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Vancomycin pharmacokinetics and pharmacodynamics

Amelia Deitchman, Daniel de Jong, April Barbour, Hartmut Derendorf
With resistance of S. aureus, the most prevalent identified pathogen in skin and soft tissue infections, on the rise, the need for safe, effective, and well-tolerated antibiotics is crucial. Ceftobiprole medocaril (BAL-5788), ceftobiprole's parenteral prodrug, is a bactericidal cephalosporin with broad Gram-positive and Gram-negative activity that has shown to be well-tolerated and noninferior to vancomycin and vancomycin plus ceftazidime in the treatment of MRSA complicated skin and skin structure infections (cSSSIs) in clinical trials...
October 2, 2016: Expert Review of Anti-infective Therapy
Juwon Yim, Jordan R Smith, Katie E Barber, Jessica A Hallesy, Michael J Rybak
INTRODUCTION: In clinical trials comparing telavancin (TLV) with vancomycin for treatment of hospital-acquired pneumonia, TLV demonstrated lower clinical cure rates than vancomycin in patients who had mixed gram-positive and -negative infections and were concomitantly treated with either aztreonam (ATM) or piperacillin/tazobactam (PTZ). Here, we investigated therapeutic interactions between TLV and ATM or PTZ in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model under simulated reduced renal function conditions...
September 2016: Infectious Diseases and Therapy
Ashley D Hall Snyder, Brian J Werth, Poochit Nonejuie, John P McRoberts, Joe Pogliano, George Sakoulas, Juwon Yim, Nivedita Singh, Michael J Rybak
Daptomycin (DAP) is being used more frequently to treat infections caused by vancomycin-resistant enterococcus (VRE). DAP tends to be less active against enterococci than staphylococci and may require high doses or combination therapy to be bactericidal. Fosfomycin (FOF) has activity against VRE and has demonstrated synergistic bactericidal activity with DAP in vitro The objective of this study was to evaluate the activity of DAP alone and in combination with FOF against VRE in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model...
October 2016: Antimicrobial Agents and Chemotherapy
Sebastian G Wicha, Charlotte Kloft
For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models...
August 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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
J Beneš, S Polívková
The advantages and disadvantages of various antibiotics used in the treatment of Clostridium difficile infection (CDI) are compared with respect to their pharmacokinetic and pharmacodynamic properties. Recommendations are made for their optimal use in clinical practice. Metronidazole is suitable for the treatment of mild forms of CDI which are essentially self-limiting. Vancomycin kills clostridia reliably but the treatment is encumbered with considerable risk of recurrence. This can be decreased by shortening the treatment to seven days and then switching to a (pulse, taper, chaser) regimen to prevent recurrence or by active restoration of the intestinal ecosystem (fecal transplant)...
2016: Epidemiologie, Mikrobiologie, Imunologie
Carlos A Rodriguez, Maria Agudelo, Yudy A Aguilar, Andres F Zuluaga, Omar Vesga
Previous studies have demonstrated that pharmaceutical equivalence and pharmacokinetic equivalence of generic antibiotics are necessary but not sufficient conditions to guarantee therapeutic equivalence (better called pharmacodynamic equivalence). In addition, there is scientific evidence suggesting a direct link between pharmacodynamic nonequivalence of generic vancomycin and promotion of resistance in Staphylococcus aureus. To find out if even subtle deviations from the expected pharmacodynamic behavior with respect to the innovator could favor resistance, we studied a generic product of piperacillin-tazobactam characterized by pharmaceutical and pharmacokinetic equivalence but a faulty fit of Hill's Emax sigmoid model that could be interpreted as pharmacodynamic nonequivalence...
2016: PloS One
Liapikou Adamantia, Torres Antoni
INTRODUCTION: Telavancin is a novel lipoglycopeptide derivative of vancomycin that has activity against Gram-positive aerobic and anerobic bacteria, for the treatment of serious infections, including complicated skin and skin structure infections (cSSSI) and pneumonia. AREAS COVERED: This article was compiled through searches on telavancin up to December 2015 in the PubMed and the databases; the FDA and European Medicine Agency (EMA) websites...
July 2016: Expert Opinion on Drug Metabolism & Toxicology
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
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
P H Van, P T Binh, N H L Minh, I Morrissey, D Torumkuney
OBJECTIVES: To investigate the susceptibility of respiratory tract infection pathogens collected between 2009 and 2011 from the SOAR study in Vietnam. METHODS: MICs were determined using Etest(®) and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: Two hundred and eighty-nine Streptococcus pneumoniae and 195 Haemophilus influenzae were collected from 11 centres. Overall, 4.8% of S...
May 2016: Journal of Antimicrobial Chemotherapy
Molly E Droege, Suzanne L Van Fleet, Eric W Mueller
Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes...
April 2016: Critical Care Nurse
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
Abdulaziz S Alobaid, Maya Hites, Jeffrey Lipman, Fabio Silvio Taccone, Jason A Roberts
The increased prevalence of obesity presents challenges for clinicians aiming to provide optimised antimicrobial dosing in the intensive care unit. Obesity is likely to exacerbate the alterations to antimicrobial pharmacokinetics when the chronic diseases associated with obesity exist with the acute pathophysiological changes associated with critical illness. The purpose of this paper is to review the potential pharmacokinetic (PK) changes of antimicrobials in obese critically ill patients and the implications for appropriate dosing...
April 2016: International Journal of Antimicrobial Agents
Nicholas S Britt, Nimish Patel, Rebecca T Horvat, Molly E Steed
While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality...
May 2016: Antimicrobial Agents and Chemotherapy
Kristen R Nichols, Emily N Israel, Christopher A Thomas, Chad A Knoderer
The American Heart Association recently published an updated scientific statement on the management of infective endocarditis in childhood. The recommendations included for vancomycin, aminoglycoside, and β-lactam dosing and monitoring are based primarily on expert opinion and do not consider available evidence for dose optimization based on pharmacokinetic and pharmacodynamic principles in pediatric patients. This is concerning because even when clinically necessary, some practitioners may be hesitant to deviate from guideline-recommended doses...
May 2016: Annals of Pharmacotherapy
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
Karrine D Brade, Jeffrey M Rybak, Michael J Rybak
Resistance among Gram-positive organisms has been steadily increasing over the last several years; however, the development of new antibiotics to treat infections caused from these organisms has fallen short of the emergent need. Specifically, resistance among Staphylococcus aureus and Enterococcus spp. to essential antibiotics is considered a major problem. Oritavancin is a semisynthetic lipoglycopeptide antibiotic that was recently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI)...
March 2016: Infectious Diseases and Therapy
Nuggehally R Srinivas
Owing to availability of scanty pharmacokinetic data, dosing decisions in morbidly obesity is increasingly challenging in the field of anti-infective drugs. However, in recent years data are emerging that describe the pharmacokinetics of anti-infective drugs in morbidly obese subjects. The objectives of the present work were: (1) to collate the recent reports pertaining to the pharmacokinetics in morbidly obese subjects for several anti-infective drugs and provide an overview of the pharmacokinetic data along with the applicable pharmacodynamics and/or clinical outcome; (2) to perform regression analysis on limited dataset for a few drugs to verify the existence of relationships between Cmax/Ctrough versus steady-state volume of distribution (Vss)/clearance to enable data prediction in morbidly obesity subjects; (3) to provide a general discussion on issues and dosing implications...
January 13, 2016: American Journal of Therapeutics
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
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