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Biotechnology Advances 2022The spread of antimicrobial resistance in Gram-positive pathogens represents a threat to human health. To counteract the current lack of novel antibiotics, alternative... (Review)
Review
The spread of antimicrobial resistance in Gram-positive pathogens represents a threat to human health. To counteract the current lack of novel antibiotics, alternative antibacterial treatments have been increasingly investigated. This review covers the last decade's developments in using nanoparticles as carriers for the two classes of frontline antibiotics active on multidrug-resistant Gram-positive pathogens, i.e., glycopeptide antibiotics and daptomycin. Most of the reviewed papers deal with vancomycin nanoformulations, being teicoplanin- and daptomycin-carrying nanosystems much less investigated. Special attention is addressed to nanoantibiotics used for contrasting biofilm-associated infections. The status of the art related to nanoantibiotic toxicity is critically reviewed.
Topics: Anti-Bacterial Agents; Daptomycin; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Teicoplanin
PubMed: 35337933
DOI: 10.1016/j.biotechadv.2022.107948 -
BMC Microbiology Jan 2023Enterococcus faecalis remains one of the most common pathogens causing infection in surgical patients. Our goal was to evaluate the antibiotic resistance of E. faecalis,...
BACKGROUND
Enterococcus faecalis remains one of the most common pathogens causing infection in surgical patients. Our goal was to evaluate the antibiotic resistance of E. faecalis, causing infections in a surgical clinic, against two antibacterial drugs, ampicillin and teicoplanin. One commonly administered in the past for such infections, ampicillin, and another newer, teicoplanin, which demonstrated exceptionally good efficacy.
METHODS
Data from 1882 isolates were retrieved from the microbiology department database during two 5-year periods. Standard biochemical methods were employed for the identification of the isolates. The prevalence of E. faecalis among patients with clinical evidence of infection in a surgical oncology ward was assessed. Confidence interval (CI) as well as standard error (SE) were calculated. Moreover, the annual incidence of E. faecalis infections in this surgical ward was recorded. The susceptibility of E. faecalis to ampicillin and teicoplanin was studied and compared using Fisher's exact test.
RESULTS AND CONCLUSION
Results showed that the incidence of E. faecalis infections in the surgical clinic was increasing. Ampicillin, in the later year period, was not statistically different from teicoplanin in treating E. faecalis infections. Consequently, ampicillin seems currently to be an effective antibiotic against such infections that could be used as empiric therapy.
Topics: Humans; Teicoplanin; Enterococcus faecalis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Ampicillin
PubMed: 36609223
DOI: 10.1186/s12866-022-02753-1 -
Scientific Reports Oct 2022Antibacterial bone biomaterial coatings appeal to orthopaedics, dentistry and veterinary medicine. Achieving the successful, stable conjugation of suitable compounds to...
Antibacterial bone biomaterial coatings appeal to orthopaedics, dentistry and veterinary medicine. Achieving the successful, stable conjugation of suitable compounds to biomaterial surfaces is a major challenge. A pragmatic starting point is to make use of existing, approved antibiotics which are known to remain functional in a stationary, immobilised state. This includes the macrocyclic glycopeptide, teicoplanin, following the discovery, in the 1990's, that it could be used as a chiral selector in chromatographic enantiomeric separations. Importantly teicoplanin works at the level of the bacterial cell wall making it a potential candidate for biomaterial functionalisations. We initially sought to functionalise titanium (Ti) with polydopamine and use this platform to capture teicoplanin, however we were unable to avoid the natural affinity of the antibiotic to the oxide surface of the metal. Whilst the interaction between teicoplanin and Ti was robust, we found that phosphate resulted in antibiotic loss. Before contemplating the covalent attachment of teicoplanin to Ti we examined whether a commercial teicoplanin stationary phase could kill staphylococci. Whilst this commercially available material could bind N-Acetyl-L-Lys-D-Ala-D-Ala it was unable to kill bacteria. We therefore strongly discourage attempts at covalently immobilising teicoplanin and/or other glycopeptide antibiotics in the pursuit of novel antibacterial bone biomaterials.
Topics: Anti-Bacterial Agents; Biocompatible Materials; Chromatography, High Pressure Liquid; Glycopeptides; Oxides; Phosphates; Staphylococcus aureus; Teicoplanin; Titanium
PubMed: 36198734
DOI: 10.1038/s41598-022-20310-8 -
Drug Design, Development and Therapy 2023To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo... (Observational Study)
Observational Study
PURPOSE
To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.
METHODS
This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.
RESULTS
The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (V), inter-compartmental clearance (Q) and volumes of the peripheral compartments (V) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m) to attain target trough concentration (C, PTA 52.8%). When eGFR > 30 mL/min/1.73 m, increasing dose and the administration times of loading doses were the preferred options to achieve target C based on the renal function and types of infection.
