scholarly journals Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population

2017 ◽  
Vol 22 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Omayma A. Kishk ◽  
Allison B. Lardieri ◽  
Emily L. Heil ◽  
Jill A. Morgan

OBJECTIVES Adult guidelines suggest an area under the curve/minimum inhibitory concentration (AUC/MIC) > 400 corresponds to a vancomycin trough serum concentration of 15 to 20 mg/L for methicillin-resistant Staphylococcus aureus infections, but obtaining these troughs in children are difficult. The primary objective of this study was to assess the likelihood that 15 mg/kg of vancomycin every 6 hours in a child achieves an AUC/MIC > 400. METHODS This retrospective chart review included pediatric patients >2 months to <18 years with a positive S aureus blood culture and documented MIC who received at least two doses of vancomycin with corresponding trough. Patients were divided into two groups: group 1 initially receiving ≥15 mg/kg every 6 hours, and group 2 initially receiving any other dosing ranges or intervals. AUCs were calculated four times using three pharmacokinetic methods. RESULTS A total of 36 patients with 99 vancomycin trough serum concentrations were assessed. Baseline characteristics were similar between groups. For troughs in group 1 (n = 55), the probability of achieving an AUC/MIC > 400 ranged from 16.4% to 90.9% with a median trough concentration of 11.4 mg/L, while in group 2 (n = 44) the probability of achieving AUC/MIC > 400 ranged from 15.9% to 54.5% with mean trough concentration of 9.2 mg/L. The AUC/MICs were not similar between the different pharmacokinetic methods used; however, a trapezoidal equation (Method A) yielded the highest correlation coefficient (r2 = 0.59). When dosing every 6 hours, an AUC/MIC of 400 correlated to a trough serum concentration of 11 mg/L. CONCLUSIONS The probability of achieving an AUC/MIC > 400 using only a trough serum concentration and an MIC with patients receiving 15 mg/kg every 6 hours is variable based on the method used to calculate the AUC. An AUC/MIC of 400 in children correlated to a trough concentration of 11 mg/L using a trapezoidal Method to calculate AUC.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S669-S669
Author(s):  
Genene A Wilson ◽  
Allison Nelson ◽  
Palak Bhagat ◽  
Deborah Bondi ◽  
Pooja Shah ◽  
...  

Abstract Background Gentamicin is commonly used for peripartum infections. Given literature supporting efficacy of once-daily dosing (ODD) of 5 mg/kg for chorioamnionitis, University of Chicago Medicine made the change from three times daily dosing (TIDD) to ODD. As gentamicin readily cross the placenta, it would be expected that maternal ODD would result in higher gentamicin neonatal serum concentrations following birth. Methods This was a single-center, retrospective chart review of all neonates born to mothers receiving peripartum ODD gentamicin within 12 hours of delivery between October 2019 and March 2020. A STAT random gentamicin serum concentration was obtained upon admission in neonates when initiation of antibiotics was desired. Specific dosing recommendations (Table 1) were developed utilizing neonatal population-based pharmacokinetics. The primary outcome was initial neonatal gentamicin serum concentration at birth. Other outcomes were also evaluated. Results were evaluated in two groups based on neonatal serum concentrations of less than 2 mcg/mL (Group 1) versus 2 mcg/mL or greater (Group 2). Table 1: Neonatal gentamicin dosing algorithm Results Thirty-two mother-newborn dyads were included in this study. Baseline demographics are shown in Table 2. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.39 kilograms. The mean initial gentamicin concentration was supratherapeutic at 3.06 + 1.92 mcg/mL among all newborns (Table 3). The mean maternal dose in Group 1 (n=11) was 3.52 mg/kg (3.34, 4.77) based on actual body weight and 4.78 mg/kg (4.34, 5.18) in Group 2 (n=21) (p=0.025). The median time between maternal gentamicin administration and time of delivery varied between the groups at 0.5 hours versus 2.63 hours, respectively (p=0.005). All newborn gentamicin concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n=8) (Figure 1). Overall protocol compliance rate was 81.3%. There were no significant differences in nephrotoxicity or ototoxicity between groups. Table 2. Baseline Demographics Table 3. Outcomes Figure 1. Comparison of maternal gentamicin time from administration to delivery and neonatal serum gentamicin concentrations Conclusion This study suggests peripartum ODD of gentamicin may lead to clinically significant serum concentrations in neonates if administered between 1 to 12 hours of birth. Further studies are warranted to evaluate the effects of maternal ODD of gentamicin on newborns. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 26 (7) ◽  
pp. 753-757
Author(s):  
Christine A. Vu ◽  
Mariawy Riollano-Cruz ◽  
Shanna R. Kowalsky

There are a limited number of studies that guide dosing of posaconazole delayed-release (DR) tablets for the pediatric population. Current FDA-approved doses are only recommended for patients 13 years and older. For younger patients, providers are faced with the challenge of recommending posaconazole doses extrapolated from adult studies or choosing an alternative agent. We report on a case of a 10-year-old patient who experienced a supratherapeutic trough serum concentration and transaminitis after receiving the extrapolated adult dosage of posaconazole DR tablets (300 mg twice daily for the first day, followed by 300 mg daily) for 7 days. In the end, the patient required a smaller dose of 200 mg daily to achieve the desired trough target concentration for the treatment of a Rhizopus neck infection. Our findings highlight the need for additional studies to determine the optimal dosing of posaconazole DR tablets for children.


