Initial Vancomycin Trough Concentration Research Articles

Clinical application of vancomycin TDM in ventilated patients with gastrointestinal cancer: a propensity-matched analysis.

Therapeutic drug monitoring (TDM) of vancomycin is widely recommended for clinical treatment. Due to the complexity of 24-h area under the curve (AUC) guided vancomycin monitoring in clinical practice, the vancomycin trough level remains the most common and practical method. The purpose of this study was designed to investigate the differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods, and further explore the clinical application of trough-guided vancomycin monitoring in patients with gastrointestinal cancer requiring mechanical ventilation. We included a total of 78 gastrointestinal cancer patients who required mechanical ventilation due to various diseases. All patients included in this study were aged 18years or older and were treated with intravenous vancomycin therapy for more than 2days due to documented or suspected Gram-positive bacterial infections, and have at least one available vancomycin plasma concentration. First, we compared the safety and efficacies of vancomycin TDM based on different monitoring methods as trough-guided monitoring or AUC-guided monitoring. Then, based on whether the initial vancomycin concentration achieving the target trough concentration (less than 48h), patients were divided into early and delayed groups, and the clinical factors were compared between them. The primary endpoints include the incidence of new-onset acute kidney injury (AKI) or renal replacement therapy (RRT), clinical success rate and 28-day all-cause mortality. Finally, the overall relationship between trough concentration and potential covariates is screened by univariate and multivariate analysis to explore potential information covariates. The research revealed that patients with gastrointestinal cancer exhibited significantly lower initial vancomycin trough concentrations (median [interquartile range (IQR)]: 6.90[5.28-11.20] mg/L). And there were no statistically significant differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods for the primary endpoint. Moreover, base on trough-guided vancomycin monitoring, the early group demonstrated a notably shorter duration of mechanical ventilation compared with the delayed group (χ2 = 4.532; p < 0.05; Fig.2E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2 = 6.607; p < 0.05; Fig.2F) and duration of vasoactive agent (χ2 = 6.106; p < 0.05; Fig.2D) were significantly shorter in the early group compared with delayed group. Multivariate regression analysis revealed that Cystatin C (Cys-C) was the most important variable for vancomycin target trough achievement (odds ratio, 5.274; 95% CI, 1.780 to 15.627; p = 0.003). Trough-guided vancomycin monitoring is a simple and effective marker of TDM for ventilated patients with gastrointestinal cancer. Timely achievement of target trough concentrations for vancomycin can improve partial clinical outcomes in Gram-positive bacterial infections. Cys-C level is a potentially valuable parameter for predicting the vancomycin concentration.

292: PREDICTION OF VANCOMYCIN TROUGH CONCENTRATION VIA MACHINE LEARNING IN THE INTENSIVE CARE UNIT

Introduction: It is difficult to predict vancomycin trough concentrations in critically ill patients as their pharmacokinetics change with the progression of both organ failure and medical intervention. This study seeks to develop a model to predict initial vancomycin trough concentration using machine learning (ML) and compare the resulting prediction’s accuracy to the population pharmacokinetic (PPK) model. Methods: A single-center retrospective observational study was conducted. Patients who had been admitted to the intensive care unit, received intravenous vancomycin, and had undergone therapeutic drug monitoring between November 2017, and December 2020, were included. Thereafter, ML models were developed with ridge regression, random forest, and LightGBM using 42 features. The deviation between the model’s predicted and measured values with the smallest mean absolute errors was compared with the deviation between the predicted and PPK models. Results: In total, 226 patients were included, and a significant difference was found between the predicted and measured values by the ML and PPK models (ML 1.59 vs PPK 4.19, difference 2.19, 95% confidence interval [1.68, 2.72]). In a subgroup analysis, patients with severe acidosis, patients who receive continuous renal replacement therapy, as well as those who are elderly and obese, showed a higher prediction accuracy using ML. The important features were determined to be renal function (creatinine clearance and serum creatinine), vancomycin dose (dose per hour and total dose), disease severity, and age. Conclusions: This study concludes that ML may be able to predict vancomycin trough concentrations more accurately than the currently used PPK model.

An Audit to Evaluate Vancomycin Therapeutic Drug Monitoring in a Neonatal Intensive Care Unit.

