Vancomycin Research Articles

Identification of Patients Who Require Two-Point Blood Sampling for the Peak and Trough Values Rather Than One-Point Blood Sampling for the Trough Value for the Evaluation of AUC of Vancomycin Using Bayesian Estimation.

It is recommended to adjust the dose of vancomycin (VCM) with a target area under the concentration-time curve (AUC) of 400-600μg·h/mL. Factors that affect the deviation between AUCs are estimated from the trough value alone and the trough and peak values using practical AUC-guided therapeutic drug monitoring (PAT) for vancomycin. In this study, factors that affect AUC were evaluated. AUCs were estimated from a single trough value and trough and peak values, and the patients were classified into those who showed a 10% or greater deviation (deviation group) and those in whom the deviation was less than 10% (no-deviation group). Risk factors related to ≥ 10% deviation of AUC were identified by univariate and multivariate analysis. As a result of univariate and multivariate analysis of 30 patients in the deviation group and 344 patients in the no-deviation group, a creatinine clearance (CLcr) of ≥ 110mL/min (odds ratio (OR) = 3.697, 95% confidence interval (CI) = 1.616-8.457, p = 0.002), heart failure with a brain natriuretic peptide (BNP) of ≥ 300pg/mL (OR = 4.854, 95%CI = 1.199-19.656, p = 0.027), and the concomitant use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (ACE-I/ARB) (OR = 2.544, 95%CI = 1.074-6.024, p = 0.034) were identified as risk factors of ≥ 10% deviation of AUC. Estimation of AUC by two-point blood sampling for the trough and peak values rather than one-point blood sampling for the trough value is suggested to improve the prediction accuracy in patients with enhanced renal function, severe heart failure, and patients using ACE-I/ARB.

Silk fibroin/chitosan thiourea hydrogel scaffold with vancomycin and quercetin-loaded PLGA nanoparticles for treating chronic MRSA osteomyelitis in rats

Chronic osteomyelitis presents significant treatment challenges, necessitating an efficient system for infection elimination and bone repair. This study developed a natural hydrogel scaffold using silk fibroin (SF) and chitosan thiourea (CST), incorporating vancomycin (VC) and quercetin (QC) loaded PLGA nanoparticles (NPs) for dual-purpose treatment. SF/CST hydrogel scaffolds exhibited homogeneous porosity and smaller interconnected pore size than pure SF and pure CST hydrogel scaffolds. Optimal PLGA/QC NPs measured 206 nm in size, displayed spherical morphology, had uniform distribution, and achieved 87 % QC loading. The release study showed sustained long-term release of VC and QC from the hydrogel scaffolds for over 20 days. Biocompatibility tests indicated that hydrogel scaffolds promoted osteoblast adhesion without cytotoxicity, with QC-containing scaffolds enhancing osteoblast growth. Antibacterial tests confirmed retained VC activity against methicillin-resistant Staphylococcus aureus (MRSA) in SF/CST. An experimental study assessed the efficacy of the hydrogel scaffolds in a MRSA-infected rat osteomyelitis model. Radiographic scores demonstrated a significant reduction for SF/CST-VC-PLGA/QC NPs compared to control, indicating reduced osteomyelitis effects. Macroscopic evaluations showed notable reductions in gross pathological effects for VC-containing groups. Histopathological assessments revealed significantly lower osteomyelitis scores and higher healing scores in the SF/CST-VC-PLGA/QC NPs, with reduced inflammatory cell infiltration and more organized connective tissue formation. In conclusion, SF/CST-VC-PLGA/QC NPs is an effective dual drug delivery system for osteomyelitis treatment, demonstrating significant antibacterial activity, enhanced bone regeneration, and reduced infection rate.

Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Specific Ribotypes

Abstract Background Reduced vancomycin (VAN) susceptibility in clinical Clostridioides difficile isolates is correlated with poor clinical outcomes. However, factors associated with infection with these strains are unknown. The goal of this study was to determine risk factors for reduced VAN susceptibility among clinical isolates of C. difficile. Methods This multicenter cohort study included adults with C. difficile infection (CDI) between 2016 and 2021. Clinical C. difficile isolates underwent agar dilution VAN susceptibility testing and ribotyping. Reduced susceptibility was defined as a minimum inhibitory concentration (MIC) > 2 µg/mL. Medical charts were reviewed for host, pathogen, and hospital characteristics and assessed for predictors of reduced VAN susceptibility. Results Five hundred and ninety-four hospitalized patients with CDI between 2016 and 2021 (female: 57%, age >65 years: 55%, White/non-Hispanic: 59%, nonsevere CDI episode: 53%) were identified. Of 594 isolates, 173 (29%) had reduced VAN susceptibility (MIC50: 2 µg/mL, MIC90: 4 µg/mL). In multivariable analysis, ribotype (RT) 027 (odds ratio [OR]: 13.4; 95% confidence interval [CI], 7.7–23.4; P < .0001) and RT 255 (OR: 2.9; 95% CI, 1.4–6.1; P = .005) were positively associated with reduced VAN susceptibility whereas RT 014–020 (OR: 0.41; 95% CI, 0.21–0.80; P = .0092) was more likely to be susceptible to VAN. The prevalence of strains with reduced VAN susceptibility increased over time (P = .0163). No patient- or hospitalization-specific variable predicted infection with reduced susceptibility strain. Conclusions Certain ribotypes, including RT 027, were the sole independent risk factors for reduced VAN susceptibility. Increased clinical surveillance of these strains, especially RT 027, and their antibiotic susceptibly is warranted to inform prescribing practices.

Fidaxomicin versus oral vancomycin for Clostridioides difficile infection among patients at high risk for recurrence based on real-world experience.

Clostridioides difficile infection (CDI) is a common nosocomial infection and is associated with a high healthcare burden due to high rates of recurrence. In 2021 the IDSA/SHEA guideline update recommended fidaxomicin (FDX) as first-line therapy. Our medical center updated our institutional guidelines to follow these recommendations, prioritizing FDX use among patients at high risk for recurrent CDI (rCDI). This pre- post- quasi-experimental study included patients with a presumptive diagnosis of CDI at risk for recurrence (age >/= 65 years, immunocompromised, severe CDI) that received vancomycin (VAN) or FDX between October 2019 to October 2022. Patients who received bezlotoxumab, had fulminant CDI, or received <10 days of the same antibiotic for their full treatment course were excluded. Patients were evaluated for rCDI within 8 weeks of completion of therapy, subsequent episodes of CDI within 12 months, and CDI-related admissions within 30 days. Of 397 CDI regimens evaluated, 196 received VAN and 201 received FDX. Rates of rCDI (9.2% vs 10%, P = 0.86), subsequent CDI within 12 months of therapy completion of therapy (19.4% vs 26%, P = 0.12) and 30-day CDI-related readmissions (3% vs 4.5%, P = 0.6) were similar between patients who received VAN versus FDX. Outcomes were similar between patients treated with FDX and VAN for the treatment of CDI among those at high risk for rCDI, using our outlined criteria. Although we observed a trend toward lower rates of rCDI among immunocompromised patients, this finding was not significant. Further investigation is needed to determine which patients with CDI may benefit from FDX.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.

Clinical Efficacy of Therapeutic Agents for Clostridioides difficile Infection Based on Four Severity Classifications.

