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Artykuły w czasopismach na temat "Aminoglycosides"

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Caldwell, Shane J., i Albert M. Berghuis. "Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2″)-Ia". Antimicrobial Agents and Chemotherapy 62, nr 7 (16.04.2018): e00202-18. http://dx.doi.org/10.1128/aac.00202-18.

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ABSTRACTThe APH(2″)-Ia aminoglycoside resistance enzyme forms the C-terminal domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme and confers high-level resistance to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides with substitutions at the N1 position. Previously determined structures of the enzyme with bound aminoglycosides have not indicated how these noncanonical substrates may bind and be modified by the enzyme. We carried out crystallographic studies to directly observe the interactions of these compounds with the aminoglycoside binding site and to probe the means by which these noncanonical substrates interact with the enzyme. We find that APH(2″)-Ia maintains a preferred mode of binding aminoglycosides by using the conserved neamine rings when possible, with flexibility that allows it to accommodate additional rings. However, if this binding mode is made impossible because of additional substitutions to the standard 4,5- or 4,6-disubstituted aminoglycoside architecture, as in lividomycin A or the N1-substituted aminoglycosides, it is still possible for these aminoglycosides to bind to the antibiotic binding site by using alternate binding modes, which explains the low rates of noncanonical phosphorylation activities seen in enzyme assays. Furthermore, structural studies of a clinically observed arbekacin-resistant mutant of APH(2″)-Ia revealed an altered aminoglycoside binding site that can stabilize an alternative binding mode for N1-substituted aminoglycosides. This mutation may alter and expand the aminoglycoside resistance spectrum of the wild-type enzyme in response to newly developed aminoglycosides.
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Zieliński, Michał, Jonathan Blanchet, Sophia Hailemariam i Albert M. Berghuis. "Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa". PLOS ONE 17, nr 8 (3.08.2022): e0269684. http://dx.doi.org/10.1371/journal.pone.0269684.

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Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as many as 15. This study presents the structural and kinetic results describing a promiscuous aminoglycoside acetyltransferase AAC(3)-IIIa. This enzyme has been crystallized in ternary complex with coenzyme A and 4,5- and 4,6-disubstituted aminoglycosides. We have followed up this work with kinetic characterization utilizing a panel of diverse aminoglycosides, including a next-generation aminoglycoside, plazomicin. Lastly, we observed an alternative binding mode of gentamicin in the aminoglycoside binding site, which was proven to be a crystallographic artifact based on mutagenesis.
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Childs-Kean, Lindsey M., Kristy M. Shaeer, Sheeba Varghese Gupta i Jonathan C. Cho. "Aminoglycoside Allergic Reactions". Pharmacy 7, nr 3 (29.08.2019): 124. http://dx.doi.org/10.3390/pharmacy7030124.

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Aminoglycosides are antimicrobial agents that are primarily used for infections caused by Gram-negative pathogens. The purpose of this article is to review the allergic reactions reported in the published literature to aminoglycoside antibiotics. A thorough PubMed search was conducted and excluded non-allergic adverse reactions to aminoglycosides. Allergic reactions to aminoglycosides occur infrequently, but can include cutaneous reactions as well as systemic reactions, including anaphylaxis. Of the evaluated aminoglycosides, gentamicin had the most reported allergic reactions, including the most reports of anaphylaxis, followed by tobramycin, and then amikacin. Most reports of allergic reactions occurred in patients who had a prior exposure to some dosage form of an aminoglycoside. Cross-reactivity among aminoglycosides is common and occurs due to the similarities in their chemical structures. Desensitization protocols to tobramycin have been described in the literature.
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Rivetti, Serena, Alberto Romano, Stefano Mastrangelo, Giorgio Attinà, Palma Maurizi i Antonio Ruggiero. "Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients". Pharmaceuticals 16, nr 10 (25.09.2023): 1353. http://dx.doi.org/10.3390/ph16101353.

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Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides. Aminoglycosides are fundamental in the treatment of numerous infectious conditions at neonatal and pediatric age. In childhood, normal auditory function ensures adequate neurocognitive and social development. Hearing damage from aminoglycosides can therefore strongly affect the normal growth of the child. This review describes the molecular mechanisms of aminoglycoside-related ototoxicity and analyzes the risk factors and the potential otoprotective strategies in pediatric patients.
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Uneme, Mio, Kazuya Ishikawa, Kazuyuki Furuta, Atsuko Yamashita i Chikara Kaito. "Overexpression of the flagellar motor protein MotB sensitizes Bacillus subtilis to aminoglycosides in a motility-independent manner". PLOS ONE 19, nr 4 (26.04.2024): e0300634. http://dx.doi.org/10.1371/journal.pone.0300634.

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The flagellar motor proteins, MotA and MotB, form a complex that rotates the flagella by utilizing the proton motive force (PMF) at the bacterial cell membrane. Although PMF affects the susceptibility to aminoglycosides, the effect of flagellar motor proteins on the susceptibility to aminoglycosides has not been investigated. Here, we found that MotB overexpression increased susceptibility to aminoglycosides, such as kanamycin and gentamicin, in Bacillus subtilis without affecting swimming motility. MotB overexpression did not affect susceptibility to ribosome-targeting antibiotics other than aminoglycosides, cell wall-targeting antibiotics, DNA synthesis-inhibiting antibiotics, or antibiotics inhibiting RNA synthesis. Meanwhile, MotB overexpression increased the susceptibility to aminoglycosides even in the motA-deletion mutant, which lacks swimming motility. Overexpression of the MotB mutant protein carrying an amino acid substitution at the proton-binding site (D24A) resulted in the loss of the enhanced aminoglycoside-sensitive phenotype. These results suggested that MotB overexpression sensitizes B. subtilis to aminoglycosides in a motility-independent manner. Notably, the aminoglycoside-sensitive phenotype induced by MotB requires the proton-binding site but not the MotA/MotB complex formation.
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Chiang, Wen-Chi, Martin Nilsson, Peter Østrup Jensen, Niels Høiby, Thomas E. Nielsen, Michael Givskov i Tim Tolker-Nielsen. "Extracellular DNA Shields against Aminoglycosides in Pseudomonas aeruginosa Biofilms". Antimicrobial Agents and Chemotherapy 57, nr 5 (11.03.2013): 2352–61. http://dx.doi.org/10.1128/aac.00001-13.

