scholarly journals 1108. Evaluation of Vancomycin Dosing in Adolescents

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S646-S646
Author(s):  
Ashley I Weaver ◽  
Genene A Wilson ◽  
Emily Belarski ◽  
Allison Nelson ◽  
Madan Kumar ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Serum Concentrations ◽  
Daily Dose ◽  
Safety Endpoint ◽  
Secondary Endpoints ◽  
Higher Doses

Abstract Background Pediatric vancomycin dosing varies based on age and renal function. Recent literature suggests previously recommended doses of 45-60 mg/kg/day may be insufficient to achieve an AUC:MIC ratio of 400-600 mg-hr/L and higher doses of at least 60 mg/kg/day may be required. However, data to guide dosing in adolescents is limited. Methods A single-center, retrospective chart review of patients aged 12 to 18 years who received vancomycin and had therapeutic drug monitoring (TDM) performed between July 2017 to June 2020 were included. The primary endpoint was the median total daily dose (TDD) of vancomycin required to achieve therapeutic serum concentrations. Secondary endpoints were to characterize how factors such as age, weight, trough versus AUC monitoring, malignancy, and trauma may influence dosing. The safety endpoint was the development of acute kidney injury (AKI). Results 130 vancomycin courses in 86 patients were included. Baseline characteristics are presented in Table 1. Of the 130 vancomycin courses, 50 courses (38%) achieved therapeutic serum concentrations at a median TDD of 49.8 mg/kg/day (IQR 42 – 59.4). This was not statistically different from the sub- or supra-therapeutic groups (p=0.22). Based on age, the median TDD for 12-14 year olds was higher at 60 mg/kg/day (IQR 45-78.8; n=14) than for 15-16 and 17-18 year olds [45.3 mg/kg/day (IQR 41.1-51; n=15), 48 mg/kg/day (IQR 42-52; n=21), respectively]. Obese patients needed a median TDD of 43.5 mg/kg/day vs at least 51 mg/kg/day in healthy and overweight patients. Finally, AUC guided dosing resulted in a slightly lower overall median TDD vs trough guided dosing (45.8 mg/kg/day vs 50.5 mg/kg/day). Additional dose requirements based on age, weight, TDM and other characteristics are presented in Table 2. Of the 15 patients who developed AKI per pRIFILE criteria, 2 were classified as injury and 3 as failure. Table 2. Total Daily Dose Course Analysis Conclusion To achieve therapeutic levels, adolescents 12 to14 years old need higher empiric doses of 60 mg/kg/day compared to 45 mg/kg/day in 15 to 18 year olds. Obese patients, however, may require lower TDD than underweight, healthy, and overweight patients. Patients that receive AUC versus trough monitoring may also require lower TDD to achieve therapeutic concentrations. More data is needed to further evaluate our findings. Disclosures All Authors: No reported disclosures

scholarly journals 1310. Implementation of AUC:MIC Pharmacy to Dose in an Academic Medical Center: A Pilot Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
Ann-Marie Idusuyi ◽  
Maureen Campion ◽  
Kathleen Belusko
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Total Daily Dose ◽  
Therapeutic Goals ◽  
Academic Medical ◽  
Progress Notes ◽  
Implementation Period

