) representing the two clinically used polymyxins] into the OM. Results Polymyxin B1 and colistin A bound to the A. baumannii OM by the initial electrostatic interactions between the Dab residues of polymyxins and the phosphates of lipid A, competitively displacing the cations from the headgroup region of the OM. Both polymyxin B1 and colistin A formed a unique folded conformation upon approaching the hydrophobic centre of the OM, consistent with previous experimental observations. Polymyxin penetration induced reorientation of the headgroups of the OM lipids near the penetration site and caused local membrane disorganization, thereby significantly increasing membrane permeability and promoting the subsequent penetration of polymyxin molecules into the OM and periplasmic space. Conclusions The thermodynamics governing the penetration of polymyxins through the outer leaflet of the A. baumannii OM were examined and novel structure–interaction relationship information was obtained at the atomic and membrane level. Our findings will facilitate the discovery of novel polymyxins against MDR Gram-negative pathogens.
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Vaara, Martti, John Fox, Günther Loidl, Osmo Siikanen, Juha Apajalahti, Frank Hansen, Niels Frimodt-Møller, Junya Nagai, Mikihisa Takano, and Timo Vaara. "Novel Polymyxin Derivatives Carrying Only Three Positive Charges Are Effective Antibacterial Agents." Antimicrobial Agents and Chemotherapy 52, no. 9 (June 30, 2008): 3229–36. http://dx.doi.org/10.1128/aac.00405-08.

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ABSTRACT The lack of novel antibiotics against gram-negative bacteria has reinstated polymyxins as the drugs of last resort to treat serious infections caused by extremely multiresistant gram-negative organisms. However, polymyxins are nephrotoxic, and this feature may complicate therapy or even require its discontinuation. Like that of aminoglycosides, the nephrotoxicity of polymyxins might be related to the highly cationic nature of the molecule. Colistin and polymyxin B carry five positive charges. Here we show that novel polymyxin derivatives carrying only three positive charges are effective antibacterial agents. NAB739 has a cyclic peptide portion identical to that of polymyxin B, but in the linear portion of the peptide, it carries the threonyl-d-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). The MICs of NAB739 for 17 strains of Escherichia coli were identical, or very close, to those of polymyxin B. Furthermore, NAB739 was effective against other polymyxin-susceptible strains of Enterobacteriaceae and against Acinetobacter baumannii. At subinhibitory concentrations, it dramatically sensitized A. baumannii to low concentrations of antibiotics such as rifampin, clarithromycin, vancomycin, fusidic acid, and meropenem. NAB739 methanesulfonate was a prodrug analogous to colistin methanesulfonate. NAB740 was the most active derivative against Pseudomonas aeruginosa. NAB7061 (linear portion of the peptide, threonyl-aminobutyryl) lacked direct antibacterial activity but sensitized the targets to hydrophobic antibiotics by factors up to 2,000. The affinities of the NAB compounds for isolated rat kidney brush border membrane were significantly lower than that of polymyxin B.
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Llobet, Enrique, Miguel A. Campos, Paloma Giménez, David Moranta, and José A. Bengoechea. "Analysis of the Networks Controlling the Antimicrobial-Peptide-Dependent Induction of Klebsiella pneumoniae Virulence Factors." Infection and Immunity 79, no. 9 (June 27, 2011): 3718–32. http://dx.doi.org/10.1128/iai.05226-11.

