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Aminoglycoside pharmacokinetics

Rajbharan Yadav, Jürgen B Bulitta, Roger L Nation, Cornelia B Landersdorfer
Optimizing antibiotic combinations is promising to combat multidrug-resistant Pseudomonas aeruginosa This study aimed to systematically evaluate synergistic bacterial killing and resistance prevention by carbapenem and aminoglycoside combinations, and to rationally optimize combination dosage regimens via mechanism-based modeling (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical P. aeruginosa isolates. Viable count profiles of total and resistant populations were quantified in 48h static-concentration time-kill studies (inoculum: 10(7...
November 7, 2016: Antimicrobial Agents and Chemotherapy
F Sörgel, R Höhl, R Glaser, C Stelzer, M Munz, M Vormittag, M Kinzig, J Bulitta, C Landersdorfer, A Junger, M Christ, M Wilhelm, U Holzgrabe
Optimized dosage regimens of antibiotics have remained obscure since their introduction. During the last two decades pharmacokinetic(PK)-pharmacodynamic(PD) relationships, originally established in animal experiments, have been increasingly used in patients. The action of betalactams is believed to be governed by the time the plasma concentration is above the minimum inhibitory concentration (MIC). Aminoglycosides act as planned when the peak concentration is a multiple of the MIC and vancomycin seems to work best when the area under the plasma vs...
October 24, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Anne Smits, Aida Kulo, John van den Anker, Karel Allegaert
INTRODUCTION: For safe and effective use of antibacterial agents in neonates, specific knowledge on the pharmacokinetics (PK) and its covariates is needed. This necessitates a stepwise approach, including prospective validation. AREAS COVERED: We describe our approach throughout almost two decades to improve amikacin exposure in neonates. A dosing regimen has been developed and validated using pharmacometrics, considering current weight, postnatal age, perinatal asphyxia, and ibuprofen use...
September 21, 2016: Expert Opinion on Drug Metabolism & Toxicology
Elizabeth A Neuner, Jason C Gallagher
Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging healthcare crisis. Infections due to CRE are associated with high morbidity and mortality, especially in critically ill patients. Due to the multi-drug resistant nature of these infections only limited treatment options are available. Antimicrobials that have been described for the treatment of CRE infections include carbapenems, polymyxins, fosfomycin, tigecycline, aminoglycosides, and ceftazidime-avibactam. Given the limited treatment options it is imperative the pharmacokinetic and pharmacodynamics (PK-PD) characteristics of these agents are considered to optimize treatment regimens...
August 9, 2016: Virulence
Eva Germovsek, Charlotte I Barker, Mike Sharland
The aminoglycosides are broad-spectrum, bactericidal antibiotics that are commonly prescribed for children, primarily for infections caused by Gram-negative pathogens. The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin. Gentamicin is the most commonly used antibiotic in UK neonatal units. Aminoglycosides are polar drugs, with poor gastrointestinal absorption, so intravenous or intramuscular administration is needed. They are excreted renally. Aminoglycosides are concentration-dependent antibiotics, meaning that the ratio of the peak concentration to the minimum inhibitory concentration of the pathogen is the pharmacokinetic-pharmacodynamic index best linked to their antimicrobial activity and clinical efficacy...
August 9, 2016: Archives of Disease in Childhood. Education and Practice Edition
Shashikant Srivastava, Chawanga Modongo, Chandima W Siyambalapitiyage Dona, Jotam G Pasipanodya, Devyani Deshpande, Tawanda Gumbo
Aminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (MDR-TB). However, formal pharmacokinetic/pharmacodynamic (PK/PD) studies to identify amikacin exposures and dosing schedules that optimize Mycobacterium tuberculosis killing have not been performed. It is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low pH. We performed time-kill studies to compare the bactericidal effect of amikacin in log-phase-growth bacilli with the sterilizing effect in semidormant bacilli at pH 5...
October 2016: Antimicrobial Agents and Chemotherapy
Matthew E Falagas, Andreas D Mavroudis, Konstantinos Z Vardakas
INTRODUCTION: A real concern in the medical community is the increasing resistance of bacteria, especially that of Gram-negative types. New antibiotics are currently under clinical development, promising to tackle severe infections caused, especially, by multi-drug resistant (MDR) bacteria and broaden the armamentarium of clinicians. AREAS COVERED: We searched PUBMED and GOOGLE databases. Combinations of already approved β-lactams or monobactams with new β-lactamase inhibitors [imipenem-cilastatin/MK-7655 (relebactam), meropenem/RPX7009 (vaborbactam), ceftaroline/avibactam, aztreonam/avibactam], new β-lactams (S-649266, BAL30072), aminoglycosides (plazomicin), quinolones (finafloxacin) and tetracyclines (eravacycline) were included in the review...
August 2016: Expert Review of Anti-infective Therapy
Joshua T Thaden, Jason M Pogue, Keith S Kaye
Antimicrobial resistance has been identified by the World Health Organization as "one of the three greatest threats to human health." Gram negative bacteria in particular drive this alarming trend. Carbapenem-resistant Enterobacteriaceae (CRE) such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter species are of particular importance as they are associated with poor clinical outcomes and are common causes for a variety of infections including bacteremia, urinary tract infection, intra-abdominal infections and pneumonia...
