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Journal of Orthopaedic Science :... Nov 2023Intrawound vancomycin powder is effective in preventing surgical site infection after spine surgery. In a previous study, vancomycin-induced cytotoxicity in osteoblasts...
BACKGROUND
Intrawound vancomycin powder is effective in preventing surgical site infection after spine surgery. In a previous study, vancomycin-induced cytotoxicity in osteoblasts was investigated in vitro, and vitamin D3 was verified to be a candidate drug aiding recovery from vancomycin-induced cytotoxicity. The treatment practices involving osteogenesis-promoting drugs vary widely. Teriparatide, an anabolic agent, highly promotes bone formation by inducing osteoblast activation, increasing bone formation and mineral density, and preventing vertebral fractures. Hence, teriparatide may be administered in combination with vancomycin.
METHODS
MC3T3-E1 cells were cultured in minimum essential medium supplemented with 10% fetal bovine serum at 37 °C in a humidified incubator containing 5% CO. The experimental concentrations of vancomycin (2500, 5000, and 7500 μg/mL) were determined based on previous reports and our preliminary experiments. Teriparatide (100 ng/mL) was administered concomitantly to prevent cytotoxicity in osteoblasts, using pulsed vancomycin for 24 h (measured at 1, 3, and 7 days). Cell numbers and morphological changes in cells treated with vancomycin or vancomycin plus 100 ng/mL teriparatide were measured. Osteoblast differentiation was assessed using alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red S staining.
RESULTS
Teriparatide showed a recovery effect when vancomycin (7500 μg/mL) was administered only for 24 h. Microscopic examination revealed that teriparatide had a protective effect on osteoblasts exposed to 7500 μg/mL vancomycin. Addition of teriparatide led to the recovery of alkaline phosphatase staining and alizarin red staining.
CONCLUSION
Vancomycin-induced cytotoxicity in osteoblasts could be inhibited by administering teriparatide concomitantly with vancomycin.
Topics: Humans; Vancomycin; Teriparatide; Alkaline Phosphatase; Cell Differentiation; Osteogenesis; Osteoblasts
PubMed: 36371341
DOI: 10.1016/j.jos.2022.09.018 -
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 -
Iranian Journal of Kidney Diseases Jul 2023Central venous catheters, frequently used in patients undergoing hemodialysis, place the patients at high risk of catheter-related infections. Therefore, it is essential... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Central venous catheters, frequently used in patients undergoing hemodialysis, place the patients at high risk of catheter-related infections. Therefore, it is essential to select the optimal prevention protocol for these infections. This study aims to compare the efficacy of the Taurolock solution and antibiotic lock in preventing tunneled catheter (permcath) related infections.
METHODS
This multicenter study was conducted between June 2020 and July 2021 on 86 hemodialysis patients with a central venous catheter from four dialysis centers in Tehran, Iran. The patients were randomly assigned into two groups. The first group received Taurolock, and the second group received antibiotic lock (a combination of vancomycin and heparin) at the end of each dialysis session. Peripheral blood and catheter blood samples were collected once before the intervention and monthly thereafter, for up to six months, and blood culture performed for detection of various bacterial strains.
RESULTS
The findings showed no significant difference in the infection rate (positive peripheral blood or catheter cultures) between the Taurolock and vancomycin groups (P > .05). Additionally, there was no significant difference in the duration of catheter implantation in individuals with positive and negative cultures (P > .05). Furthermore, no significant correlation was found between comorbidities and catheter-related infection in patients of the two groups (P > .05).
CONCLUSION
There was no significant difference between the two groups in the rate of catheter-related infection. Therefore, vancomycin lock solutions can be good alternatives to Taurolock solution for preventing catheter-related infections. DOI: 10.52547/ijkd.7615.
Topics: Humans; Vancomycin; Catheter-Related Infections; Iran; Anti-Bacterial Agents; Central Venous Catheters; Renal Dialysis
PubMed: 37634248
DOI: No ID Found -
Revista Latino-americana de Enfermagem 2022to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and...
OBJECTIVE
to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time.
METHOD
an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05).
RESULTS
concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3).
CONCLUSION
pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.
Topics: Anti-Bacterial Agents; Central Venous Catheters; Drug Stability; Heparin; Humans; Vancomycin
PubMed: 35920542
DOI: 10.1590/1518-8345.5869.3620 -
Antimicrobial Agents and Chemotherapy Aug 2022To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases,... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Ototoxicity; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 35862741
DOI: 10.1128/aac.00138-22 -
BMJ Open Sep 2023infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.
