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Chromatographic behavior of new chiral stationary phases (CSPs) Chiral-T and Chiral-V with teicoplanin and vancomycin antibiotics grafted onto superficially porous silica particles was studied in relation to dipeptide (DP) stereoisomers. The unbuffered water-methanol solutions were used as mobile phases (MPs). The effects of physical properties and molecular structure of analytes and selectors on retention and separation of DP stereoisomers are discussed herein. Chiral-T was evinced to exhibit high enantioselectivity, with highest α values attaining 16.5, 18.8 and 20.4 for Gly-Leu, dd/ll-Phe-Leu and ld/dl-Ala-Ala. At this point, Chiral-V did not exhibit enantioselectivity towards DP stereoisomers. The effect of MP composition on retention and enantioseparation of DPs was investigated. Lipophilicity of DPs was found to be an essential factor in the dependence of their retention vs. methanol concentration in МPs. Lipophobic DPs were eluted more quickly by water-rich solvents, with lipophilic DPs exhibiting an asymmetric U-shaped, or a descending dependence of retention factor vs. the methanol percentage on Chiral-T or Chiral-V, respectively. A theoretical model taking into account interaction of both solvents of a binary MP with both an analyte and adsorption sites was successfully applied so as to approximate and interpret the dependences of DP retention (monotonic and U-shaped) vs. a modifier content in MP. Water molecules were evinced to predominantly participate in competitive adsorption with DP molecules. The model predicted better solvation of lipophilic DPs by methanol and better solvation of lipophobic DPs by water. An attempt was made to verify the possibility of modeling by molecular docking the processes occurring during interaction between DP stereoisomers and CSPs, including consideration of the influence of competitive binding of eluent molecules in selector cavity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena Reshetova reports financial support was provided by Russian Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Vancomycin, a glycopeptide antibiotic used for Gram-positive bacterial infections, has been linked with drug reaction with eosinophilia and systemic symptoms (DRESS) in HLA-A*32:01-expressing individuals. This is associated with activation of T lymphocytes, for which glycolysis has been isolated as a fuel pathway following antigenic stimulation. However, the metabolic processes that underpin drug-reactive T-cell activation are currently undefined and may shed light on the energetic conditions needed for the elicitation of drug hypersensitivity or tolerogenic pathways. Here, we sought to characterise the immunological and metabolic pathways involved in drug-specific T-cell activation within the context of DRESS pathogenesis using vancomycin as model compound and drug-reactive T-cell clones (TCCs) generated from healthy donors and vancomycin-hypersensitive patients., Methods: CD4+ and CD8+ vancomycin-responsive TCCs were generated by serial dilution. The Seahorse XFe 96 Analyzer was used to measure the extracellular acidification rate (ECAR) as an indicator of glycolytic function. Additionally, T-cell proliferation and cytokine release (IFN-γ) assay were utilised to correlate the bioenergetic characteristics of T-cell activation with in vitro assays., Results: Model T-cell stimulants induced non-specific T-cell activation, characterised by immediate augmentation of ECAR and rate of ATP production (JATPglyc). There was a dose-dependent and drug-specific glycolytic shift when vancomycin-reactive TCCs were exposed to the drug. Vancomycin-reactive TCCs did not exhibit T-cell cross-reactivity with structurally similar compounds within proliferative and cytokine readouts. However, cross-reactivity was observed when analysing energetic responses; TCCs with prior specificity for vancomycin were also found to exhibit glycolytic switching after exposure to teicoplanin. Glycolytic activation of TCC was HLA restricted, as exposure to HLA blockade attenuated the glycolytic induction., Conclusion: These studies describe the glycolytic shift of CD4+ and CD8+ T cells following vancomycin exposure. Since similar glycolytic switching is observed with teicoplanin, which did not activate T cells, it is possible the master switch for T-cell activation is located upstream of metabolic signalling., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Retention and separation of enantiomers of amine derivatives of indane and tetralin (rasagiline and its analogues) on chiral stationary phases (CSPs) Chiral-T and Chiral-V with teicoplanin and vancomycin antibiotics grafted onto superficially porous silica particles under conditions of reversed-phase and polar organic chromatography were studied. The mobile phases (MP) were water-methanol and acetonitrile-methanol solvents modified with triethylamine-acetic acid buffer. The effects of molecular structure and physical properties of the analytes on enantioselective retention are discussed. The retention mechanism is hypothesized to involve the ion-ion attraction between the positively charged amino group of an analyte and the carboxylate anion of either antibiotic. The binding occurs outside of the antibiotic's aglycon basket that accounts for relatively low enantioselectivity observed. The presence of a large substitute at the analyte's amino group complicates enantiorecognition. The effect of the MP solvent composition on retention and enantioseparation was investigated. It is a complex phenomenon combined of different oppositely directed influences that resulted in different shapes, increasing, decreasing, or U-shaped, of the retention factor vs. composition dependences. A model taking into account the interaction of both solvents of a binary MP with both an analyte and an adsorption site was successfully applied to approximate a majority of the studied systems. Pros and cons of the model are discussed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena Reshetova reports financial support was provided by Russian Science Foundation., (Copyright © 2023. Published by Elsevier B.V.)