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ABSTRACTAntimicrobial peptides (APs) impose a threat to the survival of pathogens, and it is reasonable to postulate that bacteria have developed strategies to counteract them. Polymyxins are becoming the last resort to treat infections caused by multidrug-resistant Gram-negative bacteria and, similar to APs, they interact with the anionic lipopolysaccharide. Given that polymyxins and APs share the initial target, it is possible that bacterial defense mechanisms against polymyxins will be also effective against host APs. We sought to determine whether exposure to polymyxin will increaseKlebsiella pneumoniaeresistance to host APs. Indeed, exposure ofK. pneumoniaeto polymyxin induces cross-resistance not only to polymyxin itself but also to APs present in the airways. Polymyxin treatment upregulates the expression of the capsule polysaccharide operon and the loci required to modify the lipid A with aminoarabinose and palmitate with a concomitant increase in capsule and lipid A species containing such modifications. Moreover, these surface changes contribute to APs resistance and also to polymyxin-induced cross-resistance to APs. Bacterial loads of lipid A mutants in trachea and lungs of intranasally infected mice were lower than those of wild-type strain. PhoPQ, PmrAB, and the Rcs system govern polymyxin-induced transcriptional changes, and there is a cross talk between PhoPQ and the Rcs system. Our findings support the notion thatKlebsiellaactivates a defense program against APs that is controlled by three signaling systems. Therapeutic strategies directed to prevent the activation of this program could be a new approach worth exploring to facilitate the clearance of the pathogen from the airways.
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Dissertations / Theses on the topic "Polymyxin E"

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Koch, Peer-Joachim. "Untersuchungen zur Wechselwirkung von Polymyxin B mit bakteriellen Lipopolysacchariden." [S.l.] : [s.n.], 1998. http://www.diss.fu-berlin.de/1998/22/index.html.

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Saohin, Wipawee. "Studies on the stability and activity of polymyxin B solutions." Thesis, Robert Gordon University, 1997. http://hdl.handle.net/10059/606.

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The correlation between the chemical stability and the microbiological activity of polymyxin B in phosphate buffer pH 6.0 and in proprietary eye drops was evaluated. High Performance Liquid Chromatography (HPLC) was used to quantify the amount of the main components in samples stored at 43,50,55 and 60°C for a period of 500 h. The data indicated that there are significant differences in chemical stability among the different proprietary eye drops. The accurate decomposition rate constants and shelf-lives (~o) at 4°C of two of the six formulated eye drops and the standard polymyxin B solution stored in glass containers at pH 6.0 were established. It was concluded that microbiological assay by agar diffusion was unsuitable for determining the activity of control polymyxin B in phosphate buffer and polymyxin B in eye drops. Killing time determinations for polymyxin B against cell suspensions of P. aeruginosa NCTC 6750 were consequently used. Thioglycollate broth containingp- aminobenzoic acid (PABA) 0.16 %w/v and magnesium sulphate 1 %w/v was used as an inactivating recovery medium. The effect of preservatives and of second antibacterials contained in the eye drops were tested individually and combined with polymyxin B. Thiomersal 0.001 %w/v, trimethoprim 0.02 %w/v and thiomersal 0.001 %w/v plus trimethoprim 0.02 %w/v did not have an effect on the activity of polymyxin B 2000 U/ml. Neomycin was an exception and at the concentrations in the range 0.0192 to 0.16 %w/v exhibited an antagonistic effect. Chemical interaction between polymyxin B and neomycin could not be detected and it was considered that the inhibitory effect of neomycin may be the result of competition between polymyxin B and neomycin for the same binding sites on the cell surface. Gentamicin is active against P. aeruginosa NCTC 6750 and at concentrations of 0.075 and 0.036 %w/v it exhibited an additive effect with polymyxin B 2000 U/ml against the test organism. The results obtained with the samples stored at 55°C for a period of 500 h demonstrated the critical effect of pH. At a pH of 6.0 microbiological activity and chemical stability appeared optimal. The chemical stability data of five eye drop samples correlated with microbiological activity data. Exceptions were polymyxin B in one eye drop sample and control polymyxin B. These extensively decomposed samples showed good antibacterial activity which appeared to result from the activity of decomposition products. Chemical stability data for standard polymyxin B solution at pH 6.0 also correlated to microbiological activity data over the temperature range of 92 - 115°C. The polymyxin B retained detectable microbiological activity when the amount of PB1 was greater than 20%. It is suggested that the decomposition products which occurred at these higher temperatures did not possess antibacterial activity.
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Rudilla, Mateo Héctor. "Synthetic Polymyxin-based Peptides Against Multidrug Resistant Bacteria: A Therapeutic Option." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668033.