INTRODUCTION
infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT.
METHODS AND ANALYSIS
We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group).
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.
TRIAL REGISTRATION NUMBER
NCT05320068.
Topics: Adult; Humans; Vancomycin; Anti-Bacterial Agents; Clostridium Infections; Secondary Prevention; Hospitals, University
PubMed: 37709311
DOI: 10.1136/bmjopen-2023-072121 -
The Journal of International Medical... Sep 2022This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for...
OBJECTIVES
This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for exceeding the target concentration.
METHODS
This retrospective study enrolled patients aged ≥18 years who were admitted to the intensive care unit and treated with ≥3 intravenous vancomycin doses during CRRT, and who underwent vancomycin TDM. Demographic and other information were collected. Multivariate logistic regression was used assess the risk factors for exceeding the target concentration.
RESULTS
Sixty-nine patients were included, and 40.6% patients underwent TDM. Additionally, 14.5% of patients reached the optimal concentration, and 87.5% of patients who exceeded the target received a daily dose adjustment. The cumulative dose of vancomycin and serum albumin were risk factors for exceeding the target concentration in patients on CRRT.
CONCLUSIONS
Patients on CRRT did not meet the optimal vancomycin management; <50% of the patients routinely received vancomycin TDM, and <15% achieved the optimal concentration. Fewer patients in the subtherapeutic group received a daily dose adjustment than those who exceeded the target concentration. Cumulative vancomycin and serum albumin doses before TDM were the risk factors for exceeding the target concentration in CRRT patients.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Drug Monitoring; Humans; Renal Replacement Therapy; Retrospective Studies; Serum Albumin; Vancomycin
PubMed: 36177821
DOI: 10.1177/03000605221126871 -
Clinical Microbiology and Infection :... Oct 2021Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study...
OBJECTIVES
Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin.
METHODS
A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective.
RESULTS
For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs.
CONCLUSIONS
Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.
Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Broadly Neutralizing Antibodies; Clostridioides difficile; Clostridium Infections; Cost-Benefit Analysis; Fidaxomicin; Humans; United States; Vancomycin
PubMed: 33878506
DOI: 10.1016/j.cmi.2021.04.004 -
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 -
Journal of Infection and Public Health May 2022Therapeutic drug monitoring (TDM) has proven effectiveness in maintaining efficacy and reducing toxicities associated with vancomycin. A trough level of (15-20 mg/L)...
BACKGROUND
Therapeutic drug monitoring (TDM) has proven effectiveness in maintaining efficacy and reducing toxicities associated with vancomycin. A trough level of (15-20 mg/L) for MRSA serious infections is recommended. Therapeutic failure is of concern due to suboptimal routine vancomycin utilization in clinical practice. This study aims to identify factors of vancomycin TDM practice potentially associated with vancomycin-induced nephrotoxicity and therapeutic failure measured by the need to restart vancomycin therapy within 28-days and all-cause mortality in a tertiary hospital in Oman.
METHODS
A single-center retrospective cohort was conducted in a tertiary care hospital that included all adult patients aged ≥ 18 years treated with IV vancomycin for> 72 h.
RESULTS
Vancomycin therapeutic level was not achieved in 16.8% of the patients, and 47.5% had high levels (>20 mg/L). Vancomycin-induced nephrotoxicity occurred in 31.7% of the patients, it was restarted within 28-days in 18.8% of the patient, and 25.2% of the patients died during the same hospitalization. Univariate analysis showed old age (p < 0.01), higher baseline creatinine reading (p = 0.03), high vancomycin level (p = 0.03), and vancomycin-induced nephrotoxicity (p < 0.01) were associated with increased all-cause mortality. Multivariate analysis identified overweight and vancomycin-induced nephrotoxicity were independent factors associated with increased all-cause mortality (OR:1.04; p = 0.043; 95% CI 1.00-1.08) and (OR:1.96; p = 0.049; 95% CI 1.00-21.61) respectively.
CONCLUSION
Failure to achieve the recommended therapeutic vancomycin level (15-20 mg/L) is common in clinical practice and associated with poor health outcomes; hence, appropriate TDM practice is an essential exercise to improve efficacy, prevent failure and reduce serious toxicities associated with vancomycin therapy.
Topics: Adult; Anti-Bacterial Agents; Cohort Studies; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Vancomycin
PubMed: 35500543
DOI: 10.1016/j.jiph.2022.04.007