scholarly journals Effect of augmented renal clearance on the therapeutic drug monitoring of vancomycin in patients after neurosurgery

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052094907
Author(s):  
Yue Chen ◽  
Lei Liu ◽  
Man Zhu
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Renal Clearance ◽  
Normal Renal Function ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Augmented Renal Clearance ◽  
Achievement Rate ◽  
Baseline Characteristics

Objective To study the effect of augmented renal clearance (ARC) on vancomycin therapeutic drug monitoring in patients undergoing neurosurgery. Methods A retrospective observational analysis was conducted in a neurosurgery department from January 2019 to June 2019. Patients undergoing vancomycin therapeutic drug monitoring were assigned to the normal renal function or ARC group. The baseline characteristics, vancomycin therapeutic drug monitoring data, and prognosis were compared and analyzed. Results In total, 104 patients were enrolled, including 78 and 26 patients in the normal renal function and ARC groups, respectively. There were significant differences in age, weight, creatinine clearance, the vancomycin treatment duration, the total dose, the trough concentration, and the trough concentration achievement rate between the two groups. Prognosis did not differ between the two groups. The trough concentration achievement rate in the ARC group was only 19.23%. Conclusion For young, obese, or otherwise healthy patients undergoing neurosurgery, attention should be paid to the possibility of ARC and the need for individualized dose adjustment based on the results of therapeutic drug monitoring.

scholarly journals Use of Therapeutic Drug Monitoring to Characterize Cefepime-Induced Neurotoxicity

2020 ◽  
Author(s):  
Veena Venugopalan ◽  
Cara Nys ◽  
Natalie Hurst ◽  
Yiqing Chen ◽  
Maria Bruzzone ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Hospitalized Patients ◽  
Therapeutic Drug ◽  
Eeg Abnormalities ◽  
Increased Risk ◽  
Trough Concentrations ◽  
The Relationship

AbstractBackgroundThe incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.MethodsThis was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.ResultsOne-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.ConclusionCefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.

Use of continuous infusion ceftolozane–tazobactam with therapeutic drug monitoring in a patient with cystic fibrosis

2019 ◽  
Vol 76 (8) ◽  
pp. 501-504 ◽  
Author(s):  
Sarah Elizabeth Davis ◽  
Jared Ham ◽  
Jennifer Hucks ◽  
Alyssa Gould ◽  
Rachel Foster ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Therapeutic Drug Monitoring ◽  
Continuous Infusion ◽  
Renal Clearance ◽  
Drug Monitoring ◽  
Adverse Drug Events ◽  
Pulmonary Function Tests ◽  
Therapeutic Drug ◽  
Augmented Renal Clearance ◽  
Definitive Therapy

Abstract Purpose The safe and effective use of ceftolozane–tazobactam delivered via continuous infusion in a cystic fibrosis (CF) patient with reduced body weight and presumed augmented renal clearance is reported. Summary A 30-year-old woman with CF was admitted for acute pulmonary exacerbations with positive respiratory cultures for Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Escherichia coli. Susceptibility testing confirmed multidrug resistance, and the patient was transitioned to ceftolozane–tazobactam for definitive therapy. A novel strategy of administering ceftolozane–tazobactam 6 g by continuous i.v. infusion over 24 hours was initiated during hospitalization and continued at discharge for a total of 10 days. Therapeutic drug monitoring over the first 36 hours of the continuous infusion confirmed adequate exposure. The patient had clinical resolution with return to baseline of pulmonary function tests and no noted adverse drug events. Conclusion A continuous infusion regimen of ceftolozane–tazobactam was successfully used in a CF patient with augmented renal clearance.

scholarly journals Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Catherine J. Byrne ◽  
Jason A. Roberts ◽  
Brett McWhinney ◽  
Jerome P. Fennell ◽  
Philomena O'Byrne ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Therapeutic Drug Monitoring ◽  
Creatinine Clearance ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Hematological Malignancy ◽  
Therapeutic Drug ◽  
Factors Associated ◽  
Trough Concentrations

ABSTRACT The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

scholarly journals Dosing of Ertapenem in an Extreme Obesity: A Case Report of 250 kg Patient

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Jana Lass ◽  
Kadri Tamme ◽  
Karin Kipper ◽  
Joel Starkopf
Keyword(s):  
Renal Function ◽  
Case Report ◽  
Therapeutic Drug Monitoring ◽  
Normal Renal Function ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Extreme Obesity ◽  
Once Daily

Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients.

scholarly journals Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax. The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

scholarly journals N22 Nurse led therapeutic drug monitoring (TDM) of Infliximab in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
S Gleeson ◽  
K Sugrue ◽  
M Buckley ◽  
J McCarthy
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Response Assessment ◽  
Symptom Improvement ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Biologic Response ◽  
Trough Levels

Abstract Background Therapeutic drug monitoring (TDM) is the clinical practice of measuring serum drug concentrations to guide clinical decision making. Achieving therapeutic drug concentrations has been associated with clinical, endoscopic and histological outcomes in IBD. The use of TDM offers a more personalised treatment approach and is associated with sustained clinical remission. Proactive TDM was introduced to the Mercy University Hospital in 2014 for all patients on biologics. Methods One hundred patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement. Results Thirty-five per cent of patients had sub therapeutic trough levels at week 12. They subsequently received 3 increased doses of 10mgs/kg and levels were rechecked. Of these 90% achieved therapeutic levels after the dose escalation. 65% of patients had therapeutic levels at week 12. There was a correlation between therapeutic trough levels and patient reported improvement of clinical symptoms in 85% of respondents. Conclusion TDM in our unit facilitates appropriate dose 100 patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement.

