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Vancomycin AUC

Seenae Eum, Robert L Bergsbaken, Craig L Harvey, J Bryan Warren, John C Rotschafer
This study demonstrated a statistically significant difference in vancomycin minimum inhibitory concentration (MIC) for Staphylococcus aureus between a common automated system (Vitek 2) and the E-test method in patients with S. aureus bloodstream infections. At an area under the serum concentration time curve (AUC) threshold of 400 mg∙h/L, we would have reached the current Infectious Diseases Society of America (IDSA)/American Society of Health System Pharmacists (ASHP)/Society of Infectious Diseases Pharmacists (SIDP) guideline suggested AUC/MIC target in almost 100% of patients while using the Vitek 2 MIC data; however, we could only generate 40% target attainment while using E-test MIC data (p < 0...
2016: Antibiotics
Jasmine Chong, Caroline Quach, Ana C Blanchard, Philippe Guillaume Poliquin, George R Golding, Céline Laferrière, Simon Lévesque
Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV) Staphylococcus epidermidis central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak...
October 2016: Antimicrobial Agents and Chemotherapy
Shankar Lanke, Tian Yu, Joseph E Rower, Alfred H Balch, E Kent Korgenski, Catherine M Sherwin
Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013...
June 13, 2016: Journal of Clinical Pharmacology
Steven Boakes, William J Weiss, Mary Vinson, Sjoerd Wadman, Michael J Dawson
NVB333 is a novel semisynthetic lantibiotic derived from the amide coupling of 3,5-dichlorobenzylamine to the C-terminal of deoxyactagardine B. The in vitro activity of NVB333 includes efficacy against clinically relevant pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. NVB333 shows no cross-resistance with other antibiotics tested and a very low propensity for resistance development. After intravenous dosing NVB333 has high exposure in mouse plasma and shows generally improved in vivo activity compared with vancomycin in mouse infection models despite modest MIC values...
May 18, 2016: Journal of Antibiotics
S Fukumori, Y Tsuji, A Mizoguchi, H Kasai, T Ishibashi, N Iwamura, H To
WHAT IS KNOWN AND OBJECTIVE: The pharmacokinetic-pharmacodynamic parameter that best predicts the efficacy of vancomycin is the ratio of the area under the concentration versus time curve (AUC) to the minimum inhibitory concentration (MIC). A 24-h AUC (AUC24 )/MIC ratio ≥ 400 was recommended in an American consensus review, but vancomycin treatment occasionally fails despite maintenance of AUC24 /MIC ≥ 400. We evaluated the association between clinical efficacy of vancomycin and two novel pharmacokinetic parameters, the 'area under the trough level' (AUTL) and the 'area above the trough level' (AATL), in hospitalized elderly patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia...
August 2016: Journal of Clinical Pharmacy and Therapeutics
Xiyue Xiong, Dan Liu, Yichao Wang, Ting Zeng, Ying Peng
Autism spectrum disorders (ASDs) are a group of mental illnesses highly correlated with gut microbiota. Recent studies have shown that some abnormal aromatic metabolites in autism patients are presumably derived from overgrown Clostridium species in gut, which may be used for diagnostic purposes. In this paper, a GC/MS based metabolomic approach was utilized to seek similar biomarkers by analyzing the urinary information in 62 ASDs patients compared with 62 non-ASDs controls in China, aged 1.5-7. Three compounds identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), 3-hydroxyphenylacetic acid (3HPA), and 3-hydroxyhippuric acid (3HHA) were found in higher concentrations in autistic children than in the controls (p < 0...
2016: BioMed Research International
Cory M Hale, Robert W Seabury, Jeffrey M Steele, William Darko, Christopher D Miller
PURPOSE: To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400. METHODS: A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: <10, 10 to 14...