Accurate therapeutic drug monitoring (TDM) of vancomycin, meropenem, linezolid and teicoplanin are conducive to developing optimal therapeutic regimes for patients. However, the measurement status of those drugs in different laboratories has not been reported. In this study, four samples including two frozen plasma samples and two lyophilized plasma samples were measured by over 35 laboratories across China. The inter- and intra-laboratory %CV, biases (%) of laboratories and intra- and inter-measurement-system %CV were calculated and analyzed. The short-term stability and homogeneity of those drugs in samples were studied. The results of frozen and lyophilized samples were also compared to determine whether there were significant differences in their matrix effects on various measurement systems. Results showed most laboratories' intra-laboratory %CVs were less than 9% for all drugs, and the mean inter-laboratory %CVs were 18.4%, 86.4%, 19.1% and 37.1% for vancomycin, meropenem, linezolid and teicoplanin measurements, respectively. For vancomycin, the intra-measurement %CV of commercial measurement systems was found to be smaller than that of other measurement systems. For meropenem, linezolid and teicoplanin, the agreement among laboratories using self-developed methods (Liquid chromatography-mass spectrometry [LC-MS] or high-performance liquid chromatography [HPLC]) was not satisfactory as most intra-measurement system CVs% were over 20%. Drugs in lyophilized samples were found to be more stable than in frozen samples, and no obvious differences in matrix effects were found for those two kinds of processed samples on most measurement systems. In conclusion, this study depicted the measurement status of those drugs in clinical laboratories, and found the lyophilized samples were more suitable EQA material for those drugs.

Analysis of vancomycin and teicoplanin in biological fluids is vital since they are used in the treatment of hospital infections. For the determination of both glycopeptides in urine, a sensitive and accurate analytical method using high-performance liquid chromatography coupled with photodiode array and mass spectrometry was developed and validated. This research work is the first attempt to develop a chromatographic method for the determination of two glycopeptides with structural similarities. Moreover, the used non-invasive sampling method is an advantage of this research effort, especially when the blood sampling is difficult. Urine was treated with acetonitrile and 5% trichloroacetic acid, followed by solid-phase extraction. The chromatographic separation was established at a C18 column (4.6 × 150 mm, 5 μm), using a gradient method and an electrospray ionization source in a positive mode. The linearity of the method was R 2 ≥ 0.9900. The precision was estimated with a maximum coefficient of variation below 15%, while the accuracy ranged from 64 to 121%. The limit of detection and quantification of both glycopeptides ranged from 0.076 up to 0.33 mg/L and 0.33 up to 2.1 mg/L, respectively, showing the same sensitivity as the triple quadrupole mass spectrometry, which is the most frequently used method., (© 2022 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)

Introduction: Combination therapy with vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) increases the risk of acute kidney injury (AKI). Teicoplanin (TEIC) has a lower risk of AKI than VCM. Currently, the difference in AKI risk after TEIC-PIPC/TAZ combination therapy and VCM-PIPC/TAZ combination therapy is controversial. This study aimed to compare AKI incidence after treatment with these two drug combinations using propensity score matching analysis., Methods: This single-center cohort study used data extracted from patients' medical records. We included patients who received TEIC-PIPC/TAZ therapy (TEIC group) or VCM-PIPC/TAZ therapy (VCM group). After propensity score matching, AKI incidence, AKI stage, 30-day mortality, and time to AKI incidence were compared between the groups., Results: After propensity score matching, 94 patients were matched in each group. AKI incidence was significantly lower in the TEIC group than in the VCM group (10.6% vs. 23.4%, odds ratio [95% confidence interval]: 0.39 [0.17-0.88], p = 0.03). AKI stage, 30-day mortality, and time to AKI incidence were not significantly different between the groups., Conclusions: This study suggested that AKI incidence may be lower in patients undergoing combination therapy with TEIC-PIPC/TAZ than in those receiving therapy with VCM-PIPC/TAZ. To prevent the occurrence of AKI, clinicians may need to choose TEIC instead of VCM for patients receiving PIPC/TAZ., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We compared the rates of acute kidney injury (AKI), 7-day and 30-day mortalities, and resolution of AKI at discharge in combination therapies involving either teicoplanin (TEI) or vancomycin (VAN) with piperacillin-tazobactam (TZP) or meropenem (MER). In a single-center, retrospective cohort study, adult patients (>18 years) who had a baseline serum creatinine level within 24 h of admission and who received study antibiotics for at least 48 h were included. The primary outcome was AKI incidence after therapy per RIFLE criteria. Multivariate logistic regression and propensity score match analyses were employed for statistical comparisons. Data from 379 patients were evaluated. In multivariate analysis (MVA) of the whole cohort, TZP-VAN combination was associated with significantly higher rate of AKI as compared with TZP-TEI (aOR: 3.21, 95% CI, 1.36-7.57; p = 0.008) or with MER-VAN (aOR: 2.28, 95% CI, 1.008-5.18; p = 0.048). In MVA of the matched cohorts, TZP-VAN as compared with TZP-TEI and MER-VAN was associated with 3.96 times (95% CI, 1.48-10.63, p = 0.006) and 3.11 times (95% CI, 1.12-8.62; p = 0.028) increased risk of AKI, respectively. No differences between MER-TEI and MER-VAN combinations were detected. Seven-day and 30-day mortalities and resolution rates of AKI were similar in all comparisons. Teicoplanin can be preferred instead of VAN when combination with TZP is used particularly for patients with high AKI risk., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

What Is Known and Objective: Our previous report indicated that teicoplanin (TEIC) caused fewer adverse effects than vancomycin (VCM) in patients with febrile neutropenia (FN) receiving haematopoietic stem cell transplantation (HSCT). However, we observed breakthrough methicillin-resistant-Staphylococcus haemolyticus (MR-S haemolyticus) infection during TEIC therapy in these patients. In this study, we sought to compare the incidence of breakthrough Gram-positive cocci (GPC) infection during VCM and TEIC therapy in this population., Methods: A single-centre, retrospective cohort study was conducted. Patients who had received HSCT and were administered VCM (n = 19) or TEIC (n = 38) for FN from 1 September 2011 to 31 August 2019 were enrolled. We compared the incidence of breakthrough GPC infection between the VCM and TEIC groups., Results: Breakthrough GPC infection during glycopeptide therapy in febrile neutropenic patients received HSCT was observed in three patients (7.9%) in the TEIC group but in none of patients (0%) in the VCM group. MR-S haemolyticus with low glycopeptide susceptibility (TEIC MIC = 2-8 μg/mL, VCM MIC = 2-4 μg/mL) was isolated from blood cultures in all patients with breakthrough GPC infections. All breakthrough infections were cured by changing from TEIC to daptomycin (DAP)., What Is New and Conclusion: The incidence of breakthrough GPC infection during glycopeptide therapy in febrile neutropenic HSCT patients was higher in the TEIC group than in the VCM group. MR-S haemolyticus with low glycopeptide susceptibility was isolated from all patients with breakthrough GPC infection and successfully treated with DAP., (© 2020 John Wiley & Sons Ltd.)