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Pseudomonas aeruginosa and Staphylococcus aureus are nosocomial opportunistic pathogens causing a wide variety of both acute and chronic infections, such as pneumonia, bacteraemia, and urinary tract infections. Immunocompromised patients and those suffering cystic fibrosis show a particularly high susceptibility to infection by these microorganisms. Moreover, the increasing frequency of the isolation of multidrug-resistant bacteria (MDR) is a major cause for concern. Polymyxins are cyclic peptides with antimicrobial action against Gram-negative bacteria that have been available since 1949, although they were left largely unused during the seventies because of their nephrotoxicity and the availability of less toxic antimicrobials to which bacteria had not yet developed resistance. The most known polymyxin is colistin; like other cationic polypeptides, colistin is an amphipathic compound and, it is believed that this amphipathic nature is relevant to its activity against bacteria. Hence, the aim of this thesis was to synthesize antimicrobial peptides inspired in colistin scaffold and explore their antimicrobial activity against multidrug resistant bacteria such as P. aeruginosa and S. aureus, determine possible synergistic interactions with commercial antibiotics and explore their mechanisms of action. Synthesis: The main attempt in this first part was to synthesize peptides in solid phase by the Fmoc/tBu method. After synthesis, peptides were purified by preparative HPLC method and finally, peptides were characterized by MALDI-TOF. Antimicrobial activity: This part focused on the study the antimicrobial capacity of our peptides against multidrug resistant bacteria, specially P. aeruginosa and S. aureus. First peptide (AMP38) showed an acceptable antimicrobial activity against P. aureuginosa. Moreover, several imipenem-resistant P. aeruginosa were tested with AMP38 and imipenem showing a quite considerable synergistic action, both with planktonic and sessile bacteria. In addition, two peptides of the same family (CAMP113 and CAMP207) were tested against S. aureus (both planktonic and sessile) showing a surprising antimicrobial action since Gram- positive bacteria are regarding as naturally resistant to polymyxins. Moreover, these peptides showed an inordinately high selectivity index. Mechanisms of action: The final part of this doctoral thesis focused on an initial exploration of mechanisms of action of peptides above mentioned. Transmission electronic microscopy (TEM) assays were performed in order to elucidate possible interactions between peptides and outer membrane of Gram-negative bacteria. In addition, isothermal titration calorimetry assays were carried out to determine peptide-teichoic acid interactions. Data obtained from these studies are promising, being able to be a therapeutic alternative for infections produced by multidrug resistant bacteria.
Pseudomonas aeruginosa y Staphylococcus aureus son patógenos nosocomiales oportunistas causantes de una gran variedad de infecciones tanto crónicas como agudas, tales como neumonía, bacteriemia e infecciones del tracto urinario. Los pacientes inmunocomprometidos y aquellos que padecen fibrosis quística muestran una susceptibilidad particularmente alta a infectarse por estos microorganismos. Además, la mayor frecuencia de aislamientos de P. aeruginosa y S. aureus resistentes a múltiples fármacos (MDR) es una causa importante de preocupación. Las polimixinas son péptidos cíclicos con capacidad antibiótica contra las bacterias Gram- negativas que han estado disponibles desde 1949, aunque se dejaron en gran parte de usar durante los años setenta debido a su nefrotoxicidad y a la disponibilidad de otros antimicrobianos menos tóxicos a los cuales las bacterias aún no habían desarrollado resistencias. La polimixina más conocida es la colistina e, igual que otros polipéptidos catiónicos es un compuesto anfipático. Se cree que esta naturaleza anfipática es relevante en su actividad contra las bacterias. Por lo tanto, el objetivo de esta tesis fue sintetizar péptidos antimicrobianos inspirados en el esqueleto molecular de la colistina y explorar su actividad antimicrobiana contra bacterias resistentes a múltiples fármacos como P. aeruginosa y S. aureus, determinar posibles interacciones sinérgicas con antibióticos comerciales y realizar un primer acercamiento a sus mecanismos de acción. SÍNTESIS: El principal objetivo de esta primera parte fue sintetizar los péptidos en fase solida por el método Fmoc/tBu. Después de la síntesis, los péptidos se purificaron por el método de HPLC preparativo y, finalmente los péptidos se caracterizaron por MALDI-TOF. ACTIVIDAD ANTIMICROBIANA: Esta parte se centró en el estudio de la capacidad antimicrobiana de nuestros péptidos contra bacterias multirresistentes, especialmente P. aeruginosa y S. aureus. El primer péptido (AMP38) mostró una actividad antimicrobiana aceptable frente a P. aeruginosa. Además, se probaron varias cepas de P. aeruginosa resistentes a imipenem con AMP38 mostrando una actividad sinérgica bastante considerable, tanto en bacterias planctónicas como sésiles. Adicionalmente, se realizaron ensayos con dos péptidos de la misma familia (CAMP113 y CAMP207) frente a S. aureus (tanto planctónicos como sésiles) mostrando una acción antimicrobiana sorprendente, ya que las bacterias Gram-positivas como S. aureus se consideran naturalmente resistentes a las polimixinas. MECANISMOS DE ACCIÓN: La parte final de esta tesis doctoral se centró en una exploración inicial de los mecanismos de acción de los péptidos mencionados anteriormente. Se realizaron ensayos de microscopía electrónica de transmisión (TEM) para aclarar las posibles interacciones entre los péptidos y la membrana externa de las bacterias Gram-negativas. Además, se realizaron ensayos de calorimetría de titulación isotérmica para determinar las interacciones péptido-ácido teicoico. Los datos obtenidos de estos estudios son prometedores, pudiendo ser una alternativa terapéutica para las infecciones producidas por bacterias resistentes a múltiples fármacos.
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Hayashi, Satoko. "Enrichment of Salmonella in poultry for detection by polymyxin-cloth enzyme immunoassay." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0031/MQ27064.pdf.

