scholarly journals Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1421
Author(s):  
Christoph Tiede ◽  
Ute Chiriac ◽  
Daniel Dubinski ◽  
Florian J. Raimann ◽  
Otto R. Frey ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Continuous Infusion ◽  
Dose Optimization ◽  
Therapeutic Drug ◽  
Median Serum ◽  
Individualized Dosing ◽  
Reasonable Approach ◽  
Dosing Strategy ◽  
Cerebral Infections ◽  
Routine Therapeutic Drug Monitoring

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

Generation of Pharmacokinetic Data During Routine Therapeutic Drug Monitoring

1993 ◽  
Vol 15 (4) ◽  
pp. 281-288 ◽  
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

scholarly journals High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis

2018 ◽  
Vol 63 (2) ◽  
pp. e01844-18 ◽  
Author(s):  
Matthieu Grégoire ◽  
Benjamin Gaborit ◽  
Colin Deschanvres ◽  
Raphaël Lecomte ◽  
Guillaume Deslandes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cerebrospinal Fluid ◽  
Continuous Infusion ◽  
External Ventricular Drainage ◽  
High Dose ◽  
Ventricular Drainage ◽  
Content Type

ABSTRACT A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

scholarly journals 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

2021 ◽  
Vol 14 (12) ◽  
pp. 1214
Author(s):  
Catherine Feliu ◽  
Celine Konecki ◽  
Tristan Candau ◽  
Damien Vautier ◽  
Cyril Haudecoeur ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Therapeutic Drug ◽  
Beta Lactams ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer ◽  
Easy Method ◽  
Routine 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.

Therapeutic drug monitoring of linezolid: HPLC-based assays for routine quantification of linezolid in human serum and cerebrospinal fluid

2022 ◽  
pp. ejhpharm-2021-003036
Author(s):  
Stefan Günther ◽  
Andreas Reimer ◽  
Horst Vogl ◽  
Stephan Spenke ◽  
Hanns-Christian Dinges ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Therapeutic Drug

scholarly journals The Unique Pharmacometrics of Small Molecule Therapeutic Drug Tracer Imaging for Clinical Oncology

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2712
Author(s):  
Mark P. S. Dunphy ◽  
Nagavarakishore Pillarsetty
Keyword(s):  
Small Molecule ◽  
Response Assessment ◽  
Imaging Biomarkers ◽  
Cancer Drug ◽  
Therapeutic Drug ◽  
Therapeutic Drugs ◽  
Tracer Imaging ◽  
Tumor Pharmacokinetics ◽  
Dosing Strategy

Translational development of radiolabeled analogues or isotopologues of small molecule therapeutic drugs as clinical imaging biomarkers for optimizing patient outcomes in targeted cancer therapy aims to address an urgent and recurring clinical need in therapeutic cancer drug development: drug- and target-specific biomarker assays that can optimize patient selection, dosing strategy, and response assessment. Imaging the in vivo tumor pharmacokinetics and biomolecular pharmacodynamics of small molecule cancer drugs offers patient- and tumor-specific data which are not available from other pharmacometric modalities. This review article examines clinical research with a growing pharmacopoeia of investigational small molecule cancer drug tracers.

Magnetic solid-phase extraction coupled with UHPLC–MS/MS for four antidepressants and one metabolite in clinical plasma and urine samples

Bioanalysis ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 35-52
Author(s):  
Peishan Cai ◽  
Xiang Xiong ◽  
Dan Li ◽  
Yu Zhou ◽  
Chaomei Xiong
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Solid Phase Extraction ◽  
Solid Phase ◽  
Magnetic Solid Phase Extraction ◽  
Urine Samples ◽  
Therapeutic Drug ◽  
Phase Extraction ◽  
Plasma And Urine Samples ◽  
Magnetic Solid ◽  
Routine Therapeutic Drug Monitoring

