scholarly journals P01 An evaluation of vancomycin therapy in paediatric patients post guideline change

2020 ◽  
Vol 105 (9) ◽  
pp. e6.1-e6 ◽  
Author(s):  
Adedoyin Agbonin ◽  
Joanne Crook
Keyword(s):  
Adverse Effects ◽  
Renal Impairment ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Paediatric Patients ◽  
Patient Reported ◽  
The Right ◽  
Higher Doses ◽  
Trough Levels ◽  
Local Guideline

AimTo evaluate the prescribed dose of vancomycin as per local guideline and review the achieved therapeutic drug levels.MethodRetrospective data was collected from paediatric inpatients that were prescribed vancomycin for more than 24 hours during the audit period. Data was obtained from the Trust’s electronic prescribing system, LastWord. Measured standards included initial vancomycin dose, dose prescribed for renal impairment, time to first trough level and any required dose adjustments as per local guidance. The dose bands for each age group were1; birth - 6 months 15 mg/g 8 hourly; >6 months -12 months 20 mg/kg 8 hourly; >12 months – 12 years 25 mg/kg 8 hourly; >12 years 20 mg/kg 8 hourly. The number of patients achieving therapeutic vancomycin trough levels was recorded. Safety data was collected, including reported adverse effects, infusion related reactions and renal impairment. Renal impairment was defined as an increase in creatinine by 50%. Data was collected from April 2018 for 6 months. Relevant data with regards to patient demographics, dosing and drug levels were collected and analysed using Microsoft Excel.Results12 patients received 15 doses of vancomycin over 6 months. 67% of initial vancomycin doses were prescribed as per local guideline, 60% of therapeutic trough levels were taken at the right time and 71% of patients that were prescribed the correct dose and had levels taken at the right time achieved therapeutic trough levels. 12 patients required dose adjustments. One patient with renal impairment was not prescribed the recommended dose as per local guidance. One patient reported an infusion related reaction, which was overcome by increasing the infusion time. Two patients who received therapy for >7 days accumulated vancomycin and recorded high trough levels, with no adverse events. One patient reported an increase in creatinine by 50% over the treatment period.ConclusionsVancomycin has the potential to induce nephrotoxicity and ototoxicity when consistently at high serum drug levels. Due to its narrow therapeutic index, drug levels should be monitored to ensure the drug does not accumulate. The licensed dose and dose listed in the BNF for Children 2 3 has historically under dosed patients at our trust, leading to the risk of ineffective therapy and bacterial resistance. It is unclear from research what the optimal dose is for paediatric patients.More research is needed to determine the correct paediatric dose of vancomycin. Higher doses than currently recommended as per licence resulted in three quarters of patients achieving therapeutic levels, however 12 patients still required dose adjustment. No patients suffered irreversible adverse effects or toxicity, suggesting that higher doses are safe to use in the paediatric population. Further education is required for those involved in the prescribing, administering and monitoring of Vancomycin in paediatric patients to ensure its safe use. Additional monitoring is required for those receiving higher doses >7 days to prevent drug accumulation, alternatively a loading dose followed by lower maintenance dose may be a more suitable dosing regimen.ReferencesHughes S, Crook J, Ross J. Vancomycin intravenous dosing guideline - paediatrics. Chelsea and Westminster Hospital; 2017.Stockman C, Sammons H, Stakey E, et al. Unanswered Questions Regarding Optimal Pediatric Vancomycin Use. Therapeutic Drug Monitoring 2016; 38:491–420.National Institute for Health and Care Excellence. Vancomycin. Available from https://bnfc.nice.org.uk/drug/vancomycin.html [Accessed 10th Oct 2018]

scholarly journals P050 Analysis of posaconazole therapeutic drug monitoring in paediatric haematology and oncology patients