Japanese guidelines recommend metronidazole (MNZ) and vancomycin (VCM) for non-severe and severe cases of Clostridioides difficile infection (CDI), respectively. In the present study, we investigated the use of CDI antimicrobials and evaluated their clinical efficacy and validity using four severity classifications. A retrospective chart review was conducted using the data of 137 inpatients with initially positive C. difficile toxin test results and the initiation of CDI antimicrobials between April 2015 and March 2019. Patients treated with VCM or oral MNZ were included for clinical efficacy analysis of CDI antimicrobials and validation of severity classifications. The endpoints were CDI recurrence, 30-day mortality, and diarrhea cure rates. No significant differences were found between the VCM and oral MNZ groups in the CDI recurrence rate (10.4% vs. 12.7%, P = 0.707), 30-day mortality rate (12.5% vs. 5.6%, P = 0.162), and diarrhea cure rate (61.9% vs. 72.7%, P = 0.238), regardless of severity. Treatment with oral MNZ for non-severe cases was promising, confirming its usefulness according to Japanese guidelines. Further investigation of the clinical efficacy of oral MNZ in patients with first-episode CDI and evaluation of the preferred severity classification are warranted.

Efficacy and safety of vancomycin compared with those of alternative treatments for methicillin-resistant Staphylococcus aureus infections: An umbrella review.

To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359). This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives. The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.

Preparation and evaluation activity of silica nanoparticles against bacterial oral infections: in vitro study

Background: Oral infections are commonly encountered among populations and frequently result in chronic inflammatory conditions that impact the dental structures (e.g., caries), the gingival tissues surrounding the dental elements (e.g., gingivitis and endodontic lesions), as well as the supporting structures of the teeth (e.g., periodontitis). Objectives: The objective of this study is to ascertain the minimum inhibitory concentrations of silica nanoparticles in order to evaluate the antibacterial efficacy of these nanoparticles against oral pathogens. Materials and Methods: A total of 100 clinical samples were collected from individuals suffering from diverse oral infections. They were diagnosed based on the culture and microscopic characteristics, as well as the diagnosis with Vitek2 device for the purpose of diagnosis for the level of species. Molecular identification of Viridians Streptococci was performed using PCR to detect the 16sRNA gene. The study also involved the synthesis of silica nanoparticles (SiNPs) using the sol-gel technique. Characterization of the SiNPs was conducted through X-ray diffraction (XRD), transmission electron microscopy (TEM), and field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FESEM-EDX). The minimum inhibitory concentration (MIC) of the SiNPs against viridans Streptococci was evaluated using a microdilution assay with the blue-resazurin staining method. The agar well diffusion technique was utilized to assess the antibacterial efficacy of biosynthesized silica nanoparticles against Viridans Streptococci in comparison to a standard antibiotic, utilizing the minimum inhibitory concentration (MIC) as a metric. Results: Fifty pathogenic bacterial strains were obtained from clinical specimens, with the genus Streptococcus comprising 27 of these isolates, which corresponds to 54% of the overall total, thereby constituting the highest proportion observed among all species. Molecular identification of Viridans Streptococci in this study, showed that 10/10(100%) isolates were PCR positive for 16sRNA gene has been applied to pathogenic viridians streptococcal only, which include S. mitis, S. oralis and S. sanguinis. Multidrug-resistant isolates showed significant resistance to various antibiotics, including Erythromycin, Cefotaxime, Cefepime, Ceftriaxone, and Penicillin. Clindamycin also showed resistance. Augmentin showed the highest antimicrobial activity, while Trimethoprim-sulfamethoxazole, Ampicillin, and Vancomycin showed commendable activity. The MIC for the synthesized silica nanoparticles against Viridans Streptococci was determined to be 3.13 mg/mL across all bacterial isolates. The study showed that the bio-synthesized silica nanoparticles had a higher inhibition than the standard antibiotic disc Vancomycin (VA) at a concentration of 3.13 mg/ml, as the average diameter of inhibition reached 26.2 mm, respectively. Conclusion: Silica nanoparticles demonstrated significant efficacy in combating Viridans Streptococci, which are implicated in the etiology of oral infections.

Three New Ent-Kaurane Diterpenes with Antibacterial Activity from Sigesbeckia orientalis.

Three novel ent-kaurane diterpenes, namely sigesbeckin A-C (1-3), in conjunction with eight previously identified analogues (4-11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance.