Sepsis and septic shock are characterized by a release of cytokines into the circulation. These mediators contribute to the detrimental hemodynamic and metabolic effects in the early phase of septic shock. Recently, a new polystyrene-based hemoadsorption device was introduced into clinical practice (CytoSorb ® ). The adsorber binds a variety of molecules including cytokines and removes them from the circulation. Studies in septic patients have shown an improved clinical course following hemoadsorption but no increased survival. We hypothesize that not only cytokines but also antibiotics may be removed which potentially may negate any beneficial effect of the adsorber. To test this hypothesis, we performed polystyrene-based hemoadsorption in three patients in septic shock and analysed glycopeptide elimination by measuring serum levels pre- and post-adsorber. We administered both teicoplanin and vancomycin via a 60-min infusion and vancomycin via continuous infusion, additionally. When applied as 60 min infusion, vancomycin and teicoplanin were removed immediately by the adsorber. However, the adsorptive capacity of the device was saturable. Serum levels of vancomycin, but not teicoplanin, decreased to subtherapeutic levels. With continuous infusion of vancomycin, removal was less and serum levels remained in the therapeutic range. In conclusion, we show effective glycopeptide adsorption using a polystyrene-based hemoadsorber in septic patients. The dose of these antibiotics should be adjusted appropriately and early therapeutic drug monitoring is highly recommended.

Vancomycin-resistant enterococcus (VRE) is a global threat to public health. Knowledge about the occurrence of vanA-carrying enterococci in broiler and environmental samples is important as antibiotic resistance can be transferred to human bacteria. The aim of this study was to investigate the presence of VRE in broiler cloacal and environmental (house) samples and to genotype the isolates. In this study, 350 swabs were collected from broiler farms. All samples were plated onto enterococcus selective agar containing 6 mg/L vancomycin and 64 mg/L ceftazidime. Minimum inhibitory concentration (MIC) values were determined for vancomycin and teicoplanin. Vancomycin-resistant Enterococcus faecium (VREfm) was isolated from 6 out of 300 (2%) broiler cloacal samples and 13 out of 50 (26%) house samples. All E. faecium isolates had vanA genes. All VREfm isolates (19 isolates) were confirmed to be 95% similar to each other. In conclusion, although 20 years have passed since the ban on avoparcin in Turkey, the present study shows that VREfm isolates are still present in broiler production and especially in broiler houses, and most importantly, a major VREfm clone was isolated from broiler cloacal and house samples.

Application of the superficially porous particles (SPPs) grafted with chiral selectors can substantially improve resolution in chromatographic techniques. In this work, we carried out a deeper study on supercritical fluid chromatography systems with 2.7 µm SPPs bonded with teicoplanin and vancomycin. Fast separations of the majority of enantiomers of phytoalexins, substituted tryptophans, and ketamine derivatives, as representatives of important biologically active and structurally diverse chiral compounds have been achieved. The chromatographic behavior of the structurally different analytes served to characterize these separation systems. The influence of separation conditions, namely mobile phase composition, i.e. type of co-solvent and additive on retention, enantioselective resolution and enantioselectivity was examined. The success rate of baseline and partial separations in individual groups of compounds differed with the chiral stationary phase and also with mobile phase composition. The best, baseline separations for the phytoalexins were achieved on the TeicoShell column using methanol as a co-solvent and trifluoroacetic acid as an additive if used. Mostly partial separations were achieved on the vancomycin-based column for all groups of analytes. Complementary separation behavior of these CSPs was confirmed for the majority of the chiral compounds examined in this work., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)

What Is Known and Objective: Patients who receive hematopoietic stem cell transplantation (HSCT) are usually administered a calcineurin inhibitor. Because vancomycin is associated with an increased incidence of nephrotoxicity, neutropenic patients receiving HSCT are considered a high-risk population for nephrotoxicity with vancomycin. We retrospectively compared the efficacy and safety of vancomycin and teicoplanin in febrile neutropenic patients receiving HSCT., Methods: A single-centre, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received HSCT and were administered vancomycin or teicoplanin by injection for febrile neutropenia from 1 January 2012 to 31 August 2017 were enrolled. Time to attain an effective trough concentration, clinical efficacy and adverse events were compared between the two groups., Results: Time to attain an effective trough concentration of over 10 μg/mL tended to be shorter in the teicoplanin group than in the vancomycin group (median 3, 95% confidence interval [CI] 2.4-3.6 days vs median 6, 95% CI 1.5-10.5 days; hazard ratio [HR] 0.4, 95% CI 0.15-1.06; P = .066). The rate of clinical failure was lower in the teicoplanin group than in the vancomycin group (18.8% vs 53.8%, P = .113). In addition, the overall incidence of nephrotoxicity was significantly lower in the teicoplanin group (0% vs 46.2%, P = .004)., What Is New and Conclusion: Our findings suggest that administration of teicoplanin may lead to early attainment of the effective concentration with a lower rate of clinical failure and incidence of nephrotoxicity compared to vancomycin in febrile neutropenic patients receiving HSCT., (© 2019 John Wiley & Sons Ltd.)

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3 minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell., (© 2018 Wiley Periodicals, Inc.)

