2018 Research Forum

Evaluation of 2 nd generation triazoles in the treatment of coccidioidomycosis Presenter: Janet Yoon PharmD Faculty Sponsor: Jeff Jolliff PharmD BCPS BCACP AAHIVP CDE Janet Yoon PharmD 1 , Jeff Jolliff Pharm BCPS BCACP AAHIVP CDE 2 , Brittany Andruszko PharmD 3 , Arash Heidari MD 4 , Royce Johnson MD 5 1 Resident Pharmacist R1 2 Clinical Pharmacy Residency Program Director; Adjunct Professor of Pharmacy Practice, University of the Pacific 3 Clinical Pharmacist 4 Department of Medicine, Division of Infectious Disease; Health Sciences Associate Clinical Professor, David Geffen School of Medicine UCLA 5 Department of Medicine, Chief, Division of Infectious Disease; Adjunct Professor, David Geffen School of Medicine UCLA INTRODUCTION Valley fever, also known as coccidioidomycosis, is a systemic fungal infection endemic to the southwestern United States. Although most cases are self-limiting and restricted to the lungs, the disease can disseminate to the bone, soft tissue, and central nervous system in severe cases. The management largely consists of triazoles (i.e., fluconazole and itraconazole) or amphotericin B. In severe infections, these options are not always fully efficacious or well tolerated leading to failure. Newer triazole antifungals, such as posaconazole, have demonstrated benefit in patients who have failed conventional therapy. However, outcomes data is somewhat sparse. Isavuconazonium, a prodrug of isavuconazole, has shown favorable side effect profile and efficacy against Coccidioides species in vitro. However, there are no published studies regarding its efficacy in vivo. Any treatment outcomes data with these agents would contribute significantly to the limited scientific body. PURPOSE To evaluate the treatment of coccidioidomycosis with 2nd generation triazoles. METHOD Retrospective chart reviewwas conductedon patients takingposaconazole or isavuconazolebetween January 1, 2013 and April 18, 2018. For all identified patients, the outcomes were assessed using the Mycosis Study Group (MSG) score (i.e., a composite score for symptoms, serology, radiographic findings) and the documented impressions of treating medical practitioners. For CNS patients, separate predefined point system was used to compute the point total. RESULTS Of the 82 patients who received treatment during this period, 15 patients who received isavuconazole and 31 patients who received posaconazole (suspension n=12 and tablets n=19) met study criteria. After a median duration of 10 months of isavuconazole, 73.3% were improved overall and 26.6% had a stable outcome. In the posaconazole suspension group, 83.3% were improved and 16.6% were stable. 78.9% were improved and 21.1% were stable in the posaconazole tablet group. The median change in MSG score was 3 in the isavuconazole group, 3 in the posaconazole tablet group, and 5 in the posaconazole suspension group. Table 1 Change P-value

Initiation of Refractory Tx MSG Score (Median ,IQR)

Last Visit MSG Score (Median, IQR)

Isavuconazole

5 (3.5-7.5)

2 (2-3)

3 5 3

0.00328 0.00338 0.0002

Posaconazole Suspension 6.5 (3.5-8.5)

1.5 (1-3) 2 (1-2.5)

Posaconazole Tablet

5 (3.5-7.5)

6