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Vancomycin AUC

Paul Lewis
BACKGROUND: Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg*hr/L has emerged as a more robust dosing target. A simple and practical method to extrapolate AUC24 from troughs is needed. MATERIALS AND METHODS: This mathematical model computes the median and range AUC24 using the dose in mg/kg and the observed serum trough concentration...
February 27, 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
Dana Y Fuhrman, Sandra Kane-Gill, Stuart L Goldstein, Priyanka Priyanka, John A Kellum
BACKGROUND: Most studies of acute kidney injury (AKI) have focused on older adults, and little is known about AKI in young adults (16-25 years) that are cared for in an adult intensive care unit (ICU). We analyzed data from a large single-center ICU database and defined AKI using the Kidney Disease Improving Global Outcomes criteria. We stratified patients 16-55 years of age into four age groups for comparison and used multivariable logistic regression to identify associations of potential susceptibilities and exposures with AKI and mortality...
February 14, 2018: Annals of Intensive Care
Heather A Nyman, Adhish Agarwal, Harry O Senekjian, John K Leypoldt, Alfred K Cheung
INTRODUCTION: Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide dialyzers. METHODS: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1...
January 30, 2018: Hemodialysis International
Stacey Tkachuk, Kyle Collins, Mary H H Ensom
BACKGROUND: In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC...
January 17, 2018: Paediatric Drugs
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
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
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
Michael N Neely, Lauren Kato, Gilmer Youn, Lironn Kraler, David Bayard, Michael van Guilder, Alan Schumitzky, Walter Yamada, Brenda Jones, Emi Minejima
We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of ≥400, with a maximum AUC value of 800 mg · h/liter, regardless of trough concentration...
February 2018: Antimicrobial Agents and Chemotherapy
H-M Pang, X-L Qin, T-T Liu, W-X Wei, D-H Cheng, H Lu, Q Guo, L Jing
OBJECTIVE: Previous studies have demonstrated that urinary kidney injury molecule-1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL) were superior to serum creatinine (Scr) in detecting acute kidney injury (AKI), but their ability to predict clinical vancomycin-associated AKI has not been investigated. This study aimed to investigate the abilities of uKIM-1 and uNGAL individually and in combination to predict vancomycin-associated AKI. PATIENTS AND METHODS: Scr, uKIM-1, and uNGAL were measured on the day before and days 1, 2, and 3 of vancomycin therapy in a generalized adult population...
September 2017: European Review for Medical and Pharmacological Sciences
Natalie A Finch, Evan J Zasowski, Kyle P Murray, Ryan P Mynatt, Jing J Zhao, Raymond Yost, Jason M Pogue, Michael J Rybak
Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure...
December 2017: Antimicrobial Agents and Chemotherapy
Nicholas M Fusco, Richard Francisconi, Calvin J Meaney, Desiree Duman, Carla A Frederick, William A Prescott
Background: Our goal was to determine the relationship between serum vancomycin trough concentrations (VTCs) and changes in pulmonary function among individuals with an acute pulmonary exacerbation (APE) of cystic fibrosis (CF). Methods: We included subjects who were ≥6 years of age, were hospitalized for an APE of CF between May 1, 2012, and April 30, 2014, were administered vancomycin for ≥48 hours, and had a history of airway infection with methicillin-resistant Staphylococcus aureus...
September 1, 2017: Journal of the Pediatric Infectious Diseases Society
J Nicholas O'Donnell, Nathaniel J Rhodes, Thomas P Lodise, Walter C Prozialeck, Cristina M Miglis, Medha D Joshi, Natarajan Venkatesan, Gwendolyn Pais, Cameron Cluff, Peter C Lamar, Seema Briyal, John Z Day, Anil Gulati, Marc H Scheetz
Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period...
November 2017: Antimicrobial Agents and Chemotherapy
Dmitriy M Martirosov, Monique R Bidell, Manjunath P Pai, Marc H Scheetz, Susan L Rosenkranz, Corey Faragon, M Malik, R E Mendes, R N Jones, Louise-Anne McNutt, Thomas P Lodise
BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline...
August 2, 2017: BMC Infectious Diseases
Robert W Seabury, Andrew M Stoessel, Jeffrey M Steele
No abstract text is available yet for this article.
October 2017: Annals of Pharmacotherapy
Jin Yang Baek, Doo Ryeon Chung, Kwan Soo Ko, So Hyun Kim, Soo-Jin Yang, Cheol-In Kang, Kyong Ran Peck, Jae-Hoon Song
Objectives: We previously reported the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in a patient with an MRSA of ST72, a community genotype in Korea. We investigated two isogenic MRSA strains from this patient, who experienced treatment failure with vancomycin and rifampicin. Methods: We tracked the genetic alterations that confer reduced susceptibility to vancomycin on those two isogenic MRSA strains by WGS...
September 1, 2017: Journal of Antimicrobial Chemotherapy
Alexander J Lepak, Miao Zhao, David R Andes
The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four Staphylococcus aureus strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug...
July 2017: Antimicrobial Agents and Chemotherapy
Ximena Castañeda, Cristina García-de-la-Mària, Oriol Gasch, Juan M Pericas, Yolanda Armero, Dolors Soy, Javier García-González, Carlos Falces, Salvador Ninot, Manel Almela, Juan Ambrosioni, Eduardo Quintana, Barbara Vidal, David Fuster, Jaume Llopis, Sara Soto, Asuncion Moreno, Francesc Marco, Jose M Miró
The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested...
June 2017: Antimicrobial Agents and Chemotherapy
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...
January 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Joseph J Carreno, Ben Lomaestro, John Tietjan, Thomas P Lodise
This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m(2) (40 to 52 kg/m(2))...
May 2017: Antimicrobial Agents and Chemotherapy
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