Accuracy of Empiric Gentamicin Dosing Guidelines in Neonates

2010 ◽  
Vol 15 (4) ◽  
pp. 264-273
Author(s):  
Anna E. Hitron ◽  
Yao Sun ◽  
Sarah B. Scarpace
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Gestational Age ◽  
Drug Monitoring ◽  
Dose Interval ◽  
Pharmacokinetic Modeling ◽  
Therapeutic Drug ◽  
Potential Factors ◽  
New Guidelines ◽  
Dosing Accuracy ◽  
Current Guidelines

ABSTRACT OBJECTIVE To evaluate the accuracy of a neonatal gentamicin nomogram to achieve therapeutic gentamicin serum concentrations without further adjustment, allowing for decreased serum drug monitoring METHODS Retrospective single center review of all gentamicin pharmacokinetic evaluations in patients ≤ 30 days of life from July 2005 – June 2007. Patients were evaluated for postnatal age, gestational age, weight, serum creatinine, dose/interval, serum drug peaks and troughs, results of discharge hearing test and recent use of indomethacin. Logistic regression was utilized to determine potential factors impacting overall dosing accuracy, potentially allowing for decreased therapeutic drug monitoring. Factors found to be significant were incorporated into new guidelines which were evaluated through pharmacokinetic modeling. RESULTS Overall accuracy rate was 84% when empiric dosing guidelines were utilized; 16% of all doses were changed due to supratherapeutic troughs and 1% were changed due to subtherapeutic peaks. Variables found to impact the necessity for dose changes incuded gestational age (p≤0.001), weight (p≤0.001), indomethacin use (p≤0.001), number of indomethacin doses used (p≤0.001 and p=0.009 for 1–3 and 4–6 doses, respectively), and SCr in patients ≥ 7 days old (p=0.028); however, only gestational age remained a significant predictor when all other factors were considered (p=0.008). The current guidelines were changed to account for increased troughs in patients ≤ 28 weeks gestation and examined through pharmacokinetic modeling. Pharmacokinetic modeling of the new guidelines predicted an overall accuracy of 94%. CONCLUSIONS From the data gathered regarding the accuracy in patients ≥ 35 weeks gestation, we recommend to decrease therapeutic drug monitoring within this cohort. Utilizing the results of regression analysis, the current guidelines have been adjusted to allow for increased clearance in patients ≤ 28 weeks gestation, although they still need to be prospectively evaluated.

Population Pharmacokinetics of Meropenem in Preterm Infants

2021 ◽  
Vol 76 (5) ◽  
pp. 497-505
Author(s):  
Irina B. Bondareva ◽  
Sergey K. Zyryanov ◽  
Aleksandra M. Kazanova
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Pharmacokinetic Parameter ◽  
Gestational Age ◽  
Drug Monitoring ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Variability ◽  
Older Children ◽  
Term Neonates

Background. Meropenem, a broad spectrum carbapenem antibiotic, is often used for newborns despite of limited data available on neonatal pharmacokinetics. Due to pharmacokinetic and pharmacodynamic differences as well as to significant changes in the human body related to growth and maturation of organs and systems, direct scaling and dosing extrapolation from adults or older children with adjustment on patients weight can result in increased risk of toxicity or treatment failures. Aims to evaluate the pharmacokinetics of meropenem in premature neonates based on therapeutic drug monitoring data in real clinical settings. Materials. Of 53 pre-term neonates included in the pharmacokinetic/pharmacodynamic analysis, in 39 (73.6%) patients, gestational age ranged from 23 to 30 weeks. Population and individual pharmacokinetic parameter values were estimated by the NPAG program from the Pmetrics package based on peak-trough therapeutic drug monitoring. Samples were assayed by high-performance liquid chromatography. One-compartment pharmacokinetic model with zero-order input and first-order elimination was used to fit concentration data and to predict pharmacokinetic parameter (%T MIC of free drug) for virtual patients with simulated fast, moderate and slow meropenem elimination received different dosage by minimum inhibitory concentration (MIC) level. Univariate and multivariate regression analysis was used to evaluate the influence of patients covariates (gestational age, postnatal age, postconceptual age, body weight, creatinine clearance calculated by Schwartz formula, etc) on estimated meropenem pharmacokinetic parameters. Results. The identified population pharmacokinetic parameters of meropenem in pre-term newborns (elimination half-lives T1/2 = 1.93 0.341 h; clearance CL = 0.26 0.085 L/h/ kg; volume of distribution V = 0.71 0.22 L/h) were in good agreement with those published in the literature for adults, neonates and older children. Pharmacokinetic/pharmacodynamic modeling demonstrated that a meropenem dosage regimen of 90 mg/kg/day administered using prolonged 3-hour infusion every 8 hours should be considered as potentially effective therapy if nosocomial infections with resistant organisms (MIC 8 mg/L) are treated. Conclusions. Neonates and especially pre-term neonates have a great pharmacokinetic variability. Meropenem dosing in premature newborns derived from population pharmacokinetic/pharmacodynamic model can partly overcome the variability, but not all pharmacokinetic variability can be explained by covariates in a model. Further personalizing based on Bayesian forecasting approach and a patients therapeutic drug monitoring data can help to achieve desired pharmacodynamic target.

scholarly journals Assessment of Therapeutic Drug Monitoring of Vancomycin in Elderly Patients According to New Guidelines

2014 ◽  
Vol 34 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Se Jin Oh ◽  
Ki-Sook Hong ◽  
Eun Jeong Lee ◽  
Hee Jung Choi ◽  
Kyoung Ae Kong ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Elderly Patients ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
New Guidelines

scholarly journals Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

2020 ◽  
Vol 8 (3) ◽  
pp. 415 ◽  
Author(s):  
Stefan Felix Ehrentraut ◽  
Stefan Muenster ◽  
Stefan Kreyer ◽  
Nils Ulrich Theuerkauf ◽  
Christian Bode ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Therapeutic Drug ◽  
The Right ◽  
The Impact ◽  
Current Guidelines

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

scholarly journals Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

2017 ◽  
Vol 51 (01/02) ◽  
pp. 9-62 ◽  
Author(s):  
C. Hiemke ◽  
N. Bergemann ◽  
H. Clement ◽  
A. Conca ◽  
J. Deckert ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Task Force ◽  
Psychiatric Patients ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Forensic Psychiatric Patients ◽  
Substance Abuse Disorders ◽  
Forensic Psychiatric ◽  
New Guidelines

AbstractTherapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

Therapeutic drug monitoring of antifungal agents

2012 ◽  
Vol 36 (2) ◽  
pp. 1-10
Author(s):  
Werner J. Heinz ◽  
Hartwig Klinker
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Antifungal Agents ◽  
High Rate ◽  
Diagnostic Tools ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Current Guidelines ◽  
Guided Therapy

AbstractNew antifungal compounds, advanced diagnostic tools, early initiation of antifungal therapy, and the option of combination therapy have improved the treatment of fungal diseases. Despite this progress, invasive yeast and mould infections are still associated with a high rate of mortality, especially for patients with severe immunosuppression. Therapeutic drug monitoring (TDM) can both help to avoid toxic effects and improve the efficacy of antifungal agents. For flucytosine and some azoles, a TDM guided therapy is already recommended in current guidelines. Actual knowledge about different antifungal agents varies, and the options and indications for the determination of drug concentrations are likewise different for each compound. Intra- and interindividual variability of concentrations and their association with outcome and adverse events are the most important factors. They determine whether therapeutic drug monitoring may provide an option to improve therapy, which is the case for some, but not all, antifungal agents.

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.

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