We investigated the genetic basis of glycopeptide resistance in laboratory-derived strains of S. haemolyticus with emphasis on differences between vancomycin and teicoplanin. The genomes of two stable teicoplanin-resistant laboratory mutants selected on vancomycin or teicoplanin were sequenced and compared to parental S. haemolyticus strain W2/124. Only the two non-synonymous mutations, VraS Q289K and WalK V550L were identified. No other mutations or genome rearrangements were detected. Increased cell wall thickness, resistance to lysostaphin-induced lysis and adaptation of cell growth rates specifically to teicoplanin were phenotypes observed in a sequenced strain with the VraS Q289K mutation. Neither of the VraS Q289K and WalK V550L mutations was present in the genomes of 121S. haemolyticus clinical isolates. However, all but two of the teicoplanin resistant strains carried non-synonymous SNPs in vraSRTU and walKR-YycHIJ operons pointing to their importance for the glycopeptide resistance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanR A S A two-component system, comprising the histidine sensor kinase VanS A and the partner response regulator VanR A . The nature of the activating ligand for VanS A has not been identified, therefore this work sought to identify and characterise ligand(s) for VanS A . In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanS A protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanS A with different affinities (vancomycin 70μM; teicoplanin 30 and 170μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanS A , proposing them as activators of type A vancomycin resistance in the enterococci., (Copyright © 2017 Diamond Light Source Ltd. Published by Elsevier B.V. All rights reserved.)

Untreated wastewaters and treated effluents even after final disinfection contain antibiotic resistant bacteria and resistance genes before they are released into surface waters. A correlation between resistant bacteria and antibiotics in surface waters has been found, as have antibiotic resistance genes. Of particular interest are vancomycin-resistant enterococci harboring vanA gene that confers high level of resistance to glycopeptide antibiotics including teicoplanin. Therefore, in this study, river water samples were analysed to investigate vancomycin- and teicoplanin-resistant bacterial isolates harboring vanA gene. Out of 290, 15 surface water isolates displayed resistance to both antibiotics. These glycopeptide resistant enterococcal and non-enterococcal isolates, identified by 16S rRNA sequencing, were found to harbor vanA gene with sequence similarities of 50 % to 100 %. The presence of D-alanine-D-lactate ligase encoded by vanA gene was also shown for all vancomycin- and teicoplanin-resistant isolates through western blot analysis. Due to reuse of treated wastewater and release of untreated wastewaters to water bodies, antibiotic resistant bacteria and resistance genes are being introduced into surface waters and present human health risks. Therefore, surface waters are not only hot spots for vanA harboring enterococcal isolates but also non-enterococcal isolates due to gene dissemination and require special scientific consideration.

The glycopeptide antibiotics teicoplanin and vancomycin are common to treat severe Gram-positive bacterial infections. The gene vanA confers high-level resistance to these antibiotics, and these phenomena have been shown to be transferable. Release of vancomycin- and teicoplanin-resistant bacteria to surface waters is, therefore, of particular concern since they might proliferate and spread in different environments. Monitoring of the fate of vanA gene in these waters provides information on the exposure and potential threats of those bacteria for the environment and public health. Therefore, this study aimed at preparing a 25-mer-oligonucleotide DNA probe based on the 909 bp BamHI-ClaI fragment from Enterococcus faecium plasmids pVEF1 and pVEF2 through the use of Vector NTI Express Software. The newly designed vanA probe displayed highly specific hybridization with vanA-positive Enterococcus faecalis tested at 46 °C, 55 % formamide, and 0.020 M NaCl stringency conditions. In situ fluorescein hybridizations under the same stringency conditions were also used to monitor river water samples by using fluorescein microscopy. The results showed that the vanA-targeted oligonucleotide DNA probe prepared was not only highly specific but also quantitative tool for monitoring vancomycin- and teicoplanin-resistant bacteria in surface waters.

Many studies have shown that the toxic effects of local antibiotics on bone and cartilage limit orthopedic surgeons. In this study, we evaluated three antibacterial agents used locally to treat highly mortal and morbid diseases in the field of orthopedics, such as septic arthritis. Are vancomycin, teicoplanin, and linezolid, which are archenemies of Staphylococcus aureus, really toxic to chondrocytes? The purpose of the study was to investigate the effects of antibiotics, which are used against S. aureus, on human chondrocytes in vitro. Primary cell cultures obtained from gonarthrosis patients were divided into two main groups. One of these groups was designated as the control chondrocyte culture. The other group was divided into three subgroups, and each group was exposed to vancomycin, teicoplanin, or linezolid. Cell culture samples were characterized by immunophenotyping following incubation with the three different antibiotics. Before and after the agents were administered, the cultures were subjected to inverted and environmental scanning electron microscopy. The number of live cells and the proliferation rate were monitored with the MTT-assay. We found that vancomycin, teicoplanin, and linezolid do not have chondrotoxic effects. Vancomycin, teicoplanin, and linezolid had no chondrotoxic activity during in vitro culture, which supports the argument that these agents can safely be used in orthopedic surgery, especially against methicillin-resistant S. aureus agents., (Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Biofilm-associated bacteria display a decreased susceptibility towards antibiotics. Routine assessment of antibiotic susceptibility of planktonic bacteria therefore offers an insufficient prediction of the biofilm response. In this study, in vitro biofilms of eight clinical Staphylococcus epidermidis strains were subjected to treatment with vancomycin, teicoplanin, oxacillin, rifampicin and gentamicin. In addition, the biofilms were subjected to combinations of an antibiotic with rifampicin. The effects on the biofilms were assessed by crystal violet staining to determine the total biofilm biomass, staining with XTT to determine bacterial cell viability, and microscopy. Combining these methods showed that treatment of S. epidermidis biofilms with glycopeptides increased the total biofilm biomass and that these antibiotics were not effective in killing bacteria embedded in biofilms. The decreased killing efficacy was more pronounced in biofilms produced by strains that were classified as 'strong' biofilm producers. Rifampicin, oxacillin and gentamicin effectively killed biofilm-associated bacteria of all tested strains. Combining antibiotics with rifampicin increased the killing efficacy without influencing the total biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin, the increase in biofilm biomass was neutralised and also the killing efficacy was influenced in a positive way. We conclude that the combined methodology used in this study showed that glycopeptides were not effective in eradicating S. epidermidis biofilms but that combination with rifampicin improved the killing efficacy in vitro., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The first glycopeptide antibiotic was vancomycin, isolated from the soil in the 1950s; since then, the class has expanded to include teicoplanin and the new semisynthetic glycopeptides dalbavancin, oritavancin and telavancin. They are bactericidal, active against most Gram-positive organisms, and in a concentration-dependent manner, inhibit cell wall synthesis. Resistance to vancomycin has emerged, especially among enterococci and Staphylococcus aureus through a variety of mechanisms. This emerging resistance to vancomycin makes proper dosing and monitoring of the area under the curve/MIC critically important. The chief adverse effect of vancomycin is nephrotoxicity, which is also intricately related to its dose. The efficacy of the semisynthetic glycopeptides has been demonstrated in skin and soft-tissue infections, but remains to be seen in serious methicillin-resistant Staphylococcus aureus infections.