scholarly journals 1538. Who Will Benefit From Therapeutic Drug Monitoring of Ganciclovir?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S560-S561
Author(s):  
Anne-Grete Martson ◽  
Marieke G G Sturkenboom ◽  
Stefan P Berger ◽  
Kevin Damman ◽  
Erik A M Verschuuren ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Observational Study ◽  
Drug Monitoring ◽  
Drug Formulation ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Cell Transplant ◽  
Specific Patient

Abstract Background Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and pre-emptive treatment of cytomegalovirus and human herpesvirus 6. It is important to estimate the exposure to these antivirals, as deviating levels can cause adverse events or induce acquired drug resistance, which can both lead to treatment failure. Therapeutic drug monitoring (TDM) is a good tool to estimate drug exposure in these patients. With this observational study we aimed to evaluate which patients would benefit most from TDM. Methods An observational study was performed in adult solid-organ and stem cell transplant recipients on routine (val)ganciclovir (dosed according to renal function, weight and indication). As valganciclovir is a prodrug of ganciclovir, only the latter was measured. Ganciclovir trough (Ctrough) and peak (Cpeak) concentrations were measured with a validated LC-MS/MS assay. The target concentrations defined for the study were 1–2 mg/L and 2–4 mg/L for prophylaxis and treatment, respectively, and over 5 mg/L toxic. Results From June 2018 to April 2019, 66 patients were included. Within this timeframe, 236 Ctrough and 52 Cpeak were measured with median of 4 samples per patient. The median Ctrough was 1.1 mg/L and 2.3 mg/L for prophylaxis and treatment, respectively. Over 50% of the concentrations were out of the therapeutic window. The median creatinine for all measurements was 100 µmol/L. Observational analysis showed patients with kidney failure and on continuous renal replacement therapy (CVVH) had more concentrations measured out of the predefined range (Figures 1 and 2). For one individual with augmented renal clearance we observed significantly lower concentrations during routine dosing. 6 toxic concentrations were measured (5 subjects); creatinine concentrations ranged 71–527 µmol/L in these individuals. A preliminary linear-mixed model analysis did not show drug formulation, age or gender as a significant predictor for ganciclovir concentrations. Conclusion We believe that patients with decreased renal function, on CVVH or showing changes in renal function might benefit from TDM to guide therapy. TDM of ganciclovir for patients without renal failure remains debatable. Further studies with specific patient groups are needed to confirm these results. Disclosures All authors: No reported disclosures.

scholarly journals Therapeutic Drug Monitoring of Voriconazole in AIDS Patients

2021 ◽  
Author(s):  
Tingting Chen ◽  
Zhiqiang Lin ◽  
Huatang Zhang ◽  
Qingquan Zhang ◽  
Limian Hong ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Therapeutic Range ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Linear Regression Analysis ◽  
Immune Deficiency Syndrome ◽  
Therapeutic Drug ◽  
Affecting Factors ◽  
Aids Patients

Abstract Background The safety and efficacy of Voriconazole in Acquired Immune Deficiency Syndrome (AIDS) patients is difficult to guarantee. In this study, Therapeutic Drug Monitoring (TDM) of Voriconazole in AIDS patients was investigated with the aim to further verify the significance of voriconazole TDM in AIDS patients and to explore more strategies to improve individualized medication. Methods The data of AIDS patients who underwent voriconazole TDM in our hospital from May 2018 to August 2021 were collected. The basic information of patients, the results of voriconazole TDM, the individualized intervention, the affecting factors of voriconazole concentration were analyzed, as well as the relationship between voriconazole trough concentration and safety. Results A total of 46 tests of voriconazole TDM were performed in 28 AIDS patients. Only 57.14% patients reached the therapeutic range at first TDM, and 87.50% patients reached the therapeutic range after intervention based on first TDM. 21.43% patients develop voriconazole-related Adverse Drug Reactions (ADRs), and ADRs were mostly occurred when voriconazole concentration is above 5.0 µg/mL. Spearman correlation coefficient rs was calculated to be 0.729 for voriconazole trough concentration and the incidence of ADRs, exhibiting a significant, positive linear correlation (P=0. 017). 50% patients had polypharmacy and drug interactions are common. For example, rifampicin can significantly reduce the plasma concentration of voriconazole. Multiple linear regression analysis showed Hypoproteinemia was a significant factor affecting voriconazole trough concentration(P=0.006). Conclusion AIDS patients usually have a low attainment rate of voriconazole trough concentration after initiation of standard dosing regimen. The affecting factors seem multifactorial and complex, of which hypoproteinemia is of great significance. Meanwhile, we need to be alert to the effects of drug interactions. The incidence of voriconazole related ADRs is high, mostly occurring when voriconazole concentration is above 5.0 µg/mL. Therefore, TDM can provide meaningful guidance for dosage optimization of voriconazole, and the dosage adjustment method in Chinese Guideline is applicable for the population of AIDS patients.

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