RESUMEN

BACKGROUND: Higher doses of vancomycin are currently prescribed due to the emergence of bacterial tolerance and resistance. This study aimed to evaluate the efficacy and safety of the currently adopted vancomycin dosing guide in pediatric cardiology. METHODS: This was a single-center prospective cohort study with pediatric cardiac patients, younger than 14 years, from June 2020 to March 2021. The patients received intravenous vancomycin (40 mg/kg/day divided every 6-8 h) according to the department's vancomycin medication administration guide (MAG) for at least three days. RESULTS: In total, 88 cardiac patients were included, with a median age of 0.82 years (IQR: 0.25-2.9), and 51 (58%) received cardiopulmonary bypass surgery (CPB). The majority (71.6%, n = 61) achieved a serum vancomycin level within the therapeutic range (7-20 mg/L). Infants, young children, and children exposed to CPB surgery had an increased incidence of subtherapeutic vancomycin levels, [7 (29.2%); P = 0.033], [13 (54.2%); P = 0.01], and [21 (87.5%); P = 0.009] respectively. After the treatment, 8 (10%) patients had an elevated Serum creatinine (SCr) and 2 (2.5%) developed acute kidney injury (AKI). However, no significant difference was found between the patients developing AKI or an elevated SCr and the group who did not, in terms of clinical, therapeutic, and demographic characteristics, except for the decreased incidence of SCr elevation in patients receiving an ACE inhibitor, [4 (36.4%); P = 0.036]. CONCLUSION: Our institution followed MAG recommendations; however, subtherapeutic serum concentrations were evident in infants, young children, and CPB patients. Strategies to prevent AKI should be investigated, as the possible causes have not been identified in this study.

Asunto(s)

Antibacterianos , Vancomicina , Humanos , Vancomicina/administración & dosificación , Vancomicina/sangre , Lactante , Preescolar , Estudios Prospectivos , Antibacterianos/administración & dosificación , Femenino , Masculino , Niño , Adolescente , Recién Nacido , Guías de Práctica Clínica como Asunto , Lesión Renal Aguda

RESUMEN

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (µg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Asunto(s)

Lesión Renal Aguda , Antibacterianos , Biomarcadores , Creatinina , Cistatina C , Receptor Celular 1 del Virus de la Hepatitis A , Vancomicina , Humanos , Vancomicina/efectos adversos , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/sangre , Biomarcadores/orina , Biomarcadores/sangre , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/orina , Lesión Renal Aguda/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Anciano , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Cistatina C/sangre , Cistatina C/orina , Creatinina/sangre , Creatinina/orina , Tasa de Filtración Glomerular , Lipocalina 2/orina , Lipocalina 2/sangre , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina , Clusterina/orina , Clusterina/sangre

RESUMEN

Background and Objectives: The predicted serum concentrations of vancomycin are determined using population pharmacokinetic parameters. However, the accuracy of predicting vancomycin serum concentrations in the older population remains unclear. Therefore, this study aimed to investigate the accuracy of predicting vancomycin serum concentrations and identifying elements that diminish the prediction accuracy in older people. Materials and Methods: A total of 144 patients aged 75 years or older were included. The serum vancomycin concentrations in the patients were predicted based on population pharmacokinetic parameters common in Japan. We examined the accuracy of serum vancomycin concentration prediction in elderly individuals by comparing the predicted and measured serum vancomycin concentrations in each patient. The prediction accuracy was evaluated using the mean prediction error (ME) and mean absolute error of prediction (MAE) calculated from the measured and predicted serum vancomycin concentrations in each patient. Results: The ME for all patients was 0.27, and the 95% CI included 0, indicating that the predicted values were not significantly biased compared to the measured values. However, the predicted serum concentrations in the <50 kg body weight and serum creatinine (Scr) < 0.6 mg/dL groups were significantly biased compared to the measured values. The group with a history of intensive care unit (ICU) admission showed the largest values for the ME and MAE. Conclusions: Our prediction accuracy was satisfactory but tended to be lower in underweight patients, those with low creatinine levels, and patients admitted to the ICU. Patients with multiple of these factors may experience a greater degree of decreased predictive accuracy.

Asunto(s)

Antibacterianos , Vancomicina , Humanos , Anciano , Vancomicina/farmacocinética , Vancomicina/sangre , Vancomicina/uso terapéutico , Femenino , Masculino , Anciano de 80 o más Años , Estudios Retrospectivos , Antibacterianos/farmacocinética , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Japón , Creatinina/sangre

RESUMEN

BACKGROUND: This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software. METHODS: This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis. RESULTS: There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy. CONCLUSIONS: Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes.