Therapeutic drug monitoring (TDM) is routinely used for optimization of vancomycin therapy, because of exposure-related efficacy and toxicity, in addition to significant variability in pharmacokinetics, which leads to unpredictable drug exposure. The aim of this study was to evaluate target attainment and TDM of vancomycin in neonates. The authors conducted a retrospective study and collected data from medical records of all neonates who received vancomycin therapy in the neonatal intensive care unit between January 2019 and December 2019. The primary outcome was the proportion of vancomycin courses that reached target trough concentrations of 10-20 mg/L based on appropriate TDM samples collection. Secondary outcomes included proportion of courses with appropriate dose and dose frequency, and proportion of patients who achieved target concentrations after the first dose adjustment. In total, 69 patients were included, with 129 vancomycin courses. The median initial vancomycin trough concentration was 12 (range: 4-36) mg/L. The target trough concentration was achieved in 75% of courses after the initial dose with appropriate TDM, and 84% of courses after TDM-guided dose adjustments. Patients were dosed appropriately in 121/129 courses and TDM was performed correctly according to protocol in 51/93 courses. A dose adjustment was performed in 18/29 courses, to increase target attainment. This study showed that there is a need for an increase in dose to improve target attainment. There is also a need to explore more effective TDM strategies to increase the proportion of neonatal patients attaining vancomycin target trough concentrations.

An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study.

To determine the impact of initial vancomycin trough concentration (VTC) on mortality in adult patients in the intensive care unit (ICU) undergoing vancomycin therapy. During their first ICU stay, patients with initial VTC records after vancomycin treatment were recruited from the eICU Collaborative Research Database to this multicenter retrospective cohort study, and classified into four groups according to VTC: less than 10, 10–15, 15–20, and greater than 20 mg/L. Multivariable logistic regression and sensitivity analyses were performed to explore the association of VTC, as a continuous and categorical variable, with mortality. This study enrolled 7220 patients from 335 different ICUs at 208 hospitals. Multivariable logistic regression models indicated that VTC was positively correlated with ICU (odds ratio [OR], 1.028, 95% confidence interval [CI], 1.019–1.037) and hospital (OR 1.028, 95% CI, 1.020–1.036) mortalities. Moreover, compared with VTC less than 10 mg/L, VTCs of 10–15, 15–20, and greater than 20 mg/L were associated with a higher risk of ICU mortality (OR, 1.330, 95% CI, 1.070–1.653; OR, 1.596, 95% CI, 1.265–2.015; abd OR, 1.875, 95% CI, 1.491–2.357, respectively), and VTCs of 15–20 and greater than 20 mg/L were also correlated with increased hospital mortality (OR, 1.482, 95% CI, 1.225–1.793; and OR, 1.831, 95% CI, 1.517–2.210, respectively). Similar results persisted in patients with different Acute Physiology and Chronic Health Evaluation Ⅳ scores, creatinine clearance levels, ages, and body mass indexes. Our findings indicated a potential relationship of initial VTC with ICU and hospital mortalities in patients in the ICU. However, due to the retrospective nature of this study, future prospective studies or randomized controlled trials are needed to validate those results.

Low vancomycin trough concentration in neonates and young infants.

Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center. The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration: <10, 10-15, and >15mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage. Thirty-three patients were analyzed. The number of patients with <10, 10-15, and >15mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between <10 versus 10-15 and 10-15 versus >15mg/L. The numbers of patients with <10, 10-15, and >15mg/L in the simulation were 26, 6, and 1, respectively. Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Effect of serum concentration and concomitant drugs on vancomycin-induced acute kidney injury in haematologic patients: a single-centre retrospective study.

Appropriate use of vancomycin (VCM) is important in preventing acute kidney injury (AKI). Because of the high frequency of VCM use for febrile neutropenia and concomitant use of other nephrotoxic drugs, haematologic patients have a different nephrotoxic background compared with patients with other diseases. Therefore, it is unclear whether the risk factors of VCM-induced AKI identified in other patient groups are also applicable to haematologic patients. Herein, we performed a single-centre retrospective analysis to identify the factors associated with VCM-induced AKI in haematologic patients. We retrospectively analysed 150 haematologic patients to whom VCM was administered between April 2010 and March 2018 at Tokushima University Hospital. VCM-induced AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analyses were performed to identify risk factors for VCM-induced AKI. Seventeen patients had VCM-induced AKI. Multivariate analysis revealed that the risk factors of VCM-induced AKI were an initial VCM trough concentration of > 15mg/L and concomitant use of tazobactam/piperacillin (TAZ/PIPC) and liposomal amphotericin B (L-AMB). Patients with an initial VCM trough concentration of < 10mg/L showed significantly lower efficacy in febrile neutropenia. Interestingly, concomitant L-AMB use increased the incidence of VCM-induced AKI in a VCM concentration-dependent manner, whereas concomitant TAZ/PIPC increased the incidence in a VCM concentration-independent manner. The optimal initial VCM trough concentration was 10-15mg/L in haematologic patients, considering safety and effectiveness. There were differences in the effect of VCM-induced AKI between nephrotoxic drugs.

