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Aminoglycoside pharmacokinetics

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https://www.readbyqxmd.com/read/28881316/development-and-validation-of-a-sensitive-lc-ms-ms-method-without-derivatization-ion-pairing-agents-for-etimicin-quantification-in-rat-plasma-internal-ear-and-kidney
#1
Lan Yao, Fang Zhou, Mingmin Cai, Ying Peng, Jianguo Sun, Qianying Chen, Xiaoliang Jin, Guangji Wang, Jingwei Zhang
Etimicin (ETM), which belongs to the newest generation of aminoglycosides (AGs), has been proven to not only maintain but also strengthen the advantages of former AGs with relatively less toxicity. Now, it is widely applied for the treatment of bacterial infections in the clinic. Nevertheless, nephrotoxicity and ototoxicity are unavoidable issues for AGs, and while ETM is no exception, the seriousness of these issues is different. To explore the reason why ETM exhibits less toxicity and to better direct the optimization and development of new AGs, it is of great necessity and importance to monitor the pharmacokinetic behaviors of ETM in its potential toxicity target organs, the kidney and internal ear, as well as in plasma...
August 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28750947/polymyxins-for-cns-infections-pharmacology-and-neurotoxicity
#2
REVIEW
Tony Velkov, Chongshan Dai, Giuseppe D Ciccotosto, Roberto Cappai, Daniel Hoyer, Jian Li
Central nervous system (CNS) infections caused by multi-drug resistant (MDR) Gram-negative bacteria present a major health and economic burden worldwide. Due to the nearly empty antibiotic discovery pipeline, polymyxins (i.e. polymyxin B and colistin) are used as the last-line therapy against Gram-negative 'superbugs' when all other treatment modalities have failed. The treatment of CNS infections due to multi-drug resistant Gram-negative bacteria is problematic and associated with high mortality rates. Colistin shows significant efficacy for the treatment of CNS infections caused by MDR Gram-negative bacteria that are resistant to all other antibiotics...
July 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28749392/evaluation-of-evidence-for-pharmacokinetics-pharmacodynamics-based-dose-optimization-of-antimicrobials-for-treating-gram-negative-infections-in-neonates
#3
REVIEW
Nusrat Shafiq, Samir Malhotra, Vikas Gautam, Harpreet Kaur, Pravin Kumar, Sourabh Dutta, Pallab Ray, Nilima A Kshirsagar
BACKGROUND & OBJECTIVES: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections...
March 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28696058/early-postnatal-gentamicin-and-ceftazidime-treatment-in-normal-and-food-restricted-neonatal-wistar-rats-implications-for-kidney-development
#4
Ruud R G Bueters, Annelies Jeronimus-Klaasen, Roger J M Brüggemann, Lambertus P van den Heuvel, Michiel F Schreuder
BACKGROUND: Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. METHODS: On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8...
July 11, 2017: Birth defects research
https://www.readbyqxmd.com/read/28647460/a-prospective-study-evaluating-tobramycin-pharmacokinetics-and-optimal-once-daily-dosing-in-burn-patients
#5
Colin Lee, Sandra A N Walker, Scott E Walker, Winnie Seto, Andrew Simor, Marc Jeschke
BACKGROUND: Once-daily aminoglycoside dosing (ODA) is used in most patient populations to optimize antibacterial activity and reduce toxicity. Unfortunately, burn patients are excluded from ODA due to concerns over altered pharmacokinetics resulting in a shortened half-life and low peak aminoglycoside concentrations. Retrospective studies suggest that ODA may be appropriate if higher milligram/kilogram doses are used. However, no prospective clinical trials in burn patients exist to confirm these findings...
June 21, 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/28639230/intracellular-pharmacokinetics-of-antibacterials-and-their-clinical-implications
#6
REVIEW
Federico Pea
The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical implications of the intracellular pharmacokinetics of antibacterials, either from the therapeutic or toxicological perspective. The different pharmacokinetic behaviour of antimicrobials within cells is mainly related to their physicochemical properties (hydrophilicity and lipophilicity), and may have several clinical implications...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28375030/aminoglycosides-against-carbapenem-resistant-enterobacteriaceae-in-the-critically-ill-the-pitfalls-of-aminoglycoside-susceptibility
#7
Alexandre P Zavascki, Brandon O Klee, Jürgen B Bulitta
The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has brought aminoglycosides to the frontline since an aminoglycoside may be the only antimicrobial to which CRE isolates show in vitro susceptibility. The appropriateness of aminoglycoside-based therapies for severe infections by CRE is discussed considering the current breakpoints and recent pharmacokinetic (PK) studies in critically ill patients. Areas covered: Many aminoglycoside-susceptible CRE isolates present minimal inhibitory concentrations (MICs) at or slightly below the breakpoint of amikacin or gentamicin...