Asunto(s)

Antibacterianos , Área Bajo la Curva , Teorema de Bayes , Análisis Costo-Beneficio , Monitoreo de Drogas , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/economía , Vancomicina/uso terapéutico , Vancomicina/sangre , Análisis Costo-Beneficio/métodos , Monitoreo de Drogas/métodos , Monitoreo de Drogas/economía , Masculino , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/economía , Antibacterianos/farmacocinética , Antibacterianos/sangre , Persona de Mediana Edad , Anciano , Lesión Renal Aguda , Tiempo de Internación , Adulto , Configuración de Recursos Limitados

RESUMEN

AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Asunto(s)

Antibacterianos , Aprendizaje Automático , Infecciones Relacionadas con Prótesis , Vancomicina , Humanos , Femenino , Masculino , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/sangre , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Persona de Mediana Edad , Anciano , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Adulto , Tasa de Filtración Glomerular , Estudios Retrospectivos , Modelos Biológicos , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation. AIM: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms. METHOD: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked. RESULTS: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration. CONCLUSION: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology.

Asunto(s)

Antibacterianos , Monitoreo de Drogas , Aprendizaje Automático , Vancomicina , Humanos , Vancomicina/administración & dosificación , Vancomicina/farmacocinética , Vancomicina/sangre , Estudios Retrospectivos , Preescolar , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/sangre , Femenino , Lactante , Masculino , Monitoreo de Drogas/métodos , Relación Dosis-Respuesta a Droga

RESUMEN

OBJECTIVE: Individual differences challenge the treatment of vancomycin, linezolid and voriconazole in severe infections. This study aimed to build a simple and economical method for simultaneous determination of the three antibiotics in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and provided a reference for therapeutic drug monitoring (TDM) of infected patients. METHODS: The plasma samples were precipitated by acetonitrile and detected and separated on a shim-pack GIST C18 column following the gradient elution within 5 min. Mass quantification was performed on multiple reaction monitoring mode under positive electrospray ionization. RESULTS: The linear ranges of vancomycin, linezolid and voriconazole were 1.00-100.00, 0.10-15.00 and 0.10-20.00 µg·mL-1, respectively, with good linearity (R2 > 0.99). The accuracy and precision, matrix effect, extraction recovery and stability were validated, and the results all meet the acceptance criteria of China Food and Drug Administration (CFDA) guidelines. CONCLUSION: The UHPLC-MS/MS method was established and validated for the simultaneous determination of vancomycin, linezolid and voriconazole in human plasma and successfully applied to routine TDM for individualized treatment.

Asunto(s)

Monitoreo de Drogas , Linezolid , Espectrometría de Masas en Tándem , Vancomicina , Voriconazol , Humanos , Voriconazol/sangre , Linezolid/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Vancomicina/sangre , Vancomicina/farmacocinética , Monitoreo de Drogas/métodos , Reproducibilidad de los Resultados , Modelos Lineales , Límite de Detección

RESUMEN

Therapeutic drug monitoring (TDM) is a crucial clinical practice that improves pharmacological effectiveness and prevent severe drug-related adverse events. Timely reporting and intervention of critical values during TDM are essential for patient safety. In this study, we retrospectively analyzed the laboratory data to provide an overview of the incidence, distribution pattern and biochemical correlates of critical values during TDM. A total of 19,110 samples were tested for nine drug concentrations between January 1, 2019, and December 31, 2020. Of these, 241 critical values were identified in 165 patients. The most common critical values were vancomycin trough (63.4%), followed by tacrolimus trough (16.9%) and digoxin (15.2%). The primary sources of drug critical values were the department of general intensive care unit (ICU), cardiology, and surgery ICU. At baseline or the time of critical value, significant differences were found between the vancomycin, digoxin, and tacrolimus groups in terms of blood urea nitrogen (BUN), creatinine, N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and lymphocyte percentage, P < 0.05. Therefore, it is important to prioritize and closely monitor drug concentrations to reduce laboratory critical values during TDM.

