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Frontiers in Immunology 2023Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of...
BACKGROUND
Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers.
METHODS
Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified and using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples.
RESULTS
95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model and . External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI.
CONCLUSION
The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.
Topics: Animals; Mice; Toll-Like Receptor 4; Transcriptome; Vancomycin; Acute Kidney Injury
PubMed: 37063876
DOI: 10.3389/fimmu.2023.1126348 -
Journal of Microbiology, Immunology,... Aug 2017The aim of this study is to determine the best dosing strategy for vancomycin by studying the associated factors and examining correlations between the area under the...
BACKGROUND/PURPOSE
The aim of this study is to determine the best dosing strategy for vancomycin by studying the associated factors and examining correlations between the area under the plasma concentration-time curve (AUC) values and trough concentrations in children.
METHODS
Children aged 3 months to 18 years were included if they received vancomycin for more than three doses between January 1, 2010 and December 31, 2012 and had one or more serum vancomycin trough concentrations. Vancomycin clearance (CL) was calculated using the following model: CL = 0.248*Wt*(0.48/serum creatinine)*[ln (age)/7.8]. The AUC (mg-h/L) was calculated by 24-hour dose (mg/kg/d)/CL(L/h). The value of AUC divided by the minimum inhibitory concentration (MIC) of vancomycin was AUC/MIC.
RESULTS
A total of 218 children were included. The mean age was 6.0 ± 5.1 years and the mean body weight was 20 ± 11.7 kg. Vancomycin trough concentrations were moderately correlated with AUC values (r = 0.232, p < 0.01). Dosing of 15 mg/kg/dose q6h produced significantly higher AUC values (p < 0.001) and vancomycin trough concentrations (p < 0.001) compared to dosing of 10 mg/kg/dose q6h. In children receiving a 10-mg/kg/dose q6h, 5.6% (5/90) achieved the target trough concentrations of 15-20 μg/mL and 9.5% (5/90) achieved the goal AUC/MIC ≥ 400. In children receiving a 15-mg/kg/dose q6h, 13% (6/46) achieved the target trough concentrations of 15-20 μg/mL, whereas 54.3% (25/46) achieved the goal AUC/MIC ≥ 400.
CONCLUSION
A 15-mg/kg/dose q6h compared to a 10-mg/kg/dose q6h is more likely to achieve target trough concentrations of 15-20 μg/mL and the goal AUC/MIC ≥ 400.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Retrospective Studies; Serum; Vancomycin
PubMed: 26462708
DOI: 10.1016/j.jmii.2015.08.027 -
Journal of the American Chemical Society Sep 2020A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits...
A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits with kinetically controlled diastereoselective introduction of all three elements of atropisomerism. In addition to new syntheses of three of the seven amino acid subunits, highlights of the approach include a ligand-controlled atroposelective one-pot Miyaura borylation-Suzuki coupling sequence for introduction of the AB biaryl axis of chirality (>20:1 dr), an essentially instantaneous and scalable macrolactamization of the AB ring system nearly free of competitive epimerization (>30:1 dr), and two room-temperature atroposelective intramolecular SAr cyclizations for sequential CD (8:1 dr) and DE ring closures (14:1 dr) that benefit from both preorganization by the preformed AB ring system and subtle substituent effects. Combined with a protecting group free two-step enzymatic glycosylation of vancomycin aglycon, this provides a 19-step total synthesis of vancomycin. The approach paves the way for large-scale synthetic preparation of pocket-modified vancomycin analogues that directly address the underlying mechanism of resistance to vancomycin.
Topics: Anti-Bacterial Agents; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Stereoisomerism; Vancomycin
PubMed: 32885969
DOI: 10.1021/jacs.0c07433 -
Orthopaedic Surgery Nov 2017Intra-site prophylactic vancomycin in spine surgery is an effective method of decreasing the incidence of postsurgical wound infection. However, there are differences in... (Meta-Analysis)
Meta-Analysis Review
Intra-site prophylactic vancomycin in spine surgery is an effective method of decreasing the incidence of postsurgical wound infection. However, there are differences in the prophylactic programs used for various spinal surgeries. Thus, this systematic review and meta-analysis aimed to evaluate the effectiveness of using intra-wound vancomycin during spinal surgery and to explore the effects of dose-dependence and the method of administration in a subgroup analysis. A total of 628 citations or studies were searched in PubMed, Ovid, Web of Science, and Google Scholar that were published before August 2016 with the terms "local vancomycin", "intra-wound vancomycin", "intraoperative vancomycin", "intra-site vancomycin", "topical vancomycin", "spine surgery", and "spinal surgery". Finally, 19 retrospective cohort studies and one prospective case study were eligible for inclusion in the systematic review and meta-analysis. The odds of developing postsurgical wound infection without prophylactic local vancomycin use were 2.83-fold higher than the odds of experiencing wound infection with the use of intra-wound vancomycin (95% confidence interval, 2.03-3.95; P = 0.083; I = 32.2%). The subgroup analysis including the dosage and the method of administration, revealed different results compared to previous research. The value of I in the 1-g group was 27.2%, which was much lower than in the 2-g group (I = 57.6%). At the same time, the value of I was 0.0% (P = 0.792, OR = 2.70) when vancomycin powder was directly sprinkled into all layers of the wound. However, there is high heterogenicity (I = 60.0%, P = 0.007, OR = 2.83) when vancomycin powder is not exposed to the bone graft and instrumentation. There are differences found with the method of local application of vancomycin for reducing postoperative wounds and further studies are necessary, including investigations focusing on the dose-dependent effects during spinal or the topical pharmacokinetic and other orthopaedic surgeries.