Utilization of Augmented Renal Clearance in Trauma Intensive Care Scoring System to Improve Vancomycin Dosing in Trauma Patients at Risk for Augmented Renal Clearance

Background: The Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scoring system is a validated system to predict augmented renal clearance in trauma patients. This study examined the ability of the ARCTIC score to identify patients at risk for subtherapeutic vancomycin trough concentrations relative to estimated creatinine clearance (eCrCl) alone. Methods: Trauma patients admitted to the intensive care unit from September 2012 to December 2017 who received vancomycin and had a vancomycin trough concentration recorded were included. Patients were excluded if their serum creatinine concentration was >1.3 mg/dL, if they had received vancomycin doses <30 mg/kg per day, an improperly timed trough concentration measurement, or renal replacement therapy. The primary endpoint was an initial subtherapeutic vancomycin trough concentration (<10 mg/L). Classification and regression tree (CART) analysis was used to identify thresholds for the ARCTIC score and other continuous data where subtherapeutic troughs were more common. A step-wise logistic regression analysis was performed to control for confounders for subtherapeutic troughs whereby inclusion of ARCTIC was modeled sequentially after eCrCl. Results: A total of 119 patients with a mean age of 42 ± 17 years and eCrCl 142 ± 39 mL/min met the inclusion criteria. The mean daily vancomycin dose was 44 ± 9 mg/kg, and the incidence of subtherapeutic trough concentration was 46%. The CART analysis identified two variables creating three groups where subtherapeutic trough concentrations differed: eCrCl >105 mL/min and ARCTIC score ≥7, eCrCl >105 mL/min and ARCTIC score <7, and eCrCl ≤105 mL/min. The base logistic regression model identified eCrCl >105 mL/min and pelvic fracture as risk factors for subtherapeutic trough values. The final model included the addition of ARCTIC score ≥7, which improved the model significantly (p = 0.009). Predictors of subtherapeutic trough concentrations were (odds ratio [95% confidence interval]): eCrCl >105 mL/min (6.5 [1.66-25.07]), ARCTIC score ≥7 (3.26 [1.31-8.09]), and pelvic fracture (4.36 [1.27-14.93]). Conclusion: The ARCTIC score is useful when applied in conjunction with eCrCl. Patients with a eCrCl >105 mL/min and an ARCTIC score ≥7 may require a more aggressive dosing strategy.

Use of Body Surface Area for Dosing of Vancomycin.

Vancomycin weight-based dosing regimens often fail to achieve therapeutic trough serum concentration in children ≤12 years of age and rigorous studies evaluating efficacy and safety of body surface area (BSA)-based dosing regimens have not been performed. We compared vancomycin trough serum concentrations in pediatric patients receiving a weight- or BSA-based dosing regimen. This was a single-center, retrospective study evaluating pediatric patients, ages 1 to 12 years, who received vancomycin from September 2012 to October 2015. Patients received a minimum of 3 consecutive doses at the same scheduled interval within a dosing regimen prior to a measured vancomycin serum trough concentration. The primary outcome was percentage of initial vancomycin trough concentrations ≥10 mg/L. The secondary outcomes were percentage of supratherapeutic, therapeutic, and subtherapeutic vancomycin serum concentration for all patients, including a subset of overweight and obese patients, and number of nephrotoxic occurrences. BSA-based dosing regimens resulted in 50% of the initial vancomycin trough concentrations ≥ 10 mg/L compared with 17% for the weight-based dosing regimens (p < 0.0001). No statistically significant differences were noted between the 2 dosing regimens for supratherapeutic, therapeutic, or subtherapeutic trough concentrations for all patients, and for the subset of overweight and obese patients. Nephrotoxic occurrences were noted in 7% of the weight-based dosing regimens compared with none in the BSA-based dosing regimens. A BSA-based vancomycin dosing regimen resulted in significantly more initial vancomycin trough concentrations ≥10 mg/L and trended towards higher initial vancomycin trough concentrations without observable nephrotoxicity.

