Therapeutic Drug Monitoring (TDM) of Cyclosporine Using the Area Under the Curve in Children Undergoing Hematopoietic Stem Cell Transplant (HSCT)

Background Current workforce shortages within the hematopoietic stem cell transplant field necessitate capitalizing on the role of oncology-trained pharmacists. Working within an agreed-upon protocol, pharmacists are able to expand patient care delivery through optimal medication therapy management. Methods An electronic survey was developed by the Advocacy & Policy Working Committee of the American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group and distributed to pharmacists involved in the care of hematopoietic stem cell transplant patients. The primary objective was to assess the current state of collaborative practice agreements in the hematopoietic stem cell transplant setting. Results Forty-eight responses representing 41 institutions were returned. Respondents were mostly female (67%) and practiced in the adult setting (83%). Reponses represented a range of practice experience in hematopoietic stem cell transplant with the majority of the hematopoietic stem cell transplant positions (83%) funded by the department of pharmacy at an academic medical center. Of the 48 responses, 22 (46%) respondents reported having collaborative practice agreements in place; 10 (21%) respondents did not currently have collaborative practice agreements, but were planning to implement them; and 16 (33%) respondents did not have collaborative practice agreements at their institution. Clinical activities performed under a collaborative practice agreement included medication selection and dosing modifications, therapeutic drug monitoring, supportive care management, and management of comorbid conditions and chronic diseases. The most commonly cited barrier to establishing collaborative practice agreements was the inability to secure reimbursement for services provided. No respondents reported a negative impact on job satisfaction. Conclusions The results of this survey provide the pharmacy community with a robust understanding of the current landscape of hematopoietic stem cell transplant pharmacy collaborative practice agreements.

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Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00787-15 ◽

2015 ◽

Vol 59 (9) ◽

pp. 5535-5541 ◽

Cited By ~ 6

Author(s):

Piergiorgio Cojutti ◽

Natalia Maximova ◽

Federico Pea

Keyword(s):

Stem Cell ◽

Continuous Infusion ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Predictive Performance ◽

Therapeutic Drug ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Gram Negative

ABSTRACTThis study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (CSS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenemCSSwere included. A good relationship between CLMand estimated CLCRwas observed (r2= 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at aCSS/MIC ratio of ≥4 in the CLCRcategories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m2, respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCRcategories of 40 to <80 and 80 to <120 ml/min/1.73 m2. Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.

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1733. Voriconazole Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplant: How Much Is Enough, Are Low Voriconazole Levels Associated With Opportunistic Infections, and What Are the Reasons for Discontinuation?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1596 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S635-S635

Author(s):

Giorgos Hadjivassiliou ◽

Claire Rummage ◽

Craig Hoesley ◽

Matthew L Brown

Keyword(s):

Stem Cell ◽

Therapeutic Drug Monitoring ◽

Hematopoietic Stem Cell ◽

Drug Monitoring ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Therapeutic Drug ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Subtherapeutic Level

Abstract Background Patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk for invasive fungal infections with associated high morbidity and mortality that necessitates the use of prophylactic antifungals. Voriconazole is commonly used for prophylaxis, but there are no recommendations for therapeutic drug monitoring. The purpose of this study was to characterize voriconazole therapeutic drug monitoring and associated outcomes in this patient population. Methods AlloHSCT patients receiving voriconazole prophylaxis at the University of Alabama at Birmingham Hospital between March 2015 and March 2018 were included in the analysis. Serum voriconazole levels (SVL) were evaluated to determine what percentage of patients achieved prophylactic or therapeutic concentrations. Incidence of invasive fungal infections (IFI) and voriconazole discontinuation was also assessed. Results Voriconazole prophylaxis was used in 151 of 162 alloHSCT patients, and 120 patients (79%) had SVL drawn correctly (≥4 days after initiation of course). We found that 35 (29%) patients achieved a subtherapeutic level (<0.5 μg/mL), 17 (14%) prophylactic level (0.5 to 1 μg/mL), 68 (57%) therapeutic level (1 to 5.5 μg/mL), and no patients achieved a supratherapeutic level (level ≥5.5 μg/mL). Voriconazole prophylaxis was discontinued early in 60 of 151 patients. Most common etiologies for discontinuation included liver function test abnormalities (44%) and encephalopathy (21%). The average SVL was 1.2 μg/mL in those requiring discontinuation. Four patients (3%) developed an IFI while receiving prophylactic voriconazole, of which only 1 had subtherapeutic level. Conclusion Even though approximately one-third of patients achieved a subtherapeutic SVL, there was no correlation with breakthrough IFI. There was also no linear correlation between SVL and risk of adverse effects requiring discontinuation. Our observational data do not support a need for therapeutic drug monitoring in alloHSCT patients receiving prophylactic voriconazole. Disclosures All authors: No reported disclosures.

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