Invasive fungal infections cause significant mortality and morbidity. Isavuconazole (ISV) is a new triazole approved for treatment of mucormycosis and aspergillosis. Data on its effectiveness outside clinical trials and in patients receiving prior triazole prophylaxis are lacking.
We conducted a retrospective cohort study on all patients at the Cleveland Clinic 6/1/20151/31/2017 who received ISV to determine 6-week response in a population with varying underlying diseases, and previous triazole prophylaxis or treatment. Descriptive statistics and univariate associations were calculated.
33 patients were identified including Organ transplant recipients (5), Hematopoietic cell transplant recipients (7), and acute leukemia (18). 25 had lung involvement while 13 had rhino-orbital-cerebral disease. In 13 cases, a fungal pathogen was identified: Mucorales (7) and Aspergillus (6). 15 received triazole prophylaxis prior to initiating ISV. 24 received antifungal therapy immediately prior to switching to ISV: amphotericin B (1), fluconazole (1), voriconazole (16), posaconazole (4), and micafungin (2). Switching was often to broaden empiric coverage (18). 6-week response according to subgroups is presented in Figure 1.6 patients had therapeutic drug monitoring (TDM). Median level (IQR) was 6.75 (5.67.0) mcg/mL. Patients given ISV following triazole prophylaxis, those undergoing TDM, and those with an identified fungal pathogen had increased odds of complete or partial response, but this did not reach statistical significance (Figure 2). At 6 weeks mortality was 36%; complete or partial response observed in 45%. No ISV related adverse effects reported.
To our knowledge, this is the first study to assess a real-world setting and a heterogeneous population with previous triazole prophylaxis or treatment. Our 6-week response (45%) compares favorably to published trials (35% Aspergillus; 11% Mucorales). Mortality in our study (36%) is similarly comparable to trial results (19% Aspergillus; 35% Mucorales). No major safety signal was observed. Larger cohorts are needed to describe additional real-world ISV use and determine associations with patient outcomes.
V. Athans, None