Construction of a risk prediction model of vancomycin-associated nephrotoxicity to be used at the time of initial therapeutic drug monitoring: A data mining analysis using a decision tree model.

In our previous study, we built a risk prediction model of vancomycin (VCM)-associated nephrotoxicity using decision tree (DT) analysis. However, this has several limitations in clinical applications. Our objective here was to construct a clinically applicable risk prediction model to be used at the time of initial therapeutic drug monitoring (TDM), in patients with uncomplicated infections. A retrospective study was conducted at Hokkaido University Hospital. Subjects that had received VCM were extracted between November 2011 and April 2017. Nephrotoxicity was defined as an increase in serum creatinine of 0.5mg/dL or 50% or higher from baseline. The additional inclusion criteria in this study were as follows: (1) the target trough level of VCM was set to 10 to 15mg/L, and (2) the duration of therapy was 7 to 14days. Patients were assumed to have uncomplicated infections. Risk factors for nephrotoxicity were evaluated, which could be extracted at the initial TDM. In the DT analysis, a chi-squared automatic interaction detection algorithm was constructed. A total of 402 patients were enrolled, and 56 (13.9%) patients developed nephrotoxicity. In the DT analysis, concomitant medications (furosemide, piperacillin-tazobactam, and vasopressor drugs) and an initial VCM trough concentration≥15.0mg/L were extracted as predictive variables by which patients were divided into six subgroups. The incidence of nephrotoxicity was 5.2% to 70.0%, with subgroups classified as low to high risk of nephrotoxicity. The accuracy of DT model was favourable (87.1%). We propose that the DT model built in this study is applicable to clinical practice.

Evaluation of Vancomycin Dosing in Patients With Cirrhosis: Beginning De-Liver-ations about a New Nomogram.

Background: Reduced hepatic production of creatinine precursors in patients with decompensated cirrhosis leads to falsely low serum creatinine values. Therefore, when performing empiric dosing of vancomycin, an overestimation of creatinine clearance may result in significantly supratherapeutic vancomycin levels and increased risks of nephrotoxicity. Objective: The objective of the study is to evaluate vancomycin dosing requirements in patients with cirrhosis stratified by Child-Pugh Score, with subsequent comparison with doses that are recommended in the previously published and validated Kullar nomogram. Methods: A retrospective evaluation of patients with cirrhosis who received vancomycin for at least 3 full days and had at least 1 serum concentration drawn. Vancomycin daily dose and corresponding serum concentration were collected with patients stratified by Child-Pugh Score for comparison. Each patient had their vancomycin dose compared with the dose suggested by a published nomogram. Results: A total of 201 courses of vancomycin were followed. There were no significant differences between the Child-Pugh cohorts with respect to initial vancomycin dosing. There was also no significant difference in the median initial vancomycin trough concentration between the 3 cohorts (Child-Pugh A: 13.7 µg/mL [interquartile range, IQR: 10.4-22.1]; Child-Pugh B: 20.2 µg/mL [IQR: 15.1-25.9]; Child-Pugh C: 19.3 µg/mL [IQR: 14.9-25.2, P = .08]. The median vancomycin dose using the Kullar nomogram would have been 3.0 g/day (IQR: 2.0-3.75, P < .001), but the median dose actually used in this patient population was significantly less at 2.0 g/day. Nonetheless, the median vancomycin trough concentration in the entire patient population was 19.8 µg/mL (IQR: 15.4-25.9). Conclusion: In patients with cirrhosis, there was a high incidence of supratherapeutic vancomycin serum concentrations despite the fact that dosing was significantly less than that suggested by the published Kullar nomogram.

