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Chirality Dec 2022Chiral carbon nanoparticles (CNPs) represent a rapidly evolving area of research for optical and biomedical technologies. Similar to small molecules, applications of...
Chiral carbon nanoparticles (CNPs) represent a rapidly evolving area of research for optical and biomedical technologies. Similar to small molecules, applications of CNPs as well as fundamental relationships between their optical activity and structural asymmetry would greatly benefit from their enantioselective separations by chromatography. However, this technique remains in its infancy for chiral carbon and other nanoparticles. The possibility of effective separations using high performance liquid chromatography (HPLC) with chiral stationary phases remains an open question whose answer can also shed light on the components of multiscale chirality of the nanoparticles. Herein, we report a detailed methodology of HPLC for successful separation of chiral CNPs and establish a path for its future optimization. A mobile phase of water/acetonitrile was able to achieve chiral separation of CNPs derived from L- and D-cysteine denoted as L-CNPs and D-CNPs. Molecular dynamics simulations show that the teicoplanin-based stationary phase has a higher affinity for L-CNPs than for D-CNPs, in agreement with experiments. The experimental and computational findings jointly indicate that chiral centers of chiral CNPs are present at their surface, which is essential for the multiple applications of these chiral nanostructures and equally essential for interactions with biomolecules and circularly polarized photons.
Topics: Stereoisomerism; Teicoplanin; Chromatography, High Pressure Liquid; Carbon; Nanoparticles
PubMed: 36221174
DOI: 10.1002/chir.23507 -
Antimicrobial Agents and Chemotherapy Aug 1995In a randomized crossover study, the protein binding and serum bactericidal activities (SBAs) of vancomycin and teicoplanin against Staphylococcus aureus and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
In a randomized crossover study, the protein binding and serum bactericidal activities (SBAs) of vancomycin and teicoplanin against Staphylococcus aureus and Streptococcus pyogenes were investigated in six healthy volunteers. Total concentrations in serum 1 h postadministration of vancomycin and teicoplanin were 25.5 +/- 2.7 and 10.8 +/- 8.9 mg/liter, respectively; mean free concentrations were 14.6 +/- 2.0 and 0.6 +/- 0.9 mg/liter, respectively. Protein binding for vancomycin was 36.9% +/- 2.87%, and that for teicoplanin was 97.4% +/- 2.6%. SBA determined in pooled human serum at 1 h against S. aureus ranged from 1:8 to 1:32 for both vancomycin and teicoplanin. Against S. pyogenes SBA at 1 h ranged from 1:16 to 1:128 for vancomycin and 1:256 to 1:2,048 for teicoplanin. In vitro kill curve studies showed that vancomycin is slowly bactericidal and that teicoplanin is bacteriostatic. Despite having less in vitro cidal activity against the study isolates and having low or unrecordable levels of free drug in serum, teicoplanin demonstrated a similar or better SBA than vancomycin. SBA was more closely related to the total drug level (r = 0.77 for S. aureus and r = 0.79 for S. pyogenes) than the free level of teicoplanin (r = 0.59 for S. aureus and r = 0.56 for S. pyogenes). The high level of protein binding of teicoplanin did not seem to impair its antibacterial activity as measured by its SBA.
Topics: Adult; Anti-Bacterial Agents; Cross-Over Studies; Female; Humans; Male; Microbial Sensitivity Tests; Protein Binding; Serum Bactericidal Test; Staphylococcus aureus; Streptococcus pyogenes; Teicoplanin; Vancomycin
PubMed: 7486929
DOI: 10.1128/AAC.39.8.1842 -
The Pediatric Infectious Disease Journal Mar 2023Acute bacterial skin and skin structure infections (ABSSSIs) are a significant source of morbidity in children. Dalbavancin, approved for the treatment of adults and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Acute bacterial skin and skin structure infections (ABSSSIs) are a significant source of morbidity in children. Dalbavancin, approved for the treatment of adults and children with ABSSSI, has a well-established safety profile in adults. We report safety and descriptive efficacy data for the treatment of ABSSSI in children.
METHODS
Children with ABSSSI (birth-<18 years old) or sepsis (<3 months old) known/suspected to be caused by susceptible Gram-positive organisms were enrolled in this phase 3, multicenter, open-label, comparator-controlled study (NCT02814916). Children ≥3 months old were randomized 3:3:1 to receive single-dose dalbavancin, 2-dose dalbavancin, or a comparator antibiotic in 4 age cohorts; those <3 months old received single-dose dalbavancin. Clinical response and microbiologic efficacy were evaluated 48-72 hours and 14, 28 and 54 days posttreatment. Bowel flora testing and audiology were collected in a subset of patients at baseline and day 28. Adverse events (AEs) were collected throughout the study.
RESULTS
Treatment-emergent AEs occurred in 7.2%, 9.0% and 3.3% of patients in dalbavancin single-dose, dalbavancin 2-dose and comparator arms, respectively. Three serious AEs occurred in the dalbavancin single-dose arm; no treatment-related AEs, serious AEs, or AEs leading to study discontinuation were reported. Favorable clinical response at 48-72 hours was documented in 97.4%, 98.6% and 89.7% of patients. Safety and efficacy were comparable across age cohorts. The microbiologic intent-to-treat population had comparable clinical response for all baseline pathogens, including methicillin-resistant Staphylococcus aureus .
CONCLUSION
The safety profile of dalbavancin was consistent in children and adults with ABSSSI. No new safety signals were identified.