Abstract Background The new ASHP/IDSA consensus guidelines recommend area under the curve (AUC) monitoring to optimize vancomycin therapy. Little is known about the ability to implement this recommendation in a real-world setting. At UMass Memorial Medical Center (UMMMC), an AUC pharmacy to dose protocol was created to manage infectious diseases (ID) consult patients on vancomycin. The service was piloted by the pharmacy residents and 2 clinical pharmacists. The purpose of this study was to determine if a pharmacy to dose AUC protocol can safely and effectively be implemented. Methods A first-order kinetics calculator was built into the electronic medical record and live education was provided to pharmacists. Pharmacists ordered levels, wrote progress notes, and communicated to teams regarding dose adjustments. Patients were included based upon ID consult and need for vancomycin. After a 3-month implementation period, a retrospective chart review was completed. Patients in the pre-implementation group were admitted 3 months prior to AUC pharmacy to dose, had an ID consult and were monitored by trough (TR) levels. The AUC group was monitored with a steady state peak and trough level to calculate AUC. The primary outcome evaluated time to goal AUC vs. time to goal TR. Secondary outcomes included number of dose adjustments made, total daily dose of vancomycin, and incidence of nephrotoxicity. Results A total of 64 patients met inclusion criteria, with 37 patients monitored by TR and 27 patients monitored by AUC. Baseline characteristics were similar except for weight in kilograms (TR 80.0 ±25.4 vs AUC 92.0 ±26.7; p=0.049). The average time to goal AUC was 4.13 (±2.08) days, and the average time to goal TR was 4.19 (±2.30) days (p=0.982). More dose adjustments occurred in the TR group compared to the AUC (1 vs 2; p=0.037). There was no difference between the two groups in dosing (TR 15.8 mg/kg vs AUC 16.4 mg/kg; p=0.788). Acute kidney injury occurred in 5 patients in the AUC group and 11 patients in the TR group (p=0.765). Conclusion Fewer dose adjustments and less nephrotoxicity was seen utilizing an AUC based protocol. Our small pilot has shown that AUC pharmacy to dose can be safely implemented. Larger studies are needed to evaluate reduction in time to therapeutic goals. Disclosures All Authors: No reported disclosures

scholarly journals Vancomycin Dosing in Pediatric Extracorporeal Membrane Oxygenation: Potential Impacts of New Technologies

2017 ◽  
Vol 22 (5) ◽  
pp. 358-363
Author(s):  
Kevin P. Lonabaugh ◽  
Kelly J. Lunsford ◽  
Gary Y. Fang ◽  
David A. Kaufman ◽  
Samuel D. Addison ◽  
...  
Keyword(s):  
Renal Function ◽  
Extracorporeal Membrane Oxygenation ◽  
Pediatric Patients ◽  
New Technologies ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Membrane Oxygenation ◽  
Drug Concentrations ◽  
Daily Dose ◽  
Serum Vancomycin

OBJECTIVES The objective of the current study was to evaluate the doses of vancomycin used to obtain therapeutic drug concentrations in pediatric patients on extracorporeal membrane oxygenation (ECMO), using new ECMO technologies. METHODS This was a single-center, retrospective study of patients treated with vancomycin while receiving ECMO using low-volume circuit technology. RESULTS A total of 28 patients were included in the analysis of the primary endpoint. Patients had a median age of 6 weeks (0–11 years) and a median weight of 3.45 kg (2.44–37.2 kg). Ultrafiltration was used in 89.3% of patients at initiation of ECMO regardless of baseline renal function, resulting in a median urine output of 2 mL/kg/hr at the time of the final vancomycin dose. Most patients started vancomycin at the same time as ECMO. The median total daily dose was 30 mg/kg/day. The median total daily dose in a subset of patients less than one year of age was 20 mg/kg/day. Nearly all patients had at least 1 therapeutic trough serum vancomycin concentration. A total of 16 patients completed their vancomycin course using an interval of every 12 hours or shorter. Half-life was calculated in a subset of 11 patients and the mean was found to be 12.3 ± 2.8 hours. CONCLUSIONS An initial dosing interval of every 12 hours to provide a total daily dose of 30 mg/kg/day is a possible option in pediatric patients on ECMO provided that renal function is normal at baseline. Monitoring of serum vancomycin concentrations for adjustment of dosing is required throughout therapy and is still warranted.