Cystatin C–Guided Vancomycin Dosing in Critically Ill Patients: A Quality Improvement Project

The aim of the study was to determine whether a vancomycin dosing algorithm based on estimated glomerular filtration rate from creatinine and cystatin C levels (eGFRcr-cys) improves target trough concentration achievement compared to an algorithm based on estimated creatinine clearance (eCLcr) in critically ill patients. This prospective quality improvement project evaluated intensive care unit (ICU) patients started on intravenous vancomycin using one of 2 different strategies. Dosing regimens were selected and implemented after an individualized goal trough range was established (10-15 or 15-20mg/L). Steady-state goal trough achievement was compared between treatment arms with and without adjustment for potential confounders. 3 medical and surgical ICUs at a single tertiary medical center. During January 2012 to October 2013, vancomycin was dosed according to eCLcr using the Cockcroft-Gault formula (control arm). During December 2013 to May 2015, a multidisciplinary quality improvement team implemented a novel vancomycin dosing algorithm according to eGFRcr-cys using the CKD-EPI equation (intervention arm). Steady-state initial goal vancomycin trough concentration achievement. More patients in the intervention arm (67 of 135 [50%]) achieved therapeutic trough vancomycin levels than in the control arm (74 of 264 [28%]; OR, 2.53; 95% CI, 1.65-3.90; P<0.001). Improved trough achievement was maintained even after adjustment for age, sex, APACHE (Acute Physiology and Chronic Health Evaluation) III score, fluid balance, baseline CLcr, surgical admission diagnosis, presence of sepsis, and goal trough concentration range (adjusted OR, 2.79; 95% CI, 1.76-4.44; P<0.001). Clinical outcomes were similar between groups. Nonrandomized, incomplete algorithm compliance. A vancomycin dosing nomogram based on eGFRcr-cys significantly improved goal trough achievement compared to eCLcr among ICU patients with stable kidney function. Further studies are warranted to characterize the relationship between use of cystatin C-guided dosing and clinical outcomes.

Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin

Achieving vancomycin troughs of 15-20μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15-20μg/mL in the 20-mg/kg/dose sub-cohort and 10-15μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10μg/mL, respectively) and supratherapeutic troughs (>20 and >15μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98-2.22). Of 108 patients who received 15mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02-1.37). Achieving vancomycin troughs of 15-20μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20mg/kg/dose IV every 6-8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

Identification of Risk Factors for Initial Elevated Vancomyin Trough Concentrations.

Background: Recent literature suggests that elevated vancomycin trough concentrations (>20 µg/mL) may be associated with an increased risk of nephrotoxicity and lead to an increase in mortality and hospital length of stay. Objective: The purpose of this study was to identify variables that may be predictive of elevated initial vancomycin trough concentrations. Methods: Retrospective case-control study of all adult patients who had an initial vancomycin trough concentration measured between January 1, 2013, and December 31, 2014. Case patients had an initial trough concentration >20 µg/mL, while control patients had an initial trough concentration of ≤20 µg/mL. Patients were excluded from the study if they were in the intensive care unit, had unstable renal function, or if they had cystic fibrosis, solid organ transplant, or bone marrow transplant. Results: Of the 512 vancomycin trough concentrations reviewed, 54 patients met the case definition, while 140 patients were randomly selected as controls. In a multivariate model, baseline serum creatinine, body mass index, heart failure, and malignancy were all independently predictive of an initial vancomycin concentration >20 µg/mL. Conclusions: Reduced baseline renal function coupled with increasing body mass index is associated with an increased risk of an elevated initial vancomycin trough concentration. This risk is further enhanced by the presence of heart failure and/or malignancy. When these risk factors are present, it may be prudent to consider implementation of individualized dosing to achieve initial target concentrations.

Assessment of initial serum vancomycin trough concentrations and their association with initial empirical weight-based vancomycin dosing and development of nephrotoxicity in children: a multicenter retrospective study.