Asunto(s)

Digoxina , Monitoreo de Drogas , Tacrolimus , Vancomicina , Humanos , Monitoreo de Drogas/métodos , Estudios Retrospectivos , Masculino , Femenino , Tacrolimus/uso terapéutico , Tacrolimus/sangre , Vancomicina/sangre , Vancomicina/uso terapéutico , Vancomicina/farmacocinética , Persona de Mediana Edad , Anciano , Digoxina/sangre , Digoxina/uso terapéutico , Unidades de Cuidados Intensivos , Adulto , Creatinina/sangre , Nitrógeno de la Urea Sanguínea , Péptido Natriurético Encefálico/sangre

RESUMEN

This study investigated the suitability of surface modification for a long-range surface plasmon (LRSP) aptasensor using two different hydrogels, aiming at real-time monitoring of vancomycin (VCM) in undiluted serum and blood. Three different layer structures were formed on a gold surface of LRSP sensor chip using poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-N-methacryloyl-(L)-tyrosinemethylester (MAT)] (PMM) and poly[MPC-co-2-ethylhexyl methacrylate (EHMA)-co-MAT] (PMEM). The peptide aptamer for VCM was immobilized in PMM and PMEM via MAT. Among four differently prepared sensor chips, the LRSP hydrogel aptasensor with PMM, referred to as the PMM hydrogel, exhibited the highest sensor output and superior antifouling properties. Following the optimization of the PMM hydrogel preparation conditions, the shelf life of the PMM hydrogel was determined to exceed 2 weeks, and the same sensor chip could be used for 102 days without significant performance deterioration. The PMM hydrogel was then applied for VCM measurement in undiluted serum in vitro, where it demonstrated a limit of detection of 0.098 µM and a dynamic range of 0.18-100 µM, covering the therapeutic range. Additionally, the PMM hydrogel enabled the continuous measurement of various VCM concentrations in serum without rinsing and showed a concentration-dependent output in undiluted blood. These findings underscore the potential of the PMM hydrogel for real-time and direct monitoring of VCM in body fluids.

Asunto(s)

Hidrogeles , Resonancia por Plasmón de Superficie , Vancomicina , Vancomicina/sangre , Vancomicina/química , Vancomicina/farmacología , Humanos , Hidrogeles/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Aptámeros de Péptidos/química , Oro/química , Aptámeros de Nucleótidos/química , Antibacterianos/sangre , Antibacterianos/química , Antibacterianos/farmacología , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Metacrilatos/química

RESUMEN

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 µg/ml for serum and 0.5-100 µg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Asunto(s)

Antibacterianos , Meropenem , Infecciones Relacionadas con Prótesis , Líquido Sinovial , Espectrometría de Masas en Tándem , Vancomicina , Humanos , Espectrometría de Masas en Tándem/métodos , Vancomicina/sangre , Vancomicina/análisis , Vancomicina/farmacocinética , Líquido Sinovial/química , Meropenem/análisis , Meropenem/sangre , Meropenem/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/sangre , Antibacterianos/sangre , Antibacterianos/análisis , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Reproducibilidad de los Resultados , Masculino , Límite de Detección , Persona de Mediana Edad , Cromatografía Líquida con Espectrometría de Masas

RESUMEN

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability.

Asunto(s)

Antibacterianos , Enfermedad Crítica , Oxigenación por Membrana Extracorpórea , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/sangre , Estudios Retrospectivos , Enfermedad Crítica/terapia , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Adulto , Anciano , Área Bajo la Curva , Tasa de Filtración Glomerular , Terapia de Reemplazo Renal/métodos , Creatinina/sangre

RESUMEN

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (Ctrough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between Ctrough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC0-24 h/MIC (r2 = 0.27, P ≤ .05) and AUC24-48 h/MIC (r2 = 0.28, P ≤ .05), but not for Ctrough (r2 = 0.21, P > .05). There were no correlations between Ctrough (r2 = 0.26, P > .05), AUC0-24 h/MIC (r2 = -0.12, P > .05), AUC24-48 h/MIC (r2 = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and Ctrough at a cutoff value of 6.9 µg/mL. In addition, nephrotoxicity is also moderately associated with AUC0-24 h and AUC24-48 h at 505.7 and 667.1 µg•h/mL, respectively. A strong correlation between nephrotoxicity and Ctrough was observed when the cutoff value was 18.9 µg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. Ctrough was not correlated with clinical outcome. Nephrotoxicity could be predicted using Ctrough and AUC for infections with both pathogens.