Topics: Administration, Topical; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Humans; Models, Statistical; Orthopedic Procedures; Spine; Surgical Wound Infection; Treatment Outcome; Vancomycin
PubMed: 29178308
DOI: 10.1111/os.12356 -
PloS One 2023Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers.
BACKGROUND
Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers.
AIMS
Identifying barriers to compliance with vancomycin dosing and therapeutic drug monitoring guidelines (TDM) and possible ways to enhance compliance based on the healthcare providers' (HCPs) perspective.
METHODS
A qualitative study based on semi-structured interviews with HCP (physicians, pharmacists, and nurses) was conducted at two Jordanian Teaching Hospitals. Interviews were audio-recorded and analyzed through thematic analysis. The COREQ criteria for qualitative research were utilized to report the study findings.
RESULTS
A total of 34 HCPs were interviewed. HCP perceived several factors as barriers to guideline recommendation compliance. Such factors included negative perception towards prescription guidelines, lack of knowledge regarding TDM guidelines, the hierarchy of medication management, work pressure, and ineffective communication among healthcare providers. Potential strategies to optimize guidelines adaptation included providing HCPs with more training and decision support tools in addition to activating the role of clinical pharmacists.
CONCLUSIONS
The main barriers to guideline recommendations uptake were identified. Interventions should address those barriers related to the clinical environment, including enhancing interprofessional communication related to vancomycin prescription and TDM, reducing workload and providing support systems, promoting educational and training programs, in addition to adopting guidelines suitable for the local environment.
Topics: Humans; Vancomycin; Drug Monitoring; Health Personnel; Physicians; Pharmacists; Qualitative Research
PubMed: 37195936
DOI: 10.1371/journal.pone.0285717 -
Medicina (Kaunas, Lithuania) Mar 2023: Numerous studies have indicated that antibiotics may adversely affect testicular and sperm function. As an alternative to penicillin, vancomycin is a glycopeptide...
: Numerous studies have indicated that antibiotics may adversely affect testicular and sperm function. As an alternative to penicillin, vancomycin is a glycopeptide antibiotic developed to treat resistant strains of Staphylococcus aureus. A few studies have suggested that vancomycin could cause testicular toxicity and apoptosis. Vancomycin, however, has not been investigated in terms of its mechanism of causing testicular toxicity. An experiment was conducted to investigate the effects of resveratrol (20 mg/kg, oral gavage) against vancomycin (200 mg/kg, i.p.) on the testicular function of Wistar rats for one week (7 days). There were three subgroups of animals. First, saline (i.p.) was administered to the control group. Then, in the second group, vancomycin was administered. Finally, vancomycin and resveratrol were administered in combination in the third group. After seven days of vancomycin treatment, testosterone levels, sperm counts, and sperm motility were significantly reduced, but resveratrol attenuated the effects of vancomycin and restored the testosterone levels, sperm counts, and sperm motility to normal. In the presence of resveratrol, the vancomycin effects were attenuated, and the luteinizing hormone and follicular hormone levels were normalized after seven days of treatment with vancomycin. Histologically, vancomycin administration for seven days caused damage to testicular tissues and reduced the thickness of the basal lamina. However, the resveratrol administration with vancomycin prevented vancomycin's toxic effects on testicular tissue. Resveratrol showed potential protective effects against vancomycin-induced testicular toxicity in Wistar rats.
Topics: Rats; Male; Animals; Humans; Resveratrol; Rats, Wistar; Vancomycin; Sperm Count; Sperm Motility; Semen; Testicular Diseases; Testosterone
PubMed: 36984488
DOI: 10.3390/medicina59030486 -
European Journal of Drug Metabolism and... Jan 2022BACKGROUND AND OBJECTIVE: Vancomycin is often used in the ICU for the treatment of Gram-positive bacterial infection. In critically ill children, there are...
UNLABELLED
BACKGROUND AND OBJECTIVE: Vancomycin is often used in the ICU for the treatment of Gram-positive bacterial infection. In critically ill children, there are pathophysiologic changes that affect the pharmacokinetics of vancomycin. A systematic review of vancomycin pharmacokinetics and pharmacodynamics in critically ill children was performed.