To determine whether a relationship exists between initial serum vancomycin trough concentrations and initial empirical vancomycin dose, patient weight, and patient age, and to determine the risks for vancomycin-associated nephrotoxicity in pediatric patients stratified by hospital setting. Stepwise linear and multinomial logistic regression analysis of retrospectively collected data. Two geographically distinct children's tertiary care medical centers. A total of 316 pediatric patients without preexisting renal dysfunction who were managed outside of the neonatal intensive care unit and were treated with at least 3 doses of vancomycin for gram-positive bacterial infections and had at least one serum vancomycin trough concentration between January 1, 2008, and July 31, 2010. Elevated vancomycin trough concentrations had no statistically significant relationship with initial empirical vancomycin dosing across all hospital settings. Serum vancomycin trough concentrations (lower than 15mg/L or 15-20mg/L) were not associated with increased risk of nephrotoxicity. Concomitant nephrotoxic agents, however, including loop diuretics, vasopressors, angiotensin-converting enzyme (ACE) inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs) were significantly associated with the development of nephrotoxicity in medical-surgical and intensive care patients. Based on this analysis, use of loop diuretics and vasopressors increased the odds of developing nephrotoxicity (odds ratio [OR] 42.8 [p=0.001] and 18.4 [p=0.02], respectively). Use of NSAIDS and ACE inhibitors also increased the odds of developing nephrotoxicity (OR 18.6 [p=0.02] and 4.7 [p=0.03], respectively). No significant associations were found between initial empirical weight-based vancomycin dosing or elevated serum trough concentrations and development of nephrotoxicity in children; rather, nephrotoxicity was associated with combination therapy with vancomycin and other potentially nephrotoxic agents.

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children?

In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic fibrosis, an elevated baseline serum creatinine, or without a serum creatinine concentration obtained after receipt of vancomycin were excluded. Acute kidney injury was defined using adapted pediatric RIFLE criteria as an increase in serum creatinine from baseline of 50% or more. Acute kidney injury occurred in 19.4% of the 859 children included, with no difference between the 2007 and 2010 periods (18.8% vs 20%, respectively; P = .636). Intensive care unit admission (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.20-2.94) and an initial vancomycin trough concentration ≥15 mg/L (OR, 2.18; 95% CI, 1.21-3.92) were determined to be significantly associated with AKI. These results suggest an initial vancomycin serum trough concentration of ≥15 mg/L and intensive care unit admission are predictors of AKI in this pediatric population.

The Effect of Age and Weight on Vancomycin Serum Trough Concentrations in Pediatric Patients

Vancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and children. Despite more aggressive vancomycin dosing, there continues to be significant variability in vancomycin trough concentrations in pediatric patients. To determine if vancomycin trough concentrations in pediatric patients differ by age and weight, we reviewed records of hospitalized patients who received vancomycin between 2008 and 2012. Patients were divided into groups that received vancomycin 40mg/kg/day (2008-2009) or 60mg/kg/day (2010-2012). Vancomycin trough concentrations were compared between groups and within the 60mg/kg/day group, stratified by patient age and weight. After increasing the vancomycin dose from 40 to 60mg/kg/day, initial trough concentrations increased significantly in patients younger than 2 and greater than 6years of age, but not in patients between the ages of 2 and 5years. In the 60 mg/kg/day group, only 16.7% of patients between 2 and 5years of age had initial trough concentrations in the therapeutic range (10-20μg/ml). Initial trough concentrations were therapeutic in a greater proportion of patients ages 6-12years (38.7%) and 13-18years (63.0%). Patients between the ages of 13 and 18 had the highest proportion of supratherapeutic initial vancomycin trough concentrations (14.8%). Patients weighing over50kg had significantly higher trough concentrations than patients 50kg or less (17.1μg/ml vs 9.3μg/ml, p<0.001). Although increasing the vancomycin dose from 40 to 60mg/kg/day led to a significant increase in vancomycin trough concentrations, a large proportion of patients receiving 60mg/kg/day of vancomycin had trough concentrations outside of the therapeutic range. Specifically, patients younger than 6years tended to have low trough concentrations, whereas adolescents and children over50kg were more likely to have elevated trough concentrations. Vancomycin dosing strategies in pediatric patients should consider age and weight as well as renal function and indication.

Vancomycin Trough Concentrations in Overweight or Obese Pediatric Patients

To compare vancomycin trough concentrations in overweight or obese pediatric patients to those with normal body habitus, after initial dosing based on total body weight (TBW). Retrospective observational case-control study. Free-standing academic pediatric hospital. Forty-two overweight or obese pediatric patients were matched to 84 children of normal body habitus (NBH). Empiric vancomycin dosing was based on TBW and guided by an age-stratified dosing algorithm previously developed at our center. Initial steady-state vancomycin trough concentrations were retrieved from the electronic medical record. Overweight and obese children had significantly higher initial vancomycin trough concentrations compared with children who had an NBH (median 14.4μg/ml vs 10.5μg/ml, p<0.001). Initial vancomycin trough concentrations above 20μg/ml occurred more often in overweight and obese children (p=0.016). Our dosing algorithm suggested that initial vancomycin trough concentrations below 10μg/ml occurred significantly more often in children with NBH (p<0.001). Overweight and obese pediatric patients may have elevated initial vancomycin trough concentrations when empiric dosing is based on TBW. Special attention to therapeutic drug monitoring is warranted in all children.