Assessing Nephrotoxicity Associated With Different Vancomycin Dosing Modalities in Obese Patients at a Community Hospital

2021 ◽  
pp. 001857872110557
Author(s):  
Amanda Wolfe ◽  
Jonathan Bowling ◽  
Marintha R. Short ◽  
Greg Mateyoke ◽  
Steven C. Berger
Keyword(s):  
Drug Exposure ◽  
Area Under The Curve ◽  
Primary Objective ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Loading Dose ◽  
Obese Patients ◽  
Nominal Data ◽  
Primary Analysis ◽  
Days Of Therapy

Background: Vancomycin requires therapeutic drug monitoring (TDM) based on its pharmacokinetic properties, and guidelines have shifted to analyzing area under the curve over 24 hours (AUC24) rather than trough concentrations due to nephrotoxicity concerns and correlation to efficacy. Obesity is an established risk factor for vancomycin-induced nephrotoxicity due to increased drug exposure based on dosing calculations and volume of distribution estimation. The aim of this study is to assess the relationship between AUC-based versus trough-based dosing and nephrotoxicity among obese patients receiving vancomycin. Methods: This research project was conducted as a retrospective, observational, single-centered study which included obese adults who received at least 48 hours of vancomycin. The electronic medical record provided data for patients with vancomycin pharmacokinetic consults either evaluated with trough-only or AUC-based dosing. The primary objective was to compare the development of nephrotoxicity after vancomycin initiation, while secondary objectives included vancomycin loading dose exposure, total daily dose of vancomycin, and whether target TDM was attained. Nominal data were evaluated utilizing the chi-square test and continuous data using the independent samples t-test or Mann-Whitney test. The a priori level of significance was .05. Data analysis was performed using Microsoft Excel and SAS statistical software. Results: Two hundred fifty-four patients were included in the primary analysis. Four patients in the AUC cohort (6.3%) developed nephrotoxicity compared to 32 (17.4%) in the trough cohort ( P = .035). Both cohorts received a median of 4 days of therapy; however, the median loading dose per actual body weight in the AUC cohort was 20 mg/kg as compared to 16 mg/kg in the trough cohort. Of the 130 patients with available TDM in the trough cohort, 97 (74.6%) did not meet target attainment as compared to 15 of the 57 in the AUC cohort (26.3%) ( P < .001). Conclusions: AUC dosing was associated with a statistically significant reduction in AKI occurrence despite overall higher loading dose exposure as compared to the trough cohort. Though maintenance dose exposure was similar between both cohorts, patients in the AUC cohort maintained therapeutic concentrations at a higher percentage than the trough cohort.

Vancomycin Nephrotoxicity

2014 ◽  
Vol 27 (6) ◽  
pp. 545-553 ◽  
Author(s):  
Kari A. Mergenhagen ◽  
Angela R. Borton
Keyword(s):  
Risk Factors ◽  
Renal Damage ◽  
Historical Context ◽  
Severity Of Illness ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Factors Associated ◽  
Concurrent Use ◽  
Daily Dose ◽  
Trough Levels

Vancomycin earned notoriety for its tendency to cause nephrotoxicity shortly after it was introduced into practice, though the impurities responsible for historically significant rates of nephrotoxicity are of minimal concern today. Increasing usage of vancomycin has provided evidence that the drug itself can be nephrotoxic, but the exact mechanism by which this occurs has not been determined. Various studies have identified risk factors associated with development of vancomycin-associated nephrotoxicity, including total daily dose > 4 grams, trough levels > 20 mg/L, therapy exceeding 6 days, concurrent use of other nephrotoxic agents, preexisting renal disease, obesity, hypotensive episodes, and increasing severity of illness. Preventative strategies beyond risk assessment and therapeutic drug monitoring have shown little promise. Most cases of nephrotoxicity are reversible with discontinuation of vancomycin, but permanent renal damage can occur. This article is intended to serve as a practical review of vancomycin-associated nephrotoxicity, including historical context, risk factors, and common methods to evaluate and define renal dysfunction.

