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Daniel Pablo Lew - One of the best experts on this subject based on the ideXlab platform.
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underestimation of vancomycin and Teicoplanin mics by broth microdilution leads to underdetection of glycopeptide intermediate isolates of staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Pierre Vaudaux, Adriana Renzoni, Elzbieta Huggler, Louis Bernard, Tristan Ferry, Daniel Pablo LewAbstract:Broth microdilution was compared with tube macrodilution and a simplified population analysis agar method for evaluating vancomycin and Teicoplanin MICs and detecting glycopeptide-intermediate isolates of Staphylococcus aureus. Modal vancomycin and Teicoplanin MICs recorded by tube macrodilution and the agar plate assay, which both used inocula of 10(6) CFU, were significantly higher (2 microg/ml) against a panel of borderline glycopeptide-susceptible and glycopeptide-intermediate methicillin-resistant S. aureus (MRSA) bloodstream isolates compared to broth microdilution (1 microg/ml). Vancomycin and Teicoplanin MIC distributions by tube macrodilution and agar testing were also markedly different from those evaluated by broth microdilution. The 20-fold-lower inoculum size used for broth microdilution compared to macrodilution and agar MIC assays explained in part, but not entirely, the systematic trend toward lower vancomycin and Teicoplanin MICs by microdilution compared to other methods. Broth microdilution assay led to underdetection of the vancomycin-intermediate S. aureus (VISA) phenotype, yielding only three VISA isolates, for which vancomycin MICs were 4 microg/ml compared to 8 and 19 VISA isolates detected by macrodilution and agar testing, respectively. While macrodilution and agar testing detected 7 and 22 isolates with elevated Teicoplanin MICs (8 microg/ml), respectively, broth microdilution failed to detect such isolates. Detection rates of isolates with elevated vancomycin and Teicoplanin MICs by macrodilution and agar testing assays were higher at 48 h than at 24 h. In conclusion, the sensitivity of broth microdilution MIC testing is questionable for reliable detection and epidemiological surveys of glycopeptide-intermediate resistance in S. aureus isolates.
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identification by genomic and genetic analysis of two new genes playing a key role in intermediate glycopeptide resistance in staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Adriana Renzoni, William L Kelley, Christine Barras, Antoinette Monod, Elzbieta Huggler, Patrice Francois, Jacques Schrenzel, Rene Studer, Pierre Vaudaux, Daniel Pablo LewAbstract:Endogenous, low-level glycopeptide resistance in Staphylococcus aureus results from multifactorial genetic changes. Comparative genomic hybridization analysis revealed the specific deletion of a 1.8-kb segment encompassing two adjacent open reading frames (ORFs) of unknown function in a Teicoplanin-susceptible revertant (strain 14-4rev) compared to the sequence of its isogenic, Teicoplanin-resistant parental strain, strain 14-4. This provocative finding prompted us to perform a detailed genetic analysis of the contribution of this genomic segment to glycopeptide resistance. Despite repeated efforts in our laboratory, 14-4 and 14-4rev have proven refractory to most genetic manipulations. To circumvent this difficulty, we evaluated the contribution of both putative ORFs (designated Teicoplanin resistance factors trfA and trfB) on Teicoplanin resistance in a different, genetically tractable background. Genetic analysis showed that single or double trfA and/or trfB mutations abolished Teicoplanin resistance in two independent Teicoplanin-resistant derivatives of NCTC8325 strain ISP794 generated by two-step passages with the drug. The frequency of Teicoplanin-resistant mutants was markedly decreased by the absence of trfAB in the Teicoplanin-susceptible ISP794 background. Nevertheless, a low rate of Teicoplanin-resistant mutants was selected from ISP794 trfAB, thus indicating an additional contribution of trfAB-independent pathways in the emergence of low-level glycopeptide resistance. Further experiments performed with clinical glycopeptide-intermediate S. aureus isolate NRS3 indicated that the trfAB mutation could affect not only Teicoplanin resistance but also vancomycin and oxacillin resistance. In conclusion, our study demonstrates the key role of two novel loci in endogenous, low-level glycopeptide resistance in S. aureus whose precise molecular functions warrant further investigation.
Daniel W. Armstrong - One of the best experts on this subject based on the ideXlab platform.
