Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?

2020 ◽  
Author(s):  
Thomas J Dilworth ◽  
Lucas T Schulz ◽  
Warren E Rose
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Inhibitory Concentration ◽  
Drug Efficacy ◽  
Therapeutic Drug ◽  
Limited Data ◽  
Considerable Effort ◽  
Time Curve ◽  
Concentration Time ◽  
High Level

Abstract Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.

scholarly journals Optimizing the Initial Amikacin Dosage in Adults

2015 ◽  
Vol 59 (11) ◽  
pp. 7094-7096 ◽  
Author(s):  
Bryan P. White ◽  
Ben Lomaestro ◽  
Manjunath P. Pai
Keyword(s):  
Body Weight ◽  
Standard Deviation ◽  
Therapeutic Drug Monitoring ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Maintenance Dose ◽  
Therapeutic Drug ◽  
High Dose ◽  
Time Curve ◽  
Concentration Time

ABSTRACTWe report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (Cmax) and 24-h area under the concentration-time curve (AUC24) of 101 (49.4) mg/liter and 600 (387) mg · h/liter, respectively, were observed (n= 73) with 28.0 (8.47) mg/kg/day doses. An initial amikacin dose of 2,500 mg in adults weighing 40 kg to 200 kg with therapeutic drug monitoring to adjust the maintenance dose will optimize its PK and PD.

scholarly journals Appropriate Use of Glycopeptide Antibiotics and Therapeutic Drug Monitoring for Invasive Infections

2021 ◽  
Vol 96 (6) ◽  
pp. 463-477
Author(s):  
Si-Ho Kim ◽  
Soo-Youn Lee ◽  
Cheol-In Kang
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Surrogate Marker ◽  
Therapeutic Drug ◽  
Glycopeptide Antibiotics ◽  
Time Curve ◽  
Bacteriological Response ◽  
Concentration Time ◽  
Invasive Infections ◽  
Gram Positive Cocci

Vancomycin and teicoplanin are representative glycopeptide antibiotics with activities against gram-positive cocci. The area under the drug concentration–time curve (AUC)/minimal inhibitory concentration (MIC) has been extensively used as an indicator of the bacteriological response to glycopeptide antibiotics, and the trough concentration has been used as a surrogate marker for the AUC/MIC. However, the guidelines for therapeutic drug monitoring (TDM) are being revised in accordance with increasing pharmacokinetic understanding of glycopeptide antibiotics. This review describes the pharmacokinetic/pharmacodynamic characteristics of glycopeptide antibiotics and discusses their optimal use with appropriate TDM.

scholarly journals Evaluation of electrochemiluminescence immunoassays for immunosuppressive drugs on the Roche cobas e411 analyzer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1832
Author(s):  
Angela W.S. Fung ◽  
Michael J. Knauer ◽  
Ivan M. Blasutig ◽  
David A. Colantonio ◽  
Vathany Kulasingam
Keyword(s):  
Regression Analysis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Transplant Rejection ◽  
Organ Transplant ◽  
Drug Efficacy ◽  
Immunosuppressive Drugs ◽  
Therapeutic Drug ◽  
Deming Regression ◽  
Roche Cobas