Objectives: Staphylococcus aureus is a notorious bacterial pathogen and antibiotic-resistant isolates complicate current treatment strategies. We characterized S. aureus VC40, a laboratory mutant that shows full resistance to glycopeptides (vancomycin and teicoplanin MICs ≥32 mg/L) and daptomycin (MIC = 4 mg/L), to gain deeper insights into the underlying resistance mechanisms., Methods: Genomics and transcriptomics were performed to characterize changes that might contribute to development of resistance. The mutations in vraS were reconstituted into a closely related parental background. In addition, antimicrobial susceptibility testing, growth analyses, transmission electron microscopy, lysostaphin-induced lysis and autolysis assays were performed to characterize the phenotype of resistant strains., Results: Genome sequencing of strain VC40 revealed 79 mutations in 75 gene loci including genes encoding the histidine kinases VraS and WalK that control cell envelope-related processes. Transcriptomics indicated the increased expression of their respective regulons. Although not reaching the measured MIC for VC40, reconstitution of the L114S and D242G exchanges in VraS(VC40) into the susceptible parental background (S. aureus NCTC 8325) resulted in increased resistance to glycopeptides and daptomycin. The expression of VraS(VC40) led to increased transcription of the cell wall stress stimulon, a thickened cell wall, a decreased growth rate, reduced autolytic activity and increased resistance to lysostaphin-induced lysis in the generated mutant., Conclusions: We show that a double mutation of a single gene locus, namely vraS, is sufficient to convert the vancomycin-susceptible strain S. aureus NCTC 8325 into a vancomycin-intermediate S. aureus., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

What Is Known and Objective: The glycopeptide antibiotics, vancomycin and teicoplanin, are the mainstay of therapy for severe gram-positive organisms such as methicillin-resistant Staphylococcus aureus. We report a case of Stevens-Johnson syndrome (SJS) induced by sequential therapy with teicoplanin and vancomycin, in a patient with chronic obstructive pulmonary disease (COPD)., Case Summary: A 74-year-old Han Chinese with 1-year history of COPD was admitted for treatment of infective endocarditis. After teicoplanin therapy for 12 days, he developed pruritus and maculopapular over his trunk and limbs. His rash spread rapidly to most parts of the body surface area, 7 days after his anti-infection therapy was switched to vancomycin. This was stopped, but he developed SJS when teicoplanin was re-introduced. This patient recovered from his drug eruptions when both teicoplanin and vancomycin were stopped. Pharmacogenetic analyses revealed he was heterozygous with respect to two variants (rs2844682 of MUC21 and rs750332 of BAG6)., What Is New and Conclusion: Cross-reactivity between vancomycin and teicoplanin is rare. SJS attributable to sequential treatment with these two antibiotics has not been reported previously. Care should be taken when prescribing vancomycin in patients with a previous documented skin eruption to teicoplanin, especially in those who carry any susceptibility alleles to SJS/TEN., (© 2014 John Wiley & Sons Ltd.)

In this paper, the binding properties of teicoplanin and vancomycin to bovine serum albumin (BSA) were investigated using fluorescence quenching, synchronous fluorescence, Fourier transform infrared (FTIR), circular dichroism (CD) and UV-vis spectroscopic techniques and molecular docking under simulative physiological conditions. The results obtained from fluorescence quenching data revealed that the drug-BSA interaction altered the conformational structure of BSA. Meanwhile, the 3D fluorescence, CD, FTIR and UV-vis data demonstrated that the conformation of BSA was slightly altered in the presence of teicoplanin and vancomycin, with different reduced α-helical contents. The binding distances for the drug-BSA system were provided by the efficiency of fluorescence resonance energy transfer (FRET). Furthermore, the thermodynamic analysis implied that hydrogen bond and van der Waals' forces were the main interaction for the drug-BSA systems, which agreed well with the results from the molecular modeling study. The results obtained herein will be of biological significance in future toxicological and pharmacological investigation., (Copyright © 2013 John Wiley & Sons, Ltd.)

Aim: The main objective of this study is to understand the mechanism of vancomycin resistance in a Streptomyces coelicolor disrupted mutant highly resistant to vancomycin., Materials & Methods: Different techniques have been performed in the study including gene disruption, primer extension, antibiotic susceptibility tests, electron microscopy, confocal microscopy, cell wall analysis and microarrays., Results: During the phenotypical characterization of mutant strains affected in phosphate-regulated genes of unknown function, we found that the S. coelicolor SCO2594 disrupted mutant was highly resistant to vancomycin and had other phenotypic alterations such as antibiotic overproduction, impaired growth and reduction of phosphate cell wall content. Transcriptomic studies with this mutant indicated a relationship between vancomycin resistance and cell wall stress., Conclusion: We identified a S. coelicolor mutant highly resistant to vancomycin in both high and low phosphate media. In addition to Van proteins, others such as WhiB or SigE appear to be involved in this regulatory mechanism.