METHODS
Pharmacokinetic studies of vancomycin in critically ill children published up to May 2021 were included in the review provided they included children aged > 1 month. Studies including neonates were excluded. A search was performed using the PubMed, Scopus, and Google Scholar databases. The Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) was used to check for quality and reduce bias. Data on study characteristics, patient demographics, clinical parameters, pharmacokinetic parameters, outcomes, and study limitations were collected.
RESULTS
Thirteen studies were included in this review. A wide variety of dosing and sampling strategies were used in the studies. Methods for estimating vancomycin pharmacokinetics, especially the area under the curve over 24 h, varied. Vancomycin doses of 20-60 mg/kg were given daily. This resulted in high variability in pharmacokinetic parameters. Vancomycin trough level was less than 15 μg/mL in most of the studies. Vancomycin clearance ranged from 0.05 to 0.38 L/h/kg. Volume of distribution ranged from 0.1 to 1.16 L/kg. Half-life was between 2.4 and 23.6 h. Patients in the study receiving continuous vancomycin infusion had AUC < 400 µg·h/mL.
CONCLUSION
There is large variability in the pharmacokinetics of vancomycin among critically ill patients. Studies to assess the factors responsible for this variability in vancomycin pharmacokinetics are needed.
Topics: Anti-Bacterial Agents; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Male; Vancomycin
PubMed: 34750740
DOI: 10.1007/s13318-021-00730-z -
Frontiers in Bioscience (Scholar... Mar 2018We aimed to assess the anti-biofilm activity of vancomycin, maltodextrin, and their combination against vancomycin resistant (VRSA) and vancomycin-susceptible (VSSA)...
We aimed to assess the anti-biofilm activity of vancomycin, maltodextrin, and their combination against vancomycin resistant (VRSA) and vancomycin-susceptible (VSSA) strains based on an static model. Biofilms of 4 VSSA and 2 VRSA strains were grown in a 96-well static model. Vancomycin 2 mM, maltodextrin 10 mM, and both in combination were tested using tetrazolium salt (XTT), resazurin, and cfu/well counts. The efficacy of the antimicrobial solutions was expressed as the percentage reduction in metabolic activity with each method. Overall percentage reduction in the metabolic activity of VSSA was 79.3%, 34%, and 75.7% for vancomycin, maltodextrin, and their combination (p<0.001). Overall percentage reduction in metabolic activity of VRSA was 46.7%, 27.8%, and 34.6% for vancomycin, maltodextrin, and their combination (p>0.05). Maltodextrin did not improve the anti-biofilm efficacy of vancomycin in VSSA or in VRSA biofilms. XTT cannot replace cfu counts as a means of quantifying cell viability. Futures studies are needed to assess the synergistic effects of other non-antimicrobial molecules combined with vancomycin.
Topics: Anti-Bacterial Agents; Biofilms; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Polysaccharides; Staphylococcal Infections; Staphylococcus aureus; Vancomycin
PubMed: 29293434
DOI: 10.2741/s517 -
Clinical Microbiology Reviews Jan 2010The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has... (Review)
Review
Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications.
The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin; Vancomycin Resistance
PubMed: 20065327
DOI: 10.1128/CMR.00042-09 -
Biomaterials Advances Jul 2024Surgical site infection (SSI) is a common issue post-surgery which often prolongs hospitalization and can lead to serious complications such as sternal wound infection...
Surgical site infection (SSI) is a common issue post-surgery which often prolongs hospitalization and can lead to serious complications such as sternal wound infection following cardiac surgery via median sternotomy. Controlled release of suitable antibiotics could allow maximizing drug efficacy and safety, and therefore achieving a desired therapeutic response. In this study, we have developed a vancomycin laden PEGylated fibrinogen-polyethylene glycol diacrylate (PF-PEGDA) hydrogel system that can release vancomycin at a controlled and predictable rate to be applied in SSI prevention. Two configurations were developed to study effect of the hydrogel on drug release, namely, vancomycin laden hydrogel and vancomycin solution on top of blank hydrogel. The relationship between the rigidity of the hydrogel and drug diffusion was found to comply with a universal power law, i.e., softer hydrogels result in a greater diffusion coefficient hence faster release rate. Besides, vancomycin laden hydrogels exhibited burst release, whereas the vancomycin solution on top of blank hydrogels exhibited lag release. A mathematical model was developed to simulate vancomycin permeation through the hydrogels. The permeation of vancomycin can be predicted accurately by using the mathematical model, which provided a useful tool to customize drug loading, hydrogel thickness and stiffness for personalized medication to manage SSI. To evaluate the potential of hydrogels for bone healing applications in cardiovascular medicine, we performed a proof-of-concept median sternotomy in rabbits and applied the hydrogels. The hydrogel formulations accelerated the onset of osteo-genetic processes in rabbits, demonstrating its potential to be used in human.
Topics: Vancomycin; Polyethylene Glycols; Fibrinogen; Animals; Hydrogels; Delayed-Action Preparations; Anti-Bacterial Agents; Drug Liberation; Rabbits; Surgical Wound Infection; Humans
PubMed: 38795473
DOI: 10.1016/j.bioadv.2024.213896