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development and validation of a fast hplc method for methyldopa enantiomers using superficially porous particle based macrocyclic glycopeptide stationary phase
Microchemical Journal, 2021Co-Authors: Mariana Da Silva Goncalves, Daniel W. Armstrong, Lucio Mendes Cabral, Eduardo Costa Pinto, Valeria Pereira De SousaAbstract:Abstract Methyldopa is a centrally acting antihypertensive agent, whose pharmacological activity is attributed to the S-α-methyldopa enantiomer. The assessment of enantiomeric purity is an essential quality control test for chiral drugs, as the presence of certain impurities in a drug can interfere with the desired pharmacological effect. The present study was undertaken to evaluate different chiral stationary phases composed of macrocyclic glycopeptides (vancomycin, Teicoplanin and aglycone Teicoplanin) and the use of superficially porous particles for the efficient separation of methyldopa enantiomers. The reversed-phase and polar ionic elution modes were evaluated, with different proportions of solvents and additives. The influence of the flow rate and temperature on the analysis were also evaluated. Different stationary phases in different elution modes exhibited suitable selectivity and fast analysis. Total separation of the enantiomers were obtained with the Teicoplanin and Teicoplanin aglycone stationary phases. The Teicoplanin aglycone column produced excellent resolution values and very fast separation analyzes. The use of the Teicoplanin aglycone chiral stationary phase for the analysis of MDopa enantiomers is innovative and has not yet been explored in the literature. The best method was obtained and validated with Teicoplanin aglycone in the reversed-phase mode using 20mM ammonium acetate buffer pH 4.0/MeOH (20:80), column temperature of 45°C and flow rate of 1.0 mL/min, which presented a total run time less than 5 minutes, a resolution of 5.05 and good peak symmetry. The method can be used in pharmaceutical quality control laboratories and support the stereospecific synthesis of the drug.
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capillary electrophoretic enantiomeric separations using the glycopeptide antibiotic Teicoplanin
Chirality, 1996Co-Authors: Kimber L Rundlett, Mary P Gasper, Eve Y Zhou, Daniel W. ArmstrongAbstract:Teicoplanin is the third in a series of macrocyclic glycopeptide antibiotics that has been evaluated as a chiral selector in capillary electrophoresis (CE). It was used to resolve over 100 anionic racemates at low selector concentrations. Like the other related glycopeptide antibiotics, its enantioselectivity tends to be opposite to that of the ansa-type antibiotics which prefers cationic compounds, particularly amines. Factors that affect Teicoplanin-based enantioseparations include the selector concentration, pH, and the concentration of the organic modifier. The temperature and the nature and strength of the buffer are also known-to affect the stability of the chiral selector as well as the enantioseparation. Teicoplanin exhibited some features that were not noted with the other glycopeptide antibiotics. For example, it aggregates (forms micelles) in aqueous solutions and this influences its enantioselectivity. Unlike the other studied glycopeptides, Teicoplanin precipitates in alcohol-water mixtures. It also binds less to the capillary wall than vancomycin as evidenced by the faster electroosmotic flow velocity. The micellization of Teicoplanin is pH dependent so that the effect of pH on enantiorecognition is more complex for Teicoplanin than for other chiral selectors. Also it is shown that the simple model proposed to explain the role of organic modifiers in cyclodextrin-based CE enantioseparations may not apply to these and other systems. © 1996 Wiley-Liss, Inc.
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a covalently bonded Teicoplanin chiral stationary phase for hplc enantioseparations
Chirality, 1995Co-Authors: Daniel W. Armstrong, Youbang Liu, Helen K EkborgottAbstract:A macrocyclic glycopeptide antibiotic containing a hydrophobic “tail” is covalently attached to silica gel via linkage chains. This material is extensively evaluated as a chiral stationary phase (CSP) for HPLC. The relevant structural features of the Teicoplanin molecule which make it an effective chiral selector are discussed. The Teicoplanin CSP appears to have excellent enantioselectivity for native amino acids, peptides, α-hydroxycarboxylic acids, and a variety of neutral analytes including cyclic amides and amines. Enantio-separations can be achieved in the reversed phase, normal phase, and “polar-organic” modes. This chiral selector is stable and the integrity of the CSP is excellent in all separation modes. Hence it can be considered a highly effective multimodal column. Optimization of these separations is discussed in terms of both selectivity and efficiency. Results indicate that the surface loading of the chiral selector affects all relevant separation parameters. A hypothesis is proposed to explain the enhanced efficiency obtained when using Teicoplanin CSPs with higher surface coverage. It appears that Teicoplanin is a widely applicable, highly effective chiral selector for HPLC enantioseparations. © 1995 Wiley-Liss, Inc.