2019 ◽  
Vol 104 (7) ◽  
pp. e2.55-e2 ◽  
Author(s):  
Natalie Donald ◽  
Ruth Edwards ◽  
Alison Thomson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Paediatric Cancer ◽  
Oncology Patients ◽  
Paediatric Haematology ◽  
Paediatric Patients ◽  
Trough Levels

Posaconazole is a broad spectrum triazole antifungal with activity against a range of invasive fungal pathogens including Candida and Aspergillus species.1 Due to its range of activity it has been shown, by randomised controlled trials, to be superior to fluconazole and itraconazole for prevention of fungal infection in neutropenic patients,2 as well as being cost saving.1 Fungal prophylaxis with posaconazole has become the drug of choice within a paediatric cancer unit due to its broad spectrum of activity however there are significant differences in bioavailability of the suspension and tablet preparations and there is limited data relating to its use in the paediatric population.ObjectiveTo determine if the paediatric cancer unit is undertaking effective dosing and appropriate therapeutic drug monitoring (TDM) of posaconazole in paediatric haematology and oncology patients.MethodsA retrospective analysis of clinical data from 38 paediatric patients treated with posaconazole was undertaken. Patients received either 18–24-mg/kg/day posaconazole suspension in divided doses (maximum 800-mg/day,3 or 6–8-mg/kg/day posaconazole tablets (maximum 300-mg/day). Compliance with this guidance, initial and subsequent levels, efficacy and tolerability were analysed.SettingThe study was undertaken within the XXXX cancer unit; data for patients treated with posaconazole between January 2016 and August 2017 was reviewed.Key findingsThere was good compliance with the dosing advice for liquid and tablet posaconazole with 82% of patients dosed correctly. Due to this, the initial trough level of ≥0.7 mg/L was achieved in 82% of patients within 14 days of treatment initiation; there were no significant differences between formulations. Trough levels were monitored on a monthly basis for 71% of patients but dose adjustments were necessary in 34% of patients. Posaconazole had a good tolerability profile during the study with most side effects resolving on continuation of treatment however one patient had to discontinue the drug due to widespread rash. No patients developed a fungal infection whilst on posaconazole.ConclusionSafe and effective dosing and monitoring of posaconazole suspension and tablet formulations has been undertaken at the XXXX. Trough levels attained the desired target concentration of ≥0.7 mg/L in the majority of patients but dose adjustments were required with both formulations emphasising the need for regular TDM. Posaconazole was well tolerated and clinically effective in preventing fungal infection indicating its appropriateness in this patient group. From this review, a guideline for initiation and appropriate TDM of posaconazole can be developed.ReferencesDranitsaris G, Khoury H. Posaconazole versus fluconazole or itraconazole for prevention of invasive fungal infections in patients undergoing intensive cytotoxic therapy for acute myeloid leukemia or myelodysplasia: a cost effectiveness analysis. Supportive Care in Cancer. 2011; 19(11): 1807–1813.Cornely O, Maertens J, Winston D, et al. Posaconazole vs. Fluconazole or Itraconazole in Patients with Neutropenia. New England Journal of Medicine. 2007; 356(4): 348–359.Bernardo V, Cross S, Crews K, et al. Posaconazole Therapeutic Drug Monitoring in Paediatric Patients and Young Adults with Cancer. The Annals of Pharmacotherapy. 2013; 47: 976–983.

scholarly journals Vancomycin prophylaxis in paediatric patients following cardiac surgery: a retrospective evaluation of trough levels and associated variables

2020 ◽  
Vol 31 (5) ◽  
pp. 667-673
Author(s):  
Leonardo Vallesi ◽  
Tiziana Fragasso ◽  
Simona Benegni ◽  
Giulia Insom ◽  
Luca Di Chiara ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Clinical Predictors ◽  
Paediatric Patients ◽  
Number Of Patients ◽  
Vancomycin Trough ◽  
Optimal Target ◽  
Independent Association ◽  
Trough Levels