Antibiotic-resistant bacterial infection is one of the most serious clinical problems worldwide. Vancomycin, teicoplanin, daptomycin, and colistin are glycopeptide and lipopeptide antibiotics that are frequently used to treat multidrug-resistant bacterial infections. Therapeutic drug monitoring is recommended to ensure both safety and efficacy and to improve clinical outcomes. This study developed a fast, simple, and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of the concentrations of these four drugs in human plasma. The sample preparation process includes a simple protein denaturation step using acetonitrile, followed by an 11-fold dilution with 0.1% formic acid. Eight target peaks for the four drugs can be analyzed within 3 min using a Kinetex™ 2.6 μm C18 column. The mass spectrometry parameters were optimized, and two transitions for each target peak were used for multiple reaction monitoring, which provided high sensitivity and specificity. The UHPLC-MS/MS method was validated over clinical concentration ranges. The intra-day and inter-day precisions for the ratio of the peak area of each analyte to the peak area of the internal standard were all below 12.7 and 14.7% relative standard deviations, respectively. The accuracy at low, medium, and high concentrations of the eight target peaks was between 89.3 and 110.7%. The standard curves for the analytes were linear and had coefficients of determination higher than 0.997. The limits of detection were all below 70 ng mL(-1). The use of this method to analyze patient plasma samples confirmed that it is effective for the therapeutic drug monitoring of these four drugs and can be used to improve the therapeutic efficacy and safety of treatment with antibiotics., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of this work was to study the physicochemical interactions between chiral stationary phases and chiral molecules and to elucidate which of the specific interactions are more or less important. The HPLC separation of 58 aryloxyaminopropanols was performed on two chiral stationary phases containing the macrocyclic antibiotics teicoplanin or vancomycin and using a methanol/acetonitrile/acetic acid/triethylamine mobile phase (volume ratios 45/55/0.3/0.2). The resolution of enantiomers (Rij) as the target variable was predicted for the mentioned kind of compounds by means of thoroughly selected descriptors provided by the applied Dragon software. The created QSPR models can be considered as a way to explore and discover new relationships or interactions between the quantitative structure and resolution of enantiomers. For calculation and validation of the QSPR models, different modelling methodologies were applied based on MLR (multiple linear regression) and ANN (artificial neural network) techniques. Both methods exhibit an ability for successful prediction of the enantioresolution characteristics of the studied molecules. The results seem to demonstrate that it is possible to predict resolution values of enantiomeric separations of related compounds on given chromatographic systems., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Enterococcus faecium has recently emerged as a serious nosocomial pathogen. Vancomycin resistant enterococci (VRE) have been isolated in Europe and the USA since 1988. This is the first report on isolation of vancomycin resistant E. faecium (VREM) strains in Poland, from Haematological Unit patients in the Clinical Hospital in Gdańsk. In total, 6412 samples were examined between December 1996 and October 1997. Five hundred and five isolates of Enterococcus spp. were collected. One hundred and one were classified as Enterococcus faecium of which 49 were resistant to vancomycin (MIC > 256 mg/L) and teicoplanin (MIC > 256 mg/L), characteristic of the VanA phenotype. Twenty-nine patients were infected or colonized. A PCR-based specific diagnostic assay confirmed the phenotype. The multiplex PCR-restriction fragment length polymorphism patterns were consistent with VanA-type of vancomycin-resistant E. faecium for all isolates examined. These isolates were epidemiologically-related as shown by PCR-fingerprinting.

The in vitro activities of teicoplanin, daptomycin, ramoplanin, and PD127,391, a new quinolone, were compared with that of vancomycin. Teicoplanin showed the lowest MICs against Enterococcus faecalis. Ramoplanin was slightly more active than the other peptide antibiotics against oxacillin-resistant Staphylococcus aureus. The MICs of the four peptide antibiotics were similar for the oxacillin-susceptible S. aureus. Daptomycin had good activity against staphylococci but was the least active agent against E. faecalis. The MICs of vancomycin against all isolates were in general higher than those of the new antibiotics, with the exceptions of the MICs of daptomycin against E. faecalis and teicoplanin against oxacillin-resistant Staphylococcus epidermidis. PD127,391 was the most active agent against all staphylococcal isolates.

The minimum inhibitory concentration (MIC) of teicoplanin and vancomycin was determined by the agar dilution method for 186 Gram-positive bacteria from human clinical and veterinary sources. Teicoplanin MIC values were less than or equal to 4 micrograms/ml for 94% of staphylococci (group A, n = 52) and less than or equal to 2 micrograms/ml for all streptococci, enterococci, aerococci and pediococci (group B, n = 75). Seventy-eight percent of Gram-positive rods, Rhodococcus and Leuconostoc spp. (group C, n = 59) were inhibited by 4 micrograms/ml. Teicoplanin resistance (MIC greater than or equal to 16 micrograms/ml) was demonstrated for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, Leuconostoc, and S. haemolyticus. Cross-resistance between teicoplanin and vancomycin was observed for all Nocardia strains and for some strains of Lactobacillus, E. rhusiopathiae, and Leuconostoc. Three methicillin-resistant S. haemolyticus strains were either resistant or intermediately susceptible to teicoplanin and susceptible to vancomycin. Eight strains (motile enterococci four, E. rhusiopathiae three and Leuconostoc sp. one) were susceptible to teicoplanin and resistant to vancomycin. Teicoplanin disc diffusion on Danish Blood Agar with NeoSensitabs (Rosco), PDM AB Biodisc and locally prepared discs revealed a wide range of zone diameters in groups B and C. The relation between MIC values and zone diameters for teicoplanin was analysed by the error-rate bounded method. Zone size interpretive criteria as suggested by the manufacturers (greater than or equal to 15 mm) produced 2.7% (95% confidence limits 0.9-6.2%) and 1.6% (95% confidence limits 0.3-4.6%) very major errors for NeoSensitabs and PDM-disc, respectively. Using a zone size breakpoint for susceptibility of greater than or equal to 25 mm for NeoSensitabs and greater than or equal to 20 mm for PDM-disc, the proportions of very major errors were 0.5% (95% confidence limits 0.0-3.0%) at the expense of 5.9% (95% confidence limits 3.0-10.3%) indeterminate strains that belonged to E. rhusiopathiae, Leuconostoc, Lactobacillus and S. haemolyticus. However, using these zone size breakpoints five major errors (beta-haemolytic streptococci, group B three, S. aureus one, Leuconostoc sp. one) were observed for NeoSensitabs and two major errors (beta-haemolytic streptococcus, group B one, Leuconostoc sp. one) were observed for PDM-disc. Susceptibility testing against teicoplanin among these taxa should therefore include a determination of MIC.