Evelyne Jacqzaigrain - One of the best experts on this subject based on the ideXlab platform.
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population pharmacokinetics and dosing optimization of Teicoplanin in children with malignant haematological disease
Archives of Disease in Childhood, 2016Co-Authors: Wei Zhao, Daolun Zhang, Thomas Storme, Andre Baruchel, Xavier Decleves, Evelyne JacqzaigrainAbstract:Background Children with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of Teicoplanin in order to define the appropriate dosing regimen in this high-risk population. Methods The current dose of Teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of Teicoplanin was analysed using NONMEM software. The dosing regimen was optimised based on the final model. Results Eighty-five children (age range: 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n=143) were available for analysis. With the current recommended dose of 10 mg/kg/day, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min Conclusions This first population pharmacokinetic study of Teicoplanin in children with haematological malignancy provided evidence-based support to individualize Teicoplanin therapy in this vulnerable population.
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population pharmacokinetics and dosing optimization of Teicoplanin in children with malignant haematological disease
British Journal of Clinical Pharmacology, 2015Co-Authors: Wei Zhao, Daolun Zhang, Thomas Storme, Andre Baruchel, Xavier Decleves, Evelyne JacqzaigrainAbstract:Aim Children with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of Teicoplanin in order to define the appropriate dosing regimen in this high risk population. Methods The current dose of Teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of Teicoplanin were analyzed using nonmem software. The dosing regimen was optimized based on the final model. Results Eighty-five children (age range 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n = 143) were available for analysis. With the current recommended dose of 10 mg kg–1 day–1, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min<10 mg l–1). A two compartment pharmacokinetic model with first order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced Teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg l–1 h 18 mg kg–1 was required for infants, 14 mg kg–1 for children and 12 mg kg–1 for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared with the mg kg–1 basis dose, making the modelling approach an important tool for dosing individualization. Conclusions This first population pharmacokinetic study of Teicoplanin in children with haematological malignancy provided evidence-based support to individualize Teicoplanin therapy in this vulnerable population.
Ritchie H - One of the best experts on this subject based on the ideXlab platform.
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High-throughput enantioseparation of Nα-fluorenylmethoxycarbonyl proteinogenic amino acids through fast chiral chromatography on zwitterionic-Teicoplanin stationary phases
'Elsevier BV', 2020Co-Authors: Mazzoccanti G, Manetto S, Ricci A, Cabri W, Orlandin A, Catani M, Felletti S, Cavazzini A., Ye M, Ritchie HAbstract:In this study, 31 racemates of N \u3b1-FMOC (fluorenylmethoxycarbonyl) amino acids (AAs) with different chemico-physical characteristics (neutral nonpolar, neutral polar, acidic and basic) have been success- fully resolved in fast enantioselective chromatography on recently-developed zwitterionic-Teicoplanin chi- ral stationary phases (CSPs). The CSPs were prepared by covalently bonding the Teicoplanin selector on fully-porous particles of narrow dispersion particle-size distribution (particle diameter 1.9 \u3bcm) and superficially-porous particles (2.0 \u3bcm). Both the zwitterionic-Teicoplanin CSPs have proved to be ideal media for the separation of this important class of compounds. In particular, the zwitterionic CSP pre- pared on superficially-porous particles exhibited superior enantioselectivity and resolution, compared to that made of fully porous particles, in virtue of more favorable thermodynamics. The zwitterionic na- ture of these CSPs allowed avoiding the annoying effect of Donnan\u2019s exclusion of enantiomers from the stationary phase. This effect, on the opposite, was frequently observed on a commercial Teicoplanin CSP (Teicoshell) employed for comparative purposes. Noticeably, on the zwitterionic-Teicoplanin CSPs, by us- ing either acetonitrile- or methanol-rich mobile phases (MPs), it was possible to favor speed over enan- tioresolution and vice versa. This work gives further replies to the request for rapid determination of enantiomeric excess of N \u3b1-FMOC proteinogenic (and non\u2013proteinogenic) AAs, typically used as preferred chiral synthons in the solid-phase synthesis of therapeutic peptides
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High–throughput enantioseparation of Nα–fluorenylmethoxycarbonyl proteinogenic amino acids through fast chiral chromatography on zwitterionic-Teicoplanin stationary phases