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ABSTRACTWithin recent years, it has been established that extracellular DNA is a key constituent of the matrix of microbial biofilms. In addition, it has recently been demonstrated that DNA binds positively charged antimicrobials such as aminoglycosides and antimicrobial peptides. In the present study, we provide evidence that extracellular DNA shields against aminoglycosides inPseudomonas aeruginosabiofilms. We show that exogenously supplemented DNA integrates intoP. aeruginosabiofilms and increases their tolerance toward aminoglycosides. We provide evidence that biofilms formed by a DNA release-deficientP. aeruginosaquorum-sensing mutant are more susceptible to aminoglycoside treatment than wild-type biofilms but become rescued from the detrimental action of aminoglycosides upon supplementation with exogenous DNA. Furthermore, we demonstrate that exposure to lysed polymorphonuclear leukocytes, which are thought to be a source of extracellular DNA at sites of infections, increases the tolerance ofP. aeruginosabiofilms toward aminoglycosides. Although biofilm-associated aminoglycoside tolerance recently has been linked to extracellular DNA-mediated activation of thepmrgenes, we demonstrate that the aminoglycoside tolerance mediated by the presence of extracellular DNA is not caused by activation of thepmrgenes in ourP. aeruginosabiofilms but rather by a protective shield effect of the extracellular DNA.
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Ban, Yeon Hee, Myoung Chong Song, Je Won Park i Yeo Joon Yoon. "Minor components of aminoglycosides: recent advances in their biosynthesis and therapeutic potential". Natural Product Reports 37, nr 3 (2020): 301–11. http://dx.doi.org/10.1039/c9np00041k.

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This Highlight covers the recent advances in the biosynthetic pathways of aminoglycosides including their minor components, together with the therapeutic potential for minor aminoglycoside components and semi-synthetic aminoglycosides.
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Kim, Ock-Hwa, Byoung Soo Kwon, Minkyu Han, Younsuck Koh, Woo-Sung Kim, Jin-Woo Song, Yeon-Mok Oh i in. "Association Between Duration of Aminoglycoside Treatment and Outcome of Cavitary Mycobacterium avium Complex Lung Disease". Clinical Infectious Diseases 68, nr 11 (15.09.2018): 1870–76. http://dx.doi.org/10.1093/cid/ciy804.

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Abstract Background Although aminoglycosides are recommended for cavitary Mycobacterium avium complex lung disease (MAC-LD), the optimal duration of treatment is unclear. We investigated the association between duration of aminoglycoside treatment and outcomes in cavitary MAC-LD. Methods Among patients diagnosed with macrolide-susceptible cavitary MAC-LD between 2000 and 2013, 101 who received treatment up to August 2017 with a regimen containing aminoglycosides were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. The duration of aminoglycoside treatment was at the discretion of the attending physician. Results A total of 75 patients (74.3%) were administered aminoglycosides for ≥3 months (median 164 days), whereas the remaining 26 patients (25.7%) received treatment for <3 months (median 59 days). The overall treatment success rate was 63.4% (64/101). Patients treated with aminoglycosides for ≥3 months had a significantly higher success rate than those treated for <3 months (69.3% vs 46.2%; P = .035). Multivariate analysis revealed that aminoglycoside treatment for ≥3 months was a significant factor for treatment success (adjusted odds ratio, 3.602; 95% confidence interval, 1.249–10.390; P = .018). Recurrence occurred in 8 (22.9%) of 35 patients who were followed up for at least 3 years after the end of treatment; all 8 patients received aminoglycosides for ≥3 months. Conclusions Patients with cavitary MAC-LD treated with aminoglycosides for ≥3 months showed higher treatment success rate than those treated for <3 months. However, treatment for ≥3 months was not associated with the development of recurrence.
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Fong, Desiree H., i Albert M. Berghuis. "Structural Basis of APH(3′)-IIIa-Mediated Resistance to N1-Substituted Aminoglycoside Antibiotics". Antimicrobial Agents and Chemotherapy 53, nr 7 (11.05.2009): 3049–55. http://dx.doi.org/10.1128/aac.00062-09.

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ABSTRACT Butirosin is unique among the naturally occurring aminoglycosides, having a substituted amino group at position 1 (N1) of the 2-deoxystreptamine ring with an (S)-4-amino-2-hydroxybutyrate (AHB) group. While bacterial resistance to aminoglycosides can be ascribed chiefly to drug inactivation by plasmid-encoded aminoglycoside-modifying enzymes, the presence of an AHB group protects the aminoglycoside from binding to many resistance enzymes, and hence, the antibiotic retains its bactericidal properties. Consequently, several semisynthetic N1-substituted aminoglycosides, such as amikacin, isepamicin, and netilmicin, were developed. Unfortunately, butirosin, amikacin, and isepamicin are not resistant to inactivation by 3′-aminoglycoside O-phosphotransferase type IIIa [APH(3′)-IIIa]. We report here the crystal structure of APH(3′)-IIIa in complex with an ATP analog, AMPPNP [adenosine 5′-(β,γ-imido)triphosphate], and butirosin A to 2.4-Å resolution. The structure shows that butirosin A binds to the enzyme in a manner analogous to other 4,5-disubstituted aminoglycosides, and the flexible antibiotic-binding loop is key to the accommodation of structurally diverse substrates. Based on the crystal structure, we have also constructed a model of APH(3′)-IIIa in complex with amikacin, a commonly used semisynthetic N1-substituted 4,6-disubstituted aminoglycoside. Together, these results suggest a strategy to further derivatize the AHB group in order to generate new aminoglycoside derivatives that can elude inactivation by resistance enzymes while maintaining their ability to bind to the ribosomal A site.
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Trylska, Joanna, i Marta Kulik. "Interactions of aminoglycoside antibiotics with rRNA". Biochemical Society Transactions 44, nr 4 (15.08.2016): 987–93. http://dx.doi.org/10.1042/bst20160087.

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Aminoglycoside antibiotics are protein synthesis inhibitors applied to treat infections caused mainly by aerobic Gram-negative bacteria. Due to their adverse side effects they are last resort antibiotics typically used to combat pathogens resistant to other drugs. Aminoglycosides target ribosomes. We describe the interactions of aminoglycoside antibiotics containing a 2-deoxystreptamine (2-DOS) ring with 16S rRNA. We review the computational studies, with a focus on molecular dynamics (MD) simulations performed on RNA models mimicking the 2-DOS aminoglycoside binding site in the small ribosomal subunit. We also briefly discuss thermodynamics of interactions of these aminoglycosides with their 16S RNA target.
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Rozprawy doktorskie na temat "Aminoglycosides"

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Quader, Sabina, i N/A. "Selective Synthetic Modification of Aminoglycosides for Drug Targeting to Tuberculosis". Griffith University. School of Biomolecular and Physical Sciences, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20071024.151619.