Variability of Total Daily Dose of Insulin in Type 1 Diabetic Pre-Menarchal vs Post-Menarchal Females

2020 ◽  
Author(s):  
Johnna M. Sizemore ◽  
Karolina Stack ◽  
Sanjay K. Bansal ◽  
Garry Sigman ◽  
Cara Joyce
Keyword(s):  
Retrospective Chart Review ◽  
Adolescent Females ◽  
Hormonal Contraceptives ◽  
Total Daily Dose ◽  
Study Objective ◽  
Insulin Requirements ◽  
Induce Insulin Resistance ◽  
Significant Difference ◽  
Daily Dose

Abstract Study Objective Quantify the change of insulin requirements in pre- vs post-menarchal adolescent females with type 1 diabetes (T1DM) by measuring the total daily dose (TDD; units/kg/day) of insulin administered before vs after menarche in order to provide anticipatory guidance of insulin requirements in adolescent females as they progress through puberty to help reduce the long-term complications of poorly controlled T1DM. Design/Setting/Participants A retrospective chart review study was conducted which included 52 adolescent females with T1DM, after subjects who were diagnosed with T1DM after menarche, those on hormonal contraceptives, or those that had hypothyroidism, major medical comorbidities, or incomplete records were excluded. Subject demographics along with body mass index (BMI) percentile, HgbA1c (hemoglobin A1c), and TDD of insulin were collected 0-2 years pre-, 0-2 years post-, and 2-4 years post-menarche to assess differences in TDD of insulin in pre- and post-menarchal adolescent females with T1DM. Interventions None Main Outcome Measures TDD of insulin at 0-2 years pre-, 0-2 years post-, and 2-4 years post-menarche in adolescent females with T1DM. Results There was a statistically significant difference of TDD of insulin in pre- vs. post-menarchal adolescent females with T1DM after controlling for HgbA1c and BMI. Conclusions While poor glycemic control is often attributed to adolescent non-compliance of insulin administration, a physiologic process similar to polycystic ovarian syndrome may induce insulin resistance in post-pubertal adolescent females with T1DM.

scholarly journals 1569. A Translational Model to Assess the Impact of Polymyxin B Dose Fractionation on Kidney Injury

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S573-S574
Author(s):  
Jiajun Liu ◽  
Gwendolyn M Pais ◽  
Sean N Avedissian ◽  
Andrew Lee ◽  
Nathaniel J Rhodes ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Kidney Injury ◽  
Polymyxin B ◽  
Urinary Biomarkers ◽  
Dose Fractionation ◽  
Total Daily Dose ◽  
Translational Model ◽  
Urine Biomarkers ◽  
Daily Dose ◽  
The Impact

Abstract Background Progression of antimicrobial resistance has revived Polymyxin B (PB) use in clinical practice. Dose-dependent acute kidney injury (AKI) limits its clinical use. It is unclear whether dose fractionation of total daily dose can lessen kidney injury. We assessed the role of PB fractionation on AKI in a translational model that employs sensitive urine biomarkers qualified by the FDA. Methods Male Sprague–Dawley rats received 12 mg/kg/day PB subcutaneously for 3 days or equal-volume normal saline (NS). PB was administered in 3 separate fractionated daily doses: 12 mg/kg daily (QD), 6 mg/kg twice daily (BID), and 4 mg/kg thrice daily (TID). Staggered blood sampling was done on days 1 to 4 and 24 hour urine was collected at baseline, on days 1, 2, and 3. Plasma creatinine (Cr) was quantified using LCMS/MS, and 24 hour urinary biomarkers (KIM1, OPN, CLN, calbindin, GSTα, IP-10, TIMP-1, and VEGF) were assayed with MILLIPLEX Rat Kidney Toxicity Magnetic Bead Panel. Mixed-effects models were used. Results A total of 32 rats contributed to the study data. Mean Cr were constant across groups over time (Figure 1, P = 0.18). For NS group, all biomarkers remained at baseline throughout study. Significant differences were seen for fractionation schemes for KIM1 (P = 0.02), CLN (P = 0.03), IP-10 (0.007) and TIMP-1 (P = 0.04). The differences for KIM1, IP-10, and TIMP-1 were driven by higher observed values in TID than those of BID as early as day 1 (P < 0.04). Furthermore, CLN was elevated for TID when compared with BID at baseline (P = 0.048). Similarly, TID group had the highest (but non-significant) elevations for IP-10 and TIMP-1 compared with QD on study days. Amongst all urine biomarkers, KIM1 in TID exhibited the most rapid rise from baseline to day 2 (Figure2, P < 0.0001). Conclusion In this translational model in which a single total daily dose was fractionated, sensitive urinary biomarkers indicated that TID dosing was worse than BID or QD dosing; dose fractionation of PB may lead to increased AKI. In addition, KIM1 rose rapidly as an early marker for AKI. Further efforts are needed to investigate the PK-TD relationship of PB in order to decrease AKI. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of a Conservative Pharmacist-led U-500R Insulin Management Protocol in the Primary Care Setting