Topics: Adult; Humans; Child; Infant; Adolescent; Methicillin-Resistant Staphylococcus aureus; Skin Diseases, Bacterial; Teicoplanin; Anti-Bacterial Agents
PubMed: 36476623
DOI: 10.1097/INF.0000000000003798 -
Nephron 1996
Topics: Adult; Anti-Bacterial Agents; Female; Humans; Kidney Transplantation; Leukocyte Count; Platelet Count; Teicoplanin; Thrombocytopenia
PubMed: 8856285
DOI: 10.1159/000189175 -
International Journal of Molecular... Dec 2021Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low...
Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant , and . The expression of (), encoded either in the () glycopeptide antibiotic resistance gene cluster or in the genomes of , as well as and , was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Molecular Docking Simulation; Teicoplanin; Vancomycin
PubMed: 35008521
DOI: 10.3390/ijms23010097 -
Journal of Chromatography. A Sep 2021Enantioseparation of nineteen ß-amino acids has been performed by liquid chromatography on chiral stationary phases based on native teicoplanin and teicoplanin aglycone...
Enantioseparation of nineteen ß-amino acids has been performed by liquid chromatography on chiral stationary phases based on native teicoplanin and teicoplanin aglycone covalently bonded to 2.7 µm superficially porous silica particles. Separations were carried out in unbuffered (water/methanol), buffered [aqueous triethylammonium acetate (TEAA)/methanol] reversed-phase (RP) mode, and in polar-ionic (TEAA containing acetonitrile/methanol) mobile phases. Effects of pH in the RP mode, acid and salt additives, as well as counter-ion concentrations on chromatographic parameters have been studied. The structure of selectands (ß-amino acids possessing aliphatic or aromatic side chains) and selectors (native teicoplanin or teicoplanin aglycone) was found to have a considerable influence on separation performance. Analysis of van Deemter plots and determination of thermodynamic parameters were performed to further explore details of the separation performance.
Topics: Amino Acids; Chromatography, Liquid; Hydrogen-Ion Concentration; Solvents; Teicoplanin
PubMed: 34280793
DOI: 10.1016/j.chroma.2021.462383 -
BMC Infectious Diseases May 2021Many studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus... (Comparative Study)
Comparative Study
BACKGROUND
Many studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving β-lactam antibiotics for MSSA bacteremia.
METHODS
Eighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and β-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion.
RESULTS
Pittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the β-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or β-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving β-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively).
CONCLUSIONS
There were no significant difference in clinical outcomes between initial teicoplanin treatment and β-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Fever; Humans; Logistic Models; Male; Middle Aged; Propensity Score; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Treatment Outcome; beta-Lactams
PubMed: 33980167
DOI: 10.1186/s12879-021-06111-w -
International Journal of Antimicrobial... Oct 2020Dalbavancin is a novel lipoglycopeptide antibiotic with a chemical structure similar to teicoplanin. Dalbavancin has been approved and marketed since 2014 in the USA and... (Review)
Review
Dalbavancin is a novel lipoglycopeptide antibiotic with a chemical structure similar to teicoplanin. Dalbavancin has been approved and marketed since 2014 in the USA and 2015 in the European Union for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) caused by Gram-positive cocci. ABSSSIs include infectious syndromes such as erysipelas, cellulitis, major cutaneous abscesses that require incision and drainage, and both surgical and traumatic wound infections. In current clinical practice, dalbavancin is also used for cardiac implantable electronic device-related soft tissue infection and other prosthetic infections, and therefore when the presence of biofilm is a concern. In this review, we aimed to highlight our experience with the use of dalbavancin for some of the most hard-to-treat Gram-positive infections, as well as a promising strategy in terms of pharmacoeconomic effectiveness. We describe our current real-life clinical practice with the use of dalbavancin, depicting a few representative clinical cases in order to share our own practice in the hospital setting.
Topics: Anti-Bacterial Agents; Biofilms; Discitis; Economics, Pharmaceutical; Endocarditis; Gram-Positive Bacterial Infections; Osteomyelitis; Prosthesis-Related Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Teicoplanin
PubMed: 32721599
DOI: 10.1016/j.ijantimicag.2020.106107 -
Clinical Microbiology and Infection :... Apr 2016In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute... (Review)
Review
In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.
Topics: Ambulatory Care; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Lipoglycopeptides; Organophosphates; Oxazoles; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Teicoplanin; United States; United States Food and Drug Administration
PubMed: 27125562
DOI: 10.1016/S1198-743X(16)30095-7 -
International Journal of Clinical... May 2007The increasing incidence of serious infections because of Gram-positive pathogens and the rising cost in parenteral administration of antimicrobials has inspired the... (Review)
Review
The increasing incidence of serious infections because of Gram-positive pathogens and the rising cost in parenteral administration of antimicrobials has inspired the development of a novel antibiotic. Dalbavancin is the first once a week antibiotic with activity against a broad range of Gram-positive pathogens. A large multicentre, pivotal, Phase III clinical trial, which included 854 patients with complicated skin and skin structure infections, compared 1-2 doses of dalbavancin vs. linezolid. The results demonstrated non-inferiority and a comparable safety profile. With its unique pharmacokinetic profile, ease of use and excellent safety profile, dalbavancin should provide a valuable addition to the armamentarium used to treat infections because of Gram-positive cocci.
Topics: Anti-Bacterial Agents; Drug Interactions; Humans; Research Design; Teicoplanin; Treatment Outcome
PubMed: 17362476
DOI: 10.1111/j.1742-1241.2007.01318.x