Target serum concentration of vancomycin may be reached earlier with a loading dose

Abstract Background: Studies have shown the failure of vancomycin treatment against vancomycin-sensitive gram-positive bacteria is common, possibly because the drug concentration did not reach the target serum concentration in time. In this study, we conducted a retrospective analysis to determine whether the target serum concentration could be reached earlier with the first loading dose of vancomycin.Methods: A retrospective single-center study was conducted in the Department of Critical Care Medicine, Ruijin Hospital North Affiliated to Shanghai Jiao Tong University School of Medicine between June 2018 and June 2020. The study enrolled patients who were suspected or confirmed with gram-positive bacterial infection and had been treated with vancomycin. According to whether the first loading dose of vancomycin was given, the patients were divided into the loading dose and the control groups. The serum concentration of vancomycin before the second dose and that before the fifth dose were compared to determine whether the target serum concentration was reached earlier with the first loading dose. And renal functions were monitored for a week to analyze whether the loading dose caused any acute kidney injury.Results: 55 patients were finally included in the study. Of these patients, 29 received first-loading dose of vancomycin, while the remaining 26 patients underwent the traditional dose regimen of vancomycin. The concentration of vancomycin before the second dose was 10.3±6.1 mg/L in the loading group, and 5.7±4.4 mg/L in the control group, significantly higher in the former group (P=0.002). The concentration of vancomycin before the fifth dose was 12.4±7.3 mg/L in the loading group, and 10.3±6.3 mg/L in the control group, where there was no inter-group difference (P=0.251). The 28-day motality of loading dose group is significantly lower (6.7% vs 34%, P=0.026) than the control group. There were no significant changes in serum creatinine levels in both groups, and there was no statistical difference in serum creatinine levels between the two groups.Conclusions: With the loading dose of vancomycin, the target serum concentration of vancomycin could be reached earlier without causing acute kidney injuries, also the mortality might be reduced.

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Inadequacy of FDA Dosing Guidelines for Theophylline Use in Neonates

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808602000609 ◽

1986 ◽

Vol 20 (6) ◽

pp. 481-484 ◽

Cited By ~ 2

Author(s):

Jamie T. Gilman ◽

Peter Gal

Keyword(s):

Steady State ◽

Serum Concentration ◽

Oral Therapy ◽

Loading Dose ◽

Serum Concentrations ◽

Steady State Concentration ◽

Significant Difference ◽

Postconceptional Age ◽

State Concentration

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 ± 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 ± 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 ± 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (<6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p<0.001). There was no significant difference in mean projected serum concentrations between patients age 26–41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (<6.0 mg/L) serum concentrations in the majority of newborns.

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Evaluation of Two Fosphenytoin Loading Dose Regimens and Monitoring in Infants and Neonates Less Than Six Months of Age

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-25.7.617 ◽

2020 ◽

Vol 25 (7) ◽

pp. 617-622

Author(s):

Kristin K. Bohannon ◽

Noelle Leung ◽

Aaron M. Cook ◽

Elizabeth Autry ◽

Julia Gibson ◽

...

Keyword(s):

Serum Concentration ◽

Optimal Dose ◽

Time Frame ◽

Loading Dose ◽

Serum Concentrations ◽

Target Concentration ◽

Dose Time ◽

Neonates And Infants ◽

Free Serum ◽

Time Of Administration

OBJECTIVES The objectives of the study were to compare the free serum concentrations after different fosphenytoin loading dose strategies in patients younger than 6 months old and to investigate the frequency of seizure cessation following a loading dose of fosphenytoin. METHODS This retrospective cohort study included neonates and infants admitted to a 150-bed children's hospital between August 1, 2014, and February 1, 2018. Patients were included if they were younger than 6 months old and had a postload free phenytoin serum concentration collected during the specified time frame. Patients were identified through a database query screening for the inclusion criteria. Patients were separated into 2 groups with the 15 mg/kg group as per protocol and the 20 mg/kg group as noted in common practice. Data collection included demographic information, fosphenytoin dose, time of administration of the fosphenytoin loading dose, time of sampling, free phenytoin serum concentration results, concomitant antiepileptic agents, albumin serum concentration, and total bilirubin serum concentration. RESULTS Forty-one patients were included for analysis, 12 in the 15 mg/kg group and 29 in the 20 mg/kg group. The average free phenytoin concentration after the loading dose was 2.45 ± 0.54 mg/L in the 15 mg/kg group and 2.52 ± 0.66 mg/L in the 20 mg/kg group. Seizure cessation after the fosphenytoin loading dose was achieved in 3 of 12 (25%) patients in the 15 mg/kg group and in 13 of 29 (45%) patients in the 20 mg/kg group (p = 0.305). CONCLUSIONS The study demonstrates that a traditional range of fosphenytoin loading dose (15–20 mg/kg) led to elevated postloading dose free phenytoin serum concentrations in the majority of patients with a seizure cessation rate of approximately 39%. The question remains as to what the optimal dose and target concentration should be in this patient population to achieve the best efficacy without risking associated toxicities.