2017 ◽  
Vol 8 (5) ◽  
pp. 559-563 ◽  
Author(s):  
Connor Callahan ◽  
David Saudek ◽  
Amanda Shillingford ◽  
Sara Creighton ◽  
Garick Hill ◽  
...  

Background: We sought to compare clinical outcomes and resource utilization for two surgical approaches for single-stage repair of coarctation of the aorta and ventricular septal defect (VSD). Methods: This was a retrospective chart review of 21 consecutive neonates and infants undergoing single-stage repair of coarctation of the aorta and VSD. Group 1 included 13 patients with both arch repair and VSD repair completed via sternotomy. Group 2 included eight patients with off-pump arch repair via left thoracotomy followed by repositioning and VSD repair via sternotomy. Primary clinical outcome was arch reintervention. Secondary outcomes included various measures of resource utilization. Results: Group 1 patients demonstrated younger age at repair (median of 10 days vs 57 days for group 2; P = .05) and lower proximal arch z scores (−4.2 vs −2.3 for group 2; P = .003). Arch reintervention occurred in 0 of 8 patients in group 2 and 1 (7.7%) of 13 patients in group 1 ( P = nonsignificant). Group 2 was associated with lower total charges (US$68,301 vs US$211,723 for group 1; P = .0007), shorter length of stay (8 days vs 23 days for group 1; P = .004), and shorter duration of postoperative mechanical ventilation (0.5 days vs 4.0 days for group 1; P = .0008). Group 2 was also associated with shorter total cardiopulmonary bypass time (86 minutes vs 201 minutes for group 1; P = .0009). Conclusion: Single-stage two-incision repair of coarctation and VSD in appropriately selected patients may be associated with higher value of care. Confirmation of this finding will require further study based on larger numbers of patients.


1993 ◽  
Vol 4 (1) ◽  
pp. 81-90
Author(s):  
D J Leehey ◽  
B I Braun ◽  
D A Tholl ◽  
L S Chung ◽  
C A Gross ◽  
...  

A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.


2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.


2021 ◽  
Vol 26 (6) ◽  
pp. 608-614
Author(s):  
Laura A. Salemi ◽  
Anna L. Sahlstrom ◽  
Sin Yin Lim ◽  
Peter N. Johnson ◽  
Douglas Dannaway ◽  
...  

OBJECTIVE Caffeine citrate doses >5 mg/kg/day are frequently used for apnea of prematurity. The primary objective was identification of patients maintained on 5 mg/kg/day (Group 1). Secondary objectives included identification of patients requiring dose increases: 7.5 mg/kg every 24 hours (Group 2), 10 mg/kg every 24 hours (Group 3), and 5 mg/kg every 12 hours (Group 4); comparison of demographics and clinical characteristics; and identification of patients requiring dose adjustments owing to caffeine-associated tachycardia. METHODS Retrospective study of neonates born between 23 to <31 weeks' gestation, receiving caffeine between January 1, 2015, and July 31, 2019. Patients receiving caffeine <1 week, initial maintenance dose >5 mg/kg/day, or with congenital abnormalities were excluded. Descriptive and inferential statistics were performed, with a p < 0.05. RESULTS Overall, 281 patients were included, with 99 (35.2%) in Group 1; 56 (19.9%) in Group 2; 47 (16.7%) in Group 3; and 79 (28.1%) in Group 4. Significant differences in gestational age were noted, with Group 3 and 4 patients being more premature than Groups 1 and 2 (p < 0.001). Dose increases occurred at a median postnatal age and postmenstrual age of 13.0 days and 31.4 weeks in Group 2; 17.0 days and 30.3 weeks in Group 3; and 16.0 days and 30.1 weeks in Group 4. Significant differences were noted for development of tachycardia requiring dose adjustment, with Groups 3 and 4 having the highest percentage (p < 0.001). CONCLUSIONS Two-thirds received caffeine citrate doses >5 mg/kg/day, with 44% receiving 10 mg/kg/day. Further exploration is necessary to determine the optimal PNA or PMA for dose adjustments.


Author(s):  
Soo Hyun Park ◽  
Ji Young Min ◽  
Won Cul Cha ◽  
Ik Joon Jo ◽  
Taerim Kim

Understanding age-specific injury patterns allows the continued improvement of prevention strategies. This is a retrospective study analyzing the Korea Emergency Department-Based Injury In-depth Surveillance data, including those aged ≤19 years old between January 2011 and December 2017. In this study, we focused on changes in the modes of injury and severity, and prevention potential by dividing the patients into four age groups: group 1 (0–4 years), group 2 (5–9 years), group 3 (10–14 years), and group 4 (15–19 years). The most common mode of injury in younger age groups 1 and 2 was a fall or slip. Most injuries in older age groups 3 and 4 were unintentional and intentional collisions combined. Traumatic brain injuries (2.1%), intensive care unit admissions (1.8%), and overall death (0.4%) were the highest in group 4. The proportions of severe and critical injury (EMR-ISS ≥ 25) were 7.5% in group 4, 3.2% in group 3, 2.5% in group 1, and 1% in group 2. This study presents a comprehensive trend of injuries in the pediatric population in South Korea. Our results suggest the importance of designing specific injury-prevention strategies for targeted groups, circumstances, and situations.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S566-S567
Author(s):  
Krista Weaver ◽  
Madan Kumar ◽  
Allison Nelson ◽  
Palak Bhagat

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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