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Hayashi, Satoko Carleton University Dissertation Biology. "Enrichment of salmonella in poultry for detection by polymyxin-cloth enzyme immunoassay." Ottawa, 1997.

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Onaca, Ozana Simina [Verfasser]. "Functionalized polymer vesicles and interactions with Polymyxin B and derivatives / Ozana Simina Onaca." Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2008. http://d-nb.info/1034967282/34.

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Gatzeva-Topalova, Petia Z. "Biophysical and biochemical characterization of ArnA: A required enzyme in the polymyxin resistance pathway." Diss., Connect to online resource, 2005. http://wwwlib.umi.com/cr/colorado/fullcit?p3190368.

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Wang, Haiyan Carleton University Dissertation Biology. "The Polymyxin-cloth enzyme immunoassay for detection of Salmonellae and its confirmation by polymerase chain reaction." Ottawa, 1995.

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9

Chacra, Nádia Araci Bou. "Suspensão oftálmica de dexametasona e polimixina B: formulação e avaliação da eficácia antimicrobiana de conservantes." Universidade de São Paulo, 1994. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-10072008-164932/.

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Suspensões oftálmicas de dexametasona e polimixina B foram formuladas variando-se os conservantes e combinando 2 concentrações de polissorbato 20 e hidroxipropilmetilcelulose segundo o projeto fatorial 2n. A estabilidade das preparações foi avaliada através de parâmetros físicos, com ênfase na facilidade de rehomogeneização após período de repouso. Das 16 fórmulas foram selecionadas 8 para avaliação da eficácia antimicrobiana do sistema conservante pelo método de desafio, segundo B.P. 88, frente a Pseudomonas aeruginosa, Pseudomonas cepacia e Sthaphylococcus aureus. O ensaio foi precedido de validação da técnica segundo planejamento estatistico two way e split + plot. Os produtos contendo associação clorhexidina e álcool feniletílico atenderam às exigências do compêndio adotado, em oposição aos sistemas contendo cloreto de benzalcônio e EDTA, além de clorhexidina e EDTA, independente da concentração do tensoativo e agente suspensor.
Ophthalmic suspensions of dexametasone and polymyxin B were formulated varying the preservatives and combining two concentrations of polysorbate 20 and hydroxypropylmethylcellulose according to the factorial project 2n. The stability of the preparations were evaluated through physical parameters, with emphasis on the easing of the rehomogenization after a period of rest. 8 of the 16 formula were selected for an evaluation of the antimicrobial efectiveness of the preservative system through the challenge method, according to B.P. 88, against Pseudomonas aeruginosa, Pseudomonas cepacia and Sthaphylococcus aureus. The test was preceded by a validation of the technique according to statistical planning two way and split + splot. The products containing the association of chorhexidine and phenylethyl alcohol complied to the requirements of the adopted compendium, in opposition to the systems containing benzalkonium chloride and EDTA, besides clorhexidine and EDTA, not depending on the concentration of the surfactant and suspending agents.
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Luz, Daniela Inocente. "Heterorresistência e resistência adaptativa à Polimixina B em isolados de Enterobacteriaceae produtores de Klebsiella pneumoniae carbapenemase (KPC)." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/115008.