Asunto(s)

Antibacterianos , Área Bajo la Curva , Enterococcus , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus , Vancomicina , Humanos , Masculino , Femenino , Vancomicina/farmacocinética , Vancomicina/efectos adversos , Vancomicina/sangre , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Staphylococcus/efectos de los fármacos , Estudios Prospectivos , Anciano , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Enterococcus/efectos de los fármacos , Adulto , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Coagulasa/metabolismo , Resultado del Tratamiento , Anciano de 80 o más Años

RESUMEN

PURPOSE: The acute kidney injury (AKI) onset owing to vancomycin (VCM) is reported that depend on the area under the blood concentration-time curve (AUC) and occur comparison early phase (early AKI). This study aimed to investigate the occurrence of early AKI in patients treated with VCM and new indicators to avoid early AKI. METHODS: Adult patients who received VCM treatment for more than 4 days and whose trough values measured at least once on or after day 4 and serum creatinine before day 7 from the initiation of VCM administration between August 2021 and September 2022 at the Yamanashi Prefectural Central Hospital were enrolled. Early AKI (defined as AKI occurring within day 7 from VCM administration) and the association between each AUC (0-24, 24-48, 48-72, 0-48, 24-72, 0-72) were investigated. Furthermore, each AUC cut-off value for early AKI was calculated. RESULT: In total, 164 patients were enrolled; early AKI developed in 21 patients and most frequently occurred on day 4. All stratified AUC were associated with early AKI development. The AUC cut-off values were AUC0-24: 470.8 µg/mL⋅h; AUC24-48: 473.0 µg/mL⋅h; AUC48-72: 489.7 µg/mL⋅h; AUC0-48: 910.2 µg/mL⋅h; AUC24-72: 1039.2 µg/mL⋅h; and AUC0-72: 1544.0 µg/mL⋅h. CONCLUSION: The possibility of AKI development owing to the AUC accumulation of VCM was observed (accumulation toxicity). Concentration control through early-phase blood concentration measurements and a transition to AUC0-48 <910.2 µg/mL⋅h may reduce the early-phase AKI onset.

Asunto(s)

Lesión Renal Aguda , Antibacterianos , Área Bajo la Curva , Vancomicina , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/sangre , Vancomicina/efectos adversos , Vancomicina/farmacocinética , Vancomicina/sangre , Vancomicina/administración & dosificación , Masculino , Femenino , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/sangre , Factores de Riesgo , Anciano , Persona de Mediana Edad , Creatinina/sangre , Anciano de 80 o más Años , Adulto , Estudios Retrospectivos

RESUMEN

INTRODUCTION: Estimating the serum vancomycin (VCM) concentrations of lean and patients with obesity is challenging. Additionally, VCM dosing for Japanese patients undergoing hemodialysis remains particularly unclear. This study aimed to determine the impact of the physical build on serum VCM concentrations of Japanese patients undergoing hemodialysis. METHODS: This retrospective cohort study included hospitalized patients undergoing hemodialysis, who received treatment with VCM between May 1, 2019, and December 31, 2021, at Kansai Rosai Hospital, which is a 642-bed acute care hospital in Japan. Patients were divided into the following three groups based on their body mass index (BMI): lean group (≤18.5 kg/m2), normal group (18.5-25 kg/m2), and obese group (≥25 kg/m2). The VCM dose and predialysis serum VCM concentration (PVC) were compared. RESULTS: This study included 191 patients. There were 50 patients in the lean group, 85 in the normal group, and 56 in the obese group. The median loading doses per body weight were 24.0, 22.1, and 21.2 mg/kg for the lean, normal, and obese groups, respectively. The VCM dose per body weight decreased significantly with increasing BMI. The median PVCs of the lean and normal groups were approximately 15 mg/L (not significantly different). However, the median PVC of the obese group was 18.3 mg/L, which was significantly higher (P < 0.001). CONCLUSIONS: The VCM dose per body weight for Japanese patients undergoing hemodialysis should be adjusted based on the BMI.

