scholarly journals An Ensemble Model for Prediction of Vancomycin Trough Concentrations in Pediatric Patients

2021 ◽  
Vol Volume 15 ◽  
pp. 1549-1559
Author(s):  
Xiaohui Huang ◽  
Ze Yu ◽  
Shuhong Bu ◽  
Zhiyan Lin ◽  
Xin Hao ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Ensemble Model ◽  
Vancomycin Trough ◽  
Trough Concentrations

scholarly journals Challenges of Vancomycin Dosing and Therapeutic Monitoring in Neonates

2020 ◽  
Vol 25 (6) ◽  
pp. 476-484
Author(s):  
Jennifer T. Pham
Keyword(s):  
Pediatric Patients ◽  
Late Onset ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Coagulase Negative Staphylococci ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Dosing Regimens ◽  
Vancomycin Trough ◽  
Trough Concentrations

Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ≥400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ≥400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.

scholarly journals Evaluation of Vancomycin Dosing in Pediatric Cystic Fibrosis Patients

2016 ◽  
Vol 21 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Erin J. McDade ◽  
Jennifer L. Hewlett ◽  
Siby P. Moonnumakal ◽  
Carol J. Baker
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Function ◽  
Pediatric Patients ◽  
Primary Objective ◽  
Vancomycin Trough ◽  
Vancomycin Dosage ◽  
Trough Concentrations ◽  
The Mean ◽  
The Impact ◽  
Vancomycin Treatment

OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15–20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 ± 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses.

scholarly journals Use of Body Surface Area for Dosing of Vancomycin

2019 ◽  
Vol 24 (4) ◽  
pp. 296-303
Author(s):  
Elizabeth L. Sawrey ◽  
Mary W. Subramanian ◽  
Kacy A. Ramirez ◽  
Brandy S. Snyder ◽  
Brittany B. Logston ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Surface Area ◽  
Body Surface ◽  
Pediatric Patients ◽  
Obese Patients ◽  
Dosing Regimen ◽  
Trough Serum ◽  
Dosing Regimens ◽  
Vancomycin Trough ◽  
Trough Concentrations

OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

scholarly journals Does Combination Therapy With Vancomycin and Piperacillin-Tazobactam Increase the Risk of Nephrotoxicity Versus Vancomycin Alone in Pediatric Patients?

2016 ◽  
Vol 21 (4) ◽  
pp. 332-338 ◽  
Author(s):  
Katherine E. McQueen ◽  
Dana W. Clark
Keyword(s):  
Combination Therapy ◽  
Serum Creatinine ◽  
Pediatric Patients ◽  
Combination Group ◽  
Single Center ◽  
Exact Test ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
Serum Vancomycin ◽  
Vancomycin Group

OBJECTIVES: To determine if the incidence of nephrotoxicity is higher in pediatric patients treated with the combination of vancomycin and piperacillin-tazobactam, compared to patients treated with vancomycin alone. Secondary objectives were to determine if admission to an intensive care unit (ICU), higher serum vancomycin trough concentrations (>15 mg/L), or receipt of other nephrotoxic agents were related to the development of nephrotoxicity. METHODS: This was a retrospective, single-center, cohort study of 79 patients treated with vancomycin and 106 patients treated with vancomycin and pipracillin/tazobacatam (TZP). Serum creatinine was trended to determine if patients had nephrotoxicity, which was defined as at least a 100% increase in serum creatinine or an increase of ≥0.5 mg/dL from the baseline value. Fisher's exact test was used to compare the incidence of nephrotoxicity in the vancomycin group to the combination group. Secondary objectives were evaluated by using relative risk (RR). RESULTS: Nephrotoxicity developed in 3 of 79 patients (3.8%) in the vancomycin group and in 25 of 106 patients (23.6%) on combination therapy (p = 0.0001). In patients receiving only vancomycin, there was no statistically significant increase in nephrotoxicity for patients in the ICU (RR 1.85, 95% confidence interval [CI] 0.175–19.62, p = 0.61), those with higher vancomycin troughs (RR 2.32, CI 0.226–23.86, p = 0.48), or those receiving other nephrotoxic medications (RR 2.94, CI 0.2779–31.05, p = 0.37). In the combination group, having higher serum vancomycin trough concentrations increased the risk of nephrotoxicity (RR 5.22, CI 2.407–11.306, p < 0.0001). CONCLUSIONS: Combination therapy with vancomycin and TZP is potentially more nephrotoxic than vancomycin alone. ICU admissions, high vancomycin troughs (>15 mg/L), and concomitant nephrotoxic medications cannot be excluded as risk factors for the observed increase in nephrotoxicity in patients receiving vancomycin and TZP.