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As enterobactérias constituem importantes agentes causadores de infecções nosocomiais e possuem alta capacidade em adquirir mecanismos de resistência, inclusive aos carbapenêmicos, que são os principais fármacos utilizados para o tratamento das infecções causadas por esses microrganismos. Assim, as opções terapêuticas tornaram-se restritas e as polimixinas (polimixina B e colistina) voltaram a ser utilizadas na prática clínica. Estudos descrevem a ocorrência de heterorresistência à colistina em enterobactérias. Para a resistência adaptativa, não há relatos atuais para enterobactérias frente à polimixina B. O objetivo deste trabalho foi avaliar a presença destes dois fenômenos de resistência à polimixina B, e sua estabilidade, em isolados de Enterobacteriaceae produtores de Klebsiella pneumoniae carbapenemase (KPC), provenientes de pacientes hospitalizados. A avaliação da heterorresistência foi feita através da análise do perfil populacional (PAP) em 8 isolados de enterobactérias, inoculando-se diluições seriadas dos mesmos em Agar Mueller Hinton contendo diferentes concentrações de polimixina B. Os ensaios de resistência adaptativa foram realizados para os mesmos isolados, submetendo-os ao cultivo em concentrações crescentes de polimixina B. A determinação da estabilidade das subpopulações resistentes foi feita através de passagens dos isolados, por 4 dias consecutivos, em meio livre de antibiótico, e posterior determinação da CIM. A CIM foi reavaliada após 2 e 6 meses de estocagem a -80ºC para os isolados com subpopulações heterorresistentes ou com resistência induzida. Realizou-se técnica de tipagem molecular (PFGE), entre as populações originais e respectivas subpopulações resistentes. Foram avaliados 4 isolados de Klebsiella pneumoniae caracterizadas como 4 clones distintos (K1, K2, K3 e K4), assim como os 3 isolados de Enterobacter cloacae - 2 de clone idêntico (Ec1a e Ec1b), mas com perfis fenotípicos distintos e um clonalmente distinto (Ec2), e uma cepa de Escherichia coli (E1). As CIM iniciais para polimixina B, realizadas por microdiluição em caldo, foram entre 0,0625 e 0,25 μg/mL. Quatro amostras demonstraram heterorresistência (K1, K2, K3 e K4), as quais cresceram nas concentrações 2 (K2), 3 (K1, K4) e 6 μg/mL (K3), e suas CIM após 4 dias de passagem em meio livre de antibiótico se mantiveram altas (K1 4 μg/mL, K2 e K3 16 μg/mL e K4 2 μg/mL). As subpopulações heterorresistentes representaram 0,000087% a 0,00036% de suas populações originais. Três amostras demonstraram resistência adaptativa (K1, K3 e K4), as quais cresceram até concentração 64 μg/mL de polimixina B, e a CIM após 4 dias de passagem em meio livre de antibiótico foi de 32 μg/mL para os três isolados. As CIM mantiveram-se elevadas após 2 e 6 meses de estocagem, tanto para os isolados heterorresistentes como para aqueles da indução da resistência. Por PFGE, verificou-se a relação clonal entre os isolados clínicos iniciais e as subpopulações resistentes. Dos 8 isolados estudados, 4 apresentaram heterorresistência e 3 apresentaram resistência adaptativa. A avaliação da CIM após 2 e 6 meses demonstrou estabilidade das subpopulações, sugerindo o envolvimento de mecanismos moleculares para ambos os fenômenos. Estudos moleculares devem ser realizados para melhor avaliação da heterorresistência e da resistência adaptativa, e melhor compreensão do significado clínico e implicações terapêuticas destes dois fenômenos.