April 12, 2016: Journal of Pharmacy Practice
Bita Shahrami, Farhad Najmeddin, Sarah Mousavi, Arezoo Ahmadi, Mohammad Reza Rouini, Kourosh Sadeghi, Mojtaba Mojtahedzadeh
Objective. The aim of our study was to assess and validate the effectiveness of early dose adjustment of vancomycin based on first dose monitoring in achieving target recommended goal in critically ill patients. Methods. Twenty critically ill patients with sepsis received loading dose of 25 mg/kg of vancomycin and then were randomly assigned to 2 groups. Group 1 received maximum empirical doses of vancomycin of 15 mg/kg every 8 hrs. In group 2, the doses were individualized based on serum concentrations of vancomycin...
2016: Critical Care Research and Practice
Jun Hirai, Mao Hagihara, Hideo Kato, Daisuke Sakanashi, Naoya Nishiyama, Yusuke Koizumi, Yuka Yamagishi, Hiroyuki Suematsu, Hideaki Hanaki, Hiroshige Mikamo
BACKGROUND: The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model. METHODS: Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density...
June 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Emily C Benefield, Tracy M Hagemann, H Christine Allen, Kevin Farmer, Michael E Burton, Susana Chavez-Bueno, Peter N Johnson
OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline...
January 2016: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Nak-Hyun Kim, Yu Min Kang, Woong Dae Han, Kyoung Un Park, Kay-Hyun Park, Jae Il Yoo, Dong-Gun Lee, Chulmin Park, Kyoung-Ho Song, Eu Suk Kim, Sang Won Park, Nam Joong Kim, Myoung-Don Oh, Hong Bin Kim
The small-colony variant (SCV) phenotype of Staphylococcus aureus is associated with intracellular persistence and reduced antimicrobial susceptibility, which can lead to therapeutic failure. Since SCVs grow slowly and have a confusing morphology, the identification of infections due to SCV is difficult. We have identified SCVs in two patients who presented with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia complicated by surgical site infections after cardiothoracic surgery. Nine blood isolates were collected from the two patients for species identification, antimicrobial susceptibility testing, and phenotypic and genotypic characterization...
March 16, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Erik M van Maarseveen, Suzan Gipmans, Erwin Vasbinder, Manfred Petjak, Arthur R H van Zanten
BACKGROUND: To increase target attainment rates, switching the mode of administration from intermittent (InI) to continuous infusion (CoI) has been proposed. In this study, target attainment rates and interpatient variation in exposure were compared between vancomycin InI- and CoI-treated critically ill patients. METHODS: An observational cohort study was conducted among critically ill patients admitted to a level-2 intensive care unit. Adult patients (18 years or older) treated with intravenous vancomycin for various indications, including sepsis, pneumonia, and endocarditis between 2007 and 2013 were eligible for inclusion...
June 2016: Therapeutic Drug Monitoring
Rocío Álvarez, Luis E López Cortés, José Molina, José M Cisneros, Jerónimo Pachón
The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others)...
May 2016: Antimicrobial Agents and Chemotherapy
V Ramos-Martín, A Johnson, J Livermore, L McEntee, J Goodwin, S Whalley, F Docobo-Pérez, T W Felton, W Zhao, E Jacqz-Aigrain, M Sharland, M A Turner, W W Hope
OBJECTIVES: CoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage regimens. METHODS: A hollow fibre and a novel rabbit model of neonatal central line-associated bloodstream CoNS infections were developed. The results were then bridged to neonates by use of population pharmacokinetic techniques and Monte Carlo simulations...
April 2016: Journal of Antimicrobial Chemotherapy
Peng Men, Hui-Bo Li, Suo-Di Zhai, Rong-Sheng Zhao
BACKGROUND: A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research. OBJECTIVE: This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400...
2016: PloS One
Esther J H Janssen, Pyry A J Välitalo, Karel Allegaert, Roosmarijn F W de Cock, Sinno H P Simons, Catherine M T Sherwin, Johan W Mouton, Johannes N van den Anker, Catherijne A J Knibbe
Because of the recent awareness that vancomycin doses should aim to meet a target area under the concentration-time curve (AUC) instead of trough concentrations, more aggressive dosing regimens are warranted also in the pediatric population. In this study, both neonatal and pediatric pharmacokinetic models for vancomycin were externally evaluated and subsequently used to derive model-based dosing algorithms for neonates, infants, and children. For the external validation, predictions from previously published pharmacokinetic models were compared to new data...