Sequential release of vancomycin and BMP-2 from chitosan/nano-hydroxyapatite thermosensitive hydrogel for the treatment of chronic osteomyelitis

In this study, we developed scaffolds materials with microspheres to form a double sustained release system.Chitosan/nano-hydroxyapatite (CS-HA) was used as a drug carrier to construct a sustained-release system for Bone morphogenetic protein-2(BMP-2) and Vancomycin (VAN). Furthermore, VAN and BMP-2 loaded microspheres (Ms) were prepared by the emulsion ultrasonic method.The resultant composites were characterized by Scanning electron microscope (SEM), compressive strength, porosity, and biodegradation. The characterization results showed uniform porous and rough surface, enhanced thermal stability, and highest compressive strength ((1.912 ± 0.012) Kpa, the surface of the two microspheres was slightly folded and showed a regular spherical shape.The loading rate of BMP-2 was (59.611 × 10-4 ± 0.023 × 10-4)% and the encapsulation rate was (6.022 ± 0.005)%. The release rate of vancomycin and BMP-2 was 57.194% and 12.968% respectively. Osteogenic differentiation of Bone marrow mesenchymal stem cells (BMSCs) was confirmed by alkaline phosphatase quantification. The deposition of late osteogenic markers (calcium phosphates) detected by Alizarin red, which indicated extracellular matrix mineralization. The results showed that BMP-2/VAN in CS-HA hydrogel successfully achieved the sequential release of the double drugs, which could benefit bone regeneration.

Integrated Electrochemical Aptamer Biosensing and Colorimetric pH Monitoring via Hydrogel Microneedle Assays for Assessing Antibiotic Treatment.

Current methods for therapeutic drug monitoring (TDM) have a long turnaround time as they involve collecting patients' blood samples followed by transferring the samples to medical laboratories where sample processing and analysis are performed. To enable real-time and minimally invasive TDM, a microneedle (MN) biosensor to monitor the levels of two important antibiotics, vancomycin (VAN) and gentamicin (GEN) is developed. The MN biosensor is composed of a hydrogel MN (HMN), and an aptamer-functionalized flexible (Flex) electrode, named HMN-Flex. The HMN extracts dermal interstitial fluid (ISF) and transfers it to the Flex electrode where sensing of the target antibiotics happens. The HMN-Flex performance is validated ex vivo using skin models as well as in vivo in live rat animal models. Data is leveraged from the HMN-Flex system to construct pharmacokinetic profiles for VAN and GEN and compare these profiles with conventional blood-based measurements. Additionally, to track pH and monitor patient's response during antibiotic treatment, an HMN is developed that employs a colorimetric method to detect changes in the pH, named HMN-pH assay, whose performance has been validated both in vitro and in vivo. Further, multiplexed antibiotic and pH detection is achieved by simultaneously employing the HMN-pH and HMN-Flex on live animals.

Comparison of incidence of hyponatremia between linezolid and vancomycin in neonates and infants

A previous study reported that the incidence of hyponatremia after linezolid (LZD) use was higher than that with vancomycin (VCM) use in adults. However, hyponatremia due to LZD in neonates and infants was not investigated. This study aimed to compare the incidence of hyponatremia between LZD and VCM use in neonates and infants.The retrospective study was conducted at the Aichi Medical University Hospital. All patients who were cared for in NICU or GCU and received ≥3 days of LZD or VCM were included in this study. Hyponatremia was defined as serum sodium level ≤134 mEq/L and ≥5 % decrease from baseline after administration of LZD or VCM.A total of 76 patients (LZD, N = 36; VCM, N = 37) were included. There was no significant difference in the incidence of hyponatremia between the two groups (19.4 % vs 16.2 %, p = 0.72). The proportion of patients with a minimum value of serum sodium ≤134 mEq/L during treatment was 47.3 % in the LZD group and 35.1 % in the VCM group (p = 0.29), and the decrease in serum sodium level from baseline to the minimum value was 80.5 % and 78.4 %, respectively (p = 0.85).In conclusion, there was no significant difference in the incidence of hyponatremia between the LZD and VCM groups. Therefore, it is not necessary to avoid LZD use in neonates and infants because of the risk of hyponatremia.