Asunto(s)

Antibacterianos , Índice de Masa Corporal , Obesidad , Diálisis Renal , Vancomicina , Humanos , Vancomicina/sangre , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Antibacterianos/sangre , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Obesidad/sangre , Japón , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Vancomycin is a renally eliminated, nephrotoxic, glycopeptide antibiotic with a narrow therapeutic window, widely used in intensive care units (ICU). We aimed to predict the risk of inappropriate vancomycin trough levels and appropriate dosing for each ICU patient. METHODS: Observed vancomycin trough levels were categorized into sub-therapeutic, therapeutic, and supra-therapeutic levels to train and compare different classification models. We included adult ICU patients (≥ 18 years) with at least one vancomycin concentration measurement during hospitalization at Mayo Clinic, Rochester, MN, from January 2007 to December 2017. RESULT: The final cohort consisted of 5337 vancomycin courses. The XGBoost models outperformed other machine learning models with the AUC-ROC of 0.85 and 0.83, specificity of 53% and 47%, and sensitivity of 94% and 94% for sub- and supra-therapeutic categories, respectively. Kinetic estimated glomerular filtration rate and other creatinine-based measurements, vancomycin regimen (dose and interval), comorbidities, body mass index, age, sex, and blood pressure were among the most important variables in the models. CONCLUSION: We developed models to assess the risk of sub- and supra-therapeutic vancomycin trough levels to improve the accuracy of drug dosing in critically ill patients.

Asunto(s)

Antibacterianos , Unidades de Cuidados Intensivos , Aprendizaje Automático , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/administración & dosificación , Vancomicina/sangre , Femenino , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Persona de Mediana Edad , Anciano , Enfermedad Crítica , Monitoreo de Drogas/métodos , Adulto , Estudios Retrospectivos

RESUMEN

BACKGROUND: Vancomycin is being used for the treatment of a variety of infections caused by methicillin resistant Staphylococcus aureus and methicillin susceptible Staphylococcus aureus. Therapeutic drug monitoring (TDM) is highly recommended for ensuring the safe and effective therapy with vancomycin. A reliable and cost-effective bioanalytical method is required for TDM as well as pharmacokinetic studies of vancomycin. MATERIALS AND METHODS: A selective, sensitive, and cost effective HPLC method was developed and validated for quantification of vancomycin concentrations in human plasma. The mobile phase was a mixture of buffer (50 mM ammonium dihydrogen phosphate, pH 2.4) and acetonitrile 88 : 12 v/v. The separation was carried on C18 column (125 × 4.6 mm, particle size 5 µm) with isocratic flow rate of 0.370 mL/min at room temperature with UV detection at 215 nm. The method was validated for sensitivity, accuracy, and precision as well as stability of vancomycin in human plasma by following European Medicine Agency (EMA) guideline. Therapeutic drug monitoring of vancomycin was performed by quantifying the trough concentrations of vancomycin in 65 human plasma samples after administration of therapeutically relevant dose. RESULTS: The developed method was sensitive enough to quantify vancomycin concentrations as low as 0.25 mg/L in human plasma. Moreover, the method was proved accurate and precise in terms of quantifying the unknown concentration of vancomycin. The evaluation of short-term, long-term, and freeze-thaw stability proved the stability of vancomycin in human plasma. The TDM of vancomycin by using this method showed that 39 (60%) samples were within the target trough concentration range (TTCR), i.e. 10 - 20 mg/L, while 23 samples (35.4%) were below the TTCR, and 3 samples (4.6%) were above this range. CONCLUSION: The developed method is sensitive and cost effective for quantification of vancomycin in human plasma. The results of sample analysis shows that the developed method can be used reliably for TDM of vancomycin.

Asunto(s)

Antibacterianos , Monitoreo de Drogas , Vancomicina , Vancomicina/farmacocinética , Vancomicina/sangre , Humanos , Monitoreo de Drogas/métodos , Cromatografía Líquida de Alta Presión/métodos , Antibacterianos/farmacocinética , Antibacterianos/sangre , Reproducibilidad de los Resultados

RESUMEN

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.

Asunto(s)

Antibacterianos , Eliminación de Componentes Sanguíneos , Lipoproteínas LDL , Diálisis Renal , Vancomicina , Humanos , Vancomicina/sangre , Vancomicina/uso terapéutico , Vancomicina/farmacocinética , Eliminación de Componentes Sanguíneos/métodos , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Lipoproteínas LDL/sangre , Masculino , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicaciones , Persona de Mediana Edad