Enterobacteriaceae representants are important agents of nosocomial infections and have high capacity to acquire mechanisms of resistance, including carbapenems, which are the major drugs used for the treatment of infections caused by these microorganisms. Thus, treatment options become limited and polymyxins (polymyxin B and colistin) were again used in clinical practice. Studies describe the occurrence of heteroresistance to colistin in Enterobacteriaceae For adaptive resistance, there are no current reports for those microorganisms front of polymyxin B. The purpose of this study was to evaluate the presence of these two phenomena of resistance to polymyxin B, and its stability in isolates of Enterobacteriaceae Klebsiella pneumoniae carbapenemase (KPC) producing, from hospitalized patients. The evaluation of heteroresistant was made by examining the population profile (PAP) of 8 isolates of enterobacteria inoculating serial dilutions thereof in Mueller Hinton agar containing different concentrations of polymyxin B. The adaptive resistance tests were performed for the same isolates by subjecting them to growing in increasing concentrations of polymyxin B. The determination of the stability of resistant subpopulations was performed after daily sub-cultured in antibiotic-free medium for 4 consecutive days, and subsequent determination of MIC. MICs were reevaluated after 2 and 6 months of storage at -80 ° C for the isolated subpopulations with heteroresistant or induced resistance. We conducted molecular typing technique (PFGE), between the original and resistant subpopulations respective populations. Were evaluated four isolates of Klebsiella pneumoniae characterized as 4 different clones (K1, K2, K3 and K4), as well as the three isolates of Enterobacter cloacae - 2 identical clone (EC1A and Ec1b), but with different and distinct phenotypic profiles (Ec2) and a strain of Escherichia coli (E1). The initial MICs for polymyxin B, performed by broth microdilution, were between 0.0625 and 0.25 μg/mL. Four samples showed heteroresistance (K1, K2, K3 and K4), which grew at concentrations 2 (K2), 3 (K1, K4) and 6 μg/ml (K3), and their MIC after 4 days passage in antibiotic-free medium remained high (K1 4 μg/mL, K2 and K3 16 μg/mL and K4 2μg/mL). The heteroresistant subpopulations represent 0.000087% to 0.00036% of their original populations. Three samples showed adaptive resistance (K1, K3 and K4), which growth in polymyxin B concentration of 64 μg/mL and MIC after 4 days passage in antibiotic-free medium was 32 μg/ml for all three isolates. MICs remained elevated after 2 and 6 months storage, both isolates heteroresistant as those inducing resistance. By PFGE, we evaluated the clonal relationship between the initial clinical isolates and resistant subpopulations. From the 8 isolates studied, 4 isolates demonstrated heteroresistance and 3 showed adaptive resistance. The evaluation of the MIC after 2 and 6 months showed stability of subpopulations, suggesting the involvement of molecular mechanisms for both phenomena. Molecular studies should be conducted to better evaluation of heteroresistance and adaptive resistance, and understanding of clinical significance and therapeutic implications of these phenomena.
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Books on the topic "Polymyxin E"

1

Li, Jian, Roger L. Nation, and Keith S. Kaye, eds. Polymyxin Antibiotics: From Laboratory Bench to Bedside. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0.

