scholarly journals Therapeutic Drug Monitoring of Antifungal Drugs: Another Tool to Improve Patient Outcome?

2020 ◽  
Vol 9 (1) ◽  
pp. 137-149 ◽  
Author(s):  
Antonio Vena ◽  
Patricia Muñoz ◽  
Miriam Mateos ◽  
Jesus Guinea ◽  
Alicia Galar ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Antifungal Drugs ◽  
Improve Patient Outcome ◽  
Therapeutic Drug ◽  
Improve Patient

scholarly journals A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
David S. Perlin
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Human Serum Samples ◽  
Long Chain

ABSTRACT Clinicians need a better way to accurately monitor the concentration of antimicrobials in patient samples. In this report, we describe a novel, low-sample-volume method to monitor the azole-class antifungal drug posaconazole, as well as certain other long-chain azole-class antifungal drugs in human serum samples. Posaconazole represents an important target for therapeutic drug monitoring (TDM) due to its widespread use in treating invasive fungal infections and well-recognized variability of pharmacokinetics. The current “gold standard” requires trough and peak monitoring through high-pressure liquid chromatography (HPLC) or liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Other methods include bioassays that use highly susceptible strains of fungi in culture plates or 96-well formats to monitor concentrations. Currently, no method exists that is both highly accurate in detecting free drug concentrations and is also rapid. Herein, we describe a new method using reduced graphene oxide (rGO) and a fluorescently labeled aptamer, which can accurately assess clinically relevant concentrations of posaconazole and other long-chain azole-class drugs in little more than 1 h in a total volume of 100 µl. IMPORTANCE This work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or resource-limited setting.

scholarly journals An Aptamer-Based Biosensor for the Azole Class of Antifungal Drugs

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
Arkady Mustaev ◽  
Jinglei Ping ◽  
Ramya Vishnubhotla ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Field Effect ◽  
Field Effect Transistor ◽  
Drug Dosage ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Graphene Field Effect Transistor ◽  
Effect Transistor

ABSTRACT We have developed the first aptamer directed toward the azole class of antifungal drugs and a functional biosensor for these drugs. This aptamer has a unique secondary structure that allows it to bind to highly hydrophobic drugs. The aptamer works as a capture component of a graphene field effect transistor device. These devices can provide a quick and easy assay for determining drug concentrations. These will be useful for therapeutic drug monitoring of azole antifungal drugs, which is necessary to deal with the complex drug dosage profiles. This technical report describes the development of an aptamer for sensing azole antifungal drugs during therapeutic drug monitoring. Modified synthetic evolution of ligands through exponential enrichment (SELEX) was used to discover a DNA aptamer recognizing azole class antifungal drugs. This aptamer undergoes a secondary structural change upon binding to its target molecule, as shown through fluorescence anisotropy-based binding measurements. Experiments using circular dichroism spectroscopy revealed a unique G-quadruplex structure that was essential and specific for binding to the azole antifungal target. Aptamer-functionalized graphene field effect transistor (GFET) devices were created and used to measure the strength of binding of azole antifungals to this surface. In total, this aptamer and the supporting sensing platform provide a valuable tool for therapeutic drug monitoring of patients with invasive fungal infections. IMPORTANCE We have developed the first aptamer directed toward the azole class of antifungal drugs and a functional biosensor for these drugs. This aptamer has a unique secondary structure that allows it to bind to highly hydrophobic drugs. The aptamer works as a capture component of a graphene field effect transistor device. These devices can provide a quick and easy assay for determining drug concentrations. These will be useful for therapeutic drug monitoring of azole antifungal drugs, which is necessary to deal with the complex drug dosage profiles.

scholarly journals Therapeutic Drug Monitoring of Meropenem in Neonate with Necrotizing Enterocolitis: A Challenge

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Steven De Keukeleire ◽  
Daniëlle Borrey ◽  
Wim Decaluwe ◽  
Marijke Reynders
Keyword(s):  
Patient Outcome ◽  
Therapeutic Drug Monitoring ◽  
Necrotizing Enterocolitis ◽  
Drug Monitoring ◽  
Neonatal Morbidity ◽  
Added Value ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Prolonged Infusion ◽  
Dosing Strategy

Necrotizing enterocolitis (NEC) continues to be a major cause of neonatal morbidity and mortality. We describe the added value of therapeutic drug monitoring by presenting the case of a preterm infant with severe NEC treated with meropenem. Dosing strategy will achieve adequate patient outcome when treating pathogens with elevated MIC. As safe as meropenem is, there are not enough data for 40 mg/kg, every 8 h infused over 4 h; accordingly, strict monitoring of blood levels is mandatory. Based on our findings, a 4 h prolonged infusion of 40 mg/kg meropenem, every 8 h, will achieve an adequate patient outcome.

scholarly journals Therapeutic Drug Monitoring in Fungal Infections: the Dawn of Proactive Monitoring

2021 ◽  
Author(s):  
Joan Antoni Schoenenberger-Arnaiz ◽  
Ana Aragones-Eroles ◽  
Pilar Taberner-Bonastre ◽  
Arturo Morales-Portillo
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Clinical Settings ◽  
Drug Concentrations ◽  
Direct Exposure ◽  
Consensus Statements

Therapeutic Drug Monitoring (TDM) is potentially a useful tool that can be employed to increase the efficacy and decrease the toxicity of antifungal drugs. The aim of this narrative review is to provide an overview of the current use of TDM in clinical practice, and to present the evidence available regarding its use in proactive clinical settings for preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations in everyday practice. Articles concerning the use of TDM of triazoles in the treatment of fungal infections were retrieved through an electronic search using PubMed. In clinical practice, TDM has an increasingly important role in the management of antifungal drugs as a consequence of the improvement in the knowledge of the pharmacokinetics and pharmacodynamics of these drugs. The currently available evidence shows a direct exposure-response relationship for triazoles, though the PK/PD profile is unpredictable. Current guidelines and treatment consensus statements recommend the proactive TDM of voriconazole, posaconazole, and itraconazole to optimize dosage regimens and improve outcomes for adult and pediatric patients.

Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS

2010 ◽  
Vol 878 (1) ◽  
pp. 39-44 ◽  
Author(s):  
J.W.C. Alffenaar ◽  
A.M.A. Wessels ◽  
K. van Hateren ◽  
B. Greijdanus ◽  
J.G.W. Kosterink ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Antifungal Drugs ◽  
Therapeutic Drug

Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

2018 ◽  
Vol 75 (5) ◽  
pp. 316-328
Author(s):  
Christian Ansprenger ◽  
Emanuel Burri
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Morbus Crohn ◽  
Therapeutic Drug ◽  
Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

Sign in / Sign up

Export Citation Format

Share Document