July 6, 2016: Virulence
Khalid H Safi, Justina M Damiani, Julie Sturza, Samya Z Nasr
This is a prospective quality improvement project for patients with cystic fibrosis who are 5 years of age and older who were admitted for intravenous antibiotic administration as part of treatment of cystic fibrosis exacerbation. The goal of this project was to compare the pharmacokinetics of once-daily versus thrice-daily aminoglycoside use when treating cystic fibrosis exacerbation in different age groups. Of the total of 119 patient encounters, 82.4% were started on once-daily dosing, and the remainder were started on thrice-daily dosing...
2016: Global Pediatric Health
Tijana Kovačević, Sanja Avram, Dragana Milaković, Nikolina Špirić, Pedja Kovačević
OBJECTIVE: Therapeutic drug monitoring (TDM) enables individualization in the treatment to optimize clinical benefit and minimize drugs' side effects. Critically ill septic patients represent a challenge for antimicrobial treatment because of pathophysiological impact of sepsis on pharmacokinetics of drugs. The aim of this study was to assess the appropriateness of gentamicin and amikacin dosing in critically and noncritically ill patients, as well as to estimate the need for its regular therapeutic monitoring...
June 2016: Journal of Basic and Clinical Pharmacy
Amélie Marsot, Romain Guilhaumou, Camille Riff, Olivier Blin
BACKGROUND: Amikacin is an aminoglycoside commonly used in intensive care units for the treatment of patients with life-threatening Gram-negative infections. Although aminoglycosides are extensively used, the accurate determination of their optimal dosage is complicated by marked intra- and interindividual variability in intensive care unit patients. Amikacin pharmacokinetics have been described in numerous studies over the past 25 years. OBJECTIVE: This review presents a synthesis of the population pharmacokinetic models for amikacin described in critically ill patients...
June 21, 2016: Clinical Pharmacokinetics
Claire Roger, Steven C Wallis, Laurent Muller, Gilbert Saissi, Jeffrey Lipman, Jean-Yves Lefrant, Jason A Roberts
The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed...
August 2016: Antimicrobial Agents and Chemotherapy
Soha Namazi, Mohammad Mahdi Sagheb, Mohammad Mahdi Hashempour, Arman Sadatsharifi
BACKGROUND: The inappropriate use of aminoglycosides has harmful effects such as the development of resistant pathogens and the incidence of nephrotoxicity and ototoxicity. Therefore, drug utilization evaluation of these drugs may improve their usage remarkably. The aim of this study was to assess the usage pattern of amikacin in an internal medicine ward. METHODS: This cross-sectional study was conducted in the Internal Medicine Ward of Nemazee Teaching Hospital, Shiraz, Iran, in 2011...
May 2016: Iranian Journal of Medical Sciences
Marlys LeBras, Ivy Chow, Vincent H Mabasa, Mary H H Ensom
Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid...
December 2016: Neurocritical Care
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
Nynke G L Jager, Reinier M van Hest, Jeffrey Lipman, Fabio S Taccone, Jason A Roberts
Initial adequate anti-infective therapy is associated with significantly improved clinical outcomes for patients with severe infections. However, in critically ill patients, several pathophysiological and/or iatrogenic factors may affect the pharmacokinetics of anti-infective agents leading to suboptimal drug exposure, in particular during the early phase of therapy. Therapeutic drug monitoring (TDM) may assist to overcome this problem. We discuss the available evidence on the use of TDM in critically ill patient populations for a number of anti-infective agents, including aminoglycosides, β-lactams, glycopeptides, antifungals and antivirals...
July 2016: Expert Review of Clinical Pharmacology
Matthew E Falagas, Evridiki K Vouloumanou, George Samonis, Konstantinos Z Vardakas
The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria...
April 2016: Clinical Microbiology Reviews
Ryan K Shields, Cornelius J Clancy, Ellen G Press, M Hong Nguyen
Aminoglycoside treatment of carbapenem-resistant (CR) Klebsiella pneumoniae bacteremia was associated with a 70% rate (23/33) of 30-day survival. Successful treatment was associated with sources of bacteremia amenable to reliable aminoglycoside pharmacokinetics (P = 0.037), acute physiology and chronic health evaluation II (APACHE II) scores of <20 (P = 0.16), and nonfatal underlying diseases (P = 0.015). Success rates were 78% and 100% if ≥2 and all 3 factors were present, respectively. Clinicians may consider the use of aminoglycosides against CR K...
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
Erik M van Maarseveen, Arwen Sprij, Daniel J Touw
BACKGROUND: Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration <0.5 mg/L) preventing toxicity. In contrast, gentamicin-based regimens in neonatal sepsis often aim for lower peak levels and trough concentrations of 0.5-2.0 mg·L. The latter concentrations are associated with an increased risk of aminoglycoside-related toxicity. Therefore, the primary aim of this study was to assess the target attainment of a simple and practical dosing regimen designed to attain drug-free periods in newborns...
June 2016: Therapeutic Drug Monitoring
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