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Endotoxemia and endotoxin shock: Disease, diagnosis, and therapy. Basel: Karger, 2010.

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Barr, Kathryn J. Aspects of the host-parasite relationships of polymyxa betae. Norwich: University of East Anglia, 1992.

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McAllister, Stephen Mark. Liposomes as carriers for polymyxins in the treatment of cystic fibrosis lung infections. Birmingham: Aston University. Department of Pharmaceutical and Biological Sciences, 1995.

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Li, Jian, Keith S. Kaye, and Roger L. Nation. Polymyxin Antibiotics: From Laboratory Bench to Bedside. Springer, 2019.

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Book chapters on the topic "Polymyxin E"

1

Gooch, Jan W. "Polymyxin." In Encyclopedic Dictionary of Polymers, 916. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_14535.

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Moffatt, Jennifer H., Marina Harper, and John D. Boyce. "Mechanisms of Polymyxin Resistance." In Advances in Experimental Medicine and Biology, 55–71. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_5.

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Cheah, Soon-Ee, Jian Li, Phillip J. Bergen, and Roger L. Nation. "Polymyxin Pharmacokinetics and Pharmacodynamics." In Methods in Pharmacology and Toxicology, 221–60. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3323-5_10.

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Rigatto, Maria Helena, Diego R. Falci, and Alexandre P. Zavascki. "Clinical Use of Polymyxin B." In Advances in Experimental Medicine and Biology, 197–218. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_14.

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Azad, Mohammad A. K., Roger L. Nation, Tony Velkov, and Jian Li. "Mechanisms of Polymyxin-Induced Nephrotoxicity." In Advances in Experimental Medicine and Biology, 305–19. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_18.

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Velkov, Tony, and Kade D. Roberts. "Discovery of Novel Polymyxin-Like Antibiotics." In Advances in Experimental Medicine and Biology, 343–62. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_20.

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Turnidge, John, Katherine Sei, and Johan Mouton. "Polymyxin Susceptibility Testing and Breakpoint Setting." In Advances in Experimental Medicine and Biology, 117–32. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_9.

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Sánchez, M., and M. Álvarez. "Control of Acinetobacter Outbreaks with Oral Polymyxin." In Infection in the Critically Ill: an Ongoing Challenge, 147–59. Milano: Springer Milan, 2001. http://dx.doi.org/10.1007/978-88-470-2242-3_15.

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Paul, Mical, Oren Zusman, and Leonard Leibovici. "Meta-analysis of Polymyxin Use in Patients." In Advances in Experimental Medicine and Biology, 143–53. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_11.

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Tani, Tohru, Tomoharu Shimizu, Masaji Tani, Hisataka Shoji, and Yoshihiro Endo. "Anti-endotoxin Properties of Polymyxin B-immobilized Fibers." In Advances in Experimental Medicine and Biology, 321–41. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16373-0_19.

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Conference papers on the topic "Polymyxin E"

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Samira da Silva Lazaro, Luiza, LAURA DE OLIVEIRA NASCIMENTO, and JULIANA SOUZA RIBEIRO COSTA. "Polymeric nanocarriers for polymyxin B delivery." In XXV Congresso de Iniciação Cientifica da Unicamp. Campinas - SP, Brazil: Galoa, 2017. http://dx.doi.org/10.19146/pibic-2017-78347.

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Koida, E. S., and A. L. Lagonenko. "Construction and characterization of the deletion mutant of slyA gene in phytopathogenic bacteria Erwinia amylovora." In 2nd International Scientific Conference "Plants and Microbes: the Future of Biotechnology". PLAMIC2020 Organizing committee, 2020. http://dx.doi.org/10.28983/plamic2020.123.

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The regulon of global transcriptional regulator SlyA in bacteria Erwinia amylovora was examined. For that, the ΔslyA mutant was constructed. The mutant showed a decreased level of amylovoran production and polymyxin B resistance.
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DOSNE, A. M., F. DUBOR, and L. CHEDID. "Induction of plasminogen activator inhibitor (PAI) by lipopolysaccharide (LPS)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644862.

