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The Journal of Antibiotics Mar 2022Drug combinations may have a crucial role in treating infections due to multidrug resistant Acinetobacter spp. One suggested combination is colistin with teicoplanin....
Drug combinations may have a crucial role in treating infections due to multidrug resistant Acinetobacter spp. One suggested combination is colistin with teicoplanin. The effect of colistin on Acinetobacter spp. outer membrane can permit teicoplanin to its target in the cell wall. The aim of this study was to evaluate the synergistic activity of colistin and teicoplanin combination against 29 multidrug resistant isolates of Acinetobacter spp. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed using MIC and time-kill assays. The combination of 1 mg/l colistin and 10 mg/l teicoplanin showed in vitro synergism against all tested Acinetobacter isolates except one (Acinetobacter lowffii). The combination of 1 mg/l colistin and 10 mg/l teicoplanin was bactericidal at 6 h against 100% of Acinetobacter baumannii isolates with no bacterial regrowth at 24 h. The same combination was bactericidal against three out of seven non-baumannii Acinetobacter isolates. The increased concentration of teicoplanin (20 mg/l) was synergistic but still not bactericidal against the four remaining isolates. The combination of colistin and teicoplanin was synergistic against all tested Acinetobacter spp It is therefore recommended that clinical trials are conducted to clarify the therapeutic potential of the combination.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Teicoplanin
PubMed: 35091666
DOI: 10.1038/s41429-022-00509-7 -
International Archives of Allergy and... 2023Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals...
INTRODUCTION
Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders.
METHODS
Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated.
RESULTS
Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes.
CONCLUSION
We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.
Topics: Humans; Neutrophils; Ceftazidime; Teicoplanin; Escherichia coli; Interleukin-8; Anti-Bacterial Agents
PubMed: 37321197
DOI: 10.1159/000530865 -
Basic & Clinical Pharmacology &... Jan 2022Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on... (Meta-Analysis)
Meta-Analysis
Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0-13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0-15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0-12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = -17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.
Topics: Age Factors; Aged; Anti-Bacterial Agents; Humans; Incidence; Kidney Diseases; Middle Aged; Risk Factors; Serum Albumin, Human; Staphylococcal Infections; Teicoplanin
PubMed: 34714598
DOI: 10.1111/bcpt.13679 -
The Journal of Antimicrobial... Nov 2023The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is...
BACKGROUND
The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is gaining interest. As only protein-unbound drug is pharmacologically active, a sensitive assay measuring unbound and total teicoplanin is indispensable for pharmacological research and dose optimization.
OBJECTIVES
To develop and validate a UPLC-MS/MS method to quantify unbound and total teicoplanin in human serum.
METHODS
The developed assay was validated according to the ICH guideline M10 on Bioanalytical Method Validation and study sample analysis. Unbound teicoplanin was obtained by ultrafiltration. The assay was cross-validated with a quantitative microsphere (QMS) immunoassay in a side-by-side comparison using 40 patient samples.
RESULTS
With the developed and validated method, all main teicoplanin components (A2-1, A2-2/A2-3, A2-4/A2-5 and A3-1) can be quantified. Total run time was 5.5 min. Concentration range was 2.5-150 mg/L for total and 0.1-25 mg/L for unbound teicoplanin. Precision (coefficient of variation) and accuracy (bias) of total teicoplanin were 5.97% and 107%, respectively, and 7.17% and 108%, respectively, for unbound teicoplanin.Bland-Altman analysis showed total concentrations measured with the UPLC-MS/MS method were equivalent to the results of the QMS immunoassay. A total of 188 samples from 30 patients admitted to the ICU and haematology department were measured; total concentrations ranged between 2.92 and 98.5 mg/L, and unbound concentrations ranged between 0.37 and 30.7 mg/L.
CONCLUSIONS
The developed method provided rapid, precise and accurate measurement of unbound and total teicoplanin. The developed method is now routinely applied in pharmacological research and clinical practice.
Topics: Humans; Teicoplanin; Chromatography, Liquid; Tandem Mass Spectrometry; Glycopeptides
PubMed: 37757461
DOI: 10.1093/jac/dkad290 -
British Journal of Clinical Pharmacology Apr 2019
Topics: Anaphylaxis; Anesthesia; Anti-Bacterial Agents; Humans; Teicoplanin; Vancomycin
PubMed: 30421516
DOI: 10.1111/bcp.13784 -
Acta Crystallographica. Section D,... Apr 2013Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by...
Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a D-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein-peptide-antibiotic complex. The 2.05 Å resolution MBP-peptide-teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance.
Topics: Anti-Bacterial Agents; Carrier Proteins; Cell Wall; Crystallization; Crystallography, X-Ray; Glycopeptides; Ligands; Micromonosporaceae; Protein Binding; Protein Precursors; Teicoplanin
PubMed: 23519660
DOI: 10.1107/S0907444912050469 -
Scientific Reports Aug 2023Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful...
Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52-6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin.
Topics: Humans; Acute Kidney Injury; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; East Asian People; Sodium Potassium Chloride Symporter Inhibitors; Teicoplanin; Vancomycin; Japan
PubMed: 37633977
DOI: 10.1038/s41598-023-41095-4 -
Scientific Reports Sep 2022Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and...
Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2.
Topics: Anti-Bacterial Agents; Antiviral Agents; COVID-19; Cathepsins; Fluorocarbons; Glycopeptides; Gram-Positive Bacteria; Humans; SARS-CoV-2; Teicoplanin
PubMed: 36163239
DOI: 10.1038/s41598-022-20182-y -
The Journal of Antimicrobial... Jun 2022Dalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus...
OBJECTIVES
Dalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus aureus bacteraemia. Free drug concentration is a critical consideration with prolonged treatment, since free concentration-time profiles may best correlate with therapeutic effect. In support of future clinical trials, we aimed to develop a reliable and reproducible assay for measuring free dalbavancin concentrations.
METHODS
The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200 mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24 h before use with Tween 80 to assess adsorption. Dalbavancin concentrations were analysed from the plasma samples (total) and middle layer samples (free) by LC/MS/MS with isotopically labelled internal standard. Warfarin served as a positive control with known high protein binding.
RESULTS
Measurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during protein binding experiments. By the ultracentrifugation method, dalbavancin's protein binding was estimated to be approximately 99%.
CONCLUSIONS
Dalbavancin has very high protein binding. Given dalbavancin's high protein binding, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure-response studies, especially clinical trials. Future investigations should confirm if the active fraction is best predicted by the free or total fraction.
Topics: Anti-Bacterial Agents; Bacteremia; Humans; Microbial Sensitivity Tests; Polysorbates; Protein Binding; Staphylococcal Infections; Staphylococcus aureus; Tandem Mass Spectrometry; Teicoplanin
PubMed: 35488862
DOI: 10.1093/jac/dkac131 -
Joint Diseases and Related Surgery 2020This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to...
OBJECTIVES
This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to polymethylmethacrylate (PMMA) in vitro.
MATERIALS AND METHODS
This prospective study was conducted between February 2016 and June 2016. Antibiotics were added to PMMA at doses frequently used in clinical practice. The antibiotic doses added were teicoplanin (2 g, 3 g, 4 g), gentamicin (0.5 g, 0.75 g, 1 g), daptomycin (0.5 g.) and vancomycin (2 g, 3 g, 4 g). Standard cement balls (10 mm) were created. Activated L929 mouse fibroblast cell culture was used for incubation. Agar diffusion, Cell Proliferation Kit II (XTT) test and electron microscope investigations were performed to examine biocompatibility and cytotoxicity.
RESULTS
In the cytotoxicity test, teicoplanin at 4 g and daptomycin at 0.5 g doses were observed to cause reductions in viability percentages. The same doses caused 20% and 20-40% cell lysis indices during the agar diffusion test. On electron microscope images, cytotoxic effects in fibroblast cells and involvement with the surface of cement balls were observed.
CONCLUSION
Gentamicin, vancomycin and teicoplanin were observed to be non-toxic and biocompatible at commonly-used dose intervals. Teicoplanin at 4 g and daptomycin at 0.5 g doses were identified to be cytotoxic and not biocompatible. When selecting antibiotics to be added to bone cement, care should be taken that the antibiotic is non-toxic and biocompatible.
Topics: Animals; Anti-Bacterial Agents; Bone Cements; Cells, Cultured; Cytotoxicity Tests, Immunologic; Daptomycin; Dose-Response Relationship, Drug; Gentamicins; Materials Testing; Mice; Teaching Materials; Teicoplanin; Vancomycin
PubMed: 32584733
DOI: 10.5606/ehc.2020.74943