Evaluation of a vancomycin dosing nomogram based on the Modification of Diet in Renal Disease equation in intensive care unit patients

PurposeThe purpose of the study is to evaluate the effectiveness of a vancomycin nomogram using actual body weight and the Modification of Diet in Renal Disease equation to estimate renal function in intensive care unit patients. MethodsRetrospective evaluation (preimplementation group, n = 57) was conducted from March 2011 to April 2011. Prospective evaluation was conducted after nomogram implementation (postimplementation group, n = 60) from December 2011 to February 2012. ResultsThe percentage of patients with an initial vancomycin trough concentration 15 μg/mL or higher increased in the postimplementation group as compared with the preimplementation group (72% vs 39%, P = .0004). The postimplementation group also demonstrated an increase in the percentage of patients with initial trough concentration between 15 and 20 μg/mL (42% vs 19%, P = .0099), and no statistical difference in the percentage of patients with an initial trough greater than 20 μg/mL (30% vs 19%, P = .2041). There was no difference in nephrotoxicity in the postimplementation group compared with the preimplementation group (18% vs 17.5%, P = 1.0). ConclusionUse of a vancomycin nomogram increased the percentage of initial vancomycin trough concentrations 15 μg/mL or higher in intensive care unit patients and was not associated with an increased occurrence of nephrotoxicity.

Evaluation of Vancomycin Dosing and Monitoring in Adult Medicine Patients

Purpose To assess the clinical impact of a vancomycin dosing protocol and monitoring tool on initial dose, dosing interval, and trough concentrations in adult medicine patients. Methods This was a retrospective chart review of adult medicine patients who received at least one dose of vancomycin and were admitted during the pre-implementation period, February 1 to April 2009, or during the post-implementation period, June 1 to October 31, 2009. All outcomes for patients in the pre-implementation group were compared to those in the post-implementation group. The primary outcomes were frequency of appropriate initial vancomycin dose and dosing interval. The secondary outcomes included frequency of appropriate initial vancomycin trough concentrations, mean number of levels drawn per patient, and mean duration of therapy. Results A total of 450 patients were identified, with 225 patients in each study group. Patients with an appropriate initial vancomycin dose significantly increased in the post-implementation group (56% vs 40%; P &lt; .001). The number of patients with an appropriate original dosing interval (67% vs 63%; P = 0.32), appropriate initial trough concentration (44% vs 45%; P = 0.89), mean number of levels drawn (1.9 vs 2.1; P = 0.56), and duration of therapy (4.9 vs 5.0; P = 0.77) was similar between the 2 groups. Conclusions The implementation of a vancomycin empiric dosing protocol and monitoring tool had a significant impact on the initial dose. Further education regarding vancomycin dosing and monitoring is warranted to improve initial dosing interval, initial trough concentration, number of levels drawn, and duration of therapy.

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid

The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s. All patients admitted to the trauma intensive care unit from 1997 to 2008 diagnosed with MRSA VAP were retrospectively reviewed. Diagnosis required bacterial growth ≥ 100,000 colony forming units/mL from a bronchoscopic bronchoalveolar lavage, new or changing infiltrate, plus at least two of the following: fever, leukocytosis or leukopenia, or purulent sputum. Overall, 125 patients with 141 episodes of MRSA VAP were identified. Mean age was 47 years ± 21 years, median Injury Severity Score was 29 (22-43), 70% of patients were male, and the mean length of intensive care unit stay was 38 days ± 35 days. The mean initial vancomycin dose was 18.1 mg/kg/dose with a mean duration of therapy of 11 days. Clinical success was achieved in 88% (125 of 131) of episodes, with microbiological success in 89% (66 of 74) of episodes with a follow-up bronchoscopic bronchoalveolar lavage. Overall mortality was 20% (25 of 125), with death due to VAP in 12 of 25 deaths. Mean initial vancomycin trough concentrations were 10.6 mg/L in the clinical success group and 13.3 mg/L in the clinical failure group (p = not significant). High-dose vancomycin provided an acceptable cure rate for MRSA VAP in critically ill trauma patients. Therapeutic study, level III.