Virulence Factors and Susceptibility to Ciprofloxacin, Vancomycin, Triclosan, and Chlorhexidine among Enterococci from Clinical Specimens, Food, and Wastewater.

Enterococcus faecalis and E. faecium are opportunistic pathogens commonly found in the microbiota of humans and other animals as well as in the environment. This article presents the results of antimicrobial susceptibility testing using phenotypic methods (broth microdilution and standardized disk diffusion) on selected clinical, food, and wastewater isolates of E. faecalis and E. faecium. The isolates were divided into subgroups based on their sensitivity to the following antibiotics: vancomycin (VAN) and ciprofloxacin (CIP), and biocides triclosan (TCL) and chlorhexidine (CHX). The study also investigated in vitro virulence factors, including biofilm formation ability, cell surface hydrophobicity (CSH) and β-hemolysis, to explore aspects of pathogenesis. In our study, regardless of the isolation source, VAN-resistant (VAN-R) and CIP-resistant (CIP-R) E. faecalis and E. faecium were detected. The highest proportion of CIP-R strains was found among clinical isolates of E. faecalis and E. faecium, with clinical E. faecium also showing the highest proportion of VAN-R strains. But the highest proportion of VAN-R E. faecalis strains was found in wastewater samples. The highest TCL MIC90 values for E. faecalis were found in wastewater isolates, while for E. faecium, the highest TCL MIC90 values were observed in food isolates. The highest CHX MIC90 values for both E. faecalis and E. faecium were identified in clinical specimens. The results obtained for E. faecalis did not indicate differences in TCL MIC and CHX MIC values with respect to sensitivity to VAN and CIP. Higher CHX MIC50 and CHX MIC90 values were obtained for CIP-R and VAN-R E. faecium. Among the tested isolates, 97.75% of the E. faecalis isolates produced biofilm, while 72.22% of the E. faecium isolates did so as well. In biofilm-forming strength categories III and IV, statistically significantly higher proportions of CIP-susceptible (CIP-S) and VAN-susceptible (VAN-S) E. faecalis were determined. In category III, there is no statistically significant difference in E. faecium CIP sensitivity. In category IV, we had a significantly higher proportion of CIP-R strains. On the other hand, the association between the moderate or strong category of biofilm formation and E. faecium VAN susceptibility was not significant. E. faecalis isolated from wastewater had a CSH index (HI) ≥ 50%, categorizing them as "moderate", while all the other strains were categorized as "low" based on the CSH index. Among the E. faecalis isolates, cell surface hydrophobicity indices differed significantly across isolation sources. In contrast, E. faecium isolates showed similar hydrophobicity indices across isolation sources, with no significant difference found. Moreover, no correlation was found between the enterococcal cell surface hydrophobicity and biofilm formation in vitro. After anaerobic incubation, β-hemolytic activity was confirmed in 19.10% of the E. faecalis and 3.33% of the E. faecium strains.

Liquid crystal nanoparticles for oral combination antibiotic therapies: A strategy towards protecting commensal gut bacteria during treatment