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The work presented in this thesis details the synthetic modification of the clinically important aminoglycoside antibiotics, neomycin B, paromomycin and tobramycin. We sought to modify aminoglycosides by attaching lipophilic groups, including fatty acids and steroids, with a view to improving the bacterial membrane permeability of these species, and ultimately their efficacy in the treatment of tuberculosis. Our initial synthetic strategy involved direct and specific functionalization of the singular primary hydroxyl group of the aminoglycoside antibiotic neomycin B, with lipophilic groups containing carboxylic acid functions via Mitsunobu esterification. Although, direct and selective Mitsunobu acylation of the primary hydroxyl group proved unsuccessful in the case of the pseudo tetrasaccharide neomycin B, the Mitsunobu reaction did however result in selective chemistry elsewhere in the molecule and this has been exploited for modification of the ido (ring IV) and streptamine (ring II) ring systems. Under carefully controlled conditions, the Mitsunobu reaction has been used for the selective dehydration of the ido ring, to give the talo epoxide, and, under more forcing Mitsunobu dehydration conditions, an aziridine function has been introduced into the streptamine moiety. Both the epoxide and the epoxide-aziridine neomycin building blocks were utilized as synthons in subsequent chemical transformations. Seventeen novel neomycin derivatives featuring modification of ring IV and/or ring II were obtained using this approach. Explicit structural elucidation of all the synthetic intermediates and the final products was achieved using high temperature NMR spectroscopy. Direct and specific functionalization of the singular primary hydroxyl group at the C5 position of the ribose ring (ring III) of neomycin B was achieved, via a procedure based in part on selective tripsylation of the C5III primary hydroxyl group of neomycin B reported previously, followed by subsequent displacement of the tripsyl group by azide. Terminal alkyne containing lipophilic esters were then successfully attached to the ribose residue of neomycin B via Cu(I)-mediated azide-alkyne coupling reaction. In addition to the isolation of two fortuitous, new and versatile synthons i.e. monoanhydro neomycin and bis-anhydro neomycin for modification of ring IV and ring II of neomycin, a third synthon based on neomycin framework, allowing stepwise modification of ring III and ring IV was designed and synthesized. This synthon features an epoxide function in the ido ring, and a protected amine function at the C5 position of the ribose ring. Examples of the stepwise use of this synthon for further synthetic modification of the neomycin framework were demonstrated. Fourteen novel neomycin derivatives featuring modification of ring III and /or ring IV were obtained and characterized. Regioselective Mitsunobu esterification of the single primary hydroxyl group of the pseudo trisaccharide tobramycin was utilized successfully to link a variety of hydrophobic esters with tobramycin. Nine lipophilic tobramycin derivatives with significant structural diversity were synthesised and characterized. In a preliminary study, the applicability of the Mitsunobu dehydration reaction for the regioselective formation of an epoxide ring in the ido moiety of the pseudo tetrasaccharide aminoglycoside antibiotic paromomycin system was confirmed. The regioselective ring-opening of the derived epoxide with azide at C3IV of paromomycin was also successfully demonstrated. In total, forty-two new potential aminoglycoside antibiotics have been synthesized and characterized.
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Quader, Sabina. "Selective Synthetic Modification of Aminoglycosides for Drug Targeting to Tuberculosis". Thesis, Griffith University, 2007. http://hdl.handle.net/10072/367086.

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The work presented in this thesis details the synthetic modification of the clinically important aminoglycoside antibiotics, neomycin B, paromomycin and tobramycin. We sought to modify aminoglycosides by attaching lipophilic groups, including fatty acids and steroids, with a view to improving the bacterial membrane permeability of these species, and ultimately their efficacy in the treatment of tuberculosis. Our initial synthetic strategy involved direct and specific functionalization of the singular primary hydroxyl group of the aminoglycoside antibiotic neomycin B, with lipophilic groups containing carboxylic acid functions via Mitsunobu esterification. Although, direct and selective Mitsunobu acylation of the primary hydroxyl group proved unsuccessful in the case of the pseudo tetrasaccharide neomycin B, the Mitsunobu reaction did however result in selective chemistry elsewhere in the molecule and this has been exploited for modification of the ido (ring IV) and streptamine (ring II) ring systems. Under carefully controlled conditions, the Mitsunobu reaction has been used for the selective dehydration of the ido ring, to give the talo epoxide, and, under more forcing Mitsunobu dehydration conditions, an aziridine function has been introduced into the streptamine moiety. Both the epoxide and the epoxide-aziridine neomycin building blocks were utilized as synthons in subsequent chemical transformations. Seventeen novel neomycin derivatives featuring modification of ring IV and/or ring II were obtained using this approach. Explicit structural elucidation of all the synthetic intermediates and the final products was achieved using high temperature NMR spectroscopy. Direct and specific functionalization of the singular primary hydroxyl group at the C5 position of the ribose ring (ring III) of neomycin B was achieved, via a procedure based in part on selective tripsylation of the C5III primary hydroxyl group of neomycin B reported previously, followed by subsequent displacement of the tripsyl group by azide. Terminal alkyne containing lipophilic esters were then successfully attached to the ribose residue of neomycin B via Cu(I)-mediated azide-alkyne coupling reaction. In addition to the isolation of two fortuitous, new and versatile synthons i.e. monoanhydro neomycin and bis-anhydro neomycin for modification of ring IV and ring II of neomycin, a third synthon based on neomycin framework, allowing stepwise modification of ring III and ring IV was designed and synthesized. This synthon features an epoxide function in the ido ring, and a protected amine function at the C5 position of the ribose ring. Examples of the stepwise use of this synthon for further synthetic modification of the neomycin framework were demonstrated. Fourteen novel neomycin derivatives featuring modification of ring III and /or ring IV were obtained and characterized. Regioselective Mitsunobu esterification of the single primary hydroxyl group of the pseudo trisaccharide tobramycin was utilized successfully to link a variety of hydrophobic esters with tobramycin. Nine lipophilic tobramycin derivatives with significant structural diversity were synthesised and characterized. In a preliminary study, the applicability of the Mitsunobu dehydration reaction for the regioselective formation of an epoxide ring in the ido moiety of the pseudo tetrasaccharide aminoglycoside antibiotic paromomycin system was confirmed. The regioselective ring-opening of the derived epoxide with azide at C3IV of paromomycin was also successfully demonstrated. In total, forty-two new potential aminoglycoside antibiotics have been synthesized and characterized.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Faculty of Science, Environment, Engineering and Technology
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Sherwin, Catherine M. T., i n/a. "Clinical pharmacology of aminoglycosides in neonates". University of Otago. Dunedin School of Medicine, 2009. http://adt.otago.ac.nz./public/adt-NZDU20090821.160736.

