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Vancomycin pharmacokinetics

Caleb J P Economou, Jan T Kielstein, David Czock, Jiao Xie, Jonathan Field, Brent Richards, Mandy Tallot, Adam Visser, Christina Koenig, Carsten Hafer, Julius J Schmidt, Jeffrey Lipman, Jason A Roberts
OBJECTIVES: The aim of this study was to describe the population pharmacokinetics of vancomycin during prolonged intermittent renal replacement therapy (PIRRT) in critically ill patients with acute kidney injury. METHODS: Critically ill patients prescribed vancomycin across two sites had blood samples collected during 1-3 dosing intervals during which PIRRT was performed. Plasma samples were assayed with a validated immunoassay method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics® ...
March 8, 2018: International Journal of Antimicrobial Agents
Pieter J Colin, Stijn Jonckheere, Michel M R F Struys
OBJECTIVES: In this in-silico study, we investigate the clinical utility of target-controlled infusion for antibiotic dosing in an intensive care unit setting using vancomycin as a model compound. We compared target-controlled infusion and adaptive target-controlled infusion, which combines target-controlled infusion with data from therapeutic drug monitoring, with conventional (therapeutic drug monitoring-based) vancomycin dosing strategies. METHODS: A clinical trial simulation was conducted...
March 6, 2018: Clinical Pharmacokinetics
V Goti, A Chaturvedula, M J Fossler, S Mok, J T Jacob
BACKGROUND: Despite being in clinical use for about six decades, vancomycin dosing remains perplexing and complex. METHODS: A population pharmacokinetic modeling and simulation approach was used to evaluate the efficiency of the current nomogram-based dosing of vancomycin. Serum vancomycin concentrations were obtained as a part of routine therapeutic drug monitoring (TDM) from two 500-bed academic medical centers. A population pharmacokinetic model was first built using these TDM data...
February 20, 2018: Therapeutic Drug Monitoring
Abdullah Alsultan, Manal Abouelkheir, Saeed Alqahtani, Ahmad Aljabri, Ali M Somily, Sarah Alsubaie, Abdulkarim Alrabiaah, Elham Bukhari, Fahad Alzamil
INTRODUCTION: Several studies have reported that trough levels may not be optimal for monitoring vancomycin therapy, because of overexposure and nephrotoxicity risks. Therefore, we developed a population pharmacokinetic model to optimize vancomycin dosing and monitoring in pediatrics. METHODS: Data were retrospectively collected on 76 pediatric patients aged 1-12 years, admitted to general pediatric wards or ICUs at King Saud University Medical City, Riyadh, Saudi Arabia...
February 15, 2018: Pediatric Infectious Disease Journal
Chie Emoto, Trevor N Johnson, Brooks T McPhail, Alexander A Vinks, Tsuyoshi Fukuda
Simultaneous changes in several physiological factors may contribute to the large pharmacokinetic (PK) variability of vancomycin. This study was designed to systematically characterize the effects of multiple physiological factors to the altered PK of vancomycin observed in special populations. A vancomycin physiologically based pharmacokinetic (PBPK) model was developed as a PK simulation platform to quantitatively assess the effects of changes in physiologies to the PK profiles. The developed model predicted the concentration-time profiles in healthy adults and diseased patients...
February 15, 2018: CPT: Pharmacometrics & Systems Pharmacology
Elias B Chahine
Clostridium difficile is posing urgent health threats. Older studies have shown that metronidazole and vancomycin are equally effective in the treatment of Clostridium difficile infection (CDI). Given its inexpensive cost and low propensity to select antimicrobial resistant organisms, metronidazole became rapidly the drug of choice despite its pharmacokinetic limitations in the treatment of CDI. However, newer studies demonstrated that metronidazole is inferior to vancomycin, prompting clinicians to change their long-standing position on using metronidazole for mild to moderate infections and on reserving vancomycin for severe infections...
