Target Audience:

Who should attend:

• Clinical faculty from the University of Pittsburgh School of Pharmacy
• Clinical staff pharmacists employed by the University of Pittsburgh Medical Center and deployed throughout the hospital campus in unit based roles and centrally in the department of pharmacy's main pharmacy
• Student pharmacy interns currently working within the department of pharmacy
• Certified Pharmacy Technicians

Abstract:
Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised patients. Solid organ transplant and hematopoietic cell transplant recipients are at a greater risk of IFI due to suppressed T cell function and prolonged neutropenia. Current guidelines recommend the use of broad-spectrum triazole antifungals for IFI prophylaxis in patients at increased risk. Some triazole antifungals have variable, non-predictable pharmacokinetics and a narrow therapeutic window. Therapeutic drug monitoring is a useful tool to ensure drug efficacy and prevent toxicity. However, the utility of therapeutic drug monitoring for azoles is not well defined when azoles are used for prophylaxis. The newest triazole antifungal, isavuconazole, has better pharmacokinetics and may have less interpatient variability compared to its counterparts. Accordingly, the role of therapeutic drug monitoring has not been defined and no efficacy and toxicity threshold has been identified for isavuconazole. This presentation will review patients at risk of invasive fungal infections that require antifungal prophylaxis, provide an overview of azole antifungals for fungal prophylaxis, and discuss pertinent literature that will help determine if azole antifungals require routine therapeutic drug monitoring when used for fungal prophylaxis.

Educational Objectives:

Upon successful completion of this continuing pharmacy education program, the participant should be able to:

• Identify patients at risk for invasive fungal infections who require fungal prophylaxis.
• Describe the utilization and limitations of azole antifungals for fungal prophylaxis.
• Discuss literature regarding therapeutic drug monitoring of azole antifungals for fungal prophylaxis.

Pharmacy Continuing Education Credits In support of improving patient care, the University of Pittsburgh is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Pharmacy (ACPE): This knowledge-based activity provides 1.0 contact hours of continuing pharmacy education credit. The assigned universal program number(s) is JA4008223-0000-23-092-H01-P. Other Healthcare Professionals Other health care professionals will receive a certificate of attendance confirming the number of contact hours commensurate with the extent of participation in this activity.

Suggested Additional Reading:

1. Silveira FP, Husain S. Fungal infections in solid organ transplantation. Medical Mycology. 2007; 45: 305-320.
2. Barnes PD, Marr KA. Risks, diagnosis, and outcomes of invasive fungal infections in hematopoietic stem cell transplant recipients. British Journal of Haematology. 2007; 139: 519-531.
3. Gallagher J, MacDougall C. Antibiotics Simplified (4th ed.). Jones & Bartlett Learning. 2018.
4. Dropulic LK, Lenderman HM. Overview of Infections in the Immunocompromised Host. Microbiol Spectr. 2016 Aug; 4(4): 1-43.
5. Fishman JA. Infection in Organ Transplantation. Am J Transplant. 2017; 17: 856-879.
6. Aslam et al. Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33(9):e13623.
7. Patterson et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 63(4):e1-e60.
8. Prevention and Treatment of Cancer-Related Infections. NCCN Guidelines. 2020; Version 2.2020.
9. Ullmann et al. Posaconazole vs. fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007. 356(4):335-47.
10. Tomblyn et al. Guidelines for Preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15:1143-1238.
11. Gilbert et al. The Sanford guide to antimicrobial therapy. Antimicrobial therapy, inc. 2018.
12. Ashley ESD, et al. Pharmacology of Systemic Antifungal Agents. Clin Infect Dis. 2006; 43: S28-39.
13. Diflucan (fluconazole) Package Insert. Pfizer Inc. 2011
14. Sporanox (itraconazole) Package Insert. Janssen Pharmaceuticals. 2001.
15. VFEND (voriconazole) Package Insert. Pfizer Inc. 2010.
16. Noxafil (posaconazole) Package Insert. Merck & Co., Inc. 2020.
17. Cresemba (isavuconazonium sulfate) Package Insert. Astella Pharma Inc. 2019.
18. Hussaini T et al. Therapeutic Drug Monitoring of Voriconazole and Posaconazole. Pharmacotherapy. 2011; 31(2): 214-225.
19. Kang J, Lee M. Overview of therapeutic drug monitoring. Korean Journal of Internal Medicine. 2009; 24(1): 1-10.
20. Ashbee HR, et al. Therapeutic Drug Monitoring (TDM) of antifungal agents: guidelines from the British Society of Medical Mycology. J Antimicrob Chemother. 2014; 69: 1162-1176.
21. Berge et al. Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant recipients. Transpl Infect Dis. 2009; 11(3):211-9.