Antibiotics are essential for treating infections and reducing risks during medical interventions. However, many commonly used antibiotics lack the physiochemical properties for an efficient oral administration when treating systemic infection. Instead, we are reliant on intravenous delivery, which presents complications outside of clinical settings. Developing novel formulations for oral administration is a potential solution to this problem. We engineered hexosome and cubosome liquid crystal nanoparticles (LCNPs) characterized by small-angle X-ray scattering and cryogenic transmission electron microscopy, and could encapsulate the antibiotics vancomycin (VAN) and clarithromycin (CLA) with high loading efficiencies. By rationally choosing stable lipid building blocks, the loaded LCNPs demonstrated excellent resilience against enzymatic degradation in an in vitro gut model LCNP stability is crucial as premature antibiotic leakage can negatively impact the gut microbiota. In screens against the representative gut bacteria Enterococcus faecalis and Escherichia coli, our LCNPs provided a protective effect. Furthermore, we explored co-administration and dual loading strategies of VAN and CLA, and demonstrated effective loading, stability and protection for E. faecalis and E. coli. This work represents a proof of concept for the early-stage development of antibiotic-loaded LCNPs to treat systemic infection via oral administration, opening opportunities for combination antibiotic therapies.

Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics

The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA’s minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.

Risk of acute kidney injury in patients receiving vancomycin and concomitant piperacillin-tazobactam or carbapenem: a multicenter, retrospective cohort study

ABSTRACT Background Vancomycin (VAN) is empirically used with other broad-spectrum antibiotics, such as piperacillin-tazobactam (PTZ) or carbapenem (CBP). However, conflicting literature on the rates of acute kidney injury (AKI) of VAN with PTZ has been reported. Research design and methods A multicenter, retrospective cohort study of the risk of AKI was conducted in patients receiving VAN and concomitant PTZ or CBP from January 2019 and June 2023. Results In total, 514 eligible patients were included. AKI occurred in a total of 91 patients (17.70%). The prevalence of AKI was significantly higher in the VAN+PTZ group than in the VAN+CBP group (23.37% vs 15.27%, p = 0.028). The survival curves depicting the time to AKI showed the increased incidence and more rapid onset of AKI among patients in the VAN+PTZ group compared to those of the VAN+CBP group (HR 2.186, 95%CI 1.351-3.538, p = 0.0015). VAN+PTZ was associated with a consistently higher AKI rate over VAN+CBP (HR 1.762, 95%CI 1.111-2.795, p = 0.0161) throughout the 14-day combination therapy. VAN with concomitant PTZ, duration of combination therapy ≤4 days and VAN trough concentration >20 mg/L were independent risk factors associated with AKI. Conclusion The prevalence of AKI was found to be higher in patients receiving VAN+PTZ therapy compared to those receiving VAN+CBP therapy based on creatinine-defined AKI.

A novel electrochemical sensor (Au-Ag-ANCCs/r-GO/poly(L-histidine)/GCE) for the simultaneous determination of vancomycin and ceftriaxone residues in chicken meat, fish, and milk samples

The widespread use of antibiotics in humans and animals has resulted in the accumulation of their residues in food and the environment, posing significant threats to human health, the environment, and the global economy. Herein, we have developed a highly sensitive and selective electrochemical sensor by integrating gold-silver alloy nanocoral clusters (Au-Ag-ANCCs) with reduced graphene oxide (r-GO) and poly(L-histidine) composites at the surface of glassy carbon electrode (GCE). The developed sensor (Au-Ag-ANCCs/r-GO/poly(L-histidine)/GCE) was designed for the simultaneous determination of vancomycin (VAN) and ceftriaxone (CFT) residues in food samples. Its morphological and electrochemical properties were exhaustively examined using UV–Vis spectroscopy, FT-IR, XRD, SEM, EDX, EIS, and CV. The sensor showed exceptional performance in a linear range of 1.0 pM to 120 μM for VAN and 1.0 pM to 290 μM for CFT. The limits of detection were 0.11 pM for VAN and 0.017 pM for CFT, while the limits of quantification were 0.36 pM for VAN and 0.057 pM for CFT. The sensor exhibited remarkable reproducibility, repeatability, stability, and selectivity. It was successfully applied to detect VAN and CFT residues in chicken meat, fish, and milk, achieving recoveries of 96.2–102.1 % with relative standard deviation (RSD) below 5 %. Therefore, the sensor is an ideal tool for addressing the global antibiotic residue crisis in food samples.