Vancomycin Trough Concentrations in Overweight or Obese Pediatric Patients

2013 ◽  
Vol 33 (12) ◽  
pp. 1273-1277 ◽  
Author(s):  
Daniel E. Heble ◽  
Christopher McPherson ◽  
Miranda P. Nelson ◽  
David A. Hunstad
Keyword(s):  
Pediatric Patients ◽  
Vancomycin Trough ◽  
Trough Concentrations

Glomerular Filtration Rate Equations Do Not Accurately Predict Vancomycin Trough Concentrations in Pediatric Patients

2014 ◽  
Vol 48 (6) ◽  
pp. 691-696 ◽  
Author(s):  
Elizabeth L. Alford ◽  
Rebecca F. Chhim ◽  
Catherine M. Crill ◽  
M. Colleen Hastings ◽  
Bettina H. Ault ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Pediatric Patients ◽  
Rate Equations ◽  
Vancomycin Trough ◽  
Trough Concentrations

scholarly journals Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates

2018 ◽  
Vol 62 (4) ◽  
pp. e01647-17 ◽  
Author(s):  
Sheng-Hsuan Tseng ◽  
Chuan Poh Lim ◽  
Qi Chen ◽  
Cheng Cai Tang ◽  
Sing Teang Kong ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
The Relationship

ABSTRACT Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC24. A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

scholarly journals 1552. Correlation Between Vancomycin Serum Trough Concentrations and Area Under the Curve in Pediatric Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S566-S567
Author(s):  
Krista Weaver ◽  
Madan Kumar ◽  
Allison Nelson ◽  
Palak Bhagat
Keyword(s):  
Pediatric Patients ◽  
Retrospective Chart Review ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Optimal Method ◽  
Study Objective ◽  
Serum Trough ◽  
Trough Concentrations ◽  
Group 2 ◽  
Group 1

Abstract Background Despite years of experience with vancomycin (VAN), the optimal method to monitor VAN therapy in pediatric patients is still unknown. Recent pediatric data indicate serum trough concentrations lower than 10–20 mg/L or 15–20 mg/L based on indication may achieve an AUC24> 400 mg hours/L. The primary study objective was to compare AUC24 to goal VAN serum trough concentrations (STC). Methods A retrospective chart review of pediatric patients who received intravenous VAN June 1, 2018 to December 31, 2018 was completed. AUC24 was calculated using a trapezoidal method with 2 steady-state serum concentrations. A serum peak concentration was drawn 1 hour and 15 minutes following the end of infusion and an STC was drawn 30 minutes prior to infusion. Results During 25 admissions, 12 patients had a first AUC24 at goal and 13 patients had a first AUC24 below goal. Of 41 AUC24 calculations, 27 AUC24s were ≥400 mg hours/L (group 1), and 14 AUC24s were <400 mg hours/L (group 2). Median AUC24 was 561 mg hours/L for group 1 vs. 344.5 mg hours/L for group 2 (P < 0.001). Correlating Cmin and Ctrough (Ctr) for group 1 and group 2 were 12 mg/L and 13.5 mg/L vs. 6.4 mg/L and 7.3 mg/L, respectively (P < 0.001). Figure 1 shows the pharmacokinetic parameters for each group. Spearman correlation between AUC24 and Cmin was 0.87. Of the 35 subtherapeutic VAN STCs, 20 (57.1%) achieved an AUC24 ≥400 mg hours/L (P = 0.08). Subgroup analysis of AUC24 400–600 mg hours/L showed a median AUC24 of 519 mg hours/L with correlating Cmin and Ctr of 10.6 mg/L and 11.9 mg/L, respectively. The MIC was <1 in 90.9% of cases (Figure 2). The mean VAN dose required to achieve an AUC24 ≥400 mg hours/L was 77.7 mg/kg/day; dosing frequency did not appear to affect AUC24 outcome. Time to culture clearance was 2 days in group 1 and 6.5 days in group 2 (P = 0.24). No cases of nephrotoxicity were identified despite AUC24 values ranging from 265–1294 mg hours/L. Conclusion AUC24 monitoring using a 2-sample trapezoidal method was successfully implemented at this institution. The results of this study align with previous pediatric studies, supporting the use of lower serum trough concentration goals of 10–15 mg/L. Disclosures All authors: No reported disclosures.

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