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The aims of this Thesis were to investigate early markers of neonatal sepsis and patient-factors affecting the pharmacokinetics and pharmacodynamics (PKPD) of aminoglycosides in the treatment of neonatal sepsis. A prospective cohort study of neonates commenced on gentamicin for suspected sepsis was performed between 1 July 2002 and 28 February 2007. Receiver operator characteristics (ROC) plots were used to assess potential markers of sepsis against culture positive sepsis. When sepsis was first suspected, the most promising tests were interleukin (IL) IL-12(p70) with an area under the curve (95% CI) for the ROC of 0.74 (0.63-0.86), and which (with a cut-off at 75 pg/mL) had a sensitivity (95% CI) of 28% (20-36%) and a specificity of 98% (96-100%). IL-10 had a sensitivity of 17% (10-23%) and a specificity of 99% (97-100%). Retrospective studies of neonates treated with gentamicin, amikacin and netilmicin for suspected sepsis were used to identify patient characteristics that affected aminoglycoside PKPD properties. Population PK modelling used NONMEM� v.5 to determine aminoglycoside clearance (CL) and volume of distribution (V). Logistic regression was used to examine the treatment outcome measures (serum peak and trough concentrations and ototoxicity). Simulations of new dosing regimens were undertaken for netilmicin and amikacin using MATLAB� The final gentamicin PK covariate model gave CL = 0.097 x (current weight/2)[1.3] x (postnatal age/7)[0.29] and V = 1.07 x (current weight/2)[0.8]+ (confirmed sepsis) x 0.13. A 10% increase in gentamicin V in neonates with sepsis was estimated. For amikacin, 17 (35%) of 49 episodes of confirmed sepsis met the treatment failure criteria from 12 (15%) individual patients. The final amikacin PK covariate model was CL = 0.23 x (current weight/2)[0.691] x (postmenstrual age/40)[3.23] and V = 0.957 x (current weight/2)[0.89]. PD analysis determined risk factors linked to hearing impairment in neonates treated with amikacin included: co-medication with vancomycin, high C-reactive protein concentration and low gestational age. Simulation of a new amikacin dosing regimen recommended: 15 mg/kg 36 hourly, 14 mg/kg 24 hourly, and 15 mg/kg 24 hourly, for neonates [less than or equal to] 28 weeks, 29 to 36 weeks, and [greater than or equal to] 37 postmenstrual age, respectively. For netilmicin, the final PK covariate model was CL = 0.192 x (current weight/2)[1.35] x (postmenstrual age/40)[1.03], V = 1.5 x (current weight/2)[0.3]. Simulation of a new optimal dosing regimen for netilmicin was: 5 mg/kg 36 hourly, 5 mg/kg 24 hourly, 6 mg/kg 24 hourly, and 7 mg/kg 24 hourly, for neonates [less than or equal to] 27, 28 to 30, 31 to 33, and [greater than or equal to] 34 weeks postmenstrual age, respectively. IV infusions representing gentamicin administration to neonates of 2.5 kg and 0.5 kg in the NICU setting (30 minutes gentamicin infusion then a 30 minute saline flush) showed the larger neonates received 80% of the drug within 60 minutes. This increased to 90-95% by 75 minutes. However, in extremely low birth weight neonates (0.5 kg), only 60% of the intended gentamicin dose was delivered by 60 minutes (70% by 75 minutes). In conclusion: IL-12(p70) and IL-10 were identified as promising diagnostic tests to confirm sepsis in neonates. Confirmed sepsis caused a 10% increase in V of gentamicin in neonates, suggesting larger initial dosages (mg/kg) are required for effective treatment of neonates with sepsis. Aminoglycoside clearance in neonates is predominantly affected by current weight, postmenstrual age or postnatal age. Adjusting netilmicin and amikacin doses based on current weight, and dosing interval based on both postmenstrual age and current weight improves drug efficacy. Identification of co-medication with vancomycin, low gestational age, and high C-reactive protein during treatment with amikacin increases risk of hearing impairment. The delivery of gentamicin administrated by IV infusion is substantially extended in extremely low birth weight neonates.
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Buranaphalin, Sawanya. "Pharmaceutical analysis of polyamines and aminoglycosides". Thesis, University of Bath, 2009. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500693.

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Methods for polyamine derivatization with a panel of extrinsic fluorophores followed by HPLC with fluorescence and UV absorption detection have been developed. Four fluorophores were examined using polyamines and aminoglycosides. o-Phthalaldehyde (OPA) and fluorescamine are selective fluorophores that only react with primary amines; 9- fluorenylmethyl chloroformate (FMOC Cl) and dansyl chloride react with both primary and secondary amines. Reaction and HPLC conditions were optimized with each of the above fluorophores using a series of model mono- and diamines and then applied to natural and semi-synthetic polyamines. The amines that have been investigated are natural di- and polyamines: putrescine, cadaverine, spermidine, spermine, thermospermine, aminoglycosides: kanamycin, paramomycin, neomycin, and synthetic polyamine conjugates e.g. N⁴,N⁹-dioleoylspermine, N¹-cholesteryl spermine carbamate. The resultant derivatives were confirmed by off-line high resolution electrospray ionization mass spectrometry (HR ESI MS). The results show that the synthesis of polyamine derivatives in quantitative yield depends on the time of reaction, the temperature and the ratio of fluorophore reagent. Linearity of derivatization was calculated and regression coefficients ranged from 0.968 to 0.999 with good reproducibility. HR ESI MS analysis of the reaction products demonstrated complete derivatization of both primary and secondary amino groups with dansyl and FMOC fluorescence derivatives and of primary amine groups for OPA and fluorescamine derivatives. Under the ionization conditions used the dansyl derivatives showed, in addition to monovalent ions [M+H]⁺, divalent cations [M+2H]²⁺ because this chromophore contains a basic amine that can be easily protonated. FMOC derivatives gave prominent [M+Na]⁺ ions. The OPA derivatization reaction is rapid, but the products have poor stability. The derivatization with fluorescamine gave multiple products with glucosamine due to the presence of a chiral centre in the fluorophore. The relative quantum yields of the polyaminefluorophore derivatives were examined to determine the effect of intramolecular fluorescence quenching. Dansylation is the fluorescent derivatization method of choice.
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Rayet, Arjinder Kaur. "Analysis of the aminoglycosides neomycin and streptomycin". Thesis, Loughborough University, 1998. https://dspace.lboro.ac.uk/2134/26869.