Background:  Therapeutic drug monitoring of immunosuppressant drugs are used to monitor drug efficacy and toxicity and to prevent organ transplant rejection. This study evaluates the analytical performance of semi-automated electrochemiluminescence immunoassays (ECLIA) for cyclosporine (CSA), tacrolimus (TAC) and sirolimus (SRL) on the Roche cobas e 411 analyzer at a major transplant hospital to assess method suitability and limitations. Methods: Residual whole blood samples from patients undergoing immunosuppressant therapy were used for evaluation. Imprecision, linearity, functional sensitivity, method comparisons and lot-to-lot comparisons were assessed. Results: Total imprecision ranged from 3.3 to 7.1% for CSA, 3.9 to 9.4% for TAC, and 4.6 to 8.2% for SRL. Linearity was verified from 30.0 to 960.9 μg/L for CSA, from 1.1 to 27.1 μg/L for TAC, and from 0.5 to 32.3 µg/L for SRL. The functional sensitivity met the manufacturer’s claims and was determined to be <6.5 μg/L for CSA, 1.1 μg/L for TAC, and <0.1 µg/L for SRL (CV≤20%). Deming regression analysis of method comparisons with the ARCHITECT immunoassay yielded slopes of 0.917 (95%CI: 0.885-0.949) and r of 0.985 for CSA, 0.938 (95%CI: 0.895-0.981) and r of 0.974 for TAC, and 0.842 (0.810-1.110) and r of 0.982 for SRL. Deming regression analysis of comparisons with the LC–MS/MS method yielded slopes of 1.331 (95%CI: 1.167-1.496) and r of 0.969 for CSA, 0.924 (95%CI: 0.843-1.005) and r of 0.984 for TAC, and 0.971 (95%CI: 0.913-1.030) and r of 0.993 for SRL. Conclusions: The cobas e 411 ECLIA for CSA, TAC, and SRL have acceptable precision, linearity, and functional sensitivity. The method comparisons correlated well with the ARCHITECT immunoassay and LC–MS/MS and is fit for therapeutic drug monitoring

scholarly journals N797 Therapeutic drug monitoring after thiopurine initiation improves drug efficacy

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S489-S490
Author(s):  
W. Dijkstra-Heida ◽  
C. Smids ◽  
M. van Luin ◽  
G. Huisman-de Waal ◽  
M. de Leest ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Efficacy ◽  
Therapeutic Drug

scholarly journals Combining Therapeutic Drug Monitoring with Biosimilars, a Strategy to Improve the Efficacy of Biologicals for Treating Inflammatory Bowel Diseases at an Affordable Cost

2017 ◽  
Vol 35 (1-2) ◽  
pp. 61-68 ◽  
Author(s):  
Ann Gils
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Drug Efficacy ◽  
European Medicines Agency ◽  
Therapeutic Drug ◽  
Treatment Switching ◽  
Loss Of Response ◽  
Drug Concentrations ◽  
Bowel Diseases

Background: Biologicals provide a tight disease control but not all patients respond favourably to treatment. Some patients do not respond at all (primary non-responders), while other patients respond initially but show loss of response over time (secondary non-responders). Drug concentrations in the serum of patients can be monitored and correlated with biological, clinical or endoscopic response. Therapeutic thresholds have been defined for infliximab and adalimumab. The European Medicines Agency has approved 3 biosimilars of infliximab and new biosimilars are waiting approval. Key Messages: Distinguishing primary non-responders from patients with insufficient drug exposure during induction through drug serum concentration determination will improve drug efficacy. Current algorithms to guide treatment of patients with secondary loss of response take into account that patients with high titers of anti-drug antibodies (ADA) do not respond to dose intensification and that patients with therapeutic drug concentrations cannot be switched to biologicals within class. For patients in clinical remission, the cost of biological treatment can be decreased by dose tapering patients with supra-therapeutic concentrations and/or by switching patients with adequate drug concentrations and no formation of ADA to biosimilar, whereas efficacy can be increased by dose-intensifying patients with low or transient ADA and by switching patients with persistent ADA to biologicals within or out-off class. Conclusions: As an objective tool, therapeutic drug monitoring can identify patients who are eligible for dose tapering, intensification of treatment, cessation of treatment, switching within- or out-of-class and switching to biosimilar.

scholarly journals Therapeutic Drug Monitoring in Rheumatic Diseases

2016 ◽  
Vol 16 (2) ◽  
pp. 33-37
Author(s):  
Alexandra NG Hoi-Yan ◽  
Chi Chiu Mok
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Tumor Necrosis ◽  
Drug Efficacy ◽  
Drug Level ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Underlying Diseases ◽  
Individual Pharmacokinetics ◽  
Necrosis Factor

Abstract The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors).

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