2020 ◽  
Vol 11 ◽  
pp. 215013272097382
Author(s):  
Cyndi Dumont ◽  
Leah Fitzgerald ◽  
Connie A. Valdez
Keyword(s):  
Insulin Dose ◽  
Retrospective Chart Review ◽  
Total Daily Dose ◽  
Point Reduction ◽  
Daily Insulin Dose ◽  
Management Protocol ◽  
Daily Dose ◽  
The Impact ◽  
Total Daily Dosage

Objective The objective of this quality assurance study is to evaluate the impact of a conservative, pharmacist-led, U-500R insulin management protocol on diabetes control (A1c) and total daily dosage requirements between August 2016 and August 2018. Methods This was a retrospective chart review of adult patients, aged 18 to 79, with type 2 diabetes and managed with insulin, at 2 federally qualified healthcare clinics in Denver, Colorado. To determine if our conservative pharmacist-led U-500R insulin management protocol impacted efficacy and total daily dosage requirements when converting patients from U-100 to U-500R insulin, we compared the most effective dose of U-500R (defined as the total daily dose (TDD) of U-500R insulin at A1c goal or the lowest tolerated A1c) to the baseline A1c and TDD of U-100 insulin at time of conversion. Results Following conversion of U-100 to U-500R insulin, patients required an average of 21 fewer units of insulin with U-500R than U-100 and achieved an average A1c of 7.2% which reflected a reduction of 3.5 points from baseline. Five patients (62.5%) achieved A1c goal per ADA guidelines, and all patients achieved at least a 1.7 point reduction in A1c, with 1 patient achieving a 6.7 point reduction. Two patients (25%) were still in the process of U-500R titration at the time of data collection, and 1 patient (12.5%) did not achieve goal A1c while under pharmacy management at these clinics. Four of the five patients who achieved A1c goal did so with an overall reduction in total daily insulin dose (average of 57.5 units less than original U-100 dose) resulting in an average A1c decrease of 3.6 points.

Epidemiology of opioid pharmacy claims in the United States

2018 ◽  
Vol 4 (3) ◽  
pp. 145 ◽  
Author(s):  
Rachel E. Williams, PhD, MS ◽  
Timothy J. Sampson, BS ◽  
Linda Kalilani, MBBS, PhD ◽  
John I. Wurzelmann, MD, MPH ◽  
Stephen W. Janning, PharmD
Keyword(s):  
United States ◽  
Older Patients ◽  
The United States ◽  
Total Daily Dose ◽  
Insurance Claims ◽  
Pharmacy Claims ◽  
The Us ◽  
Daily Dose ◽  
Higher Doses ◽  
Morphine Equivalent