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The aim of the study was the determination of neomycin and streptomycin aminoglycoside antibiotics in bovine kidney tissue at trace levels. The aminoglycosides contain no chromophore making detection difficult by conventional spectrophotometric detection and are highly polar making separation from tissue samples a multistep clean-up procedure.
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Shrestha, Sanjib K. "Novel Aminoglycosides: Bioactive Properties and Mechanism of Action". DigitalCommons@USU, 2013. https://digitalcommons.usu.edu/etd/2073.

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Fungicide discovery is relatively neglected when compared to the investment in the development of antibacterial, antiviral, and anti-cancer therapeutics. Due to extensive use of currently available fungicides in agriculture and medicine, resistance is emerging among plant and animal pathogenic fungi. This necessitates the search for novel antifungal agents that are effective and less toxic and that do not promote resistance. FG08 and K20 are novel aminoglycoside analogs synthesized from kanamycin B and A, respectively. The antimicrobial properties of these analogs were tested in vitro against a wide range of agriculturally and clinically important fungal pathogens. Both compounds showed broad-spectrum antifungal properties, but they did not inhibit bacteria such as Escherichia coli and Staphylococcus aureus. The hemolytic activities and cytotoxicities of FG08 and K20 were also evaluated. They showed no toxicity or lowered toxicity against animal cells at their antifungal minimum inhibitory concentrations (MICs). The fungicidal mechanisms of action of FG08 and K20 were examined using intact cells of Saccharomyces cerevisiae, Cryptococcus neoformans, hyphae of Fusarium graminearum. FG08 and K20 caused SYTOX Green dye uptake and potassium efflux by intact cells, indicating that they increase plasma membrane permeability. FG08 and K20 also caused leakage of pre-loaded calcein from small unilamellar vesicles (SUVs) composed of lipids that mimic the lipid composition of fungal membranes, further suggesting increased membrane permeability as their mechanism of action. The synergistic interactions of K20 with six azoles (such as itraconazole, and fluconazole) were investigated against a wide array of fungal pathogens. The in vitro results revealed strong synergy between K20 and azoles against plant and human pathogenic fungi. Their synergies were furthered confirmed by time kill curves and disk diffusion methods. In conclusion, FG08 and K20 are broad-spectrum antifungal agents that do not inhibit bacteria. At their antifungal MICs, they are not toxic to animal cells, but they inhibit fungi by interacting with the fungal plasma membrane, leading to pore formation. These novel aminoglycoside analogs appear attractive for applications as fungicides in agriculture and medicine.
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Xi, Hongjuan. "Thermodynaimic [sic] study of nucleic acids recognition by aminoglycosides". Connect to this title online, 2007. http://etd.lib.clemson.edu/documents/1202499410/.

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Dahl, Russell Scott. "Synthesis of aminoglycosides and amino-C-glycosides from glycals /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3158462.

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Patwardhan, Anjali A. "Mechanistic studies of copper(II) aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme". Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1060971975.

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Thesis (Ph. D.)--Ohio State University, 2003.
Title from first page of PDF file. Document formatted into pages; contains xv, 91 p.; also includes graphics (some col.) Includes bibliographical references (p. 82-91). Available online via OhioLINK's ETD Center
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Pinto, Nelson Schumacher John. "Pharmacokinetics of Amikacin after a single intravenous dose". Auburn, Ala., 2009. http://hdl.handle.net/10415/1848.

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Książki na temat "Aminoglycosides"

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Abbas, Ali. Approaches to novel aminoglycosides. Manchester: University of Manchester, 1995.

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Parsons, Paul Philip. Aminoglycosides and renal electrolyte handling. Manchester: University of Manchester, 1995.

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Kinzy, Willy. Die Trichloracetimidatmethode zur Synthese von Glycokonjugaten mit Glucosamin als Komponente. Konstanz: Hartung-Gorre, 1986.

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Brown, Thomas E. R. A clinical pharmacokinetic monitoring manual for theophylline, vancomycin and aminoglycosides. Toronto: St. Michael's Hospital, 1989.

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Ihnat, Richard G. Aminoglycoside-associated dizziness in geriatric patients: A prospective observation cohort study. [S.l: s.n.], 1991.

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Rudis, Maria. Efficacy of medical housestaff education by a pharmacist on aminoglycoside prescribing. Toronto: [s.n.], 1990.

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Arya, D. P. Aminoglycoside antibiotics: From chemical biology to drug discovery. Hoboken, N.J: Wiley-Interscience, 2007.

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Alipour, Misagh. Evaluation of bactericidal activity of liposomal aminoglycosides against strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. Sudbury, Ont: Laurentian University, 2005.

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Audiovestibular toxicity of drugs. Boca Raton, Fla: CRC Press, 1989.

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Duff, W. Patrick. Antibiotic use in obstetrics and gynecology. Philadelphia: W.B. Saunders Co., 1992.

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Części książek na temat "Aminoglycosides"

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Finberg, Robert W., i Roy Guharoy. "Aminoglycosides". W Clinical Use of Anti-infective Agents, 57–62. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4614-1068-3_9.

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Bhandari, Prasan. "Aminoglycosides". W Pharmacology Mind Maps for Medical Students and Allied Health Professionals, 545–50. Boca Raton, FL : CRC Press/Taylor & Francis, 2020.: CRC Press, 2019. http://dx.doi.org/10.1201/9780429023859-63.

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Bulik, Catharine C., Charles H. Nightingale i David P. Nicolau. "Aminoglycosides". W Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics, 201–22. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-0-387-75613-4_9.

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Armstrong, Eliana S., Corwin F. Kostrub, Robert T. Cass, Heinz E. Moser, Alisa W. Serio i George H. Miller. "Aminoglycosides". W Antibiotic Discovery and Development, 229–69. Boston, MA: Springer US, 2011. http://dx.doi.org/10.1007/978-1-4614-1400-1_7.