Aim: Routine therapeutic drug monitoring is highly recommended since common antidepressant combinations increase the risk of drug–drug interactions or overlapping toxicity. Materials & methods: A magnetic solid-phase extraction by using C18-functionalized magnetic silica nanoparticles (C18-Fe3O4@SiO2 NPs) as sorbent was proposed for rapid extraction of venlafaxine, paroxetine, fluoxetine, norfluoxetine and sertraline from clinical plasma and urine samples followed by ultra-HPLC–MS/MS assay. Results: The synthesized C18-Fe3O4@SiO2 NPs showed high magnetization and efficient extraction for the analytes. After cleanup by magnetic solid-phase extraction, no matrix effects were found in plasma and urine matrices. The analytes showed LODs among 0.15–0.75 ng ml-1, appropriate linearity (R ≥ 0.9990) from 2.5 to 1000 ng ml-1, acceptable accuracies 89.1–110.9% with precisions ≤11.0%. The protocol was successfully applied for the analysis of patients’ plasma and urine samples. Conclusion: It shows high potential in routine therapeutic drug monitoring of clinical biological samples.

Elimination of glycopeptide antibiotics by cytokine hemoadsorption in patients with septic shock: A study of three cases

2020 ◽  
Vol 43 (12) ◽  
pp. 753-757 ◽  
Author(s):  
Thomas Dimski ◽  
Timo Brandenburger ◽  
Colin MacKenzie ◽  
Detlef Kindgen-Milles
Keyword(s):  
Septic Shock ◽  
Clinical Practice ◽  
Continuous Infusion ◽  
Clinical Course ◽  
Serum Levels ◽  
Metabolic Effects ◽  
Adsorptive Capacity ◽  
Therapeutic Drug ◽  
Glycopeptide Antibiotics ◽  
Sepsis And Septic Shock

Sepsis and septic shock are characterized by a release of cytokines into the circulation. These mediators contribute to the detrimental hemodynamic and metabolic effects in the early phase of septic shock. Recently, a new polystyrene-based hemoadsorption device was introduced into clinical practice (CytoSorb®). The adsorber binds a variety of molecules including cytokines and removes them from the circulation. Studies in septic patients have shown an improved clinical course following hemoadsorption but no increased survival. We hypothesize that not only cytokines but also antibiotics may be removed which potentially may negate any beneficial effect of the adsorber. To test this hypothesis, we performed polystyrene-based hemoadsorption in three patients in septic shock and analysed glycopeptide elimination by measuring serum levels pre- and post-adsorber. We administered both teicoplanin and vancomycin via a 60-min infusion and vancomycin via continuous infusion, additionally. When applied as 60 min infusion, vancomycin and teicoplanin were removed immediately by the adsorber. However, the adsorptive capacity of the device was saturable. Serum levels of vancomycin, but not teicoplanin, decreased to subtherapeutic levels. With continuous infusion of vancomycin, removal was less and serum levels remained in the therapeutic range. In conclusion, we show effective glycopeptide adsorption using a polystyrene-based hemoadsorber in septic patients. The dose of these antibiotics should be adjusted appropriately and early therapeutic drug monitoring is highly recommended.

scholarly journals Optimizing Pharmacokinetics-Pharmacodynamics of Antimicrobial Management in Patients with Sepsis: A Review

2020 ◽  
Vol 222 (Supplement_2) ◽  
pp. S132-S141 ◽  
Author(s):  
Kady Phe ◽  
Emily L Heil ◽  
Vincent H Tam
Keyword(s):  
Therapeutic Drug ◽  
Optimal Care ◽  
Risk Of Death ◽  
Physiological Alterations ◽  
Increased Risk ◽  
Individualized Dosing ◽  
Antimicrobial Management ◽  
Diagnostic Technology ◽  
Aggressive Interventions ◽  
The Impact

Abstract Critically ill patients with sepsis or septic shock are at an increased risk of death. Early and aggressive interventions are essential for improving clinical outcomes. There are a number of therapeutic and practical challenges in the management of antimicrobials in patients with sepsis. These include the timely selection and administration of appropriate antimicrobials, significant physiological alterations that can influence antimicrobial pharmacokinetics, and significant interpatient variability of antimicrobial concentrations using standard dosing approaches. Understanding the impact of these factors on the probability of attaining pharmacokinetic-pharmacodynamic target goals is essential to guide optimal therapy. Using rapid diagnostic technology could facilitate timely selection of antimicrobials, and therapeutic drug monitoring would provide a more individualized dosing approach. Using an interdisciplinary sepsis team would also be beneficial in coordinating efforts to overcome the challenges encountered during this critical period to ensure optimal care.

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