Abstract OBJECTIVES Therapeutic drug monitoring during vancomycin administration is recommended. However, little information is available in case of paediatric vancomycin prophylaxis. The aim of this study was to analyse vancomycin trough levels on postoperative day (POD) 2 and 3 after paediatric cardio-surgery to assess the clinical predictors and outcomes associated with vancomycin concentrations and to evaluate whether adjustments are effective to target optimal levels. METHODS A retrospective study was conducted in paediatric patients receiving vancomycin prophylaxis after elective cardio-surgery. Adjustments were made if levels between 20 and 30 (halving subsequent dose) or ˃30 mg/l (dose withheld) were found. RESULTS Vancomycin doses of the 100 examined children (3.7–6.4 years) were 12.8 (2.5), 9.4 (5.4) and 9.7 (4.5) mg/kg, on POD1, 2 and 3, respectively (P = 0.0001). The 200 vancomycin trough levels decreased from 16.9 (11.4) on POD2 to 14.6 (8.5) on POD3 (P = 0.003). Overall, 66 troughs were sub-target, 68 reached the optimal target and 66 were supra-target. On POD2 and 3, 32 and 27 dose adjustments were required, leading to a reduced number of patients with supra-target troughs. Neonates showed a higher number of supra-target levels with respect to non-neonatal patients on both POD2 (P = 0.003) and 3 (P = 0.0001). At multivariable regression analysis, vancomycin levels showed independent association with weight and creatinine levels on both POD2 and 3. Vancomycin levels correlated with ventilation days (P = 0.31, P = 0.039), but not with methicillin-resistant Staphylococcus aureus positivity (P = 0.69). CONCLUSIONS Vancomycin prophylaxis in paediatric cardio-surgery requires strict therapeutic drug monitoring and several dosage adjustments. Supra-target troughs are frequent and neonatal age, weight and creatinine levels significantly affect vancomycin concentrations.

scholarly journals Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study

2021 ◽  
Vol 10 (22) ◽  
pp. 5311
Author(s):  
Anna Pękala ◽  
Rafał Filip
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Therapeutic Drug ◽  
Induction Phase ◽  
Drug Levels ◽  
Trough Levels

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.

scholarly journals Clinical utility of therapeutic drug monitoring of antiepileptic drugs

2019 ◽  
Vol 10 (4) ◽  
pp. 344-355 ◽  
Author(s):  
Zanab Al-Roubaie ◽  
Elena Guadagno ◽  
Agnihotram V. Ramanakumar ◽  
Afsheen Q. Khan ◽  
Kenneth A. Myers
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Effects ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Seizure Control ◽  
Therapeutic Drug ◽  
Seizure Outcome ◽  
Randomized Controlled ◽  
Patient Reported ◽  
Positive Effect

ObjectiveTo systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.MethodsWe searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.ResultsSixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.ConclusionsIf optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

scholarly journals P001 What is the role of antidrug antibody and drug level testing in patients treated with infliximab and adalimumab?

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Miriam Cox ◽  
Ruth Smith ◽  
Graeme Wild ◽  
Lisa Dunkley
Keyword(s):  
Clinical Evidence ◽  
Therapeutic Drug ◽  
Dosing Schedule ◽  
Drug Levels ◽  
Drug Concentrations ◽  
Antidrug Antibody ◽  
Patient Reported ◽  
Antibody Levels ◽  
Active Disease ◽  
Normal Antibodies

