Blood Concentrations Of Vancomycin Research Articles

Monitoring of Blood Concentration and Clinical Efficacy of Vancomycin in the Treatment of Patients with Critically Ill Infections

We attempt to discuss the clinical efficacy and safety of vancomycin in different blood concentrations in patients with critically ill infections. We collected 50 patients who received vancomycin treatment from infectious diseases department in our hospital from June 2017 to June 2021. Monitored the trough concentration of vancomycin and selected the trough concentration after reaching the steady state. We divided patients into three groups according to the minimum blood concentration value i.e. minimum blood concentration <10 mg/l (n=16), minimum blood concentration 10 mg/l~15 mg/l (n=18) and minimum blood concentration >15 mg/l (n=16), compare the clinical effective rate and adverse reactions rate among the three groups of patients. 16 cases, 18 cases and 16 cases were enrolled into the three groups of minimum blood concentration <10, 10-15, >15 mg/l and the clinical cure rates were 68.8 %, 66.7 % and 66.7 % respectively. The differences in effective rates among the groups had no statistical significance (p=0.983); the overall adverse reactions rate in 50 patients was 18 % (9/50) and adverse reactions rate in minimum blood concentration >15 mg/l group was (43.8 %, 7/16), especially it is acute renal dysfunction, which is statistically different from the other two groups (p=0.025). The high blood concentration of vancomycin in patients with critically ill infection does not increase its clinical efficacy, but will increase adverse reactions rate in patients and provide a basis for providing the best vancomycin dose in clinical practice.

Impact of Area Under the Concentration–Time Curve on the Prevalence of Vancomycin-Induced Nephrotoxicity in Combination With Tazobactam/Piperacillin or Cefepime: A Single-Institution Retrospective Study

PurposeRisk for vancomycin-induced nephrotoxicity (VIN) is reportedly reduced by AUC-guided vancomycin dosing. However, it remains unknown whether the increased VIN risk in combination treatment with vancomycin and tazobactam/piperacillin, which is a VIN risk factor, can be diminished by AUC-guided vancomycin dosing (vancomycin-AUC). The aim of this study was to assess whether the evaluation of vancomycin-AUC + tazobactam/piperacillin (VT) combination therapy could prevent VIN. MethodsThe data from patients who received VT or vancomycin + cefepime (VC; the control group) at Tokushima University Hospital (Kuramoto, Japan) between April 2010 and March 2020 were analyzed in this retrospective study. The between-group difference in the prevalence of VIN onset, stratified by AUC, was investigated. The AUC of vancomycin was calculated using the Bayesian method with the blood concentration of vancomycin. The risk factors and probability of VIN onset from the vancomycin exposure–toxicity curve were evaluated using the logistic model. FindingsThe prevalences of VIN were 29.5% (18/61) and 7.1% (3/42) in the VT and VC groups, respectively. Multivariate logistic regression analysis of data from all patients revealed concurrent use of tazobactam/piperacillin (odds ratio [OR] = 4.59; P = 0.039) and AUC increase (OR = 1.01; P < 0.01) as risk factors for VIN, but only concurrent use of tazobactam/piperacillin was identified as a risk factor in patients with an AUC of <600 μg · h/mL, the guideline-recommended value (OR = 9.52; P = 0.041). Moreover, the vancomycin exposure–toxicity curve showed that in the guideline-recommended AUC range, VIN probability was consistently higher and the slope of VIN probability was greater in the VT group than in the VC group. ImplicationsVIN risk was higher with VT than with VC, even when the AUC was controlled to the guideline-recommended range. These results strongly suggest that VIN prevention may be difficult with AUC-guided vancomycin dosing in patients receiving VT.

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents.

Various population pharmacokinetic (PopPK) models for vancomycin in children and adolescents have been constructed to optimize the therapeutic regimen of vancomycin. However, little is known about their predictive performance when extrapolated to different clinical centres. Therefore, the aim of this study was to externally validate the predictability of vancomycin PopPK model when extrapolated to different clinical centres and verify its applicability in an independent data set. The published models were screened from the literature and evaluated using an external data set of a total of 451 blood concentrations of vancomycin measured in 220 Chinese paediatric patients. Prediction- and simulation-based diagnostics and Bayesian forecasting were performed to evaluate the predictive performance of the models. Ten published PopPK models were assessed. Prediction-based diagnostics showed that none of the investigated models met all the standards (median prediction error (MDPE) ≤ ±20%, median absolute prediction error (MAPE) ≤30%, PE% within ±20% (F20 ) ≥35% and PE% within ±30% (F30 ) ≥50%), indicating unsatisfactory predictability. In simulation-based diagnostics, both the visual predictive checks (VPC) and the normalized prediction distribution error (NPDE) indicated misspecification in all models. Bayesian forecasting results showed that the accuracy and precision of individual predictions could be significantly improved with one or two prior observations, but frequent monitoring might not be necessary in the clinic, since Bayesian forecasting identified that greater number of samples did not significantly improve the predictability. Model 3 established by Moffett et al showed better predictability than other models. The 10 published models performed unsatisfactorily in prediction- and simulation-based diagnostics; none of the published models was suitable for designing the initial dosing regimens of vancomycin. Pharmacokinetic characteristics and covariates, such as weight, renal function, age and underlying disease should be taken into account when extrapolating the vancomycin model. Bayesian forecasting combined with therapeutic drug monitoring based on model 3 can be used to adjust vancomycin dosing regimens.