Gram-positive organisms such as Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, Enterococcus spp., and Streptococcus spp. have in recent years emerged as significant pathogens in hospitals and are now being isolated more frequently than gram-negative bacilli. These organisms are often multidrug resistant. Therefore, alternative agents with potent activity against gram-positive organisms are of considerable interest. In addition to the glycopeptide antibiotic vancomycin and the aminoglycoside antibiotic arbekacin, which can be used in MRSA infections, teicoplanin, RP 59500 and daptomycin are now under basic research in Japan. These antimicrobial agents are very active against gram-positive organisms, including MRSA and appear to be potent agents against infections due to gram-positive cocci, particularly MRSA.

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.

The in-vitro activity of four peptide antibiotics against 43 penicillin-resistant Streptococcus pneumoniae isolated from cerebrospinal fluid (CSF) was evaluated. The activity of SKF104662 was slightly greater to that of vancomycin, teicoplanin and daptomycin (MICs for 90% of the isolates tested 0.06, 0.25, 0.12 and 0.25 mg/L, respectively) and superior to the other 15 drugs tested. The serotype of these penicillin-resistant strains was also determined. The strains that belonged to the predominant serotype 9 were resistant only to penicillin. All six erythromycin- and clindamycin-resistant strains belonged to serotype 6 and three of them were also resistant to chloramphenicol and tetracycline (plus penicillin).

We evaluated the in vitro activity of teicoplanin compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) derived from cystic fibrosis (CF) sputum. Teicoplanin had a slightly lower median minimum inhibitory concentration (MIC) for these strains (0.25 micrograms/ml) than did vancomycin (0.5 micrograms/ml). Inoculum size increased the MICs similarly for both drugs, and pH variations did not significantly affect their activity. The presence of serum and sputum in the growth media decreased the activity of both drugs, although this was more pronounced for teicoplanin which is highly protein bound. We conclude that teicoplanin has activity against this pathogen and might be evaluated in clinical protocols designed to address this emerging clinical problem.

Teicoplanin, although more active than vancomycin [by minimum inhibitory concentration (MIC)], produces smaller inhibition zones in sensitivity testing with 30-microgram disks. Our data support the hypothesis that this is due to lower diffusion of teicoplanin in agar media. After 6 hr of incubation, approximately 70% of vancomycin, but only 20% of teicoplanin entered the agar from a paper disk charged with 30 micrograms of antibiotic. This is due to a difference between the diffusion coefficients: 0.47 mm2/hr for teicoplanin and 0.72 mm2/hr for vancomycin. With the methodology used in this work, it is possible to calculate the range of concentrations of the antibiotic occurring at times likely to include the critical time--the time when the inhibition zone is formed--of most strains at any given distance from the reservoir. One can thus estimate the breakpoint diameter for a given MIC breakpoint; for example, an MIC breakpoint of less than or equal to 4 micrograms/ml would correspond to a greater than or equal to 15-mm breakpoint diameter for vancomycin (30-microgram disk) and a greater than or equal to 13-mm breakpoint diameter for teicoplanin (30-microgram disk).

Objective: To compare and contrast the pharmacology, activity and clinical efficacy of two glycopeptide antibiotics, vancomycin and teicoplanin., Data Sources: English language literature search using MEDLINE, Index Medicus, relevant textbooks and product information literature., Study Selection: Over 200 publications were examined extending back to the period of initial Phase I trials with vancomycin., Data Extraction and Synthesis: Many publications covered similar ground and came to the same conclusions. In these instances one or two of the best pieces were chosen as cited reference material. Conflicting results and conclusions are discussed and an attempt is made to interpret the findings., Conclusion: Vancomycin and teicoplanin show differences in activity both in vitro and in vivo. Vancomycin is superior against coagulase-negative staphylococci and reliable dosage regimens are available. Teicoplanin, however, needs to be given in significantly larger doses than initially thought necessary to maximise clinical efficacy. Teicoplanin has a lower incidence of side effects but in clinical practice this advantage is small. Vancomycin remains the glycopeptide of choice for the treatment of infections due to Gram-positive bacteria.

A 38-year-old male patient developed severe signs of type 1 allergy after treatment with vancomycin. By the basophil histamine release test, the patient's isolated basophil leucocytes were shown to react IgE dependent after challenge with vancomycin and teicoplanin. This indicates that the patient is type 1 allergic towards vancomycin and teicoplanin.

Vancomycin was found to coinduce DD-carboxypeptidase activity, together with resistance, in eight low- or high-level glycopeptide-resistant strains of enterococci. The constitutively resistant mutant (MT10) of a low-level-resistant strain of Enterococcus faecium (D366) spontaneously expressed a level of carboxypeptidase similar to that of the induced strain D366. Pentapeptide, UDP-MurNac-pentapeptide, as well as D-alanyl-D-alanine were in vitro substrates for the carboxypeptidase which was not inhibited by penicillin. The level of vancomycin resistance correlated roughly with the level of carboxypeptidase activity. We infer from these results that the carboxypeptidase is one component of the glycopeptide resistance mechanism.