Abstract Background/Aims  Approximately 30-40% of rheumatology patients fail to respond to first-line biologics. Secondary inefficacy is mediated by immune complex formation between biologic agents and anti-drug antibodies. Anti-drug antibody testing has been undertaken at Sheffield Teaching Hospitals since October 2015. However, there are currently no national guidelines or consensus on what levels of anti-drug antibodies are clinically significant or what changes to therapy are suggested as a consequence of these tests. We aimed to review the reasons for and outcomes of anti-drug antibody levels tested at STH in patients on Adalimumab or Infliximab. Methods  Retrospective review of records of all Rheumatology patients having antidrug antibody levels tested October 2015 - April 2019. Results  237 patients were included in this analysis. The mean age of patients was 48 years. 43% were male. The most common reasons for testing antibody levels were clinical evidence of a flare in disease (n = 92) and patient reported worsening of symptoms (n = 88). 66% (n = 157) of antibody levels tested were negative, 21% (n = 49) of tests were strongly positive (antibody titre >50). Serum drug concentrations were subtherapeutic in 20 % (n = 47), therapeutic in 22% (n = 51) and supratherapeutic in 38% (n = 91). In 51% of patients (n = 119) the current treatment regime was continued. However, 38% (n = 90) changed biologics, and dosing schedule was changed in 2% (n = 6). Antibody titres were more likely to be strongly positive in patients who had clinically active disease compared to those who had symptoms but no clinical evidence of disease (30% vs 10% p = 0.009). Those with strongly positive antibodies were more likely to switch biologics than those with normal antibodies (84% vs 28%, p = 0.01). Patients with clinically active disease but normal antibodies and drug levels were more likely to switch biologics than patients with no evidence of active disease but positive antibodies (p = 0.03). Underlying diagnosis (p = 0.23) or concomitant DMARD use (p = 0.92) were not associated with positive autoantibodies. Of the 47 patients with subtherapeutic drug levels, 61% (n = 29) had strongly positive anti-drug antibodies and 73% (n = 34) subsequently switched biologics. 49% (n = 111) of patients had both therapeutic drug levels and normal antibodies. Of these, 22% (n = 25) switched biologics. Of the 25 patients that switched biologics 24% (n = 6) did not have evidence of active disease and 76% (n = 19) had active disease. Conclusion  33% of patients had positive autoantibodies. 39% of patients switched biologics following testing. There was no protective effect of DMARDs identified. Patients with active disease were more likely to have positive antibodies and to switch biologics than those with no clinical evidence of disease. 25% of patients had subtherapeutic drug levels. However, only 2% of patients had a dose schedule adjustment. Therefore, dosing schedule alterations could be considered in these patients prior to escalating to a more expensive biologic. Disclosure  M. Cox: None. R. Smith: None. G. Wild: None. L. Dunkley: None.

scholarly journals Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease

2021 ◽  
Vol 8 (1) ◽  
pp. e000788
Author(s):  
Shaina Sekhri ◽  
Bharat Rao ◽  
Akanksha Mohananey ◽  
Poonam Beniwal-Patel ◽  
Alexandra Bruss ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Drug ◽  
Extraintestinal Manifestation ◽  
Cross Sectional ◽  
Patient Reported ◽  
Serum Trough ◽  
Inflammatory Bowel ◽  
Trough Levels ◽  
Serum Trough Levels

BackgroundInfliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.ObjectiveWe aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.DesignIn this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.ResultsOut of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).ConclusionsThis study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn’s disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.

scholarly journals Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonja E. Zapke ◽  
Stefan Willmann ◽  
Scott-Oliver Grebe ◽  
Kristin Menke ◽  
Petra A. Thürmann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Pbpk Model ◽  
Clinical Population ◽  
Pbpk Modeling ◽  
Additional Patient ◽  
Therapeutic Drug ◽  
Model Parameters ◽  
Drug Levels ◽  
Trough Levels

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

scholarly journals Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 683-691 ◽  
Author(s):  
Thomas Greuter ◽  
Michel H. Maillard ◽  
Pascal Juillerat ◽  
Pierre Michetti ◽  
Frank Seibold ◽  
...  
Keyword(s):  
Decision Making ◽  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Loss Of Response ◽  
Antidrug Antibody ◽  
Antibody Titers ◽  
Inflammatory Bowel ◽  
Trough Levels

<b><i>Background:</i></b> Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. <b><i>Methods:</i></b> To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. <b><i>Results:</i></b> The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. <b><i>Conclusion:</i></b> A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

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