BACKGROUND: Teicoplanin (TEIC) is a nephrotoxic agent. However, little is known about the effects of concomitant medications on nephrotoxicity. In this study, we investigated the effects of concomitant drugs on nephrotoxicity.
METHODS: A retrospective observational case-control study was conducted on patients (≥18 years) who started TEIC at the Tokyo Dental College, Ichikawa General Hospital, between January 2013 and April 2023. The primary outcome was nephrotoxicity, defined as an increase in serum creatinine levels of ≥50 % or ≥0.5 mg/dL from baseline. Logistic regression analysis was used to determine the risk factors for nephrotoxicity associated with TEIC. In addition, we investigated the relationship between nephrotoxicity and predicted free TEIC concentrations.
RESULTS: Of 305 patients, 43 (14.1 %) developed nephrotoxicity. The multivariate logistic regression analysis identified that serum albumin (odds ratio [OR] = 0.50, 95 % confidence interval [CI] 0.27-0.89, p = 0.02), concomitant use of loop diuretics (OR = 2.22, 95 % CI 1.10-4.59, p = 0.03), antivirals (OR = 3.24, 95 % CI 1.32-7.62, p < 0.01), and vasopressors (OR = 2.57, 95 % CI 1.10-5.78, p = 0.03) were the associated risk factors for nephrotoxicity in patients administered with TEIC. In 216 patients, predicted TEIC concentrations were 3.6 [interquartile range (IQR), 2.6-4.9] μg/mL in the nephrotoxicity group versus 3.6 [IQR, 2.5-4.7] μg/mL in the non-nephrotoxicity group, with no significant difference (p = 0.69).
CONCLUSIONS: Our results indicate the importance of modifying the concomitant use of loop diuretics, antivirals, and vasopressors.

BACKGROUND: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016.
METHODS: This study investigated 55 MRSA bloodstream isolates (02/2015-02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16-33 and 19-362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM).
RESULTS: S.aureus BSI strain 19-362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16-33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16-33 (p < 0.05) compared to 19-362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin.
CONCLUSIONS: In light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.

1,4-dihydropyridine (DHP) scaffold occupies a prominent position among all heterocyclic compounds owing to its versatile pharmacological properties, particularly its well-known calcium channel blocking activity. In the quest of developing new calcium channel blockers, fifty seven 5-oxo-hexahydroquinoline (HHQ) derivatives carrying DHP framework in a condensed ring system were recently synthesized as racemic mixtures. Due to their potential as drug candidates, enantiomers arising from the asymmetric center at the C-4 position of the HHQ ring were separated. Four modern columns packed with 2.7 µm superficially porous particles bonded with a chiral selector were used. The chiral selectors were three macrocyclic glycopeptide selectors: vancomycin, teicoplanin, and a macrocyclic derivative called nico. The fourth bonded selector was the dinitrobenzamido-tetrahydrophenanthrenyl derivative called Whelko. The four chromatographic modes were assayed with the mobile phase compositions: reversed phase with acetonitrile/buffer 30/70 %v/v, normal phase with hexane/ethanol 80/20 %v/v, and subcritical fluid chromatography with CO2/methanol 80/20 %v/v at 25 °C. The WhelkoShell column was the most effective in separating this set of 57 compounds. Several enantioresolution factors passed 20 with enantioselectivity ratios higher than 4. Molecular modeling showed that the compounds had a T-shape that fitted well the molecular structure of the WhelkoShell selector in the normal or subcritical modes. Additionally, seven compounds had a second chiral center. The NicoShell column was able to separate all four stereoisomers of these compounds in the reversed phase mode. The preparative production of pure enantiomers of these compounds would be straightforward using the WhelkoShell column in the subcritical mode.

Peritoneal dialysis (PD) is a vital treatment modality for renal failure patients, facilitating the removal of excess fluid and unwanted substances. However, peritonitis, a significant complication experienced by PD patients, necessitates careful selection of antibiotics to ensure successful treatment. Commonly used antibiotics in PD patients, such as cephalosporins and glycopeptides like vancomycin, have been associated with undesirable side effects and high failure rates. In response to these challenges, teicoplanin, a novel glycopeptide antibiotic, has gained attention due to its similar range of activity to vancomycin, extended half-life, reduced side effects, and improved elimination. The objective of this study is to comprehensively review the efficacy, mechanism of action, adverse effects, and pharmacological benefits of teicoplanin in peritoneal dialysis patients. Our research involved an extensive review of 21 articles from reputable databases, including Google Scholar, PubMed, and ScienceDirect. The data extracted from these studies was meticulously evaluated to comprehensively understand teicoplanin\'s clinical profile in this specific patient population. Major findings of these studies are that glycopeptide-based regimens have higher cure rates over first-generation cephalosporins or fluoroquinolones, and teicoplanin demonstrated several advantages over vancomycin, such as a higher therapeutic index, good tolerance, longer half-life, lower rates of nephrotoxicity, improved elimination while being equally effective. Teicoplanin is typically administered to peritoneal dialysis patients with a loading dose of 400 mg, aiming to achieve a trough concentration of 10-15 mg/dl. Teicoplanin\'s improved tolerability and lack of regular serum level monitoring requirements make it a promising alternative to traditional antibiotics for clinical use.

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (β-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and β-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

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.

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon.
METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments.
RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020).
CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.

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BACKGROUND: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications.
METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections.
RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients\' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6).
CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

Taking into account the drug resistance of antibiotics, teicoplanin has been banned in the veterinary field. Also, it brings threat to people\'s health when they eat foods containing teicoplanin residue. In addition, the abuse of teicoplanin in humans and food animals also poses a potential risk to water. Therefore, it is crucial to purify teicoplanin from food before quantifying its amount. In this study, researchers employed boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) for the isolation of teicoplanin. The 3-fluoro-4-formylphenylboronic acid-functionalized silica nanoparticle substrate was first used as the supporting material for immobilizing teicoplanin. Next, the substrate surface was coated with an imprinting coating whose thickness could be controlled, produced through the self-copolymerization of dopamine and m-aminophenylboronic acid (APBA) in water. After the template was removed, 3D cavities that matched the template were created in the imprinting layer. The prepared teicoplanin-imprinted silica nanoparticles exhibited several significant satisfactory results such as good specificity, high binding capacity (46.9 ± 2.3 mg g-1), moderate binding constant ((5.46 ± 0.18) × 10-5 M-1), fast kinetics (8 min) and low binding pH (pH 5.0) toward teicoplanin. The teicoplanin-imprinted silica nanoparticles could still be reused after seven cycles of adsorption-desorption, which indicated a high chemical stability. In addition, recoveries of the proposed method for teicoplanin at three spiked levels in milk and water ranged from 91.8 to 105.6% and 92.3 to 97.4%, respectively. The teicoplanin-imprinted silica nanoparticles are capable of identifying the target teicoplanin in real samples in a simple, fast, selective and efficient manner.