RESUMEN

Vancomycin continuous infusion (CI) has suggested benefits over intermittent infusion: reduced nephrotoxicity, higher target attainment, and simpler therapeutic drug monitoring (TDM). Empiric dosing regimens range from 30-60 mg/kg/day and it is unclear which regimen results in optimal exposure. This study evaluates whether a dosing regimen of 45 mg/kg/day after a 20 mg/kg loading dose for patients with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min results in adequate exposure. We retrospectively analyzed plasma concentrations from patients treated with vancomycin CI as routine clinical care between February and October 2021. Patients under 18 years old, with renal replacement therapy, reduced creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration < 50 mL min/1.73 m2) or outpatient antibiotic therapy were excluded. Dose, renal function, and blood draw procedures were assessed for each measured vancomycin sample. Initially, 121 samples were included. Subsequently, 7 samples, 6 of which with concentrations ≥ 40 mg/L, were verified to be incorrectly drawn and excluded. With doses of 40-50 mg/kg/day concentrations ranged from 18.4-61.0 mg/L. Only 25% were within the target window of 17-25 mg/L and 15% were ≥ 40 mg/L. Supratherapeutic concentrations were observed in 89% of samples from patients dosed 40-60 mg/kg/day with eGFR 50-80 mL/min. Concluding, an empiric dosing regimen of 45 mg/kg results in too high vancomycin exposure and thus we recommend lower doses and differentiation according to renal function. Additionally, when measuring concentrations over 40 mg/L incorrect sampling must be excluded before dose adjustment and the large variability in exposure between patients, warrants the need for swift TDM.

Asunto(s)

Antibacterianos , Monitoreo de Drogas , Tasa de Filtración Glomerular , Vancomicina , Humanos , Vancomicina/administración & dosificación , Vancomicina/farmacocinética , Vancomicina/efectos adversos , Vancomicina/sangre , Estudios Retrospectivos , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/efectos adversos , Antibacterianos/sangre , Femenino , Persona de Mediana Edad , Anciano , Monitoreo de Drogas/métodos , Infusiones Intravenosas , Adulto , Relación Dosis-Respuesta a Droga , Anciano de 80 o más Años

RESUMEN

We report on the development of an on-site therapeutic drug monitoring (TDM) method for vancomycin (VCM) utilizing a portable spectrometer and commercially available immunoturbidimetric assay reagents designed for automated clinical chemistry analyzers. The method enables the quantification of VCM in plasma samples within 10 min, with a good correlation between the measured values and the theoretical values (r2 = 0.995). The intra and inter-day precisions were found to be below 12.5% and 17.7%, respectively. Moreover, we established a correlation between the quantitative values using this method and those measured through HPLC-UV and automated clinical chemistry analyzers, showing good reliability (R2 = 0.970 and 0.951, respectively). This method allows anyone to rapidly perform TDM at the bedside and is expected to be used to evaluate appropriate drug therapy.

Asunto(s)

Monitoreo de Drogas , Vancomicina , Monitoreo de Drogas/métodos , Monitoreo de Drogas/instrumentación , Vancomicina/sangre , Vancomicina/análisis , Humanos , Análisis Espectral/métodos , Cromatografía Líquida de Alta Presión

RESUMEN

BACKGROUND: It is usually difficult for the trough concentration of vancomycin to reach the recommended lower limit of 10 mg/L per the label dose in the paediatric population. Moreover, children with haematologic diseases who suffer from neutropenia are more likely to have lower exposure of vancomycin, and the risk factors have been poorly explored. METHOD: We reviewed and analysed the initial trough concentration of vancomycin and synchronous cytometry and biochemical parameters in the blood of 1453 paediatric patients with haematologic diseases over a 6 year period, from 2017 to 2022. RESULTS: Forty-five percent of the enrolled children had vancomycin trough concentrations below 5 mg/L after receiving a dose of 40 mg/kg/day, and the multiple regression showed that age (OR = 0.881, 95% CI 0.855 to 0.909, P < 0.001), BMI (OR = 0.941, 95% CI 0.904 to 0.980, P = 0.003) and the glomerular filtration rate (OR = 1.006, 95% CI 1.004 to 1.008, P < 0.001) were independent risk factors. A total of 79.7% of the children experienced augmented renal clearance, which was closely correlated to age-associated levels of serum creatinine. The vancomycin trough concentration was higher in children with aplastic anaemia than in those with other haematologic diseases due to a higher BMI and a lower glomerular filtration rate. CONCLUSION: Age-associated augmented renal clearance and low BMI values contributed to suboptimal trough concentrations of vancomycin in children with haematologic diseases, and the effects of long-term use of cyclosporine and glucocorticoids need to be taken into account.

Asunto(s)

Enfermedades Hematológicas , Vancomicina , Niño , Humanos , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Índice de Masa Corporal , Enfermedades Hematológicas/tratamiento farmacológico , Vancomicina/sangre , Vancomicina/uso terapéutico