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Dalhoff, A. "Aminoglycosides". W Antibiotics and Chemotherapy, 120–23. Basel: KARGER, 1997. http://dx.doi.org/10.1159/000059302.

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Finberg, Robert W., i Roy Guharoy. "Aminoglycosides". W Clinical Use of Anti-infective Agents, 75–80. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-67459-5_10.

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Veyssier, P., i A. Bryskier. "Aminocyclitol Aminoglycosides". W Antimicrobial Agents, 453–69. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815929.ch16.

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Decker, Brian S., i Bruce A. Molitoris. "Aminoglycosides and vancomycin". W Clinical Nephrotoxins, 267–92. Boston, MA: Springer US, 2008. http://dx.doi.org/10.1007/978-0-387-84843-3_12.

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Berkov-Zrihen, Yifat, i Micha Fridman. "Synthesis of Aminoglycosides". W Modern Synthetic Methods in Carbohydrate Chemistry, 161–90. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2013. http://dx.doi.org/10.1002/9783527658947.ch6.

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Verpooten, Gert A., Paul M. Tulkens i William M. Bennett. "Aminoglycosides and vancomycin". W Clinical Nephrotoxins, 105–20. Dordrecht: Springer Netherlands, 1998. http://dx.doi.org/10.1007/978-94-015-9088-4_7.

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Streszczenia konferencji na temat "Aminoglycosides"

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WANG, QI, i PETER S. STEYGER. "TRAFFICKING OF AMINOGLYCOSIDES INTO ENDOLYMPH IN VIVO". W Proceedings of the 10th International Workshop on the Mechanics of Hearing. WORLD SCIENTIFIC, 2009. http://dx.doi.org/10.1142/9789812833785_0072.

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Huang, Lei, i Zhixiong Guo. "Nano Filtration and Sensing of Aminoglycosides Using Whispering-Gallery Mode Resonators". W ASME 2012 Third International Conference on Micro/Nanoscale Heat and Mass Transfer. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/mnhmt2012-75174.

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For the first time optical WGM micro resonator embedded in a microelectrofluidic system with integrated functions in sensing and nano filtration was proposed. Aminoglycosides were considered as the analyte molecules. The filtration process and analyte concentration were traced by measuring the WGM resonance frequency shift. A correlation between the frequency shift, and the analyte feed concentration and the applied voltage gradient was obtained, which reveals a linear relationship between the resonance frequency shift and the analyte concentration and an exponential growth with the applied voltage gradient. The applied voltage gradient influences the filtration capability through its effect on adsorption and desorption processes. The second-order WGM was found to be able to provide a higher sensitivity as compared with the first-order. The WGM sensor was found to function at pico Molar concentration.
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Wu, Lingzhi, Lihua Tang, Xiaofei Hu i Dong Hu. "Thermodynamic studies of the interaction of phosphatidylinositol phosphate with aminoglycosides antibiotics". W 2011 International Conference on Remote Sensing, Environment and Transportation Engineering (RSETE). IEEE, 2011. http://dx.doi.org/10.1109/rsete.2011.5966304.

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"Phenotypes and genotypes of Aminoglycosides resistance in Klebsiella pneumonia isolated from Borujerd hospitals". W International Conference on Medicine, Public Health and Biological Sciences. CASRP Publishing Company, Ltd. Uk, 2016. http://dx.doi.org/10.18869/mphbs.2016.123.

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Blanco Garcia, P., M. Anton Martinez, S. Maganto Garrido, M. Montero Lázaro, A. Pariente Junquera, A. Fijó Prieto, C. Guitián Bermejo, C. Mesa Arevalo i MT Sánchez Sánchez. "4CPS-119 A real-life study of pharmacokinetic monitoring: nephrotoxic impact of aminoglycosides and vancomycin". W 28th EAHP Congress, Bordeaux, France, 20-21-22 March 2024. British Medical Journal Publishing Group, 2024. http://dx.doi.org/10.1136/ejhpharm-2024-eahp.223.

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Muntyan, Victoria S., Mariia E. Vladimirova, Alexey M. Afonin, Alexey N. Muntyan i Marina L. Roumiantseva. "ANALYSIS OF SALT-SENSITIVE AND SALT-TOLERANT SINORHIZOBIUM MELILOTI STRAINS USING DNA MICROARRAY, PHENOTYPE MICROARRAY AND GENOME MINING TECHNIQUES". W 23rd SGEM International Multidisciplinary Scientific GeoConference 2023. STEF92 Technology, 2023. http://dx.doi.org/10.5593/sgem2023/6.1/s25.15.

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Nodule bacteria increase the resistance of host plants to abiotic stress factors; however, the role of the genetic potential of rhizobia in the formation of productive salt-tolerant plant-microbial symbiosis remains underestimated. The aim of the study was to evaluate the pool of genes responsible for the salt tolerance of the alfalfa microsymbiont, Sinorhizobium meliloti, using the DNA microarray technique, phenotype microarray (PM), NGS and NNGS-technologies and genome mining (antismash 5.0). As a result of the analysis of the genomes of strains contrastingly different in salt tolerance, it was found that nucleotide changes in genes in salt-sensitive strains occurred significantly more often in genomic islands located on the chromosome. The genome of the salttolerant strain contained at least 25 genes involved in the DNA replication and repair and metabolism of nucleotides (1 KEGG group), amino acids (8 KEGG groups), lipids (2 KEGG groups), and carbohydrates (4 KEGG groups). Genomic analysis of the saltsensitive strain revealed 2 unique secondary metabolite biosynthesis gene clusters on pSymB (NAGGN) and on the cryptic plasmid (phosphonate and ectoine), while both gene clusters are involved in the synthesis of substances that involved in osmotic stress response. In the genomes of salt-tolerant phenotype strains, changes occurred in a smaller number of genes belonging to other KEGG groups. Two unique clusters of antibiotic synthesis, the class of macrolides (conglobactin) and aminoglycosides (2- deoxystreptamine), as well as an additional cluster of synthesis of thioamitide RiPPs, were identified on the chromosome of a salt-tolerant strain using genome mining. The use of the PM technique made it possible to show that the salt-tolerant strain is resistant to 10 beta-lactam antibiotics, 7 cephalosporins, 9 aminoglycoside antibiotics, 5 tetracyclines, polymyxin E, and 16 antibiotics that block the synthesis of DNA, RNA, enzymes and proteins, while the salt-sensitive strain grew up on alternative sources of organic sulfur and carbon. The revealed characteristics of strains that contrastingly differ in stress tolerance are promising for their use in agrobiotechnology.
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Kaye, Stephen, Keri McLean, Daniel M. Foulkes, Marta Sloniecka, Dominic Byrne, Atikah S. Haneef, Craig Winstanley, Neil G. Berry i David G. Fernig. "P-18 Impact of fluoroquinolones and aminoglycosides on P. aeruginosa virulence factor production and cytotoxicity". W 2022 Proceedings of the Bowman Club Meeting, 25th March. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/bmjophth-2022-bcm.15.