Vancomycin-lock therapy for prevention of catheter-related bloodstream infection in very low body weight infants

BackgroundThis study was to evaluate the effectiveness and safety of vancomycin- lock therapy for the prevention of catheter-related bloodstream infection (CRBSI) in very low body weight (VLBW) preterm infant patients.MethodsOne hundred and thirty-seven cases of VLBW preterm infants who retained peripherally inserted central catheters (PICCs) were retrospectively reviewed, including 68 treating with heparin plus vancomycin (vancomycin-lock group) and 69 with heparin only (control group). The incidence of CRBSI, related pathogenic bacteria, adverse events during the treatment, complications, antibiotic exposure, PICC usage time, hospital stay, etc. were compared between the above two groups.ResultsThe incidence rate of CRBSI in the vancomycin-lock group (4.4%, 3/68) was significantly less than in the control group (21.7%, 15/69, p = 0.004). Total antibiotic exposure time during the whole observation period was significantly shorter in the group than in the control group (11.2 ± 10.0 vs 23.6 ± 16.1 d; p < 0.001). No hypoglycemia occurred during the locking, and the blood concentrations of vancomycin were not detectable.ConclusionsVancomycin-lock may effectively prevent CRBSI in Chinese VLBW preterm infants and reduce the exposure time of antibiotics, without causing obvious side complications.

Increased Vancomycin Clearance in Patients with Solid Malignancies.

Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.

Augmented Renal Clearance of Vancomycin in Hematologic Malignancy Patients

The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.

Investigation on transition of blood concentration of vancomycin administered in patients undergoing SHEDD-fA

Investigation on transition of blood concentration of vancomycin administered in patients undergoing SHEDD-fA

Clinical study of vancomycin for appropriate dosing in severe infective patients with augmented renal clearance

To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CLCR). A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CLCR was calculated. ARC was defined as 12 h-CLCR > 130 mL×min-1×1.73 m-2. According to 12 h-CLCR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CLCR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CLCR. The predictive value of 12 h-CLCR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CLCR was (114.31±73.38) mL×min-1×1.73 m-2. The 12 h-CLCR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min-1×1.73 m-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CLCR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CLCR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg-1×d-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CLCR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min-1×1.73 m-2. The results showed that as 12 h-CLCR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CLCR≥69.83 mL×min-1×1.73 m-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg-1×d-1. Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CLCR, the higher the 12 h-CLCR, the more the dosage of vancomycin is. When 12 h-CLCR is greater than or equal to 69.83 mL×min-1×1.73 m-2, the dosage of vancomycin should be higher than the conventional dosage.

Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients.

Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10-15 mg/L and 15-20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CLCr) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CLCr values of 80 mL/min, and the rate constant of CL with the CLCr changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.

Assessment of optimal initial dosing regimen with vancomycin pharmacokinetics model in very low birth weight neonates.

Pharmacokinetic of vancomycin in very low birth weight neonates showed big variety, and limited data were available due to very minor population. These facts make it difficult to adjust its optimal initial dosage. Therefore, this study was to develop optimal dosing regimen of vancomycin in very low birth weight neonates. Between 2010 and 2015, low birth weight neonates (≤1500g) were included in a population pharmacokinetics analysis. Based on the pharmacokinetic parameters we estimated, we simulated individual blood concentrations of vancomycin and evaluated the probability of its pharmacokinetics/pharmacodynamics (PK/PD) target attainment, such as 24-h area under the concentration-time curve (AUC24)/MIC (≥400) and blood trough concentration (10-20μg/mL), as primary measure for several dosing regimens by Monte Carlo simulation method. Ten patients were prescribed vancomycin and detected its blood concentrations as routine pharmacy practice to adjust the dosage. Aone-compartment model was used and clearance significantly correlated with serum creatinine and the volume of infusion. In this model, vancomycin dose at 10mg/kg three times a day (TID) was predicted to result 86.7% of neonates for an MIC of 1μg/mL achieving AUC/MIC of ≥400 and 30.6% of the neonates for an MIC of 2μg/mL. Moreover, the probability of reaching the target trough concentration was 70.5% for patients treated with vancomycin 10mg/kg TID. We recommended vancomycin 10mg/kg TID as initial dosage regimens for low birth weight neonates infected with the pathogens showed MIC of ≤1μg/mL.

Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold.

Background:Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA) bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo.Methods:According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate) were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated.Results:In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L), and the function and histomorphology of the liver and kidney were all normal.Conclusion:According to ISO standards, the V-BHA/PAA scaffold is considered to have sufficient safety for clinical utilization.