Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center

2020 ◽  
Vol 58 (7) ◽  
pp. 996-999 ◽  
Author(s):  
Andrew M Borman ◽  
Jessica M Hughes ◽  
Debra Oliver ◽  
Mark Fraser ◽  
Julie Sunderland ◽  
...  
Keyword(s):  
Clinical Trials ◽  
United Kingdom ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Reference Center ◽  
Prolonged Therapy ◽  
Dosing Regimens

Abstract We determined isavuconazole serum concentrations for 150 UK patients receiving standard isavuconazole dosing regimens, including serial therapeutic drug monitoring for several patients on prolonged therapy. Mean trough isavuconazole concentrations in these patients were virtually identical to those reported previously from clinical trials, although greater variability was seen in patients below 18 years of age. Serial monitoring in patients receiving prolonged therapy suggested gradual, near-linear accumulation of the drug over many weeks.

Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 70-77 ◽  
Author(s):  
Filip Baert
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Treatment Guidelines ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Short Term ◽  
Clear Dose Response ◽  
Inflammatory Bowel

In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines.

scholarly journals Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Dennis Kühn ◽  
Carlos Metz ◽  
Frederik Seiler ◽  
Holger Wehrfritz ◽  
Sophie Roth ◽  
...  
Keyword(s):  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Therapeutic Drug Monitoring ◽  
Extracorporeal Membrane Oxygenation ◽  
Replacement Therapy ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

scholarly journals Therapeutic drug monitoring in special populations

1998 ◽  
Vol 44 (2) ◽  
pp. 415-419 ◽  
Author(s):  
Philip D Walson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Diagnostic Testing ◽  
Drug Effects ◽  
Special Populations ◽  
Therapeutic Drug ◽  
Drug Reactions ◽  
Drug Concentrations ◽  
Dosing Regimens ◽  
Multiple Drugs

Abstract Therapeutic drug monitoring (TDM) is commonly used to maintain “therapeutic” drug concentrations. Even in compliant patients, with “average” drug kinetics, TDM is useful to identify the causes of unwanted or unexpected responses, prevent unnecessary diagnostic testing, improve clinical outcomes, and even save lives. TDM has greatest promise in certain special populations who are: (a) prone to under- or overrespond to usual dosing regimens, (b) least able to tolerate, recognize, or communicate drug effects, or who are (c) intentionally or accidentally misdosed. TDM is especially useful in patients at the extremes of age, in adolescents, and in patients who are either taking multiple drugs or expressing unusual pharmacokinetics as a result of physiological, environmental, or genetic causes. Less-well-appreciated uses of TDM include prevention of dangerousunderdosing of patients, investigation of adverse drug reactions, and identification of serious medication errors, even for a number of drugs that are not traditionally monitored. TDM can be useful for some drugs in any patient and for most drugs in some special populations.

scholarly journals What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 638
Author(s):  
Ming G. Chai ◽  
Menino O. Cotta ◽  
Mohd H. Abdul-Aziz ◽  
Jason A. Roberts
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Therapeutic Drug Monitoring ◽  
Patient Outcomes ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Statistical Modelling ◽  
Therapeutic Drug ◽  
Dosing Regimens ◽  
Point Of Care System

Antimicrobial dosing in the intensive care unit (ICU) can be problematic due to various challenges including unique physiological changes observed in critically ill patients and the presence of pathogens with reduced susceptibility. These challenges result in reduced likelihood of standard antimicrobial dosing regimens achieving target exposures associated with optimal patient outcomes. Therefore, the aim of this review is to explore the various methods for optimisation of antimicrobial dosing in ICU patients. Dosing nomograms developed from pharmacokinetic/statistical models and therapeutic drug monitoring are commonly used. However, recent advances in mathematical and statistical modelling have resulted in the development of novel dosing software that utilise Bayesian forecasting and/or artificial intelligence. These programs utilise therapeutic drug monitoring results to further personalise antimicrobial therapy based on each patient’s clinical characteristics. Studies quantifying the clinical and cost benefits associated with dosing software are required before widespread use as a point-of-care system can be justified.

Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice

2020 ◽  
Vol 42 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Gauri G. Rao ◽  
Robyn Konicki ◽  
Dario Cattaneo ◽  
Jan-Willem Alffenaar ◽  
Deborah J. E. Marriott ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Current Clinical Practice ◽  
Dosing Regimens

scholarly journals Impact of Triazole Therapeutic Drug Monitoring Availability and Timing

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Erin K. McCreary ◽  
Meg Bayless ◽  
Ahn P. Van ◽  
Alexander J. Lepak ◽  
Donald A. Wiebe ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcomes ◽  
Antifungal Therapy ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Reference Laboratory ◽  
Serum Concentrations ◽  
Concentration Result ◽  
The Impact

ABSTRACT Therapeutic drug monitoring (TDM) is an established strategy to optimize antifungal therapy with certain triazoles. While established relationships exist between concentration and safety or efficacy, the impact of TDM timing on outcomes is unknown. We report clinical outcomes, including antifungal exposure and mortality, in patients receiving institutional versus reference laboratory TDM. The availability of in-house triazole assays reduced the time to drug concentration result (12 versus 68 h; P < 0.001) and time to achieve therapeutic serum concentrations (10 versus 31 days; P < 0.001). Subtherapeutic concentrations were associated with higher patient mortality (32% versus 13.3%; P = 0.036).

Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A pilot two-center study

2020 ◽  
Author(s):  
Albrecht Eisert ◽  
Christian Lanckohr ◽  
Janina Frey ◽  
Otto Frey ◽  
Sebastian G. Wicha ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Severe Disease ◽  
Therapeutic Drug ◽  
Prolonged Infusion ◽  
Minimal Inhibitory Concentrations ◽  
Drug Concentrations ◽  
Dosing Regimens ◽  
Higher Doses ◽  
Extended Infusion

Abstract Background : Sepsis is a severe disease with complex pathophysiology and high mortality. Meropenem is frequently used in sepsis to treat the underlying infection. Studies have shown that standard doses of meropenem are frequently inadequate due to high pharmacokinetic and pharmacodynamic variability. Therapeutic drug monitoring (TDM) of meropenem is not widely available, and increased empiric dosing recommendations are needed. Methods : We compared two empiric dosing schemes of meropenem using extended infusion (120 minutes) in 32 patients with sepsis in the ICUs at two different hospitals. One regimen was 3x 2 g meropenem/ 24 h for two days, followed by 3x 1 g meropenem/ 24 h; the other regimen was 4x 1 g meropenem/ 24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the dosing interval was above various target minimal inhibitory concentrations (MICs) for each regimen (%fT >MIC ). Results : Both regimens led to a sufficiently high %fT >MIC for pathogens with target MICs below 4 mg/L. When higher MICs were targeted, the %fT >MIC of 4x 1 g meropenem decreased faster than that of 3x 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide drug concentrations deemed appropriate for clinical improvement. Conclusions : The results of this pilot study can guide clinicians in their choice of an empirical dosing scheme when prescribing meropenem in the absence of TDM. If pathogens with low MICs (<4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant clones require higher doses. The control of β-lactam therapy by therapeutic drug monitoring is desirable.

Probability Assessment Approach to Therapeutic Drug Monitoring: Tobramycin

DICP ◽  
1989 ◽  
Vol 23 (3) ◽  
pp. 240-244 ◽  
Author(s):  
Richard L. Slaughter
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Cost Benefit ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Probability Assessment ◽  
Serum Concentrations ◽  
Specific Patient ◽  
Assessment Approach ◽  
Toxic Concentrations

Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough >2.0 μg/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough < 2.0 μg/mL, peak >4.0 μg/mL), these patients were older (64 ± 11 vs. 54 ± 18years; p < 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p < 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 ± 45 vs. 74 ± 27 mL/min; p < 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by ≥30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent). Therefore, routine measurement of serum concentrations in this group would have limited cost-benefit potential. It is concluded that a probability assessment approach can be used to facilitate the therapeutic monitoring of tobramycin.

Developing an isotope dilution UHPLC–MS/MS method to quantify linezolid in human plasma: application to therapeutic drug monitoring

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 991-1001
Author(s):  
Yanping Guan ◽  
Xiaoxia Yu ◽  
Ying Wang ◽  
Qinhai Li ◽  
Dan Liang ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
The Us ◽  
Dosing Regimens ◽  
Us Fda ◽  
Isocratic Mode

Aim: To optimize clinical efficacy and reduce the drug-exposure-related toxicity of linezolid, whose concentrations show wide inter-variabilities, a simple and reliable quantitative assay for therapeutic drug monitoring is necessary. Results: A UHPLC–MS/MS assay has been established for determination of linezolid in human plasma and fully validated according to the US FDA guidelines. After a simple, isotope-dilluted precipitation with methanol, the analytes were separated by a straightforward isocratic mode and the MS/MS was conducted under the ESI+ mode fitted with SRM. The calibration curves proved acceptable linearity in the range of 0.1–30.0 µg/ml. Conclusion: The present assay is currently used in routine clinical practice, being applied to therapeutic drug monitoring and helps to optimize individual dosing regimens and manage adverse effects in ICU patients.

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