Objective: To describe opioid pharmacy claims patterns in the United States among an insured population.Design: Information was obtained from the US insurance claims database, IMS Lifelink™, between 1997 and 2002. Descriptive statistics of opioid claims patterns were described with stratification by gender, age, and year of use.Results: The prevalence of insured people with opioid claims increased from 17.1 percent in 1997 to 18.4 percent in 2002. Among people with an opioid claim, 24 percent had ≥30 days and 10 percent had ≥90 days of days supplied based on the insurance claims. Prevalence varied by type of opioid; 56 percent of people with a claim received propoxyphene, 43 percent received codeine, 23 percent received oxycodone, and 17 percent received hydrocodone. Sustained-release opioids were found among 6 percent of those with a claim. With respect to the dose of opioids in the pharmacy claims (expressed as morphine equivalent total daily dose), 71 percent had claims for <50 mg, 55 percent had claims for 50-99 mg, and 24 percent had claims for ≥100 mg. Women, individuals with cancer, and older patients had significantly more pharmacy claims as well as claims for higher doses of opioids (p < 0.05). Internal medicine and family practice specialists were responsible for 22.4 percent and 20.9 percent of all opioid claims.Conclusions: Opioid pharmacy claims increased slightly over time. Older patients, women and patients with a cancer diagnosis had significantly more opioid claims and claims for higher doses than the younger patients, men, and those without cancer.

scholarly journals Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Tamara van Donge ◽  
Marc Pfister ◽  
Julia Bielicki ◽  
Chantal Csajka ◽  
Frederique Rodieux ◽  
...  
Keyword(s):  
Neonatal Intensive Care ◽  
Demographic Characteristics ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Dosing Interval ◽  
Model Based ◽  
Optimal Dosing ◽  
Daily Dose ◽  
Dosing Regimens ◽  
Trough Concentrations

ABSTRACTOptimal dosing of gentamicin in neonates is still a matter of debate despite its common use. We identified gentamicin dosing regimens from eight international guidelines and seven Swiss neonatal intensive care units. The dose per administration, the dosing interval, the total daily dose, and the demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg/kg/day), and patient demographic characteristics that were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine the achievement of efficacious peak gentamicin concentrations according to predefined MICs (Cmax/MIC ≥ 10) and safe trough concentrations (Cmin≤ 2 mg/liter) with recommended dosing regimens. MIC targets of 0.5 and 1 mg/liter were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines allow to achieve effective peak concentrations for MICs ≤ 0.5 mg/liter but not higher. Model-based simulations indicate that to attain peak gentamicin concentrations of ≥10 mg/liter, a dose of 7.5 mg/kg should be administered using an extended dosing interval regimen. Trough concentrations of ≤2 mg/liter can be maintained with a dosing interval of 36 to 48 h in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.

FEEDBACK CONTROL OF FSH IN THE MALE: ROLE OF OESTROGEN

1973 ◽  
Vol 74 (3) ◽  
pp. 449-460 ◽  
Author(s):  
Patrick C. Walsh ◽  
Ronald S. Swerdloff ◽  
William D. Odell
Keyword(s):  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Oestrogen Therapy ◽  
Serum Concentrations ◽  
Elderly Men ◽  
Normal Range ◽  
Oestrogen Treatment ◽  
Serum Lh ◽  
Higher Doses

ABSTRACT Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay in a group of elderly men following castration and oestrogen therapy. Prior to orchiectomy, mean serum concentrations of LH and FSH were within the normal range. Two days following castration, serum LH concentrations increased in all eight patients; higher levels of LH were subsequently measured in all but one patient after periods of time ranging from 49 to 210 days. Serum FSH levels, measured in three patients following castration, increased in a pattern parallel to LH changes. Ethinyl oestradiol (EOe) in doses ranging from 5 to 300 μg/day was administered to ten men who had been castrated 3 to 72 months earlier. Oestrogen treatment suppressed both LH and FSH in a parellel manner in nine of ten patients. LH was first suppressed to intact levels in one of eight patients treated with 20 μg/day of EOe, in two of six patients treated with 50 μg/day, and in one patient by 80 μg/day. FSH was not suppressed to precastration levels until 50 μg/day of EOe was administered; this dose suppressed three of six patients. Higher doses of EOe (150–300 μg/day) suppressed both LH and FSH to levels below the sensitivity of the assay. These data fail to demonstrate any differential effect of oestrogen on LH and FSH release.

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