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The Effect of Oral Loading Doses of Cholecalciferol on the Serum Concentration of 25-OH-Vitamin-D

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000192 ◽

2014 ◽

Vol 84 (1-2) ◽

pp. 45-54 ◽

Cited By ~ 4

Author(s):

Rasmus Bo Jansen ◽

Ole Lander Svendsen

Keyword(s):

Vitamin D ◽

Serum Concentration ◽

Vitamin D Deficiency ◽

Vitamin D3 ◽

Dose Response ◽

Interindividual Variation ◽

Loading Dose ◽

Severe Vitamin ◽

Target Value ◽

25 Oh Vitamin D

Background/Objectives: Severe vitamin D deficiency can be treated with oral loading doses of cholecalciferol. Our objective was to develop an algorithm to accurately calculate the amount of cholecalciferol needed for a loading dose, and what factors should be taken into account.Methods: Two studies were conducted on subjects with Vitamin D deficiency. Study 1 was observational, retrospective and included 88 subjects treated with a daily supplementation of cholecalciferol. 60 of these furthermore received a loading dose, calculated by an algorithm.Study 2 was prospective and included 29 subjects treated with a cholecalciferol loading dose, calculated by an algorithm developed based on data from study 1, which included BMI.Results: Baseline 25OH-vit.D was below 25 nmol/L (study 1) and 23 nmol/L (study 2). Subjects were given a single loading dose of cholecalciferol, averaging 172,000 IU (study 1) and 212,000 IU (study 2), based on their baseline 25OH-vit.D level.25OH-vit.D increased by 35 nmol/L (study 1) and 56 nmol/L (study 2)(range 113.0, SD 29.79) respectively. In study 2 the increase lead to an end 25OH-vit.D of 79 nmol/L - not significantly different from the target value of 80 nmol/L (P = 0.46). The increase in 25OH-vit.D in study 1 was significantly lower than in study 2 (P<0.001).Conclusion: When calculating loading doses of cholecalciferol, taking subject BMI into account gives a better estimate of the loading dose of vitamin D3 needed to treat vitamin D deficiency. It does not, however, remove the large interindividual variation in dose-response.

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Vancomycin Serum Concentration after 48 h of Administration: A 3-Years Survey in an Intensive Care Unit

Antibiotics ◽

10.3390/antibiotics9110793 ◽

2020 ◽

Vol 9 (11) ◽

pp. 793

Author(s):

Nicolas Perin ◽

Claire Roger ◽

Grégory Marin ◽

Nicolas Molinari ◽

Alexandre Evrard ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Serum Concentration ◽

Primary Outcome ◽

Kidney Injury ◽

Loading Dose ◽

Duration Of Treatment ◽

Icu Patients ◽

Vancomycin Concentration ◽

Serum Vancomycin

The present study assessed the proportion of intensive care unit (ICU) patients who had a vancomycin serum concentration between 20 and 25 mg/L after 24–48 h of intravenous vancomycin administration. From 2016 to 2018, adult ICU patients with vancomycin continuous infusion (CI) for any indication were included. The primary outcome was the proportion of patients with a first-available vancomycin serum concentration between 20–25 mg/L at 24 h (D2) or 48 h (D3). Of 3894 admitted ICU patients, 179 were included. A median loading dose of 15.6 (interquartile range (IQR) = (12.5–20.8) mg/kg) was given in 151/179 patients (84%). The median daily doses of vancomycin infusion for D1 and D2 were 2000 [(IQR (1600–2000)) and 2000 (IQR (2000–2500)) mg/d], respectively. The median duration of treatment was 4 (2–7) days. At D2 or D3, the median value of first serum vancomycin concentration was 19.8 (IQR (16.0–25.1)) with serum vancomycin concentration between 20–25 mg/L reported in 43 patients (24%). Time spent in the ICU before vancomycin initiation was the only risk factor of non-therapeutic concentration at D2 or D3. Acute kidney injury occurred significantly more when vancomycin concentration was supra therapeutic at D2 or D3. At D28, 44 (26%) patients had died. These results emphasize the need of appropriate loading dose and regular monitoring to improve vancomycin efficacy and avoid renal toxicity.

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Fibronexus-Like Adhesion Sites are Present at the Invasive Zones of Human Epidermoid Carcinomas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053280 ◽

1982 ◽

Vol 40 ◽

pp. 106-109

Author(s):

Irwin I. Singer

Keyword(s):

Cell Cycle ◽

Serum Concentration ◽

Substrate Binding ◽

High Serum ◽

Adhesion Sites ◽

Substrate Adhesion ◽

Focal Contacts ◽

Adhesion Complex ◽

Low Serum

Our previous results indicate that two types of fibronectin-cytoskeletal associations may be formed at the fibroblast surface: dorsal matrixbinding fibronexuses generated in high serum (5% FBS) cultures, and ventral substrate-adhering units formed in low serum (0.3% FBS) cultures. The substrate-adhering fibronexus consists of at least vinculin (VN) and actin in its cytoplasmic leg, and fibronectin (FN) as one of its major extracellular components. This substrate-adhesion complex is localized in focal contacts, the sites of closest substratum approach visualized with interference reflection microscopy, which appear to be the major points of cell-tosubstrate adhesion. In fibroblasts, the latter substrate-binding complex is characteristic of cultures that are arrested at the G1 phase of the cell cycle due to the low serum concentration in their medium. These arrested fibroblasts are very well spread, flattened, and immobile.

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