Wearable Microneedle Biosensor for Real-Time I-Situ Antibiotic Monitoring

Current methods for therapeutic drug monitoring (TDM) have a long turnaround time as they involve collecting patients' blood samples followed by transferring the samples to localized medical laboratories where sample processing and analysis are performed. To enable real-time and minimally invasive TDM, we have developed a microneedle (MN) biosensor to monitor the levels of two important antibiotics, vancomycin (VAN) and gentamicin (GEN). The MN biosensor is composed of a hydrogel MN (HMN), and an aptamer-functionalized flexible (Flex) electrode, named HMN-Flex. The HMN extracts dermal interstitial fluid (ISF) and transfers it to the Flex electrode where sensing of the target antibiotics happens. The HMN-Flex performance has been validated in-vitro using skin models as well as in-vivo in live rat animal models. Furthermore, we leveraged data from the HMN-Flex system to construct pharmacokinetic profiles for VAN and GEN and compared these profiles with conventional blood-based measurements.

In vitro and in vivo evaluation of the layer-by-layer vancomycin with poly(ε-caprolactone) nanosphere-coated Schanz pins for prolonged release

In this research, the effect of layer-by-layer (spray and dip) coating followed by annealing of vancomycin (VCM) and poly(ε-caprolactone) nanospheres (PCLnp) on Schanz pins for prolonged antibacterial activity was investigated. Nanospheres were prepared using the high-pressure homogenizer method and characterized by both functional groups and particle size. The in vitro release profile revealed that after 28 days, the cumulative release of VCM from the VCM-PCLnp coated pins was 753.68 ± 0.19 μg. The coated pins released VCM at a concentration greater than the minimum inhibitory concentration (MIC) and sustained this release for 28 days. Irritation, hemolysis, sensitization, and cytotoxicity assays confirmed that VCM-PCLnp coated pins were highly biocompatible. Additionally, antibacterial assays against methicillin-resistant Staphylococcus aureus (MRSA) revealed prolonged antibacterial resistance. Specifically, the assays demonstrated effective inhibition of Staphylococcus aureus (S. aureus), including the methicillin-resistant strain. This approach involves coating the implants with antibiotics and polymeric nanospheres using a layer-by-layer (dip and spray) method to prolong their antibacterial activity. The results of this study show great promise for successfully treating implant-associated infections. Consequently, we recommend this method for coating other medical devices.

Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality

In this study, it was aimed to determine the effect of sinapic acid (SNP), a polyphenol with antioxidant, anti-inflammatory and antibacterial properties, on testicular damage caused by vancomycin (VCM), a widely used antibiotic against gram positive bacteria. A total of 35 male Sprague Dawley rats were used in the study, divided into five groups: control, VCM, SNP, VCM + SNP 10, and VCM + SNP 20. Following a week of oral administration, the rats were euthanized under sevoflurane anesthesia. While the VCM group had a significant increase in MDA levels, the SNP administration inhibited the increase in MDA levels. VCM led to a significant decrease in GSH levels, SOD, CAT, and GPx activity in the testicular tissue of rats, while SNP administration increased these antioxidant levels. SNP administration decreased the mRNA expression levels of VCM induced Nrf-2, HO-1, and NQO1 in testicular tissue while increasing the levels of MAPK14, MAPK15, JNK, P53, Apaf-1, Caspase-3, Caspase-6, Caspase-9, and Beclin-1 mRNA transcript levels. The VCM group showed a significant increase in Bax and NF-κB levels in testicular tissue, while Bcl-2 levels decreased. VCM significantly decreased sperm motility and increased the percentage of damaged sperm in rats. Histopathological results revealed that VCM caused disruption of basement membranes and disorganization of seminiferous tubules, but SNP administration preserved testicular histology. As a result, VCM increased oxidative stress, apoptosis, and autophagy in the testicular tissue of rats, altered testicular histopathology, and decreased sperm quality, while SNP decreased these effects.