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Antunes, Marcelo M., Adriana A. Antunes i Galba M. Campos - Takaki. "Importance of High Levels Detention by Enterococcus Resistance (HLR) to Aminoglycosides in the Treatment of Serious Infections from Hospital". W Proceedings of the II International Conference on Environmental, Industrial and Applied Microbiology (BioMicroWorld2007). WORLD SCIENTIFIC, 2009. http://dx.doi.org/10.1142/9789812837554_0104.

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Huang, David, Stanley Jordan, Arlene Reisman i Ozlem Equils. "Renal Function Among Patients With Nosocomial Pneumonia Treated With Linezolid Or Vancomycin With And Without Concomitant Aminoglycosides By Diabetes Status". W 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.a4750.

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"PREVALENCE OF BACTERIAL AND PARASITIC URINARY TRACT INFECTION AMONG ASYMPTOMATIC FEMALES IN RURAL COMMUNITIES OF OGBOMOSO." W International Conference on Public Health and Humanitarian Action. International Federation of Medical Students' Associations - Jordan, 2022. http://dx.doi.org/10.56950/eklu3082.

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Urinary tract infection is one of the most important infection causing serious diseases in tropical and sub- tropical countries of Africa. Several factors have been associated with the high prevalence of urinary tract infections in Nigeria. This study was carried out to determine the urinary tract infection status among two hundred and forty (240) asymptomatic females over a period of six weeks (March to April 2022) among 240 females between the 20-50 years of age at Iluju and Saamo village, Ogbomoso, Oyo state, Nigeria. Two hundred and forty urine samples were collected from the females. The mid- stream urine samples collected were examined microscopically for the presence of parasites, after which they were cultured, biochemical findings and antimicrobial susceptibility tests were also carried out. Out of the 240 samples, only 1(0.4%) was found positive for parasitic infection. 34(14.2%) were found to harbour Escherichia coli, 18(7.5%) were positive for Proteus mirabilis, 8(3.3%) were infected by Klebsiella pneumonia, 45(18.8%) had Staphylococcus aureus. Prevalence was found to be higher in women of reproductive age 21-25years (78%) than women above 40years (10.5%). The antimicrobial suspectibility profile indicates that the fluoroquinlonones were the most active antibacterial agents followed by the aminoglycosides. Trimethorim, oxacillim, amoxicillin showed very poor activity. This may be due to long term use of these drugs. The socio- economic status as well as the hygiene practice of the women influence the prevalence of urinary tract infections. Most of the women 134(55.8%) were aware about Urinary tract infection and 106 (44.2%) were unaware. Thus, the high infection rate among asymptomatic females in these villages were due to poor hygiene, lack of good toilet facilities and poor socio- economic status. Keywords: Bacterial, Parasitic, Rural, Ogbomoso, Females, hygiene
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Raporty organizacyjne na temat "Aminoglycosides"

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Ilgu, Muslum. Deciphering the details of RNA aminoglycoside interactions: from atomistic models to biotechnological applications. Office of Scientific and Technical Information (OSTI), styczeń 2012. http://dx.doi.org/10.2172/1048539.

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McCarthy, Noel, Eileen Taylor, Martin Maiden, Alison Cody, Melissa Jansen van Rensburg, Margaret Varga, Sophie Hedges i in. Enhanced molecular-based (MLST/whole genome) surveillance and source attribution of Campylobacter infections in the UK. Food Standards Agency, lipiec 2021. http://dx.doi.org/10.46756/sci.fsa.ksj135.

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This human campylobacteriosis sentinel surveillance project was based at two sites in Oxfordshire and North East England chosen (i) to be representative of the English population on the Office for National Statistics urban-rural classification and (ii) to provide continuity with genetic surveillance started in Oxfordshire in October 2003. Between October 2015 and September 2018 epidemiological questionnaires and genome sequencing of isolates from human cases was accompanied by sampling and genome sequencing of isolates from possible food animal sources. The principal aim was to estimate the contributions of the main sources of human infection and to identify any changes over time. An extension to the project focussed on antimicrobial resistance in study isolates and older archived isolates. These older isolates were from earlier years at the Oxfordshire site and the earliest available coherent set of isolates from the national archive at Public Health England (1997/8). The aim of this additional work was to analyse the emergence of the antimicrobial resistance that is now present among human isolates and to describe and compare antimicrobial resistance in recent food animal isolates. Having identified the presence of bias in population genetic attribution, and that this was not addressed in the published literature, this study developed an approach to adjust for bias in population genetic attribution, and an alternative approach to attribution using sentinel types. Using these approaches the study estimated that approximately 70% of Campylobacter jejuni and just under 50% of C. coli infection in our sample was linked to the chicken source and that this was relatively stable over time. Ruminants were identified as the second most common source for C. jejuni and the most common for C. coli where there was also some evidence for pig as a source although less common than ruminant or chicken. These genomic attributions of themselves make no inference on routes of transmission. However, those infected with isolates genetically typical of chicken origin were substantially more likely to have eaten chicken than those infected with ruminant types. Consumption of lamb’s liver was very strongly associated with infection by a strain genetically typical of a ruminant source. These findings support consumption of these foods as being important in the transmission of these infections and highlight a potentially important role for lamb’s liver consumption as a source of Campylobacter infection. Antimicrobial resistance was predicted from genomic data using a pipeline validated by Public Health England and using BIGSdb software. In C. jejuni this showed a nine-fold increase in resistance to fluoroquinolones from 1997 to 2018. Tetracycline resistance was also common, with higher initial resistance (1997) and less substantial change over time. Resistance to aminoglycosides or macrolides remained low in human cases across all time periods. Among C. jejuni food animal isolates, fluoroquinolone resistance was common among isolates from chicken and substantially less common among ruminants, ducks or pigs. Tetracycline resistance was common across chicken, duck and pig but lower among ruminant origin isolates. In C. coli resistance to all four antimicrobial classes rose from low levels in 1997. The fluoroquinolone rise appears to have levelled off earlier and among animals, levels are high in duck as well as chicken isolates, although based on small sample sizes, macrolide and aminoglycoside resistance, was substantially higher than for C. jejuni among humans and highest among pig origin isolates. Tetracycline resistance is high in isolates from pigs and the very small sample from ducks. Antibiotic use following diagnosis was relatively high (43.4%) among respondents in the human surveillance study. Moreover, it varied substantially across sites and was highest among non-elderly adults compared to older adults or children suggesting opportunities for improved antimicrobial stewardship. The study also found evidence for stable lineages over time across human and source animal species as well as some tighter genomic clusters that may represent outbreaks. The genomic dataset will allow extensive further work beyond the specific goals of the study. This has been made accessible on the web, with access supported by data visualisation tools.
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Jorgensen, Frieda, Andre Charlett, Craig Swift, Anais Painset i Nicolae Corcionivoschi. A survey of the levels of Campylobacter spp. contamination and prevalence of selected antimicrobial resistance determinants in fresh whole UK-produced chilled chickens at retail sale (non-major retailers). Food Standards Agency, czerwiec 2021. http://dx.doi.org/10.46756/sci.fsa.xls618.