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It has been shown that, under culture conditions, human endothelial cells synthetize plasminogen activator inhibitor (PAI) which neutralize urokinase and tissue plasminogen activator.Treatment of human endothelial cells with LPS (50 ngto 10 μg/ml) from S. enteritidis resulted in a dose-dependent increase in PAI production.Fibrinoenzymographic analysis showed that incubation of supernatantfrom LPS-treated cells with urokinase of low and high mol. w. (33.000 and 55.000) led to disappearance of the two urokinase lytic bands and formation of high mol. w. complexes (Mr 93.000 and 107.000). The mol. w. of the urokinase binding factor was calculated to be near 50.000. Polymyxin B and colimycin could suppress this effect of LPS. Injection of LPS (30 ng-30 yg/kg in the rat led to a considerable decrease in the fibrinolytic activity of plasma euglobulins which clot lysis time was prolonged from 55 up to morethan 240 min. This hypofibrinolytic state was associated with PAI detected in euglobulins and in plasma.Large complexes (Mr 80.000-105.000) were formed between exogenous urokinase of low and high mol. w. mixed with post LPS plasma or euglobulins. Polymyxin B and Colimycin could prevent the hypofibrinolytic response to low doses of LPS. These results suggest thatPAI generation in endotoxemia could be due in part to the direct effect of LPS on endothelium.
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Carneiro, Jose, Cindy Freire, Maria Lopes Moreira, Manuela Carneiro, Jose Monteiro Júnior, and Jose Freire. "In silico study of the polymyxin resistance in the genomes of Pseudomonas aeruginosa." In 4th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2018. http://dx.doi.org/10.3390/ecmc-4-05583.

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Selva-O’callaghan, A., C. Vizcaino, J. C. Ruiz-Rodriguez, E. Trallero-Araguás, N. Ramos, C. Berastegui, A. Gil Vila, M. A. Martinez, X. Solanich, and R. Ferrer. "SAT0475 Anti-mda5 (+) clinically amyopathic dermatomyositis-associated rapidly progressive interstitial lung disease: role of hemoperfusion with polymyxin." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.2594.

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Malheiro, Rui Filipe, Vera Marisa Costa, Maria de Lourdes Bastos, and Félix Carvalho. "In vitro toxicity of α-amanitin in human kidney cells and evaluation of protective effect of polymyxin B." In 5th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2019. http://dx.doi.org/10.3390/ecmc2019-06360.

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Chung, Chi Ryang, Kyung Hwa Choi, Se Yeol Lee, Seung Yong Park, Seoung Ju Park, So Ri Kim, Yong Chul Lee, Yang Keun Rhee, and Heung Bum Lee. "Hemoperfusion With Polymyxin B-Immobilized Fiber Column In Patient With Septic Shock And DIC Arising From Nonperforated Appendicitis." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6012.

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Lee, J. H. "The Usefullness of Direct Hemoperfusion with Polymyxin B-Immobilized Fiber in Patients with Acute Exacerbation of Interstitial Lung Disease." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a3069.

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Tachibana, Kazunobu, Yoshikazu Inoue, Yasushi Inoue, Akihide Nishiyama, Chikatoshi Sugimoto, Yoshinobu Matsuda, Taisuke Tsuji, et al. "Serological And Clinical Evaluation Of Acute Exacerbation Of Idiopathic Interstitial Pneumonias Treated By Direct Hemoperfusion With Polymyxin B-immobilized Fiber Column." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a3989.

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Azuma, A., S. Abe, H. Hayashi, T. Ogura, T. Baba, and T. Oh. "Beneficial Effect of Polymyxin B Immobilized Fiber Cartridge Treatment in Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Prospective Multicenter Cohort Study." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1899.

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Reports on the topic "Polymyxin E"

1

Chia, John K. Polymyxin B(PMB)-Specific Monoclonal Antibodies. Fort Belvoir, VA: Defense Technical Information Center, January 1991. http://dx.doi.org/10.21236/ada231817.

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