CONCLUSION
The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.
Topics: Humans; Teicoplanin; Anti-Bacterial Agents; Critical Illness; Prospective Studies; Kidney; Microbial Sensitivity Tests
PubMed: 37546521
DOI: 10.2147/DDDT.S413662 -
Journal of Korean Medical Science Feb 2023Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant . Despite some... (Review)
Review
BACKGROUND
Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant . Despite some comparable advantages, there is no guideline or clinical recommendation for teicoplanin in the pediatric population, unlike vancomycin where abundant studies and the recently revised guideline on therapeutic drug level monitoring (TDM) exist.
METHODS
The systematic review was performed in accordance with the preferred reporting items for systematic reviews. Two authors (JSC and SHY) searched PubMed, Embase, and Cochrane Library databases using relevant terms independently.
RESULTS
Fourteen studies were finally included with a total of 1,380 patients. TDM was available in 2,739 samples collected in the nine studies. Dosing regimens varied widely, and eight studies used recommended dosing regimens. Timing for measuring TDM was mostly 72-96 hours or longer after the initiation of the first dose, which was expected to be a steady-state. The majority of studies had target trough levels of 10 µg/mL or above. Three studies reported that the clinical efficacy and treatment success rate of teicoplanin was 71.4%, 87.5%, and 88%. Adverse events associated with teicoplanin use were described in six studies with a focus on renal and/or hepatic impairment. Except for one study, no significant relation was noted between the incidence of adverse events and trough concentration.
CONCLUSION
Current evidence on teicoplanin trough levels in pediatric populations is insufficient due to heterogeneity. However, target trough levels with favorable clinical efficacy are achievable by recommended dosing regimen in the majority of patients.
Topics: Humans; Child; Teicoplanin; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Drug Monitoring; Staphylococcal Infections
PubMed: 36808548
DOI: 10.3346/jkms.2023.38.e62 -
Journal of Global Antimicrobial... Mar 2021Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we...
OBJECTIVES
Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model.
METHODS
Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program.
RESULTS
Target values offC/MIC (r = 0.94) of teicoplanin for static effect and 1 log kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC/MIC (r = 0.92) of teicoplanin for static effect and 1 log kill against MSSA were 30.4 and 70.56, respectively. Target values of fC/MIC (r = 0.91) of teicoplanin for static effect and 1 log kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC/MIC (r = 0.92) of teicoplanin for static effect and 1 log kill against MRSA were 54.8 and 76.4, respectively.
CONCLUSION
These results suggest thatfC/MIC and fAUC/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.
Topics: Animals; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcus aureus; Teicoplanin; Thigh
PubMed: 33290889
DOI: 10.1016/j.jgar.2020.11.014 -
Journal of Clinical Microbiology Sep 2016The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant... (Review)
Review
The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit in vitro activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate in vitro activity against VRE. These new Gram-positive agents are reviewed here.
Topics: Anti-Infective Agents; Drug Approval; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Organophosphates; Oxazoles; Teicoplanin; United States; Vancomycin-Resistant Enterococci
PubMed: 26962092
DOI: 10.1128/JCM.03395-15 -
Chemical Research in Toxicology Feb 2022Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug...
Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug reactions, particularly following previous exposure to vancomycin. In this study, we generated teicoplanin-specific monoclonal T-cell populations from healthy volunteers expressing HLA-A*32:01 and defined pathways of T-cell activation and HLA allele restriction. Teicoplanin-responsive T-cells were CD8+, HLA class I-restricted, and cross-reacted with the lipoglycopeptide daptomycin in proliferation and cytokine/cytolytic molecule (granzyme B, Perforin, and FasL) release assays. These data show that teicoplanin activates T-cells, which may play a role in the pathogenesis of teicoplanin-induced adverse events, in HLA-A*32:01 positive donors.
Topics: Anti-Bacterial Agents; HLA-A Antigens; Healthy Volunteers; Humans; T-Lymphocytes; Teicoplanin
PubMed: 35107993
DOI: 10.1021/acs.chemrestox.1c00425 -
Antimicrobial Agents and Chemotherapy Sep 2017The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of...
The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).
Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Extracorporeal Membrane Oxygenation; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Monte Carlo Method; Mycoses; Myocardial Infarction; Myocarditis; Prospective Studies; Renal Replacement Therapy; Shock, Cardiogenic; Teicoplanin; Young Adult
PubMed: 28674057
DOI: 10.1128/AAC.01015-17 -
Antimicrobial Agents and Chemotherapy Jun 2017The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough...
The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h ( < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).
Topics: Aged; Anti-Bacterial Agents; Female; Hematologic Neoplasms; Humans; Kidney Function Tests; Male; Microbial Sensitivity Tests; Middle Aged; Protein Binding; Serum Albumin; Teicoplanin
PubMed: 28320714
DOI: 10.1128/AAC.02466-16