June 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28184305/once-daily-aerosolised-tobramycin-in-adult-patients-with-cystic-fibrosis-in-the-management-of-pseudomonas-aeruginosa-chronic-infection
#8
Marco Mantero, Andrea Gramegna, Giovanna Pizzamiglio, Alice D'Adda, Paolo Tarsia, Francesco Blasi
It is estimated that about 60-70% of Cystic Fibrosis patients develop Pseudomonas aeruginosa chronic infection, with progressive loss of lung function, as well as increased antibiotic resistance and mortality. The current strategy is to maintain lung function by chronic suppressive antipseudomonas antibiotic therapy. Tobramycin inhalation solution was the first approved aerosolised antibiotic to be used against P. aeruginosa; inhalatory tobramycin frequency of administration is twice daily and inhalation time is estimated to be 15 to 20 min...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28096164/pharmacodynamics-of-ceftaroline-plus-ampicillin-against-enterococcus-faecalis-in-an-in-vitro-pharmacokinetic-pharmacodynamic-model-of-simulated-endocardial-vegetations
#9
Brian J Werth, Laura M Shireman
The combination of ampicillin plus ceftaroline has been suggested to be more reliably synergistic against Enterococcus faecalis than ampicillin plus ceftriaxone using time-kill methods. The purpose of this study was to determine if this trend persists in a two-compartment model of simulated endocardial vegetations (SEV) using clinically relevant pharmacokinetic exposures of these antimicrobials. Three clinically derived E. faecalis strains were included in the study. The MICs of study antimicrobials were determined by broth microdilution...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28095918/anti-staphylococcal-activity-resulting-from-epithelial-lining-fluid-elf-concentrations-of-amikacin-inhale-administered-via-the-pulmonary-drug-delivery-system
#10
Islam M Ghazi, Mordechai Grupper, David P Nicolau
BACKGROUND: Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections...
January 17, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#11
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28062683/population-pharmacokinetic-modelling-monte-carlo-simulation-and-semi-mechanistic-pharmacodynamic-modelling-as-tools-to-personalize-gentamicin-therapy
#12
C C Llanos-Paez, S Hennig, C E Staatz
Population pharmacokinetic modelling, Monte Carlo simulation and semi-mechanistic pharmacodynamic modelling are all tools that can be applied to personalize gentamicin therapy. This review summarizes and evaluates literature knowledge on the population pharmacokinetics and pharmacodynamics of gentamicin and identifies areas where further research is required to successfully individualize gentamicin therapy using modelling and simulation techniques. Thirty-five studies have developed a population pharmacokinetic model of gentamicin and 15 studies have made dosing recommendations based on Monte Carlo simulation...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27999047/efficacy-and-pharmacokinetics-of-me1100-a-novel-optimized-formulation-of-arbekacin-for-inhalation-compared-with-amikacin-in-a-murine-model-of-ventilator-associated-pneumonia-caused-by-pseudomonas-aeruginosa
#13
Norihito Kaku, Yoshitomo Morinaga, Kazuaki Takeda, Kosuke Kosai, Naoki Uno, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
Background: Arbekacin is an aminoglycoside that shows strong antimicrobial activity against Gram-positive bacteria, including MRSA, as well as Pseudomonas aeruginosa . The therapeutic effectiveness of arbekacin is directly related to C max at the infection site. To maximize drug delivery to the respiratory tract and minimize the systemic toxicity, arbekacin optimized for inhalation, ME1100, is under development. In this study, we investigated the efficacy and pharmacokinetics of ME1100 in a murine model of ventilator-associated pneumonia caused by P...
April 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27993702/computational-identification-of-potent-inhibitors-for-streptomycin-3%C3%A2-adenylyltransferase-of-serratia-marcescens
#14
Dhamodharan Prabhu, Ramasamy Vidhyavathi, Jeyaraman Jeyakanthan
Serratia marcescens is an opportunistic pathogen responsible for the respiratory and urinary tract infections in humans. The antibiotic resistance mechanism of S. marcescens is mediated through aminoglycoside modification enzyme that transfer adenyl group from substrate to antibiotic through regiospecific transfers for the inactivation of antibiotics. Streptomycin 3(″)-adenylyltransferase acts on the 3' position of the antibiotic and considered as a novel drug target to overcome bacterial antibiotic resistance...
February 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27821448/optimization-of-synergistic-combination-regimens-against-carbapenem-and-aminoglycoside-resistant-clinical-pseudomonas-aeruginosa-isolates-via-mechanism-based-pharmacokinetic-pharmacodynamic-modeling
#15
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 prevention of resistance by carbapenem and aminoglycoside combinations and to rationally optimize combination dosage regimens via a mechanism-based mathematical model (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical P. aeruginosa isolates...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27778050/-pharmacokinetics-and-pharmacodynamics-of-antibiotics-in-intensive-care
#16
REVIEW
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...
February 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/27623706/the-amikacin-research-program-a-stepwise-approach-to-validate-dosing-regimens-in-neonates
#17
REVIEW
Anne Smits, Aida Kulo, John van den Anker, Karel Allegaert
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. This regimen has been developed based on clinical and therapeutic drug monitoring (TDM) data collected during routine care, and subsequently underwent prospective validation...
February 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27589330/pharmacodynamic-and-pharmacokinetic-considerations-in-the-treatment-of-critically-ill-patients-infected-with-carbapenem-resistant-enterobacteriaceae
#18
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...
May 19, 2017: Virulence
https://www.readbyqxmd.com/read/27506599/what-do-i-need-to-know-about-aminoglycoside-antibiotics
#19
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...
April 2017: Archives of Disease in Childhood. Education and Practice Edition
https://www.readbyqxmd.com/read/27458215/amikacin-optimal-exposure-targets-in-the-hollow-fiber-system-model-of-tuberculosis
#20
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
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