Quantification of 15 Antibiotics Widely Used in the Critical Care Unit with a LC-MS/MS System: An Easy Method to Perform a Daily Therapeutic Drug Monitoring

Potential under- or overdose of antibiotics may occur in intensive care units due to high variability in plasma concentrations. The risk is either treatment failure or toxicity. Thus, therapeutic drug monitoring of antibiotics may guide dosing adjustment, maximising antibacterial efficacy and minimising toxicity. The aim of this study was to develop and validate a method for the analysis of 15 antibiotics including beta-lactams, linezolid, fluoroquinolones, daptomycin, and clindamycin to have a complete panel in the management of infections. We proposed to develop a fast, sensitive, and quantitative method for the analysis of 15 antibiotics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS) technology. this method required only 100 µL of plasma and consisted of a rapid liquid–liquid deproteinisation using methanol. Calibration curves ranged from 0.078 to 500 mg/L depending on the molecules, and were defined according to a therapeutic range. Inter- and intra-assay precisions values were less than 15%. This work described the development and the full validation of a precise, sensitive and accurate assay using UPLC-MS/MS technology. After validation, this new assay was successfully applied to routine therapeutic drug monitoring.

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Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring

Biomedical Chromatography ◽

10.1002/bmc.2726 ◽

2012 ◽

Vol 26 (12) ◽

pp. 1519-1528 ◽

Cited By ~ 63

Author(s):

Mai Shibata ◽

Sachiyo Hashi ◽

Haruka Nakanishi ◽

Satohiro Masuda ◽

Toshiya Katsura ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Therapeutic Drug Monitoring ◽

Tandem Mass Spectrometry ◽

Antiepileptic Drugs ◽

Drug Monitoring ◽

Ultra Performance Liquid Chromatography ◽

Therapeutic Drug ◽

Tandem Mass ◽

Routine Therapeutic Drug Monitoring

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Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽

10.3390/antibiotics10030263 ◽

2021 ◽

Vol 10 (3) ◽

pp. 263

Author(s):

Carolina Osorio ◽

Laura Garzón ◽

Diego Jaimes ◽

Edwin Silva ◽

Rosa-Helena Bustos

Keyword(s):

Side Effects ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Bacterial Resistance ◽

Plasma Concentrations ◽

Resistant Bacteria ◽

Therapeutic Drug ◽

Therapeutic Success ◽

Favorable Clinical Outcome ◽

And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

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Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02025-12 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1888-1894 ◽

Cited By ~ 28

Author(s):

William W. Hope ◽

Michael VanGuilder ◽

J. Peter Donnelly ◽

Nicole M. A. Blijlevens ◽

Roger J. M. Brüggemann ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Fungal Infections ◽

Plasma Concentrations ◽

Therapeutic Drug ◽

Cell Transplant ◽

Multiple Model ◽

Pharmacokinetic Variability ◽

Hematopoietic Stem ◽

Wide Range

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

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Generation of Pharmacokinetic Data During Routine Therapeutic Drug Monitoring

Therapeutic Drug Monitoring ◽

10.1097/00007691-199308000-00004 ◽

1993 ◽

Vol 15 (4) ◽

pp. 281-288 ◽

Cited By ~ 17

Author(s):

E. El Desoky ◽

J. Meinshausen ◽

K. Bühl ◽

G. Engel ◽

A. Harings-Kaim ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Pharmacokinetic Data ◽

Routine Therapeutic Drug Monitoring

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Implementation of routine therapeutic drug monitoring: Aminoglycosides and vancomycin

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2007.05.097 ◽

2007 ◽

Vol 32 (1) ◽

pp. S45

Author(s):

R. Benkő ◽

E. Hajdú ◽

M. Matuz ◽

G. Soós

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Routine Therapeutic Drug Monitoring

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Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central Nervous System Aspergillosis?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00705-18 ◽

2018 ◽

Vol 62 (9) ◽

Cited By ~ 4

Author(s):

François Danion ◽

Vincent Jullien ◽

Claire Rouzaud ◽

Manal Abdel Fattah ◽

Simona Lapusan ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Therapeutic Drug Monitoring ◽

Invasive Aspergillosis ◽

Drug Monitoring ◽

Standard Treatment ◽

Plasma Concentrations ◽

Therapeutic Drug ◽

Life Threatening ◽

Trough Plasma

ABSTRACT Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.

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SPCCTDM, a Catalogue for Analysis of Therapeutic Drug Monitoring Related Contents

Computational Knowledge Discovery for Bioinformatics Research ◽

10.4018/978-1-4666-1785-8.ch018 ◽

2013 ◽

pp. 319-328

Author(s):

Sven Ulrich ◽

Pierre Baumann ◽

Andreas Conca ◽

Hans-Joachim Kuss ◽

Viktoria Stieffenhofer ◽

...

Keyword(s):

Drug Therapy ◽

Therapeutic Drug Monitoring ◽

Text Mining ◽

Drug Monitoring ◽

Text Analysis ◽

Scientific Evidence ◽

Plasma Concentrations ◽

Therapeutic Drug ◽

Drug Reactions ◽

First Time

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

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