February 1, 2018: Annals of Pharmacotherapy
Antonio C Arrieta, John S Bradley, Myra W Popejoy, Mekki Bensaci, Anjana Grandhi, Paula Bokesch, Chad Glasser, Lihong Du, Nicholas A Kartsonis
BACKGROUND: Staphylococcus aureus, including community-associated methicillin-resistant S. aureus, is an important cause of pediatric bacteremia. Daptomycin is a well-established treatment option for gram-positive bacteremia in adults, but its safety and efficacy in children require confirmation. METHODS: This was a randomized (2:1), evaluator-blinded, multi-center, phase 4 clinical trial comparing intravenous daptomycin with standard-of-care (SOC) for treatment of S...
February 3, 2018: Pediatric Infectious Disease Journal
Mathieu Genuini, Mehdi Oualha, Naïm Bouazza, Florence Moulin, Jean-Marc Treluyer, Fabrice Lesage, Sylvain Renolleau, Sihem Benaboud
OBJECTIVE: Describe and assess a continuous infusion dosing scheme of vancomycin therapy in critically ill children. DESIGN: Retrospective single-center study, January to June 2015. SETTING: PICU located within a French tertiary academic pediatric hospital. PATIENTS: All children admitted in the PICU from January 2015 to June 2015, receiving continuous infusion of vancomycin therapy. INTERVENTIONS: None...
February 1, 2018: Pediatric Critical Care Medicine
Mark Arnold Thomas Blaskovich, Karl A Hansford, Mark Stuart Butler, ZhiGuang Jia, Alan Edward Mark, Matthew A Cooper
Glycopeptide antibiotics (GPA) are a key weapon in the fight against drug resistant bacteria, with vancomycin still a mainstream therapy against serious Gram-positive infections more than 50 years after it was first introduced. New, more potent semisynthetic derivatives that have entered the clinic, such as dalbavancin and oritavancin, have superior pharmacokinetic and target engagement profiles that enable successful treatment of vancomycin-resistant infections. In the face of resistance development, with multi-drug resistant (MDR) S...
January 24, 2018: ACS Infectious Diseases
Frédéric Peyrusson, Paul M Tulkens, Françoise Van Bambeke
Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examines in vitro its activity against intracellular Staphylococcus aureus (involved in the persistent character of skin and skin structure infections) using a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (C s [apparent bacteriostatic effect] reached at an extracellular concentration of about 0...
January 22, 2018: Antimicrobial Agents and Chemotherapy
Sheng-Hsuan Tseng, Chuan Poh Lim, Qi Chen, Cheng Cai Tang, Sing Teang Kong, Paul Chi-Lui Ho
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 vancomycin 24-hour area under the concentration-time curve to MIC ratio (AUC24/MIC, hr) > 400 as the best predictor of successful treatment against MRSA infections when MIC (mg/L) is ≤ 1. The relationship between steady state vancomycin trough concentrations and AUC24 (mg ⋅ hr/L) has not been studied in an Asian neonatal population...
January 22, 2018: Antimicrobial Agents and Chemotherapy
Valentin Al Jalali, Markus Zeitlinger
Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented...
January 13, 2018: Clinical Pharmacokinetics
Muhammad Usman, Manfred Fobker, Georg Hempel
PURPOSE: The aim of this study was to evaluate the influence of age and other possible covariates on vancomycin clearance in order to define a possible cut off value of age for dose optimization in elderly patients from data obtained during therapeutic drug monitoring. MATERIALS AND METHODS: Population pharmacokinetic analysis of 256 samples obtained from 144 patients was performed by using NONMEM<sup>®</sup>. A one-compartment model was applied as the base model with first-order conditional estimation method with interaction (FOCE-I)...