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Campylobacter spp. are the most common bacterial cause of foodborne illness in the UK, with chicken considered to be the most important vehicle for this organism. The UK Food Standards Agency (FSA) agreed with industry to reduce Campylobacter spp. contamination in raw chicken and issued a target to reduce the prevalence of the most contaminated chickens (those with more than 1000 cfu per g chicken neck skin) to below 10 % at the end of the slaughter process, initially by 2016. To help monitor progress, a series of UK-wide surveys were undertaken to determine the levels of Campylobacter spp. on whole UK-produced, fresh chicken at retail sale in the UK. The data obtained for the first four years was reported in FSA projects FS241044 (2014/15) and FS102121 (2015 to 2018). The FSA has indicated that the retail proxy target for the percentage of highly contaminated raw whole retail chickens should be less than 7% and while continued monitoring has demonstrated a sustained decline for chickens from major retailer stores, chicken on sale in other stores have yet to meet this target. This report presents results from testing chickens from non-major retailer stores (only) in a fifth survey year from 2018 to 2019. In line with previous practise, samples were collected from stores distributed throughout the UK (in proportion to the population size of each country). Testing was performed by two laboratories - a Public Health England (PHE) laboratory or the Agri-Food & Biosciences Institute (AFBI), Belfast. Enumeration of Campylobacter spp. was performed using the ISO 10272-2 standard enumeration method applied with a detection limit of 10 colony forming units (cfu) per gram (g) of neck skin. Antimicrobial resistance (AMR) to selected antimicrobials in accordance with those advised in the EU harmonised monitoring protocol was predicted from genome sequence data in Campylobacter jejuni and Campylobacter coli isolates The percentage (10.8%) of fresh, whole chicken at retail sale in stores of smaller chains (for example, Iceland, McColl’s, Budgens, Nisa, Costcutter, One Stop), independents and butchers (collectively referred to as non-major retailer stores in this report) in the UK that are highly contaminated (at more than 1000 cfu per g) with Campylobacter spp. has decreased since the previous survey year but is still higher than that found in samples from major retailers. 8 whole fresh raw chickens from non-major retailer stores were collected from August 2018 to July 2019 (n = 1009). Campylobacter spp. were detected in 55.8% of the chicken skin samples obtained from non-major retailer shops, and 10.8% of the samples had counts above 1000 cfu per g chicken skin. Comparison among production plant approval codes showed significant differences of the percentages of chicken samples with more than 1000 cfu per g, ranging from 0% to 28.1%. The percentage of samples with more than 1000 cfu of Campylobacter spp. per g was significantly higher in the period May, June and July than in the period November to April. The percentage of highly contaminated samples was significantly higher for samples taken from larger compared to smaller chickens. There was no statistical difference in the percentage of highly contaminated samples between those obtained from chicken reared with access to range (for example, free-range and organic birds) and those reared under standard regime (for example, no access to range) but the small sample size for organic and to a lesser extent free-range chickens, may have limited the ability to detect important differences should they exist. Campylobacter species was determined for isolates from 93.4% of the positive samples. C. jejuni was isolated from the majority (72.6%) of samples while C. coli was identified in 22.1% of samples. A combination of both species was found in 5.3% of samples. C. coli was more frequently isolated from samples obtained from chicken reared with access to range in comparison to those reared as standard birds. C. jejuni was less prevalent during the summer months of June, July and August compared to the remaining months of the year. Resistance to ciprofloxacin (fluoroquinolone), erythromycin (macrolide), tetracycline, (tetracyclines), gentamicin and streptomycin (aminoglycosides) was predicted from WGS data by the detection of known antimicrobial resistance determinants. Resistance to ciprofloxacin was detected in 185 (51.7%) isolates of C. jejuni and 49 (42.1%) isolates of C. coli; while 220 (61.1%) isolates of C. jejuni and 73 (62.9%) isolates of C. coli isolates were resistant to tetracycline. Three C. coli (2.6%) but none of the C. jejuni isolates harboured 23S mutations predicting reduced susceptibility to erythromycin. Multidrug resistance (MDR), defined as harbouring genetic determinants for resistance to at least three unrelated antimicrobial classes, was found in 10 (8.6%) C. coli isolates but not in any C. jejuni isolates. Co-resistance to ciprofloxacin and erythromycin was predicted in 1.7% of C. coli isolates. 9 Overall, the percentages of isolates with genetic AMR determinants found in this study were similar to those reported in the previous survey year (August 2016 to July 2017) where testing was based on phenotypic break-point testing. Multi-drug resistance was similar to that found in the previous survey years. It is recommended that trends in AMR in Campylobacter spp. isolates from retail chickens continue to be monitored to realise any increasing resistance of concern, particulary to erythromycin (macrolide). Considering that the percentage of fresh, whole chicken from non-major retailer stores in the UK that are highly contaminated (at more than 1000 cfu per g) with Campylobacter spp. continues to be above that in samples from major retailers more action including consideration of interventions such as improved biosecurity and slaughterhouse measures is needed to achieve better control of Campylobacter spp. for this section of the industry. The FSA has indicated that the retail proxy target for the percentage of highly contaminated retail chickens should be less than 7% and while continued monitoring has demonstrated a sustained decline for chickens from major retailer stores, chicken on sale in other stores have yet to meet this target.
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