The minimum inhibitory concentrations (MICs) of vancomycin and teicoplanin were determined for 32 coagulase-negative staphylococci strains recovered from blood specimens from pediatric intensive care patients. All the strains were susceptible to vancomycin (MIC less than 4 mg/l). Sixteen strains were susceptible to teicoplanin (MIC less than 4 mg/l) and the sixteen remaining strains exhibited intermediate susceptibility, with MICs of 8 mg/l (10 strains) or 16 mg/l (6 strains). Inhibition zone diameters seen with vancomycin during agar diffusion susceptibility testing were consistently greater than 17 mm. Inhibition zones obtained with teicoplanin were 17 mm or more in diameter for 30 strains and under 17 mm in diameter for 2 strains. For 14 strains (44%), agar diffusion testing failed to detect the decreased susceptibility to teicoplanin revealed by MIC determinations. The agar diffusion method does not seem reliable for the determination of in vitro susceptibility to teicoplanin.

We conducted a time-kill study comparing the combination of vancomycin plus gentamicin versus teicoplanin plus gentamicin against 20 clinical isolates each, of enterococci, S. aureus and coagulase-negative staphylococci. The concentrations of vancomycin and teicoplanin were selected so that cultures containing these drugs alone contained 10(3) to 10(6) cfu/ml after 24 hr, mostly 2 to 4 times the MIC for each isolate. In this way we could be certain that synergism or antagonism would not go undetected. One-fourth of the gentamicin MIC for each isolate was used throughout the study. In vitro bactericidal synergy was considered to be present when vancomycin plus gentamicin or teicoplanin plus gentamicin yielded at least a 2 log 10 decline in cfu/ml compared to vancomycin or teicoplanin alone. There was no significant difference between the two antibiotic combinations against these gram-positive cocci. The antibiotic combinations showed synergy against 75 per cent of enterococcal isolates, 70 per cent of S. aureus isolates and 50 per cent of coagulase-negative staphylococcal isolates when measured at 24 hr of incubation. Five (25%) enterococcal strains resistant to the synergistic effect of the antibiotic combinations had gentamicin MICs greater than 64 mg/L. For staphylococcal isolates, no association was found between synergy and gentamicin susceptibility, methicillin resistance, or tolerance to vancomycin or teicoplanin.

A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted. Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg q12h for three doses. Vancomycin was administered at 15 mg/kg q12h i.v. Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.). Of 53 patients enrolled, 50 were judged to be evaluable. Among these, 25 received teicoplanin and 25 received vancomycin. At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy. Both groups had similar sites of infection and microbial pathogens. Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67). Failures occurred with two vancomycin patients but no teicoplanin patients. Clinical response was indeterminate for two patients in each group. Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02). Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02). Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02). Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups. Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population.

The in vitro activities of teicoplanin and vancomycin against 288 gram positive cocci were determined by broth macrodilution method. MIC 90 values for teicoplanin were lmcg/ml for coagulase positive staphylococci (n = 115), 4 mcg/ml for coagulase negative staphylococci (n = 93), 0.50 mcg/ml for S. faecalis (n = 50) and 0.125 mcg/ml for S. pyogenes (n = 30). MIC 90 values for vancomycin were lmcg/ml 1 mcg/ml, 1 mcg/ml and 0.25 mcg/ml respectively. We were not able to detect in vitro resistance against teicoplanin and vancomycin.

The in-vitro effects of therapeutic concentrations of teicoplanin and vancomycin on the adherence, spontaneous mobility, chemotaxis, phagocytic and candidacidal capacity of human polymorphonuclear leukocytes (PMNs) were studied. Adherence was not affected by the tested concentrations of teicoplanin. A progressive diminishing of adherence was observed in relation to the control, which reached 30% with the maximum concentration of vancomycin (50 mg/L), although this was not statistically significant. An increase in spontaneous mobility was noted after 30 min incubation in the presence of any one of the tested concentrations of both antibiotics, although the results were only significant (P less than 0.05) for 50 mg/L of teicoplanin. Chemotaxis increased, although not significantly (P greater than 0.05) in the presence of 10 and 50 mg/L of teicoplanin, and diminished with respect to the control very significantly (P less than 0.019) when 1 and 50 mg/L of vancomycin were tested. The study of the phagocytic and candidacidal capacity of the PMNs on Candida albicans showed that teicoplanin had a favourable effect on both functions, even though the differences were not statistically significant.

Teicoplanin is a new glycopeptide antibiotic with a chemical structure related to vancomycin. The proposed advantages of teicoplanin over vancomycin are discussed. These include lower incidence of side-effects, lower toxicity (especially in combination with aminoglycosides), lower dosage frequency and the possibility of intramuscular administration. There is only a limited number of studies comparing both agents; more studies are still needed before firm conclusions can be drawn. Therapeutic drug monitoring is not usually necessary for teicoplanin; the situation is not clear for vancomycin. There is some doubt whether the incidence of resistance is as infrequent for teicoplanin as it is for vancomycin. Teicoplanin appears to be a promising alternative to vancomycin, but more data are needed on the relative clinical efficacy and the development of resistance to both drugs.

Vancomycin, teicoplanin, daptomycin, and coumermycin were investigated for immunomodulatory activity on both humoral and cell-mediated immune responses in Balb/c mice. All four antibiotics did not produce any interference with these responses as measured by hemolytic plaque assay and delayed-type hypersensitivity to sheep red blood cells. The administration of these antibiotics for seven days did not affect the peripheral blood leukocyte count or spleen weights. When these antibiotics were tested for their interaction with human polymorphonuclear phagocytic activity, no alteration in this activity was observed. These findings suggest that vancomycin, teicoplanin, daptomycin, and coumermycin may be safely used for the treatment of infections without altering host-defence mechanisms.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.

This study describes the evaluation of a murine bacteraemia model for assessing antibiotic efficacy in normal and neutropenic mice infected with coagulase-negative staphylococci. In one such evaluation, it was found that there was no significant (P greater than 0.05) difference in the ability of teicoplanin or vancomycin to protect normal or neutropenic CD-1 mice, lethally-infected with Staphylococcus haemolyticus. However, about a four-fold increase of either antibiotic was needed to protect the immunocompromised animals.