February 2018: International Journal of Clinical Pharmacology and Therapeutics
R Cohen, E Grimprel
Progress in the knowledge of antibiotic mechanisms of action allows to determine the pharmacodynamics/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the bacterial species implicated, the location of the infection, and the severity of the disease, these parameters may vary. The PK/PD parameters described in this paper, focus only on blood compartments. These PK/PD parameters best predict efficacy in the most frequent infections (e...
December 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Lin Song, Cui-Yao He, Nan-Ge Yin, Fang Liu, Yun-Tao Jia, Yao Liu
Population pharmacokinetic (PPK) modelling is an easy and impartment method for estimating drug concentration for use inindividualized therapy, especially for young patients and to help protect drug-induced diseases. The purpose of this study was to develop a PPK model for effective dosing of vancomycin in Chinese neonates and young infants. The PPK modelling tool Phoenix® NLME™ was use to assess demographic and routine clinical pharmacokinetic (PK) data retrospectively collected for patients admitted to Children's Hospital of Chongqing Medical University between 2011 and 2016...
December 1, 2017: Oncotarget
Katrina Hui, Lydia Upjohn, Michelle Nalder, Kirsty Buising, Eugenie Pedagogos, Craig Nelson, Carl M J Kirkpatrick, David C M Kong
OBJECTIVES: This study aimed to systematically evaluate if non-weight-based (non-WBD) or weight-based dosing (WBD) of vancomycin led to a higher proportion of patients achieving the pharmacokinetic/pharmacodynamic target. METHODS: Studies from January 1985 to February 2017 were identified through Cochrane, MEDLINE and EMBASE databases. Those conducted in adults with end-stage renal disease receiving high-flux haemodialysis and intravenous vancomycin were included...
December 25, 2017: International Journal of Antimicrobial Agents
Alessia Savoldi, Anna M Azzini, David Baur, Evelina Tacconelli
PURPOSE OF REVIEW: Skin and soft-tissue infections (SSIs) are among the commonest infections encountered in clinical practice. Spread of methicillin-resistant Staphylococcus aureus SSIs continues to increase in both health care and community settings and presents a challenge for the best treatment choice. Vancomycin has been the mainstay of SSIs treatment, but recently its use has been questioned because of concerns about its efficacy, tolerability, and unfavorable pharmacokinetic/pharmacodynamic profile...
April 2018: Current Opinion in Infectious Diseases
Andre Harvin, John J J Mellett, Daren Knoell, Jay Mirtallo, Ryan W Naseman, Nicole Brown, Crystal R Tubbs
PURPOSE: The implementation of a prioritized scoring tool to improve time to pharmacist intervention is described. SUMMARY: At the Ohio State University Wexner Medical Center, pharmacists are accepted providers of therapeutic drug monitoring of vancomycin and aminoglycosides. At the onset of this initiative and despite the implementation of an integrated electronic medical record (EMR), management of pharmacokinetically monitored medications was conducted using a paper monitoring form...
January 1, 2018: American Journal of Health-system Pharmacy: AJHP
Fawzy Elbarbry
After more than six decades of its use as the mainstay antibiotic for the treatment of multidrug-resistant Gram-positive bacterial infections, dosing and monitoring of vancomycin therapy have not been optimized. The current vancomycin therapeutic guidelines recommend empiric doses of 15-20 mg/kg administered by intermittent infusion every 8-12 h in patients with normal kidney function. Additionally, the guidelines recommend trough concentration of 15-20 mg/L as a therapeutic goal for adult patients with severe infections...
December 19, 2017: European Journal of Drug Metabolism and Pharmacokinetics
M Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Acute bacterial skin and skin structure infections (ABSSIs), defined as a bacterial infection of the skin with a lesion size area of at least 75 cm, are a leading cause of hospital admission and ambulatory care visits worldwide. Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) and by European Medicines Agency (EMA) for ABSSSIs. The authors review and provide updates of efficacy and safety by several studies on dalbavancin. Areas covered: A PubMed search was performed for relevant literature...
December 20, 2017: Expert Opinion on Drug Metabolism & Toxicology
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