'Elsevier BV', 2020Co-Authors: Mazzoccanti G, Manetto S, Ricci A, Cabri W, Orlandin A, Catani M, Felletti S, Cavazzini A., Ye M, Ritchie HAbstract:In this study, 31 racemates of Nα-FMOC (fluorenylmethoxycarbonyl) amino acids (AAs) with different chemico-physical characteristics (neutral nonpolar, neutral polar, acidic and basic) have been successfully resolved in fast enantioselective chromatography on recently-developed zwitterionic-Teicoplanin chiral stationary phases (CSPs). The CSPs were prepared by covalently bonding the Teicoplanin selector on fully-porous particles of narrow dispersion particle-size distribution (particle diameter 1.9 µm) and superficially-porous particles (2.0 µm). Both the zwitterionic-Teicoplanin CSPs have proved to be ideal media for the separation of this important class of compounds. In particular, the zwitterionic CSP prepared on superficially-porous particles exhibited superior enantioselectivity and resolution, compared to that made of fully porous particles, in virtue of more favorable thermodynamics. The zwitterionic nature of these CSPs allowed avoiding the annoying effect of Donnan's exclusion of enantiomers from the stationary phase. This effect, on the opposite, was frequently observed on a commercial Teicoplanin CSP (Teicoshell) employed for comparative purposes. Noticeably, on the zwitterionic-Teicoplanin CSPs, by using either acetonitrile- or methanol-rich mobile phases (MPs), it was possible to favor speed over enantioresolution and vice versa. This work gives further replies to the request for rapid determination of enantiomeric excess of Nα-FMOC proteinogenic (and non–proteinogenic) AAs, typically used as preferred chiral synthons in the solid-phase synthesis of therapeuti
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High–throughput enantioseparation of Nα–fluorenylmethoxycarbonyl proteinogenic amino acids through fast chiral chromatography on zwitterionic-Teicoplanin stationary phases
'Elsevier BV', 2020Co-Authors: Mazzoccanti G, Manetto S, Ricci A, Cabri W, Orlandin A, Catani M, Felletti S, Cavazzini A., Ye M, Ritchie HAbstract:In this study, 31 racemates of Nα-FMOC (fluorenylmethoxycarbonyl) amino acids (AAs) with different chemico-physical characteristics (neutral nonpolar, neutral polar, acidic and basic) have been successfully resolved in fast enantioselective chromatography on recently-developed zwitterionic-Teicoplanin chiral stationary phases (CSPs). The CSPs were prepared by covalently bonding the Teicoplanin selector on fully-porous particles of narrow dispersion particle-size distribution (particle diameter 1.9 µm) and superficially-porous particles (2.0 µm). Both the zwitterionic-Teicoplanin CSPs have proved to be ideal media for the separation of this important class of compounds. In particular, the zwitterionic CSP prepared on superficially-porous particles exhibited superior enantioselectivity and resolution, compared to that made of fully porous particles, in virtue of more favorable thermodynamics. The zwitterionic nature of these CSPs allowed avoiding the annoying effect of Donnan's exclusion of enantiomers from the stationary phase. This effect, on the opposite, was frequently observed on a commercial Teicoplanin CSP (Teicoshell) employed for comparative purposes. Noticeably, on the zwitterionic-Teicoplanin CSPs, by using either acetonitrile- or methanol-rich mobile phases (MPs), it was possible to favor speed over enantioresolution and vice versa. This work gives further replies to the request for rapid determination of enantiomeric excess of Nα-FMOC proteinogenic (and non–proteinogenic) AAs, typically used as preferred chiral synthons in the solid-phase synthesis of therapeutic peptides
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High-throughput enantioseparation of N\u3b1-fluorenylmethoxycarbonyl proteinogenic amino acids through fast chiral chromatography on zwitterionic-Teicoplanin stationary phases
'Elsevier BV', 2020Co-Authors: Mazzoccanti G, Manetto S, Ricci A, Cabri W, Orlandin A, Catani M, Felletti S, Cavazzini A., Ye M, Ritchie HAbstract:In this study, 31 racemates of N \u3b1-FMOC (fluorenylmethoxycarbonyl) amino acids (AAs) with different chemico-physical characteristics (neutral nonpolar, neutral polar, acidic and basic) have been success- fully resolved in fast enantioselective chromatography on recently-developed zwitterionic-Teicoplanin chi- ral stationary phases (CSPs). The CSPs were prepared by covalently bonding the Teicoplanin selector on fully-porous particles of narrow dispersion particle-size distribution (particle diameter 1.9 \u3bcm) and superficially-porous particles (2.0 \u3bcm). Both the zwitterionic-Teicoplanin CSPs have proved to be ideal media for the separation of this important class of compounds. In particular, the zwitterionic CSP pre- pared on superficially-porous particles exhibited superior enantioselectivity and resolution, compared to that made of fully porous particles, in virtue of more favorable thermodynamics. The zwitterionic na- ture of these CSPs allowed avoiding the annoying effect of Donnan\u2019s exclusion of enantiomers from the stationary phase. This effect, on the opposite, was frequently observed on a commercial Teicoplanin CSP (Teicoshell) employed for comparative purposes. Noticeably, on the zwitterionic-Teicoplanin CSPs, by us- ing either acetonitrile- or methanol-rich mobile phases (MPs), it was possible to favor speed over enan- tioresolution and vice versa. This work gives further replies to the request for rapid determination of enantiomeric excess of N \u3b1-FMOC proteinogenic (and non\u2013proteinogenic) AAs, typically used as preferred chiral synthons in the solid-phase synthesis of therapeutic peptides
Flavia Marinelli - One of the best experts on this subject based on the ideXlab platform.