February 2016: Antimicrobial Agents and Chemotherapy
Maria Souli, Ilias Karaiskos, Lambrini Galani, Sofia Maraki, Efstathia Perivolioti, Athina Argyropoulou, Athina Charissiadou, Levantia Zachariadou, Sofia Tsiplakou, Vassiliki Papaioannou, Helen Tsorlini, Helen Katsifa, Vasiliki Baka, Paraskevi Pantazi, Angeliki Paschali, Anna Kyratsa, Eleftheria Trikka-Graphakos, Panagiota Giannopoulou, Evangelos Vogiatzakis, Helen Moraitou, Helen Papadogeorgaki, Helen Avgerinou, Theofano Panagea, Angeliki Pantazatou, Efthymia Petinaki, Giannoula Stamatopoulou, Marina Toutouza, Ioanna Karatzoglou, Konstantina Kontopoulou, Maria Orfanidou, Irene Karantani, Panteleimon Fytas, Konstantina Tzanetou, Evangelia Platsouka, Polyzo Kazila, Anastasia Chli, Ntina Statiri, Helen Giamarellou
PURPOSE: To evaluate the in vitro efficacy of several anti-staphylococcal agents against a nationwide collection of contemporary Staphylococcus aureus clinical isolates from several healthcare centres in Greece. METHODS: Thirty hospitals throughout Greece (18 in Attica) provided all clinical isolates of S.aureus from April 2012 to May 2013 to a central lab to be re-submitted to susceptibility testing. The MICs were evaluated by Vitek® 2 with the exception of ceftaroline (OXOID M...
December 4, 2015: Infectious Diseases
Yukihiro Hamada, Joseph L Kuti, David P Nicolau
Vancomycin is considered a first-line antibiotic for complicated skin and skin structure infections (cSSSI) because of the risk of methicillin-resistant Staphylococcus aureus (MRSA). The vancomycin exposure of tissue can vary widely in patients with cSSSI, yet most models test only the average exposure. The in vitro pharmacodynamic model was used to simulate three tissue exposure levels attained by administering vancomycin at 1 g every 12 h (q12h), based on the median (50th), 25th, and 10th percentile tissue area under the concentration-time curve (AUC) values observed during an in vivo microdialysis study of diabetic patients...
February 2016: Antimicrobial Agents and Chemotherapy
Jennifer Le, Pamela Ny, Edmund Capparelli, James Lane, Becky Ngu, Richard Muus, Gale Romanowski, Tiana Vo, John Bradley
BACKGROUND: Limited studies incorporating population-based pharmacokinetic modeling have been conducted to determine pharmacodynamic indices associated with nephrotoxicity during vancomycin exposure in children. METHODS: A retrospective cohort analysis was conducted from September 2003 to December 2011 at 2 hospitals. Nephrotoxicity was defined as an increase in serum creatinine concentration (SCr) by ≥0.5 mg/dL, or ≥50% increase in baseline SCr, either persisting for ≥2 consecutive days...
December 2015: Journal of the Pediatric Infectious Diseases Society
Glaucia T F Seixas, Orlei R Araujo, Dafne C B Silva, Rodrigo G Arduini, Antonio S Petrilli
To obtain pharmacokinetic and pharmacodynamic data for vancomycin in a cohort of critically ill pediatric oncology patients, we analyzed 256 measurements of vancomycin concentrations in 94 patients. Variables were tested as possible risk factors for vancomycin-related nephrotoxicity or death for 28 days. We found the following: mean vancomycin trough serum concentration, 15.6 ± 12.4 μg/mL; mean vancomycin clearance, 0.16 ± 0.098 L/h/kg; and mean vancomycin distribution volume, 1.04 ± 0.11 L/kg. Only 13...
March 2016: Journal of Pediatric Hematology/oncology
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