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specificity of induction of glycopeptide antibiotic resistance in the producing actinomycetes
The Journal of Antibiotics, 2018Co-Authors: Elisa Binda, Pamela Cappelletti, Flavia Marinelli, Giorgia Letizia MarconeAbstract:Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by Gram-positive pathogens. It is widely believed that glycopeptide-resistance determinants (van genes) are ultimately derived from the producing actinomycetes. We hereby investigated the relationship between the antimicrobial activity of vancomycin and Teicoplanins and their differential ability to induce van gene expression in Actinoplanes teichomyceticus—the producer of Teicoplanin—and Nonomuraea gerenzanensis—the producer of the Teicoplanin-like A40926. As a control, we used the well-characterized resistance model Streptomyces coelicolor. The enzyme activities of a cytoplasmic-soluble d,d-dipeptidase and of a membrane-associated d,d-carboxypeptidase (corresponding to VanX and VanY respectively) involved in resistant cell wall remodeling were measured in the actinomycetes grown in the presence or absence of subinhibitory concentrations of vancomycin, Teicoplanin, and A40926. Results indicated that actinomycetes possess diverse self-resistance mechanisms, and that each of them responds differently to glycopeptide induction. Gene swapping among Teicoplanins-producing actinomycetes indicated that cross-talking is possible and provides useful information for predicting the evolution of future resistance gene combinations emerging in pathogens.
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resistance to glycopeptide antibiotics in the Teicoplanin producer is mediated by van gene homologue expression directing the synthesis of a modified cell wall peptidoglycan
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Fabrizio Beltrametti, Arianna Consolandi, Lucia Carrano, Francesca Bagatin, Roberta Rossi, Livia Leoni, Elisabetta Zennaro, Enrico Selva, Flavia MarinelliAbstract:Glycopeptide resistance has been studied in detail in enterococci and staphylococci. In these microorganisms, high-level resistance is achieved by replacing the C-terminal d-alanyl-d-alanine of the nascent peptidoglycan with d-alanyl-d-lactate or d-alanyl-d-serine, thus reducing the affinities of glycopeptides for cell wall targets. Reorganization of the cell wall is directed by the expression of the van gene clusters. The identification of van gene homologs in the genomes of several glycopeptide-producing actinomycetes suggests the involvement of a similar self-resistance mechanism to avoid suicide. This report describes a comprehensive study of self-resistance in Actinoplanes teichomyceticus ATCC 31121, the producer of the clinically relevant glycopeptide Teicoplanin. A. teichomyceticus ATCC 31121 showed a MIC of Teicoplanin of 25 μg/ml and a MIC of vancomycin of 90 μg/ml during vegetative growth. The vanH , vanA , and vanX genes of A. teichomyceticus were found to be organized in an operon whose transcription was constitutive. Analysis of the UDP-linked peptidoglycan precursors revealed the presence of UDP-glycomuramyl pentadepsipeptide terminating in d-alanyl-d-lactate. No trace of precursors ending in d-alanyl-d-alanine was detected. Thus, the van gene complex was transcribed and expressed in the genetic background of A. teichomyceticus and conferred resistance to vancomycin and Teicoplanin through the modification of cell wall biosynthesis. During Teicoplanin production (maximum productivity, 70 to 80 μg/ml), the MIC of Teicoplanin remained in the range of 25 to 35 μg/ml. Teicoplanin-producing cells were found to be tolerant to high concentrations of exogenously added glycopeptides, which were not bactericidal even at 5,000 μg/ml.
